International Urology and Nephrology

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Online ISSN: 1573-2584
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The IELT scores were plotted as Scatter dot plots with Median with interquartile range. P ≤ 0.001*** and P ≤ 0.0001**** were considered statistically significant
  • Ali Haydar YılmazAli Haydar Yılmaz
  • Ahmet Emre CinisliogluAhmet Emre Cinislioglu
  • Saban Oğuz DemirdöğenSaban Oğuz Demirdöğen
  • [...]
  • Isa ÖzbeyIsa Özbey
Purpose Premature ejaculation (PE) is a common sexual dysfunction that significantly affects the quality of life of the patient and their partner. We aimed to compare the efficacy and safety of the combination therapy with biofeedback-guided pelvic floor exercise therapy (BFT) and dapoxetine 30 mg. Methods Sixty-five patients diagnosed with lifelong PE were included in the study. Patients were divided into three groups as BFT, dapoxetine 30 mg and a combination of BFT and dapoxetine 30 mg. The patients were compared with the intravaginal ejaculatory latency time (IELT) pre-treatment and post-treatment 1st and 3rd months. Results The mean IELTs of the patients in Group 1 were 40 s in pre-treatment, 115 s at the end of the 4th week and 140 s at the end of the 12th week. The IELT values of the patients in Group 2 were 40 s in pre-treatment, 145 s in the 4th week and 170 s in the 12th week. The IELT values were calculated in Group 3 as 42.5 s in pre-treatment, 185 s in the 4th week and 205 s in the 12th week When the IELT was statistically compared between the groups at 1st and 3rd months, the duration in the combination group was found to increase significantly (p < 0.001). Conclusion Combination therapy with BFT and dapoxetine 30 mg in lifelong PE treatment is a good alternative with a low side effect profile and acceptable continuous efficiency.
Nocturia pathophysiology diagnosis algorithm
Global polyuria diagnosis algorithm
Non-global polyuria diagnosis algorithm
Nocturia is the complaint that an individual has to wake up at night one or more times to urinate. It is a frequent condition among older adults and entails detrimental effects with regard to sleeping, sexual activity, comfort, depression, mental function and vitality. It is clinically important to distinguish it from global polyuria, defined as a urinary rate ≥ 125 ml/h (3000 ml/day), as well as from nocturnal polyuria, which is an abnormally large volume of urine during sleep associated with a decreased daytime urine production. A Frequency Volume Chart (FVC), overnight water deprivation test with renal concentrating capacity test, and the nocturnal bladder capacity index are some of the methods that help establish the underlying pathology of this condition and hence define an adequate treatment plan.
Body-weights, blood–glucose concentrations, and relative bladder weights of the diabetic rats. In this figure, we present the body-weights (A), blood–glucose concentrations (B), and relative bladder weights (C) of the experimental rats. The bodyweights of diabetes rats were remarkably lower compared with the Control + excipient group, and we observed no obvious change in the body-weights after resveratrol treatment. A (n = 6 for each group; ns.: no statistical significance; ****P < 0.0001); Blood–glucose concentrations and relative bladder weights of diabetic rats were higher than those of the Control + excipient group, and oral resveratrol had an effect on the blood–glucose concentration (B) but had a certain effect on relative bladder weights (C) (n = 6 for each group; *P < 0.05; ****P < 0.0001)
Histological changes in the bladders of diabetes rats. In this figure, we present the representative macroscopic (A–D) and histological (E–H) findings of the rat bladders. Macroscopically, the bladder wall was thickened with edema in the (C) STZ + excipient group compared with the (A) Control + excipient group. After the use of resveratrol, the edema of the bladder tissue and the thickening of the bladder wall was alleviated (D). A histological examination of the H&E staining showed inflammatory cell infiltration, edema, and hemorrhage (G) in the lamina propria in the STZ + excipient group, but no significant histological changes were found in the Control + excipient and Control + resveratrol groups (E, F). We observed a substantial amelioration of the injury and inflammation in the STZ + resveratrol group (H) after the resveratrol treatment
Resveratrol reduced mRNA expression of inflammatory factors in the bladders of diabetes rats. According to the qPCR analysis, compared with the Control + excipient group, the mRNA expressions of the STZ + excipient group were increased, and were expressed as NF-κB (A), TNF-α (B), IL-6 (C), and IL-1β (D) (n = 6 for each group; ns.: no statistical significance; ****P < 0.0001). Compared with the inflammatory factor mRNA expression in the DSM tissues of diabetic rats treated with excipient, that of the STZ + resveratrol rats demonstrated a significant decrease (n = 6 for each group; ns.: no statistical significance; ****P < 0.0001)
Resveratrol reduced inflammatory factor protein expression in the bladders of diabetes rats. We used Western blotting to detect the IL-6, IL-1β, TNF-α and NF-κB proteins in the DSM tissue in each group (A). We compared the expression levels of the proteins in the DSM tissues: NF-κB (B), TNF-α (C), IL-6 (D), and IL-1β (E). Compared with the Control + excipient, the protein levels of the STZ + excipient group were significant increased (n = 10 for each group; ns.: no statistical significance; ****P < 0.0001). After the oral administration of resveratrol, the protein content was remarkably more decreased in the diabetic rats than in the excipient-treated diabetic rats. (n = 10 for each group; ns.: no statistical significance; ***P < 0.001; ****P < 0.0001)
Purpose In this paper, we aimed to prove that resveratrol can inhibit inflammation in the detrusor smooth muscle of diabetic rats, which may provide a new direction for diabetic cystopathy (DCP) treatment. Methods We induced a Sprague–Dawley (SD) rat model of type 1 diabetes by intraperitoneal injections of streptozotocin (STZ). Then, we separated the SD rats into four groups: (1) an excipient-treated control group; (2) a resveratrol-treated control group; (3) an excipient-treated streptozotocin (STZ)-injected group; and (4) a resveratrol-treated STZ-injected group. We administered the resveratrol or excipient by intragastric administration. After 12 weeks of diabetes induction, we measured the blood–sugar concentrations and bladder weights, and we took the bladder tissues of each group of rats for hematoxylin–eosin staining to observe the histological changes. We used real-time quantitative polymerase chain reaction (qPCR) and Western blotting to analyze the expression levels of tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), interleukin (IL)-6, and IL-1β. Results The bodyweights of the diabetic rats were appreciably reduced, while the bladder weights and blood–glucose concentrations were substantially increased. Oral resveratrol could not improve the changes in the bodyweights and blood–glucose concentrations, but it had a certain effect on the bladder weights. In a macroscopic evaluation, the bladder walls of the STZ-induced diabetes rats were thickened, and, from the H&E staining, we could see that the bladder tissues of the diabetic rats had inflammatory cell infiltration, edema, and the capillary congestion of the mucosa and lamina propria. After resveratrol treatment, the bladder-wall thickening was reduced, and the tissue damage and inflammation were significantly ameliorated. We could associate all these changes with markedly heightened expressions of TNF-α, IL-1β, IL-6, and NF-κB in the detrusor smooth muscle (DSM) tissues of the diabetic rats. Oral treatment with resveratrol alleviated the expressivity of the inflammatory cytokines in the DSM tissues. Conclusions Resveratrol treatment ameliorated the histological changes in the bladder and inhibited the expressions of DSM–tissue inflammatory factors in diabetes rats. Resveratrol may provide a new direction of research for the treatment of diabetic cystopathy.
Purpose Acute kidney injury (AKI) induced by renal ischaemia/reperfusion (I/R) during renal transplantation has been reported to be linked to the regulation of SIRT2, one of the members of SIRTUINS family. Current work is attempted to explore the influence and mechanism of SIRT7 in renal cell apoptosis controlled by miR-152-3p during renal I/R injury. Methods Three databases were used to select the miRNAs regulating the expression of SIRT7. Overexpression and inhibition of miR-152-3p and Luciferase assay were employed to certify the modulation of miR-152-3p to SIRT7 in cells. RT-qPCR assay was used to measure the mRNA levels. Western blot assay was employed to determine the expression of proteins. TUNEL assay and Flow Cytometry were conducted to analyze cell apoptosis. Results SIRT7 expression decreased in tissues of AKI patients and rats underwent renal I/R, which was associated with enhanced impairment of renal function. SIRT7 downregulation was attributed to the direct inhibition by miR-152-3p due to binding and inhibiting its seed sequence in 3′-UTR of SIRT7 mRNA. Consequently, the upregulation of miR-152-3p led to an inhibition of SIRT7 expression, an increase in expression of extrinsic apoptosis molecules containing FOXO3a, Bim, and caspase3, and apoptotic renal cells; while miR-152-3p inhibition abolished these phenotypes. Conclusion SIRT7 downregulation by miR-152-3p is a leading cause of renal cell apoptosis and functional impairment induced by renal I/R. Inhibition of miR-152-3p to restore SIRT7 expression can be a promising strategy against renal I/R injury.
Flow of the patients through the study
Introduction and objectives Data on the use of single step dilatation technique during pediatric percutaneous nephrolithotomy (PCNL) in the literature is sparse. In this prospective randomized study, we aimed to compare the safety, efficacy, and perioperative complications of single step versus serial tract dilatation using Alken metal telescopic dilators during pediatric PCNL. Methods Patients undergoing PCNL were randomized into two groups according to the dilatation technique used. In group A, Alken telescopic serial metal dilatation was utilized, and in group B, single step dilatation was performed. Inclusion criteria included children < 18 years with stone burden from 2 to 4 cm, located in the renal pelvis ± one calyx, who were candidates for PCNL. The primary outcomes were access time and complications’ rate. The secondary outcomes were dilatation fluoroscopy time, operative duration, stone free rate, postoperative hospital stay, hemoglobin deficit, and need for blood transfusion. Both outcomes were evaluated and compared between both treatment groups. Results A total of 70 patients were randomized into group A (35 patients) and group B (35 patients). Access was successfully obtained in all procedures. All the procedures were performed through a single tract. Access time and dilatation fluoroscopy time were shorter in group B (statistically significant). Patients in group A had higher rate of complications (statistically significant). Intraoperative bleeding requiring blood transfusion was less in single track dilatation than serial metal track dilatation. Conclusions Compared to serial metal track dilatation, single step dilatation showed comparable operative time and stone free rate, with significantly reduced access time and dilatation fluoroscopy time.
Representative images of the serial ultrasonographic exam of the lower urinary tract. A, B, and C: Lesions identified until the 8th week of the protocol. D, E, and F: Lesions identified during the 15th week of the protocol. G: Normal bladder
Images representative of hematoxylin–eosin and immunohistochemical Ki-67 and TLR-4 in the urothelium. Carcinogenesis scenario: Sham (Group 1) versus castration (Group 2). Different letters denote p < 0.05
Images representative of hematoxylin–eosin and immunohistochemical expression of Ki-67 and TLR-4 in the urothelium. Treatment scenario: Sham-BCG (Group 3) versus Castration-BCG (Group 4). Different letters denote p < 0.05
Co-dependency diagram of innate (TLR; “ignition”) and adaptive (checkpoint; “brake”) immune responses as a multi-targeted immunotherapy strategy (developed by the author)
Purpose Among diverse Pattern Recognition Receptors (PRRs), Toll-like receptor-4 (TLR-4) is a key urothelial trigger for innate immune response impacting urothelial bladder carcinoma (BC). Androgen activation promotes immunotolerance, playing an immunoregulatory role by unknown mechanisms. We explored the castration impact on urothelial TLR-4 modulation in carcinogenesis and immunotherapeutic scenario. Methods Intact (SHAM) versus castrated male Fisher-344 rats were evaluated in 2 scenarios: (A) Carcinogenesis: After randomization to SHAM (n = 5) and Castration (n = 5), carcinogenesis was induced by four intravesical doses of 1.5 mg/kg n-methyl-n-nitrosourea (MNU) every 15 days. (B) Treatment: After ultrasonographic confirmed MNU-induced papillary BC on week 8, rats were randomized to SHAM (n = 5) and Castration (n = 5) and offered 6 weekly intravesical treatment of 10⁶ CFU of bacillus Calmette Guerin (BCG) in 0.2 ml saline. After 15 weeks the urinary bladders underwent histopathology. Urothelial cell proliferation was measured by Ki-67 immunohistochemistry (IHC), and TLR-4 expression was quantified by IHC and WB. Results Castration induced higher TLR-4 urothelial expression (p = 0.007) and anticarcinogenic effect with fewer urothelial tumors (60 vs. 80%) and lower urothelial cell proliferation compared to intact animals (p = 0.008). In the intravesical BCG treatment setting, castration has potentialized the BCG activation of TLR-4 (p = 0.007) with no residual in situ carcinoma compared to intact animals, suggesting the potential to amplify the BCG immune response. Conclusion To our knowledge, this is the first description of TLR-4 urothelial expression hormonal modulation. The described castration-mediated immunomodulation will help to improve the knowledge of urothelial cancer gender diversities and PRRs modulations with treatment implications.
The deposition of PMPs in the kidneys of patients with different pathological stages of DN. A PMP deposition was detected by immunofluorescent staining. CD61, a specific biomarker of PMPs, was stained red, and WT-1 was stained green (scar bar, 100 μm). B The mean fluorescence intensity of CD61 was quantified by ImageJ software (mean ± SD, n = 3). *P < 0.05 compared with IIa; **P < 0.01 compared with IIb
A PMP deposition in podocytes of diabetic rats was assessed by immunofluorescent staining. Ctrl: normal controls, DM: STZ-induced diabetic rats, DM + Asp: STZ-induced diabetic rats treated with aspirin (15 mg/kg). CD61 was stained red, and WT-1 was stained green. Nuclei were stained with DAPI (blue) (scar bar, 40 μm). B Ultrastructural observation of podocytes in diabetic rats was detected by immune electron microscopy. CD61-positive PMPs (red arrows) were present in podocytes of diabetic rats by immune electron microscopy (scar bar, from 100 to 500 nm). C CD61 expression in PMPs was assessed by Western blot. D Z-stack analysis of PMP deposition in podocytes. Podocytes were incubated with activated PMPs (aPMPs) for 4 h at 37 °C. Uptake of PMPs was observed by confocal microscopy using immunofluorescent staining. CD61 was stained red, and nuclei were stained with DAPI (blue). Original magnification × 1000
The rats were randomly divided into three groups: Ctrl, normal controls; DM, STZ-induced diabetic rats; and DM + ASP, STZ-induced diabetic rats treated with aspirin (15 mg/kg). A Histopathological changes in the glomeruli were evaluated by periodic acid-Schiff staining (scar bar, 20 μm). B Observation of the kidney ultrastructure was assessed by transmission electron microscopy (scar bar, 0.2 μm)
A The rats were randomly divided into three groups: Ctrl, normal controls; DM, STZ-induced diabetic rats; and DM + ASP, STZ-induced diabetic rats treated with aspirin (15 mg/kg). TNF-α, MCP-1 and IL-1β protein expression in kidneys of different groups at 12 weeks was assessed by Western blot. B Podocytes were incubated with activated PMPs (aPMPs, 0.5 μg/ml) or inactivated PMPs (iPMPs, 0.5 μg/ml) for 24 h at 37 °C. TNF-α and MCP-1 protein expression was then measured by western blot. The relative density of protein bands was quantified and normalized to β-actin (mean ± SD, n = 3). *P < 0.05 compared with Ctrl
The rats were randomly divided into three groups: Ctrl, normal controls; DM, STZ-induced diabetic rats; and DM + ASP, STZ-induced diabetic rats treated with aspirin (15 mg/kg). α-SMA, fibronectin, and podocin protein expression in rats of different groups at 12 weeks was assessed by A immunofluorescent staining (scar bar, 50 μm) and B western blot. The relative density of protein bands was quantified and normalized to β-actin (mean ± SD, n = 3). *P < 0.05 compared with Ctrl. C Podocytes were incubated with aPMPs (2 μg/ml) or iPMPs (2 μg/ml) for 24 h at 37 °C. Here, α-SMA, fibronectin, and podocin protein expression was measured by immunofluorescent staining (scar bar, 20 μm)
Background Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in the developed world. Podocyte injury is a critical cellular event involved in the progression of DN. Our previous studies demonstrated that platelet-derived microparticles (PMPs) mediated endothelial injury in diabetic rats. This study aimed to investigate whether PMPs are deposited in podocytes and to assess their potential effects on podocyte injury in DN. Methods The deposition of PMPs in podocytes was assessed by immunofluorescent staining and electron microscopy. The changes in renal pathology and ultra-microstructure were assessed by periodic acid-Schiff staining and electron microscopy, respectively. The expression of inflammatory cytokines and extracellular matrix proteins was measured by immuno-histochemical staining and western blot. Results PMPs were widely deposited in podocytes of glomeruli in diabetic patients and animal models and closely associated with DN progression. Interestingly, aspirin treatment significantly inhibited the accumulation of PMPs in the glomeruli of diabetic rats, alleviated mesangial matrix expansion and fusion of foot processes, and decreased the protein expression of inflammatory cytokines and extracellular matrix secretion. An in vitro study further confirmed the deposition of PMPs in podocytes. Moreover, PMP stimulation induced the phenotypic transition of podocytes through decreased podocin protein expression and increased protein expression of α-SMA and fibronectin, which was correlated with increased production of inflammatory cytokines. Conclusion Our findings demonstrated for the first time that the deposition of PMPs in podocytes contributed to the development of DN.
Negative correlation between Apelin-13 level and glomerular filtration rate (Apelin-13; picogram/ml)
Positive correlation between Apelin-13 level and Homeostatic Model Assessment-Insulin Resistance (HOMA-IR)
Positive correlation between Apelin-13 level and microalbumin/creatinine ratio
Purpose There is no clear information about the level of Apelin-13 in patients with diabetic nephropathy (DN). In this study, we investigated whether there is a relationship between Apelin-13 level and the severity of the disease in patients with DN. Methods In our case–control study, we included patients who applied to the endocrinology outpatient clinic in 2019. Patients without a history of diabetes were determined as the healthy group (group 1). The patients were divided into 4 groups according to their microalbumin and creatinine levels. Venous blood samples were obtained from all patients for routine laboratory parameters and Apelin-13 levels. Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) for insulin resistance was calculated using the formula: plasma glucose X insulin level/405. Results Albumin was found to be significantly lower in group 5 (p = 0.032), hemoglobin A1c, microalbumin/creatinine and HOMA-IR values were found to be significantly lower in group 1 (p < 0.001 for each). Apelin-13 level was found to be significantly higher in group 4 and group 5 (p < 0.001). A negative correlation was found between Apelin-13 and GFR (r = − 0.286, p = 0.003). A positive correlation was found between Apelin-13 and HOMA-IR (r = 0.309, p = 0.009) and microalbumin/creatinine (r = 0.296, p < 0.001). Conclusion In patients with DN, Apelin-13 level increases with the severity of the disease and can be used as a biomarker for staging of DN.
Background Ureteral stricture (US) is a fibrotic process that leads to urinary tract obstruction and even kidney damage, with the characteristic of reduced extracellular matrix (ECM) degradation and increased collagen synthesis. Verapamil, as a calcium channel blocker, was reported to prevent scar formation. Our work aimed to investigate the biological effects and mechanism of verapamil in US. Methods Fibroblasts were subjected to transforming growth factor-beta 1 (TGF-β1) to stimulate collagen synthesis, and the messenger ribonucleic acid (mRNA) and protein expressions in fibroblasts were assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. The location of phosphorylation-signal transducer and activator of transcription 3 (p-STAT3) and Jund proto-oncogene subunit (JunD) in fibroblasts were determined by immunofluorescence (IF). The binding relationship between signal transducer and activator of transcription 3 (STAT3) and collagen type I alpha1 (COL1A1)/collagen type III alpha 1 chain (COL3A1) and the binding relationship between JunD and tissue inhibitor of metalloproteinases-1 (TIMP-1) were verified by dual luciferase reporter gene and chromatin Immunoprecipitation (ChIP) assays. Results Herein, we found that verapamil could inhibit TGF-β1/Ca2 + ⁄calmodulin-dependent protein kinase II (CaMK II)-mediated STAT3 activation in fibroblasts, and STAT3 inhibition repressed collagen production. In addition, verapamil could inhibit TGF-β1/CaMK II-mediated Mothers against DPP homolog 3 (Smad3)/JunD pathway activation in fibroblasts, and JunD silencing inhibited TIMP1 (a matrix metalloproteinase inhibitor) expression. Our subsequent experiments revealed that STAT3 bound with COL1A1 promoter and COL3A1 promoter and activated their transcription, and JunD bound with TIMP1 promoter and activated its transcription. Moreover, as expected, STAT3 activation could eliminate the inhibitory effect of verapamil treatment on TGF-β1-induced collagen production in fibroblasts, and JunD overexpression reversed the inhibitory effect of verapamil treatment on TGF-β1-induced TIMP1 expression in fibroblasts. Conclusion Verapamil inhibited collagen production and TIMP-1 expression in US by blocking CaMK II-mediated STAT3 and Smad3/JunD pathways.
Purpose American Urology Association guidelines recommend genetic testing for patients with recurrent stones and urine oxalate > 75 mg/day. The goal of this study was to examine the treatment of patients in this category in a large multidisciplinary adult stone clinic. Methods Patients were evaluated from a single institution between 2006 and 2019. Those with at least one level of urinary oxalate excretion (uOx) above 75 mg/day were identified. A chart review identified enteric risk factors and genetic testing results. Patients without an identifiable enteric cause were considered idiopathic. Results A total of 4229 separate 24-h urine collections in 1302 patients were reviewed. At least one measurement of uOx above 75 mg/day was found in 103 (7.9%) patients. Enteric hyperoxaluria (EH) was seen in 28 (27%) and idiopathic hyperoxaluria (IH) in 76 (74%). 20 (71%) patients in the EH group had undergone gastric bypass. The median uOx was significantly higher level in the EH group (121.0 vs. 93.0 mg/day). For the entire cohort, there was a drop in uOx (− 33.8 mg/day) with medical and dietary therapy after a follow-up of 46.6 months. The final oxalate was higher in EH (88.9 vs. 60.1 mg/day). Only one patient had referral for genetic testing and was found to have primary hyperoxaluria type 2. Conclusions The most common cause of significant hyperoxaluria in patients with recurrent nephrolithiasis remains idiopathic. Patients with IH have more significant improvement in uOx compared to EH; however, both groups had hyperoxaluria at last follow-up. Rate of genetic testing is low despite guideline recommendations.
Receiver operating characteristic curves of the NLR, PLR, and SII for differentiating SLE patients. ROC for NLR was represented by the blue line with an AUC = 0.723 (95% CI 0.636–0.810, p = 0.001) with a sensitivity of 52.1% and a specificity of 94.2%, the ROC for PLR was represented by the green line with an AUC = 0.666 (95% CI 0.573–0.758, p = 0.001) with a sensitivity of 56.5% and a specificity of 74.2%, and the ROC for SII was represented by the red line with an AUC = 0.626 (95% CI 0.540–0.707, p = 0.01) with a sensitivity of 36.2% and a specificity of 94.2%. The optimum cut-off point for NLR, PLR and SII were 2.95, 148.6 and 761, respectively. NLR neutrophil–lymphocyte ratio, PLR platelet–lymphocyte ratio, SII systemic immune inflammation index, SLE systemic lupus erythamatosus, ROC receiver operating characteristic, AUC area under the curve
Receiver operating characteristic curve of the NLR for differentiating SLE patients with nephritis from those without nephritis. The area under the ROC curve for NLR was 0.635 (95% CI 0.509–0.762, p = 0.049) at a cut-off value of 2.32, with a sensitivity of 78.5% and a specificity of 56.2%. NLR neutrophil–lymphocyte ratio, ROC receiver operating characteristic
Purpose Systemic immune inflammation index (SII) has been used as a marker of inflammatory status in various diseases, but its role in systemic lupus erythematosus (SLE) is unknown. We aimed to investigate the role of SII in SLE and its association with disease activity and renal involvement. Methods In this retrospective study, 76 patients with SLE were compared with 76 age- and gender-matched healthy control group in terms of SII, neutrophil–lymphocyte ratio (NLR), and platelet–lymphocyte ratio (PLR). SLE Disease Activity Index 2000 system (SLEDAI-2 K) was used to divide the SLE patients into an inactive group (SLEDAI-2 K < 9) and an active group (SLEDAI-2 K ≥ 9). Correlations between the ratios and both disease activity and renal involvement were analyzed. Results SLE patients had a higher level of SII compared with controls. The ability of SII in predicting SLE (AUC = 0.626) was lower than NLR (AUC = 0.723) and PLR (AUC = 0.666). SII was positively correlated with C-reactive protein (r = 0.288. p = 0.01), but no association between SII and SLEDAI-2 K scores was found. Significantly higher values of NLR, but not SII, were detected in patients with nephritis (p = 0.04). The best NLR cut-off value to predict SLE patients with nephritis was 2.32, with 78.5% sensitivity and 56.2% specificity. Conclusion For the first, we demonstrated that SII level was elevated in patients with SLE. However, NLR is a better marker than SII in predicting SLE and could serve as an indicator of nephritis. Larger-scale studies should be carried out to confirm our results.
  • María Teresa Melgarejo SeguraMaría Teresa Melgarejo Segura
  • Fátima del ToyosCastilloFátima del ToyosCastillo
  • Yaiza Yáñez CastilloYaiza Yáñez Castillo
  • [...]
  • Miguel Arrabal MartínMiguel Arrabal Martín
Purpose To provide our single-center experience with an approach to refractory stress urinary incontinence (SUI) with permanent urethral ligation (PUL) and suprapubic tube (SPT) placement, in hopes of contributing to the limited body of research surrounding this surgical treatment option for patients with end-stage urethra (ESU). Methods All patients undergoing PUL with SPT placement from 01/01/2018 to 04/30/2022 were identified from an institutional database. Institutional Review Board exempt status was granted for the conduct of this study. Patients were seen postoperatively at 1 month and 1 year. If there were any concerns of incontinence, an antegrade urethrogram via the SPT was performed. Descriptive statistics were used to evaluate patients. Results Seven patients underwent PUL with SPT in our timeframe and were included in the study. All patients previously had an AUS placed, and two patients had a urethral sling previously placed. The median follow-up time was 21 months, ranging between 2 and 48 months. Complications included bladder spasms (43%) and continued leakage per urethra (14%). Of the 7 patients, 6 have reported continence through their urethra at their most recent follow-up. Conclusion This initial data suggest that PUL with SPT placement may be a viable surgical approach to treating refractory SUI, especially for patients with ESU who wish to avoid the morbidity associated with more formal supravesical diversion. Further study of this technique and longer follow-up is required to determine its long-term efficacy and tolerability for patients.
Purpose Because of many unanswered questions regarding men’s health, a literature review was performed to better understand the role of testosterone and testosterone replacement therapy (TRT) in the management of hypogonadism and aging related prostate gland diseases (ARPGD) including prostate cancer (PCa) and benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS). Methods The PubMed database was screened for pertinent peer reviewed articles published during the last four decades that culminated in the positions and recommendations in this paper. Results Hypogonadism seriously impacts men’s health, and the diagnosis remains controversial. The incidence of ARPGD is projected to increase worldwide and treatment still has significant limitations. There is compelling evidence that lower, not higher, testosterone levels trigger the development of PCa and BPH through androgen receptor over-expression. TRT was found to be safe and effective in treating hypogonadism including in PCa survivors and those harboring PCa. There is also evidence that TRT might reduce the incidence and prevalence of ARPGD. Conclusions and recommendations This review synthesizes a wide-ranging compendium of basic science and clinical research that strongly encourages altering the present approach to diagnosing and treating men with hypogonadism and ARPGD. These findings underscore the importance of avoiding significant testosterone decline and support the use of TRT. Ten recommendations are offered as a framework for the way forward. It is now time for clinicians, payers, researchers, funding agencies, professional associations, and patient advocacy groups to embrace this new paradigm to increase longevity and improve the quality of life.
Placement of electrodes/electronics integrally embedded into fabric
The battery-powered device attached to the sock
of allocation, randomization, and intervention
Purpose Transcutaneous posterior tibial nerve stimulation (TPTNS) for the treatment of overactive bladder syndrome (OAB), with or without urge urinary incontinence (UUI) using electrodes imbedded in the fabric of a conventional sock and an attachable battery-operated stimulation device (ZIDA®—Exodus Innovations, Sufa, Israel), was compared for effectiveness and safety to a sham procedure in a prospective, blinded, randomized, controlled trial. Methods Forty patients with diagnosed with OAB were recruited from a single site. There were two groups: a treatment group (21 patients, mean age 64), which used an active ZIDA® activation device (ZIDA) and a sham control group (SCG, 19 patients, mean age 72) randomized in a 1:1 ratio. After individual fitting of the sock and face-to-face instruction in the use of the device, patients in both groups self-administered the treatment once weekly for 30 min at home for a duration of 12 weeks. Prior to randomization and in Week 12, patients completed two 3-day bladder diaries and a quality-of-life (QOL) survey. Treatment success was defined as at least a 50% reduction in urgency voids with or without incontinence or at least a 30% reduction in 24-h frequency from baseline to Week 12. The key secondary endpoint was change in QOL from baseline to Week 12. Results The success rate for the primary endpoint in the ZIDA group was 80% (n = 16/20) versus 39% (n = 7/18) in the SCG (p = 0.02). For QOL, the least squares mean difference in change from baseline to Week 12 between the ZIDA and sham control arms total score was − 12.7 (95% CI − 20.2 to − 5.1). No significant adverse effects were observed. Conclusion TPTNS using the ZIDA home-based stimulation device offers a safe and effective treatment for patients with OAB syndrome and improves QOL. Trial regestration TRN: NCT04470765.
Boxplot of the mean change in prostate dimensions before and after aquablation at 3 months
Purpose This study aimed to investigate the functional and urodynamic outcome of Aquablation in patients with acute urinary retention (AUR) on catheters. Methods Men aged 50–70 who failed medical treatment of BPO with AUR failing to wean off urethral catheter were recruited to undergo Aquablation. Individuals were assessed pre-operatively and at 3 and 6 months after surgery. The primary outcome was defined by the success rate of weaning off catheter. Secondary outcomes were measured by a change in prostate size, symptom scores and urodynamic parameters. Results Twenty patients underwent Aquablation between June 2019 and September 2020. Mean duration of the urethral catheter in-situ was 5.9 ± 4.9 weeks and mean prostate size of the cohort pre-operatively was 60.8 ± 15.8 cc. A second pass Aqaublation treatment was performed in 14 patients. Five patients failed to wean off the catheter on the first attempt after surgery, requiring another attempt 1 week later which were all successful. At 3 months after the operation, a significant reduction in prostate volume was observed (60.8 ± 15.8 cc vs 24.9 ± 10.3 cc, p < 0.001). No change in international index of erectile function (IIEF) was found (baseline: 16.1 ± 5.8; 3-month: 14.9 ± 6.4; p = 0.953). Mean bladder outlet obstruction index was 14.2 ± 23.0 at 6 months upon urodynamic assessment with 75% of patients had a resolution of detrusor overactivity. Reduction in prostate length was found to be more significant than a reduction in width and height after Aquablation (R = 0.693, p = 0.039). Conclusion From the early data of a single centre, Aquablation was shown to provide a consistent improvement in symptoms, uroflowmetry and urodynamic parameters in patient with a urethral catheter. Results from our study suggest that improvement from Aquablation is reproducible in patients with AUR.
Gender differences of overall survival and cancer-specific survival in patients with T2N0M0 bladder cancer before (A) and after (B) propensity score matching
Distribution of propensity scores (A) and standardized difference change line plot (B) of propensity score matching
Gender differences of overall survival and cancer-specific survival in each treatment subgroup before (A) and after (B) propensity score matching
The trend changes of overall survival of patients under various treatment methods before (A) and after (B) propensity score matching
Purpose To explore the gender differences in survival under different treatments in localized muscle-invasive bladder cancer (MIBC), and to find clinical strategies to improve the poor prognosis of female with bladder cancer (BC). Methods Patients with localized MIBC were collected in the SEER database from 2010 to 2016 to analyze the gender differences in clinical characteristics. Propensity score matching was used to balance the effects of confounding factors. Kaplan–Meier method and Cox proportional hazards regression model were performed to compare the overall survival (OS) and cancer-specific survival (CSS) of patients between different treatment subgroups. Results The entire cohort included 13,272 T2N0M0 MIBC patients, with a male-to-female incidence of 3:1. Compared with male patients, females had a higher age of onset and more blacks. There were more female patients undergoing bladder-sparing surgery (BSS) alone, and the OS and CSS were worse than those in males. The gender difference showed statistical significance in the BSS group, but not in the radical cystectomy (RC) group. Conclusion The survival of localized MIBC patients can be affected by treatments. Multi-modality treatment and RC may improve the survival prognosis of female patients.
Minimally invasive therapy for children with myelomeningocele and neurogenic lower urinary tract dysfunction. A-1 Detrusor overactivity and detrusor sphincter dyssynergia with hydronephrosis and recurrent urinary tract infection (UTI), A-2 after urethral and detrusor Botox injection, the bladder compliance improved and patient could void spontaneously, B-1 detrusor underactivity (DU) with low compliance and recurrent UTI, B-2 after detrusor Botox injection, bladder compliance improved and patient could use abdominal straining to voiding
Surgical procedures for children with myelomeningocele and neurogenic lower urinary tract dysfunction. A-1 Bilateral high-grade vesicoureteral reflux (VUR) and low bladder compliance, recurrent UTI, A-2 after cutaneous vesicostomy, bladder compliance improved, VUR resolved and no UTI occurred; B-1 detrusor underactivity (DU) and tight bladder neck, B-2 after transurethral incision of bladder neck, patient voided efficiently by abdominal straining, C-1 DU and low bladder compliance, recurrent UTI, C-2 after autoaugmentation, bladder compliance improved, patient voided by clean intermittent catheterization without incontinence, D-1 low bladder compliance persisted after initial autoaugmentation, urinary incontinence, D-2 after augmentation enterocystoplasty, bladder compliance improved, no more incontinence, patient was continent and voided by CIC
Receiver-operating characteristic curve of the bladder compliance among patients with myelomeningocele who received surgical treatment or minimally invasive therapy, the cutoff point was > 20.5 mL/cm H2O with a sensitivity of 0.842 and specificity of 0.789
Purpose Neurogenic lower urinary tract dysfunction (NLUTD) is common among children with myelomeningocele (MMC). If NLUTD is not appropriately managed, recurrent urinary tract infection (UTI) can persist and may affect upper urinary tract function. This study investigated the usefulness of videourodynamic study (VUDS) in the urological management of MMC. Methods We retrospectively analyzed 57 patients with MMC who underwent VUDS and received urological treatments at the hospital, including surgeries, minimally invasive therapies, and conservative management. The baseline VUDS parameters of patients who received different treatments were evaluated, and the treatment outcomes of the different treatment subgroups were compared. Results There were 29 male and 28 female patients with a mean age of 24.1 ± 15.9 years upon enrollment. Patients had dysuria or urinary retention (n = 42, 73.7%), urinary incontinence (n = 40, 70.2%), recurrent UTI (n = 35, 61.4%), hydronephrosis (n = 27, 47.4%), and vesicoureteral reflux (n = 26, 45.6%). VUDS revealed detrusor sphincter dyssynergia in 32 (56.1%) patients, bladder neck dysfunction in 13 (22.8%), and intrinsic sphincter deficiency in 20 (35.1%). Among them, 21 (36.8%) received surgical intervention, 17 (29.8%) minimally invasive therapy, and 19 (33.3%) conservative management. After a mean follow-up of 8.5 years, the incidence rates of recurrent UTI (61.4% vs 31.6%, p = 0.001), hydronephrosis (47.4% vs 14.0%, p < 0.0001), urinary incontinence (70.2% vs 35.1%, p < 0.0001), and vesicoureteral reflux (45.6% vs 21.1%, p < 0.001) decreased. The overall global response assessment rate was 73.7%, and patients who underwent surgery had the best rate (90.5%). The predictive value of bladder compliance for treatment selection was > 20.5 ml/cm H2O. Conclusion VUDS can be used to comprehensively assess lower and upper urinary tract dysfunction among patients with MMC. To improve NLUTD and prevent complications, minimally invasive therapies or surgical procedures should be recommended to patients with MMC who have low bladder compliance.
Port placement strategy using Xi surgical robot
Upper-tract urothelial carcinoma is a relatively rare malignancy. Current guidelines strongly recommend radical nephroureterectomy with bladder cuff excision and template-based lymph node dissection for all high-risk upper-tract urothelial carcinomas. Although the open approach is still considered the standard of care, evolution of minimally invasive approaches especially the robotic-assisted approach, has been found to be oncologically equivalent. Since its initial description in 2006, the surgical technique as well as the robotic surgical system has gone through a major evolution. With well-established advantages of the minimally invasive approach, robotic radical nephroureterectomy also has the ability to address both upper and lower urinary tract simultaneously without the need of patient repositioning, standardized single docking technique, ease of performing crucial steps like excision of ureterovesical junction and bladder cuff with watertight cystotomy closure, allowing perioperative instillation of intra-vesical chemotherapy. Robot-assisted radical nephro-ureterectomy and template-based lymph node dissection is gradually emerging as the current standard of care to achieve the best possible oncologic and functional outcomes. In this review article we are focusing on the evolution of this approach in the management of upper-tract urothelial carcinoma along with a review of oncologic outcomes.
Purpose The efficacy of the antioxidants vitamin E (VitE) and vitamin C (VitC) on male infertility is uncertain. Therefore, this research systematically assessed the influences of VitE and VitC on male infertility. Methods We did a meta-analysis of randomized controlled trials (RCTs) to analyze semen parameters, pregnancy rate, and adverse effects (AEs) between VitE and VitC groups and control groups by searching Cochrane Library, Excerpta Medica Database (Embase), PubMed, China Biology Medicine disc (CBMdisc), and Web of Science up to June 2020. Results We screened 11 studies (832 patients) that met the inclusion criteria. The evidence quality ranged from moderate to low. The pregnancy rate was obviously better in the VitE group than in the control group (relative risk (RR) 1.86, 95% confidence interval (CI) 1.02–3.41). Compared with the control group, VitE and VitC significantly improved progressive motility (standardized mean difference (SMD) 0.38, 95% CI 0.22–0.55), sperm concentration (SMD 0.21, 95% CI 0.09–0.34), sperm morphology (SMD 0.32, 95% CI 0.09–0.55), and total sperm number (SMD 0.28, 95% CI 0.12–0.43) without AEs. Conclusion This study suggests that VitC and VitE can improve the spousal pregnancy rate and semen parameters in infertile men without AEs.
a–d Intraoperative findings
Location of ureteral tumor
a, b Pathological results of endometriosis
a, b Cystography and postoperative CTU
Background This study was designed to evaluate the feasibility of laparoscopic ureteral reimplantation with a Boari flap for long-segment ureteric avulsion or ureteric strictures of the middle and lower ureters. By observing its curative effect and prognosis, we can provide a safer and reliable treatment option for patients with middle and lower ureteral injury. Methods In this study, of the eight cases under study, five were diagnosed with long-segment ureteric strictures, one had long-segment ureteric avulsion, one was diagnosed with ureteral rupture caused by surgical injury of appendicitis, and the remaining one underwent ureterostomy after ureteral injury. The location of ureteral injury was in the middle lower segment. All eight patients underwent laparoscopic ureteral reimplantation with a Boari flap from January 2018 to October 2021. In this study, two patients were treated with a Boari bladder flap with psoas hitching. All procedures were performed by the same surgeon with over 20 years of experience in urological surgery. Results The mean length of ureteric avulsion or ureteric strictures was 7.94 cm (range, 4–15 cm). Laparoscopic ureteral reimplantation with a Boari flap was performed successfully between 120 and 240 min. The mean duration of postoperative hospital stay was 6 days, and no major complications related to the procedure in the perioperative period occurred. Postoperative follow-up showed no obvious hydronephrosis on computed tomography urography or urinary ultrasound in all eight patients. Postoperative reexamination did not reveal any significant hydronephrosis, urinary tract infection, or ureteral reflux, and none of the postoperative renal functions were abnormal. Conclusions Laparoscopic ureteral reimplantation with a Boari flap is safe and feasible for experienced physicians. In our case, the length/width ratio of bladder flap is more than 4:1, with good blood supply and no obvious complications, it provides a longer alternative length.
Cumulative sum cohort analysis curve of complication rate (CR). Competency is reached after 13th case and proficiency is achieved by the 70th case
Introduction The learning curves for minimally invasive pyeloplasty techniques have been described in the past. However, the learning curve in achieving competency in open pyeloplasty has not been described. Hence, we aim to evaluate a single surgeon series of open pyeloplasty technique using the cumulative sum (CUSUM) methodology. Methods We retrospectively reviewed all open pyeloplasties performed by a single surgeon (AJL) between January 2008 and March 2020. Collected variables included: sex, age at surgery, operative time, hospital stay, pre-operative ultrasound, pre-operative nuclear scans, pre-operative anteroposterior diameter, associated anomalies, laterality (left or right), type of stent, pre-operative split renal function, and duration of follow-up. A CUSUM analysis was used: the highest peak, plateau and downward trends for complications (defined as Clavien–Dindo classification ≥ 3b) were identified on the plot and set as the transition points between five phases (learning, competency, proficiency, case-mix, and mastery). Results Based on the CUSUM analysis, the index surgeon reached the competency phase after performing their 13th open pyeloplasty and became proficient after the 70th case. In the case-mix phase (104th–126th cases), where the surgeon may be performing more complex cases while increasing trainee involvement, there was a slight increase in complication rates. After the 126th case, the surgeon entered the mastery phase, where there was consistent decreasing trend in complications. Conclusions Surgeons performing open pyeloplasty in children following completion of their surgical training will continue to learn through their early cases until achieving competency. Technical competency may be reached after the 13th case. Patient summary In this report, we looked at the number of cases to become proficient in open pyeloplasty procedure in children. A surgeon may achieve technical proficiency in the procedure after their 13th case.
Total testosterone levels according to timeline
Total testosterone variation levels at T0 × T1; T1 × T2; T0 × T2
Objective To evaluate total testosterone (TT) kinetics and its predictors 6 months after the discontinuation of clomiphene citrate (CC) in patients with hypogonadism. Materials and methods Consecutive patients with normal testicles and male hypogonadism defined by TT < 300 ng/dl in the presence of signs or symptoms according to the previous consensus were prospectively evaluated in a urologic outpatient clinic by TT levels at baseline (T0), after a daily dose of 50 mg CC for 40 days (T1), and after the washout period of 6 months of CC discontinuation (T2). Results Among 75 patients, mean age 56.8 years, testosterone at T1 > 300 ng/dl was achieved by 69 (92%), 450–600 ng/dl by 32 (42.6%), and > 600 ng/dl by 27 (36.0%). 18 subjects (24%) maintained asymptomatic and TT levels over 300 ng/dl at T2. Age negatively related to testosterone response and T1 response > 810 ng/dl predicts a median gain of 166.5 ng/dl at 6 months of CC discontinuation. Conclusions CC is a compelling option to treat male hypogonadism, although a chronic treatment is needed in most patients. About one in every four patients respond to a CC short trial to "reboot" the physiology. Further understanding of TT kinetics in these patients in the long term is warranted.
Holographic images of right renal hilar tumor (A anterior view of kidney and renal hilar tumor; B anterior view, kidney erased to clearly demonstrate the tumor and renal artery/vein, collecting system and their relationship with the tumor; C posterior view of kidney and renal hilar tumor; D posterior view, kidney erased to clearly demonstrate the tumor and renal artery/vein, collecting system and their relationship with the tumor)
Real-time navigation with holographic image during RAPN (A the operation room set-up with the NAVIGATOR workstation besides the surgeon console. B TilePro multi-input screen displays the real-time endoscopic view in the upper part and integrated holographic image with the real-time endoscopic view and intracorporeal ultrasound images in the lower part. C The navigation image showed the integrated images with renal artery and vein. D The navigation image showed the supplemental tumor artery after the renal tumor erased on holographic image
A Holographic image showing the renal tumor, renal vein, upper pole artery branch and ureter. B After the renal tumor was erased, the underlying renal artery and its branches were clearly shown on holographic image. The simulation of clamping the renal artery branches to the tumor bed are shown as well. C and D The tumor bed artery branches corresponding to the simulation, clipped outside the kidney with Hem-o-lok clips
Objectives To evaluate the clinical value of the holographic imaging technology in combination with robotic-assisted partial nephrectomy (RAPN) for renal hilar tumor treatment. Patients and methods From Dec. 2018 to Dec. 2021, patients diagnosed with renal hilar tumor were included in this retrospective study. Before the surgery, the engineers established the holographic image models based on the enhanced CT data. The models were used in patient consultation, pre-surgery planning and surgery simulation. During the RAPN, the navigation was achieved by real-time overlapping of the holographic images on the robotic surgery endoscopic views. The navigation technique helped the surgeon to identify the important anatomic structures such as tumor, renal vein, renal artery, and pelvis. Results There were total of eight patients with renal hilar tumor who underwent RAPN combined with holographic imaging technique. The mean age was 57.3 years, the median ASA score was 2. The mean tumor size was 42.4 mm and the median RENAL Nephrometry score was 9.5. The clinical stages were cT1a (37.5%) and cT1b (62.5%). All the procedures were performed uneventfully by one surgeon. The mean operative time was 144.3 min, and the mean warm ischemia time was 27.9 min. The mean estimated blood loss was 86.3 ml. There was no conversion to open surgery or radical nephrectomy. There were no Clavien–Dindo ≥ 3 perioperative complications. Conclusions Using the holographic imaging technique, the pre-surgery planning, simulation of renal arterial clamp and excision of the tumor, and intraoperative navigation were feasible and helpful in facilitating RAPN.
Flow chart of the participants in the study
Receiver operating characteristics (ROC) curve of ACR, TC/HDL-C and combined predictor in differentiation of CKD progression
Purpose Although dyslipidemia can cause kidney damage, whether it independently contributes to the progression of chronic kidney disease (CKD) remains controversial. The research aims to evaluate the predictive value of serum lipids and their ratios in the progression of CKD. Methods The retrospective, case–control study included 380 adult subjects with CKD stage 3–4 (G3-4) at baseline. The end point of follow-up was the progression of CKD, defined as a composite of renal function rapid decline [an annual estimated glomerular filtration rate (eGFR) decline > 5 mL/min/1.73 m²] or the new-onset end-stage renal disease (ESRD) [eGFR < 15 mL/min/1.73 m²]. Logistic regression analysis was performed to examine the association between CKD progression and lipid parameters. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive power of lipid parameters in the progression of CKD. Results Over a median follow-up of 3.0 years, 96 participants (25.3%) developed CKD progression. In multivariable logistic regression analysis, logarithm-transformed urinary albumin-to-creatinine ratio (log ACR) [odds ratio (OR) 1.834;95% confidence interval (CI) 1.253–2.685; P = 0.002] and total cholesterol to high-density lipoprotein cholesterol ratio (TC/HDL-C) [OR 1.345; 95% CI 1.079–1.677; P = 0.008] were independently associated with CKD progression. The ROC curve showed the combined predictor of ACR and TC/HDL-C ratio was acceptable for CKD progression diagnosis (area under the ROC curve [AUC] = 0.716, sensitivity 50.0%, specificity 84.2%), and the cut-off value was − 0.98. Conclusions The combination of TC/HDL-C ratio and ACR had predictive value in the progression of CKD, and may help identify the high-risk population with CKD.
Flow chart of patients enrolled. Patients selected for coronary angiography were those with angina, altered myocardial scan and 2 or more major cardiovascular risk factors
Cumulative survival free of myocardial infarction of patients who underwent and did not undergo coronary angiography
Cumulative survival free of myocardial infarction of patients with and without significant CAD
Cumulative survival of patients with myocardial infarction dying of myocardial infarction or by other causes
Cumulative survival of patients with myocardial infarction treated either by early coronary intervention or medically
Background The incidence of myocardial infarction (MI) is elevated in patients receiving renal replacement therapy (RRT). We hypothesized that an invasive strategy of assessment of coronary artery disease (CAD) will identify patients more prone to developing MI. Methods This was a single-center observational cohort study that included 1678 patients receiving RRT (hemodialysis and renal transplantation) assessed for CAD prospectively and analyzed retrospectively. Endpoints were the incidence of MI and death. Results The median follow-up was 43 months, and 180 patients experienced an MI with a mortality rate of 74%. Multivariate analysis showed that diabetes (HR 1.633; 95% CI 1.165–2.289), prior MI (HR 1.724; 95% CI 1.153–2.579), and CAD (HR 2.073; 95% CI 1.400–3.071) were predictors of MI. Altered myocardial scan did not correlate with MI. At the discretion of the attending physicians, 20/180 patients (11%) underwent coronary intervention that was associated with a higher cumulative survival (Log-rank 0.007). Conclusion Patients with CAD suffered an MI more frequently, independently of symptoms and risk factors for MI, including noninvasive testing. Because of the elevated rate of the lethality of MI, invasive coronary studies may be indicated in select patients on RRT. Once an MI occurs, our data suggest that an invasive therapeutic approach is warranted.
Study flow diagram. AKI acute kidney injury, ICU intensive care unit
Gating strategy for M1 and M2 Macrophages (A) and B cells (B)
Flow cytometry of B cells. Percentage of B cells of all patients (A) and stratified according to renal recovery status (B). D0, day 0; D2, day 2 of acute kidney injury
Flow cytometry of urinary mononuclear phagocytic cells (MPCs). Percentage of MPCs of all patients (A) and stratified according to renal recovery status (B). Percentage of subtypes of MPCs is shown subsequently: M1 macrophages (C), M2 macrophages (D) and dendritic cells (E) according to renal recovery status. D0 day 0, D2 day 2 of acute kidney injury
Purpose Cellular mechanisms involved in human renal recovery after an episode of acute kidney injury (AKI) are understudied. We aim to characterize the urinary immune cell phenotype of patients with AKI and evaluate its ability to predict renal recovery. Methods A prospective study of critically ill patients with stage ≥ 2 AKI by KDIGO and sterile leukocyturia at admission was performed. Urine samples were collected fresh at day 0 and 2 and samples were analyzed by flow cytometry for different leukocytes. Patients were categorized in renal recovery or no-recovery groups. Results 28 patients were included, all with sepsis, 60.7% of which recovered renal function. The main urinary leukocytes present were neutrophils, followed by mononuclear phagocytic cells and B cells. Patients who recovered renal function had more M2 macrophages at day 2 (p = 0.043) and less B cells at admission (p = 0.006). M2 macrophages had an AUC-ROC of 0.796 (0.601–0.990) for recovery prediction and B cells an AUC-ROC of 0.743 (0.560–0.926) for no recovery. B regulatory cells were found in the urine of AKI patients. Conclusions The urinary immune cell phenotype of severe AKI patients was composed essentially of neutrophils, mononuclear phagocytic cells and B cells. Our data suggest that M2 macrophages may promote and B cells preclude renal recovery. More studies are needed to validate our results and further explore the role of immune cells in renal recovery.
a Distribution of chronicity index with lupus classes. b Distribution of activity index with lupus classes
a Kaplan–Meier curve for complete renal response with baseline activity index. b Kaplan–Meier curve for complete renal response with baseline chronicity index. c Kaplan–Meier curve for complete renal response based on immunosuppression regimens. d Kaplan–Meier curve for complete renal response based on lupus class
Introduction Early response to therapy is associated with favourable long-term outcome in LN. The working group of revision of ISN/RPS classification guidelines for LN recommended modified National Institute of Health (NIH) activity and chronicity scoring system to evaluate active and chronic lesions. Data on usefulness of modified NIH scoring system to determine complete renal response (CR) in LN are sparse. Methods We retrospectively studied 80 LN patients diagnosed from June/2018 to April/2020, who has followed up for more ≥ 6 months in our hospital. CR was defined by inactive urinary sediment, urine PCR of 0.5 g/g in a 24 h urine collection and normalization/stabilization of renal function. Pathologic lesions were described as per revised 2018 ISN/RPS classification and the modified NIH scoring system. Patients were grouped by AI (low, 0–5; moderate, 6–11; high, 12–24) and CI (low, 0–2; moderate, 3–5; high, 6–12). Time to event was analysed using Kaplan–Meier curves. Prognostic variables for CR were analysed by multivariable Cox proportional hazard models. Results With a median follow-up of 8 months, 50 patients (62.5%) achieved CR. Kaplan–Meier curves showed lower CR with high AI groups (p value = 0.001) and moderate/high CI groups (p value < 0.001). Moderate and high CI with HR of 0.088 (0.034–0.229) p value < 0.001 and Glomerulosclerosis Score with HR of 0.155 (0.072–0.331) p value < 0.001 were significant determinant of CR. Conclusion Moderate and high CI scores were associated with lower chances of CR in LN. Glomerulosclerosis of CI was significant determinant of CR.
Purpose Difficulties in sexual functioning are very frequent in patients with chronic kidney disease (CKD). Sexual dysfunction (SD) can significantly diminish the quality of life (QOL) of affected individuals. The aim of this study was to determine the prevalence of SD in female patients undergoing chronic hemodialysis (CHD) and after renal transplantation (RTx) and to compare these groups with each other and with healthy control. Methods The survey was conducted among 123 female participants in a relationship, 28 of them undergoing CHD, 39 after RTx, and 56 healthy women without CKD. For the assessment of the sexual function and comorbidities, the Female Sexual Function Index (FSFI) questionnaire and Ifudu Comorbidity Index were used, respectively. Results Median age of all female participants was 60 (50–68). The median age of female CHD patients was 66 (61.3–72.8), RTx patients 56 (48–61), and the control group 59.5 (47.5–67.75). Among all participants, CHD female patients had the lowest scores in all sexual functioning domains. Compared to their age-adjusted control group, CHD patients had lower scores in desire, orgasm, and FSFI full score, whereas RTx patients had lower total FSFI scores and scores in all domains except for desire compared to their controls. Women with lower education, in marriage, and with more comorbidities had lower scores in sexual function domains. Conclusion Our study shows that SD in female patients undergoing CHD treatment or those after RTx is substantially higher than that in healthy women. We suggest that female patient treated for CKD should have proper care regarding their sexual health, and differences in demographic and medical factors should be taken into consideration during the treatment management.
Molecular effects of Mg²⁺ in renal fibrosis. Mg²⁺ promotes the expression of TRPM7 (cation channel, top left), leading to an increased level of intracellular Mg²⁺ and inhibition of Nrf2 activation by PI3K/Akt and PKC. Mg²⁺ also promotes the secretion of klotho protein and inhibits the TLR-4/NF-κB signaling pathway. This reduces the activation and nuclear translocation of NF-κB, thus reducing the production of inflammatory cytokines that are related to fibrosis. Mg²⁺ also inhibits the L-type calcium channel (top right), leading to a decreased intracellular concentration of Ca²⁺ and decreased production of reactive oxygen species. This inhibits fibrosis pathways (such as TGF-β/Smad2/3 and MAPK signaling). Mg²⁺ can also reduce the accumulation of BAX on the mitochondrial membrane, reduce the activity of the caspase cascade, and regulate cell apoptosis, thereby reducing fibrosis
Purpose Renal fibrosis (RF) is the main pathological feature of chronic kidney disease (CKD). The main focus of research on treatment for CKD is to develop strategies that delay or prevent RF from progressing to end-stage renal disease (ESRD). Inflammation and oxidative stress occur during all stages of CKD. The magnesium cation (Mg²⁺) can reduce inflammation and oxidative stress, regulate apoptosis, and improve RF, and magnesium-based therapies are promising new treatments that can prevent RF. We reviewed the current evidence on the effects of magnesium in RF and examined the possible mechanism of magnesium in delaying RF. Methods We searched PubMed, Web of Science, and EMBASE for articles on magnesium and fibrosis, with a focus on magnesium and RF. Results Inflammation, oxidative stress, and apoptosis are related to the occurrence of CKD. Previous research showed that Mg²⁺ inhibits the differentiation of inflammatory cells, down-regulates the production of inflammatory cytokines, reduces inflammation, and reduces the production of reactive oxygen species (ROS) and oxidative stress. In addition, Mg²⁺ also regulates apoptosis and protects renal tubular function. Magnesium may also regulate TRPM6/7, promote the secretion of klotho protein and improve renal fibrosis. Therefore, Mg²⁺ can protect the kidney from damage and slow down the progression of RF through many molecular and cellular effects. Some of the anti-fibrotic effects of Mg²⁺ may be related to its antagonism of intracellular Ca²⁺. Conclusion Magnesium may prevent the progression of renal fibrosis and delay CKD by reducing renal inflammation and oxidative stress, and by regulating fibrosis-related signaling pathways and cytokines.
Number and proportion of ePRT cases per year 2010–2018
a Graft survival estimates by GFR groups—all donor. b Graft survival estimates by GFR groups—live vs deceased donor
a Patient survival estimates for preemptive renal transplants at all GFR groups and all types of donors. b Patient survival estimates by GFR groups—live vs deceased donor
Geographic distribution of ePRTs
Background: Preemptive renal transplants (PRT) confer better outcomes than renal transplants performed after initiation of hemodialysis. PRTs are occurring at progressively higher residual recipient renal function. Methods: We evaluated donor, recipient, and transplant characteristics of 26,384 preemptive transplants between 2010 and 2019 using the United Network of Organ Sharing (UNOS) database. Recipients of PRTs were divided into four distinct groups depending upon the glomerular filtration rate (GFR) (GFR [Formula: see text] 10, 10 < GFR [Formula: see text] 15, 15 < GFR [Formula: see text] 19 and > 19, ml/min/1.73 m2) at the time of transplant. We followed graft and patient survival for five years and assessed donor, recipient, and transplant characteristics such as race, gender, and type of insurance. Results: PRTs occurring at GFR > 19 ml/min (early preemptive renal transplants, ePRT) from live and deceased donors were not associated with improved graft nor patient survival compared to the other preemptive transplants. PRTs occurring at GFR range of 10-15 ml/min conferred the best graft survival. Black donor-recipient pairs were 54% less likely to be involved in ePRT, while non-Hispanic White donor-recipient pairs were 20% more likely to receive ePRT. Conclusion: ePRT represents misallocation of valuable organ resources and a waste of native renal function. There is no evidence that ePRT is associated with superior graft or patient survival compared to the other preemptive transplants. Conversely, ePRT produces poorer graft and patient survival outcomes compared to the other PRTs. GFR range of 10-15 ml/min is optimal and associated with superior outcomes.
Genetic and environmental factors influencing the risk of IgA nephropathy (IgAN) and how such factors may interact
The interactions of gene, inflammations and change of immune status in the pathogenesis of IgAN
The International IgA nephropathy prediction tool, integrating environmental, clinical and pathological factors
IgA nephropathy (IgAN) is the usual form of glomerulonephritis worldwide; however, the pathogenesis remains complex and uncertain. The interactions of gene, immune and environment lead to the variability of IgAN clinical presentations. Except for gene, it is still a question that what kind of the external factors that may cause IgAN. We summarized exposome, microbiome and infectome may be involved in the pathogenesis of IgAN through literature. Based on the above discoveries, we proposed a hypothesis of the course of IgAN that gene determines the internal cause, while skin and mucosa inflammations are the conditions of inducing immune disorders, the low point of immune disorders and change of immune status caused by internal and external environment lead to the disease onset. Therefore, a more detailed clinical phemomics of IgAN was required to be collected for further study.
Flowchart of patients in this study
Cumulative incidence of end-stage kidney disease in all patients with type 2 diabetes according to the presence of metabolic syndrome (A), or according to the number of metabolic syndrome components (B)
Purpose To investigate the prognostic value of metabolic syndrome (MetS) and its relationship with renal structure changes in patients with type 2 diabetes and associated diabetic nephropathy (DN). Methods 411 Chinese patients with type 2 diabetes and biopsy-confirmed DN were enrolled in this retrospective study. MetS was defined according to the modified criteria of the 2005 International Diabetes Federation. Baseline demographics and clinical information at the time of renal biopsy were extracted from the hospital’s electronic medical records system. Renal pathological findings were assessed according to Renal Pathology Society system. Univariate and multivariate logistic regression analyses were performed to define the pathological covariates associated with MetS. A competing risk model, with death as the competing risk, was used to estimate the sub-distribution hazard ratio (SHR) of MetS for end-stage kidney disease (ESKD). Results 224 (55%) patients had MetS. Patients with MetS had poor renal function and more severe interstitial fibrosis tubular atrophy scores (IFTA) than those without MetS. Multivariate logistic regression analysis revealed that IFTA was significantly associated with MetS (odds ratio per score increase 1.45, 95% confidence interval [CI] 1.02–2.05). Of the patients with DN at risk, 40% of patients progressed to ESKD. After adjusting for renal function and pathological parameters, the presence of MetS was an independent predictor for progression to ESKD (SHR 1.93, 95% CI 1.34–2.79). The SHRs for progression to ESKD also increased as the number of MetS components increased. Additionally, adding the IFTA scores improved the prognostic power of a model that only contained MetS and clinical covariates for predicting future ESKD. Conclusion MetS is an independent prognostic predictor of ESKD in patients with T2D and DN, while adding the IFTA scores increased the prognostic value of MetS for renal outcome.
Associations of physical activity at starting point and its trajectory over time with all-cause mortality. Cox proportional-hazards regression with restricted cubic splines (with three knots) demonstrates the association of physical activity at starting point (A) and its change (B) with all-cause death. Each model is adjusted for age, sex, body mass index, dialysis vintage, atherosclerotic heart disease, congestive heart failure, comorbidity index score, and hemoglobin level. The hazard ratio is represented by solid lines and 95% confidence intervals by shaded areas
Joint association of physical activity at starting point and its trajectory with clinical outcomes; all-cause death (A), cardiovascular events (B). Patients are classified into four groups based on the combination of physical activity at starting point (< 4000 or ≥ 4000 steps per day) and its change over time (< + 46 or ≥  + 46 steps per day). Cox proportional-hazards regression and Fine–Gray proportional sub-distribution hazards models are used to examine the joint association of physical activity at starting point and its trajectory with clinical outcomes. Each model is adjusted for age, sex, BMI, dialysis vintage, atherosclerotic heart disease, congestive heart failure, comorbidity index score, hemoglobin, serum albumin, and C-reactive protein levels. BMI body mass index, HR hazard ratio, SHR sub-distribution hazard ratio
PurposeWe examined whether physical activity measured at starting point and its trajectory over time were simultaneously associated with vital prognosis.Methods This retrospective cohort study included 295 ambulatory maintenance hemodialysis patients (mean age 63.9 years; 54.6% male). We measured physical activity at index date (starting point) and its change over 1 year as predictors, and all-cause death and cardiovascular events were assessed as the outcomes. Two groups each of high versus low physical activity at starting point (based on 4000 steps per day) and no decline versus decline (based on a predicted mean slope) were created. Cox proportional-hazards regression and Fine–Gray proportional sub-distribution hazards model were used to examine associations between physical activity and its trajectory and clinical outcomes.ResultsDecline in physical activity over 1 year was associated with a higher risk of all-cause death and cardiovascular events, irrespective of the physical activity at starting point. Furthermore, both lower physical activity at starting point and decrease in physical activity over time were independently associated with a higher risk of all-cause death and cardiovascular events in models in which each exposure was mutually adjusted. Compared to other groups that worsened in either exposure, the lowest risk for death/cardiovascular events was observed in the high at starting point/no decline over time group.Conclusions Both physical activity at starting point and its change over time were independently associated with vital prognosis. The assessment of both exposures provides additional prognostic information for the assessment of each exposure.
Survival between patients with and without calcified cerebral medial arteries. ACM middle cerebral arteries
Purpose We have analyzed markers of accelerated atherosclerosis like large artery stiffness, ankle-brachial index, carotid and vertebral duplex ultrasonography and their possible associations with the incidence of intracranial calcifications, clinical course of hemodialyzed patients, and cardiovascular mortality. Methods A computed tomographic scan of the head was performed for any neurological indication on 100 hemodialyzed patients. Eleven intracranial arteries were analyzed for calcification score, while internal carotid arteries and vertebral arteries were excluded in cerebral artery calcification score. As a control group for assessing intracranial calcifications, we have analyzed computed tomographic scans from diabetic patients who had an acute stroke. Results Deceased patients had significantly higher values of augmentation index and pulse wave velocity, lower ankle-brachial index, and higher internal carotid arteries peak systolic value than survived patients. Deceased patients had significantly higher number of calcified middle cerebral arteries as well as significantly higher intracranial artery calcification score and cerebral artery calcification score. Hemodialyzed patients had significantly higher both intracranial and cerebral artery calcification scores than diabetic control group. Age and calcified middle cerebral arteries had increased HR of 1.08 and 1.36 for cardiovascular mortality. Conclusion This study showed that large artery stiffness and not the presence of peripheral arterial disease or carotid artery stenosis have the prognostic role of middle cerebral arteries’ calcifications and cardiovascular mortality in hemodialyzed patients. The presence of middle cerebral arteries’ calcifications diagnosed by a non-invasive method should be considered a marker of middle-sized conduit arteries atherosclerosis, subclinical brain damage, and future fatal cardiovascular events.
A Example of computed tomography image analysis and lumbar skeletal muscles measurement as highlighted in red using OsiriX Lite; and B Semi-diagrammatic matrix highlights correlated variables between L3 skeletal muscle index (SMI) with height, weight, body mass index (BMI), total muscle cross-sectional area in cm² (TMCA) and mean muscle attenuation (MA) of the total muscle cross-sectional area (Hounsfield units). Positive correlations are displayed in blue; while negative correlations in red. The color intensity and the size of the circle are proportional to the correlation coefficients
Early hospital readmission probability curves where patients were stratified according to the presence or absence of low muscle mass as defined by radiological measures. Patients with low muscle mass had a greater risk of early hospital readmission following kidney transplantation (Frailty model aHR = 4.24, 95% CI 1.40–12.90, p = 0.01)
Purpose Patients exhibiting features of frailty and sarcopenia increasingly are presenting for kidney transplantation (KT) assessment. Sarcopenia, when ascertained by radiological measures, is associated with a higher transplant waiting list mortality; but studies on post-operative outcomes are lacking. We aimed to determine the clinical significance of low muscle mass in chronic kidney disease (CKD) patients subsequently receiving KT. Methods We retrospectively analyzed 63 patients with Stage 4–5 CKD who, between 2012 and 2020, had undergone abdominal computed tomography (CT) scanning up to 2 years before KT. The degree of skeletal muscle loss was assessed using the total cross-sectional skeletal muscle area at the third lumbar vertebral level (L3). Cox proportional-hazards regression and Frailty models were used to identify risk factors for early hospital readmission post KT. Results Thirty-four patients (54%) displayed low muscle mass, which was independently associated with a lower serum creatinine and phosphate, lower body mass index, lower mean muscle attenuation of the L3 cross-sectional area, and higher serum parathyroid hormone (for all p < 0.05). Deceased donor transplant recipients (n = 45) with low muscle mass demonstrated greater hospital readmissions within 30 days of KT [adjusted hazard ratio (HR) = 4.24, 95% CI 1.40–12.90, p = 0.01]. Conclusion Low muscle mass is highly prevalent in the pre-transplant CKD population and is associated with increased hospital readmission in the early post-transplant period.
Study flow diagram. A Flowchart of all the participants. B Flowchart of the subgroup analysis. AKI acute kidney injury, ICU intensive care unit
30-day mortality of new-onset AKI patients and matched non-AKI controls. A New-onset AKI patients subgrouped according to the duration of kidney injury compared to the controls. B New-onset AKI patients subgrouped according to the severity of kidney injury compared to the controls. AKI acute kidney injury
Purpose This study aimed to evaluate the attributable mortality of new-onset acute kidney injury (AKI). Methods The data in the present study were derived from a multi-center, prospective cohort study in China that was performed at 18 Chinese ICUs. A propensity-matched analysis was performed between matched patients with and without AKI selected from all eligible patients to estimate the attributable mortality of new-onset AKI. Results A total of 2872 critically ill adult patients were eligible. The incidence of new-onset AKI was 29.1% (n = 837). After propensity score matching, 788 patients with AKI were matched 1:1 with 788 controls (patients without AKI). Thirty-day mortality was significantly higher among the patients with AKI than among their matched controls (25.5% versus 17.4%, p < 0.001). Subgroup analysis in terms of AKI classification showed that there was no significant difference (p = 0.509) in 30-day mortality between patients with stage 1 AKI and their matched controls. The attributable mortality values of stage 2 and stage 3 AKI were 12.4% [95% confidence interval (CI) 2.6–21.8%, p = 0.013] and 16.1% (95% CI 8.2–23.8%, p < 0.001), respectively. The attributable mortality of persistent AKI was 15.7% (95% CI 8.8–22.4%, p = 0.001), while no observable difference in 30-day mortality was identified between transient AKI patients and their matched non-AKI controls (p = 0.229). Conclusion The absolute excess 30-day mortality that is statistically attributable to new-onset AKI is substantial (8.1%) among general ICU patients. However, neither stage 1 AKI nor transient AKI increases 30-day mortality.
Division of study population in risk groups and distribution of outcomes (deaths and dialysis) in each group
Kaplan–Meier survival analysis
Background Risk assessment tools for predicting mortality and end-stage renal disease (ESRD) in the elderly with CKD have received growing attention. However, integrating risk equations into a multidimensional approach of elderly with CKD stage 3b-4 is lacking. Methods In this prospective observational study, we enrolled CKD stage 3b-4 patients aged ≥ 65 years. Bansal score for predicting mortality risk and Kidney Failure Risk Equation (KFRE) for estimating progression to ESRD were applied. Predicted outcome was compared with actual clinical end-points. All patients underwent comprehensive geriatric assessment (CGA), which is an interdisciplinary multidimensional process for geriatric evaluation and management. Results Participants (N = 184) were divided into two groups, according to Bansal score: Group 1 (low-risk of death, Bansal score < 7, N = 69) and Group 2 (high-risk of death, Bansal score ≥ 7, N = 115). Group 2 displayed a substantially higher cardiovascular disease burden than Group 1 and was significantly more likely to be depressed and at risk of malnutrition, according to CGA. Thirty-seven patients died, and 16 started dialysis. Group 2 displayed significantly higher all-cause mortality. In the univariable Cox regression, Group 2 had a fourfold increase in the risk of all-cause mortality, as compared with Group 1 (HR = 4.29, 95% CI 1.88–10.26, P < 0.001). Multivariable stepwise Cox analysis showed that Bansal score above 7 remained significantly associated with all-cause mortality (HR = 3.96, 95% CI 1.68–9.29, P < 0.001). Group 2 also displayed higher event rates for dialysis initiation. In Group 1, only four patients started dialysis, and three out of them had a high-risk of progression at baseline, according to KFRE. Conclusions Using risk stratification tools and CGA in a population of elderly with advanced CKD, we found that two-thirds of the patients were at high risk of death, malnutrition and depression, with multimorbidity and four times worse probability of survival than those at lower risk of death.
Purpose A previous immunofluorescent study suggests that, in collapsing glomerulopathy, most hyperplastic podocytes that stained positively for a progenitor cell marker CD133 are derived from CD133 + parietal epithelial cells. In pathology practice, not all renal biopsies with collapsing glomerulopathy show the typical morphologic features for this entity, which include florid podocyte hyperplasia, collapsing glomerular capillary loops, and cystic tubular dilation. This study was made to determine if CD133 staining using an immunohistochemical method can be used to confirm hyperplastic podocytes and identify extensive acute tubular injury in collapsing glomerulopathy. Methods Twenty-one collapsing glomerulopathy biopsies were stained for CD133 and compared with 15 biopsies with focal segmental glomerulosclerosis, not otherwise specified (FSGS). Results All patients with collapsing glomerulopathy were of African American descent with prominent renal failure and nephrotic range proteinuria. In contrast, the FSGS group consisted of patients from a variety of ethnic backgrounds with nephrotic range proteinuria but relatively low serum creatinine. The striking finding was that all collapsing glomerulopathy cases showed positive CD133 staining in the clusters of hyperplastic podocytes. There was significantly higher CD133-positive staining rate for hyperplastic podocytes (38%) in the glomeruli of the collapsing glomerulopathy group when compared to small clusters of hyperplastic podocytes in the FSGS group (8%). In addition, when compared to the relatively weak CD133 staining in the proximal tubules of the FSGS group, the proximal tubules of the collapsing glomerulopathy group all showed diffuse and strong CD133 staining as a feature of severe acute tubular injury, which corresponded to the high serum creatinine levels in these patients. Conclusion Our data indicate that the combination of the distinctive mosaic CD133 staining in hyperplastic podocytes and the diffuse tubular CD133 staining is helpful in supporting a diagnosis of collapsing glomerulopathy.
A Principal Co-ordinate Analysis (PCO) of the microbiome profiles for multiple patients. B Principal Co-ordinate Analysis (PCO) of the microbiome profiles for drug treatments (calcium acetate versus sucroferric oxyhydroxide)
Clustering analysis and microbiome profiles (at genus level) for the samples considered in this study
Purpose It has been proved that the gut microbiome is altered in patients with chronic kidney disease. This contributes to chronic inflammation and increases cardiovascular risk and mortality, especially in those undergoing hemodialysis. Phosphate binders may potentially induce changes in their microbiome. This trial aimed to compare the changes in the gut microbiome of hemodialysis patients treated with calcium acetate to those treated with sucroferric oxyhydroxide. Methods Twelve hemodialysis patients were distributed to receive calcium acetate or sucroferric oxyhydroxide for 5 months. Blood samples (for biochemical analysis) and stool samples (for microbiome analysis) were collected at baseline, 4, 12, and 20 weeks after treatment initiation. Fecal DNA was extracted and a 16S rRNA sequencing library was constructed targeting the V3 and V4 hypervariable regions. Results Regarding clinical variables and laboratory parameters, no statistically significant differences were observed between calcium acetate or sucroferric oxyhydroxide groups. When analyzing stool samples, we found that all patients were different ( p = 0.001) among themselves and these differences were kept along the 20 weeks of treatment. The clustering analysis in microbial profiles grouped the samples of the same patient independently of the treatment followed and the stage of the treatment. Conclusion These results suggest that a 5-month treatment with either calcium acetate or sucroferric oxyhydroxide did not modify baseline diversity or baseline bacterial composition in hemodialysis patients, also about the high-variability profiles of the gut microbiome found among these patients.
Error bars of SARS-CoV-2 IgG antibodies showing the means and respective 95% CI over 4 measurement cycles on long-term follow-up in 24 hemodialysis patients, one way ANOVA p <  = 0.001 with the exceptions of comparisons between the second and third measurements (p = 0.065) and between the third and fourth measurement (p = 0.120)
Long-term evolution of SARS-CoV-2 IgG antibodies in AU/ mL and the respective neutralizing effect in 24 patients on hemodi- alysis
Purpose The predictive value of antibody titers after the first SARS-CoV-2 vaccination and long-term trajectories of antibody titers in hemodialysis patients are unknown. Methods SARS-CoV-2 IgG antibodies and their neutralizing effect six weeks after the first and second vaccination were analysed in 30 hemodialysis patients. IgG titers served to classify participants as responders or non-responders and to calculate sensitivity, specificity, and accuracy. Associations between potential risk factors and post-vaccine non-response were analysed by Mann–Whitney- U test and Chi-Squared test. Long-term follow-up analysis (ANOVA) on the evolution of neutralizing IgG-titers was performed in 24 participants 94 and 135 days after the second immunization. Results IgG antibodies ≥ 1 AU/L (mean 9 ± 20 AU/L) after the first dose were found in 20 patients (66.7%). After the second dose only two participants (6.7%) remained sero-negative and 16.6% showed neutralizing levels below 30%, whereas 25 patients showed IgG antibodies with the high neutralizing activity of 86 ± 18%. Positive IgG antibodies 6 weeks after the first vaccination predicted vaccination effectiveness after two cycles with a specificity of 100%, sensitivity of 76%, and accuracy of 87%. Even low-dose immunosuppressive therapy increased the relative risk for non-response after the first and second dose 1.9 (95% CI 0.8–4.6) and 4.9 (95% CI 1.0–23.8) times, respectively. Over a period of about 4.5 months IgG titers slowly declined by 51% from baseline or by 0.45 AU/mL per day, respectively. Conclusion Two cycles of SARS-CoV-2 vaccination-induced high seroconversion rates comparable to the general population. Immunosuppressive medication is a major risk factor for vaccination non-response. Mounted IgG antibodies showed a high neutralizing capacity as evidence of protective effectiveness. IgG antibodies after the first dose may serve to predict later vaccination outcome. Patients on dialysis display a more rapid decline in antibody titers on long-term follow-up compared to healthy controls.
Benefits of intradialytic ONS. Benefits of oral nutritional supplementation during dialysis and indications on how to ingest the supplement, based on the main questions of hemodialysis patients
Mean quality of life score at baseline and after 3 months of intradialytic ONS in HD patients diagnosed with PEW. The QoL data are shown descriptively as the mean and standard error of score [0–100], whereby 100 indicates a better QoL. T tests for paired samples or Mann–Whitney U were used to compare data at baseline and 3 months. *Significantly different versus baseline status (P < 0.05)
Purpose The study assessed the impact of intradialytic oral nutritional supplementation on the quality of life in patients receiving hemodialysis and diagnosed with protein energy wasting. Methods A pre-test post-test quasi-experimental study was conducted before and after 3 months of intradialytic oral nutritional supplementation on 109 older hemodialysis patients. We measured before and after 3 months of intradialytic oral nutritional supplementation, the quality of life score, the burden of kidney disease, three quality of life scales and the mental and physical health status using KDQoL-SF™ 1.3, body composition and biochemical parameters of nutritional condition. Results The mean age of the patients was 69.4 ± 3.4 years, 59% were male, and the time on dialysis was 63.5 ± 52.6 months. Comparing the baseline with month 3 of intradialytic oral nutritional supplementation, we observed to better quality of life. In contrast to malnutrition, score, specifically increased significantly score of symptoms/problems list related to hemodialysis, sexual function, social and cognitive function, sleep, pain, energy/fatigue and general state of health. Significant changes were also found in nutritional status, energy intake and body composition indicators. After 3 months of intradialytic oral nutritional supplementation, we observed a nutritional status recovery in one or more indicators in 92% of the patients . Conclusion Our findings indicate that 3 months of intradialysis oral nutritional supplementation improves the components of physical and mental quality of life and nutritional status in older patients receiving hemodialysis diagnosed with loss of protein energy. These results are relevant to improve the experience of patients with protein energy loss receiving hemodialysis.
PurposeTo determine the ratio of renal disease necessitating immunosuppressive treatment in lupus patients who are clinically asymptomatic by means of renal disease. It was also examined whether silent lupus nephritis is associated with any of the non-renal clinical findings.Methods All kidney biopsies performed in lupus patients between 1990 and 2009 at the Rheumatology Department of Ege University Faculty of Medicine were retrospectively screened. Among the 258 kidney biopsies screened, 54 had no clinical renal findings but had active disease together with anti-dsDNA positivity and/or hypocomplementemia. Patients were classified into two groups who require and do not require immunosuppressive therapy according to their final pathological results at biopsy. The frequency of serious renal involvement in the sample was calculated. Then subgroups were compared with each other in terms of the clinical and laboratory features using Statistical Package for Social Sciences version 13 software.ResultsThirteen of the 54 patients (24%) had severe renal involvement requiring immunosuppressant therapy. When the groups were compared to each other, it was found that serositis and hematologic involvement were significantly more frequent in patients who needed immunosuppressive treatment (42.9% versus 10.0%; p = 0.003 and 64.3% versus 37.5; p = 0.039).Conclusion Even in the absence of clinical renal manifestations, active patients at high risk of renal disease such as hypocomplementemia, anti-ds DNA positivity may have severe renal disease requiring immunosuppressive treatment. Thus, renal biopsy indications in lupus patients should better be revaluated.
PurposeTo compare clinical, pathological, and long-term renal outcomes of children with Henoch–Schonlein purpura nephritis (HSPN) and IgA nephropathy (IgAN).Methods The medical records of patients diagnosed as HSPN and IgAN during childhood were evaluated retrospectively. HSPN and IgAN groups were compared in terms of gender, age, upper respiratory infection history, blood pressure; presence of nephrotic and/or nephritic syndrome; hemoglobin level, leukocyte count, C-reactive protein (CRP), serum albumin (sAlb), creatinine, complement 3 (sC3), complement 4 (sC4) and immunoglobulin A (sIgA) levels; estimated glomerular filtration rate (eGFR) and proteinuria levels; and renal pathology findings at the onset of disease; total follow-up time; and blood pressure, eGFR and proteinuria levels at the last visit.ResultsFifty-four patients were enrolled in the study [38 (70%) HSPN and 16 (30%) IgAN]. The median follow-up time was 60.5 and 72.0 months in HSPN and IgAN groups, respectively (p > 0.05). The HSPN and IgAN groups were also not different in terms of gender, age at the onset; leukocyte count, eGFR, sC3-sC4-sIgA levels; and the presence of endocapillary, extracapillary and mesangial proliferation, tubular atrophy, interstitial fibrosis and IgA, IgM, C3 accumulation in renal tissue. Upper respiratory tract infection history was more common in children with IgAN (8/16 vs 8/38, p = 0.045). sAlb (3.96 ± 0.58 vs 4.40 ± 0.46 g/dL, p = 0.005), hemoglobin (12.1 ± 1.3 vs 13.3 ± 1.2 g/dL, p = 0.004,) and the incidence of mesangial IgG deposition (15/38 vs 11/16, p = 0.049) were lower, while CRP (16.3 ± 7.2 vs 7.8 ± 4.4 mg/L, p = 0.002) and proteinuria (72.1 ± 92.4 vs 34.2 ± 37.9 mg/m2/24 h, p = 0.041) was higher in HSPN group at the onset of disease. Proteinuria and eGFR were similar between the two groups at last visit.Conclusion Children with HSPN and IgAN have little clinical and histological differences in our population. The most prominent difference at presentation with nephritis was higher proteinuria in HSPN probably associated with inflammation due to systemic vasculitis. Long-term renal outcome was good in both HSPN and IgAN.
Flowchart of inclusion and exclusion of populations with kidney stones
Flowchart of inclusion and exclusion of healthy physical examination populations
Purpose The current research is aimed at analyzing the relationship between kidney stone (KS) and abdominal aortic calcification (AAC) and the relationship between KS components and AAC. Methods This is a retrospective, case–control study. Kidney stone formers (KSFs) were treated at the Department of Urology, West China Hospital, Sichuan University for urological calculus disease from January 2014 to January 2020. Matched non-stone formers (non-SFs) were drawn from the same hospital for routine health examination from January 2018 to February 2019. Research-related information was collected and reviewed retrospectively from the hospital’s computerized records. AAC were evaluated using available results of computed tomography imaging and abdominal vascular ultrasound. The relationships of AAC between KSFs and non-SFs were compared. The composition of renal calculi was analyzed by Fourier-transform infrared spectrophotometer. KSFs were divided into AAC groups and non-AAC based on AAC. The relationship of the composition of renal calculi between AAC and non-AAC were compared. The independent-sample t test, the chi-squared test and binary logistics regression were performed. Results Altogether, 4516 people were included, with 1027 KSFs and 3489 non-SFs. There were no significant differences in the laboratory parameters between KSFs and non-SFs. The association between the presence of AAC and KS was significant in multivariable model 2 [adjusting hypertension, diabetes mellitus, fasting blood glucose, uric acid, serum triglyceride (TG), serum calcium, and urine pH] (OR 5.756, 95% CI 4.616–7.177, p < 0.001). The result of KSFs showed that calcium oxalate calculi (CaOx) was significantly associated with AAC in multivariable model 3 (adjusting age, hypertension, diabetes mellitus, drinking history, smoking history, and TG) (OR 1.351, 95% CI 1.002–1.822, p = 0.048). Conclusions The current study pioneered the revelation of the relationship between CaOx and AAC. Through an elimination of the confounding factors, the study demonstrated that KS and AAC were connected.
Analysis of gut microbiota α-diversity in MHD patients with or without sarcopenia *P < 0.05
Analysis of β-diversity of gut microbiota in MHD patients with or without sarcopenia
Analysis of gut microbiota at genus level in MHD patients with or without sarcopenia
Purpose Maintenance hemodialysis (MHD) patients are at high risk of sarcopenia. Gut microbiota affects host metabolic and may act in the occurrence of sarcopenia importantly. This study aimed to study the characterization of the gut microbiota in MHD patients with sarcopenia, and to further reveal the complex pathophysiology of sarcopenia in MHD patients. Methods Fecal samples and clinical data were collected from 30 MHD patients with sarcopenia, and 30 age-and-sex-matched MHD patients without sarcopenia in 1 general hospital of Jiangsu Province from December 2020 to March 2021. 16S rRNA sequencing technology was used to analyze the genetic sequence of the gut microbiota for evaluation of the diversity, species composition, and differential microbiota of the two groups. Results Compared to MHD patients without sarcopenia, the ACE index of patients with sarcopenia was lower ( P = 0.014), and there was a structural difference in the β-diversity between the two groups ( P = 0.001). At the genus level, the relative abundance of Tyzzerella_4 in the sarcopenia group was significantly higher than in the non-sarcopenia group ( P = 0.039), and the relative abundance of Megamonas ( P = 0.004), Coprococcus_2 ( P = 0.038), and uncultured_bacterium_f_Muribaculaceae ( P = 0.040) decreased significantly. Conclusion The diversity and structure of the gut microbiota of MHD patients with sarcopenia were altered. The occurrence of sarcopenia in MHD patients may be influenced by gut microbiota.
Time course of clinical parameters after the start of tofogliflozin treatment. a HbA1c (%), *p < 0.05 vs. baseline data. b Body weights (kg), *p < 0.05, vs. baseline data. c eGFR (ml/min/1.73m²). d Blood urea nitrogen (mg/dL). e Systolic blood pressure (mmHg). f Hemoglobin (g/dL), *p < 0.05 vs. baseline data
Time course of urinary biomarkers after the start of the tofogliflozin regimen. a NGAL (μg/gCre). b NAG (U/gCre). c 8-OHdG (ng/mgCre). d Na (mEq/gCre)
PurposeThe sodium-glucose cotransporter 2 (SGLT2) inhibitors comprise a new class of glucose-lowering drugs for individuals with diabetes. Large-scale clinical trials indicated that SGLT2 inhibitors have both a cardiovascular-protective and renal-protective effects. A reduction in glomerular hyperfiltration and a decrease in albuminuria are suspected as the main causes of SGLT2 inhibitors' renoprotective effect. The effects of SGLT2 inhibitors on tubular damage in non-albuminuric diabetic patients are unclear.Methods The SGLT2 inhibitor tofogliflozin (20 mg, 1 × /day) was orally administered to 14 non-albuminuric diabetic patients. Serum and urine samples were collected at baseline (before) and after the start of tofogliflozin treatment. Hemoglobin A1c, hemoglobin, estimated glomerular filtration rate (eGFR), body weight, and blood pressure (BP) were analyzed as clinical parameters at baseline and 1, 3, and 6 months later. Urinary neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl-β-d-glucosaminidase were measured as tubular damage markers and the urinary 8-hidroxydeoxyguanosine (8-OHdG) values were measured as an oxidative stress marker at baseline and at 1 and 3 months.ResultsCompared to baseline, the patients' HbA1c values and body weights were significantly decreased post-tofogliflozin administration, and their eGFR values were decreased at 3 months but recovered at 6 months; the hemoglobin concentrations were significantly increased at 3 and 6 months and the urinary NGAL level tended to be decreased at 3 months. No significant changes in blood urea nitrogen, BP, NAG, urine sodium concentration, or urinary 8-OHdG values occurred. The effect of this SGLT2 inhibitor was not influenced by the use of an angiotensin receptor blocker or dipeptidyl-peptidase 4 inhibitor.Conclusion For individuals with non-albuminuric diabetes, tofogliflozin has a good glucose-lowering effect and might have a tubular-protective effect.
Top-cited authors
Adrian Covic
  • Universitatea de Medicina si Farmacie Grigore T. Popa Iasi
Carlos Musso
  • Hospital Italiano de Buenos Aires
Michael Chancellor
David J Goldsmith
  • St George's, University of London
Baris Afsar
  • T.C. Süleyman Demirel Üniversitesi