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en: N-methyl-2-pyridone-5-carboxamide (N-Me-2PY) has potent anti-fibrotic and anti-inflammatory activity in a fibrotic kidney model: is it an old uremic toxin?

en: N-Me-2PY, N-Me-4PY, and nicotinamide N-oxide (NNO) inhibited TGFβ1-induced fibrosis and inflammatory gene expression in kidney fibroblasts. N-Me-2PY strongly suppressed the expression of types I and III collagen, αSMA, and IL-6. N-Me-2PY also suppressed TGFβ1-induced type I collagen and IL-6 expression in renal tubular epithelial cells. No toxic effect was observed with N-Me-2PY treatment, while attenuating renal fibrosis and tubular dilation in UUO mice. Suppression of various fibrosis- and inflammation-related genes was also observed. N-Me-2PY did not inhibit TGFβ1-induced Smad3 phosphorylation but inhibited Akt phosphorylation, suggesting that N-Me-2PY exerts anti-fibrotic and anti-inflammatory effects through Akt inhibition, similar to pirfenidone.

ja: NAD + metabolites, such as N-Me-2PY, are not uremic toxins but are potential therapeutic agents that have anti-fibrotic effects in CKD.

en: Clinical and Experimental Nephrology

ja: Clinical and Experimental Nephrology


en: Efficacy of molnupiravir and sotrovimab in Japanese dialysis patients with COVID-19 in clinical practice during the Omicron (BA.1 and BA.2) pandemic.

en: Sotrovimab showed efficacy in Omicron BA.1 but attenuated in BA.2. Molnupiravir also showed efficacy in BA.2, suggesting administration of molnupiravir would be important.

ja: A total of 1480 patients were included. The mortality of the molnupiravir, sotrovimab, and combination groups were significantly improved compared to the control group (p < 0.001). Multivariate analysis indicated that antiviral therapy improves the survival of dialysis patients with COVID-19 (hazard ratio was 0.184 for molnupiravir, 0.389 for sotrovimab, and 0.254 for combination groups, respectively).

en: Therapeutic Apheresis and Dialysis

ja: Therapeutic Apheresis and Dialysis


en: PCK1 Protects against Mitoribosomal Defects in Diabetic Nephropathy in Mouse Models.

en: PCK1 preserves mitoribosomal function and may play a novel protective role in DN.

en: Journal of the American Society of Nephrology


en: T-Cell Response and Antibody Production Induced by the COVID-19 Booster Vaccine in Japanese Chronic Kidney Disease Patients Treated with Hemodialysis.

en: COVID test (T-SPOT) were measured prior to, three weeks after, and three months after the booster administration. The HD group had significantly higher SARS-CoV-2 IgG levels and neutralizing antibody titers against the original strain at three weeks and three months after the booster vaccination compared to the control group, albeit the HD group had lower SARS-CoV-2 IgG levels and neutralizing antibody titers before the booster administration. Moreover, the HD group had significantly higher T-SPOT levels at all three time points compared to the control group. The HD group also had significantly higher local and systemic adverse reaction rates than the control group. By booster vaccination, HD patients could acquire more effective SARS-CoV-2-specific humoral and cellular immunity than the control group.

en: Vaccines

ja: Vaccines


en: Sodium benzoate attenuates 2,8-dihydroxyadenine nephropathy by inhibiting monocyte/macrophage TNF-α expression.

en: Sodium benzoate (SB), a known D-amino acid oxidase (DAO) enzyme inhibitor, has an anti-inflammatory effect, although its role in renal damage has not been explored. 2,8-dihydroxyadenine crystal induced chronic kidney disease, in which TNF-α is involved in the pathogenesis, was established by oral adenine administration in C57BL/6JJcl mice (AdCKD) with or without SB to investigate its renal protective effects. SB significantly attenuated AdCKD by decreasing serum creatinine and urea nitrogen levels, and kidney interstitial fibrosis and tubular atrophy scores. The survival of AdCKD mice improved 2.6-fold by SB administration. SB significantly decreased the number of infiltrating macrophages observed in the positive F4/80 immunohistochemistry area and reduced the expression of macrophage markers and inflammatory genes, including TNF-α, in the kidneys of AdCKD. Human THP-1 cells stimulated with either lipopolysaccharide or TNF-α showed increased expression of inflammatory genes, although this was significantly reduced by SB, confirming the anti-inflammatory effects of SB. SB exhibited renal protective effects in AdCKD in DAO enzyme deficient mice, suggesting that anti-inflammatory effect of SB was independent of DAO enzyme activity. Moreover, binding to motif DNA sequence, protein level, and mRNA level of NF-κB RelB were significantly inhibited by SB in AdCKD kidneys and lipopolysaccharide treated THP-1 cells, respectively. We report that anti-inflammatory property of SB is independent of DAO enzymatic activity and is associated with down regulated NF-κB RelB as well as its downstream inflammatory genes such as TNF-α in AdCKD.

en: Scientific Reports

ja: Scientific Reports


en: Canagliflozin protects the cardiovascular system through effects on the gut environment in non-diabetic nephrectomized rats.

en: The increases in colonic glucose concentration, Lactobacillus numbers and tight junction protein expression, and the decreases in serum uremic toxin concentrations and cardiac interstitial fibrosis may have been caused by the inhibition of SGLT1 by canagliflozin because similar effects were not identified in tofogliflozin-treated rats.


en: Drug-induced de novo thrombotic microangiopathy diagnosed 2 years after renal transplantation: A case report and literature review

en: Renal Replacement Therapy

ja: Renal Replacement Therapy


en: Investigation for the efficacy of COVID-19 vaccine in Japanese CKD patients treated with hemodialysis.

en: Dialysis patients are predisposed to severe disease and have a high mortality rate in coronavirus disease 2019 (COVID-19) due to their comorbidities and immunocompromised conditions. Therefore, dialysis patients should be prioritized for vaccination. This study aimed to examine how long the effects of the vaccine are maintained and what factors affect antibody titers.

ja: HD patients had significantly lower antibody titers than age- and sex-matched non-dialysis individuals over 3 months after vaccination. Dialysis time was identified as a factor affecting SARS-CoV-2 IgG titers in HD group, with longer dialysis time resulting in higher maximum SARS-CoV-2 IgG titers.


en: Proximal-tubule molecular relay from early Protein diaphanous homolog 1 to late Rho-associated protein kinase 1 regulates kidney function in obesity-induced kidney damage.

en: The small GTPase protein RhoA has two effectors, ROCK (Rho-associated protein kinase 1) and mDIA1 (protein diaphanous homolog 1), which cooperate reciprocally. However, temporal regulation of RhoA and its effectors in obesity-induced kidney damage remains unclear. Here, we investigated the role of RhoA activation in the proximal tubules at the early and late stages of obesity-induced kidney damage. In mice, a three-week high-fat-diet induced proximal tubule hypertrophy and damage without increased albuminuria, and RhoA/mDIA1 activation without ROCK activation. Conversely, a 12-week high-fat diet induced proximal tubule hypertrophy, proximal tubule damage, increased albuminuria, and RhoA/ROCK activation without mDIA1 elevation. Proximal tubule hypertrophy resulting from cell cycle arrest accompanied by downregulation of the multifunctional cyclin-dependent kinase inhibitor p27Kip1 was elicited by RhoA activation. Mice overexpressing proximal tubule-specific and dominant-negative RHOA display amelioration of high-fat diet-induced kidney hypertrophy, cell cycle abnormalities, inflammation, and renal impairment. In human proximal tubule cells, mechanical stretch mimicking hypertrophy activated ROCK, which triggered inflammation. In human kidney samples from normal individuals with a body mass index of about 25, proximal tubule cell size correlated with body mass index, proximal tubule cell damages, and mDIA1 expression. Thus, RhoA activation in proximal tubules is critical for the initiation and progression of obesity-induced kidney damage. Hence, the switch in the downstream RhoA effector in proximal tubule represents a transition from normal to pathogenic kidney adaptation and to body weight gain, leading to obesity-induced kidney damage.

en: Kidney International

ja: Kidney International


en: Effectiveness of SARS-CoV-2 vaccines on hemodialysis patients in Japan: A nationwide cohort study.

en: Our prospective observational study showed that SRAS-CoV-2 vaccination in hemodialysis patients is vital for reducing need of oxygen supplementation and mortality risk.

en: Therapeutic Apheresis and Dialysis


en: Diagnosis of monoclonal immunotactoid glomerulopathy with positive λ chain by immunoelectron microscopy.

en: We report the case of a 73-year-old-man who developed immunotactoid glomerulopathy (ITG). ITG is a rare disease characterized by proliferative glomerulonephritis and capillary wall deposits with a 10-60 nm diameter microtubular substructure. In monoclonal ITG, immunofluorescence analysis typically exhibits IgG with light chain restriction. Recent reviews recommend distinguishing monoclonal ITG from polyclonal ITG because monoclonal ITG is associated with a higher incidence of hematological disorders and better responsiveness to clone-directed therapy and renal prognosis. In our case, IgG, IgA, and IgM were negative by routine immunofluorescence; however, immunoelectron microscopy revealed positive λ chain. At 6 months after renal biopsy, the IgG λ chain was detected in the serum and urine, reflecting possible monoclonality. Therefore, it is useful to perform immunoelectron microscopy and follow-up with serum and urine protein electrophoresis and immunofixation to diagnose monoclonal ITG, even when routine immunofluorescence shows negative or nonspecific findings.

en: CEN Case Reports

ja: CEN Case Reports


en: Committee report: Questionnaire survey on the treatment of COVID-19 in patients receiving dialysis therapy.

en: Our survey revealed a variety of treatment practices in each facility. Further evidence and innovations are required to improve the prognosis of patients with COVID-19 receiving dialysis therapy.

ja: Sixty-six centers (62.9%) responded to the questionnaire. Antivirals were administered in 27.7% of facilities treating mild disease (most patients received favipiravir) and 66.7% of facilities treating moderate disease (most patients with moderate or more severe conditions received remdesivir). Whether and how remdesivir is administered varies between centers. Steroids were initiated most frequently in moderate II disease (50.8%), while 43.1% of the facilities initiated steroids in mild or moderate I disease. The type of steroid, dose, and the duration of administration were generally consistent, with most facilities administering dexamethasone 6 mg orally or 6.6 mg intravenously for 10 days. Steroid pulse therapy was administered in 48.5% of the facilities, and tocilizumab was administered in 25.8% of the facilities, mainly to patients on ventilators or equivalent medications, or to the cases of exacerbations. Furthermore, some facilities used a polymethylmethacrylate membrane during dialysis, nafamostat as an anticoagulant, and continuous hemodiafiltration in severe cases. There was limited experience of polymyxin B-immobilized fiber column-direct hemoperfusion and extracorporeal membrane oxygenation. The discharge criteria for patients receiving dialysis therapy were longer than those set by the Ministry of Health, Labor and Welfare in 22.7% of the facilities.


en: Effects of a remote patient monitoring system for patients on automated peritoneal dialysis: a randomized crossover controlled trial.

en: The study was registered in the Japan Registry of Clinical Trials (jRCT Number: jRCTs032190005).

ja: Significant improvements were observed in the TSQM-9 subscales of Effectiveness (64.4 ± 18.8 vs. 57.8 ± 18.8; P = 0.006) and Convenience (76.3 ± 15.4 vs. 63.3 ± 17.3; P < 0.001) in patients on Sharesource®. Moreover, Sharesource® reduced the total amount of healthcare resource consumption (0.80 ± 1.32 vs. 1.87 ± 2.39 times/12 weeks; P = 0.02) and consultation time during regular monthly visits (813 ± 269 vs. 1024 ± 292 s; P < 0.001). A significant increase in ultrafiltration volume was found associated with more frequent modification of APD prescription in patients with Sharesource®. Sharesource® also improved the HRQOL subscale of General Health and Vitality.

en: International Urology and Nephrology

ja: International Urology and Nephrology


en: Home-Based Exercise Program Ameliorates Renal Function Decline in Patients With CKD Stage 4.

en: Kidney International Reports

ja: Kidney International Reports


en: Home-based aerobic exercise and resistance training for severe chronic kidney disease: a randomized controlled trial.

en: Our 6 month home-based exercise programme improved aerobic capacity and HRQOL in patients with Stage 4 CKD, with possible beneficial effects on kidney function and CKD-related parameters.

en: Journal of Cachexia, Sarcopenia and Muscle


en: Fabry disease associated with multiple myeloma: a case report.

en: Fabry disease (FD) is an X-linked genetic lysosomal disorder caused by alpha-galactosidase A (GLA) deficiency. Multiple myeloma (MM) predominately affects older adults, which ranks as the second commonest hematological malignancy. Their overlap has rarely been reported. We present a case of the coexistence of FD and MM in a patient. We report the case of a 68-year-old woman who was referred to our hospital for the evaluation of thoracic spine tumor with bone destruction. On admission, her serum creatinine (Cr) level was elevated to 12.70 mg/dL from the baseline value of 0.91 mg/dL. Bone marrow aspiration revealed MM. Renal biopsy showed myeloma cast nephropathy, which was the primary cause of acute kidney injury. Renal pathology also showed podocyte swelling and tubule myeloid bodies in a mosaic pattern compatible with female FD. Consequently, the patient was diagnosed as FD based on the germ line mutation in GLA. The patient was treated with bortezomib and dexamethasone therapy, which significantly improved the renal function. This is the second case demonstrating a potential pathogenic relationship between FD and MM. Since FD is one of the few genetic diseases for which there are therapeutic agents with fewer side effects, diagnostic value of FD is high. If an MM patient has multiple organ abnormalities or any familial history, the physician should suspect FD.


en: Efficacy of dexmedetomidine on peritoneal dialysis catheter insertion.

en: The use of DEX in PD catheter insertion under spinal anesthesia could safely improve operative analgesia.

ja: 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.


en: Pre-emptive Short-term Nicotinamide Mononucleotide Treatment in a Mouse Model of Diabetic Nephropathy.

en: salvage pathway, both of which indicate NMN legacy effects on DN.

en: Journal of the American Society of Nephrology


en: Development of nephropathy in an adult patient after Fontan palliation for cyanotic congenital heart disease.

en: Cyanotic congenital heart disease is occasionally associated with kidney dysfunction, which is known as cyanotic nephropathy or cyanotic glomerulopathy. The clinical presentation of cyanotic nephropathy includes proteinuria, decreased estimated glomerular filtration rate, hyperuricemia, thrombocytopenia, or polycythemia. Although advances in surgical procedures have improved the prognosis of cyanotic congenital heart diseases, adult cases of cyanotic nephropathy are still rare, and there are few reports of kidney biopsy in adults with cyanotic nephropathy. Here, we present the case of a 41-year-old patient with Fontan palliation who developed nephrotic range proteinuria and had a kidney biopsy, which showed glomerular hypertrophy with segmental glomerulosclerosis around vascular poles, suggesting adaptive focal segmental glomerulosclerosis. This case provides further understanding of kidney dysfunction due to cyanotic congenital heart disease and shows the need for attention in the management for prevention of progression to end-stage renal disease and in the selection of renal replacement therapy.

en: CEN Case Reports


en: Diabetic condition induces hypertrophy and vacuolization in glomerular parietal epithelial cells.

en: Diabetic nephropathy (DN) is accompanied by characteristic changes in the glomerulus, but little is known about the effect of diabetes on parietal epithelial cells (PECs). In this study, a descriptive analysis of PECs was undertaken in diabetic db/db mice and in diabetic patients. PEC hypertrophy was significantly more prominent in diabetic mice than in nondiabetic mice, and this was evident even at the early stage. Additionally, the number of vacuoles in PECs was markedly increased in diabetic mice, suggesting the presence of cellular injury in PECs in DN. Although rare, binuclear cells were observed in mice with early diabetes. In cultured PECs, a high glucose condition, compared with normal glucose condition, induced cellular hypertrophy and apoptosis. Flow cytometry showed that some PECs in the G0 phase reentered the cell cycle but got arrested in the S phase. Finally, in human diabetic subjects, hypertrophy and vacuolization were observed in the PECs. Our data showed that PECs undergo substantial changes in DN and may participate in rearrangement for differentiation into podocytes.

en: Scientific Reports


en: Malignancy-associated membranous nephropathy with PLA2R double-positive for glomeruli and carcinoma.

en: Phospholipase A2 receptor (PLA2R) is the most common primary target antigen of idiopathic membranous nephropathy (MN) although PLA2R antibodies are also reported to be present in malignancy-associated MN. However, a case of PLA2R-positive MN secondary to PLA2R-positive carcinoma has not been reported. A 26-year-old Japanese woman presented with general fatigue, fever, and nonproductive cough. Computed tomography demonstrated a left kidney mass with pathologic diagnosis of Xp11.2 translocation renal cell carcinoma (RCC). After the second time of administration with Sunitinib, the patients exhibited significant proteinuria and hypoalbuminemia. Renal biopsy revealed a diagnosis of diffuse MN secondary to RCC. Immunofluorescence staining showed granular patterns positive for immunoglobulin (Ig) G, IgA, and C3c. PLA2R and IgG1-3 were positive, while IgG4 was negative. For the treatment of severe nephrotic syndrome, we attempted steroid therapy without any clinical improvement. Open nephrectomy was performed and surprisingly, RCC was stained for PLA2R with polarity for the basal side. At outpatient follow-up, 4 months after the operation, urinary protein had still persisted, although serum albumin was slightly increased. We report a case of PLA2R-positive MN secondary to PLA2R-positive RCC.


en: Exercise Parameters Predict Technique Survival in Patients on Peritoneal Dialysis.

en: 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.

en: Blood Purification

ja: Blood Purification


en: The effect of aldosterone and aldosterone blockade on the progression of chronic kidney disease: a randomized placebo-controlled clinical trial.

en: /year, p = 0.0047). In the final intervention study, in the eplerenone group, eGFR dropped at 6 months after the initiation of the study, and thereafter eGFR was maintained until the end of the study. At 24 months and 36 months, eGFR was significantly higher in the eplerenone group than in the placebo group. In conclusion, MRA can be an effective strategy in preventing CKD progression, especially in patients with high plasma aldosterone.


en: 学術委員会血液浄化療法の機能・効率に関する小委員会報告 血液透析濾過器の性能評価と使い分け

en: Journal of Japanese Society for Dialysis Therapy

ja: 日本透析医学会雑誌