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ABSTRACT: Klotho constitutes the receptor for fibroblast growth factor 23 (FGF23). However, the effects of FGF23 on renal and circulating klotho are not well-known. In vivo experiments were performed to assess the effects of FGF23 (10 μg/kg), parathyroid hormone (PTH, 10 μg/kg), and 1,25-dihydroxy-vitamin D3 (1,25VD, 1 μg/kg) on renal expression and serum concentration of klotho in Wistar rats. Phosphate excretion was increased at 3 h after FGF23 administration (p < 0.05). Renal klotho expressions and serum klotho levels were elevated at 3 h (p < 0.01) by FGF23. At 24 h, phosphate excretion was still elevated (p < 0.05), and serum phosphate, 1,25VD, and PTH were reduced (p < 0.05). However, serum and renal klotho returned to the control level at 24 h. PTH markedly increased phosphate excretion after 24 h (p < 0.01). There were increases in FGF23 at 3 and 24 h, and 1,25VD at 24 h after PTH administration (p < 0.05). Serum klotho concentration and renal klotho expression were elevated by PTH at 3 or 24 h. After 24 h of exposure to 1,25VD, considerable increases in serum FGF23, calcium, and phosphate were seen (p < 0.05), but PTH was decreased (p < 0.01). 1,25 VD elevated renal klotho expression and serum klotho (p < 0.05) at 3 h, but returned to control levels at 24 h. Our data indicate that FGF23 rapidly increases renal klotho expression and serum klotho. The present findings are consistent with the notion that PTH increases phosphate excretion at least in part through elevations of FGF23 and klotho. Moreover, our results suggest that 1,25VD increases klotho expression independently of FGF23.
Pflügers Archiv - European Journal of Physiology 03/2013; · 4.46 Impact Factor
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Kidney International 10/2012; 82(8):934. · 6.61 Impact Factor
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ABSTRACT: The caspase family of enzymes participates in apoptotic and proinflammatory reactions in any cell. Here we studied the role of caspase activation in the tubular epithelium of diseased kidneys using mice transgenic for the baculovirus pan-caspase inhibitor p35 gene held in a nonexpressed state (control mice) but target-expressed in the renal proximal tubule cells when crossed with mice expressing Cre recombinase under the control of the γ-glutamyltransferase promoter. Proinflammatory and profibrogenic parameters such as the number of monocytes and fibroblasts in the kidneys were significantly increased at 28 days in the control mice, but not in the renal tubule-targeted mice expressing p35 in a nephrotoxic serum nephritis model of disease. These cellular changes paralleled the number of apoptotic tubular cells and protein levels of active caspase-3 in the kidneys at 7 and 28 days of both the control and proximal tubule-targeted mice. Surprisingly, all of these parameters were not significantly affected at 7 and 28 days by targeted p35 expression in tubular epithelium when compared with nontargeted control mice in a model of adriamycin nephrosis. Thus, our study shows the critical role of caspase activation in the tubular epithelium in apoptosis along with proinflammatory and profibrogenic processes in nephrotoxic serum nephritis but not adriamycin nephrosis.
Kidney International 07/2012; 82(9):980-9. · 6.61 Impact Factor
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ABSTRACT: Previous studies have reported that high-salt intake paradoxically activates tubuloglomerular feedback (TGF) in type 1 diabetes. Using Zucker lean (ZL) and diabetic fatty (ZDF) rats on normal and high-salt diets, renal hemodynamics and the renin-angiotensin system (RAS) were characterized. On normal salt diet, glomerular filtration rate (GFR) was higher in ZDF than ZL rats. Autoregulation of GFR was less efficient and lithium clearance was lower in ZDF rats than ZL rats. Salt load reduced GFR in ZDF rats with restoration of lithium clearance and partial improvement in autoregulatory index (AI). The administration of 8-cyclopentyl-1,3-dipropylxanthine, a selective adenosine-1 receptor antagonist to ZDF rats on a high-salt diet abolished the improvement of AI in GFR. However, this effect was seen by neither (Cx40)GAP27 nor (Cx37,43)GAP27, which inhibits connexin (Cx) 40 or Cx37. Renal ANG II was higher in ZDF than ZL rats on normal salt diet, but the difference was eliminated by a salt load. The present data provide the first demonstration for a salt paradox in type 2 diabetes and implicate that in addition to Cx alterations, an enhanced proximal reabsorption attenuates TGF, underlying glomerular hyperfiltration and RAS activation. These data suggest that a high-salt diet standardizes distal delivery in diabetes, suppressing the RAS, and improving GFR autoregulation and hyperfiltration through adenosine.
AJP Regulatory Integrative and Comparative Physiology 06/2012; 303(5):R495-504. · 3.34 Impact Factor
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Tsuneo Takenaka,
Takeru Seto,
Mika Okayama,
Eriko Kojima,
Yuka Nodaira,
Keita Sueyoshi,
Tomohiro Kikuta,
Yusuke Watanabe, Tsutomu Inoue,
Hiroshi Takane,
Yoichi Ohno,
Hiromichi Suzuki
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ABSTRACT: Background: Our previous retrospective study showed that benidipine was superior to amlodipine (AM) for reducing proteinuria and preserving the augmentation index (AI) in patients with chronic kidney disease (CKD). Methods: The present study enrolled CKD patients whose blood pressure was not well controlled by an angiotensin receptor blocker (ARB) and a calcium channel blocker other than AM or azelnidipine (AZ). Either AM (5 mg) or AZ (16 mg) was prescribed randomly. Clinical parameters, including proteinuria, serum creatinine, and AI, were measured before initiation of AM or AZ and 1 year later to assess the long-term effect on renal function and central blood pressure. Results: Brachial and central blood pressures were similarly reduced in both groups. However, pulse rate increased in the AM group, but decreased in the AZ group (+3 ± 1 vs. -2 ± 1 bpm, p < 0.0001). The reduction of proteinuria was greater in the AZ group (-29 ± 2 vs. -38 ± 3%, p < 0.01). Improvement of AI adjusted for a pulse rate of 75 bpm was larger in the AZ group than in the AM group (-4 ± 1 vs. -9 ± 1%, p < 0.05). In both groups, estimated GFR remained unchanged throughout the observation period. Conclusion: In hypertensive patients with CKD, combined treatment with AZ and an ARB decreases proteinuria and preferentially improves arterial reflection.
American Journal of Nephrology 04/2012; 35(5):416-23. · 2.54 Impact Factor
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Journal of hypertension 02/2012; 30(2):429-32; author reply 432. · 4.02 Impact Factor
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Mika Okayama, Tsutomu Inoue,
Yuka Nodaira,
Yumi Kimura,
Kanako Nobe,
Takeru Seto,
Keita Sueyoshi,
Hiroshi Takane,
Tsuneo Takenaka,
Hirokazu Okada,
Hiromichi Suzuki
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ABSTRACT: Peritonitis remains a leading complication of peritoneal dialysis (PD). The aim of this observational retrospective cohort study, conducted at our single center, was to determine the risk factors for peritonitis. A Cox proportional hazards model was used for the multivariate analysis. The event investigated was peritonitis, and the variables studied were sex, age, diabetes mellitus, use of statins, and several laboratory values including albumin and total cholesterol. All PD patients who visited our clinic from January 2005 to September 2011 and who had complete medical records for at least 3 years were included. Among the 82 patients who met the criteria (mean period of observation: 1086 +/- 752 days; mean age: 62.0 +/- 12.3 years), 47 had experienced at least 1 episode of peritonitis. Aging was a significant risk factor for peritonitis, with a relative risk of 1.04 per year (p = 0.014). In our study, aging--rather than diabetes mellitus, efficiency of PD, or nutrition status--was an important risk factor for PD-associated peritonitis. Poor PD technique because of advanced age might be one of the reasons for this result.
Advances in peritoneal dialysis. Conference on Peritoneal Dialysis 01/2012; 28:50-4.
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Kanako Nobe, Tsutomu Inoue,
Yuka Nodaira,
Yumi Kimura,
Mika Okayama,
Shiko Gen,
Takeru Seto,
Keita Sueyoshi,
Hiroshi Takane,
Tsuneo Takenaka,
Hirokazu Okada,
Hiromichi Suzuki
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ABSTRACT: A broad consensus has not been reached on the appropriate timing for cessation of peritoneal dialysis (PD). Decreasing urine volume, repeated and refractory peritonitis, and deterioration of the peritoneal membrane are major reasons to stop PD. Also, the link between length of time on PD and encapsulating peritoneal sclerosis (EPS) should be an additional concern. The aim of the present study was to investigate patients who had been on continuous ambulatory PD (CAPD) for a long time. All patients undergoing CAPD at our kidney center for more than a decade from January 1990 to September 2011 were included in the study. Among more than 436 CAPD patients, 11 met the inclusion criteria. Their mean PD duration was 12.3 +/- 3.1 years. Mean age at CAPD introduction had been 46.0 +/- 10.1 years. All patients had nondiabetic nephropathy as the underlying cause of their end-stage renal disease. At least 2 of the 11 had developed EPS, and 1 had subsequently died from EPS. Patients on prolonged CAPD for more than a decade are still rare. The CAPD modality may be continued if it is efficiently maintained within an acceptable level, but EPS remains a serious complication of prolonged PD.
Advances in peritoneal dialysis. Conference on Peritoneal Dialysis 01/2012; 28:74-8.
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ABSTRACT: Although peritoneal dialysis (PD) has been recommended for initial dialysis therapy, a larger proportion of patients with end-stage renal disease choose hemodialysis (HD) instead. Several previous studies comparing the outcomes of these two therapies, including survival rates and cardiovascular events, have not clearly demonstrated the superiority of one over the other. Our recent study indicated that, compared with HD or PD alone, renal replacement therapy with HD and PD in combination prolongs survival and reduces cardiovascular events. However, the use of combination dialysis therapy is not widely accepted. We set out to analyze the efficacy of combination dialysis therapy with PD and HD in patients who started with PD as initial dialysis therapy. Our single-center retrospective cohort study included 401 patients (165 women, 236 men; 61 +/- 12 and 62 +/- 9 years of age respectively) who started PD during 1995-2005. Chart and electronic databases were used to obtain information on the course of dialysis therapy, including mortality and cardiovascular events. Treatment with HD and PD in combination was used in 103 patients. During 5 years of follow-up after the start of PD, 80 patients died. We observed no differences in cumulative mortality between the men (49, 200%) and women (31, 18%) and no difference in the cumulative incidence of catheter removal for various reasons (35% vs. 31%). There was a significant difference (p < 0.05) in the time of HD start between men and women. In men on PD, HD therapy was started 22 +/- 2 months after the start of PD; in women, it was started 38 +/- 7 months after PD start. Although women have a survival advantage in both the general and the dialysis patient population, women on PD experience mortality similar to that in men. The reasons for those findings have not been fully explained. The present analysis suggests that an early start to HD therapy will prolong the survival of patients on PD, especially men.
Advances in peritoneal dialysis. Conference on Peritoneal Dialysis 01/2012; 28:68-73.
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ABSTRACT: Recent studies have clearly demonstrated that start ing treatment with peritoneal dialysis (PD) is superior to starting with conventional hemodialysis (HD) because PD preserves residual renal function for a longer period. Similarly, because of the frequency of treatments, home HD (HHD) is also superior to conventional HD. The accumulated evidence suggests that a combination of PD and HHD might be a new and effective method for patients receiving dialysis therapy. We analyzed 10 patients who, over the past 10 years, were started on PD and who were then transferred to HHD. Electronic databases were used to examine changes in their health status. Mean age was 58 +/- 8 years in these 2 female and 8 male patients. Mean duration of PD was 6.9 +/- 2.4 years. The average total duration of dialysis therapy was 9.7 +/- 1.9 years. The main reason for the transition from PD to HHD was loss of residual renal function. To the time of writing, no serious complications (including cardiovascular events and calcium homeostasis) had occurred. All patients continue to receive dialysis therapy and have been able to lead a nearly normal social life. Major laboratory findings include serum albumin 4.2 +/- 0.2 g/dL, hemoglobin 10.2 +/- 1.4 g/dL (half the patients were not using erythropoiesis-stimulating agents), serum creatinine 7.5 +/- 2.5 mg/dL, blood urea nitrogen 36 +/- 17 mg/dL, serum phosphate 4.3 mg/dL. In two thirds of the patients, blood pressure was controlled without antihypertensive agents. No patient had left ventricular hypertrophy. In this analysis, we found that relatively young subjects preferred PD first, with later transfer to HHD; that PD is superior as an introduction to dialysis therapy; that patients starting with PD prefer self medical treatment; and that all patients were free from the various complications that are encountered during long-term dialysis therapy. We suggest that patients who need dialysis therapy consider this new dialysis approach of "PD first and transfer to HHD."
Advances in peritoneal dialysis. Conference on Peritoneal Dialysis 01/2012; 28:106-11.
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ABSTRACT: The relationship between nurses and peritoneal dialysis (PD) patients begins from the time of the selection of medical treatment for renal replacement therapy. There are various roles in this field that involve nurses, not only in providing technical guidance to patients but also in relaying dietary restrictions including those on fluid and diet, in providing information on public welfare for dialysis patients and in fostering interactions between the patient and doctors, nutritionists, social workers and medical support staff. The nurse plays an important role in the success of a PD training program. Only highly trained nurses should carry out PD training. The nurse trains the patient or a family member as a helper to perform PD. The ultimate goal is to make a plan to help the patient maintain his or her general condition and expand the quality of life by self-care. However, the most important role of nurses is to display empathy to the patient, that is, to put themselves in the patient's position, to foster an ongoing interaction between themselves and the patient and to listen to the patient and understand what is in the mind of the patient.
Contributions to nephrology 01/2012; 177:64-70. · 1.49 Impact Factor
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ABSTRACT: Both continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) have their advantages regarding the treatment of patients with renal failure. In CAPD, solute removal is sometimes insufficient in patients who have a relatively large muscle mass that produces high levels of creatinine. To compensate for this deficiency, frequent exchanges and large peritoneal dialysate volumes are required. Alternatively, CAPD and HD as a combined modality of treatment for patients needing dialysis therapy has been proposed. Our experiences with three groups of patients are described. First, in 2003, 7 cases (6 males and 1 female; average age 54.3 ± 4.5 years; mean duration of CAPD therapy 4.3 ± 1.1 years; average weekly creatinine clearance (WCC) was 45.2 ± 1.7 l/1.73 m(2)) were treated with once-a-week HD therapy (3.5 h; 200 ml/h). Addition of once-a-week HD therapy improved WCC to 66 ± 7.1 liters/1.73 m(2). This improvement was due not only to the addition of HD therapy but also to an increase in creatinine clearance for 3 consecutive days after the completion of once-a-week HD therapy. Both creatinine clearance and ultrafiltration were significantly increased. Other clinical parameters such as blood pressure control, weight control, and dosage of erythropoietin were significantly improved after introducing this therapy. Second, we followed 9 CAPD patients who underwent an additional weekly HD for more than 3 years. Similar improvements were obtained in this long-term study as seen in the short-term study. Besides, the incidence of peritonitis decreased dramatically from 0.13 to 0.09 episodes/patient-year (p < 0.05) during the 3-year study. These data suggest that the combined use of CAPD and HD improves solute clearance in CAPD patients who are insufficiently dialyzed. Third, based on these data, we examined the efficacy of an early start of combination therapy and found that it stabilized dialysis therapy and prolonged the duration of CAPD. Combined with several of the previous several reports and our present experience, it is suggested that an early start of HD therapy will prolong the survival rate in patients on CAPD with physically stable conditions.
Contributions to nephrology 01/2012; 177:71-83. · 1.49 Impact Factor
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ABSTRACT: Zinc deficiency leads to decreased cellular immune responses. The overproduction of nitrogen species derived from inducible nitric oxide synthase (iNOS), its enzyme, and interleukine-1 beta (IL-1β), and inflammatory cytokine have been implicated in immune responses. The goal of this study was to investigate the effects of lipopolysaccharide (LPS)-induced changes in NO metabolites, iNOS, and IL-1β protein expression in the lungs of zinc-deficient rats. Male Sprague-Dawley rats (body weight, 100 g) were divided into two groups and were fed either a zinc-deficient diet (ZnD) or a zinc-containing diet (Cont). After 4 weeks on these diets, rats received a 10-mg/kg dose of LPS injected via the tail vein and were then maintained for an additional 72 h. To determine total NO concentrations in the blood, serum zinc concentration, iNOS protein expression, IL-1β, and iNOS immunohistochemistry, blood and lung samples were obtained at pre-LPS injection, 5, 24, and 72 h after injection. Total NO levels were significantly increased at 5, at 24, and at 72 h after LPS injection compared with pre-LPS injection level in ZnD group; significant changes in total NO levels was elevated at 5 h from at pre-LPS level but not significant changes from basal level at 24 and 72 h in the control group. Based on western blot analyses and immunohistochemistry, clear bands indicating iNOS and IL-1β protein expression and iNOS antibody-stained inflammatory cells were detected at 5 and 24 h in the ZnD group and 5 h in the Cont group, not observed at 24 and 72 h in the control group. These results suggest that zinc deficiency induces overexpression of iNOS and IL-1β proteins from inflammatory cells around the alveolar blood vessels, resulting in overproduction of total NO and persisted inflammatory response in the zinc-deficient rat lung. Taken together, overexpression of LPS-induced iNOS, overproduction of iNOS-derived NO, and overexpression of IL-1β may induce nitrosative and oxidative stresses in the lung, and these stresses may be involved low immunity of zinc deficiency states.
Biological trace element research 09/2011; 145(3):375-81. · 1.92 Impact Factor
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Tsutomu Inoue,
Eito Kozawa,
Hirokazu Okada,
Kouichi Inukai,
Shinichi Watanabe,
Tomohiro Kikuta,
Yusuke Watanabe,
Tsuneo Takenaka,
Shigehiro Katayama,
Junji Tanaka,
Hiromichi Suzuki
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ABSTRACT: Interstitial fibrosis and hypoxia accelerate the progression of CKD, but clinical tools to quantitate these factors in patients are lacking. Here, we evaluated the use of two magnetic resonance imaging (MRI) techniques, diffusion-weighted (DW)-MRI and blood oxygen level-dependent (BOLD)-MRI, to assess kidney fibrosis and hypoxia of the cortex in 142 patients with either diabetic nephropathy (n = 43), CKD without diabetes (n = 76), or acute kidney injury (AKI) (n = 23). Apparent diffusion coefficient (ADC) values of DW-MRI correlated with estimated glomerular filtration rates (eGFR) in the diabetic nephropathy and CKD groups (r(2) = 0.56 and r(2) = 0.46, respectively). Although the T2* values of BOLD-MRI and eGFR displayed good correlation in the CKD group (r(2) = 0.38), we did not observe a significant correlation between these values in the diabetic nephropathy group, suggesting that factors other than tubulointerstitial alteration determine the degree of hypoxia in the renal cortex. In the AKI group, neither the T2* nor ADC values correlated with eGFR. Renal biopsies from patients with CKD demonstrated that the T2* and ADC MRI values correlated with renal pathology. Taken together, ADC and T2* values appear to serve as accurate indices for evaluating renal tubulointerstitial alterations and parenchymal hypoxia, respectively, in the cortex. Functional MRI can thus contribute to multilateral, noninvasive, in vivo assessment of kidney function.
Journal of the American Society of Nephrology 08/2011; 22(8):1429-34. · 9.66 Impact Factor
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Kazuyuki Nakagome,
Mitsuru Imamura,
Hirokazu Okada,
Kimito Kawahata, Tsutomu Inoue,
Kumiko Hashimoto,
Hiroaki Harada,
Takehiro Higashi,
Rie Takagi,
Kazuhisa Nakano,
Koichi Hagiwara,
Minoru Kanazawa,
Makoto Dohi,
Makoto Nagata,
Sho Matsushita
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ABSTRACT: Allergic airway inflammation is generally considered a Th2-type immune response. Recent studies, however, demonstrated that Th17-type immune responses also play important roles in this process, especially in the pathogenesis of neutrophilic airway inflammation, a hallmark of severe asthma. We previously reported that dendritic cells release dopamine to naive CD4(+) T cells in Ag-specific cell-cell interaction, in turn inducing Th17 differentiation through dopamine D1-like receptor (D1-like-R). D1-like-R antagonist attenuates Th17-mediated diseases such as experimental autoimmune encephalomyelitis and autoimmune diabetes. However, the effect of antagonizing D1-like-R on Th17-mediated airway inflammation has yet to be studied. In this study, we examined whether D1-like-R antagonist suppresses OVA-induced neutrophilic airway inflammation in OVA TCR-transgenic DO11.10 mice and then elucidated the mechanism of action. DO11.10 mice were nebulized with OVA or PBS, and some mice received D1-like-R antagonist orally before OVA nebulization. D1-like-R antagonist significantly suppressed OVA-induced neutrophilic airway inflammation in DO11.10 mice. It also inhibited the production of IL-17 and infiltration of Th17 cells in the lung. Further, D1-like-R antagonist suppressed the production of IL-23 by lung CD11c(+) APCs. In contrast, D1-like-R antagonist did not increase Foxp3(+) regulatory T cells in the lung. D1-like-R antagonist neither suppressed nonspecific LPS-induced neutrophilic airway inflammation nor OVA-induced eosinophilic airway inflammation. These results indicate that D1-like-R antagonist could suppress Th17-mediated neutrophilic airway inflammation, raising the possibility that antagonizing D1-like-R serves as a promising new strategy for treating neutrophil-dominant severe asthma.
The Journal of Immunology 04/2011; 186(10):5975-82. · 5.79 Impact Factor
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ABSTRACT: Vascular calcification (VC) and arterial stiffness (AS) are major contributors to cardiovascular disease, and in chronic kidney disease, VC and AS are correlated. Disorders of calcium and phosphate metabolism contribute to the progression of VC and to increases in AS. The efficacy of cinacalcet (CIN) in reducing AS in patients on continuous ambulatory peritoneal dialysis (CAPD) has not been determined. The present study enrolled 19 CAPD patients (12 women, 7 men; mean age: 62.2 +/- 3.6 years) with serum intact parathyroid hormone (iPTH) greater than 500 ng/dL (mean value: 675 +/- 106 ng/dL) in whom daily oral treatment with CIN 25 mg was started. If administration of CIN for 3 months failed to reduce the level of iPTH to less than 300 ng/dL, the dose of CIN was increased to 50 mg daily. Before the start of CIN and at 3 years after the start of CIN, pulse wave velocity (PWV) was determined. In 11 patients, levels of iPTH were reduced to less than 300 ng/dL; levels in the rest of the patients remained high. We observed no significant differences in PWV before CIN and at 3 years after CIN start (1856 +/- 198 cm/s vs. 1726 +/- 187 cm/s). Multivariate regression analysis of PWV demonstrated that both systolic blood pressure and changes in serum levels of phosphate contributed to decreases in PWV In patients receiving CAPD, VC and AS might be the result of higher systolic blood pressure and increased serum levels of phosphate.
Advances in peritoneal dialysis. Conference on Peritoneal Dialysis 01/2011; 27:134-9.
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ABSTRACT: The newly developed erythropoiesis agent darbepoetin alpha (DA) allows for once-monthly dosing in the treatment of anemia in patients on dialysis. This dosing schedule has prompted some studies to examine the efficacy of DA in patients on continuous ambulatory peritoneal dialysis (CAPD). In the present study, we assessed whether intravenous (IV) administration of DA once monthly is effective for maintaining hemoglobin levels near 10.5 g/dL in patients on CAPD. This single-center prospective cohort study included 52 clinically stable patients (25 men, 27 women; mean age: 59 +/- 10 years). All patients had been on a stable weekly or twice monthly regimen of recombinant human erythropoietin (rHuEPO) before initiation of the study. To determine the monthly dose of DA, the previously used mean weekly dose of rHuEPO was divided by 200 to determine the equivalent weekly dose of DA in micrograms; that number was then multiplied by 4 to generate the monthly dose requirement. For example, if 3000 IUrHuEPO was being administered weekly, then the monthly dose of DA was calculated to be 60 microg (3000/200 x 4). All patients received a monthly dose of DA the first month, and hemoglobin and other routine laboratory tests were performed monthly for 24 consecutive weeks. In 26 patients, the calculated monthly DA dose remained stable. The monthly dose was increased by 25% in 22 patients and by 50% in 4 patients. With regard to iron stores and iron availability for erythropoiesis, no significant differences were observed in the patients on various doses of DA. Nonsignificant differences in weekly creatinine clearance as determined using the PD Adequest software (Baxter Healthcare, Tokyo, Japan) were observed between the groups. No clinically meaningful differences in other laboratory values between the groups were observed. Once-monthly administration of DA is not always sufficient to maintain hemoglobin levels in patients on CAPD when adequate dialysis therapy is not achieved.
Advances in peritoneal dialysis. Conference on Peritoneal Dialysis 01/2011; 27:60-4.
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ABSTRACT: The age of new dialysis patients is rapidly increasing. In the present study, we examined clinical presentation in new peritoneal dialysis (PD) patients 80 years of age or older at our hospital. Data were collected from the records of patients newly starting continuous ambulatory PD (CAPD) therapy between January 2005 and July 2010. During that period, 11 patients 80 years of age or older (average age: 83.1 +/- 3.8 years) were introduced to PD therapy. The reason for dialysis was hypertensive nephrosclerosis in 8 patients, and chronic glomerulonephritis, chronic tubulointerstitial nephritis, and an unknown primary disease in 1 patient each; there were no cases of diabetic nephropathy. At dialysis start, average serum creatinine was 6.1 +/- 1.4 mg/dL, arterial wall calcification was found by computed tomography or chest radiography in 10 of 11 patients (90.9%), and aortic or mitral valve calcification, or both, was found by echocardiography in 3 patients (27.3%). By the end of January 2011, 8 patients had died. Average survival after the start of PD was 31.9 +/- 22.3 months. Hypertensive nephrosclerosis, a cause less often seen in younger patients, was the most common primary disease among our elderly dialysis patients. As we previously reported, vascular and valvular calcification are important factors for determining prognosis; however, no significant relationships were observed in the present study, probably because almost all the patients had such calcifications.
Advances in peritoneal dialysis. Conference on Peritoneal Dialysis 01/2011; 27:71-6.
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ABSTRACT: We previously reported that peritoneal dialysis (PD)-associated peritonitis is a major cause of PD catheter removal. Another major cause is disease of the gastrointestinal tract, including neoplasm and perforation. In the present study, we reviewed the records of patients who underwent catheter removal at our hospital for reasons other than peritoneal infection--and for gastrointestinal disease in particular. Data were collected from the records of patients who received continuous ambulatory PD (CAPD) therapy between 2004 and 2010 at the Department of Nephrology, Saitama Medical University. Mean duration of CAPD was 6.2 +/- 4.7 years, and mean age at onset was 64.5 +/- 9.6 years. During the investigation period, catheters were removed from 13 patients (4 men, 9 women) because of gastrointestinal disease: gastric cancer in 3 cases, colon cancer in 3 cases, perforation of the lower gastrointestinal tract in 3 cases, and other reasons in 4 cases. Examination of pathology specimens obtained from 6 patients-including 1 in whom contrast-enhanced computed tomography indicated the presence of encapsulating peritoneal sclerosis (EPS)-revealed mild fibrosis in the subserous layer. No patient died of infection after a surgical procedure. Moreover, throughout the observation period, no patient developed new EPS or postoperative ileus. The present study suggests that CAPD itself seems to be free of untoward effects during the postoperative course in these patients.
Advances in peritoneal dialysis. Conference on Peritoneal Dialysis 01/2011; 27:77-81.
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ABSTRACT: It is not clear whether interstitial fibroblasts or tubular epithelial cells are primarily responsible for the profibrotic effects of NF-κB activation during renal fibrogenesis. Here, we crossed mice carrying a conditional IκB dominant-negative transgene (IκBdN) with mice transgenic for cell-specific FSP1.Cre (FSP1(+) fibroblasts) or γGT.Cre (proximal tubular epithelia) and challenged all progeny with unilateral ureteral obstruction. We determined NF-κB activation by nuclear localization of phosphorylated p65 ((p)p65) in renal tissues after 7 days. We observed inhibition of NF-κB activation in interstitial cells and tubular epithelia in obstructed kidneys of FSP1.Cre;IκBdN and γGT.Cre;IκBdN mice, respectively, compared with IκBdN controls (P < 0.05). Deposition of extracellular matrix, however, was significantly lower in the obstructed kidneys of FSP1.Cre;IκBdN mice but not in γGT.Cre;IκBdN mice (P < 0.05). In addition, levels of mRNA encoding the profibrotic PAI-1, fibronectin-EIIIA, and type I (α1) procollagen were significantly lower in obstructed kidneys of FSP1.Cre;IκBdN mice compared with γGT.Cre;IκBdN mice (P < 0.05). Taken together, these data support a profibrotic role for fibroblasts, but not proximal tubular epithelial cells, in modulating NF-κB activation during renal fibrogenesis.
Journal of the American Society of Nephrology 12/2010; 21(12):2047-52. · 9.66 Impact Factor
