Journal of Nephrology最新文献

{"title":"Genome-wide polygenic risk score for estimated glomerular filtration slope predicts chronic kidney disease in a Taiwanese population.","authors":"Gwo-Tsann Chuang, Chia-Ni Hsiung, Tony Pan-Hou Che, Kook-Hwan Oh, Sue K Park, Sungji Moon, Sangjun Lee, Cassianne Robinson-Cohen, Adriana M Hung, Wen-Yi Li, Yi-Cheng Chang","doi":"10.1007/s40620-025-02380-9","DOIUrl":"https://doi.org/10.1007/s40620-025-02380-9","url":null,"abstract":"<p><strong>Background: </strong>Kidney function decline is associated with cardiovascular disease and various other morbidities. Previous studies regarding polygenic risk scores of estimated glomerular filtration rate (eGFR) change were generally based on individuals of European ancestry and not validated on populations of East Asian ancestry.</p><p><strong>Methods: </strong>We conducted a genome-wide association study for eGFR slope among 26,755 non-diabetic individuals from the Taiwan Biobank. We developed an eGFR slope polygenic risk score and validated its prediction power on chronic kidney disease (CKD) in another sample with 58,777 non-diabetic individuals.</p><p><strong>Results: </strong>Eight candidate loci associated with eGFR slope (P-value ranging from 1.56 × 10^-6 to 8.73 × 10^-6) located in the SLC9A9, SLC26A8, DEPTOR, OBP2B, PRMT8, C19orf44 genes and an intergenic locus between MTMR12-ZFR genes were identified and a polygenic risk score for eGFR slope was constructed. The polygenic risk score was validated externally to be significantly associated with CKD in another set of individuals (P-value = 0.0182; odds ratio = 0.753; 95% confidence interval: 0.5936-0.9504).</p><p><strong>Conclusions: </strong>We constructed a genome-wide polygenic risk score for eGFR decline and externally validated its use in predicting CKD in another Taiwan population. Our eGFR slope polygenic risk score might be useful for clinical CKD risk assessment in future, especially for East Asians.</p>","PeriodicalId":16542,"journal":{"name":"Journal of Nephrology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response predictors and long-term outcomes of preprandial single-daily cyclosporine in children with steroid-dependent nephrotic syndrome.","authors":"Yasuko Urushihara, Shuichiro Fujinaga, Tomohiko Nishino, Daishi Hirano, Koji Sakuraya, Yoshiyuki Ohtomo, Satoshi Masutani","doi":"10.1007/s40620-025-02379-2","DOIUrl":"https://doi.org/10.1007/s40620-025-02379-2","url":null,"abstract":"<p><strong>Background: </strong>Although single-daily cyclosporine may offer an effective therapeutic option with increased compliance and reduced nephrotoxicity, response predictors and long-term outcomes following this regimen remain unclear in children with steroid-dependent nephrotic syndrome.</p><p><strong>Methods: </strong>A retrospective study was conducted between October 2005 and December 2021 on children with steroid-dependent nephrotic syndrome caused by minimal change disease (MCD) who were treated with preprandial single-daily cyclosporine to maintain 2-h post-dose levels of 500-700 ng/mL. The primary endpoint was the time to treatment failure after single-daily cyclosporine initiation. The secondary endpoint was the long-term outcome at last visit.</p><p><strong>Results: </strong>After initiating single-daily cyclosporine therapy in 48 children, 31 patients, including 18 who did not experience relapse during treatment, were able to discontinue steroids (response group), while 17 patients experienced treatment failure. The median time to the first relapse after nephrotic syndrome diagnosis was significantly shorter in the treatment failure group than in the response group (2.1 vs. 4.3 months, p = 0.014). Multivariable Cox proportional hazard regression analysis identified two independent risk factors for treatment failure: early first relapse < 2.2 months after nephrotic syndrome diagnosis (hazard ratio: 7.79, 95% confidence interval: 2.29-26.48, p = 0.001) and higher prior relapse rate (hazard ratio: 1.41 per episode increase, 95% confidence interval: 1.07-1.86, p = 0.016). None of the patients progressed to chronic kidney disease Stage 3 or higher.</p><p><strong>Conclusions: </strong>Single-daily cyclosporine may offer a promising treatment option for children with steroid-dependent nephrotic syndrome caused by MCD, particularly for those who do not experience early relapse following nephrotic syndrome diagnosis and have lower prior relapse rate.</p>","PeriodicalId":16542,"journal":{"name":"Journal of Nephrology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of electrical muscle stimulation during hemodialysis in older patients with frailty: a crossover randomized controlled trial.","authors":"Yuta Suzuki, Kentaro Kamiya, Keika Hoshi, Shinya Tanaka, Manae Harada, Takaaki Watanabe, Takahiro Shimoda, Shohei Yamamoto, Yusuke Matsunaga, Ryota Matsuzawa, Atsuhiko Matsunaga","doi":"10.1007/s40620-025-02383-6","DOIUrl":"10.1007/s40620-025-02383-6","url":null,"abstract":"<p><strong>Background: </strong>While electrical muscle stimulation during hemodialysis has been reported to improve physical performance in middle-aged patients, clinical evidence regarding its efficacy in older patients with frailty remains limited.</p><p><strong>Methods: </strong>In this crossover trial, we randomly assigned 18 older patients (aged ≥ 65 years) with frailty receiving maintenance hemodialysis in a 1:1 ratio to the study intervention. Group 1 underwent electrical muscle stimulation first, followed by a five-week washout period, and then the control session without electrical muscle stimulation. Group 2 received the control session first, followed by the electrical muscle stimulation sessions. Eligible patients had physical frailty defined by a Short Physical Performance Battery (SPPB) score of 4-9 points. Electrical muscle stimulation was conducted for 30-40 min per day, 3 days a week, over 5 weeks, during hemodialysis sessions. The primary outcome was the difference in quadriceps isometric strength before and after the treatment period.</p><p><strong>Results: </strong>Among 18 patients who were randomized, 16 patients were included in the intention-to-treat analysis (median age: 76 years [Q1 to Q3, 72 to 79]; men: 38%; median SPPB: 6 points [Q1 to Q3, 5 to 9]). The median change in quadriceps isometric strength (Q1 to Q3) was 1.5%dry weight (%DW) (0.2 to 4.2) during the electrical muscle stimulation intervention period and - 3.6%DW (- 7.7 to - 1.6) during the control period (P = 0.0027).</p><p><strong>Conclusions: </strong>Our trial found that intradialytic electrical muscle stimulation was associated with improved quadriceps isometric strength in older patients with frailty, indicating a potential benefit of intradialytic electrical muscle stimulation intervention for physical performance, also in these subjects.</p><p><strong>Trial registration: </strong>The study was registered in a public trial registry (UMIN-CTR, number: UMIN000032501).</p>","PeriodicalId":16542,"journal":{"name":"Journal of Nephrology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteocalcin as a predictor of bone fracture in children with chronic kidney diseases.","authors":"Happy Sawires, Shrouk Abdallah, Mohamed Ramadan, Radwa Abdel-Halim, Yasmin Ramadan","doi":"10.1007/s40620-025-02385-4","DOIUrl":"10.1007/s40620-025-02385-4","url":null,"abstract":"<p><strong>Background: </strong>The associations between biochemical indicators of osteocalcin and bone health are fairly well established in adults through observational studies. In this context, our objective was to assess serum level of uncarboxylated osteocalcin (uOC) and its relation to the incidence of bone fractures other bone health indices in children with CKD.</p><p><strong>Methods: </strong>We enrolled 102 patients classified into two groups: group A: CKD without KRT; group B: CKD on regular HD. The patients were followed throughout the study period. The study's endpoint was either the occurrence of a bone fracture or the conclusion of the study period. Another 22 healthy individuals were involved as a control group. We measured uOC and various indicators of bone health including bone-specific alkaline phosphatase (BAP) on the same day of the fracture or at the end of the study period.</p><p><strong>Results: </strong>uOC was found significantly higher in CKD children in comparison to the control group (p <0.001). Moreover, its level was significantly higher in the HD group compared to CKD without KRT group (p = 0.047). In patients with fractures, uOC and BAP were significantly higher compared with patients without fractures (p < 0.001 and 0.019, respectively). By logistic regression analysis, uOC was the only predictor of bone fractures (p = 0.027, OR = 1.011).</p><p><strong>Conclusion: </strong>Elevated uOC levels were observed in children with CKD who experienced fractures, and these levels showed a correlation with BAP. Furthermore, uOC appears to be a reliable indicator of bone fractures in this population.</p>","PeriodicalId":16542,"journal":{"name":"Journal of Nephrology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obinutuzumab in Rituximab-resistant and recurrent membranous nephropathy: a case-series.","authors":"Krita Sridharan, Basu Gopal, Scott Wilson, Alan Pham, Holly Hutton","doi":"10.1007/s40620-025-02224-6","DOIUrl":"10.1007/s40620-025-02224-6","url":null,"abstract":"<p><strong>Background: </strong>Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults, with high risk of progression to end-stage kidney disease when untreated. Rituximab is commonly used in its treatment however many patients do not respond. Obinutuzumab is a novel anti-CD20 monoclonal antibody for which there is increasing observational evidence in treatment-resistant membranous nephropathy. The majority of evidence for its use relates to anti-phospholipase A2 receptor-(PLA2R) associated membranous nephropathy.</p><p><strong>Methods: </strong>This was a single-centre case-series of all patients at a tertiary nephrology centre in Melbourne, Australia, treated with Obinutuzumab for membranous nephropathy, between January 2023 and June 2024. All patients who received Obinutuzumab were included in this case-series, irrespective of PLA2R status.</p><p><strong>Results: </strong>Out of 5 patients with treatment-resistant membranous nephropathy, 3 had PLA2R-associated membranous nephropathy which had previously been refractory to, or relapsed on Rituximab therapy. All 3 patients with PLA2R-positive membranous nephropathy achieved complete immunological and clinical remission after receiving Obinutuzumab. The case of secondary PLA2R-negative membranous nephropathy only achieved partial remission after Obinutuzumab before unexpectedly dying from another cause. The case of recurrent PLA2R-associated membranous nephropathy in a renal allograft did not respond to Obinutuzumab.</p><p><strong>Conclusion: </strong>This case-series supports the existing evidence in favour of Obinutuzumab for treatment-resistant PLA2R-associated membranous nephropathy. To our knowledge it is the first reported use of Obinutuzumab in sarcoidosis-associated membranous nephropathy.</p>","PeriodicalId":16542,"journal":{"name":"Journal of Nephrology","volume":" ","pages":"1809-1818"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tangential biopsy angle and needle depth for adequacy and safety outcomes in ultrasound-guided native kidney biopsy-a single-center experience in a high-risk population.","authors":"Ittikorn Spanuchart, Thanaporn Supachokchaiwattana, Kanin Thammavaranucupt, Kaewpitcha Pichitpichatkul, Suchin Worawichawong, Chinnarat Bua-Ngam","doi":"10.1007/s40620-025-02362-x","DOIUrl":"10.1007/s40620-025-02362-x","url":null,"abstract":"<p><strong>Background: </strong>Kidney biopsy is crucial for diagnosing kidney diseases but involves risks, notably bleeding, which must be balanced with diagnostic precision. This study examines the effect of the biopsy needle's cortical tangential angle and depth on specimen adequacy and safety outcomes.</p><p><strong>Methods: </strong>This single-center, retrospective study reviewed electronic medical records from kidney biopsies performed between January 1, 2016 and December 31, 2020. Included were patients undergoing real-time ultrasound-guided percutaneous kidney biopsies. Exclusion criteria were pediatric patients, renal mass or transplant biopsies, and cases with incomplete records. Primary variables included biopsy needle cortical tangential angle and depth. Outcomes were tissue adequacy and safety, with complications assessed within 24 h.</p><p><strong>Results: </strong>Out of 443 biopsies performed, 124 met the inclusion criteria. Our patient population had a mean BMI of 27.17 kg/m², which met the criteria for obesity based on BMI standards for Asians, and they also had relatively small kidneys (< 9 cm) with parenchymal thinning. Biopsies at angles of 30°-60° yielded more glomeruli (12 vs. 5, p < 0.001) and had a higher pathologist-reported adequacy (82.67% vs. 59.18%, p = 0.004). Needle depth did not significantly impact adequacy. Major complications occurred in 12.90% of cases, with blood transfusions required in 8.06% and embolizations in 3.23%. All technical factors lost statistical significance after adjusting for confounders, except for increased echogenicity, which remained significant.</p><p><strong>Conclusions: </strong>The optimal needle angle for kidney biopsies is 30°-60° for the highest diagnostic yield compared to angles < 30° or > 60°. Our study did not reveal statistically significant differences in major complications between these angle ranges. This greater understanding of the relationship between biopsy angle, needle trajectory depth, and diagnostic and safety outcomes offers valuable insights for optimizing kidney biopsy procedures.</p>","PeriodicalId":16542,"journal":{"name":"Journal of Nephrology","volume":" ","pages":"1947-1955"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144742354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of conserved gene expression changes across common glomerular diseases by spatial transcriptomics.","authors":"Jeong Min Cho, Minji Kang, Sehoon Park, Jaeik Oh, Hyunah Ku, Ha Yeon Shin, Jung Hun Koh, Semin Cho, Yaerim Kim, Soojin Lee, Yong Chul Kim, Seung Seok Han, Kwon-Wook Joo, Yon Su Kim, Seung Hee Yang, Kyung Chul Moon, Hajeong Lee, Hyun Je Kim, Dong Ki Kim","doi":"10.1007/s40620-025-02233-5","DOIUrl":"10.1007/s40620-025-02233-5","url":null,"abstract":"<p><strong>Background: </strong>Glomerular diseases encompass a group of kidney diseases that may share common gene expression pathways. Here, we analyzed glomerular-specific gene expression profiles across various glomerular diseases.</p><p><strong>Methods: </strong>We performed spatial transcriptomic profiling using formalin-fixed paraffin-embedded kidney biopsy specimens of controls and patients with five types of glomerular diseases using the GeoMx Digital Spatial Profiler. Disease-representative glomerular regions of interest (ROIs) were configured, probed with oligonucleotide barcodes linked with target complimentary sequence. The UV-cleaved barcodes were amplified to generate libraries and subsequently sequenced. Common differentially expressed genes across glomerular diseases were identified and Gene Ontology annotation was performed using the ToppGene suite.</p><p><strong>Results: </strong>The mean age of patients with glomerular diseases and kidney donors was 49.5 ± 12.2 and 49.5 ± 9.8 years, respectively. A total of 35 differentially expressed genes were consistently downregulated in glomeruli across the disease compared to the control, while none of the differentially expressed genes were consistently upregulated. Twelve of 35 downregulated differentially expressed genes, including the two hub genes JUN and FOS, were annotated with molecular function Gene Ontology terms related to DNA-binding transcription factor activity. The annotated biological process Gene Ontology terms included response to lipid-related (17/35 differentially expressed genes), response to steroid hormone (12/35 differentially expressed genes), or cell cycle regulation (10/35 differentially expressed genes). Xenium and immunofluorescence staining confirmed the reduced expression of JUN, ZFP36, and KLF9 in intraglomerular cells of glomerular diseases.</p><p><strong>Conclusions: </strong>Identifying common differentially expressed genes by spatial transcriptomic analysis provides insights into the underlying molecular mechanisms of glomerular diseases and may lead to novel assessment or therapeutic strategies.</p>","PeriodicalId":16542,"journal":{"name":"Journal of Nephrology","volume":" ","pages":"1819-1829"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of TRF-budesonide in IgA nephropathy treatment: a meta-analysis.","authors":"Jiayi Li, Hongqin Tai, Bo Yang, Jiayu Xu, Chenchen Zhou, Jing Xu, Cheng Xue, Zhiguo Mao","doi":"10.1007/s40620-025-02341-2","DOIUrl":"10.1007/s40620-025-02341-2","url":null,"abstract":"<p><strong>Background: </strong>IgA nephropathy (IgAN) is a common glomerular disease characterized by IgA glomerular, typically mensangial deposition, often leading to progressive kidney damage.</p><p><strong>Methods: </strong>This meta-analysis assessed the efficacy and safety of TRF-budesonide in IgAN patients, using data from four randomized controlled trials involving 774 participants. We calculated the mean differences in estimated glomerular filtration rate (eGFR) and urine-to-protein-creatinine ratio (UPCR) compared to baseline, with 95% confidence intervals (CIs) after 9 months of treatment and at the end of the follow-up period, while also summarizing adverse events.</p><p><strong>Results: </strong>TRF-budesonide significantly reduced UPCR (weighted mean difference [WMD] = - 0.39 g/g, 95% CI - 0.51, - 0.26, p < 0.00001, I² = 0%) and slowed the decline in eGFR (WMD = 5.39 ml/min/1.73 m², 95% CI 3.68, 7.10, p < 0.00001, I² = 0%), with these effects persisting throughout the follow-up period. However, TRF-budesonide was associated with a higher incidence of adverse events such as acne (OR = 5.04, 95% CI 2.46, 10.34, p < 0.0001), facial edema (OR = 10.12, 95% CI 2.31, 44.22, p = 0.002), hypertension (OR = 4.86, 95% CI 2.40, 9.85, p < 0.0001), and muscle spasms (OR = 3.03, 95% CI 1.64, 5.60, p = 0.0004). Despite these side effects, serious systemic effects were exceptional.</p><p><strong>Conclusions: </strong>TRF-budesonide demonstrated efficacy and a tolerable safety profile in the treatment of IgAN.</p>","PeriodicalId":16542,"journal":{"name":"Journal of Nephrology","volume":" ","pages":"1797-1808"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144731815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Targeting autophagy in autoimmune glomerular diseases.","authors":"Claudio Ponticelli, Gabriella Moroni","doi":"10.1007/s40620-025-02360-z","DOIUrl":"10.1007/s40620-025-02360-z","url":null,"abstract":"","PeriodicalId":16542,"journal":{"name":"Journal of Nephrology","volume":" ","pages":"2021"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144731814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting autophagy in autoimmune glomerular diseases.","authors":"Claudio Ponticelli, Gabriella Moroni","doi":"10.1007/s40620-025-02267-9","DOIUrl":"10.1007/s40620-025-02267-9","url":null,"abstract":"<p><p>Autophagy is a natural process whereby damaged or dying parts of a cell are eliminated and recycled. The term autophagy usually refers to macroautophagy, which is one of three types of autophagy, alongside microautophagy and chaperone-mediated autophagy. Autophagy is activated by adenosine monophosphate-activated protein kinase (AMPK) and inhibited by mammalian target of rapamycin (mTOR) through their interference with Unc-51-like kinase 1 (ULK1). Dysregulated autophagy is deeply involved in autoimmune glomerular diseases. Upregulated autophagy can induce inflammation and activate innate and adaptive immunity. However, autophagy may also exert a protective role on podocytes, enhance endothelial cell function, and preserve proximal tubular epithelial cells during ischemic or endotoxic acute kidney injury (AKI). Hydroxychloroquine (HCQ) can downregulate increased autophagy and is widely used in lupus nephritis. HCQ causes alkalinization, which results in vacuolization of lysosomes and inhibition of their functions. By inhibiting autophagic activity, HCQ may reduce inflammation and innate immunity, inhibit the activation of T cells, restore the T helper 17/T regulator balance, restrict the production of pro-inflammatory cytokines, and modulate co-stimulatory molecules. This reduces the risk of flares, spares the dosage of glucocorticoids, improves lupus activity, and prevents the thrombotic effects of anti-phospholipid antibodies. Recent studies showed that HCQ can also reduce proteinuria in IgA nephropathy (IgAN) and membranous nephropathy (MN). Drugs that improve mitochondrial function or enhance autophagy, such as metformin, sodium-glucose co-transporter 2 (SGLT2) inhibitors or mTOR inhibitors, may exert protective effects on podocytes and reduce proteinuria in MN or focal segmental glomerulosclerosis (FSGS).</p>","PeriodicalId":16542,"journal":{"name":"Journal of Nephrology","volume":" ","pages":"1761-1772"},"PeriodicalIF":2.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}