<div><h3>Rationale & Objective</h3><div>To identify, appraise, and synthesize relevant epidemiologic studies to better understand the relations between blood pressure (BP) and outcomes in patients with kidney failure receiving maintenance peritoneal dialysis (PD) and to examine how the available evidence aligns with current clinical guidelines.</div></div><div><h3>Study Design</h3><div>Systematic review and meta-analysis.</div></div><div><h3>Setting & Participants</h3><div>We conducted a comprehensive search of 5 databases (PubMed, Web of Science, Embase, CINAHL, Cochrane Library) through April 2023 (and abstracts from leading nephrology conferences from 2019-2023). Studies were eligible if they included patients receiving maintenance PD and reported associations between BP levels and all-cause mortality.</div></div><div><h3>Exposures</h3><div>Systolic BP, diastolic BP, or presence/absence of hypertension.</div></div><div><h3>Outcome</h3><div>All-cause mortality.</div></div><div><h3>Analytical Approach</h3><div>Dual independent screening and full-text review were performed. Where appropriate, data were then pooled using a random-effects meta-analysis. Adjusted data were not required for inclusion.</div></div><div><h3>Results</h3><div>Thirty observational studies were included in the systematic review. Twenty-three studies were retrospective; 7 were prospective. Sixteen studies were single center, 13 were multicenter, and one study was unclear as it was presented only in abstract form. More than two-thirds were from Asia. Of the 28 full-length articles, only 9 had BP as the primary exposure, with the rest including BP only as a covariate in multivariable models. In the meta-analysis, compared with systolic BP 100-140 mm Hg, systolic BP >140 mm Hg was associated with a statistically nonsignificant 15% higher risk of all-cause mortality (RR, 1.15; 95% CI, 0.99-1.34). No association was found between diastolic BP >90 mm Hg (vs diastolic BP ≤90 mm Hg) and mortality (RR, 0.92; 95% CI, 0.53-1.57).</div></div><div><h3>Limitations</h3><div>High level of heterogeneity and high risk of bias among the included studies.</div></div><div><h3>Conclusions</h3><div>The existing epidemiology literature is unable to offer definitive guidance regarding BP treatment targets for PD patients due to heterogeneity, risk of bias, and lack of statistical significance.</div></div><div><h3>Plain-language Summary</h3><div>Some individual studies have reported that among patients with kidney failure treated with chronic peritoneal dialysis, higher blood pressure level is not correlated with higher risk of death, which differs from what is observed in the general population. However, experts continue to recommend lowering blood pressure as a treatment. We systematically reviewed and summarized the medical literature published before April 2023 concerning blood pressure level and risk of death among patients with kidney failure treated with chronic peritoneal dialys
目的识别、评估和综合相关流行病学研究，以更好地了解接受维持性腹膜透析（PD）的肾衰竭患者血压（BP）与预后之间的关系，并检查现有证据与当前临床指南的一致性。研究设计：系统回顾和荟萃分析。截止到2023年4月，我们对5个数据库（PubMed, Web of Science, Embase， CINAHL, Cochrane Library）进行了全面检索（以及2019-2023年主要肾脏病会议的摘要）。如果研究纳入了接受维持性PD治疗的患者，并报告了血压水平与全因死亡率之间的关联，则该研究是合格的。暴露：收缩压、舒张压或是否存在高血压。OutcomeAll-cause死亡率。分析方法：进行了双重独立筛选和全文综述。在适当的情况下，使用随机效应荟萃分析汇总数据。纳入不需要调整后的数据。结果本系统评价纳入了30项观察性研究。23项研究是回顾性的；7个是前瞻性的。16项研究是单中心的，13项是多中心的，还有一项研究不清楚，因为它只是以抽象的形式呈现。超过三分之二的学生来自亚洲。在28篇全文文章中，只有9篇文章将BP作为主要曝光，其余文章仅将BP作为多变量模型中的协变量。在荟萃分析中，与收缩压100-140毫米汞柱相比，收缩压和140毫米汞柱与全因死亡风险增加15%相关（RR, 1.15; 95% CI, 0.99-1.34），统计学上无显著性差异。舒张压≤90 mm Hg （vs舒张压≤90 mm Hg）与死亡率无相关性（RR, 0.92; 95% CI, 0.53-1.57）。局限性纳入的研究存在高度异质性和高偏倚风险。结论现有的流行病学文献由于存在异质性、偏倚风险和缺乏统计学意义，无法为PD患者的BP治疗靶点提供明确的指导。一些个体研究报道，在接受慢性腹膜透析治疗的肾衰竭患者中，较高的血压水平与较高的死亡风险无关，这与在一般人群中观察到的情况不同。然而，专家们仍然建议将降低血压作为一种治疗方法。我们系统地回顾和总结了2023年4月之前发表的关于慢性腹膜透析治疗肾衰竭患者血压水平和死亡风险的医学文献。我们发现已发表的研究有许多局限性，我们得出结论，需要更多的研究来产生更好的数据，以帮助医生决定如何最好地控制这些脆弱的高风险人群的血压。
{"title":"Blood Pressure Level and Risk of All-Cause Mortality in Patients With Kidney Failure on Maintenance Peritoneal Dialysis: A Systematic Review and Meta-Analysis of Observational Studies","authors":"Viangkaeo Lee , Haleh Siami , Vanessa-Giselle Peschard , Mohsen Malekinejad , Emily Huang , Peggy Tahir , Chi-yuan Hsu","doi":"10.1016/j.xkme.2025.101193","DOIUrl":"10.1016/j.xkme.2025.101193","url":null,"abstract":"<div><h3>Rationale & Objective</h3><div>To identify, appraise, and synthesize relevant epidemiologic studies to better understand the relations between blood pressure (BP) and outcomes in patients with kidney failure receiving maintenance peritoneal dialysis (PD) and to examine how the available evidence aligns with current clinical guidelines.</div></div><div><h3>Study Design</h3><div>Systematic review and meta-analysis.</div></div><div><h3>Setting & Participants</h3><div>We conducted a comprehensive search of 5 databases (PubMed, Web of Science, Embase, CINAHL, Cochrane Library) through April 2023 (and abstracts from leading nephrology conferences from 2019-2023). Studies were eligible if they included patients receiving maintenance PD and reported associations between BP levels and all-cause mortality.</div></div><div><h3>Exposures</h3><div>Systolic BP, diastolic BP, or presence/absence of hypertension.</div></div><div><h3>Outcome</h3><div>All-cause mortality.</div></div><div><h3>Analytical Approach</h3><div>Dual independent screening and full-text review were performed. Where appropriate, data were then pooled using a random-effects meta-analysis. Adjusted data were not required for inclusion.</div></div><div><h3>Results</h3><div>Thirty observational studies were included in the systematic review. Twenty-three studies were retrospective; 7 were prospective. Sixteen studies were single center, 13 were multicenter, and one study was unclear as it was presented only in abstract form. More than two-thirds were from Asia. Of the 28 full-length articles, only 9 had BP as the primary exposure, with the rest including BP only as a covariate in multivariable models. In the meta-analysis, compared with systolic BP 100-140 mm Hg, systolic BP >140 mm Hg was associated with a statistically nonsignificant 15% higher risk of all-cause mortality (RR, 1.15; 95% CI, 0.99-1.34). No association was found between diastolic BP >90 mm Hg (vs diastolic BP ≤90 mm Hg) and mortality (RR, 0.92; 95% CI, 0.53-1.57).</div></div><div><h3>Limitations</h3><div>High level of heterogeneity and high risk of bias among the included studies.</div></div><div><h3>Conclusions</h3><div>The existing epidemiology literature is unable to offer definitive guidance regarding BP treatment targets for PD patients due to heterogeneity, risk of bias, and lack of statistical significance.</div></div><div><h3>Plain-language Summary</h3><div>Some individual studies have reported that among patients with kidney failure treated with chronic peritoneal dialysis, higher blood pressure level is not correlated with higher risk of death, which differs from what is observed in the general population. However, experts continue to recommend lowering blood pressure as a treatment. We systematically reviewed and summarized the medical literature published before April 2023 concerning blood pressure level and risk of death among patients with kidney failure treated with chronic peritoneal dialys","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 2","pages":"Article 101193"},"PeriodicalIF":3.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-29DOI: 10.1016/j.xkme.2025.101236
Nils Müller, Anne Krüger, Alexander Reshetnik
Although metabolic acidosis is a common phenomenon, its differential diagnoses include a variety of rare conditions. Among the causes of high anion gap metabolic acidosis is an accumulation of 5-oxoproline or pyroglutamic acid. It is commonly understood that development can occur in the context of high-dose paracetamol intake and either relevant clinical risk factors or comedication with flucloxacillin or oxacillin. As a rare condition, it has become well-known only to specialized clinicians. We reported a case of high anion gap metabolic acidosis caused by 5-oxoproline in a middle-aged male treated only with high-dose flucloxacillin. Our patient had neither a history of paracetamol use nor classical risk factors to a degree, making the development of 5-oxoproline/pyroglutamic acidosis plausible. Although there have been plenty of case reports of this condition because of the coadministration of paracetamol/acetaminophen and flucloxacillin/oxacillin, to our knowledge, this is only the second published case of 5-oxoproline acidosis without paracetamol use, making it either highly unusual or potentially underdiagnosed. Therefore, we suggest considering 5-oxoproline/pyroglutamic acidosis when evaluating the etiology of metabolic acidosis in patients on high-dose flucloxacillin/oxacillin, even without a history of concomitant or previous paracetamol exposure or other classical risk factors.
{"title":"An Unusual Case of 5-Oxoproline Acidosis","authors":"Nils Müller, Anne Krüger, Alexander Reshetnik","doi":"10.1016/j.xkme.2025.101236","DOIUrl":"10.1016/j.xkme.2025.101236","url":null,"abstract":"<div><div>Although metabolic acidosis is a common phenomenon, its differential diagnoses include a variety of rare conditions. Among the causes of high anion gap metabolic acidosis is an accumulation of 5-oxoproline or pyroglutamic acid. It is commonly understood that development can occur in the context of high-dose paracetamol intake and either relevant clinical risk factors or comedication with flucloxacillin or oxacillin. As a rare condition, it has become well-known only to specialized clinicians. We reported a case of high anion gap metabolic acidosis caused by 5-oxoproline in a middle-aged male treated only with high-dose flucloxacillin. Our patient had neither a history of paracetamol use nor classical risk factors to a degree, making the development of 5-oxoproline/pyroglutamic acidosis plausible. Although there have been plenty of case reports of this condition because of the coadministration of paracetamol/acetaminophen and flucloxacillin/oxacillin, to our knowledge, this is only the second published case of 5-oxoproline acidosis without paracetamol use, making it either highly unusual or potentially underdiagnosed. Therefore, we suggest considering 5-oxoproline/pyroglutamic acidosis when evaluating the etiology of metabolic acidosis in patients on high-dose flucloxacillin/oxacillin, even without a history of concomitant or previous paracetamol exposure or other classical risk factors.</div></div>","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 3","pages":"Article 101236"},"PeriodicalIF":3.4,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146081364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-26DOI: 10.1016/j.xkme.2025.101234
Zhejia Tian , Samira Soltani , Johann Bauersachs , Kai M. Schmidt-Ott , Anette Melk , Bernhard M.W. Schmidt
<div><h3>Rationale & Objectives</h3><div>The cardiovascular-kidney-metabolic (CKM) syndrome is defined as the intricate interplay among metabolic risks, chronic kidney disease (CKD) and the cardiovascular system. The deteriorating CKM syndrome contributes to untimely morbidity and mortality. We aim to characterize gender- and age-related disparities in the prevalence of CKM syndrome over the last 2 decades.</div></div><div><h3>Study Design</h3><div>A cross-sectional population-based survey.</div></div><div><h3>Setting & Participants</h3><div>A total of 32,848 US adults participating in the NHANES survey from 1999 to 2020.</div></div><div><h3>Exposures</h3><div>Gender, age (18-44, 45-64, and ≥65), and period (1999-2002, 2003-3008, 2009-2014, and 2015-2020).</div></div><div><h3>Outcomes</h3><div>Prevalence of CKM stages.</div></div><div><h3>Analytical approach</h3><div>Sample weights and Taylor series linearization method were applied to estimate prevalence and standard errors representative of the noninstitutionalized US adult population. For trend analysis across cycles, survey-weighted logistic regression was employed.</div></div><div><h3>Results</h3><div>Young women aged < 45 years were classified more often, but with decreasing prevalence, in stages without CKM defining factors (22.7% of women vs 13.5% of men) and more often in stages with cardiovascular organ damage (13.4% of women vs 6.5% of men). Elderly women were increasingly classified in stages with cardiovascular organ damage over the last 20 years, reaching the same prevalence as men in the most recent period (25.3 % [95% CI, 20.0 %-30.6 %] of women vs 30.5 [95% CI, 25.7-35.3%] of men aged > 65 years).</div></div><div><h3>Limitations</h3><div>NHANES data allow for assessing CKM stages with cardiovascular organ damage mainly based on self-reporting during interviews.</div></div><div><h3>Conclusions</h3><div>We demonstrate an increasing proportion of women in advanced CKM stages over the last 20 years. Whereas the overrepresentation of younger women in the low-risk stages almost disappeared, elderly women in the last period showed almost the same risk of being in stages with cardiovascular organ damage as elderly men. Our analysis highlights an urgent need of preventive measures especially tailored to women.</div></div><div><h3>Plain-language Summary</h3><div>Cardiovascular-kidney-metabolic (CKM) syndrome describes the combined impact of heart, kidney, and metabolic health on overall well-being. We examined its prevalence among US adult population and explored differences between women and men across different age groups, using data from over 32,000 adults collected from 1999 to 2020. The results showed that younger women under 45 years were previously more likely to be in the low-risk group; however, this advantage has declined over the past 20 years. Among older adults (over 65 years), women had a comparable risk to men for organ damage associated with cardiovascular-kid
{"title":"Gender-related and Age-related Disparities in Prevalence of the Cardiovascular-Kidney-Metabolic Syndrome Among US Adults From 1999-2020: An Analysis of the NHANES Survey","authors":"Zhejia Tian , Samira Soltani , Johann Bauersachs , Kai M. Schmidt-Ott , Anette Melk , Bernhard M.W. Schmidt","doi":"10.1016/j.xkme.2025.101234","DOIUrl":"10.1016/j.xkme.2025.101234","url":null,"abstract":"<div><h3>Rationale & Objectives</h3><div>The cardiovascular-kidney-metabolic (CKM) syndrome is defined as the intricate interplay among metabolic risks, chronic kidney disease (CKD) and the cardiovascular system. The deteriorating CKM syndrome contributes to untimely morbidity and mortality. We aim to characterize gender- and age-related disparities in the prevalence of CKM syndrome over the last 2 decades.</div></div><div><h3>Study Design</h3><div>A cross-sectional population-based survey.</div></div><div><h3>Setting & Participants</h3><div>A total of 32,848 US adults participating in the NHANES survey from 1999 to 2020.</div></div><div><h3>Exposures</h3><div>Gender, age (18-44, 45-64, and ≥65), and period (1999-2002, 2003-3008, 2009-2014, and 2015-2020).</div></div><div><h3>Outcomes</h3><div>Prevalence of CKM stages.</div></div><div><h3>Analytical approach</h3><div>Sample weights and Taylor series linearization method were applied to estimate prevalence and standard errors representative of the noninstitutionalized US adult population. For trend analysis across cycles, survey-weighted logistic regression was employed.</div></div><div><h3>Results</h3><div>Young women aged < 45 years were classified more often, but with decreasing prevalence, in stages without CKM defining factors (22.7% of women vs 13.5% of men) and more often in stages with cardiovascular organ damage (13.4% of women vs 6.5% of men). Elderly women were increasingly classified in stages with cardiovascular organ damage over the last 20 years, reaching the same prevalence as men in the most recent period (25.3 % [95% CI, 20.0 %-30.6 %] of women vs 30.5 [95% CI, 25.7-35.3%] of men aged > 65 years).</div></div><div><h3>Limitations</h3><div>NHANES data allow for assessing CKM stages with cardiovascular organ damage mainly based on self-reporting during interviews.</div></div><div><h3>Conclusions</h3><div>We demonstrate an increasing proportion of women in advanced CKM stages over the last 20 years. Whereas the overrepresentation of younger women in the low-risk stages almost disappeared, elderly women in the last period showed almost the same risk of being in stages with cardiovascular organ damage as elderly men. Our analysis highlights an urgent need of preventive measures especially tailored to women.</div></div><div><h3>Plain-language Summary</h3><div>Cardiovascular-kidney-metabolic (CKM) syndrome describes the combined impact of heart, kidney, and metabolic health on overall well-being. We examined its prevalence among US adult population and explored differences between women and men across different age groups, using data from over 32,000 adults collected from 1999 to 2020. The results showed that younger women under 45 years were previously more likely to be in the low-risk group; however, this advantage has declined over the past 20 years. Among older adults (over 65 years), women had a comparable risk to men for organ damage associated with cardiovascular-kid","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 3","pages":"Article 101234"},"PeriodicalIF":3.4,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146081234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-26DOI: 10.1016/j.xkme.2025.101232
Nathan Meyer , Maxwell Donelan , Hossein Moradi Rekabdarkolaee , Brandon M. Varilek , Surachat Ngorsuraches , Patti Brooks , Jerry Schrier , Semhar Michael
<div><h3>Rationale & Objective</h3><div>Traditional survival models assume all patients receiving kidney replacement therapy (KRT) may be grouped into one population, overlooking long-term survivors, particularly successful transplant recipients, and may fail to appreciate the disparities in minority populations. On the other hand, a mixture survival model allows for the estimation of hazard and odds ratios of all-cause mortality in patients with kidney failure undergoing either dialysis or transplantation.</div></div><div><h3>Study Design</h3><div>This retrospective cohort study analyzed survival outcomes using a proportional hazards mixture survival model, comparing results to a traditional Cox proportional hazards model with time-varying modality of treatment.</div></div><div><h3>Setting & Participants</h3><div>Data from the United States Renal Data System included 2,228,693 patients initiating KRT between 2000 and 2020.</div></div><div><h3>Predictors</h3><div>Key predictors included demographics, comorbid conditions, socioeconomic status, geographic location, and rurality.</div></div><div><h3>Outcomes</h3><div>The primary outcome was all-cause mortality. The mixture survival model distinguishes between patients’ characteristics associated with long-term survival (ie, primarily those with successful transplants) and short-term survival (ie, those at a greater risk of mortality over time, such as patients treated with dialysis).</div></div><div><h3>Analytical Approach</h3><div>Both a Cox proportional hazards model and a proportional hazards mixture survival model were applied to all patients.</div></div><div><h3>Results</h3><div>Findings from both models were largely consistent, but the mixture survival model revealed new insights into racial disparities. In the Cox model, American Indian individuals had an adjusted hazard ratio of 0.63 compared with White individuals (95% CI. 0.62-0.63) and 0.74 for Black individuals compared with White (95% CI, 0.74-0.74). The mixture model confirmed these trends but also showed that American Indian individuals were 1.59 times more likely to not have a long-term survival than White individuals (95% CI, 1.415-1.797) and Black individuals were 1.35 times more likely to not be in the long-term surviving group than White individuals (95% CI, 1.310-1.397). Additional disparities were observed by socioeconomic and geographic factors.</div></div><div><h3>Limitations</h3><div>Data collected at the beginning of dialysis may not fully capture patients’ health trajectories.</div></div><div><h3>Conclusions</h3><div>The mixture survival model provides a more comprehensive understanding of mortality disparities for patients with kidney failure receiving KRT by distinguishing between short-term and long-term survivability. The findings highlight the need for targeted interventions to improve long-term outcomes for minority patients.</div></div><div><h3>Plain-language Summary</h3><div>Kidney failure affects minority
{"title":"Estimating Short-Term and Long-Term Survival for Patients With Kidney Failure Using a Mixture Survival Model","authors":"Nathan Meyer , Maxwell Donelan , Hossein Moradi Rekabdarkolaee , Brandon M. Varilek , Surachat Ngorsuraches , Patti Brooks , Jerry Schrier , Semhar Michael","doi":"10.1016/j.xkme.2025.101232","DOIUrl":"10.1016/j.xkme.2025.101232","url":null,"abstract":"<div><h3>Rationale & Objective</h3><div>Traditional survival models assume all patients receiving kidney replacement therapy (KRT) may be grouped into one population, overlooking long-term survivors, particularly successful transplant recipients, and may fail to appreciate the disparities in minority populations. On the other hand, a mixture survival model allows for the estimation of hazard and odds ratios of all-cause mortality in patients with kidney failure undergoing either dialysis or transplantation.</div></div><div><h3>Study Design</h3><div>This retrospective cohort study analyzed survival outcomes using a proportional hazards mixture survival model, comparing results to a traditional Cox proportional hazards model with time-varying modality of treatment.</div></div><div><h3>Setting & Participants</h3><div>Data from the United States Renal Data System included 2,228,693 patients initiating KRT between 2000 and 2020.</div></div><div><h3>Predictors</h3><div>Key predictors included demographics, comorbid conditions, socioeconomic status, geographic location, and rurality.</div></div><div><h3>Outcomes</h3><div>The primary outcome was all-cause mortality. The mixture survival model distinguishes between patients’ characteristics associated with long-term survival (ie, primarily those with successful transplants) and short-term survival (ie, those at a greater risk of mortality over time, such as patients treated with dialysis).</div></div><div><h3>Analytical Approach</h3><div>Both a Cox proportional hazards model and a proportional hazards mixture survival model were applied to all patients.</div></div><div><h3>Results</h3><div>Findings from both models were largely consistent, but the mixture survival model revealed new insights into racial disparities. In the Cox model, American Indian individuals had an adjusted hazard ratio of 0.63 compared with White individuals (95% CI. 0.62-0.63) and 0.74 for Black individuals compared with White (95% CI, 0.74-0.74). The mixture model confirmed these trends but also showed that American Indian individuals were 1.59 times more likely to not have a long-term survival than White individuals (95% CI, 1.415-1.797) and Black individuals were 1.35 times more likely to not be in the long-term surviving group than White individuals (95% CI, 1.310-1.397). Additional disparities were observed by socioeconomic and geographic factors.</div></div><div><h3>Limitations</h3><div>Data collected at the beginning of dialysis may not fully capture patients’ health trajectories.</div></div><div><h3>Conclusions</h3><div>The mixture survival model provides a more comprehensive understanding of mortality disparities for patients with kidney failure receiving KRT by distinguishing between short-term and long-term survivability. The findings highlight the need for targeted interventions to improve long-term outcomes for minority patients.</div></div><div><h3>Plain-language Summary</h3><div>Kidney failure affects minority ","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 3","pages":"Article 101232"},"PeriodicalIF":3.4,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146081368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-24DOI: 10.1016/j.xkme.2025.101231
Steven Fishbane MD, Pratap Upadrista MBBS, Hitesh H. Shah MD
Composite study endpoints have made it possible to reduce the sample size and lower the cost of certain clinical trials. In nephrology trials, the use of composite endpoints has led to opportunities but has also created challenges in the interpretation of study results. In this perspective, we review how composite outcomes work and why there are risks attendant to their use. We also provide examples of the use of composite outcomes from specific nephrology trials and certain problems that resulted.
{"title":"Composite Primary Outcomes in Nephrology Clinical Trials","authors":"Steven Fishbane MD, Pratap Upadrista MBBS, Hitesh H. Shah MD","doi":"10.1016/j.xkme.2025.101231","DOIUrl":"10.1016/j.xkme.2025.101231","url":null,"abstract":"<div><div>Composite study endpoints have made it possible to reduce the sample size and lower the cost of certain clinical trials. In nephrology trials, the use of composite endpoints has led to opportunities but has also created challenges in the interpretation of study results. In this perspective, we review how composite outcomes work and why there are risks attendant to their use. We also provide examples of the use of composite outcomes from specific nephrology trials and certain problems that resulted.</div></div>","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 3","pages":"Article 101231"},"PeriodicalIF":3.4,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146081367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-24DOI: 10.1016/j.xkme.2025.101233
Chloe Borden , Iman Chaudhry , Rhyan Maditz , Sarah Mazzola , Ronit Salomon Kent , Kristen Tomaszewski , Xiangling Wang
Genetic testing is increasingly used to assist the precise diagnosis and clinical management of suspected genetic kidney diseases; however, mitochondrial DNA (mtDNA) analysis remains underutilized. Here we report a 61-year-old man who presented with chronic kidney disease (CKD), microscopic hematuria since childhood, bilateral sensorineural hearing loss (SNHL), and peripheral polyneuropathy. Laboratory reports showed serum creatinine 1.5 mg/dL with an estimated glomerular filtration rate of 55 mL/min/1.73m2, no proteinuria, and a negative serological workup. Kidney biopsy demonstrated focal segmental glomerulosclerosis (FSGS) with segmental thinning of glomerular basement membrane and dysmorphic mitochondria. A 401 renal disease gene panel was negative, including type IV collagen genes. mtDNA analysis identified a pathogenic variant in the MT-TV gene (m.1642 G>A; NC_012920.1) with 2% heteroplasmy in leukocyte-derived DNA, confirmed in urine-derived DNA at 5% heteroplasmy. Genetic counseling was offered along with systemic evaluation revealing left ventricular hypertrophy on echocardiogram. The patient was started on levocarnitine and coenzyme Q10 with multidisciplinary care. This is the first reported case of FSGS with dysmorphic mitochondria and a pathogenic MT-TV variant confirmed via both leukocyte-derived and urine-derived DNA. It supports the role of mitochondrial dysfunction in CKD and highlights the importance of mtDNA analysis in the evaluation of FSGS and unexplained CKD.
{"title":"Mitochondrial DNA Analysis Should Be Considered in the Genetic Assessment of Focal Segmental Glomerulosclerosis or Unexplained Chronic Kidney Disease: A Case Report","authors":"Chloe Borden , Iman Chaudhry , Rhyan Maditz , Sarah Mazzola , Ronit Salomon Kent , Kristen Tomaszewski , Xiangling Wang","doi":"10.1016/j.xkme.2025.101233","DOIUrl":"10.1016/j.xkme.2025.101233","url":null,"abstract":"<div><div>Genetic testing is increasingly used to assist the precise diagnosis and clinical management of suspected genetic kidney diseases; however, mitochondrial DNA (mtDNA) analysis remains underutilized. Here we report a 61-year-old man who presented with chronic kidney disease (CKD), microscopic hematuria since childhood, bilateral sensorineural hearing loss (SNHL), and peripheral polyneuropathy. Laboratory reports showed serum creatinine 1.5 mg/dL with an estimated glomerular filtration rate of 55 mL/min/1.73m<sup>2</sup>, no proteinuria, and a negative serological workup. Kidney biopsy demonstrated focal segmental glomerulosclerosis (FSGS) with segmental thinning of glomerular basement membrane and dysmorphic mitochondria. A 401 renal disease gene panel was negative, including type IV collagen genes. mtDNA analysis identified a pathogenic variant in the <em>MT-TV</em> gene (m.1642 G>A; NC_012920.1) with 2% heteroplasmy in leukocyte-derived DNA, confirmed in urine-derived DNA at 5% heteroplasmy. Genetic counseling was offered along with systemic evaluation revealing left ventricular hypertrophy on echocardiogram. The patient was started on levocarnitine and coenzyme Q10 with multidisciplinary care. This is the first reported case of FSGS with dysmorphic mitochondria and a pathogenic <em>MT-TV</em> variant confirmed via both leukocyte-derived and urine-derived DNA. It supports the role of mitochondrial dysfunction in CKD and highlights the importance of mtDNA analysis in the evaluation of FSGS and unexplained CKD.</div></div>","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 3","pages":"Article 101233"},"PeriodicalIF":3.4,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146048953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-16DOI: 10.1016/j.xkme.2025.101228
Yujia Wang , Kaiqi Huang , Caiming Chen , Keng Ye , Kunmei Lai , Xuan Tao , Hong Chen , Yanfang Xu
Drug-induced type II crescentic glomerulonephritis is an uncommon but severe renal syndrome, rarely linked to pharmaceutical agents, with no established association to Chinese herbal medicines to date. In this case report, we described 4 patients who developed biopsy-confirmed type II crescentic glomerulonephritis within 1-4 weeks following exposure to Chinese herbal products. Key histopathologic findings included crescent formation in ≥50% of glomeruli and immunofluorescence demonstrating granular mesangial deposits of immunoglobulin G and C3, accompanied by prominent acute tubulointerstitial injury. Clinically, 75% of cases presented with macroscopic hematuria, reflecting severe glomerular capillary damage. The therapeutic regimen comprised intravenous methylprednisolone, cyclophosphamide, and plasma exchange. Persistent hematuria and a longer duration of drug exposure were associated with slower and incomplete renal recovery during follow-up. Our case report suggested that Chinese herbal medicine may be a potential environmental trigger for crescentic glomerulonephritis and highlight the value of clinical inquiry into herbal product use in cases of rapidly progressive glomerulonephritis. Further toxicovigilance and compound-specific risk assessments are urgently needed.
{"title":"Chinese Herb-Induced Type II Crescentic Glomerulonephritis: A Case Report of Four Patients","authors":"Yujia Wang , Kaiqi Huang , Caiming Chen , Keng Ye , Kunmei Lai , Xuan Tao , Hong Chen , Yanfang Xu","doi":"10.1016/j.xkme.2025.101228","DOIUrl":"10.1016/j.xkme.2025.101228","url":null,"abstract":"<div><div>Drug-induced type II crescentic glomerulonephritis is an uncommon but severe renal syndrome, rarely linked to pharmaceutical agents, with no established association to Chinese herbal medicines to date. In this case report, we described 4 patients who developed biopsy-confirmed type II crescentic glomerulonephritis within 1-4 weeks following exposure to Chinese herbal products. Key histopathologic findings included crescent formation in ≥50% of glomeruli and immunofluorescence demonstrating granular mesangial deposits of immunoglobulin G and C3, accompanied by prominent acute tubulointerstitial injury. Clinically, 75% of cases presented with macroscopic hematuria, reflecting severe glomerular capillary damage. The therapeutic regimen comprised intravenous methylprednisolone, cyclophosphamide, and plasma exchange. Persistent hematuria and a longer duration of drug exposure were associated with slower and incomplete renal recovery during follow-up. Our case report suggested that Chinese herbal medicine may be a potential environmental trigger for crescentic glomerulonephritis and highlight the value of clinical inquiry into herbal product use in cases of rapidly progressive glomerulonephritis. Further toxicovigilance and compound-specific risk assessments are urgently needed.</div></div>","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 2","pages":"Article 101228"},"PeriodicalIF":3.4,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fanconi syndrome is a generalized dysfunction of the renal proximal tubule, leading to growth failure and rickets during childhood. There are few reports of this syndrome in neonates, especially in extremely low-birth-weight infants. We present a case of an extremely low-birth-weight Asian girl with bone fragility because of Fanconi syndrome without underlying diseases. She was born at 29 weeks of gestation and weighed 418 g (–5.2SD). Based on blood and urine analyses, she was diagnosed with Fanconi syndrome. Metabolic acidosis was easily corrected with bicarbonate supplementation. However, the control of the rickets was very difficult, with multiple bone fractures observed despite supplementation of calcium, phosphorus, and vitamin D. Her renal tubular function finally improved at 6 months of age, and oral supplementation of bicarbonate, calcium, and phosphorus was discontinued before discharge. The genetic test for inherited causes of Fanconi syndrome showed no abnormalities. Hypoperfusion during the fetal period was assumed to be one of the causes of Fanconi syndrome in this case.
{"title":"An Extremely Low-Birth-Weight Infant With Bone Fragility Due to Fanconi Syndrome","authors":"Rei Yoshida, Miku Hosokawa, Toshiko Ukawa, Chisa Tsurisawa, Yoshiya Hisaeda, Shusuke Amagata, Tomohiro Takeda, Atsushi Nakao","doi":"10.1016/j.xkme.2025.101227","DOIUrl":"10.1016/j.xkme.2025.101227","url":null,"abstract":"<div><div>Fanconi syndrome is a generalized dysfunction of the renal proximal tubule, leading to growth failure and rickets during childhood. There are few reports of this syndrome in neonates, especially in extremely low-birth-weight infants. We present a case of an extremely low-birth-weight Asian girl with bone fragility because of Fanconi syndrome without underlying diseases. She was born at 29 weeks of gestation and weighed 418 g (–5.2SD). Based on blood and urine analyses, she was diagnosed with Fanconi syndrome. Metabolic acidosis was easily corrected with bicarbonate supplementation. However, the control of the rickets was very difficult, with multiple bone fractures observed despite supplementation of calcium, phosphorus, and vitamin D. Her renal tubular function finally improved at 6 months of age, and oral supplementation of bicarbonate, calcium, and phosphorus was discontinued before discharge. The genetic test for inherited causes of Fanconi syndrome showed no abnormalities. Hypoperfusion during the fetal period was assumed to be one of the causes of Fanconi syndrome in this case.</div></div>","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 2","pages":"Article 101227"},"PeriodicalIF":3.4,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-16DOI: 10.1016/j.xkme.2025.101223
Savino Sciascia , Massimo Radin , Irene Cecchi , Alice Barinotti , Francesco Trevisani , Roberta Fenoglio , Emanuele De Simone , Dario Roccatello , Paola Cassoni , Antonella Barreca
<div><h3>Rationale & Objective</h3><div>Thrombotic microangiopathy (TMA) as seen in antiphospholipid syndrome nephropathy (APSN) is associated with poor kidney outcomes. Caveolin-1 (Cav-1) has emerged as a potential marker of endothelial damage and microvascular injury.</div></div><div><h3>Study Design</h3><div>This retrospective study investigates the diagnostic potential value of Cav-1 immunohistochemistry in APSN-related TMA.</div></div><div><h3>Setting & Participants</h3><div>Patients were retrieved from the Piedmont and Aosta Valley Rare Disease Registry, from which a total of 771 APS cases had been recorded.</div></div><div><h3>Exposure</h3><div>Only case with biopsy-proven renal involvement were included.</div></div><div><h3>Outcomes</h3><div>Cases were classified into three histopathological clusters: TMA (APSN-TMA), hyperplastic vasculopathy, and subendothelial edema. Immunohistochemical staining for Cav-1 was performed and graded based on expression in peritubular and glomerular capillaries.</div></div><div><h3>Analytical Approach</h3><div>Clinical and laboratory data, including antiphospholipid antibody profiles, were correlated with Cav-1 expression.</div></div><div><h3>Results</h3><div>Out of 771 patients with APS, a total of 11 patients with primary APS and renal involvement were retrieved (1.43%). APSN-TMA was identified in 7 (63.3%) cases, hyperplastic vasculopathy in 2 (18.1%), and subendothelial edema in 2 (18.1%). Cav-1 expression was significantly higher in APSN-TMA cases in both glomerular (<em>P</em> < 0.001) and peritubular (<em>P</em> < 0.05) capillaries compared with other clusters, with 5 of 7 APSN-TMA cases exhibiting diffuse (grade III) staining. Triple antiphospholipid antibody positive testing was more prevalent in APSN-TMA cases, reinforcing their distinct pathophysiological profile.</div></div><div><h3>Limitations</h3><div>The small sample size warrants validation in larger cohorts, and Cav-1 expression, although associated with APSN, might not be disease-specific.</div></div><div><h3>Conclusions</h3><div>APSN-TMA is a rare manifestation of a rare disease. Cav-1 is strongly associated with APSN-TMA and may serve as a novel marker for its diagnosis and stratification. Given the poor renal prognosis of APSN-TMA, identifying affected patients is crucial for optimizing management strategies.</div></div><div><h3>Plain-Language Summary</h3><div>Antiphospholipid syndrome (APS) is an autoimmune condition that can cause blood clots in many organs, including the kidneys. In some patients, a type of severe small-vessel injury called thrombotic microangiopathy develops, leading to poor kidney outcomes. Diagnosing this form of kidney damage can be challenging. In our study, we examined kidney tissue from people with APS using a special stain for a protein called Caveolin-1, which is found in damaged blood vessel cells. We found that high Caveolin-1 levels were strongly linked to the most aggressive form of APS-rel
{"title":"Caveolin-1 as a Marker of Endothelial Damage in Primary Antiphospholipid Syndrome Nephropathy","authors":"Savino Sciascia , Massimo Radin , Irene Cecchi , Alice Barinotti , Francesco Trevisani , Roberta Fenoglio , Emanuele De Simone , Dario Roccatello , Paola Cassoni , Antonella Barreca","doi":"10.1016/j.xkme.2025.101223","DOIUrl":"10.1016/j.xkme.2025.101223","url":null,"abstract":"<div><h3>Rationale & Objective</h3><div>Thrombotic microangiopathy (TMA) as seen in antiphospholipid syndrome nephropathy (APSN) is associated with poor kidney outcomes. Caveolin-1 (Cav-1) has emerged as a potential marker of endothelial damage and microvascular injury.</div></div><div><h3>Study Design</h3><div>This retrospective study investigates the diagnostic potential value of Cav-1 immunohistochemistry in APSN-related TMA.</div></div><div><h3>Setting & Participants</h3><div>Patients were retrieved from the Piedmont and Aosta Valley Rare Disease Registry, from which a total of 771 APS cases had been recorded.</div></div><div><h3>Exposure</h3><div>Only case with biopsy-proven renal involvement were included.</div></div><div><h3>Outcomes</h3><div>Cases were classified into three histopathological clusters: TMA (APSN-TMA), hyperplastic vasculopathy, and subendothelial edema. Immunohistochemical staining for Cav-1 was performed and graded based on expression in peritubular and glomerular capillaries.</div></div><div><h3>Analytical Approach</h3><div>Clinical and laboratory data, including antiphospholipid antibody profiles, were correlated with Cav-1 expression.</div></div><div><h3>Results</h3><div>Out of 771 patients with APS, a total of 11 patients with primary APS and renal involvement were retrieved (1.43%). APSN-TMA was identified in 7 (63.3%) cases, hyperplastic vasculopathy in 2 (18.1%), and subendothelial edema in 2 (18.1%). Cav-1 expression was significantly higher in APSN-TMA cases in both glomerular (<em>P</em> < 0.001) and peritubular (<em>P</em> < 0.05) capillaries compared with other clusters, with 5 of 7 APSN-TMA cases exhibiting diffuse (grade III) staining. Triple antiphospholipid antibody positive testing was more prevalent in APSN-TMA cases, reinforcing their distinct pathophysiological profile.</div></div><div><h3>Limitations</h3><div>The small sample size warrants validation in larger cohorts, and Cav-1 expression, although associated with APSN, might not be disease-specific.</div></div><div><h3>Conclusions</h3><div>APSN-TMA is a rare manifestation of a rare disease. Cav-1 is strongly associated with APSN-TMA and may serve as a novel marker for its diagnosis and stratification. Given the poor renal prognosis of APSN-TMA, identifying affected patients is crucial for optimizing management strategies.</div></div><div><h3>Plain-Language Summary</h3><div>Antiphospholipid syndrome (APS) is an autoimmune condition that can cause blood clots in many organs, including the kidneys. In some patients, a type of severe small-vessel injury called thrombotic microangiopathy develops, leading to poor kidney outcomes. Diagnosing this form of kidney damage can be challenging. In our study, we examined kidney tissue from people with APS using a special stain for a protein called Caveolin-1, which is found in damaged blood vessel cells. We found that high Caveolin-1 levels were strongly linked to the most aggressive form of APS-rel","PeriodicalId":17885,"journal":{"name":"Kidney Medicine","volume":"8 2","pages":"Article 101223"},"PeriodicalIF":3.4,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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