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Estimated potassium intake and the progression of chronic kidney disease. 估计的钾摄入量与慢性肾病的进展。
IF 4.8 2区 医学 Q1 TRANSPLANTATION Pub Date : 2025-06-30 DOI: 10.1093/ndt/gfae277
Tatsuya Suenaga, Shigeru Tanaka, Hiromasa Kitamura, Kazuhiko Tsuruya, Toshiaki Nakano, Takanari Kitazono

Background: Lower potassium intake is associated with a higher risk of chronic kidney disease (CKD) in the general population. However, there are no stated recommendations on potassium intake in the CKD population owing to limited evidence of benefits from potassium intake and concerns about the risk of hyperkalaemia. This study aimed to investigate the relationship between potassium intake and CKD progression.

Methods: A total of 4314 patients aged 18 years or older in Japan were prospectively followed for 5 years using data from the Fukuoka Kidney Disease Registry study. The patients were divided into quartiles according to estimated potassium intake levels assessed by the Tanaka formula from spot urine samples. The primary outcome was CKD progression, which was defined as a composite of a 1.5-fold increase in creatinine concentrations from baseline and development of end-stage kidney disease. We evaluated the relationship between estimated potassium intake and CKD progression using Cox proportional hazards models.

Results: A total of 1490 patients showed CKD progression during the follow-up with an incidence rate of 90.1/1000 person-years. Patients in the lowest estimated potassium intake quartile had higher hazard ratios for CKD progression than those in the highest quartiles in the multivariable-adjusted Cox models [hazard ratio (95% confidence interval) 1.24 (1.03-1.48)]. Similarly, each 1-standard deviation decrease in estimated potassium intake as a continuous variable was associated with a higher risk of CKD progression [hazard ratio (95% confidence interval) 1.10 (1.03-1.19)].

Conclusions: Lower estimated potassium intake is associated with CKD progression in patients with CKD. Therefore, we recommend adequate potassium intake, taking care not to cause serious adverse events.

背景和假设:在普通人群中,钾摄入量越低,患慢性肾脏疾病(CKD)的风险越高。然而,由于有关钾摄入量益处的证据有限以及对高钾血症风险的担忧,目前还没有关于慢性肾脏病人群钾摄入量的明确建议。本研究旨在调查钾摄入量与慢性肾脏病进展之间的关系:方法:利用福冈肾脏病登记研究的数据,对日本总计 4314 名 18 岁或以上的患者进行了为期 5 年的前瞻性随访。根据定点尿样中的田中公式评估的估计钾摄入水平,将患者分为四等分。主要结果是慢性肾脏病进展,即肌酐浓度比基线增加 1.5 倍和发展为终末期肾脏病。我们使用 Cox 比例危险模型评估了估计钾摄入量与 CKD 进展之间的关系:结果:共有 1490 名患者在随访期间出现 CKD 进展,发病率为 90.1/1000 人年。在多变量调整后的 Cox 模型中,估计钾摄入量最低的四分位数患者的 CKD 进展危险比高于估计钾摄入量最高的四分位数患者(危险比 [95% 置信区间],1.24 [1.03-1.48])。同样,作为连续变量,估计钾摄入量每降低1个标准差,CKD进展的风险就会升高(危险比[95% 置信区间],1.10 [1.03-1.19]):结论:钾的估计摄入量较低与慢性肾脏病患者的慢性肾脏病进展有关。因此,我们建议患者摄入足够的钾,同时注意不要引起严重的不良反应。
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引用次数: 0
The future of glucagon-like peptide-1 receptor agonists in cardiovascular-kidney-metabolic diseases considerations from the ERA Diabesity Working Group. 胰高血糖素样肽-1受体激动剂在心血管-肾脏代谢疾病中的应用前景
IF 4.8 2区 医学 Q1 TRANSPLANTATION Pub Date : 2025-05-30 DOI: 10.1093/ndt/gfaf008
Matias Trillini, Trond Geir Jenssen, William Patrick Martin, Enrique Morales
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引用次数: 0
Patients with membranous lupus nephritis form two clusters with different prognoses. 鉴别膜性狼疮性肾炎患者的两个不同集群:基于无监督分析的高风险概况识别。
IF 4.8 2区 医学 Q1 TRANSPLANTATION Pub Date : 2025-05-30 DOI: 10.1093/ndt/gfae295
Zhipeng Wang, Wang Xiang, Yiqin Wang, Jianwen Yu, Xin Wang, Hongjian Ye, Haishan Wu, Ruihan Tang, Xi Xia, Wei Chen

Background and hypothesis: Membranous lupus nephritis (MLN) traditionally includes class V (alone), and may be associated with other classes (III or IV). The clinical, therapeutic, and prognostic relevance of the classification remains controversial.

Methods: A retrospective cohort of 412 MLN patients from the First Affiliated Hospital of Sun-Yat Sen University was followed for a median of 65.68 (interquartile range 23.13-131.70) months. The primary outcomes were adverse renal events including all-cause death and ESRD. Phenotypes were identified and validated using unsupervised clustering analysis (K-means), principal component analysis and decision tree analysis.

Results: Distinct clinical and pathological differences were noted between the traditional class IV + V and classes V + III and V, while class V + III and class V exhibited high similarities in clinical features and prognosis (P = 0.074). K-means clustering revealed high-risk (n = 180) and low-risk (n = 232) groups, with significant differences in adverse renal outcomes (9.2% vs 4.1%, P < 0.001). To recognize the high-risk profile of MLN patients, a decision tree based on Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, hemoglobin, serum creatinine, traditional classification, and activity index of renal biopsy accurately clustered patients in the development (95.8% accuracy) and validation (87.1% accuracy) cohorts.

Conclusions: Two novel phenotypic clusters, more predictive than traditional classifications, enhance high-risk profile identification and prognostic accuracy.

背景与假设:膜性狼疮肾炎(MLN)传统上包括V类(单独),并可能与其他III或IV类(III或IV)相关。该分类的临床、治疗和预后相关性仍存在争议。方法:对中山大学第一附属医院的4.12例MLN患者进行回顾性随访,中位随访65.68个月(IQR: 23.13 ~ 131.70)。主要结局是肾脏不良事件,包括全因死亡和终末期肾脏疾病(ESRD)。表型鉴定和验证采用无监督聚类分析(K-means),主成分分析(PCA)和决策树分析。结果:传统IV + V类患者临床病理差异明显,传统V + III类与V类患者临床特征及预后高度相似(P = 0.074)。K-means聚类揭示了高危组(n = 180)和低危组(n = 232)在不良肾脏结局方面存在显著差异(9.2% vs. 4.1%)。结论:两种新型表型聚类比传统分类更具预测性,增强了高风险特征识别和预后准确性。
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引用次数: 0
Characteristics, treatment and disease burden among stage 3-4 chronic kidney disease patients with and without type 2 diabetes in Finland during 2016-2022. 2016-2022 年期间芬兰患有和未患有 2 型糖尿病的 3-4 期慢性肾病患者的特征、治疗和疾病负担。
IF 4.8 2区 医学 Q1 TRANSPLANTATION Pub Date : 2025-05-30 DOI: 10.1093/ndt/gfae242
Kaj Metsärinne, Johan Bodegård, Iiro Toppila, Kristiina Uusi-Rauva, Line Elmerdahl Frederiksen, Satu Brinkmann

Background: Real-world evidence on the management of chronic kidney disease (CKD) with and without type 2 diabetes (T2D) is limited. This study described the characteristics, treatment and disease burden in patients with stage 3-4 CKD with and without T2D in Finland.

Methods: This cohort study used data from primary and hospital care in five municipalities in Finland to identify adults with stage 3-4 CKD, defined as having either one estimated glomerular filtration rate (eGFR) measurement of 15-59 mL/min/1.73 m2 followed by a second measurement taken ≥90 days later, or a registered CKD diagnosis. Prevalence was determined on 31 December 2022, and a cohort of incident stage 3-4 CKD patients was followed from the first date fulfilling eligibility criteria since 1 January 2016 (index) until death or 31 December 2022, and analyzed by T2D status.

Results: The prevalence of stage 3-4 CKD was 6.3%. Among the 12 474 incident stage 3-4 CKD patients, the majority were non-T2D (73%). The median age was similar for non-T2D and T2D CKD patients, respectively. Baseline albuminuria screening was 9% among non-T2D and 53% among T2D. The use of kidney-protective treatments at index was also lower in non-T2D patients (47%), compared with T2D patients (69%). The use of kidney-protective treatments remained unchanged during 12 months after index. Healthcare resource utilization was high, and CKD or heart failure contributed considerably more to the all-cause healthcare costs than atherosclerotic diseases, regardless of T2D status. In both CKD subgroups, 10% had died within 1 year.

Conclusions: In Finland, CKD is highly prevalent and associated with high risks and low use of albuminuria testing and kidney-protective medications. Most CKD patients were non-T2D, which showed lower use of preventive management and similar risks compared with T2D patients. These findings call for an urgent need for improved awareness and risk management, especially in non-T2D CKD patients.

背景:有关患有或未患有 2 型糖尿病(T2D)的慢性肾脏病(CKD)管理的实际证据非常有限。本研究描述了芬兰伴有或不伴有 T2D 的 3-4 期 CKD 患者的特征、治疗和疾病负担:这项队列研究使用了芬兰五个城市的初级医疗和医院医疗数据,以确定患有 3-4 期慢性肾脏病的成年人,其定义为:估算肾小球滤过率(eGFR)测量值为 15-59 毫升/分钟/1.73 平方米,且第二次测量值相隔≥90 天,或已注册慢性肾脏病诊断。2022 年 12 月 31 日确定了患病率,并从 2016 年 1 月 1 日(指数)起满足资格标准的首个日期开始,对 3-4 期 CKD 患者队列进行随访,直至死亡或 2022 年 12 月 31 日,并按 T2D 状态进行分析:结果:3-4 期 CKD 患病率为 6.3%。在12 474名3-4期慢性肾脏病患者中,大多数为非T2D患者(73%)。非终末期肾病患者和终末期肾病患者的中位年龄相似。非终末期肾病患者的基线白蛋白尿筛查率为 9%,而终末期肾病患者的基线白蛋白尿筛查率为 53%。与 T2D 患者(69%)相比,非 T2D 患者在指数时使用肾脏保护治疗的比例也较低(47%)。在发病后的 12 个月内,保护肾脏治疗的使用率保持不变。医疗资源利用率很高,与动脉粥样硬化性疾病相比,无论是否患有 T2D,慢性肾脏病或心力衰竭对全因医疗费用的贡献都要大得多。在两个慢性肾脏病亚组中,10%的人在一年内死亡:结论:在芬兰,慢性肾脏病的发病率很高,风险也很高,但白蛋白尿检测和肾脏保护药物的使用率却很低。大多数慢性肾脏病患者为非终末期肾脏病患者,与终末期肾脏病患者相比,预防性治疗的使用率较低,风险相似。这些发现表明,迫切需要提高人们的认识,加强风险管理,尤其是在非 T2D CKD 患者中。
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引用次数: 0
Correction to: Management of adult patients with podocytopathies: an update from the ERA Immunonephrology Working Group. 更正:荚膜细胞病变成年患者的管理:ERA 免疫肾脏病工作组的最新进展。
IF 4.8 2区 医学 Q1 TRANSPLANTATION Pub Date : 2025-05-30 DOI: 10.1093/ndt/gfae215
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引用次数: 0
Seasonal variations in the association between proteinuria and kidney failure. 蛋白尿、慢性肾脏病和肾衰竭之间关系的季节性变化。
IF 4.8 2区 医学 Q1 TRANSPLANTATION Pub Date : 2025-05-30 DOI: 10.1093/ndt/gfae278
Takayuki Kawaoka, Yusuke Sakaguchi, Tatsufumi Oka, Yuta Asahina, Koki Hattori, Yohei Doi, Nobuhiro Hashimoto, Yasuo Kusunoki, Satoko Yamamoto, Masafumi Yamato, Ryohei Yamamoto, Isao Matsui, Masayuki Mizui, Jun-Ya Kaimori, Yoshitaka Isaka

Background and hypothesis: Proteinuria exhibits seasonal fluctuations, decreasing in summer and increasing in winter. It is unknown whether the association between proteinuria and the risk of kidney failure varies by season.

Methods: The Osaka Consortium for Kidney Disease Research (OCKR) database contained retrospective data from 15 367 patients with estimated glomerular filtration rates of 10-60 mL/min/1.73 m2, who were referred to the Department of Nephrology at five clinical centers in Japan, between 2010 and 2021. Multivariate Cox models were used to examine the associations of urinary protein-to-creatinine ratio (UPCR) in summer (UPCRsummer) and winter (UPCRwinter), with kidney failure defined as initiation of kidney replacement therapy. LASSO was used to compare the strength of the association between UPCRsummer and UPCRwinter with respect to kidney failure. We also assessed whether seasonal fluctuations in UPCR were associated with kidney failure.

Results: The median (interquartile range) UPCRwinter was 0.89 (0.22, 2.69) g/gCre, 46% higher than UPCRsummer [0.61 (0.16, 1.87) g/gCre]. During a median follow-up of 3.0 years, 1585 patients developed kidney failure. In time-dependent Cox models, UPCRwinter showed a higher hazard of kidney failure [1.66 per 1-standard deviation (SD) increase; 95% confidence interval (CI) 1.60-1.73] than UPCRsummer (1.45 per 1-SD increase; 95% CI 1.41-1.48). LASSO identified that UPCRwinter was more strongly associated with kidney failure than UPCRsummer. Furthermore, higher percentage changes in UPCRwinter relative to UPCRsummer was associated with a higher hazard of kidney failure.

Conclusions: Proteinuria in winter exhibited stronger associations with kidney failure than that in summer. Seasonal fluctuations in UPCR should not be overlooked in the management of chronic kidney disease to make reasonable clinical decisions.

背景和假设:蛋白尿呈季节性波动,夏季减少,冬季增加。蛋白尿与肾衰竭风险之间的关系是否因季节而异尚属未知:大阪肾脏病研究联合会(OCKR)数据库中包含了 15 367 名患者的回顾性数据,这些患者的估计肾小球滤过率为 10-60 mL/min/1.73m2,他们在 2010 年至 2021 年期间被转诊到日本五个临床中心的肾脏科。研究人员使用多变量 Cox 模型研究了夏季(UPCRsummer)和冬季(UPCRwinter)尿蛋白肌酐比值(UPCR)与肾衰竭(定义为开始肾脏替代治疗)的相关性。我们使用 LASSO 方法比较了夏季和冬季尿蛋白肌酐比值与肾衰竭的关联强度。我们还评估了 UPCR 的季节性波动是否与肾衰竭有关:UPCRwinter 的中位数[四分位距]为 0.89 [0.22, 2.69] g/gCre,比 UPCRsummer(0.61 [0.16, 1.87] g/gCre)高出 46%。在中位 3.0 年的随访期间,有 1 585 名患者出现了肾衰竭。在时间依赖性 Cox 模型中,UPCRwinter 的肾衰竭风险(每增加 1 个标准差 [SD] 为 1.66;95% 置信区间 [CI],1.60-1.73)高于 UPCRsummer(每增加 1 个标准差为 1.45;95% 置信区间 [CI],1.41-1.48)。LASSO 发现,与 UPCRsummer 相比,UPCRwinter 与肾衰竭的相关性更强。此外,UPCR冬季相对于UPCR夏季的百分比变化越大,肾衰竭的风险越高:结论:冬季蛋白尿与肾衰竭的相关性高于夏季。结论:冬季蛋白尿比夏季蛋白尿与肾衰竭的关联性更强。在治疗慢性肾功能衰竭时,不应忽视 UPCR 的季节性波动,以便做出合理的临床决策。
{"title":"Seasonal variations in the association between proteinuria and kidney failure.","authors":"Takayuki Kawaoka, Yusuke Sakaguchi, Tatsufumi Oka, Yuta Asahina, Koki Hattori, Yohei Doi, Nobuhiro Hashimoto, Yasuo Kusunoki, Satoko Yamamoto, Masafumi Yamato, Ryohei Yamamoto, Isao Matsui, Masayuki Mizui, Jun-Ya Kaimori, Yoshitaka Isaka","doi":"10.1093/ndt/gfae278","DOIUrl":"10.1093/ndt/gfae278","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>Proteinuria exhibits seasonal fluctuations, decreasing in summer and increasing in winter. It is unknown whether the association between proteinuria and the risk of kidney failure varies by season.</p><p><strong>Methods: </strong>The Osaka Consortium for Kidney Disease Research (OCKR) database contained retrospective data from 15 367 patients with estimated glomerular filtration rates of 10-60 mL/min/1.73 m2, who were referred to the Department of Nephrology at five clinical centers in Japan, between 2010 and 2021. Multivariate Cox models were used to examine the associations of urinary protein-to-creatinine ratio (UPCR) in summer (UPCRsummer) and winter (UPCRwinter), with kidney failure defined as initiation of kidney replacement therapy. LASSO was used to compare the strength of the association between UPCRsummer and UPCRwinter with respect to kidney failure. We also assessed whether seasonal fluctuations in UPCR were associated with kidney failure.</p><p><strong>Results: </strong>The median (interquartile range) UPCRwinter was 0.89 (0.22, 2.69) g/gCre, 46% higher than UPCRsummer [0.61 (0.16, 1.87) g/gCre]. During a median follow-up of 3.0 years, 1585 patients developed kidney failure. In time-dependent Cox models, UPCRwinter showed a higher hazard of kidney failure [1.66 per 1-standard deviation (SD) increase; 95% confidence interval (CI) 1.60-1.73] than UPCRsummer (1.45 per 1-SD increase; 95% CI 1.41-1.48). LASSO identified that UPCRwinter was more strongly associated with kidney failure than UPCRsummer. Furthermore, higher percentage changes in UPCRwinter relative to UPCRsummer was associated with a higher hazard of kidney failure.</p><p><strong>Conclusions: </strong>Proteinuria in winter exhibited stronger associations with kidney failure than that in summer. Seasonal fluctuations in UPCR should not be overlooked in the management of chronic kidney disease to make reasonable clinical decisions.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1234-1242"},"PeriodicalIF":4.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
NephroCheck AKI risk scores (TIMP-2 and IGFBP7) in pregnancy. 妊娠期肾检查AKI风险评分(TIMP-2和IGFBP7)。
IF 4.8 2区 医学 Q1 TRANSPLANTATION Pub Date : 2025-05-30 DOI: 10.1093/ndt/gfaf031
Katherine Clark, Jennifer Joslin, Carolyn Gill, Priscilla Smith, Hayley Martin, Hayley Tarft, Frances Conti-Ramsden, Lucy C Chappell, Marlies Ostermann, Kate Bramham
{"title":"NephroCheck AKI risk scores (TIMP-2 and IGFBP7) in pregnancy.","authors":"Katherine Clark, Jennifer Joslin, Carolyn Gill, Priscilla Smith, Hayley Martin, Hayley Tarft, Frances Conti-Ramsden, Lucy C Chappell, Marlies Ostermann, Kate Bramham","doi":"10.1093/ndt/gfaf031","DOIUrl":"10.1093/ndt/gfaf031","url":null,"abstract":"","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1254-1257"},"PeriodicalIF":4.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
IL-12/23 blocker ustekinumab for the treatment of ANCA-associated glomerulonephritis. IL-12/23阻滞剂Ustekinumab治疗anca相关性肾小球肾炎
IF 4.8 2区 医学 Q1 TRANSPLANTATION Pub Date : 2025-05-30 DOI: 10.1093/ndt/gfaf005
Jonas Engesser, Christian F Krebs, Ulf Panzer
{"title":"IL-12/23 blocker ustekinumab for the treatment of ANCA-associated glomerulonephritis.","authors":"Jonas Engesser, Christian F Krebs, Ulf Panzer","doi":"10.1093/ndt/gfaf005","DOIUrl":"10.1093/ndt/gfaf005","url":null,"abstract":"","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1066-1068"},"PeriodicalIF":4.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Genetic testing in a national cohort of adults with chronic kidney disease of unknown origin. 全国不明原因慢性肾病成人队列中的基因检测。
IF 4.8 2区 医学 Q1 TRANSPLANTATION Pub Date : 2025-05-30 DOI: 10.1093/ndt/gfae270
Amber de Haan, Mark Eijgelsheim, Liffert Vogt, Ewout J Hoorn, Joris I Rotmans, Gijs Fortrie, Roos F J Marsman, Tonia C Rothuizen, H Siebe Spijker, Laura R Claus, Constantijn J A M Konings, Femke Waanders, Joan Doornebal, Andrea B Kramer, Aaltje Y Adema, Bert van der Zwaag, Albertien M van Eerde, Nine V A M Knoers, Martin H de Borst

Background: Chronic kidney disease (CKD) remains unexplained in at least 20% of patients. Massively parallel sequencing (MPS) can be a valuable diagnostic tool in patients with unexplained CKD, but prospective data from routine clinical practice are limited. We aimed to determine the diagnostic yield and relevance of MPS-based gene panel testing in patients with unexplained CKD in a real-world context. We additionally examined barriers to implementation of genetic testing.

Methods: In this prospective cohort study, we recruited patients with unexplained CKD (estimated glomerular filtration rate <60 ml/min/1.73 m2 without underlying clinical diagnosis) with onset at <50 years of age who underwent MPS-based multigene panel testing from 11 academic and non-academic hospitals across the Netherlands. In patients with a (likely) pathogenic variant, we verified that the variant likely explained the clinical phenotype. A nationwide online survey was sent to all Dutch nephrologists and residents to investigate potential barriers for gene panel testing.

Results: A diagnostic variant was identified in 59/340 participants (17%). Most common diagnostic variants were in NPHP1 (13 patients), COL4A3 (12 patients), COL4A4 (5 patients), COL4A5 (6 patients) and PAX2 (5 patients). A genetic diagnosis led to at least one clinical consequence in 73% of patients. Main barriers reported by Dutch nephrologists (N = 71) included genetic illiteracy (53%), difficulties with test selection (51%) and a lack of time (43%).

Conclusions: MPS-based multigene panel testing yielded a genetic diagnosis in 17% of patients with unexplained CKD. Our findings support the relevance of MPS in the diagnostic workup of adults with unexplained CKD with onset at <50 years of age. Additionally, our results underline the need to improve genetic education among nephrologists to better the implementation of MPS-based diagnostic testing in clinical practice.

背景和假设:至少有 20% 的慢性肾脏病(CKD)患者的病因不明。大规模平行测序(MPS)可作为不明原因慢性肾脏病患者的重要诊断工具,但来自常规临床实践的前瞻性数据十分有限。我们的目的是在现实世界中确定对不明原因的 CKD 患者进行基于 MPS 的基因组检测的诊断率和相关性。此外,我们还研究了实施基因检测的障碍:在这项前瞻性队列研究中,我们招募了不明原因的 CKD 患者(eGFR 结果):59/340名参与者(17%)发现了诊断变异。最常见的诊断变异位于 NPHP1(13 名患者)、COL4A3(12 名患者)、COL4A4(5 名患者)、COL4A5(6 名患者)和 PAX2(5 名患者)。在 73% 的患者中,基因诊断至少导致了一种临床后果。荷兰肾病专家(71 人)报告的主要障碍包括不了解遗传学知识(53%)、难以选择检测方法(51%)和缺乏时间(43%):结论:在不明原因的慢性肾脏病患者中,17% 的患者通过基于 MPS 的多基因面板检测获得了基因诊断。我们的研究结果支持 MPS 在对发病原因不明的成人慢性肾功能衰竭患者的诊断工作中的相关性。
{"title":"Genetic testing in a national cohort of adults with chronic kidney disease of unknown origin.","authors":"Amber de Haan, Mark Eijgelsheim, Liffert Vogt, Ewout J Hoorn, Joris I Rotmans, Gijs Fortrie, Roos F J Marsman, Tonia C Rothuizen, H Siebe Spijker, Laura R Claus, Constantijn J A M Konings, Femke Waanders, Joan Doornebal, Andrea B Kramer, Aaltje Y Adema, Bert van der Zwaag, Albertien M van Eerde, Nine V A M Knoers, Martin H de Borst","doi":"10.1093/ndt/gfae270","DOIUrl":"10.1093/ndt/gfae270","url":null,"abstract":"<p><strong>Background: </strong>Chronic kidney disease (CKD) remains unexplained in at least 20% of patients. Massively parallel sequencing (MPS) can be a valuable diagnostic tool in patients with unexplained CKD, but prospective data from routine clinical practice are limited. We aimed to determine the diagnostic yield and relevance of MPS-based gene panel testing in patients with unexplained CKD in a real-world context. We additionally examined barriers to implementation of genetic testing.</p><p><strong>Methods: </strong>In this prospective cohort study, we recruited patients with unexplained CKD (estimated glomerular filtration rate <60 ml/min/1.73 m2 without underlying clinical diagnosis) with onset at <50 years of age who underwent MPS-based multigene panel testing from 11 academic and non-academic hospitals across the Netherlands. In patients with a (likely) pathogenic variant, we verified that the variant likely explained the clinical phenotype. A nationwide online survey was sent to all Dutch nephrologists and residents to investigate potential barriers for gene panel testing.</p><p><strong>Results: </strong>A diagnostic variant was identified in 59/340 participants (17%). Most common diagnostic variants were in NPHP1 (13 patients), COL4A3 (12 patients), COL4A4 (5 patients), COL4A5 (6 patients) and PAX2 (5 patients). A genetic diagnosis led to at least one clinical consequence in 73% of patients. Main barriers reported by Dutch nephrologists (N = 71) included genetic illiteracy (53%), difficulties with test selection (51%) and a lack of time (43%).</p><p><strong>Conclusions: </strong>MPS-based multigene panel testing yielded a genetic diagnosis in 17% of patients with unexplained CKD. Our findings support the relevance of MPS in the diagnostic workup of adults with unexplained CKD with onset at <50 years of age. Additionally, our results underline the need to improve genetic education among nephrologists to better the implementation of MPS-based diagnostic testing in clinical practice.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1225-1233"},"PeriodicalIF":4.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Long-term outcomes of IgA nephropathy in China. 中国 IgA 肾病的长期疗效。
IF 4.8 2区 医学 Q1 TRANSPLANTATION Pub Date : 2025-05-30 DOI: 10.1093/ndt/gfae252
Xue Shen, Pei Chen, Muqing Liu, Lijun Liu, Sufang Shi, Xujie Zhou, Jicheng Lv, Hong Zhang

Background: The long-term prognosis of immunoglobulin A nephropathy (IgAN) and the optimal target for proteinuria treatment remain controversial. This study, utilizing a large prospective cohort from China, aims to assess the long-term outcomes of IgAN and to explore the definition of proteinuria remission.

Methods: We enrolled 2141 patients with biopsy-proven IgAN, all with at least 12 months of follow-up, from a prospective IgAN cohort at Peking University First Hospital. We utilized Kaplan-Meier analysis, Cox regression and an estimated glomerular filtration rate (eGFR) slope calculated via a linear mixed model to investigate kidney outcomes.

Results: The median (Q1, Q3) baseline proteinuria was 1.26 (0.65, 2.40) g/day, and the eGFR was 80 (52, 103) mL/min/1.73 m2. After a mean follow-up of 5.8 (±4.4) years, 509 (24%) patients progressed to end-stage kidney disease (ESKD). The median kidney survival time was 12.4 years, the annual event rate of ESKD was 41.1 per 1000 person-years and the 15-year kidney survival rate was 40%. Time-averaged proteinuria level was strongly associated with kidney failure (adjusted hazard ratio 1.76, 95% confidence interval 1.65 to 1.88). Restriction cubic spline analysis indicated that the risk of ESKD increases rapidly when time-average proteinuria exceeded 0.5 g/day. There was no significant difference in long-term kidney survival between patients with proteinuria <0.3 g/day and those with 0.3-0.5 g/day, with both groups demonstrating a better prognosis.

Conclusion: The long-term outcomes for patients with IgAN under current treatment strategies remain poor, with most progressing to ESKD within 15 years. Patients with time-averaged proteinuria ≥0.5 g/day experience worse kidney outcomes, challenging the previous view that proteinuria <1.0 g/day was associated with a low risk of kidney failure.

背景与假设:IgA肾病(IgAN)的长期预后和蛋白尿的最佳治疗目标仍存在争议。本研究利用来自中国的大型前瞻性队列,旨在评估 IgAN 的长期预后,并探讨蛋白尿缓解的定义:方法:我们从北京大学第一医院的前瞻性 IgAN 队列中招募了 2 141 名经活检证实的 IgAN 患者,所有患者均接受了至少 12 个月的随访。我们采用卡普兰-梅耶分析、Cox回归和线性混合模型计算的eGFR斜率来研究肾脏的预后:中位(Q1,Q3)基线蛋白尿为 1.26 (0.65, 2.40) g/d,估计 GFR 为 80 (52, 103) mL/min/1.73m2。平均随访 5.8 (±4.4) 年后,509(24%)名患者发展为终末期肾病(ESKD)。肾脏存活时间中位数为 12.4 年,ESKD 年发生率为每 1000 人年 41.1 例,15 年肾脏存活率为 40%。时间平均蛋白尿水平与肾衰竭密切相关(调整后 HR:1.76,95%CI:1.65 至 1.88)。限制立方样条分析表明,当时间平均蛋白尿超过 0.5 克/天时,ESKD 的风险迅速增加。蛋白尿患者的长期肾脏存活率没有明显差异:在目前的治疗策略下,IgAN 患者的长期预后仍然很差,大多数患者会在 15 年内发展为 ESKD。时间平均蛋白尿≥ 0.5 克/天的患者的肾脏预后较差,这对之前认为蛋白尿
{"title":"Long-term outcomes of IgA nephropathy in China.","authors":"Xue Shen, Pei Chen, Muqing Liu, Lijun Liu, Sufang Shi, Xujie Zhou, Jicheng Lv, Hong Zhang","doi":"10.1093/ndt/gfae252","DOIUrl":"10.1093/ndt/gfae252","url":null,"abstract":"<p><strong>Background: </strong>The long-term prognosis of immunoglobulin A nephropathy (IgAN) and the optimal target for proteinuria treatment remain controversial. This study, utilizing a large prospective cohort from China, aims to assess the long-term outcomes of IgAN and to explore the definition of proteinuria remission.</p><p><strong>Methods: </strong>We enrolled 2141 patients with biopsy-proven IgAN, all with at least 12 months of follow-up, from a prospective IgAN cohort at Peking University First Hospital. We utilized Kaplan-Meier analysis, Cox regression and an estimated glomerular filtration rate (eGFR) slope calculated via a linear mixed model to investigate kidney outcomes.</p><p><strong>Results: </strong>The median (Q1, Q3) baseline proteinuria was 1.26 (0.65, 2.40) g/day, and the eGFR was 80 (52, 103) mL/min/1.73 m2. After a mean follow-up of 5.8 (±4.4) years, 509 (24%) patients progressed to end-stage kidney disease (ESKD). The median kidney survival time was 12.4 years, the annual event rate of ESKD was 41.1 per 1000 person-years and the 15-year kidney survival rate was 40%. Time-averaged proteinuria level was strongly associated with kidney failure (adjusted hazard ratio 1.76, 95% confidence interval 1.65 to 1.88). Restriction cubic spline analysis indicated that the risk of ESKD increases rapidly when time-average proteinuria exceeded 0.5 g/day. There was no significant difference in long-term kidney survival between patients with proteinuria <0.3 g/day and those with 0.3-0.5 g/day, with both groups demonstrating a better prognosis.</p><p><strong>Conclusion: </strong>The long-term outcomes for patients with IgAN under current treatment strategies remain poor, with most progressing to ESKD within 15 years. Patients with time-averaged proteinuria ≥0.5 g/day experience worse kidney outcomes, challenging the previous view that proteinuria <1.0 g/day was associated with a low risk of kidney failure.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"1137-1146"},"PeriodicalIF":4.8,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
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Nephrology Dialysis Transplantation
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