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Introduction: Despite excellent biocompatibility, insertion of silicone peritoneal dialysis (PD) catheters can induce minor foreign body reaction, affecting long-term patient outcomes. We evaluated the effect of eosinophilic reaction associated with PD catheter insertion on outcomes of patients initiating PD. Methods: Eosinophilic reaction to PD catheter insertion was defined as the ratio of peripheral blood eosinophil count at 1 week after insertion (E1W) to pre-insertion eosinophil count (E0), and the association of E1W/E0 with technique survival, peritonitis-free survival, and heart failure (HF)-related hospitalization-free survival was analyzed. Results: This retrospective cohort study included 116 patients (89 male patients) who underwent PD catheter insertion between January 2008 and June 2018 (61.3 ± 12.9 years). The follow-up duration was 46.2 (23.8–75.3) months. E1W was significantly higher than E0 (median, 333 vs. 234/μL, p < 0.001), with a median E1W/E0 of 1.54. The log-rank test showed that technique survival, peritonitis-free survival, and HF-related hospitalization-free survival were significantly better in patients with E1W/E0 < 1.54 than in those with E1W/E0 ≥ 1.54 (p = 0.002, p = 0.01; HR 2.19, p < 0.001; HR 2.15, p < 0.001, respectively). Conclusion: Eosinophilic reaction at the time of PD catheter insertion is a novel marker that may predict outcomes in patients initiating PD.

Dexmedetomidine (DEX) is a sedative agent with minimal respiratory and hemodynamic effects. The present study aimed to evaluate its effectiveness in peritoneal dialysis (PD) catheter insertion. This single-center retrospective study included patients who underwent PD catheter insertion under spinal anesthesia in our hospital between January 2016 and December 2020. Patients were divided into the DEX and non-DEX groups according the use of DEX. After 1:1 propensity score matching to adjust for age, sex, body mass index, mean blood pressure (BP), and Charlson comorbidity index, we compared operation-related outcomes, including peak numerical rating scale (NRS), occurrence of nausea, vital signs, or operative time between the two groups. Of a total of 44 patients, 9 patients received DEX, and 35 did not. After propensity score matching, each group consisted of 8 patients. Peak NRS was significantly lower (P = 0.003) in the DEX group compared with the non-DEX group. Maximum mean BP during the operation was also significantly lower in the DEX group compared with the non-DEX group (P = 0.020), with no significant differences in minimum mean BP between the two groups (P = 0.831). The DEX group showed a trend of shortened operative time (P = 0.068). There were no significant differences in the occurrence of nausea (P = 1.000). Moreover, there was no clinically important adverse event associated with use of DEX. The use of DEX in PD catheter insertion under spinal anesthesia could safely improve operative analgesia.

The number of elderly patients requiring dialysis is continuously increasing. In Japan, many patients undergo hemodialysis; however, it has been associated with huge stress-mainly on the cardiovascular system-and requires frequent hospital visits. Conversely, peritoneal dialysis is much less invasive with a much lower frequency of hospital visits than that of hemodialysis; therefore, it is suitable for elderly patients. In addition, peritoneal dialysis, which originally had a high affinity for home care, has become more useful for elderly patients with renal failure thanks to the recent introduction of a cloud-based remote monitoring system at home. We performed percutaneous placement of a peritoneal dialysis catheter to reduce physical invasiveness and initiate peritoneal dialysis. The Barthel Index before hospitalization was 0 but increased to 65 at discharge. Further technology advancements in peritoneal dialysis are expected in the future. The cloud-based remote monitoring system is also expected to maintain or increase activities of daily living and the quality of life in elderly patients with renal failure with decreased activities of daily living.

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease. Although several cases of BP in end-stage renal disease patients receiving peritoneal dialysis (PD) or hemodialysis have been reported, the incidence of BP in these patients remains unknown. We recently experienced three PD patients diagnosed with BP. The skin injury was likely to be a trigger of BP in all the three PD patients. Nifedipine and icodextrin exposures were possible factors directly or indirectly affecting the onset of BP, because they were common in the three cases. We also report that the incidence of BP in PD patients was 3/478.3 person-years in a single-center 10-year study. This case series with a literature survey describes that the skin and tissue injuries are potential triggers responsible for the onset of BP in dialysis patients and that the incidence of BP in these patients seems to be much higher than that in the general population.

Objective: The incremental shuttle walking test (ISWT) is an important marker of aerobic capacity in patients on peritoneal dialysis (PD). This study aimed to evaluate its predictive value for PD-related outcomes. Methods: This single-center cohort study recruited outpatients on maintenance PD from our hospital between March 2017 and March 2018. Exercise capacity was assessed using measurement of ISWT and handgrip and quadriceps strength. Patients were divided into 2 groups according to the median of exercise capacity and prospectively followed up until cessation of PD, death, or the study end (October 2019). The primary end point of this study was technique survival rate, and secondary outcomes were rates of peritonitis-free survival and PD-related hospitalization-free survival. Results: Among the 50 participants, age and PD vintage were [median (IQR)] 62.5 (58.3–70) and 3.5 (1.3–6.5) years, respectively. At the end of the study, 3 of the 28 participants (11%) in the long-ISWT group and 13 of the 22 participants (59%) in the short-ISWT group were transferred to hemodialysis. The short-ISWT group showed lower technique survival rate (p < 0.001), peritonitis-free survival rate (p = 0.01), and PD-related hospitalization-free survival rate (p < 0.01) than the long-ISWT group, whereas those survival rates did not differ when participants were divided by handgrip or quadriceps strength. Multivariate analysis revealed lower ISWT to be independently associated with technique failure (p = 0.002). Conclusion: The ISWT is an important predictor of technique survival for patients on PD. Monitoring and enhancing ISWT as a marker of aerobic capacity might improve PD-related outcomes.

Background Peritonitis is a common and clinically important complication in patients receiving peritoneal dialysis (PD). Antibiotic administration is essential for PD-related peritonitis, but routes of administration have not been established enough. Here, we performed a systematic review to assess the efficacy and safety of intraperitoneal (IP) antibiotic administration compared to intravenous (IV) antibiotic administration in patients with PD-related peritonitis. Methods Cochrane CENTRAL, MEDLINE, and Ichushi-Web were searched in June 2017. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed, and articles were screened by four independent reviewers. Results Two randomized controlled trials (113 patients) were identified. IP antibiotic administration was more effective than IV antibiotic administration. The pooled risk difference between IP and IV was 0.13 (95% CI − 0.17 to 0.43). Safety assessment indicated less frequency of side effects in patients receiving IP antibiotic administration. The pooled risk ratios of IV to IP regarding adverse drug reaction-related and administration route-related side effects were 5.13 (0.63 to 41.59) and 3.00 (0.14 to 65.90), respectively. Conclusion The systematic review and meta-analysis suggested that IP antibiotic administration is more effective and safer in patients with PD-related peritonitis compared to IV antibiotic administration.

We aimed to investigate the effects of exercise on renal outcomes in patients undergoing peritoneal dialysis (PD). In a post-hoc analysis of a randomized controlled trial of a 12-week home-based exercise program involving 47 patients undergoing PD, we excluded 18 patients with anuria and analyzed 13 and 16 patients in the usual care and exercise groups, respectively. The primary outcomes were weekly renal creatinine clearance (CCr) and urinary biomarkers: liver-type fatty acid-binding protein (L-FABP) and the microalbumin-to-creatinine ratio (ACR). Although the maintenance of weekly renal CCr in the exercise group was not significantly different compared with that in the usual care group (P = .09), urinary L-FABP levels (P = .02) and ACR (P = .04) were significantly decreased in the exercise group. To the best of our knowledge, this is the first study to demonstrate the beneficial effects of exercise on renal outcomes in patients undergoing PD.

Background This article is a duplicated publication from the Japanese version of “2019 JSDT Guidelines for Peritoneal Dialysis” with permission from the Japanese Society for Dialysis Therapy (JSDT). This clinical practice guideline (CPG) was developed primarily by the Working Group on Revision of Peritoneal Dialysis (PD) Guidelines of the Japanese Society for Dialysis Therapy. Recently, the definition and creation process for CPGs have become far more rigorous; traditional methods and formats no longer adhere to current standards. To improve the reliability of international transmission of our findings, CPGs are created in compliance with the methodologies developed by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) working group. Part 2 of this PD guideline is the first CPG developed by our society that conforms to the GRADE approach. Methods Detailed processes were created in accordance with the Cochrane handbook and the GRADE approach developed by the GRADE working group. Results Clinical question (CQ)1: Is the use of renin-angiotensin system inhibitors (RAS inhibitors), such as angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB), effective in PD patients? Recommendation: We suggest the usage of RAS inhibitors (ACEI and ARB) in PD patients (GRADE 2C). CQ2: Icodextrin or glucose solution: which is more useful as a dialysate among patients with PD? Recommendation: We suggest using icodextrin when managing body fluids in PD patients (GRADE 2C). CQ3: Is it better to apply or not apply mupirocin/gentamicin ointment to the exit site? Recommendation: We suggest not applying mupirocin/gentamicin ointment to the exit sites of PD patients (GRADE 2C). CQ4: Which surgical approach is more desirable when a PD catheter is placed, open surgery or laparoscopic surgery? No recommendation. CQ5: Which administration route of antibiotics is better in PD patients with peritonitis, intravenous or intraperitoneal? Recommendation: We suggest intraperitoneal administration of antibiotics in PD patients with peritonitis (GRADE 2C). Note: The National Insurance does not currently cover intraperitoneal administration. CQ6: Is peritoneal dialysis or hemodialysis better as the first renal replacement therapy in diabetic patients? No recommendation. Conclusions In the future, we suggest that society members construct their own evidence to answer CQs not brought up in this guideline, and thereby show the achievements of Japan worldwide.

Potential effects of aerobic and resistance training in peritoneal dialysis (PD) patients have been partially elucidated. We investigated effects of a home-based exercise program on physical functioning and health-related quality of life (HRQOL) in PD patients. Patients were randomly assigned to exercise (n = 24) and usual care (n = 23) groups. The exercise patients performed aerobic exercise thrice weekly and resistance training twice weekly at home for 12 weeks. The usual care patients received no specific intervention. The distance in incremental shuttle walking test significantly improved in the exercise group compared with the usual care group (P = 0.02). Among the HRQOL subscales assessed using the Kidney Disease Quality of Life-Short Form questionnaire, kidney disease component summary (P = 0.03), physical role functioning (P = 0.01), emotional role functioning (P P P = 0.03). There were no reported adverse events associated with the intervention. To our knowledge, this is the first randomized controlled trial to indicate the beneficial effects of a 12-week home-based exercise program exclusively in PD patients.

Background Muscle wasting, common and progressive in uremic patients, is associated with a high probability for morbidity, lower health-related quality of life (HRQOL), and mortality. However, exercise tolerance in peritoneal dialysis (PD) patients has not been fully elucidated. The aim of this study was to evaluate exercise capacity, its determinants, and its association with HRQOL in PD patients. Methods Outpatients treated with PD at Keio University Hospital from December 2016 to March 2018 were included in this single-center cross-sectional observational study. Exercise capacity was assessed by incremental shuttle walking test (ISWT) and handgrip and quadriceps strength. In addition to evaluation of PD-related parameters, HRQOL was assessed by the Kidney Disease Quality of Life-Short Form questionnaire. Results Among the 50 recruited PD outpatients, age and PD vintage were 63.8 ± 9.6 and 3.8 ± 2.8 years, respectively. Physical examination revealed ISWT of 312.0 ± 138.2 m, handgrip strength of 27.5 ± 6.9 kg, and quadriceps strength of 23.3 ± 10.0 kg. Multivariate analysis showed that younger age and male sex were significantly associated with higher ISWT and handgrip and quadriceps strength. Skeletal mass index (SMI) remained a significant predictor of handgrip and quadriceps strength. Moreover, only ISWT was strongly correlated with higher HRQOL scores, including physical, mental, and kidney-specific domains, even after adjustment for age and sex. Conclusions Exercise tolerance in PD patients was partially determined by age, sex, and SMI. Moreover, this is the first study to demonstrate the strong relationship between aerobic capacity and HRQOL in PD patients.

The risk factors for intradialytic systolic blood pressure decline remain poorly understood. We aimed to identify clinical and laboratory predictors of the intradialytic systolic blood pressure decline, considering its seasonal variation. In a retrospective cohort of 47,219 hemodialysis sessions of 307 patients undergoing hemodialysis over one year in three dialysis clinics, the seasonal variation and the predictors of intradialytic systolic blood pressure decline (predialysis systolic blood pressure--nadir intradialytic systolic blood pressure) were assessed using cosinor analysis and linear mixed models adjusted for baseline or monthly hemodialysis-related variables, respectively. The intradialytic systolic blood pressure decline was greatest and least in the winter and summer, respectively, showing a clear seasonal pattern. In both models adjusted for baseline and monthly hemodialysis-related parameters, calcium channel blocker use was associated with a smaller decline (-4.58 [95% confidence interval (CI), -5.84 to -3.33], P < 0.001; -3.66 [95% CI, -5.69 to -1.64], P < 0.001) and α blocker use, with a greater decline (3.25 [95% CI, 1.53-4.97], P < 0.001; 3.57 [95% CI, 1.08-6.06], P = 0.005). Baseline and monthly serum phosphorus levels were positively correlated with the decline (1.55 [95% CI, 0.30-2.80], P = 0.02; 0.59 [95% CI, 0.16-1.00], P = 0.007), and baseline and monthly normalized protein catabolic rates were inversely correlated (respectively, -22.41 [95% CI, -33.53 to -11.28], P < 0.001; 9.65 [95% CI, 4.60-14.70], P < 0.001). In conclusion, calcium channel blocker use, α blocker avoidance, and serum phosphorus-lowering therapy may attenuate the intradialytic systolic blood pressure decline and should be investigated in prospective trials.

Aims Remote monitoring (RM) can improve management of chronic diseases. We evaluated the impact of RM in automated peritoneal dialysis (APD) in a simulation study. Materials and methods We simulated 12 patient scenarios with common clinical problems and estimated the likely healthcare resource consumption with and without the availability of RM (RM+ and RM- groups, respectively). Scenarios were evaluated 4 times by randomly allocated nephrologist-nurse teams or nephrologist-alone assessors. Results The RM+ group was assessed as having significantly lower total healthcare resource consumption compared with the RM- group (36.8 vs. 107.5 total episodes of resource consumption, p = 0.002). The RM+ group showed significantly lower "unplanned hospital visits" (2.3 vs. 11.3, p = 0.005), "emergency room visits" (0.5 vs. 5.3, p = 0.003), "home visits" (0.5 vs. 5.8, p = 0.016), "exchanges over the telephone" (18.5 vs. 57.8, p = 0.002), and "change to hemodialysis" (0.5 vs. 2.5, p = 0.003). Evaluations did not differ between nephrologist-nurse teams vs. nephrologist-alone assessors. Conclusion RM can be expected to reduce healthcare resource consumption in APD patients. .

Background Peritonitis secondary to bowel perforation is a rare and potentially fatal complication in peritoneal dialysis (PD) patients. However, the early diagnosis of bowel perforation is difficult in PD patients because the initial symptoms and signs of bowel perforation are similar to those of PD-associated peritonitis. Furthermore, the risk of bowel perforation in PD patients is unclear. Here, we present a case of intestinal perforation located at the site of adhesive intestinal obstruction in a PD patient. Case presentation A 73-year-old man on PD presented with progressive worsening of abdominal pain and cloudy peritoneal fluid. The peritoneal fluid cell count was increased to 980/ml and peritoneal dialysis-associated peritonitis was diagnosed. Computed tomography showed local adhesions causing agglomeration of the dilated intestine. He initially responded to antibiotic treatment; however, his abdominal pain was rapidly worsened after resumption of oral intake. On hospital day 23, computed tomography showed loss of contents from the dilated intestine and discharge of fecal material from the PD tube was noted. Thus, small bowel perforation was diagnosed, and he underwent ileocecal resection with colostomy creation. As indicators of EPS was not evident, PD catheter was removed. Since then, he has been on maintenance of hemodialysis since then. Conclusion The findings of the present case suggest that adhesive intestinal obstruction in PD patients can increase the risk of intestinal perforation. Careful monitoring for the early detection of intestinal perforation is required in such cases.

Background: Cyst infection is a complication sometimes seen in patients with autosomal dominant polycystic kidney disease (ADPKD) and often shows through a positive blood culture. However, there have been no reports of ADPKD patients whose cyst infection propagate to peritoneal fluid leading to positive peritoneal fluid culture. Case presentation: A 74-year-old Japanese man with ADPKD under peritoneal dialysis (PD) was presented with left flank pain, fever, and chills at our hospital. He did not show any symptoms or signs suggestive of peritonitis. There were no elevated cell counts or polymorphonuclear leucocytes in his PD fluid. There were some complicated cysts found in computed tomography and magnetic resonance imaging examinations. We clinically diagnosed him as having a renal cyst infection rather than PD-related peritonitis. We initiated treatment by administering ceftriaxone with an immediate favorable response. As the possibility of accompanying prostatitis still remained, we switched to intravenous levofloxacin on the second day. On the 10th day, Helicobacter cinaedi was detected in 2 sets of blood culture as well as in PD fluid. We switched back to ceftriaxone and this treatment was entirely successful. Conclusions: This is the first report of H cinaedi cyst infection which propagates to peritoneal fluid in a patient with ADPKD.

Most infections related to peritoneal dialysis (PD) are caused by common bacteria, and non-tuberculous mycobacteria are rare. The clinical characteristics and prognosis of PD patients with non-tuberculous mycobacterial infections were investigated at our hospital. Non-tuberculous mycobacteria were detected in 11 patients (exit-site infection, tunnel infection, and peritonitis in 3, 5, and 3 patients, respectively). Mycobacterium fortuitum, Mycobacterium chelonae, and Mycobacterium abscessus were identified in 4, 2, and 2 patients, respectively. Most patients with peritonitis or tunnel infection required catheter removal. During the study period (2007 – 2017), peritonitis occurred in 44 patients, including 3 patients (6.8%) with non-tuberculous mycobacterial peritonitis. When non-tuberculous mycobacterial infection occurs, multi-agent antibiotic therapy, unroofing surgery, and/or catheter replacement should be performed to prevent peritonitis.

Calciphylaxis presents with painful purpura and intractable skin ulcers on the trunk and particularly the distal extremities, and it mainly occurs in patients on chronic dialysis. A 66-year-old man with renal failure due to diabetic nephropathy was on peritoneal dialysis alone for 1 year, followed by peritoneal dialysis combined with hemodialysis for 3 years. He developed calciphylaxis of the penis, which was diagnosed from the skin biopsy findings and clinical observation. To treat this condition, PD was stopped and HD was performed three times a week. In addition, warfarin therapy was discontinued and infusion of sodium thiosulfate was performed. The penile ulcers decreased in size and pain was markedly improved, so the patient was discharged from hospital. Following discharge, PD was resumed after changing the peritoneal dialysis fluid to bicarbonate-buffered dialysate. The penile ulcers eventually resolved completely. There have been very few reports about calciphylaxis in patients on combined dialysis modalities. In our patient, penile calciphylaxis progressed when lactate-buffered peritoneal dialysis fluid was used and resolved after switching to bicarbonate-buffered fluid together with cessation of warfarin therapy and infusion of sodium thiosulfate.

Background Peritonitis is one of the most frequent reasons for withdrawal of peritoneal dialysis (PD). Although most cases of PD-related peritonitis can be treated with antibiotics, it is occasionally refractory and culture-negative. Summary The causes of refractory PD-related peritonitis include antibiotic-resistant bacteria, fungal peritonitis, biofilm formation in PD catheters, bacterial translocation from the gastrointestinal tract, and encapsulating peritoneal sclerosis. Among them, culture-negative peritonitis is notable, and non-tuberculous mycobacteria (NTM) can be a cause of culture-negative peritonitis. In the present study, the treatment and outcomes of NTM peritonitis and exit site infections were investigated by collecting data from relevant reviews published during the last 10 years. Catheter removal was required in 92.2% of the patients with NTM peritonitis, and withdrawal of PD was performed in 91.9%. The overall mortality rate (including unrelated deaths) was 12.4% in patients with NTM peritonitis. Among patients with NTM exit site infections, 33.3% developed peritonitis, and catheter removal was required in 50.0%. A lower percentage of patients stopped PD when the catheter was removed without developing peritonitis (37.5%) than when it was removed after the onset of peritonitis (91.9%). Changing the exit site or unroofing was performed in 12.5% of the patients with NTM exit site infections. In addition, these infections resolved with antibiotics alone or without antibiotics in 18.8 and 12.5% of the patients, respectively, while 6.25% of the patients died. Key Messages: NTM peritonitis often requires catheter removal or withdrawal of PD, and the associated mortality is not low. Thus, prevention of NTM peritonitis is important. In patients with NTM exit site infections, appropriate antimicrobial therapy and/or PD catheter removal should be performed to prevent peritonitis.

New erythropoiesis-stimulating agents with a longer half-life have been developed for the treatment of anemia in patients with end-stage renal disease. This study evaluated the efficacy of darbepoetin alfa (DA) and long-acting epoetin beta pegol (continuous erythropoietin receptor activator, CERA) in patients on peritoneal dialysis (PD). Twenty-nine patients who had undergone PD for at least 6 months and were iron replacement-naive and negative for inflammatory parameters were enrolled. Hemoglobin (Hgb) levels and blood pressure were evaluated before and after switching from DA to CERA. Percent transferrin saturation (TSAT), serum ferritin levels and blood pressure were also assessed. Twenty-eight patients were subject to the analysis, excluding one patient with a decrease in Hgb by ≥10%. Switching from DA to CERA did not alter Hgb levels. The doses of DA and CERA after 12 month treatment of each agent were 118.48 ± 79.63 and 89.88 ± 47.50 μg/4 weeks, respectively (conversion ratio, 1:0.76). The CERA dose administered during the final 6 months was abated, compared with that given during the initial 6 months (P = 0.035). The frequency of CERA injection over a 12-month period was less than that of DA (10.0 ± 3.0 vs. 16.4 ± 5.0, P

In this study, we examined the association between chronic kidney disease (CKD) and insulin resistance. In a patient cohort with nondiabetic stages 2-5 CKD, estimated glomerular filtration rate (eGFR) was negatively correlated and the plasma aldosterone concentration was independently associated with the homeostasis model assessment of insulin resistance. Treatment with the mineralocorticoid receptor blocker spironolactone ameliorated insulin resistance in patients, and impaired glucose tolerance was partially reversed in fifth/sixth nephrectomized rats. In these rats, insulin-induced signal transduction was attenuated, especially in the adipose tissue. In the adipose tissue of nephrectomized rats, nuclear mineralocorticoid receptor expression, expression of the mineralocorticoid receptor target molecule SGK-1, tissue aldosterone content, and expression of the aldosterone-producing enzyme CYP11B2 increased. Mineralocorticoid receptor activation in the adipose tissue was reversed by spironolactone. In the adipose tissue of nephrectomized rats, asymmetric dimethylarginine (ADMA; an uremic substance linking uremia and insulin resistance) increased, the expression of the ADMA-degrading enzymes DDAH1 and DDAH2 decreased, and the oxidative stress increased. All of these changes were reversed by spironolactone. In mature adipocytes, aldosterone downregulated both DDAH1 and DDAH2 expression, and ADMA inhibited the insulin-induced cellular signaling. Thus, activation of mineralocorticoid receptor and resultant ADMA accumulation in adipose tissue has, in part, a relevant role in the development of insulin resistance in CKD.

Background The Scientific Academy Committee of Japanese Society for Dialysis Therapy (JSDT) has developed 14 clinical practice guidelines (CPGs) and their revised editions independently or in cooperation with other organizations and translated many of them into English to make them available to the world. These guidelines were presented in a user-friendly textbook-like format and were useful for many healthcare professionals engaged in dialysis therapy. However, because the definition and the process for developing CPGs have recently become more rigorous worldwide, the conventional process of development and the format of JSDT no longer meet the requirements for CPGs. Method Since 2012, JSDT, with its Guideline Developing Working Group (formerly Guideline Subcommittee), had evaluated several CPGs developing systems. The working group evaluated the advantages and disadvantages of several CPGs developing systems. The most important point of them which JSDT would adopt for their own system was to be based on evidence and be able to receive international recognition. Results In Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system, the quality of evidence was evaluated by systematic review on each clinical outcome by systematic review panel. After the report from the systematic review panel, the CPG panel grades the strength of recommendation on each CPG statement. GRADE system was the most frequently used for developing CPGs by many human healthcare societies in the world. If JSDT adopt GRADE system, it is necessary for us to learn how to assess the quality of evidence through a systematic review, to develop a system for determining the strength of recommendation on the basis of a systematic review, and to decide how to manage any conflicts of interest. Conclusions JSDT should provide the useful information from Japanese experiences on chronic dialysis to the world. In order to achieve this aim, we concluded that the most reasonable approach is to utilize the data from JSDT Renal Data Registry in a more creative manner, publish such data for the world as evidence, and develop CPGs in accordance with a globally recognized methodology, GRADE. Notification The current manuscript is the position statement of JSDT for developing future CPGs and the second publication of “Policy for Developing Clinical Practice Guidelines (CPGs) of the Japanese Society for Dialysis Therapy” on J Jpn Soc Dial Ther 2016; 49: 453-62 (in Japanese), with permission.

Background Current status and clinical significance of interventional nephrology has not been reported from Japan. Methods Questionnaires were mailed twice to the directors of all 534 Japanese certificated nephrology training institutions in 2014. The main questions were current performance, categorized annual procedure volume and managers of peritoneal dialysis (PD) access, vascular access (VA) surgery, endovascular intervention, and kidney biopsy. Frequencies of nephrologist involvement between high volume center and low volume center and association between the level of nephrologists’ involvement to each procedure and annual procedure volume were examined. Results 332 (62.2%) institutions answered performance of all procedures and 328 (61.4%) institutions answered all procedure volume. Kidney biopsy, VA surgery, endovascular intervention and PD access surgery were performed by any doctors in 94.2, 96.3, 88.4, and 76.2% and each involvement of nephrologist was 93.9, 54.1, 53.1 and 47.6%, respectively. Cochran–Armitage analyses demonstrated significant increases in all 4 procedure volume with greater management by nephrologists (p

OBJECTIVE: We examined whether aldosterone/Rho/Rho-kinase pathway contributed to obesity-associated nephropathy. SUBJECTS: C57BL/6J mice were fed a high fat or low fat diet, and mice on a high fat diet were treated with a mineralocorticoid receptor antagonist, eplerenone. RESULTS: The mice on a high fat diet not only developed obesity, but also manifested renal histological changes, including glomerular hypercellularity and increased mesangial matrix, which paralleled the increase in albuminuria. Furthermore, enhanced Rho-kinase activity was noted in kidneys from high fat diet-fed mice, as well as increased expressions of inflammatory chemokines. All of these changes were attenuated by eplerenone. In high fat diet-fed mice, mineralocorticoid receptor protein levels in the nuclear fraction and SGK1, an effector of aldosterone, were upregulated in kidneys, although serum aldosterone levels were unaltered. Furthermore, aldosterone and 3β-hydroxysteroid dehydrogenase in renal tissues were upregulated in high fat diet-fed mice. Finally, in cultured mesangial cells, stimulation with aldosterone enhanced Rho-kinase activity, and pre-incubation with eplerenone prevented the aldosterone-induced activation of Rho kinase. CONCLUSION: Excess fat intake causes obesity and renal injury in C57BL/6J mice, and these changes are mediated by an enhanced mineralocorticoid receptor/Rho/Rho-kinase pathway and inflammatory process. Mineralocorticoid receptor activation in the kidney tissue and the subsequent Rho-kinase stimulation are likely to participate in the development of obesity-associated nephropathy without elevation in serum aldosterone levels.

Background. Peritoneal fibrosis (PF) and angiogenesis are typical morphological changes, leading to loss of peritoneal functions in patients undergoing peritoneal dialysis. The small G protein, Rho, and its downstream effector Rho-kinase have been shown to be involved in the tissue fibrosis process. This study was undertaken to investigate the role of Rho-kinase in the pathogenesis of these alterations. Methods. PF was induced by intraperitoneal administration of chlorhexidine (CHX) in male rats (CHX group). These rats were treated with a Rho-kinase inhibitor, fasudil (Fas group). Human pleural mesothelial cells, MeT-5A cells, were stimulated by glucose with or without another Rho-kinase inhibitor, Y-27632. Results. Peritoneal damage including peritoneal thickening, fibrous changes, macrophage migration and angiogenesis were evident in the CHX group and were ameliorated in the Fas group. The expression of markers of tissue fibrosis, such as transforming growth factor (TGF)-b, fibronectin and a-smooth muscle cell actin, were increased in the CHX group and were downregulated by fasudil. Similar results were also seen with an inducer of angiogenesis, vascular endothelial growth factor (VEGF). Rho-kinase was activated in the peritoneum of the CHX group, which was inhibited by fasudil. In MeT-5A cells, high glucose increased TGF-b expression and VEGF secretion, which were blocked by Y-27632. Conclusions. The activation of Rho-kinase is involved in peritoneal damage at multiple stages including tissue fibrosis and angiogenesis. The inhibition of Rho-kinase constitutes a novel strategy for the treatment of PF.

症例は46歳，女性．41歳時に骨盤部胞巣状軟部肉腫の治療に伴い右骨盤半裁，人工股関節置換術を施行された．2005年に腎動脈狭窄に対して経皮的腎血管拡張術を施行されたが徐々に腎機能が悪化し，2007年1月に腹膜透析（CAPD）が導入された．2008年3月に転倒し，右大腿骨骨折にて当院整形外科に入院，観血整復固定術・自家腓骨移植術を施行された．5月15日より腹痛を認めたが腹膜炎の所見は認めず，5月21日退院となった．5月29日外来受診時は血液検査所見に異常所見はなかったが，5月30日より腹痛出現，徐々に症状増悪し，6月5日当院を受診し腹膜炎疑いにて緊急入院した．抗生剤の点滴静注（ceftazidime hydrate（CAZ）1 g/日，cefazolin sodium（CEZ）1 g/日，vancomycin hydrochloride（VCM）1 g/日）および腹腔内投与CAZ 1 g/日，CEZ 1 g/日）を施行したが，症状改善せずCAPD排液細胞数は540/μLから940/μLへ上昇した．第5病日，排液細菌培養にて複数菌が判明し，第6病日には腹痛が増悪し，排液は黄色混濁し排液細胞数5,200/μL，腹部CTにてfree airを認め緊急手術となった．大腿骨頭置換のボルトの背側の骨盤腔の間隙に小腸が嵌頓し，回腸末端部より30 cm口側に嵌頓部の穿孔を認めた．術後は集中治療室にて持続的血液透析濾過を施行し，同時にエンドトキシン吸着を施行した．術後経過は順調であり，腹膜透析から血液透析へ移行した．本症例では抗生物質の無効，CAPD排液の色調異常，CAPD排液培養から複数菌の検出などから，通常の細菌性急性腹膜炎ではないと判断し，腹部CTで確定診断に至った．骨盤あるいはその支持組織への侵襲手術後の骨盤内間隙に腸管嵌頓を誘発し，CAPDの中止を余儀なくされた症例を経験した．

The development of obesity involves multiple mechanisms. Here, we identify adipocyte signaling through the guanosine triphosphatase Rho and its effector Rho-kinase as one such mechanism. Mice fed a high-fat diet (HFD) showed increased Rho-kinase activity in adipose tissue compared to mice fed a low-fat diet. Treatment with the Rho-kinase inhibitor fasudil attenuated weight gain and insulin resistance in mice on a HFD. Transgenic mice overexpressing an adipocyte-specific, dominant-negative form of RhoA (DN-RhoA TG mice) showed decreased Rho-kinase activity in adipocytes, decreased HFD-induced weight gain, and improved glucose metabolism compared to wild-type littermates. Furthermore, compared to HFD-fed wild-type littermates, DN-RhoA TG mice on a HFD showed decreased adipocyte hypertrophy, reduced macrophage recruitment to adipose tissue, and lower expression of mRNAs encoding various adipocytokines. Lipid accumulation in cultured adipocytes was associated with increased Rho-kinase activity and increased abundance of adipocytokine transcripts, which was reversed by a Rho-kinase inhibitor. Direct application of mechanical stretch to mature adipocytes increased Rho-kinase activity and stress fiber formation. Stress fiber formation, which was also observed in adipocytes from HFD-fed mice, was prevented by Rho-kinase inhibition and in DN-RhoA TG mice. Our findings indicate that lipid accumulation in adipocytes activates Rho to Rho-kinase (Rho-Rho-kinase) signaling at least in part through mechanical stretch and implicate Rho-Rho-kinase signaling in inflammatory changes in adipose tissue in obesity. Thus, inhibition of Rho-Rho-kinase signaling may provide a therapeutic strategy for disrupting a vicious cycle of adipocyte stretch, Rho-Rho-kinase signaling, and inflammation of adipose tissue that contributes to and aggravates obesity.

Sirt1, a NAD-dependent protein deacetylase, is reported to regulate intracellular metabolism and attenuate reactive oxidative species (ROS)-induced apoptosis leading to longevity and acute stress resistance. We created transgenic (TG) mice with kidney-specific overexpression of Sirt1 using the promoter sodium-phosphate cotransporter IIa (Npt2) driven specifically in proximal tubules and investigated the kidney-specific role of Sirt1 in the protection against acute kidney injury (AKI). We also elucidated the role of number or function of peroxisome and mitochondria in mediating the mechanisms for renal protective effects of Sirt1 in AKI. Cisplatin-induced AKI decreased the number and function of peroxisomes as well as mitochondria and led to increased local levels of ROS production and renal tubular apoptotic cells. TG mice treated with cisplatin mitigated AKI, local ROS, and renal tubular apoptotic tubular cells. Consistent with these results, TG mice treated with cisplatin also exhibited recovery of peroxisome number and function, as well as rescued mitochondrial function; however, mitochondrial number was not recovered. Immunoelectron microscopic findings consistently demonstrated that the decrease in peroxisome number by cisplatin in wild type mice was restored in transgenic mice. In HK-2 cells, a cultured proximal tubule cell line, overexpression of Sirt1 rescued the cisplatin-induced cell apoptosis through the restoration of peroxisome number, although the mitochondria number was not restored. These results indicate that Sirt1 overexpression in proximal tubules rescues cisplatin-induced AKI by maintaining peroxisomes number and function, concomitant up-regulation of catalase, and elimination of renal ROS levels. Renal Sirt1 can be a potential therapeutic target for the treatment of AKI.

AIM Cerebrovascular disease (CVD) is a major determinant of the prognosis in end-stage renal diseases (ESRD). The purpose of this study was to examine whether factors associated with arterial stiffness contributed to the development of CVD in patients with ESRD. METHODS CVD (lacunes and carotid/intracranial artery stenosis) was evaluated with brain magnetic resonance imaging (MRI), and carotid/intracranial artery magnetic resonance angiography (MRA) in 44 pre-dialytic patients. The severity of CVD was evaluated by the number of lacunes and the degree of stenosis, respectively. The association between CVD and atherosclerotic parameters was evaluated. RESULTS Patients with severe lacunes (n=18) manifested older age, lower diastolic blood pressure, serum creatinine and albumin, and higher CRP and serum calcium than those with absent-moderate lacunes (n=26). When assessed by multivariate analysis, only baPWV was adopted as an independent risk factor for severe lacunes. Furthermore, baPWV and i-PTH were associated with the severity of carotid/intracranial artery stenosis, both of which were independent of other risk factors, including age and diabetes. CONCLUSIONS Arterial stiffness may constitute a novel determinant predicting the severity of CVD in pre-dialytic patients besides classical risk factors.

NAD(+)-dependent protein deacetylase Sirt1 regulates cellular apoptosis. We examined the role of Sirt1 in renal tubular cell apoptosis by using HK-2 cells, proximal tubular cell lines with or without reactive oxygen species (ROS), H(2)O(2). Without any ROS, Sirt1 inhibitors enhanced apoptosis and the expression of ROS scavenger, catalase, and Sirt1 overexpression downregulated catalase. When apoptosis was induced with H(2)O(2), Sirt1 was upregulated with the concomitant increase in catalase expression. Sirt1 overexpression rescued H(2)O(2)-induced apoptosis through the upregulation of catalase. H(2)O(2) induced the nuclear accumulation of forkhead transcription factor, FoxO3a and the gene silencing of FoxO3a enhanced H(2)O(2)-induced apoptosis. In conclusion, endogenous Sirt1 maintains cell survival by regulating catalase expression and by preventing the depletion of ROS required for cell survival. In contrast, excess ROS upregulates Sirt1, which activates FoxO3a and catalase leading to rescuing apoptosis. Thus, Sirt1 constitutes a determinant of renal tubular cell apoptosis by regulating cellular ROS levels.

A 79-year-old woman with progressive systemic sclerosis (PSS) presented with acute pulmonary edema, hypertension and renal failure. Administration of angiotensin-converting enzyme (ACE) inhibitor under suspicion of PSS renal crisis resulted in worsening of the renal function, which necessitated hemodialysis. Magnetic resonance arteriogram (MRA) demonstrated stenosis of the right renal artery, and ischemic nephropathy was diagnosed. Renal function improved after the discontinuation of ACE inhibitor. ACE inhibitor/angiotensin II receptor blocker (ARB), which is recommended for PSS renal crisis, should be avoided in ischemic nephropathy. In elderly PSS patients, careful exclusion of ischemic nephropathy is warranted before the administration of ACE inhibitor/ARB.

Renal failure can cause the deterioration of glucose metabolism and increase blood glucose fluctuations, which have been reported to be a factor in the progression of vascular disorders. Little information is available on the daily variation in blood glucose levels in patients with end-stage renal disease (ESRD) and peritoneal dialysis (PD). Daily plasma glucose excursion was evaluated by continuous glucose monitoring (CGM) for 24–72 h. Fourteen ESRD patients without type 2 diabetic nephropathy (non-diabetic patients) and six ESRD patients with type 2 diabetic nephropathy (diabetic patients) participated in this study. ESRD patients started PD which were undergone in only the daytime, and not in the night time. As the PD solution, Dianeal®1.5 % PD-2N (1.5 L) was infused intraperitoneally for 3 h three times daily. The patients received standard meals with a total calorie intake of 30 kcal/kg/day and a protein intake of 0.8 g/kg/day before and after initiation of PD. Daily glucose profiles were measured both 2 week before and 1 week after the commencement of PD with CGM system (CGMS). CGMS parameters were compared between before and after the initiation of PD. In non-diabetic patients with ESRD, the maximum glucose concentration (GC) and area under the curve (AUC) of GC >140 mg/dL significantly decreased after PD initiation. In diabetic patients with ESRD, the mean GC, SD, minimum value, AUC of GC >140 mg/dL, and maximum nocturnal GC significantly decreased, while the percentage of nocturnal GC