-
[show abstract]
[hide abstract]
ABSTRACT: Background Although 80% of the dialysis patients in Hong Kong are treated with peritoneal dialysis (PD), most received continuous ambulatory PD (CAPD), while automated PD (APD) accounts for 5% of the patients. Recent evidence suggests that clinical outcomes are different for CAPD and APD in specific subgroups of patients. Methods We reviewed the clinical outcome of 90 consecutive incident APD patients and 180 CAPD patients in our center. Results The median follow up was 21.9 months (inter-quartile range, 9.5 to 46.5 months). The APD group was younger and had a lower Charlson's score than the CAPD group. Furthermore, the APD group had a highly skewed distribution of the Charlson's score, indicating the possibility of two different groups of patients. Multivariate analysis showed that in addition to the treatment mode (APD versus CAPD) and Charlson's score, there was a significant interaction between the two (p = 0.043) on patient survival. For patients with Charlson's score ≤6, the APD group had a significantly better patient survival than the CAPD group (78.3% vs 65.4% at 5-year, p = 0.039), while for patients with Charlson's score ≥7, the APD group had a worse patient survival than the CAPD group (16.3% vs 48.4% at 5 years, p = 0.028). Similarly, Charlson's score and its interaction with treatment mode, but not the APD group per se, were independent predictors of technique survival (p = 0.013). For patients with Charlson's score ≥7, the APD group had a significantly lower technique survival than the CAPD group (8.8% vs 34.3%, p = 0.001), while for patients with Charlson's score ≤6, the technique survival was similar (44.4% vs 42.5%, p = 0.15). Peritonitis-free survival was 35.2% and 32.2% for APD and CAPD groups, respectively (p = 0.021), and the difference was not affected by Charlson's score. Conclusions Comorbid diseases had a significant interaction with the mode of PD on patient and technique survival of incident PD patients. Our result suggests that APD may offer benefit in, and only in, young patients with minimal comorbid diseases.
Nephrology 03/2013; · 1.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: The treatment of immunoglobulin A (IgA) nephropathy with normal renal function and minimal proteinuria is unknown. METHODS: We randomly assigned 60 patients with IgA nephropathy, proteinuria <0.5 g/day, normal blood pressure and renal function to ramipril 2.5 mg daily or no treatment. Patients were followed for 5 years for the development of hypertension, proteinuria, or impaired renal function. RESULTS: The blood pressure of the treatment group was marginally lower than the control group throughout the study period. At 60 months, the event-free survival was marginally higher for the treatment group as compared with the control group (81.1% vs 70.5%, P=.27). The proteinuria-free survival was similar at 82.9% and 79.3% for the treatment and control groups, respectively (P=.6); hypertension-free survival was 86.4% and 79.3% (P=.2). After 60 months of follow-up, the estimated glomerular filtration rate (GFR) was 108.1±29.0 mL/min/1.73 m(2) for the treatment group and 105.7±17.7 mL/min/1.73 m(2) for the control group (P=.7), but the difference was not statistically significant. None of the patients developed impaired renal function. The rate of GFR decline was similar between the treatment and control groups (-0.39±2.57 vs -0.59±1.63 mL/min/1.73 m(2) per year, respectively, P=.7). In general, the study medication was well tolerated. Two patients needed to stop prematurely because of cough and dizziness. CONCLUSION: For early IgA nephropathy patients with minimal proteinuria, normal blood pressure, and normal renal function, treatment with 2.5 mg/daily of ramipril for 5 years does not offer any benefit.
The American journal of medicine 02/2013; 126(2):162-168. · 4.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: There is no reliable clinical test to predict the reversibility of acute-on-chronic renal failure. We study whether urinary biomarkers could be used as a noninvasive prognostic marker in patients with acute-on-chronic renal failure. METHODS: We studied 39 adult patients with pre-existing chronic renal impairment presenting to us with acute-on-chronic renal failure. Urinary neutrophil gelatinase-associated lipocalin (NGAL) level was measured. The mRNA of kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), alpha-1-microglobulin (α1M), sodium/hydrogen exchanger-3 (NHE3), beta-2 microglobulin (β2M), and N-acetyl-β-D-glucosaminidase (NAG) in urinary sediment were quantified.RESULTS: Urinary NGAL level significantly correlated with the serum creatinine at presentation (r=0.762, p< 0.0001) but not baseline serum creatinine. Urinary sediment β2M expression significantly correlated with baseline glomerular filtration rate (GFR) (r= -0.400, p=0.012). Urinary α1M and NHE3 expressions were significantly higher in ischemic acute tubular necrosis than other causes of acute kidney injury (p< 0.0001 and p=0.006, respectively). Urinary α1M expression significantly correlated with the degree of improvement in renal function (r=0.387, p=0.026), as well as the estimated GFR 6 months later (r=0.386, p=0.027).CONCLUSION: In patients with acute-on-chronic renal failure, urinary NGAL level correlates with the severity of renal failure, while urinary α1M expression correlates with the degree of renal function recovery. Quantification of urinary α1M mRNA may be developed as an non-invasive tool for risk stratification of this group of patients.
Disease markers 01/2013; · 1.64 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: MicroRNAs are a group of non-coding RNA molecules that play important roles in the pathogenesis of various kidney diseases. We investigate the urinary sediment miRNA levels of adult patients with nephrotic syndrome. METHODS: We study 20 patients with diabetic glomerulosclerosis (DGS), 21 with minimal change nephropathy (MCN) or focal glomerulosclerosis (FGS), 23 with membranous nephropathy (MGN), and 10 healthy controls. Urinary sediment miRNA levels are quantified. RESULTS: Urinary sediment miR-29a, miR-192, and miR-200c levels were significantly different between diagnosis groups. Post hoc analysis showed that urinary miR-638 level was significantly lower in all causes of nephrotic syndrome than healthy controls, while the DGS group had lower urinary miR-192 level than other diagnosis groups. In contrast, the MCN/FGS group had higher urinary miR-200c level than other diagnosis groups. For each specific pathology group, urinary level of several miRNA targets significantly correlated with kidney function and histological scarring. CONCLUSIONS: Urinary miR-29a, miR-192 and miR-200c levels have characteristic alterations amongst patients with different causes of nephrotic syndrome. Our results suggest that urinary miRNA levels has the potential of being developed as the diagnosis tool and marker of disease severity in adult nephrotic syndrome.
Clinica chimica acta; international journal of clinical chemistry 01/2013; · 2.54 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Background: MicroRNAs (miRNAs) play important roles in the progression of renal fibrosis. We studied the urinary levels of miR-21, miR-29 family and miR-93, which are downstream mediators of the transforming growth factor-β(1) (TGF-β(1)), in patients with immunoglobulin A (IgA) nephropathy. Methods: We studied the urinary miRNA levels of 43 IgA nephropathy patients and 13 healthy controls. Results: The IgA nephropathy group had significantly lower urinary miR-29b and miR-29c, but higher miR-93 levels than controls. Proteinuria significantly correlated with urinary levels of miR-29b (r = -0.388, p = 0.003) and miR-29c (r = -0.409, p = 0.002). Glomerular filtration rate significantly correlated with urinary levels of miR-21 (r = 0.338, p = 0.028), miR-29b (r = 0.333, p = 0.031) and miR-29c (r = 0.304, p = 0.050). Urinary miR-93 level significantly correlated with glomerular scarring (r = -0.392, p = 0.010). Urinary miRNA level of SMAD3, but not TGF-β(1), correlated with urinary miR-21 (r = 0.624, p < 0.001), miR-29b (r = 0.566, p < 0.001), miR-29c (r = 0.619, p < 0.001) and miR-93 (r = 0.332, p = 0.032). Conclusions: Urinary miR-29b and miR-29c levels correlated with proteinuria and renal function, while urinary miR-93 level correlated with glomerular scarring. More importantly, urinary levels of these miRNA targets significantly correlated with urinary SMAD3 level. Our results suggest that these miRNA targets are regulated by the TGF-β(1)/SMAD3 pathway and they may play important roles in the development of progressive renal fibrosis in IgA nephropathy.
American Journal of Nephrology 10/2012; 36(5):412-418. · 2.54 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Peritoneal dialysis-associated peritonitis secondary to Campylobacter organisms is uncommon. Few studies have assessed either treatment or clinical outcomes. METHODS: We reviewed all Campylobacter peritonitis episodes occurring in a single dialysis unit from 1994 to 2011. RESULTS: During the study period, 12 episodes of Campylobacter peritonitis (0.45% of all peritonitis episodes) were recorded. Diarrhea was uncommon (8.3%). The overall primary response rate was 91.7%; the complete cure rate was 75.0%. Among 6 patients who failed to respond to standard antibiotics by day 5, all improved after administration of an oral macrolide (erythromycin or clarithromycin). Of those 6 patients, 5 experienced a complete cure, and 1 patient experienced relapse of culture-negative peritonitis. No patient required Tenckhoff catheter removal or temporary hemodialysis support. The 30-day mortality was 0%. CONCLUSIONS: Campylobacter peritonitis might not respond to first-line conventional antibiotics, and an oral macrolide is recommended if Campylobacter is confirmed. The findings from our analysis do not support the use of fluoroquinolone, which is associated with a high resistance rate.
Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. 10/2012;
-
[show abstract]
[hide abstract]
ABSTRACT: To study the role of tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK)/Fn14 and the interferon-inducible protein (IP-10)/CXCR3 axis in lupus nephritis (LN).
We studied 113 patients with LN who had had repeat renal biopsies. Glomerular and tubulointerstitial messenger RNA expression of TWEAK, Fn14, IP-10, and CXCR3 were quantified.
Glomerular Fn14 expression decreased when changed from proliferative or mixed nephritis to membranous nephropathy (p = 0.016), and increased when changed from membranous to proliferative or mixed nephritis (p = 0.0006). On the other hand, tubulointerstitial TWEAK expression decreased when changed from proliferative or mixed nephritis to membranous nephropathy (p = 0.004), and increased when changed from membranous nephropathy to proliferative nephritis (p = 0.010). Tubulointerstitial IP-10 expression decreased when changed from proliferative or mixed nephritis to membranous nephropathy (p < 0.0001). Histological activity index correlated significantly with the glomerular expression of Fn14 (r = 0.421, p < 0.0001) and tubulointerstitial expression of TWEAK (r = 0.413, p < 0.0001) and IP-10 (r = 0.472, p < 0.0001).
Glomerular Fn14 and tubulointerstitial TWEAK and IP-10 expression appeared to have consistent changes in relation to the histological class of LN and correlated with the histological activity index. Our findings suggest a specific role of these genes in the pathogenesis of LN.
The Journal of Rheumatology 08/2012; 39(10):1942-7. · 3.69 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Background: Evidence indicates that microRNAs (miRNA) play a role in the pathogenesis of chronic kidney diseases (CKD). We explored the possibility of using urinary miRNA as non-invasive biomarkers for CKD. Methods: We quantified miRNA expression in urinary sediment of 56 CKD patients who underwent kidney biopsy. Patients were followed for 16.2 ± 15.5 months.Results: Patients with diabetic glomerulosclerosis had lower urinary miR-15 expression, while those with IgA nephropathy had higher urinary miR-17 expression, than other diagnosis groups. Baseline proteinuria had significant inverse correlation with urinary expression of miR-15, miR-192, and miR-216a; baseline renal function correlated with urinary expression of miR-15, miR-17, miR-192, and miR-217. The rate of renal function decline correlated with urinary expression of miR-21 (r=0.301, p=0.026) and miR-216a (r=0.515, p < 0.0001). Patients with a high urinary expression of miR-21 and miR-216a had better dialysis-free survival than those with low expression (log rank test, p=0.005 and p=0.003, respectively). Conclusions: Urinary miR-21 and miR-216a expression correlated with the rate of renal function decline and risk of progression to dialysis-dependent renal failure. Our results suggest that urinary miRNA profiling has the potential of further development as biomarkers of CKD.
Disease markers 08/2012; 33(3):137-44. · 1.64 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Studies in hemodialysis patients suggest that the "surprise" question can help to identify a group of patients with a high mortality risk who should receive priority for palliative care interventions. However, the same instrument has not been tested in peritoneal dialysis (PD) patients. ♢ Method: We studied 367 prevalent PD patients from a single dialysis center. Three clinicians independently answered the "surprise" question (Would I be surprised if this patient died within the next 12 months?) according to their clinical impression of the individual patient. Patients are then classified into "yes" (yes, surprised) and "no" (no, not surprised) groups. All patients were followed for 12 months. ♢ RESULTS: In this cohort, 109 patients (29.7%) were allocated to the "no" group, and 258 (70.3%), to the "yes" group. Patients in the "no" group were older and had high prevalences of pre-existing ischemic heart disease, cerebrovascular disease, and peripheral vascular disease. The "no" group had a higher score on the Charlson comorbidity index and a higher malnutrition-inflammation score. At 12 months, 44 patients had died. Mortality was 24.8% in the "no" group and 6.6% in the "yes" group. Multivariate analysis showed that an opinion of "Not surprised if dies in the next 12 months" was an independent predictor of 12-month mortality, with an associated 3.594 excess mortality risk (95% confidence interval: 1.411 to 9.151; p = 0.007). The positive predictive value of this opinion was 24.8%, and its negative predictive value was 93.4%. ♢ CONCLUSIONS: The "surprise" question has the potential to help identify a group of PD patients with high short-term mortality. Its use may contribute to a decision to refer PD patients for early palliative care assessment.
Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. 08/2012;
-
[show abstract]
[hide abstract]
ABSTRACT: Dialysis, particularly haemodialysis, is associated with an increased risk of cardiovascular disease. A new study confirms that hypokalaemia confers an excess cardiovascular risk and contributes disproportionately to the high risk of death in patients on peritoneal dialysis, which may partially account for the fact that observed cardiac risk is similar for patients on peritoneal dialysis and haemodialysis.
Nature Reviews Nephrology 07/2012; 8(9):501-3. · 7.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Background: Myeloid-related protein 8/14 (MRP8/14) is released by cells of myeloid lineage upon inflammatory challenges. Experimental data suggested that MRP8/14 is important in the initiation and progression of inflammation and cardiovascular diseases. We examined the relation between serum MRP8/14 level and cardiovascular disease in Chinese peritoneal dialysis (PD) patients. Methods: We studied 102 new PD patients (58 males, mean age 57.3 ± 11.9 years). Baseline serum MRP8/14 was determined and grouped to quartiles for analysis. All patients were then followed for an average of 23.9 ± 6.9 months. Results: There was a trend of lower 3-year cardiovascular event-free survival for patient quartiles with high serum MRP8/14 levels (log-rank test, p = 0.064). The 3-year actuarial survival was significantly lower for quartile groups with higher MRP8/14 levels (96.0, 94.7, 72.9, and 62.5% for quartiles 1-4, respectively, p = 0.003). Cox regression analysis showed that serum MRP8/14 level and Kt/V were independent predictors of actuarial survival; in this model, every 1 μg/ml increase in serum MRP8/14 level confers a 25.1% increase in risk of death (95% confidence interval, 1.3-54.4%, p = 0.037). There was no significant difference in technique survival between the MRP8/14 quartile groups. Conclusion: A high baseline serum MRP8/14 level was associated with a lower actuarial survival in Chinese PD patients. The pathogenic role of MRP8/14 in the cardiovascular disease of PD patients needs further investigation.
Kidney and Blood Pressure Research 06/2012; 35(6):489-496. · 1.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We aimed to gain an understanding of patient concerns while on a transplantation waiting list in areas with long transplant waiting time.
The study population comprised patients with organ failure on the transplant waiting list in Hong Kong. They were invited to complete a questionnaire survey. Demographic data and waiting time were collected. Respondents rated their chance of getting transplanted, their subjective concerns and feelings, level of happiness and support received.
A total of 442 patients on the waiting list for kidney, liver, lung and heart-lung transplants completed the questionnaire survey. The majority of patients (93.0%) were waiting for kidney transplantation. More than half of the respondents (63.3%) had been waiting for more than 3 years. Patients with longer transplant waiting times had lower self-estimated chance of receiving a transplant (P = 0.004). Self-estimated chance of getting transplanted was positively associated with the happiness score (P < 0.0001). Issues of most concerns to the patients waiting for organ transplants were: inconvenience of therapy (48.2%), disease progression (47.9%), burden to family (59.5%) and financial difficulties (52.3%). More female patients on the waiting list (50.0% vs 25.7% in male) reported concerns about suffering associated with the illnesses. 21.7% of patients considered the level of support received inadequate.
Our patients had long waiting time for transplantation, which is associated with a lower perceived chance of getting a transplant. Attention to more psychosocial support to these patients waiting for organ transplant is important. Promoting and improving organ donation would be the ultimate way to help these patients.
Nephrology 05/2012; 17(5):514-8. · 1.31 Impact Factor
-
Shui-Lian Yu,
Paul Ks Chan,
Chun-Kwok Wong, Cheuk-Chun Szeto,
Suzanne C Ho,
Karine So,
May My Yu,
So-Fan Yim,
Tak-Hong Cheung,
Martin Cs Wong,
Jo Lk Cheung,
Apple Cm Yeung,
Edmund K Li,
Lai-Shan Tam
[show abstract]
[hide abstract]
ABSTRACT: Prevalence of an abnormal Papanicolaou smear was significantly increased in lupus patients in cross-sectional studies, associated with a higher prevalence of high-risk human papillomavirus (HPV) infection. The nucleic acid-specific Toll-like receptors (TLRs) locate at the endolysosomal compartments and trigger the induction of cytokines for the innate immune response. This study evaluated whether abnormal host innate immune response in lupus patients may enhance HPV persistence.
Protein levels of TLRs 3, 7, 8 and 9 in cervical epithelial cells of lupus patients and controls with or without HPV infection were assessed using flow cytometry. Characteristics associated with the differential expression of TLRs in systemic lupus erythematosus (SLE) were elucidated. The effect and interferon-stimulated genes (ISGs) (ISG15 and Mx-1) gene expressions were then measured in oncogenic HeLa (HPV18), CaSki (HPV) and C33A (HPV negative) cell lines using flow cytometry and quantitative real-time PCR. Ex vivo productions of cytokines and interferon-gamma (IFN-γ) upon TLR ligands stimulations were subsequently measured using cytometric bead array and ELISA.
For subjects with HPV infection, levels of TLR3 and TLR7 were significantly lower in lupus patients compared with controls. Significantly decreased TLRs 7, 8 and 9 levels were observed in HPV-negative SLE compared to healthy controls. For SLE with and without HPV infection, TLR7 and 9 levels were significantly lower in infected SLE than those in HPV-negative patients. Independent explanatory variables associated with down-regulation of TLR7 level included HPV infection and a higher cumulative dose of prednisolone; while a higher cumulative dose of hydroxychloroquine and HPV infection were associated with down-regulation of TLR9 level. In cervical cell lines, TLRs 3, 7, 8, 9 protein levels and antiviral ISG15 and Mx-1 gene expressions were inhibited in two oncogenic HPV types. Functional data showed that the induction of pro-inflammatory cytokines by TLR ligands (R837, ssRNA and ODN2395) was greatly impaired in CaSki and HeLa than C33A cells.
In conclusion, prednisolone and TLR antagonist (hydroxychloroquine) may down-regulate protein levels of TLR7 and TLR9 in lupus patients, thereby decreasing the innate immune response against HPV infection. Upon infection, HPV further down-regulate TLR7 and 9 levels for viral persistence. Furthermore, reduction of nucleic acid-sensing TLRs 7, 8 and 9 in carcinogenic HPVs ensures that the expression of inducible pro-inflammatory cytokines is minimized to prevent the expression of antiviral ISGs (ISG15 and Mx-1) on a biologically relevant antiviral response.
Arthritis research & therapy 04/2012; 14(2):R80. · 4.27 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) can counteract inflammation and atherosclerosis, both common causes of morbidity in peritoneal dialysis (PD) patients. We examined the relation between serum soluble TRAIL (sTRAIL) levels and the outcome of Chinese PD patients.
We studied 116 new PD patients (67 males, age 56.7 ± 13.4 years). Baseline serum sTRAIL level was determined and grouped to tertiles 1 (lowest) to 3 (highest). All patients were followed for 20.9 ± 7.0 months.
Patient survival was 83.4%, 74.2% and 100% for tertiles 1 to 3, respectively, at 24 months (P = 0.021). Multivariate Cox regression analysis showed that serum sTRAIL level was an independent predictor of patient survival after adjusting for confounding factors (adjusted hazard ratio 0.962, 95% confidence interval [CI] 0.935-0.991, P = 0.010).
A higher baseline serum sTRAIL level was associated with a better survival of PD patients. The detailed mechanism deserves further investigation.
Nephrology 04/2012; 17(5):466-71. · 1.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The renin-angiotensin system (RAS) plays an important role in the pathophysiology of cardiovascular and renal diseases. In chronic kidney disease (CKD), blockade of RAS by angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) has been shown to reduce proteinuria and retard the progression of renal function deterioration. However, aldosterone, another key hormone of the RAS, is not directly targeted by ACEI or ARB. Hyperaldosteronism, apart from promoting sodium and fluid retention, causes inflammation and fibrosis in the heart and kidney. Studies have shown that although plasma aldosterone level shows an initial decrease following ACEI or ARB treatment, it returns to pretreatment level or even increases paradoxically after prolonged treatment. This "aldosterone breakthrough" forms the basis of adding mineralocorticoid receptor (MR) antagonist on top of ACEI or ARB for renal protection. New insights into the pathophysiological role of aldosterone in CKD further expands its potential indications, and there was a growing body of evidence in the past 10 years, which showed a substantial antiproteinuric effect and possibly a considerable renoprotective effect of MR antagonist. Since aldosterone does not act on the efferent glomerular arteriole and has no effect on intraglomerular hemodynamics, the very fact that MR antagonist ameliorates proteinuria sheds light on the physiology of glomerular permeability barrier. This review summarizes the data regarding the theoretical benefit as well as clinical use of MR antagonist in renal diseases.
Renal Failure 04/2012; 34(6):810-7. · 0.82 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We studied the levels of miR-146a and miR-155 in the urine sediment of SLE patients. The levels of miR-146a and miR-155 in the urine sediment of 40 SLE patients who were receiving calcitriol treatment and 13 healthy controls were determined with real-time quantitative polymerase chain reaction. The levels of urinary miR-146a and miR-155 in patients with SLE were significantly higher than that in healthy controls. Calcitriol treatment reduced the levels of urinary miR-155 in patients with SLE. The level of urinary miR-146a significantly correlated with estimated glomerular filtration rate (r = 0.242, P = 0.008). The level of urinary miR-155 significantly correlated with proteinuria (r = 0.407, P < 0.001) and systemic lupus erythematosus disease activity index (r = 0.278, P = 0.002). The level of urinary miR-146a reversely correlated with the urinary expression of TNF-α (r = -0.247, P = 0.012). Our results suggested that miR-146a and miR-155 might play important roles in the pathophysiology of SLE and the levels of urinary miR-146a and miR-155 could be used as potential markers for diagnosis, disease activity, and therapeutic response.
Clinical Rheumatology 03/2012; 31(3):435-40. · 2.00 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Pathogenetic mechanisms underlying albuminuria are not completely understood. Heavy metals might lead to atherosclerosis and kidney damage. miR-21, 126, 155 and 221 regulated endothelial function and might contribute to the development of albuminuria. To date, no clinical trial has explored the relationship between miRNAs, microalbuminuria and heavy metals in human. In this study, we aimed to examine the association between microalbuminuria, miRNAs and heavy metals in adolescents.
From a cross-sectional, population-recruited study, we identified 60 school children aged 12-19 years with microalbuminuria (defined as spot urine albumin-creatinine ratio >3.5 mg/mmol). We compared the urine heavy metals (arsenic, mercury, cadmium and lead) and miRNAs levels (miR-21,126, 155 and 221) with another 60 age-and sex-matched normoalbuminuric adolescents as control.
Mean age of the study cohort was 15.5±2.1 years. 43% were boys. Among the four miRNAs tested, only miR-21 was associated with microalbuminuria (p=0.02). Urinary arsenic and lead levels had a negative association with both miR-21 and miR-221. No significant association was found between heavy metals examined and microalbuminuria.
The results of our study suggest an association between microalbuminuria, miR-21 and heavy metals (arsenic and lead). This might imply that miR-21 is involved in the pathogenetic mechanisms linking heavy metals exposure and albuminuria.
Clinica chimica acta; international journal of clinical chemistry 03/2012; 413(13-14):1053-7. · 2.54 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We quantified the urine sediment and supernatant levels of microRNA (miRNA) targets related to epithelial-mesenchymal transition in 51 patients with bladder cancer and in 24 controls. We found that patients with bladder cancer had depressed levels of the miR-200 family, miR-192, and miR-155 in urinary sediment. The urinary level of these miRNAs may be developed as noninvasive markers for bladder cancer.
MicroRNAs (miRNA) have been implicated to play an important role in the pathogenesis of a variety of cancers. We studied the levels of miRNAs related to epithelial-mesenchymal transition (EMT) in the urine of patients with bladder cancer.
The expression of the miR-200 family, miR-205, miR-192, miR-155, and miR-146a in the urine sediment and supernatant of 51 patients with bladder cancer and in 24 controls was determined by real-time quantitative polymerase chain reaction.
Compared with controls, the patients with bladder cancer had a lower expression of the miR-200 family, miR-192, and miR-155 in the urinary sediment; lower expression of miR-192; and higher expression of miR-155 in the urinary supernatant. The expression of the miR-200 family, miR-205, and miR-192 in the urine sediment significantly correlated with urinary expression of EMT markers, including zinc finger E-box-binding homeobox 1, vimentin, transforming growth factor β1, and Ras homolog gene family, member A. Furthermore, the levels of miR-200c and miR-141 in the urine sediment became normalized after surgery.
We found that the urinary miR-200 family, miR-155, miR-192, and miR-205 levels are depressed in patients with bladder cancer. The level of these miRNA targets in urine has the potential to be developed as noninvasive markers for bladder cancer.
Clinical Genitourinary Cancer 03/2012; 10(2):106-13. · 2.61 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The single-nucleotide polymorphism (SNP) -717A→G substitution, rs2794521, was found in the promoter of the C-reactive protein (CRP) gene. Functional studies showed that A allele promoter has higher transcriptional activity than the G allele. This study investigated the association between this SNP and the outcome of Chinese patients undergoing peritoneal dialysis (PD).
The study included 441 new PD patients (232 men; mean age ± SD, 56.7±13.5 years). CRP genotyping was determined; patients were followed for 41.3±18.3 months for cardiovascular events.
For the entire cohort, 5-year event-free survival rates did not differ between the AA and AG/GG groups (35.7% and 31.9%, respectively; P=0.64). However, there was significant interaction between plasma cholesterol levels and CRP genotype groups on event-free survival (P=0.04 for interaction). For patients with cholesterol levels of 200 mg/dl or greater, the 5-year event-free survival rate in the AG/GG group was significantly better than that in the AA group (54.7% versus 40.0%; P=0.04), whereas there was no difference in event-free survival between genotype groups for patients with cholesterol levels less than 200 mg/dl.
CRP gene -717AG or GG genotypes is associated with cardiovascular benefit to Chinese PD patients with cholesterol levels of 200 mg/dl or greater. These findings suggest a complex interaction among cholesterol, CRP, and cardiovascular disease in PD patients.
Clinical Journal of the American Society of Nephrology 02/2012; 7(2):304-9. · 5.23 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: MicroRNAs (miRNAs) play important roles in the pathogenesis of autoimmune diseases. We studied the intra-renal expression of miRNA targets that were reported to be differentially expressed in peripheral blood or urine between lupus nephritis (LN) patients and normal controls.
We quantified the expression of in glomerulus and tubulointerstitium of miR-146a, miR-155, miR-198 miR-638 and miR-663 in 42 patients with LN and 10 healthy controls.
As compared with controls, LN patients had lower glomerular expression of miR-638 (P < 0.001) but higher tubulointerstitial expression of this target (P = 0.001). Both glomerular and tubulointerstitial expression of miR-198 were higher in LN patients than controls (P < 0.001). For miR-146a, LN patients only had higher expression in glomerulus (P = 0.005) but not in tubulointerstitium. Tubulointerstitial miR-638 expression was significantly correlated with proteinuria (r = 0.404; P = 0.022) and disease activity score (r = 0.454; P = 0.008), while glomerular miR-146a expressions were correlated with estimated GFR (r = 0.453; P = 0.028) and histological activity index (r = 0.494; P = 0.027).
We found that intra-renal expression of miR-638, miR-198 and miR-146a are differentially expressed between LN patients and normal controls. Furthermore, the degree of change in glomerular miR-146a and tubulointerstitial miR-638 expression correlated with clinical disease severity. The results suggested that these miRNA targets may play a role in the pathogenesis of lupus nephritis.
Nephrology 02/2012; 17(4):346-51. · 1.31 Impact Factor