American Journal of Nephrology最新文献

{"title":"Associations of Causes of Chronic Kidney Disease with Disease Progression and Mortality: Insights from the Fukuoka Kidney Disease Registry Study.","authors":"Hiromasa Kitamura, Shigeru Tanaka, Hiroto Hiyamuta, Kazuhiko Tsuruya, Takanari Kitazono, Toshiaki Nakano","doi":"10.1159/000543201","DOIUrl":"10.1159/000543201","url":null,"abstract":"<p><strong>Introduction: </strong>The Kidney Disease: Improving Global Outcomes guidelines recognize the importance of causes of chronic kidney disease (CKD), glomerular filtration rate, and albuminuria as predictors of kidney outcome and prognosis. However, compared with biopsy-proven causes, there has been limited research regarding the relationship between clinically diagnosed causes of CKD and patient prognosis.</p><p><strong>Methods: </strong>We examined 3,119 patients with non-dialysis-dependent CKD who participated in the Fukuoka Kidney disease Registry Study, a multicenter prospective cohort study. Patients were divided into six groups: IgA nephropathy, chronic glomerulonephritis (non-biopsy-proven), diabetic nephropathy, hypertensive nephrosclerosis, chronic interstitial nephritis, and polycystic kidney disease. The primary outcomes included a composite kidney outcome, defined as a 1.5-fold increase in serum creatinine and/or the development of end-stage kidney disease, and all-cause mortality. The risks of these outcomes were estimated using a Fine-Gray proportional subdistribution hazards model. Patients with IgA nephropathy, the most prevalent primary glomerulonephritis, served as the reference group.</p><p><strong>Results: </strong>During the median follow-up period of 5 years, 1,221 patients developed the composite kidney outcome, and 346 patients died. Compared with IgA nephropathy, the multivariable-adjusted subdistribution hazard ratios (sHRs) for the composite kidney outcome were significantly higher in diabetic nephropathy (sHR 1.45) and polycystic kidney disease (sHR 2.07) groups, whereas the chronic interstitial nephritis group had a significantly lower risk (sHR 0.71). The risk of all-cause mortality was significantly higher in the hypertensive nephrosclerosis group (sHR 1.90).</p><p><strong>Conclusion: </strong>The causes of CKD were associated with risks of the composite kidney outcome and all-cause mortality, highlighting their clinical relevance in predicting prognosis. These findings suggest that different causes of CKD have distinct impacts on patient outcomes, emphasizing the importance of tailoring management strategies according to the underlying causes.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-11"},"PeriodicalIF":4.3,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune Checkpoint Inhibitor-Related Acute Kidney Injury: Management and Challenges.","authors":"Nada Youssef, Ala Abudayyeh","doi":"10.1159/000543323","DOIUrl":"10.1159/000543323","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) have been increasingly used over the past decade for treatment of several cancer types. Despite the excellent cancer response they provide, their use has been associated with serious immune-related adverse events affecting multiple systems including the kidney. Currently, limited data are available to guide treatment of acute kidney injury secondary to ICI use (ICI-AKI) due to tubulointerstitial nephritis or glomerulonephritis. Another huge obstacle is the safety of resuming ICI following an episode of ICI-AKI.</p><p><strong>Summary: </strong>Acute tubulointerstitial nephritis (ATIN) is the most common pathology associated with ICI-AKI, followed by other less common forms of glomerulonephritis. Management of this disorder is very challenging. Corticosteroids therapy remains the mainstay treatment for patients with ICI-ATIN. Use of other immunosuppressants for ICI-ATIN and recurrent ICI-ATIN has been also described in the literature. In patients with ICI-related glomerulonephritis, the use of rituximab is the more common approach reported in the literature. Regarding the safety to resume ICI following an episode of ICI-AKI, this decision should be made following a multidisciplinary approach on a case-by-case basis.</p><p><strong>Key messages: </strong>Limited evidence is available to guide management in patients with ICI-AKI. More prospective studies are needed in the future to better guide treatment of cancer patients with ICI-AKI.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-12"},"PeriodicalIF":4.3,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex Differences in the Risk of Bladder Cancer among Kidney Transplant Recipients and Patients with Kidney Failure Receiving Hemodialysis: A Nationwide Cohort Study.","authors":"Hoon Yu, Sung Jin Kim, Yoonjong Bae, Mina Kim, Chan-Young Jung","doi":"10.1159/000543298","DOIUrl":"10.1159/000543298","url":null,"abstract":"<p><strong>Introduction: </strong>Although both patients with kidney failure (KF) receiving hemodialysis (HD) and kidney transplantation (KT) recipients (KTRs) have a high risk of bladder cancer, how this risk changes in the transition from dialysis to KT is unknown. In this study, we aimed to investigate the risk of bladder cancer in KTRs and patients on HD.</p><p><strong>Methods: </strong>This was a nationwide longitudinal cohort study of 66,547 participants from the National Health Insurance Service cohort who started HD for patients with KF or who received KT from 2002 to 2020. The primary outcome was the diagnosis of bladder cancer, which was defined as the composite of diagnostic codes and either hospitalization or ≥2 outpatient visits for bladder cancer.</p><p><strong>Results: </strong>During mean follow-ups of 4.2 and 7.9 years in the HD and KT groups, respectively, the incidence rates of bladder cancer were 1.1/1,000 and 0.3/1,000 person-years, respectively. In the time-dependent multivariable Cox models, compared to patients on HD, the adjusted hazard ratio (aHR) for bladder cancer among KTRs was 0.36 (95% confidence interval [CI], 0.21-0.60; p < 0.001). Among men, this aHR was 0.29 (95% CI, 0.15-0.55; p < 0.001); however, no statistically significant association between the kidney replacement therapy modality and the risk of bladder cancer was observed among women. Landmark analysis performed to avoid immortal time bias by redefining time zero as a specific landmark time (2 and 5 years after HD initiation or KT) revealed similar results.</p><p><strong>Conclusion: </strong>The risk of bladder cancer was significantly lower among KTRs than that among patients receiving HD, particularly among men.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-9"},"PeriodicalIF":4.3,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between Noninvasive Liver Biomarkers and Graft Outcomes in Kidney Transplantation Recipients.","authors":"Jaeyun Lee, Chung Hee Baek, Soon Bae Kim, Chan-Young Jung","doi":"10.1159/000542914","DOIUrl":"10.1159/000542914","url":null,"abstract":"<p><strong>Introduction: </strong>Although studies have suggested that metabolic risk profiles are prognostic factors in kidney transplantation recipients (KTRs), the prognostic value of fatty liver, a known surrogate of metabolic risk, in KTRs remains to be elucidated. The objective of this study was to investigate the association between noninvasive liver biomarkers used to assess hepatic steatotic and fibrotic burdens and graft outcomes in KTRs.</p><p><strong>Methods: </strong>A total of 3,092 patients who underwent deceased or living donor kidney transplantation (KT) between January 2000 and December 2022 were enrolled. Postoperative hepatic fibrotic burdens of KTRs were assessed using the fibrosis-4 (FIB-4) score and the non-alcoholic fatty liver disease fibrosis score (NFS). The primary outcome was a composite of 50% estimated glomerular filtration rate (eGFR) decline and graft failure. Secondary outcomes included individual outcomes of 50% eGFR decline, graft failure, and acute rejection.</p><p><strong>Results: </strong>For the primary outcome, during a mean follow-up of 6.0 years, the composite outcome occurred in 519 (16.8%) participants. When stratified into three groups according to FIB-4 score categories, the highest score group (FIB-4 ≥2.67) had a 2.05-fold (95% confidence interval [CI], 1.44-2.91; p < 0.001) higher risk of the composite outcome compared to the lowest score group (FIB-4 <1.30). Furthermore, the highest score group showed higher risk of the secondary outcomes, with hazard ratios (95% CI) of 1.75 (1.16-2.66), 1.62 (1.06-2.46), and 2.23 (1.43-3.46) for 50% eGFR decline, acute rejection, and graft failure, respectively. Similar findings were observed for NFS.</p><p><strong>Conclusions: </strong>Higher hepatic fibrotic burdens were associated with unfavorable graft outcomes in KTRs.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-11"},"PeriodicalIF":4.3,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A New Model of Chronic Kidney Disease, Metabolic Derangements, and Heart Failure with Preserved Ejection Fraction in Aging Swine.","authors":"Alejandro R Chade, Darla L Tharp, Rhys Sitz, Elizabeth A McCarthy, Kumar Shivam, Sara Kazeminia, Alfonso Eirin","doi":"10.1159/000543327","DOIUrl":"10.1159/000543327","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic kidney disease (CKD) and heart failure with preserved ejection fraction (HFpEF) are more prevalent in the elderly. There is a lack of large animal models that allow the study of the impact of age on CKD and HFpEF in a translational fashion. This manuscript reports the first large preclinical model of CKD-HFpEF and metabolic derangements in naturally aged swine.</p><p><strong>Methods: </strong>CKD-HFpEF was induced in naturally aged (6-9 years old) and young (3 months old) pigs, followed for 14 weeks, and compared to normal young and old controls (n = 5/group). Renal and cardiac hemodynamics were quantified in vivo by multidetector-CT, echocardiography, and pressure-volume relationship studies. Renal and cardiac microvascular (MV) architecture (3D-micro-CT) and morphometric analysis (staining) were investigated ex vivo.</p><p><strong>Results: </strong>Both young and old pigs developed CKD-HFpEF, but the renal, cardiac, and metabolic phenotype was accentuated in aging animals. Aging and CKD-HFpEF influenced fasting insulin levels and insulin resistance, glomerular filtration rate, cortical MV density, glomerulosclerosis, perivascular fibrosis, and tubular injury. Tubule-interstitial fibrosis and peritubular capillary density were influenced by aging, CKD-HFpEF, and their interaction (2-way ANOVA). Similarly, cardiac MV density, perivascular fibrosis, and myocardial remodeling were influenced by aging and CKD-HFpEF, and E/A by their interaction. Notably, renal and cardiac MV density correlated with renal and cardiac functional and structural changes.</p><p><strong>Conclusion: </strong>Our study establishes the first large animal model of aging CKD-HFpEF, allowing the investigation of age as a biological variable in cardiorenal and metabolic diseases. This new platform could foster new age-related research toward developing therapeutic interventions in CKD-HFpEF.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-14"},"PeriodicalIF":4.3,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performance of New Race-Free eGFR Equations for Predicting Complications in Chronic Kidney Disease: From the KNOW-CKD Study.","authors":"Jaehee Koh, Jihyun Yang, Kyu-Beck Lee, Jayoun Kim, Jong Cheol Jeong, Yaeni Kim, Tae-Hyun Yoo, Kook-Hwan Oh, Young Youl Hyun","doi":"10.1159/000543324","DOIUrl":"10.1159/000543324","url":null,"abstract":"<p><strong>Introduction: </strong>The National Kidney Foundation (NKF) and the American Society of Nephrology (ASN) developed new race-free eGFR equations and recommended using these new equations in 2021. However, clinical implication of these new equations is not determined in Korean adults. Thus, this study aimed to evaluate performances of these new race-free eGFR equations in predicting complications in Korean chronic kidney disease (CKD) patients.</p><p><strong>Methods: </strong>This study analyzed 1,727 participants from the KNOW-CKD cohort. We selected anemia, hyperkalemia, acidosis, hyperphosphatemia, and hyperparathyroidism as five complications of CKD. We determined cross-sectional associations between complications and four eGFR equations. These eGFRs were calculated from 2009 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation (2009 eGFRCr), 2012 CKD-EPI Creatinine-Cystatin C equation (2012 eGFRCrCys), 2021 CKD-EPI Creatinine equation (2021 eGFRCr), and 2021 CKD-EPI Creatinine-Cystatin C equation (2021 eGFRCrCys).</p><p><strong>Results: </strong>All associations between complications as continuous variables and eGFR by four equations were similar. All associations between complications as dichotomous variable and eGFR values form four equations were similar. For example, C-statistics (95% confidence interval) of the logistic model for anemia and eGFRs were 0.826 (0.806-0.845), 0.827 (0.806-0.846), 0.838 (0.819-0.857), and 0.839 (0.820-0.858) for 2009 eGFRCr, 2012 eGFRCrCys, 2021 eGFRCr, and 2021 eGFRCrCys, respectively. In addition, cross-validated areas under the curve for ROC analysis after predictive modeling for all complications were not significant different according to different eGFR equations.</p><p><strong>Conclusion: </strong>New race-free eGFR equations showed similar performances to existing equations for predicting complications in Korean patients with CKD.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"1-8"},"PeriodicalIF":4.3,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Off-Label Use of Mycophenolate Mofetil in Immunoglobulin A Nephropathy: A Systematic Review and Meta-Analysis.","authors":"Luda Feng, Xuan Song, Xinyi Shi, Mingzhen Qin, Ning Liang, Boyang Li, Boya Zhang, Jianguo Qin","doi":"10.1159/000541576","DOIUrl":"10.1159/000541576","url":null,"abstract":"<p><strong>Introduction: </strong>Mycophenolate mofetil (MMF) is widely used off-label in patients with immunoglobulin A nephropathy (IgAN), although the literature does not consistently agree on its efficacy and safety.</p><p><strong>Methods: </strong>We systematically searched PubMed, Embase, CENTRAL, CNKI, VIP, Wanfang Data, and SinoMed from their inception to August 2023. We included randomized controlled trials that enrolled patients of IgAN who received MMF treatment and compared effects with placebo or as an add-on therapy to usual care. Literature screening, risk of bias assessment, and data extraction were independently conducted in duplicate. Fixed-effects or random-effects meta-analyses were performed for pooling data where eligible. The primary outcomes were the composite kidney outcomes of major adverse kidney events (MAKDE) defined as doubling of serum creatinine, end-stage renal disease (ESRD), or death from a kidney disease-related or cardiovascular cause.</p><p><strong>Results: </strong>Of 13 studies identified, 918 participants (463 [50.4%] treated with MMF) with IgAN were included in the analysis. MMF treatment in IgAN was associated with decreasing the occurrence of MAKDE (relative risk [RR], 0.32; 95% confidence interval [CI], 0.13-0.77), reducing proteinuria (RR, 1.41; 95% CI, 1.22-1.64), and lessening the probability of doubling blood creatinine (RR, 0.32, 95% CI, 0.14-0.72). No significant differences were detected in the incidence of ESRD (RR, 0.87, 95% CI, 0.38-2.03), or progression of chronic kidney disease (RR, 1.01; 95% CI, 0.22-4.57). Patients receiving MMF had a higher risk of infection (RR, 2.20; 95% CI, 1.21-4.00).</p><p><strong>Conclusion: </strong>MMF administration in IgAN indicates promising in decreasing the occurrence of MAKDE, reducing proteinuria level, and lessening the probability of doubling blood creatinine, but also comes with the risk of infection. These findings tend to be introduced to non-Caucasian population. The long-term favorable effects that MMF improved kidney outcomes still need further cross-regional and cross-ethnical verification.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"35-47"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum.","authors":"","doi":"10.1159/000542861","DOIUrl":"10.1159/000542861","url":null,"abstract":"","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"121"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin A Deficiency Disturbs Ret Expression and Induces Urinary Tract Developmental Abnormalities in Mice.","authors":"Minghui Yu, Haixin Ju, Ningli Ye, Jing Chen, Lei Sun, Xiaohui Wu, Hong Xu, Qian Shen","doi":"10.1159/000541289","DOIUrl":"10.1159/000541289","url":null,"abstract":"<p><strong>Introduction: </strong>Moderate vitamin A levels during pregnancy are strongly related to normal embryonic development in both animal models and population studies. Abnormal development of urinary tract system is linked to either an excess or a shortage of vitamin A. The relationships among maternal vitamin A deficiency prior to conception, moderate vitamin A supplementation during pregnancy, and abnormal urinary system development in offspring are unclear.</p><p><strong>Methods: </strong>By creating preconception and preconception + pregnancy vitamin A insufficiency mouse models, we investigated whether moderate vitamin A treatment during pregnancy may reduce the prevalence of CAKUT and increase distant vitamin A levels in offspring, as well as any potential pathways involved.</p><p><strong>Results: </strong>We effectively established a prepregnancy vitamin A-deficient mouse model by providing a particular diet with or without vitamin A for 4 weeks. The offspring of the hypovitaminosis A model group presented a greater proportion of neonatal urinary tract developmental malformations. Abnormalities in ureteral bud emergence and key molecules during renal development, such as p-Plcγ and Ret, may be the primary causes of offspring development of CAKUT as a result of mothers' hypovitaminosis A. Normal vitamin A diets, on the other hand, may help mitigate the teratogenic consequences of prepregnancy hypovitaminosis A, as well as defects produced by ureteral budding and major molecular changes.</p><p><strong>Conclusion: </strong>In contrast, the administration of normal vitamin A feeds during pregnancy may ameliorate the teratogenic effects of prepregnancy hypovitaminosis A to a certain extent and may also ameliorate the abnormalities associated with ureteral budding and key molecular changes.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"187-197"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Implementation of Nephrologist-Led Genomic Testing for Glomerular Diseases in Singapore: Rationale and Protocol.","authors":"Cynthia Lim, Ru Sin Lim, Jason Choo, Esther Huimin Leow, Gek Cher Chan, Yaochun Zhang, Jun Li Ng, Hui-Lin Chin, Ee Shien Tan, Jeannette Goh, Naline Gandhi, Yong Hong Ng, Mya Than, Indra Ganesan, Siew Le Chong, Celeste Yap, Sing Ming Chao, Breana Cham, Sylvia Kam, Jiin Ying Lim, Irene Mok, Hui Zhuan Tan, Jia Liang Kwek, Tung Lin Lee, Ziyin Wang, Su Mein Goh, Regina Lim, See Cheng Yeo, Boon Wee Teo, Yi Da, David Matchar, Kar Hui Ng","doi":"10.1159/000542942","DOIUrl":"10.1159/000542942","url":null,"abstract":"<p><strong>Introduction: </strong>The early diagnosis and appropriate treatment of monogenic glomerular diseases can reduce kidney failure, avoid unnecessary investigations such as kidney biopsies and ineffective treatment with immunosuppressants, guide transplant decisions, and inform the genetic risks of their family members. Yet, genetic testing for kidney disease is underutilized in Singapore. We aimed to implement a nephrologist-led genetic service and evaluate the acceptance, adoption, utility, and cost-effectiveness of genetic testing for monogenic glomerular disease in Singapore.</p><p><strong>Methods: </strong>We will perform a prospective, multi-centre, type II hybrid effectiveness-implementation study with a post-design to evaluate both implementation and clinical outcomes of nephrologist-led genetic testing for suspected genetic glomerular kidney diseases. The multi-disciplinary implementation team will train \"genetic nephrologists\" to provide pre- and post-test counselling, order targeted exome panel sequencing for suspected glomerular kidney diseases (persistent microscopic haematuria and/or albuminuria or proteinuria in the absence of known causes, steroid-resistant primary nephrotic syndrome, apparent familial IgA nephropathy, or chronic kidney disease with no apparent cause), and interpret genetic test results; create workflows for patient referral, evaluation and management, and discuss genetic results at regular genomic board meetings. The outcomes are acceptance, appropriateness and adoption among patients and nephrologists, utility (proportion of patients who received genetic testing and have a confirmed diagnosis of genetic glomerular disease), and cost-effectiveness.</p><p><strong>Conclusion: </strong>This study will create and evaluate a nephrologist-led genetic service, develop an efficient variant curation process, and inform future recommendations on the optimal referral and genetic testing strategy for monogenic glomerular disease in Singapore. This will facilitate the future mainstreaming of genetic testing that will enable precision medicine in kidney care.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"158-171"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}