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Abstract Background S100A12 protein is an endogenous receptor ligand for advanced glycation end products. In this study, the plasma S100A12 level was assessed as an independent predictor of mortality, and its utility in clinical settings was examined. Methods In a previous cross-sectional study, plasma S100A12 levels were measured in 550 maintenance hemodialysis patients to determine the association between S100A12 and the prevalence of cardiovascular diseases (CVD). In this prospective study, the risk of mortality within a two-year period was determined. An integer scoring system was developed to predict mortality on the basis of the plasma S100A12 levels. Results Higher plasma S100A12 levels (≥18.79 ng/mL) were more closely associated with higher all-cause mortality than lower plasma S100A12 levels (P = 0.001). Multivariate Cox proportional hazards analysis revealed higher plasma S100A12 levels [hazard ratio (HR), 2.267; 95% confidence interval (CI), 1.195–4.302; P = 0.012], age ≥65 years (HR, 1.961; 95%CI, 1.017–3.781; P = 0.044), serum albumin levels P = 0.012), and history of CVD (HR, 2.068; 95%CI, 1.146–3.732; P = 0.016) to be independent predictors of two-year all-cause mortality. The integer score was derived by assigning points to these factors and determining total scores. The scoring system revealed trends across increasing scores for predicting the all-cause mortality [c-statistic = 0.730 (0.656–0.804)]. The resulting model demonstrated good discriminative power for distinguishing the validation population of 303 hemodialysis patients [c-statistic = 0.721 (0.627–0.815)]. Conclusion The results indicate that plasma S100A12 level is an independent predictor for two-year all-cause mortality. A simple integer scoring system was therefore established for predicting mortality on the basis of plasma S100A12 levels.

Abstract Background Infective endocarditis is significantly more common in haemodialysis patients as compared with the general population, the causative pathogen is generally Staphylococcus aureus; there have been no previously reported cases of infective endocarditis caused by a Salmonella species in haemodialysis patients. Case Presentation We report the case of a 68 year-old woman on haemodialysis who developed infective endocarditis as a result of Salmonella enteritidis. Although we treated the patient with ceftriaxone combined with ciprofloxacin, infective endocarditis was not detected early enough and unfortunately developed into cerebral septic emboli, which ultimately resulted in death. Conclusion Although there are several reports that Salmonella endocarditis without cardiac failure can be successfully treated with antibiotics alone, early surgical intervention is essential for some cases to prevent life-threatening complications. Transesophageal echocardiography should be performed in any patient with high clinical suspicion of infective endocarditis. To the best of our knowledge, this is the first case-report of Salmonella endocarditis in a haemodialysis patient.

Background: The Chiari network mostly causes no symptoms but may occasionally be involved in thrombus formation in the right atrium. We present a case of right atrial thrombus discovered in the postoperative course of blunt cardiac rupture., Case Presentation: A 19-year-old female injured in a motor vehicle accident was transported to the hospital in a state of shock. Echocardiography revealed pericardial effusion. Cardiopulmonary arrest was imminent, so a clamshell thoracotomy was performed. A laceration at the right atrial junction of the superior vena cava was observed and sutured. Echocardiography on post-injury day 6 showed a floating thrombus in the right atrium. Anticoagulation therapy was started, the thrombus was reduced, and the patient was discharged on day 27 without sequelae. Six months later, echocardiography showed a filamentous structure and the presence of the Chiari network., Conclusion: Right intra-atrial thrombi are rare and may warrant a search of the Chiari network in conditions where hypercoagulation is anticipated., Competing Interests: The authors declare no conflicts of interest. Dr. Yasuyuki Kuwagata is an Editorial Board member of the Acute Medicine & Surgery journal and a co‐author of this article. To minimize bias, this author was excluded from all editorial decision‐making related to the acceptance of this article for publication., (© 2024 The Author(s). Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Introduction: A reduced salt intake is a vital lifestyle modification in the management of hypertension. Initiatives aimed at decreasing the intake of salt are based on the preference by humans for a salt taste. Salt intake behavior appears to be affected by the balance between attraction to a low salt taste and aversion to a high salt taste. However, aversion to a high salt taste has not yet been quantitively investigated in both healthy individuals and patients with chronic kidney disease (CKD)., Methods: Assessments of gustatory and aversion thresholds for salt, bitter, sour, and sweet tastes were performed using a stimulant-impregnated test strip in healthy subjects and patients with CKD., Results: In a pilot taste test of 125 healthy subjects, the number of participants with an aversive reaction increased at higher salt concentrations. The threshold for normal taste perception was arbitrarily defined as 10% NaCl, with 47.2% of healthy subjects displaying an aversive reaction. In taste tests performed by 70 patients with CKD, 10% were unable to recognize a salt taste, even at the highest concentration (20% NaCl), suggesting a significant impairment in taste perception in patients with CKD. Only 15.7% of patients with CKD exhibited a normal aversion to NaCl, whereas 78.6% showed the complete loss of aversion to salt., Conclusion: The present results confirmed the anticipated aversive response to a high salt taste in humans and demonstrated its impairment in patients with CKD, implying that patients with CKD have reduced resistance to a high salt intake., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

The immense public health burden of diabetic kidney disease (DKD) has led to an increase in research on the pathophysiology of advanced DKD. The present study focused on the significance of proinflammatory vascular cell adhesion molecule 1 (VCAM1)+ tubules in DKD progression. A retrospective cohort study of DKD patients showed that the percentage of VCAM1+ tubules in kidney samples was correlated with poor renal outcomes. We established an advanced DKD model by partial resection of the kidneys of db/db mice and demonstrated that it closely resembled the human advanced DKD phenotype, with tissue hypoxia, tubular DNA damage, tissue inflammation, and high tubular VCAM1 expression. Luseogliflozin ameliorated tissue hypoxia and proinflammatory responses, including VCAM1+ expression, in tubules. These findings suggest the potential of tubular VCAM1 as a histological marker for poor DKD outcomes. SGLT2 inhibitors may attenuate tissue hypoxia and subsequent tissue inflammation in advanced DKD, thereby ameliorating tubular injury., Competing Interests: T. Kusaba reports receiving commercial research support from Taisho Pharmaceutical and speaker’s bureau honoraria from AstraZeneca., (© 2024 The Author(s).)

Background: This multi-institutional, observational study examined whether the outcomes after peritoneal dialysis (PD) catheter placement in Japan meet the audit criteria of the International Society for Peritoneal Dialysis (ISPD) guideline and identified factors affecting technique survival and perioperative complications., Methods: Adult patients who underwent first PD catheter placement for end-stage kidney disease between April 2019 and March 2021 were followed until PD withdrawal, kidney transplantation, transfer to other facilities, death, 1 year after PD start or March 2022, whichever came first. Primary outcomes were time to catheter patency failure and technique failure, and perioperative infectious complications within 30 days of catheter placement. Secondary outcomes were perioperative complications. Appropriate statistical analyses were performed to identify factors associated with the outcomes of interest., Results: Of the total 409 patients, 8 who underwent the embedded catheter technique did not have externalised catheters. Of the 401 remaining patients, catheter patency failure occurred in 25 (6.2%). Technical failure at 12 months after PD catheter placement calculated from cumulative incidence function was 15.3%. On Cox proportional hazards model analysis, serum albumin (hazard ratio (HR) 0.44; 95% confidence interval (CI) 0.27-0.70) and straight type catheter (HR 2.14; 95% CI 1.24-3.69) were the independent risk factors for technique failure. On logistic regression analysis, diabetes mellitus was the only independent risk factor for perioperative infectious complications (odds ratio 2.70, 95% CI 1.30-5.58). The occurrence rate of perioperative complications generally met the audit criteria of the ISPD guidelines., Conclusion: PD catheter placement in Japan was proven to be safe and appropriate., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors have read and understood Peritoneal Dialysis International’s policy on conflicts of interest disclosures. TS has received speaker honorarium from Baxter Healthcare and received research grant from Terumo Corporation. HI has received research grant from Baxter Healthcare. KU has received salaries from an endowed chair at Baxter Healthcare. KU has received research grant, also from Baxter Healthcare. NW has received speaker honorarium from Baxter Healthcare. MY has received speaker honorarium from Terumo Corporation. DK has received speaker honorarium from JMS Co., Ltd. KT has received speaker honorarium from Baxter Healthcare and JMS Co., Ltd. The other authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Streptozotocin (STZ), an anti-cancer drug that is primarily used to treat neuroendocrine tumors (NETs) in clinical settings, is incorporated into pancreatic β-cells or proximal tubular epithelial cells through the glucose transporter, GLUT2. However, its cytotoxic effects on kidney cells have been underestimated and the underlying mechanisms remain unclear. We herein demonstrated that DNA damage and subsequent p53 signaling were responsible for the development of STZ-induced tubular epithelial injury. We detected tubular epithelial DNA damage in NET patients treated with STZ. Unbiased transcriptomics of STZ-treated tubular epithelial cells in vitro showed the activation of the p53 signaling pathway. STZ induced DNA damage and activated p53 signaling in vivo in a dose-dependent manner, resulting in reduced membrane transporters. The pharmacological inhibition of p53 and sodium-glucose transporter 2 (SGLT2) mitigated STZ-induced epithelial injury. However, the cytotoxic effects of STZ on pancreatic β-cells were preserved in SGLT2 inhibitor-treated mice. The present results demonstrate the proximal tubular-specific cytotoxicity of STZ and the underlying mechanisms in vivo. Since the cytotoxic effects of STZ against β-cells were not impaired by dapagliflozin, pretreatment with an SGLT2 inhibitor has potential as a preventative remedy for kidney injury in NET patients treated with STZ., (© 2023. The Author(s).)

Based on recent clinical trials using sodium-glucose co-transporter 2 inhibitor (SGLT2i) demonstrating the significant improvement of outcomes of diabetic kidney disease (DKD), the paradigm shift from "glomerulocentric" to "tubule centric" pathophysiology in DKD progression has been highlighted. Several responsible mechanisms for renoprotective effects by SGLT2i have been proposed recently, but the changes in proximal tubule-specific gene expression by SGLT2i in diabetic mice have not been elucidated. We report the analysis of the proximal tubular-specific pathway, demonstrating the downregulation of oxidative phosphorylation in dapagliflozin-treated db/db mice, a type 2 diabetic model. After 8-week treatment of dapagliflozin for db/db mice having a proximal tubule-specific tdTomato reporter, tdTomato-positive cells were isolated by FACS. Pathway analysis of RNA sequencing of isolated tubular epithelia revealed that oxidative phosphorylation was downregulated in dapagliflozin-treated mice. However, depletion of renal tissue ATP content in db/db mice was ameliorated by dapagliflozin administration. Pimonidazole staining demonstrated renal cortical tissue hypoxia in db/db mice, which was improved by dapagliflozin administration. This study suggests that dapagliflozin can ameliorate the excessive oxygen and ATP consumption, and subsequent tissue hypoxia in the diabetic kidney, which may explain, in part, the responsible mechanisms of the renoprotective effects of dapagliflozin., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Heart failure is frequently accompanied by kidney failure and co-incidence of these organ failures worsens the mortality in patients with heart failure. Recent clinical observations revealed that increased kidney venous pressure, rather than decreased cardiac output, causes the deterioration of kidney function in patients with heart failure. However, the underlying pathophysiology is unknown. Here, we found that decreased blood flow velocity in peritubular capillaries by kidney congestion and upregulation of endothelial nuclear factor-κB (NF-κB) signaling synergistically exacerbate kidney injury. We generated a novel mouse model with unilateral kidney congestion by constriction of the inferior vena cava between kidney veins. Intravital imaging highlighted the notable dilatation of peritubular capillaries and decreased kidney blood flow velocity in the congestive kidney. Damage after ischemia reperfusion injury was exacerbated in the congestive kidney and accumulation of polymorphonuclear leukocytes within peritubular capillaries was noted at the acute phase after injury. Similar results were obtained in vitro, in which polymorphonuclear leukocytes adhesion on activated endothelial cells was decreased in flow velocity-dependent manner but cancelled by inhibition of NF-κB signaling. Pharmacological inhibition of NF-κB for the mice subjected by both kidney congestion and ischemia reperfusion injury ameliorated the accumulation of polymorphonuclear leukocytes and subsequent exacerbation of kidney injury. Thus, our study demonstrates the importance of decreased blood flow velocity accompanying activated NF-κB signaling in aggravation of kidney injury. Hence, inhibition of NF-κB signaling may be a therapeutic candidate for the vicious cycle between heart and kidney failure with increased kidney venous pressure., (Copyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

A 75-year-old man with fever was diagnosed with alveolar hemorrhage. Antineutrophil cytoplasmic antibodies for myeloperoxidase and proteinase 3 were absent. He received corticosteroid therapy, which immediately improved his symptoms and chest radiological findings. After the discontinuation of corticosteroids, fever and general fatigue relapsed, and renal function deteriorated with hematuria and proteinuria. A nerve conduction study revealed mononeuritis multiplex. Renal biopsy demonstrated focal necrotizing crescentic glomerulonephritis with endocapillary proliferative lesions, immunofluorescence C3 deposits, and electron-microscopic subepithelial hump-like deposits. Nephritis-associated plasmin receptor (NAPlr) and plasmin activity, biomarkers of infection-related glomerulonephritis, were positive in glomeruli. Although pathological findings suggested infection-related glomerulonephritis (IRGN), clinical manifestations, such as alveolar hemorrhage and mononeuritis multiplex, suggested systemic small vessel vasculitis. After corticosteroid therapy, systemic symptoms disappeared, and the gradual amelioration of hematuria and proteinuria was observed. Based on the clinical symptoms for which steroid therapy was effective, the patient was considered to have systemic small vessel vasculitis, the etiology of which may have been associated with infection., (© 2021. Japanese Society of Nephrology.)

Kidney hypertrophy is a common clinical feature in patients with diabetes and is associated with poor renal outcomes. Initial cell proliferation followed by cellular hypertrophy are considered the responsible mechanisms for diabetic kidney hypertrophy. However, whether similar responses against hyperglycemia continue in the chronic phase in diabetes is unclear. We performed lineage tracing analysis of proximal tubular epithelia using novel type 2 diabetic mice with a tamoxifen-inducible proximal tubule-specific fluorescent reporter. Clonal analysis of proximal tubular epithelia demonstrated that the labeled epithelia proliferated in type 2 diabetic mice. Based on the histological analysis and protein/DNA ratio of sorted labeled tubular epithelia, there was no evidence of cellular hypertrophy in type 2 diabetic mice. Lineage tracing and histological analyses of streptozocin-induced type 1 diabetes also revealed that cellular proliferation occurs in the chronic phase of type 1 diabetes induction. According to our study, epithelial proliferation accompanied by SGLT2 upregulation, rather than cellular hypertrophy, predominantly occurs in the hypertrophic kidney in both type 1 and type 2 diabetes. An increased number of SGLT2+ tubular epithelia may be an adaptive response against hyperglycemia, and linked to the hyper-reabsorption of sodium and glucose observed in type 2 diabetes patients., (© 2022. The Author(s).)

Cisplatin is a commonly used anticancer drug, but nephrotoxicity is a dose-limiting adverse effect. Recent experimental and clinical observations have demonstrated that multiple injections of cisplatin induce the transition to chronic kidney disease; however, the underlying mechanisms remain unclear. We found that multiple injections of higher doses of cisplatin in a shorter interval affected the severity of kidney injury, causing kidney fibrosis to develop at a later time point. An additional injection of cisplatin during the recovery period after a prior injury, when proximal tubule epithelia are actively proliferating, induced substantial tubular injury by inducing more severe DNA damage than that induced by a single injection. Lineage tracing analysis of proximal tubular epithelia demonstrated that the tubular epithelia that underwent multiple rounds of cell division after multiple injections of cisplatin existed at the chronic phase, and these populations often expressed vcam1 + , suggesting the induction of proinflammatory failed-repair tubular epithelia. Our study revealed that as cisplatin exerts cytotoxic effects on actively proliferating cells, additional cisplatin injections before the completion of tubular repair exacerbates kidney injury through cumulative DNA damage. Appropriate both the setting of dosage and dosing intervals, with careful monitoring, are essential to prevent nephrotoxicity of repeated cisplatin treatment in cancer patients., (© 2021. The Author(s).)

Background: Alport syndrome is an inherited disorder characterized by progressive renal disease, variable sensorineural hearing loss, and ocular abnormalities. Although many pathogenic variants in COL4A3 and COL4A4 have been identified in patients with autosomal Alport syndrome, synonymous mutations in these genes have rarely been identified., Methods: We conducted in silico splicing analysis using Human Splicing Finder (HSF) and Alamut to predict splicing domain strength and disruption of the sites. Furthermore, we performed in vitro splicing assays using minigene constructs and mRNA analysis of patient samples to determine the pathogenicity of four synonymous variants detected in four patients with suspected autosomal dominant Alport syndrome ( COL4A3 [c.693G>A (p.Val231=)] and COL4A4 [c.1353C>T (p.Gly451=), c.735G>A (p.Pro245=), and c.870G>A (p.Lys290=)])., Results: Both in vivo and in vitro splicing assays showed exon skipping in two out of the four synonymous variants identified (c.735G>A and c.870G>A in COL4A4 ). Prediction analysis of wild-type and mutated COL4A4 sequences using HSF and Alamut suggested these two variants may lead to the loss of binding sites for several splicing factors, e.g. , in acceptor sites and exonic splicing enhancers. The other two variants did not induce aberrant splicing., Conclusions: This study highlights the pitfalls of classifying the functional consequences of variants by a simple approach. Certain synonymous variants, although they do not alter the amino acid sequence of the encoded protein, can dramatically affect pre-mRNA splicing, as shown in two of our patients. Our findings indicate that transcript analysis should be carried out to evaluate synonymous variants detected in patients with autosomal dominant Alport syndrome., Competing Interests: T. Horinouchi reports receiving research funding from Otsuka Pharmaceutical Co. Ltd.; K. Iijima reports receiving research funding from Air Water Medical Inc., Astellas Pharma Inc., Eisai Co. Ltd., JCR Pharmaceutical Co. Ltd., Mochida Pharmaceutical Co. Ltd., Nihon Pharmaceutical Co. Ltd., Otsuka Pharmaceutical Co. Ltd., Shionogi & Co. Ltd., and Zenyaku Kogyo Co. Ltd.; receiving consulting fees from Astellas Pharma Inc., Boehringer Ingelheim, Kyowa Kirin Co. Ltd., Ono Pharmaceutical Co. Ltd., and Takeda Pharmaceutical Co.; receiving honoraria from Astellas Pharma Inc., Chugai Pharmaceutical Co. Ltd., Integrated Development Associates Co. Ltd., Kyowa Hakko Kirin Co. Ltd., Shionogi & Co. Ltd., and Zenyaku Kogyo Co. Ltd.; serving as a scientific advisor for, or member of, CJASN and Pediatric Nephrology (on the editorial board); receiving grant support from Daiichi Sankyo Co. Ltd.; and having consultancy agreements with JCR Pharmaceuticals Co. Ltd., Kyowa Hakko Kirin Co. Ltd., Ono Pharmaceutical Co. Ltd., Sanofi K.K., Takeda Pharmaceutical Co. Ltd., and Zenyaku Kogyo Co. Ltd. K. Iijima and K. Nozu report having filed a patent application for the development of antisense nucleotides for exon skipping therapy in Alport syndrome. M. Matsuo reports serving as an advisor to Daiichi Sankyo Co. Ltd. (Japan) and JCR Pharma Co. Ltd. (Japan), and being a research professor at the Nucleic Acid Drug Discovery Department that is financially supported by KNC Laboratories Co. Ltd. Inc. (Japan). K. Nakanishi reports receiving honoraria from Asahi Kasei Corporation, Astellas Pharma Inc., AstraZeneca, Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., JCR Pharmaceuticals Co. Ltd., Kyowa Hakko Kirin Co. Ltd., Miyarisan Pharmaceutical Co. Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co. Ltd., Sanofi K.K., Taisho Toyama Pharmaceutical Co., and Teijin Pharma Ltd.; and receiving research funding from Asahi Kasei Corporation, Astellas Pharma Inc., Chugai Pharmaceutical Co. Ltd., CSL Behring, Daiichi Sankyo Co. Ltd., JCR Pharmaceuticals Co. Ltd., MSD K.K., Otsuka Pharmaceutical Co. Ltd., Pfizer Inc., Sanofi K.K., and Shionogi & Co. Ltd. K. Nozu reports receiving lecture fees from Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Novartis Pharma Co. Ltd., and Sumitomo Dainippon Pharma Co. Ltd.; having patents and inventions with Daiichi Sankyo Pharmaceutical Company; receiving consulting fees from Kyowa Kirin Co. Ltd.; and receiving lecture fees from Novartis Pharmaceuticals Corporation. K. Tamagaki reports receiving research funding from Baxter International Inc., Chugai Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Eli Lilly Japan K.K., JMS Co. Ltd., Kissei Pharmaceutical Co. Ltd., Kyowa Hakko Kirin Co. Ltd., Merck & Co. Inc., Mitsubishi Tanabe Pharma Corporation, Nippon Boehringer Ingelheim Co. Ltd., Otsuka Pharmaceutical Co. Ltd., Sanofi K.K., Takeda Pharmaceutical Co. Ltd., Teijin Pharma Ltd., and Torii Pharmaceutical Co. Ltd. All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

Glomerulopathy with fibronectin deposits (GFND) is a rare hereditary kidney disease with autosomal dominant inheritance. A 21-year-old woman who had been diagnosed with GFND 10 years ago was admitted for investigation of a rapid decline in her renal function, hemolytic anemia, and cardiac dysfunction. A renal biopsy showed GFND accompanied by extraglomerular vascular lesions. Comprehensive treatments against hypertension and anemia improved the renal function. Although there have been few reports of vascular lesions in GFND, we suspect that endothelial hyperpermeability resulting from hypertension caused the fibronectin deposition and narrowing of the extraglomerular vascular lumens, thereby accelerating hypertension and inducing hemolytic anemia.

Purpose: To report the endovascular treatment for acute progressive and very-late-onset multiple segmental small-artery stenoses in transplanted kidney parenchyma presenting with rapidly deteriorating renal function and refractory hypertension in a 65-year-old man., Case Report: Nineteen years ago, the patient received a living renal transplant via end-to-end anastomosis of the right internal iliac artery for kidney failure caused by chronic glomerulonephritis. His transplant renal function (creatinine: 0.9 mg/dL) and blood pressure were stable for 18 years. Then rapid worsening of renal function (creatinine: 2.5 mg/dL) and refractory hypertension occurred. Magnetic resonance angiography and renal angiography showed multiple small segmental artery stenoses in the transplanted kidney. At the 1-month follow-up consultation, total occlusion of 2 branches traversing the inferior pole of the kidney was observed, revealing acute progression of artery stenosis. Balloon angioplasty was successfully performed on those branches; renal function improved (creatinine: 1.3 mg/dL), and blood pressure was sufficiently controlled., Conclusions: This is a rare case that revealed very-late-onset multiple segmental renal artery stenoses with acute progression in the transplant kidney. Even multiple small segmental artery stenoses can reduce transplant renal function in the chronic phase and progress rapidly. Early percutaneous transluminal angioplasty may thus be feasible and important for preventing graft loss., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Close contact is unavoidable in the care of patients with neuromuscular diseases (NMD). In addition, respiratory physiotherapy and noninvasive ventilation generate massive amounts of aerosols. Caring for a patient suffering from coronavirus disease-19 raises concerns about the risk of infection not only to the caregiver and/or medical staff but also to other individuals in contact with these personnel. We reviewed the points to be noted in infection control when a patient with neuromuscular diseases receiving respiratory care is infected with COVID-19 and summarizes the recommendation. Infected patients must be isolated in a negative-pressure or actively ventilated room. Clear zoning separating clean and infected areas should be performed for pathogen containment. Caregivers should wear appropriate personal protective equipment and thoroughly clean their hands. Leak-prevention measures and the use of proper respiratory circuits and filters with virus-removal performance are crucial to reducing aerosols in noninvasive ventilation. Although respiratory physiotherapy is essential, treatment should be minimized in consideration of the infection state and sputum status, and alternative therapies such as postural drainage should be carefully considered. Infection control is distinctly obligate; however, it impairs the quality of life and activity of daily living significantly. We should implement it with enough ethical consideration, adequate explanation, and patient consent. We hope that this paper will contribute to appropriate COVID-19 infection control in patients with neuromuscular diseases requiring respiratory care., Competing Interests: The authors have no conflict of interest to report., (© 2021 Societas Neurologica Japonica (Japanese Society of Neurology) and John Wiley & Sons Australia, Ltd.)

Nail-patella syndrome (NPS) is a multi-system disorder characterized by hypoplastic nails, hypoplastic patella, skeletal deformities, and iliac horns, which is caused by heterozygous variants of LMX1B. Nephropathy ranging from mild urinary abnormality to end-stage renal disease occurs in some individuals with NPS. Because of the low prevalence of NPS and the lack of longitudinal studies of its kidney involvement, the clinical, pathological, and genetic features characterizing severe nephropathy remain unclear. We conducted a Japanese survey of NPS with nephropathy, and analyzed their clinical course, pathological features, and factors associated with severe renal phenotype. LMX1B gene analysis and luciferase reporter assay were also performed. Among 13 NPS nephropathy cases with genetic validation, 5 patients who had moderate-to-massive proteinuria progressed to advanced chronic kidney disease or end-stage renal disease. Pathological findings in the early phase did not necessarily correlate with renal prognosis. Variants associated with deteriorated renal function including a novel variants were confined to the N-terminal region of the LIM domain and a short sequence in the LMX1B homeodomain, which were distinct from reported variants found in isolated nephropathy without extrarenal manifestation (LMX1B-associated nephropathy). Luciferase reporter analysis demonstrated that variants in patients with severe renal phenotype caused haploinsufficiency, but no dominant-negative effects on promoter activation. A distinct proportion of NPS nephropathy patients progressed to end-stage renal disease in adolescence or young adulthood. Patients with moderate or severe proteinuria, especially those with variants in specific regions of LMX1B, should be monitored for potential deterioration of renal function.

Tubular atrophy is a common pathological feature of kidney fibrosis. Although fibroblasts play a predominant role in tissue fibrosis, the role of repairing tubular epithelia in tubular atrophy is unclear. We demonstrated the essential role of focal adhesion kinase (FAK)-mediated intratubular epithelial-mesenchymal transition (EMT) in the pathogenesis of tubular atrophy after severe ischemia-reperfusion injury (IRI). Actively proliferating tubular epithelia undergoing intratubular EMT were noted in the acute phase of severe IRI, resulting in tubular atrophy in the chronic phase, reflecting failed tubular repair. Furthermore, FAK was phosphorylated in the tubular epithelia in the acute phase of severe IRI, and its inhibition ameliorated both tubular atrophy and interstitial fibrosis in the chronic phase after injury. In vivo clonal analysis of single-labeled proximal tubular epithelial cells after IRI using proximal tubule reporter mice revealed substantial clonal expansion after IRI, reflecting active epithelial proliferation during repair. The majority of these proliferating epithelia were located in atrophic and nonfunctional tubules, and FAK inhibition was sufficient to prevent tubular atrophy. In vitro, transforming growth factor-β induced FAK phosphorylation and an EMT phenotype, which was also prevented by FAK inhibition. In an in vitro tubular epithelia gel contraction assay, transforming growth factor-β treatment accelerated gel contraction, which was suppressed by FAK inhibition. In conclusion, injury-induced intratubular EMT is closely related to tubular atrophy in a FAK-dependent manner.

Background: IgA nephropathy is the most common glomerulonephritis. Secondary IgA nephropathy complicated with systemic diseases, including psoriasis, is also often reported. Generalized pustular psoriasis is a form of psoriasis characterized by sterile pustules on reddened skin and fever. Infliximab, one of the first-line therapies for severe psoriasis, has also been reported to cause systemic vasculitis and IgA nephropathy. We herein report a case of IgA nephropathy activated during infliximab treatment for generalized pustular psoriasis., Case Presentation: A 28-year-old woman presented with episodic gross hematuria, increasing proteinuria, and renal dysfunction. She had been receiving anti-TNFα therapy with infliximab because of generalized pustular psoriasis for 3 years, but her skin symptoms worsened following withdrawal during pregnancy. After delivery, her skin symptoms improved with the resumption of infliximab, but clinical signs suggested glomerulonephritis, and renal biopsy showed active IgA nephropathy. Infliximab was discontinued, and the combination of corticosteroids, tonsillectomy, and secukinumab, an IL-17A inhibitor, improved both the skin symptoms and the glomerulonephritis., Conclusions: In our case, the activity of IgA nephropathy was exacerbated by anti-TNFα therapy but was improved by the combination of corticosteroids, tonsillectomy, and an IL-17A inhibitor against the original disease. Autoimmune diseases may underlie the development of secondary IgA nephropathy associated with anti-TNFα therapy, and so further studies are needed to better understand the association between molecular-targeted drugs and IgA nephropathy.

Background: Erythropoietin-stimulating agents (ESAs) are used to treat anemia in patients with chronic kidney disease, enabling maintenance of stable hemoglobin levels and eliminating the need for multiple transfusions. Epoetin-beta pegol (C.E.R.A.) is a continuous erythropoietin receptor activator created by integrating a large methoxy-polyethylene-glycol-polymer chain into the erythropoietin molecule, which provides it with a longer half-life. On rare occasions, cases of antibody-mediated pure red cell aplasia (PRCA) related to ESAs are reported. They are characterized by abrupt onset of severe transfusion-dependent anemia, despite ESA therapy. We herein report a case of antibody-mediated PRCA in a dialysis patient receiving C.E.R.A., Case Presentation: A 44-year-old man with end-stage renal failure had been receiving continuous ambulatory peritoneal dialysis for 2 years. C.E.R.A. was administered subcutaneously as a sole ESA once a month at the hospital since 4 years ago for the treatment of renal anemia and his hemoglobin level was well controlled at 12 g/dl. From 10 months before diagnosis, however, his hemoglobin level suddenly declined, necessitating frequent transfusions. Based on the results of a bone marrow examination and detection of anti-C.E.R.A. antibodies, the patient was diagnosed with antibody-mediated PRCA. After successful elimination of the antibodies using oral prednisolone plus cyclosporine, the patient was re-administrated C.E.R.A. intravenously, as there are few reports of antibody-mediated PRCA related to ESA using that administration route. He responded to the C.E.R.A., and his anemia dramatically improved, eliminating the need for blood transfusions., Conclusions: This is the first reported case of recovery from an antibody-mediated PRCA with C.E.R.A. after its re-administration following a reversal of the antibody. It has been suggested that the additional large pegylation chain makes C.E.R.A. less likely to trigger antibody generation than other ESAs. Following successful treatment of antibody-mediated PRCA using immunosuppressive therapy, C.E.R.A. can be re-administered intravenously to treat renal anemia.

The DNA damage response after kidney injury induces cell cycle arrest in renal tubular epithelial cells, resulting in the secretion of pro-fibrotic cytokines, thereby promoting interstitial fibrosis in a paracrine manner. Phosphorylation of ataxia-telangiectasia mutated (ATM) is the initial step in the DNA damage response and subsequent cell cycle arrest; however, the effects of ATM inhibition on the injured kidney have not been explored. Pharmacological ATM inhibition by KU55933 in cisplatin-treated mice did not ameliorate, but instead exacerbated cisplatin-induced DNA damage and tubular injury, thereby increasing mortality. Analysis of isolated tubular epithelia by FACS from bigenic SLC34a1-CreERt2; R26tdTomato proximal tubular-specific reporter mice revealed that KU55933 upregulated p53 and subsequent pro-apoptotic signaling in tubular epithelia of cisplatin-treated mice, leading to marked mitochondrial injury and apoptosis. In addition, KU55933 attenuated several DNA repair processes after cisplatin treatment, including single-strand DNA repair and Fanconi anemia pathways, suggesting that DNA repair after dual treatment of cisplatin and KU55933 was not sufficient to prevent the cisplatin-induced tubular injury. Our study suggested that ATM inhibition does not increase DNA repair after cisplatin-induced DNA damage and exacerbates tubular injury through the upregulation of p53-dependent pro-apoptotic signaling. Acute kidney injury must be carefully monitored when ATM inhibitors become available in clinical practice in the future.

Objectives: To identify the factors associated with the risk of diffuse alveolar hemorrhage (DAH) in patients with microscopic polyangiitis (MPA), focusing on other preexisting lung involvements such as interstitial lung disease (ILD) and airway disease. Methods: In this retrospective cohort study, we analyzed consecutive patients with myeloperoxidase-antineutrophil cytoplasmic antibody-positive MPA who had undergone chest computed tomography (CT) before starting treatment between 2006 and 2016. Patients who already had DAH at initial CT imaging were excluded. CT images were evaluated for the presence of ILD and airway disease. The association between preexisting lung involvements and the development of DAH was assessed using logistic regression models adjusted for various clinical characteristics. Results: We identified 113 patients (median age 72 years; median follow-up duration 39 months), and 27 (24%) of them developed DAH during the follow-up. Airway disease was identified in 41 (36%) patients and was independently associated with the development of DAH (adjusted odds ratio 6.86, 95% confidence interval 1.85-25.4). However, ILD identified in 45 (40%) patients was not associated with DAH. Conclusion: Our findings suggest that DAH in MPA occurs frequently in patients with airway disease. Attention to preexisting airway disease may help predict the development of DAH.

Backgrounds: The clinical features of autosomal dominant polycystic kidney disease (ADPKD) differ among patients even if they have the same gene mutation in PKD1 or PKD2. This suggests that there is diversity in the expression of other modifier genes or in the underlying molecular mechanisms of ADPKD, but these are not well understood., Methods: We primarily cultured solute carrier family 12 member 3 (SLC12A3)-positive urine-derived distal tubular epithelial cells from 6 ADPKD patients and 4 healthy volunteers and established immortalized cell lines. The diversity in receptor tyrosine kinase (RTK) phosphorylation by phospho-RTK array in immortalized tubular epithelial cells was analyzed., Results: We noted diversity in the activation of several molecules, including Met, a receptor of hepatocyte growth factor (HGF). Administration of golvatinib, a selective Met inhibitor, or transfection of small interfering RNA for Met suppressed cell proliferation and downstream signaling only in the cell lines in which hyperphosphorylation of Met was observed. In three-dimensional culture of Madin-Darby canine kidney (MDCK) cells as a cyst formation model of ADPKD, HGF activated Met, resulting in an increased total cyst number and total cyst volume. Administration of golvatinib inhibited these phenotypes in MDCK cells., Conclusion: Analysis of urine-derived tubular epithelial cells demonstrated diverse RTK phosphorylation in ADPKD, and Met phosphorylation was noted in some patients. Considering the difference in the effects of golvatinib on immortalized tubular epithelial cells among patients, this analysis may aid in selecting suitable drugs for individual ADPKD patients., (© 2020 S. Karger AG, Basel.)

Non-dipping nocturnal blood pressure (BP) pattern is a predictor of the future decline of renal function; however, it is unclear whether it is still a risk for chronic kidney disease (CKD) patients with normal BP. To solve this question, a retrospective cohort study was conducted, and 1107 CKD patients who underwent ambulatory blood pressure monitoring (ABPM) were enrolled. We divided patients into 4 groups based on their nocturnal BP dipping pattern (dipper or non-dipper) and average 24-hour BP (hypertension or normotension). The cumulative incidence of composite renal outcomes, including a 40% reduction in eGFR, the induction of renal-replacement therapy, or death from renal causes, was analyzed. Overall, 86.1% of participants were non-dippers and 48.2% of them were normotensive. During the median follow-up period of 4.72 years, the incidence of renal composite outcomes was highest in hypertensive non-dipper patients, and was similar between normotensive dipper and non-dipper patients. Multivariate regression analysis revealed that the 24-hour systolic BP, amount of urinary protein, and hemoglobin values were associated with the incidence of renal outcomes. In conclusion, our ABPM-based analysis revealed that a non-dipping BP pattern with normotension does not predict the future incidence of composite renal outcomes in CKD patients.

Background: When we encounter glomerulonephritis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides demonstrating many plasma cell infiltrations, histological overlapping of immunoglobulin G4-related disease (IgG4-RD) often comes into the differential diagnosis. No previous study has focused on the degree of plasma cells in the kidney infiltrate in ANCA-associated glomerulonephritis (ANCA-GN), and the significance of massive plasma cell infiltrate has not been investigated., Methods: To clarify the plasma cell ratio in renal biopsy specimens of ANCA-GN and the histological characteristic of "plasma cell-rich" ANCA-GN, 20 cases of ANCA-GN were reviewed and clinicopathologically analyzed., Results: Plasma cell ratio was widely distributed between 1.4 and 81%, and the median ratio was 10%. Three patients were categorized in "plasma cell-rich" ANCA-GN, defined as over 45% plasma cell ratio. They tended to include many active glomerular lesions compared to chronic lesions and to display severe tubulointerstitial inflammation. It is suggested that plasma cell-rich ANCA-GN may be acute onset of the disease, and the target of early inflammation may also be in the tubulointerstitial region. Two of the three plasma cell-rich ANCA-GN cases demonstrated numerous IgG4+ cells, but no bird's-eye pattern fibrosis or obliterative phlebitis., Conclusions: Plasma cell-rich ANCA-GN is not rare and demonstrates distinct clinicopathological characteristics. This study also reminds us that the presence of the significant number of plasma cells in ANCA-GN, as such, is not a histological diagnostic basis for overlap ANCA-GN and IgG4-related disease.

Dietary salt restriction is essential for managing fluid retention in patients with chronic kidney disease (CKD). In this retrospective cohort study, we investigated weight loss from the perspective of fluid status in CKD patients during a 7-day hospitalization period while consuming a low-salt diet (5 g/day). Among 311 patients, the median weight loss (interquartile range, maximum) was 0.7 (0.0-1.4, 4.7) kg on Day 4 and 1.0 (0.3-1.7, 5.9) kg on Day 7. Patients were classified into quartiles based on pre-hospital urinary salt excretion (quartile [Q] 1, 1.2-5.7; Q2, 5.8-8.4; Q3, 8.5-11.3; Q4, 11.4-29.2 g/day). Weight loss was significantly greater in Q3 and Q4 than in Q1. The body mass index (BMI) and urinary salt excretion in the first 24 hours after admission were independently associated with rapid weight loss on Day 4 by multivariate logistic regression analysis. In conclusion, CKD patients with a high salt intake or high BMI exhibit rapid weight loss within a few days of consuming a low-salt diet. Dietary salt restriction is effective for reducing proteinuria in these patients, but long-term observation is needed to confirm the sustained effects.

Background: Little is known about salt taste dysfunction among hemodialysis (HD) patients. This study aimed to elucidate the prevalence of salt taste dysfunction and its relationship with interdialytic weight gain (IDWG) among HD patients., Methods: A single-center cross-sectional study involving 99 maintenance HD patients was conducted in September 2015. Salt taste threshold was measured using a salt-impregnated test strip. Salt taste dysfunction was defined as a recognition threshold of ≥0.8%. IDWG was calculated as the mean value of weight gain at the beginning of each week during a 1-month period before the taste test. We performed a multivariate analysis using the standard linear regression model to investigate the association between salt taste dysfunction and IDWG., Results: Among the 99 participants, 42% had a recognition threshold of 0.6%, whereas 38% had a recognition threshold of ≥1.6%. Overall, the prevalence of salt taste dysfunction was 58%. The mean (±SD) IDWG was 4.9% (±1.7%), and there was no significant difference in IDWG between the two groups with (4.9%) and without (4.8%) salt taste dysfunction (P = 0.90). A multivariate analysis indicated that salt taste dysfunction is not significantly associated with IDWG (mean difference = 0.06; 95% confidence interval = - 0.27 to 0.40)., Conclusions: The prevalence of salt taste dysfunction was very high among HD patients who had a unique distribution of salt taste recognition thresholds with two peaks. We found no significant association between salt taste dysfunction and IDWG.

The lack of a decrease in nocturnal blood pressure is a risk factor for the progression of chronic kidney disease (CKD); however, it currently remains unknown whether it is a risk factor in normotensive CKD patients. We conducted a retrospective cohort study and enrolled 676 CKD patients who underwent ambulatory blood pressure monitoring (ABPM). According to their nocturnal blood pressure dipping pattern (>10%: dipper or <10%: non-dipper) and average 24-h systolic blood pressure (>130/80 mmHg: hypertension or <130/80 mmHg: normotension), patients were divided into four groups. The estimated glomerular filtration rate (eGFR) decline over 2 years and relevant clinical parameters were analyzed among groups. Among all participants, 82.7% were non-dippers and half of them were normotensive. The eGFR decline was the most rapid in hypertensive non-dipper patients (4.73 ± 0.45 ml/min/1.73 m 2 /2 years), and was not significantly different between normotensive non-dipper (1.31 ± 0.49 ml/min/1.73 m 2 /2 years) and dipper patients (1.69 ± 0.80 ml/min/1.73 m 2 /2 years). A multivariate regression analysis revealed that the amount of urinary protein (95% confidence interval (CI): 1.51-2.63), 24-h systolic blood pressure (95% CI 1.13-1.45), and eGFR (95% CI 1.02-1.44) were associated with a rapid eGFR decline. We conclude that, according to the ABPM-based analysis, a non-dipping blood pressure pattern in normotensive CKD patients does not predict the risk of a rapid decline in eGFR. This suggests that the control of blood pressure, rather than its circadian rhythm, is essential for the preservation of eGFR.

Background: X-linked Alport syndrome (XLAS) is a progressive hereditary nephropathy caused by mutations in the COL4A5 gene. Genotype-phenotype correlation in male XLAS is relatively well established; relative to truncating mutations, nontruncating mutations exhibit milder phenotypes. However, transcript comparison between XLAS cases with splicing abnormalities that result in a premature stop codon and those with nontruncating splicing abnormalities has not been reported, mainly because transcript analysis is not routinely conducted in patients with XLAS., Methods: We examined transcript expression for all patients with suspected splicing abnormalities who were treated at one hospital between January of 2006 and July of 2017. Additionally, we recruited 46 males from 29 families with splicing abnormalities to examine genotype-phenotype correlation in patients with truncating ( n =21, from 14 families) and nontruncating ( n =25, from 15 families) mutations at the transcript level., Results: We detected 41 XLAS families with abnormal splicing patterns and described novel XLAS atypical splicing patterns ( n =14) other than exon skipping caused by point mutations in the splice consensus sequence. The median age for developing ESRD was 20 years (95% confidence interval, 14 to 23 years) among patients with truncating mutations and 29 years (95% confidence interval, 25 to 40 years) among patients with nontruncating mutations ( P =0.001)., Conclusions: We report unpredictable atypical splicing in the COL4A5 gene in male patients with XLAS and reveal that renal prognosis differs significantly for patients with truncating versus nontruncating splicing abnormalities. Our results suggest that splicing modulation should be explored as a therapy for XLAS with truncating mutations., (Copyright © 2018 by the American Society of Nephrology.)

Clinical and experimental studies have shown that sodium glucose co-transporter 2 inhibitors (SGLT2i) contribute to the prevention of diabetic kidney disease progression. In order to clarify its pharmacological effects on the molecular mechanisms underlying the development of diabetic kidney disease, we administered different doses of the SGLT2i, ipragliflozin, to type 2 diabetic mice. A high-dose ipragliflozin treatment for 8 weeks lowered blood glucose levels and reduced urinary albumin excretion. High- and low-dose ipragliflozin both inhibited renal and glomerular hypertrophy, and reduced NADPH oxidase 4 expression and subsequent oxidative stress. Analysis of glomerular phenotypes using glomeruli isolation demonstrated that ipragliflozin preserved podocyte integrity and reduced oxidative stress. Regarding renal tissue hypoxia, a short-term ipragliflozin treatment improved oxygen tension in the kidney cortex, in which SGLT2 is predominantly expressed. We then administered ipragliflozin to type 1 diabetic mice and found that high- and low-dose ipragliflozin both reduced urinary albumin excretion. In conclusion, we confirmed dose-dependent differences in the effects of ipragliflozin on early diabetic nephropathy in vivo. Even low-dose ipragliflozin reduced renal cortical hypoxia and abnormal hemodynamics in early diabetic nephropathy. In addition to these effects, high-dose ipragliflozin exerted renoprotective effects by reducing oxidative stress in tubular epithelia and glomerular podocytes.

Nephrotic syndrome (NS) rarely occurs in post-hematopoietic stem cell transplantation (HSCT) recipients but represents the renal manifestation of graft-versus-host disease (GVHD). Membranous nephropathy (MN) accounts for almost two thirds of post-HSCT NS and is caused by immune complex deposition. Renal thrombotic microangiopathy (TMA) without fulfillment of clinical criteria for TMA has been underreported because of reduced opportunity for histological examination. However, renal TMA has recently been reported in association with GVHD and humoral immunological reactions. Although both MN and TMA after HSCT are associated with GVHD and immunological abnormalities, these diseases are exceptionally coexistent in renal biopsy specimens. We herein describe a case of post-HSCT NS, histologically showing overlapped lesions of TMA and MN. Renal biopsy specimen after presentation of NS revealed early stage MN and TMA with evidence of chronicity. TMA was thought to have preceded MN, and renal biopsy at the phase of pre-nephrotic proteinuria might reveal earlier histological changes of isolated renal TMA. Detection of subclinical renal TMA earlier by spontaneous renal biopsy can help prevent progression of renal injury or overlapping of other renal pathologies. We also demonstrated Th2 predominant intraglomerular infiltration of lymphocytes by immunohistochemistry., (© 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Circadian clocks in mammals function in most organs and tissues throughout the body. Various renal functions such as the glomerular filtration and excretion of electrolytes exhibit circadian rhythms. Although it has been reported that the expression of the clock genes composing molecular oscillators show apparent daily rhythms in rodent kidneys, functional variations of regional clocks are not yet fully understood. In this study, using macroscopic bioluminescence imaging method of the PER2::Luciferase knock-in mouse kidney, we reveal that strong and robust circadian clock oscillation is observed in the medulla. In addition, the osmotic pressure in the inner medulla shows apparent daily fluctuation, but not in the cortex. Quantitative-PCR analysis of the genes contributing to the generation of high osmotic pressure or the water re-absorption in the inner medulla, such as vasopressin receptors (V1aR, V2R), urea transporter (UT-A2) and water channel (Aqp2) show diurnal variations as well as clock genes. Deficiency of an essential clock gene Bmal1 impairs day-night variations of osmotic pressure gradient in the inner medulla, suggesting that circadian clocks in the medulla part of the kidney may regulate the circadian rhythm of cortico-medullary osmotic pressure gradient, and may contribute physiological day-night rhythm of urination.

Background: Nail-patella syndrome (NPS) is an autosomal dominant disorder caused by mutations in the LMX1B gene and is characterized by nail dysplasia, skeletal abnormalities, and nephropathy. We herein report a case of steroid-resistant nephrotic syndrome (SRNS) prior to overt orthopedic symptoms in a patient with NPS., Case Presentation: A 24-year-old woman presented to our hospital with knee pain. She had poorly developed nails, hypoplastic patellas, dislocation of the elbows, and iliac horns in the pelvis. At the age of 7, she developed nephrotic syndrome and was diagnosed with primary focal segmental glomerulosclerosis by renal biopsy. She received long-term corticosteroid therapy with no obvious response. Her clinical course and orthopedic manifestations indicated NPS, and a genetic analysis showed a de novo mutation in the LMX1B gene (c.819 + 1G > A). Nephropathy in this case was considered to be associated with NPS. Therefore, we discontinued corticosteroids without the exacerbation of nephrotic syndrome., Conclusions: Patients with NPS may develop nephrotic syndrome prior to overt orthopedic symptoms and only show non-specific findings in renal biopsy at an early stage of NPS nephropathy. Hereditary nephrotic syndrome, often presenting as childhood-onset SRNS, may also be difficult to diagnose in patients with the following conditions: renal symptoms prior to overt extrarenal symptoms, de novo mutations, and non-specific findings in renal biopsy. Therefore, in the management of SRNS in children, we need to reconsider the possibility of hereditary diseases such as NPS even without a family history.

Background: The pathophysiological mechanisms of cisplatin nephrotoxicity include the reduction of renal blood flow, as well as tubular epithelial cell toxicity. The objective of this study was to investigate the influence of lower blood pressure and decreased food intake on the incidence of cisplatin nephrotoxicity., Methods: We conducted a retrospective cohort study at a university hospital between 2011 and 2012. We identified hospitalized adult patients with head and neck cancer, esophageal cancer, or gastric cancer, who received intravenous cisplatin administration. The primary outcome was the incidence of cisplatin nephrotoxicity defined as the increase in serum creatinine after cisplatin administration more than 1.5 times from baseline., Results: The study participants included 182 patients, in whom we observed a total of 442 cycles of cisplatin chemotherapy. The incidence of cisplatin nephrotoxicity was observed in 41 of 182 cycles with initial administration. Multivariate logistic regression analysis showed that systolic blood pressure was independently associated with cisplatin nephrotoxicity (adjusted odds ratio 0.75, 95% confidence interval 0.57 to 0.95 for each 10 mmHg). The use of renin-angiotensin system (RAS) inhibitors was also associated with cisplatin nephrotoxicity (3.39, 1.30 to 8.93). Among quartiles of systolic blood pressure in all cycles of chemotherapy, the incidence of nephrotoxicity in the lower blood pressure group was significantly higher than that in the higher blood pressure group for patients taking non-solid food (P = 0.037), while there was no significant difference for patients taking solid food (P = 0.67)., Conclusions: Lower blood pressure and the use of RAS inhibitors were associated with the incidence of cisplatin nephrotoxicity, and lower blood pressure had a greater influence on nephrotoxicity in patients who could not take solid food. Discontinuation of antihypertensive medication including RAS inhibitors before cisplatin chemotherapy should be considered, which may be beneficial for patients with lower blood pressure.