American Journal of Nephrology最新文献

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Associations of Causes of Chronic Kidney Disease with Disease Progression and Mortality: Insights from the Fukuoka Kidney Disease Registry Study. 慢性肾脏疾病病因与疾病进展和死亡率的关系:来自福冈肾脏疾病登记(FKR)研究的见解
IF 4.3 3区 医学
American Journal of Nephrology Pub Date : 2025-01-08 DOI: 10.1159/000543201
Hiromasa Kitamura, Shigeru Tanaka, Hiroto Hiyamuta, Kazuhiko Tsuruya, Takanari Kitazono, Toshiaki Nakano
{"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}
引用次数: 0
Immune Checkpoint Inhibitor-Related Acute Kidney Injury: Management and Challenges. 免疫检查点抑制剂相关急性肾损伤的管理和挑战。
IF 4.3 3区 医学
American Journal of Nephrology Pub Date : 2025-01-07 DOI: 10.1159/000543323
Nada Youssef, Ala Abudayyeh
{"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}
引用次数: 0
Sex Differences in the Risk of Bladder Cancer among Kidney Transplant Recipients and Patients with Kidney Failure Receiving Hemodialysis: A Nationwide Cohort Study. 肾移植受者和接受血液透析的肾衰竭患者膀胱癌风险的性别差异:一项全国性队列研究
IF 4.3 3区 医学
American Journal of Nephrology Pub Date : 2025-01-07 DOI: 10.1159/000543298
Hoon Yu, Sung Jin Kim, Yoonjong Bae, Mina Kim, Chan-Young Jung
{"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}
引用次数: 0
Association between Noninvasive Liver Biomarkers and Graft Outcomes in Kidney Transplantation Recipients. 非侵入性肝脏生物标志物与肾移植受者移植结果的关系。
IF 4.3 3区 医学
American Journal of Nephrology Pub Date : 2025-01-07 DOI: 10.1159/000542914
Jaeyun Lee, Chung Hee Baek, Soon Bae Kim, Chan-Young Jung
{"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}
引用次数: 0
A New Model of Chronic Kidney Disease, Metabolic Derangements, and Heart Failure with Preserved Ejection Fraction in Aging Swine. 衰老猪慢性肾脏疾病、代谢紊乱和心力衰竭的新模型。
IF 4.3 3区 医学
American Journal of Nephrology Pub Date : 2025-01-02 DOI: 10.1159/000543327
Alejandro R Chade, Darla L Tharp, Rhys Sitz, Elizabeth A McCarthy, Kumar Shivam, Sara Kazeminia, Alfonso Eirin
{"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}
引用次数: 0
Performance of New Race-Free eGFR Equations for Predicting Complications in Chronic Kidney Disease: From the KNOW-CKD Study. 新的无种族eGFR方程预测慢性肾脏疾病并发症的性能:来自KNOW-CKD研究
IF 4.3 3区 医学
American Journal of Nephrology Pub Date : 2025-01-02 DOI: 10.1159/000543324
Jaehee Koh, Jihyun Yang, Kyu-Beck Lee, Jayoun Kim, Jong Cheol Jeong, Yaeni Kim, Tae-Hyun Yoo, Kook-Hwan Oh, Young Youl Hyun
{"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}
引用次数: 0
Off-Label Use of Mycophenolate Mofetil in Immunoglobulin A Nephropathy: A Systematic Review and Meta-Analysis. 在免疫球蛋白 A 肾病中标示外使用霉酚酸酯:系统回顾与元分析》。
IF 4.3 3区 医学
American Journal of Nephrology Pub Date : 2025-01-01 Epub Date: 2024-09-25 DOI: 10.1159/000541576
Luda Feng, Xuan Song, Xinyi Shi, Mingzhen Qin, Ning Liang, Boyang Li, Boya Zhang, Jianguo Qin
{"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}
引用次数: 0
Erratum. 勘误表。
IF 4.3 3区 医学
American Journal of Nephrology Pub Date : 2025-01-01 Epub Date: 2024-12-09 DOI: 10.1159/000542861
{"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}
引用次数: 0
Phosphorus Restriction Prevents Rapamycin-Induced Kidney Damage in Rats. 限磷能预防雷帕霉素诱发的大鼠肾损伤
IF 4.3 3区 医学
American Journal of Nephrology Pub Date : 2025-01-01 Epub Date: 2024-10-09 DOI: 10.1159/000541411
Ana I Raya, Angela Vidal, Ignacio López, Mariano Rodríguez, Escolástico Aguilera-Tejero, Carmen Pineda
{"title":"Phosphorus Restriction Prevents Rapamycin-Induced Kidney Damage in Rats.","authors":"Ana I Raya, Angela Vidal, Ignacio López, Mariano Rodríguez, Escolástico Aguilera-Tejero, Carmen Pineda","doi":"10.1159/000541411","DOIUrl":"10.1159/000541411","url":null,"abstract":"<p><strong>Introduction: </strong>There are conflicting reports about the effect or rapamycin on the kidneys. Rapamycin is known to promote phosphaturia that may be associated to renal injury.</p><p><strong>Methods: </strong>Detailed histopathological studies were performed on the kidneys of rats with normal (control) and reduced (Nx) renal mass that were treated with rapamycin (1.3 mg/kg for 22 days) or placebo. The effect of rapamycin was also evaluated in control and Nx rats fed different amounts of phosphorus: 0.6% P (NP), 1.2% P (HP), and 0.2% P (LP). Quantitative scores of kidney lesions were obtained for interstitial nephritis (IN), tubular damage (TD), and nephrocalcinosis (NC).</p><p><strong>Results: </strong>When compared with placebo, rapamycin administration to Nx rats resulted in significant increases in IN (4.17 ± 0.74 vs. 1.51 ± 0.53%) and TD (14.45 ± 1.51 vs. 8.61 ± 1.83%). Rapamycin also increased NC both in control (0.86 ± 0.23 vs. 0.14 ± 0.06%) and Nx (0.86 ± 0.32 vs. 0.15 ± 0.14%) rats. In control rats receiving rapamycin, feeding HP aggravated IN (3.25 ± 0.48%), TD (22.47 ± 4.56%), and NC (3.66 ± 0.75%), while feeding LP prevented development of any renal lesions. In Nx rats treated with rapamycin, HP intake also increased IN (8.95 ± 1.94%), TD (26.86 ± 3.95%), and NC (2.77 ± 0.60%), whereas feeding LP reduced all lesions to lower levels than in rats fed NP. Rapamycin treatment increased fractional excretion of P (FEP), and an excellent correlation between scores for renal lesions and FEP was found.</p><p><strong>Conclusion: </strong>Rapamycin has deleterious effects on kidney pathology causing lesions that are located mainly at tubular and tubulointerstitial level. Rapamycin-induced kidney damage is more evident in rats that already have decreased renal function and seems to be related to the phosphaturic effect of the drug. Dietary P restriction prevents kidney damage in rats treated with rapamycin.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"48-57"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387299","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}
引用次数: 0
Obinutuzumab May Be an Effective and Safe Option for Adult Minimal Change Disease and Focal Segmental Glomerulosclerosis Patients after Multitarget Therapy Including Rituximab. 对于接受过包括利妥昔单抗在内的多靶点治疗的成人微小病变和局灶节段性肾小球硬化症患者来说,奥比妥珠单抗可能是一种有效而安全的选择。
IF 4.3 3区 医学
American Journal of Nephrology Pub Date : 2025-01-01 Epub Date: 2024-10-11 DOI: 10.1159/000541972
Yuxin Lin, Yixuan Pan, Quan Han, Jianhang Xu, Junni Wang, Xin Lei, Liangliang Chen, Yaomin Wang, Pingping Ren, Lan Lan, Jianghua Chen, Fei Han
{"title":"Obinutuzumab May Be an Effective and Safe Option for Adult Minimal Change Disease and Focal Segmental Glomerulosclerosis Patients after Multitarget Therapy Including Rituximab.","authors":"Yuxin Lin, Yixuan Pan, Quan Han, Jianhang Xu, Junni Wang, Xin Lei, Liangliang Chen, Yaomin Wang, Pingping Ren, Lan Lan, Jianghua Chen, Fei Han","doi":"10.1159/000541972","DOIUrl":"10.1159/000541972","url":null,"abstract":"<p><strong>Introduction: </strong>Rituximab has proven effective and safe in pediatric and adult minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) patients with frequently relapsing nephrotic syndrome. However, its efficacy diminishes in several patients who experience nephrotic syndrome relapsing in short durations or failing to achieve remission. We aimed to explore the efficacy and safety of obinutuzumab, a novel anti-CD20 antibody, in these patients.</p><p><strong>Methods: </strong>A retrospective case series study at our center included 11 adult MCD or FSGS patients who presented with nephrotic syndrome characterized by short-duration relapses or lack of remission after multitarget therapy, including rituximab. Primary outcomes included the first relapse-free time, relapse rate during follow-up, and the use of immunosuppressants after obinutuzumab. All adverse events were recorded.</p><p><strong>Results: </strong>Eleven adult patients (median age 26.0 years, 81.9% males) received an average obinutuzumab dose of 2.0 (1.0, 2.0) g during a median follow-up period of 17.0 (12.0, 22.0) months. The first relapse-free time was 12.1 (10.8, 18.9) months. Two patients with FSGS experienced relapses, while the remaining maintained remission by the end of follow-up. Six patients (54.5%) achieved cessation of corticosteroids and immunosuppressants within 3 months after obinutuzumab. Adverse events were mostly mild.</p><p><strong>Conclusion: </strong>Obinutuzumab may be an efficient and safe option for inducing remission in adult MCD and FSGS patients who presented with nephrotic syndrome relapsing in short durations or failed to achieve remission after multitarget therapy, including rituximab. It was effective in maintaining remission in MCD patients, while its efficacy in maintaining remission in FSGS patients remained uncertain.</p>","PeriodicalId":7570,"journal":{"name":"American Journal of Nephrology","volume":" ","pages":"111-120"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455857","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}
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