Nephrology (Carlton, Vic.)最新文献

{"title":"C3 Glomerulopathy in Autoinflammatory-Pancytopenia Syndrome: A Case Report.","authors":"Shaimaa Sayed","doi":"10.1111/nep.70300","DOIUrl":"https://doi.org/10.1111/nep.70300","url":null,"abstract":"<p><p>Autoinflammatory-pancytopenia syndrome (AIPCS) is a rare autosomal recessive disease caused by a mutation in the deoxyribonuclease II (DNASE2) gene. It has mainly haematological manifestations and recurrent fevers. The kidney could be involved in the form of proteinuria, membranoproliferative glomerulonephritis (MPGN) or immune complex deposition rather than acute kidney injury (AKI) or C3 glomerulopathy (C3G). A six-year-old male child presented with high-grade fever, AKI, generalized edema and hypertension. He had a history of recurrent hospital admission with fever, arthritis, skin rash and recurrent infections in the form of diarrhoea and chest infection. He had stunted growth, pallor, hepatosplenomegaly (HSM) and skin hyperpigmentation at the sites of the healed vasculitic skin rash. He was diagnosed with hemophagocytic lymphohistiocytosis and received its protocol of treatment with improvement of fever. However, pancytopenia and HSM were still progressive. Laboratory investigations revealed pancytopenia, impaired kidney function tests and heavy-range proteinuria with persistent low C3 level. Kidney biopsy revealed C3 deposition suggestive of C3G, with 20% global glomerulosclerosis, mild interstitial fibrosis and tubular atrophy (10%). Kidney function tests normalized after receiving intravenous methylprednisolone, but proteinuria is still persistent, which indicates that AKI was on top of chronic kidney disease in the presence of C3G. Whole exome sequencing revealed a homozygous (missense) variant of uncertain significance with pathogenic evidence in exon-6 of the DNASE2 gene causing AIPCS. In conclusion, C3G is a new form of kidney involvement associated with AIPCS. Kidney histopathology should be combined with phenotypic-genotypic aspects of AIPCS.</p>","PeriodicalId":520716,"journal":{"name":"Nephrology (Carlton, Vic.)","volume":"31 10","pages":"e70300"},"PeriodicalIF":1.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rates of Deceased Donor Kidney Transplantation in Highly Sensitised Patients in Aotearoa New Zealand: A Data Linkage Analysis.","authors":"Amy O R Thomas, James A Hedley, Reshma Shettigar, Nicholas B Cross, Ian Dittmer, Heather Dunckley, Angela C Webster","doi":"10.1111/nep.70295","DOIUrl":"https://doi.org/10.1111/nep.70295","url":null,"abstract":"<p><strong>Aim: </strong>To compare the observed rates of kidney transplantation among highly and non-highly sensitised patients on the deceased donor waiting list in Aotearoa New Zealand, and characterise associations with high sensitisation, to inform potential changes in the National Kidney Allocation Scheme.</p><p><strong>Methods: </strong>Patients listed for deceased donor kidney transplantation between 2006 and 2019 were identified using linked health data from the AcceSS and Equity in Transplantation platform. Highly sensitised patients were defined as having a panel reactive antibody (PRA) or calculated panel reactive antibody (cPRA) ≥ 80%, then stratified into groups of 80-94, 95-98 and ≥ 99%. Individual-level characteristics associated with sensitisation were identified using linear regression, and transplantation rates between sensitisation groups were compared using a Cox proportional hazards model.</p><p><strong>Results: </strong>Factors associated with increased sensitisation included prior transplant, female sex, younger age and non-European ethnicity (all p < 0.001). Increasing sensitisation was associated with reduced transplantation rate (p < 0.001). Compared with PRA/cPRA < 80%, the chance of transplantation was lower for those with PRA/cPRA 80%-94% (HR: 0.75, 95% CI: 0.54-1.04), PRA/cPRA 95%-98% (HR: 0.38, 95% CI: 0.23-0.60) and PRA/cPRA ≥ 99% (HR: 0.10, 95% CI: 0.05-0.17).</p><p><strong>Conclusion: </strong>Highly sensitised patients on the deceased donor waiting list in Aotearoa New Zealand experience reduced rates of kidney transplantation. The lowest rates are seen in patients with a cPRA of ≥ 99%, which highlights this group as a key target population for future modifications to the National Kidney Allocation Scheme.</p>","PeriodicalId":520716,"journal":{"name":"Nephrology (Carlton, Vic.)","volume":"31 10","pages":"e70295"},"PeriodicalIF":1.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct Complement Activation Profiles Between NELL1- and PLA2R-Associated Membranous Nephropathy: A Clinicopathological and Proteomic Study.","authors":"Taihei Suzuki, Kang Dedong, Kunio Kawanishi, Masataka Ueda, Yuki Kajio, Kazuki Kobayashi, Nobuhiro Kanazawa, Mayumi Takahashi-Kobayashi, Joichi Usui, Masaki Baba, Hirokazu Honda, Kazuho Honda, Masayuki Iyoda","doi":"10.1111/nep.70288","DOIUrl":"10.1111/nep.70288","url":null,"abstract":"<p><strong>Aim: </strong>Primary membranous nephropathy (MN) is classified into antigen-defined subtypes, most commonly M-type phospholipase A2 receptor (PLA2R)-associated MN and neural epidermal growth factor-like 1 (NELL1)-associated MN. Whether complement activation differs between these subtypes remains unclear. This study compared their clinicopathological features and complement-related protein expression.</p><p><strong>Methods: </strong>We retrospectively compared PLA2R-associated MN (n = 17) and NELL1-associated MN (n = 9), including five additional NELL1-associated MN cases from an external institution. Glomerular C3 and C4d deposition were assessed by immunostaining, with quantitative C4d analysis using digital pathology. Complement-related proteins were additionally evaluated by laser microdissection-assisted data-dependent acquisition mass spectrometry in cases with available proteomic data.</p><p><strong>Results: </strong>Patients with NELL1-associated MN were older and showed greater interstitial fibrosis and tubular atrophy than those with PLA2R-associated MN. Glomerular IgG4 and C3 deposition were significantly lower in NELL1-associated MN. Quantitative analysis demonstrated lower glomerular C4d deposition in NELL1-associated MN at both the glomerulus and patient levels, whereas C4d intensity was not significantly correlated with serum anti-PLA2R antibody titres. In the proteomic analysis, C3, C5 and complement factor H were numerically more abundant in PLA2R-associated MN than in NELL1-associated MN, although these differences were not statistically significant.</p><p><strong>Conclusion: </strong>NELL1-associated MN and PLA2R-associated MN differ not only in clinical and histological features but also in glomerular complement deposition. Reduced C3 and C4d deposition in NELL1-associated MN suggests less prominent glomerular complement activation than in PLA2R-associated MN, supporting biological heterogeneity among antigen-defined MN subtypes.</p>","PeriodicalId":520716,"journal":{"name":"Nephrology (Carlton, Vic.)","volume":"31 10","pages":"e70288"},"PeriodicalIF":1.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13647480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149140375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal Divergence Does Not Necessarily Establish Aetiological Autonomy of Chronic Kidney Disease of Non-Traditional Aetiology.","authors":"Wenjie Ge, Yingying Qian","doi":"10.1111/nep.70294","DOIUrl":"https://doi.org/10.1111/nep.70294","url":null,"abstract":"","PeriodicalId":520716,"journal":{"name":"Nephrology (Carlton, Vic.)","volume":"31 10","pages":"e70294"},"PeriodicalIF":1.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Post-Transplant Lactate Dehydrogenase Stratifies the Severity of Delayed Graft Function After Deceased-Donor Kidney Transplantation.","authors":"Samuel Sultan, Mike Fruscione, Jolie Murcko, Alexandra Erhardt, Alexey Zendel, Josue Alvarez-Casas, Choli Hartono, Vaqar Ahmed, Fu Luan, Woojin James Chon, Angelica Del Vecchio, Jessica Spiegel, Michael Wynd, Melissa Chaung, David Serur, Michael Goldstein","doi":"10.1111/nep.70286","DOIUrl":"https://doi.org/10.1111/nep.70286","url":null,"abstract":"<p><strong>Aim: </strong>Early graft dysfunction after kidney transplantation is heterogeneous, ranging from transient delayed graft function (DGF) to prolonged dialysis dependence and primary nonfunction (PNF). Biomarkers that reflect the severity of early graft injury remain limited. We evaluated whether early post-transplant lactate dehydrogenase (LDH) is associated with the severity of graft dysfunction.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of 339 deceased-donor kidney transplant recipients at a single centre between March 2023 and May 2024. Peak LDH during post-operative Days 1-3 was categorized into quartiles and evaluated continuously. Outcomes included DGF, PNF, duration of dialysis dependence and longitudinal eGFR. Multivariable logistic regression adjusted for donor and recipient factors; sensitivity analyses evaluated LDH functional form, maintenance immunosuppression and additional clinical covariates.</p><p><strong>Results: </strong>DGF occurred in 20.5%, 19.5%, 28.4% and 51.2% of recipients across LDH quartiles Q1-Q4, respectively (p < 0.001), indicating a nonlinear association with risk concentrated at higher LDH values. In adjusted categorical analysis, Q4 had substantially higher odds of DGF than Q1 (adjusted OR = 3.88; 95% CI = 1.82-8.28; p < 0.001), whereas Q2 and Q3 were not significantly different from Q1. Peak LDH remained associated with DGF when modelled continuously (adjusted OR = 1.10 per 100 U/L; 95% CI = 1.02-1.18) and after adjustment for de novo belatacept use. All six PNF events occurred in Q4. Higher LDH was also associated with lower longitudinal eGFR, particularly in Q4.</p><p><strong>Conclusion: </strong>Early post-transplant LDH was associated with the severity of early graft dysfunction, with a nonlinear increase in DGF risk concentrated at higher LDH values. Because LDH is routinely available in the first post-operative days but has only modest stand-alone discrimination, it may be most useful as one component of early risk assessment. Prospective multicentre validation is needed before LDH-based thresholds are used to direct management.</p>","PeriodicalId":520716,"journal":{"name":"Nephrology (Carlton, Vic.)","volume":"31 10","pages":"e70286"},"PeriodicalIF":1.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149122967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mediation Analysis of Urine Osmolality and Response to Tolvaptan in Autosomal Dominant Polycystic Kidney Disease: A Post Hoc Assessment.","authors":"Ryo Matsuura, Kent Doi, Zhen Zhang, Katherine Maringer, Sachin Hajarnis, Yoshifumi Hamasaki","doi":"10.1111/nep.70292","DOIUrl":"10.1111/nep.70292","url":null,"abstract":"<p><strong>Aim: </strong>Tolvaptan delays growth in total kidney volume (TKV) and decline in estimated glomerular filtration rate (eGFR) among individuals with autosomal dominant polycystic kidney disease (ADPKD) at elevated risk of rapid progression. We evaluated changes in urine osmolality (Uosm) after treatment initiation as a potential biomarker of long-term response.</p><p><strong>Methods: </strong>This was a post hoc analysis of TEMPO 3:4, a 3-year, randomized, placebo-controlled trial of tolvaptan. Causal mediation analysis assessed if the effect of tolvaptan on longer-term outcomes of change in eGFR and TKV at month 36 was mediated by change in Uosm at week 3. Analyses were performed separately for non-Japanese and Japanese participants.</p><p><strong>Results: </strong>The average causal mediation effect (ACME) of change in Uosm on eGFR at month 36 was statistically significant (2.4; 95% quasi-Bayesian confidence interval [CI] 1.2, 3.6) in the non-Japanese cohort (n = 948). In the Japanese cohort (n = 138), whereas the ACME for change in Uosm was non-significant (-0.3 [95% CI: -2.3, 1.7]), the average direct effect (ADE) of tolvaptan on eGFR was statistically significant (8.4 [95% CI 3.1, 12.4]). For percentage change in TKV, the ADE of tolvaptan was statistically significant in both the non-Japanese (-8.3 [95% CI: -10.5, -6.3]) and Japanese cohorts (-12.0 [95% CI: -17.4, -7.5]).</p><p><strong>Conclusion: </strong>This study supported short-term change in Uosm as a predictive biomarker of longer-term kidney function in a non-Japanese cohort; the relationship was not significant in the smaller Japanese cohort. Tolvaptan exhibited a direct treatment effect on the growth of kidney volume in both cohorts of ADPKD patients.</p>","PeriodicalId":520716,"journal":{"name":"Nephrology (Carlton, Vic.)","volume":"31 10","pages":"e70292"},"PeriodicalIF":1.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149083680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Spectrum and Family-Based Cascade Screening in Vietnamese Families With Autosomal Dominant Polycystic Kidney Disease.","authors":"Nguyen Thi An Thuy, Van Khanh Tran, Ngoc Lan Nguyen, Le Thi Phuong, Thi Ha Vu, Thi Nhu Cao, Truong Minh Do, Phan Long Nguyen, Thao Linh Tran, Tran Nhat Minh Dang, Thinh Huy Tran, Trung Dung Nghiem","doi":"10.1111/nep.70290","DOIUrl":"https://doi.org/10.1111/nep.70290","url":null,"abstract":"<p><strong>Aim: </strong>Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited causes of kidney failure. We performed a whole-exome sequencing study that aimed to characterize the spectrum of PKD1 and PKD2 variants in a Vietnamese ADPKD cohort and to evaluate the clinical utility of family-based cascade genetic testing.</p><p><strong>Methods: </strong>This cross-sectional descriptive study included 40 unrelated patients with clinically diagnosed polycystic kidney disease. Variants were identified in probands using whole-exome sequencing. Family-based genetic testing was subsequently performed using Sanger sequencing in 104 relatives. Cascade screening was restricted to families with pathogenic or likely pathogenic variants, whereas variant of uncertain significance families were evaluated separately through segregation analysis to support variant interpretation and potential reclassification. Clinical and genetic characteristics were described and exploratory genotype-phenotype analyses were performed.</p><p><strong>Results: </strong>Genetic testing identified PKD1 variants in 77.5% of patients, PKD2 variants in 17.5% and no ADPKD-related variants in 5.0%. A total of 37 potentially relevant variants were detected, including 31 in PKD1 (83.8%) and six in PKD2 (16.2%). Nine novel variants were identified. PKD1 carriers were younger than PKD2 carriers (p = 0.029) at the time of evaluation. Apart from this age difference, no other clinical characteristics differed significantly according to gene type or variant class. Cascade screening of 89 relatives from families with pathogenic or likely pathogenic variants revealed that 53 (59.6%) carried the familial variant, whereas 36 (40.4%) did not. Among 53 variant-positive relatives, 34 (64.2%) were symptomatic and 19 (35.8%) were asymptomatic at the time of evaluation. In contrast, no variant-negative relatives showed clinical evidence of ADPKD (p < 0.001). These findings are consistent with autosomal dominant segregation of the familial variant and support the clinical utility of cascade screening.</p><p><strong>Conclusion: </strong>This study expands the known genetic spectrum of ADPKD in Vietnamese families and demonstrates the predominance of PKD1 variants in this cohort. Family-based cascade screening was useful for identifying variant-positive relatives before overt clinical manifestation, thereby supporting earlier surveillance and genetic counselling.</p>","PeriodicalId":520716,"journal":{"name":"Nephrology (Carlton, Vic.)","volume":"31 10","pages":"e70290"},"PeriodicalIF":1.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer Risk in Haemodialysis Patients Compared With That in the General Population: A Multicenter Questionnaire-Based Study in Okinawa, Japan.","authors":"Yoko Arakawa, Yuriko Ishida, Akira Higa, Takeshi Tana, Takuhiro Moromizato, Kentaro Kohagura, Kunitoshi Iseki","doi":"10.1111/nep.70293","DOIUrl":"10.1111/nep.70293","url":null,"abstract":"<p><strong>Aim: </strong>Dialysis patients face a heightened risk of cancer, particularly kidney cancer. The global aging of dialysis patients suggests that managing cancer may become a critical factor in future healthcare. Given that the chronic uremic state is a cancer risk factor, dialysis patients may face an elevated risk for all cancers. However, the epidemiology of nonkidney cancers, such as colorectal cancer, remains to be fully elucidated.</p><p><strong>Methods: </strong>This was a retrospective cohort study targeting 74 dialysis facilities in Okinawa Prefecture, Japan. The subjects were patients who received dialysis for a minimum of 90 days between 2015 and 2019 and were diagnosed with cancer after initiating dialysis during this period. The cancer incidence ratio for the study population (21 655 person-years) was then compared with that of the general Okinawan population using standardized incidence ratios.</p><p><strong>Results: </strong>A total of 404 cancer cases were collected from 56 facilities (76%). The standardized incidence ratios for all cancers was 1.36, with the risk of kidney cancer increasing with longer dialysis vintage. Patients with a dialysis vintage of less than 2 years showed an increased risk of colorectal and lung cancer. The risk of breast cancer was similar to that of the general population.</p><p><strong>Conclusion: </strong>The present study revealed that not all cancer risks were increased among patients receiving haemodialysis. Screening for colorectal and lung cancer in the first 2 years after commencement of dialysis may be important. Further research is needed to determine the efficacy of this approach for patients receiving dialysis.</p>","PeriodicalId":520716,"journal":{"name":"Nephrology (Carlton, Vic.)","volume":"31 10","pages":"e70293"},"PeriodicalIF":1.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinal Disease Risk With Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors Versus Long-Acting Erythropoiesis-Stimulating Agents in Patients With Non-Dialysis Chronic Kidney Disease: A Real-World Database Analysis in Japan.","authors":"Kento Hoshino, Yusuke Sasabuchi, Yoshihisa Miyamoto, Yohei Hashimoto, Hideo Yasunaga","doi":"10.1111/nep.70297","DOIUrl":"https://doi.org/10.1111/nep.70297","url":null,"abstract":"<p><strong>Aim: </strong>Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors constitute novel oral pharmacotherapy for anaemia in chronic kidney disease (CKD). Although a possible HIF-PH inhibitor-induced increase in vascular endothelial growth factor could exacerbate retinal diseases, real-world evidence is limited, particularly among Japanese non-dialysis patients.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study using the DeSC administrative claims database (DeSC Healthcare Inc., Tokyo, Japan; December 2019 to June 2023). We identified patients with CKD who newly used HIF-PH inhibitors or long-acting erythropoiesis-stimulating agents (ESAs). The primary outcome was the first treatment-requiring retinal disease. We employed the matching weight method using high-dimensional propensity scores to adjust for confounding and inverse probability of censoring weights (IPCW) to account for informative censoring.</p><p><strong>Results: </strong>The study included 74 530 treatment-naïve patients (mean age: 84.7 years; 49 928 ESA users; 24 602 HIF-PH inhibitor users). The risk of retinal diseases did not differ significantly between the HIF-PH inhibitor and ESA groups. The adjusted hazard ratio (HR) with matching weights was 0.65 [95% confidence interval (CI): 0.37-1.12]. The HR with matching weights and IPCW was 0.55 (95% CI: 0.22-1.38). Sensitivity analyses supported these findings. Negative control analysis using cataracts yielded an adjusted HR of 0.85 (95% CI: 0.67-1.07). Subgroup analyses showed no increased risk across categories.</p><p><strong>Conclusions: </strong>HIF-PH inhibitors were not associated with an increased risk of treatment-requiring retinal disease. These real-world data suggest the retinal safety of HIF-PH inhibitors in non-dialysis patients with CKD. Retinal concerns may not necessarily be a limiting factor while selecting HIF-PH inhibitors for non-dialysis patients with CKD.</p>","PeriodicalId":520716,"journal":{"name":"Nephrology (Carlton, Vic.)","volume":"31 10","pages":"e70297"},"PeriodicalIF":1.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149221307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nintedanib-Associated Glomerular Endothelial Injury With Secondary Collapsing Focal Segmental Glomerulosclerosis: Potential Role of Sodium-Glucose Cotransporter 2 Inhibition.","authors":"Yoshitaka Furuto, Hirotsugu Hashimoto, Daiki Yoshino, Sayako Ikeda, Akio Namikawa, Dai Sato, Hiroko Takahashi, Teppei Morikawa, Yuko Shibuya","doi":"10.1111/nep.70274","DOIUrl":"10.1111/nep.70274","url":null,"abstract":"<p><p>Nintedanib (NIB), a small-molecule tyrosine kinase inhibitor (TKI), is approved for idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated interstitial lung disease. Although nephrotoxicity is uncommon, cases of nephrotic syndrome (NS), acute kidney injury (AKI) and glomerular lesions including thrombotic microangiopathy (TMA) and anti-glomerular basement membrane (GBM) nephritis have been reported. However, the optimal management of NIB-associated glomerular disease remains undefined. We report a 69-year-old man with IPF, hypertension, diabetes and underlying chronic kidney disease who developed persistent NS and renal dysfunction 16 months after initiation of NIB. Kidney biopsy demonstrated glomerular endothelial injury with microangiopathic features, accompanied by secondary collapsing focal segmental glomerulosclerosis (FSGS) and background diabetic kidney disease. Despite discontinuation of NIB and intensification of renin-angiotensin system inhibition and mineralocorticoid receptor blockade, nephrotic-range proteinuria persisted. Subsequent initiation of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin was temporally associated with a gradual and sustained reduction in proteinuria, with partial remission achieved while preserving the estimated glomerular filtration rate. To our knowledge, this is the first report of NIB-associated glomerular endothelial injury with secondary collapsing FSGS in which SGLT2i initiation was temporally associated with sustained proteinuria reduction under concomitant supportive therapy. TKIs may induce both endothelial and podocyte injury and therapeutic options beyond drug withdrawal remain limited. In this context, SGLT2 inhibition may represent a potential adjunctive therapeutic strategy in selected cases with underlying chronic kidney disease and warrants further systematic evaluation.</p>","PeriodicalId":520716,"journal":{"name":"Nephrology (Carlton, Vic.)","volume":"31 9","pages":"e70274"},"PeriodicalIF":1.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13529372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}