Pub Date : 2025-12-24DOI: 10.1016/j.ekir.2025.103749
Wenjie Guo , Jie Luo , Zhixiao Li , Xue Li , Yingying Zhang , Jingyi Yang
{"title":"Revisiting Vincristine for FSGS: Proof-of-Mechanism Arrives, but Whom Should We Treat?","authors":"Wenjie Guo , Jie Luo , Zhixiao Li , Xue Li , Yingying Zhang , Jingyi Yang","doi":"10.1016/j.ekir.2025.103749","DOIUrl":"10.1016/j.ekir.2025.103749","url":null,"abstract":"","PeriodicalId":17761,"journal":{"name":"Kidney International Reports","volume":"11 3","pages":"Article 103749"},"PeriodicalIF":5.7,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035549","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}
Pub Date : 2025-12-24DOI: 10.1016/j.ekir.2025.103746
Orlando M. Gutiérrez , Ashutosh Tamhane , Jennifer A. Frey , Ching Min Chu , Lauren Shingler , Alexander Keister , Alexander L. Bullen , Byron C. Jaeger , Suzanne E. Judd , Edward D. Siew , Michael G. Shlipak , Joseph V. Bonventre , Emily B. Levitan , Jesse C. Seegmiller , Henry E. Wang , Joachim H. Ix
Introduction
Endogenous measures of impaired kidney tubule secretion are associated with kidney function decline. Whether they associate with future acute kidney injury (AKI) risk is unclear.
Methods
In 397 participants of the Reasons for Geographic and Racial Differences in Stroke study who underwent coronary artery bypass graft (CABG) surgery (mean age: 66 years, 29% female), we examined the association of a summary secretion score of 11 endogenous secretion markers (measured at a median 5.5 years before CABG) with AKI risk following CABG, adjusting for confounders including estimated glomerular filtration rate (eGFR) and albuminuria.
Results
A total of 177 participants developed AKI (≥ 0.3 mg/dl or 1.5× creatinine increase) following CABG. Individuals who developed AKI were older, more likely to be men, have diabetes, lower eGFR and greater albuminuria at the baseline visit. In models adjusted for age, sex, race, urine creatinine, time from baseline to CABG, diabetes, hypertension, and body mass index, a higher (signifying better) secretion score was associated with lower risk of AKI (risk ratio [RR] comparing 4th to 1st quartile: 0.49, 95% confidence interval [CI]: 0.32–0.74). The results did not meaningfully differ after further adjusting for eGFR and albuminuria (RR: 0.58, 95% CI: 0.38–0.89), or when secretion score was analyzed as a continuous variable (RR per 1 SD higher score: 0.85, 95% CI: 0.71–1.01). Associations were stronger in women (RR: 0.75, 95% CI: 0.59–0.95) than men (RR: 0.89, 95% CI: 0.69–1.16) in fully adjusted models (Pinteraction = 0.01).
Conclusion
In community-based adults, greater estimated tubular secretion at times of relative health is associated with lower risk of AKI following CABG.
{"title":"Kidney Tubule Secretion and AKI After Cardiac Surgery","authors":"Orlando M. Gutiérrez , Ashutosh Tamhane , Jennifer A. Frey , Ching Min Chu , Lauren Shingler , Alexander Keister , Alexander L. Bullen , Byron C. Jaeger , Suzanne E. Judd , Edward D. Siew , Michael G. Shlipak , Joseph V. Bonventre , Emily B. Levitan , Jesse C. Seegmiller , Henry E. Wang , Joachim H. Ix","doi":"10.1016/j.ekir.2025.103746","DOIUrl":"10.1016/j.ekir.2025.103746","url":null,"abstract":"<div><h3>Introduction</h3><div>Endogenous measures of impaired kidney tubule secretion are associated with kidney function decline. Whether they associate with future acute kidney injury (AKI) risk is unclear.</div></div><div><h3>Methods</h3><div>In 397 participants of the Reasons for Geographic and Racial Differences in Stroke study who underwent coronary artery bypass graft (CABG) surgery (mean age: 66 years, 29% female), we examined the association of a summary secretion score of 11 endogenous secretion markers (measured at a median 5.5 years before CABG) with AKI risk following CABG, adjusting for confounders including estimated glomerular filtration rate (eGFR) and albuminuria.</div></div><div><h3>Results</h3><div>A total of 177 participants developed AKI (≥ 0.3 mg/dl or 1.5× creatinine increase) following CABG. Individuals who developed AKI were older, more likely to be men, have diabetes, lower eGFR and greater albuminuria at the baseline visit. In models adjusted for age, sex, race, urine creatinine, time from baseline to CABG, diabetes, hypertension, and body mass index, a higher (signifying better) secretion score was associated with lower risk of AKI (risk ratio [RR] comparing 4th to 1st quartile: 0.49, 95% confidence interval [CI]: 0.32–0.74). The results did not meaningfully differ after further adjusting for eGFR and albuminuria (RR: 0.58, 95% CI: 0.38–0.89), or when secretion score was analyzed as a continuous variable (RR per 1 SD higher score: 0.85, 95% CI: 0.71–1.01). Associations were stronger in women (RR: 0.75, 95% CI: 0.59–0.95) than men (RR: 0.89, 95% CI: 0.69–1.16) in fully adjusted models (<em>P</em><sub>interaction</sub> = 0.01).</div></div><div><h3>Conclusion</h3><div>In community-based adults, greater estimated tubular secretion at times of relative health is associated with lower risk of AKI following CABG.</div></div>","PeriodicalId":17761,"journal":{"name":"Kidney International Reports","volume":"11 3","pages":"Article 103746"},"PeriodicalIF":5.7,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145929213","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}
Pub Date : 2025-12-24DOI: 10.1016/j.ekir.2025.103745
Johannes J. Kovarik , Tarik Shoumariyeh , Oliver Domenig , Marko Poglitsch , Hanna Tinel , Chantal Kopecky , Klaus G. Schmetterer , Marcus D. Säemann , Christopher C. Kaltenecker
Introduction
The nephroprotective effects of renin-angiotensin system (RAS) blockade after kidney transplantation (KTx) remain ambiguous. It has been shown that chymase and not angiotensin (Ang)-converting enzyme (ACE) is the most efficient Ang II–forming enzyme. Here, we investigated the efficacy of the novel and highly selective chymase inhibitor fulacimstat (BAY 1142524) on Ang II formation in human allograft biopsy tissue.
Methods
In this cross-sectional, exploratory single-center study we analyzed biopsy samples of KTx recipients (n = 55) and healthy kidney donors (n = 13) with and without therapeutic RAS blockade. Using a mass spectrometry–based approach and using specific enzyme inhibitors, we performed metabolic assays to study enzyme activities of ACE and chymase and their specific contribution to intrarenal Ang II formation.
Results
In contrast to healthy kidneys, a distinct shift from ACE toward chymase-dependent Ang II formation was observed in aged (> 2 years) kidney allografts. Irrespective of RAS blockade, we demonstrated high efficacy of fulacimstat (BAY 1142524) to inhibit endogenous chymase-dependent Ang II formation in biopsy tissues of human kidney allografts.
Conclusion
Chymase is the key enzyme for Ang II production in aged graft vintage (> 2 years). Selective inhibition of tissue-specific chymase with fulacimstat (BAY 1142524) inhibits Ang II formation in human kidney allografts, indicating potential therapeutic effects.
{"title":"Fulacimstat Reduces Angiotensin II in Kidney Allografts in a Cross-Sectional Exploratory Study","authors":"Johannes J. Kovarik , Tarik Shoumariyeh , Oliver Domenig , Marko Poglitsch , Hanna Tinel , Chantal Kopecky , Klaus G. Schmetterer , Marcus D. Säemann , Christopher C. Kaltenecker","doi":"10.1016/j.ekir.2025.103745","DOIUrl":"10.1016/j.ekir.2025.103745","url":null,"abstract":"<div><h3>Introduction</h3><div>The nephroprotective effects of renin-angiotensin system (RAS) blockade after kidney transplantation (KTx) remain ambiguous. It has been shown that chymase and not angiotensin (Ang)-converting enzyme (ACE) is the most efficient Ang II–forming enzyme. Here, we investigated the efficacy of the novel and highly selective chymase inhibitor fulacimstat (BAY 1142524) on Ang II formation in human allograft biopsy tissue.</div></div><div><h3>Methods</h3><div>In this cross-sectional, exploratory single-center study we analyzed biopsy samples of KTx recipients (<em>n</em> = 55) and healthy kidney donors (<em>n</em> = 13) with and without therapeutic RAS blockade. Using a mass spectrometry–based approach and using specific enzyme inhibitors, we performed metabolic assays to study enzyme activities of ACE and chymase and their specific contribution to intrarenal Ang II formation.</div></div><div><h3>Results</h3><div>In contrast to healthy kidneys, a distinct shift from ACE toward chymase-dependent Ang II formation was observed in aged (> 2 years) kidney allografts. Irrespective of RAS blockade, we demonstrated high efficacy of fulacimstat (BAY 1142524) to inhibit endogenous chymase-dependent Ang II formation in biopsy tissues of human kidney allografts.</div></div><div><h3>Conclusion</h3><div>Chymase is the key enzyme for Ang II production in aged graft vintage (> 2 years). Selective inhibition of tissue-specific chymase with fulacimstat (BAY 1142524) inhibits Ang II formation in human kidney allografts, indicating potential therapeutic effects.</div></div>","PeriodicalId":17761,"journal":{"name":"Kidney International Reports","volume":"11 3","pages":"Article 103745"},"PeriodicalIF":5.7,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035487","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}
Pub Date : 2025-12-24DOI: 10.1016/j.ekir.2025.103740
Rasha Shemies , Abir Farouk Megahed , Abdel-Hady El-Gilany , Tamer Gaber , Reem Farouk , Rowida Hossny , Eman Basuony , Hebat-Allah Elbahnasawy , Dina Edward , Abdelrahman Badra , Abeer Abd Eltawab , Amany Samir , Afaf Mohamed Fahmy , Oriana De Marco , Mario Salomone , Giorgina Barbara Piccoli , Nagy-Sayed Ahmed
{"title":"Pregnancy in Women on Hemodialysis in Egypt","authors":"Rasha Shemies , Abir Farouk Megahed , Abdel-Hady El-Gilany , Tamer Gaber , Reem Farouk , Rowida Hossny , Eman Basuony , Hebat-Allah Elbahnasawy , Dina Edward , Abdelrahman Badra , Abeer Abd Eltawab , Amany Samir , Afaf Mohamed Fahmy , Oriana De Marco , Mario Salomone , Giorgina Barbara Piccoli , Nagy-Sayed Ahmed","doi":"10.1016/j.ekir.2025.103740","DOIUrl":"10.1016/j.ekir.2025.103740","url":null,"abstract":"","PeriodicalId":17761,"journal":{"name":"Kidney International Reports","volume":"11 3","pages":"Article 103740"},"PeriodicalIF":5.7,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078959","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}
Pub Date : 2025-12-24DOI: 10.1016/j.ekir.2025.103744
Melvin Chan , Oliver Gross
{"title":"Alporting Trouble Down the Tubules","authors":"Melvin Chan , Oliver Gross","doi":"10.1016/j.ekir.2025.103744","DOIUrl":"10.1016/j.ekir.2025.103744","url":null,"abstract":"","PeriodicalId":17761,"journal":{"name":"Kidney International Reports","volume":"11 3","pages":"Article 103744"},"PeriodicalIF":5.7,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035546","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}
Pub Date : 2025-12-24DOI: 10.1016/j.ekir.2025.103748
William J. Mason , Jennifer C. Chandler , Alice M. Gage , Gideon Pomeranz , Karen L. Price , Marilina Antonelou , Scott R. Henderson , Laura Perin , Stefano Da Sacco , Alan D. Salama , David A. Long , Ruth J. Pepper
{"title":"Response to the Letter to the Editor Entitled “Revisiting Vincristine for FSGS: Proof-of-Mechanism Arrives, but Whom Should we Treat?”","authors":"William J. Mason , Jennifer C. Chandler , Alice M. Gage , Gideon Pomeranz , Karen L. Price , Marilina Antonelou , Scott R. Henderson , Laura Perin , Stefano Da Sacco , Alan D. Salama , David A. Long , Ruth J. Pepper","doi":"10.1016/j.ekir.2025.103748","DOIUrl":"10.1016/j.ekir.2025.103748","url":null,"abstract":"","PeriodicalId":17761,"journal":{"name":"Kidney International Reports","volume":"11 3","pages":"Article 103748"},"PeriodicalIF":5.7,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146078958","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}
Pub Date : 2025-12-23DOI: 10.1016/j.ekir.2025.103739
Christopher Paschen , Maximilian C. Koeller , Juliane Hennenberg , Johannes Kläger , Maja Nackenhorst , Andre Oszwald , Michael Kammer , Nicolas Kozakowski , Dietmar Tamandl , Heinz Regele , Rainer Oberbauer
Introduction
Obesity is an established risk factor for chronic kidney disease (CKD). However, excess visceral adipose tissue (VAT) termed visceral obesity (VO) can occur in individuals with normal body mass index (BMI) or overweight. VO is associated with impaired kidney function but its effect on kidney morphology remains unclear. This study aimed to examine the association of VO with glomerular ultrastructure, podocyte morphometry (podometrics), and the kidneys’ ability for compensation after uninephrectomy in normal BMI and overweight individuals.
Methods
VAT was retrospectively quantified in computed tomography (CT) of 52 patients (BMI < 30 kg/m2) who underwent nephrectomy for nonmetastatic renal tumor without previous chemotherapy or immunotherapy. VO was defined as VAT area ≥ 100 cm2. Histological sections from nontumorous kidney regions were examined using deep learning–supported glomerular morphometry and podometrics (podocyte count, density, and nuclear volume). Renal compensation in the first year after nephrectomy (change in estimated glomerular filtration rate [ΔeGFR]) was assessed using linear regression.
Results
Of the 52 subjects with normal BMI or overweight, 35 were diagnosed with VO and exhibited a larger glomerular volume (2.6 ± 0.7 vs. 2.0 ± 0.5 ×106 μm3; P = 0.004), lower podocyte density (194 ± 50 vs. 243 ± 59 per 106 μm3; P = 0.003), and podocyte nuclear hypertrophy (226 ± 27 vs. 195 ± 22 μm3; P < 0.001). VO was associated with impaired eGFR compensation after uninephrectomy (ΔeGFR: −24 ± 15 vs. −12 ± 12 ml/min per 1.73 m2, P = 0.03). Structural changes, including glomerular enlargement (P = 0.005), podocyte density (P = 0.01), and nuclear hypertrophy (P = 0.003), were significantly associated with reduced ΔeGFR.
Conclusion
VO was associated with glomerular and podocyte changes, and impaired kidney function compensation after nephrectomy in normal BMI and overweight individuals. These data suggest that VAT quantification could guide individual decision making in subjects planned for nephrectomy.
肥胖是慢性肾脏疾病（CKD）的一个确定的危险因素。然而，被称为内脏肥胖（VO）的多余内脏脂肪组织（VAT）可能发生在正常体重指数（BMI）或超重的个体中。VO与肾功能受损有关，但其对肾脏形态的影响尚不清楚。本研究旨在探讨VO与正常BMI和超重个体非肾切除术后肾小球超微结构、足细胞形态学（podometrics）和肾脏代偿能力的关系。方法回顾性分析52例因非转移性肾肿瘤行肾切除术且既往未接受化疗或免疫治疗的患者（BMI < 30 kg/m2）的svat计算机断层扫描（CT）。VO定义为VAT面积≥100 cm2。使用深度学习支持的肾小球形态测定法和足量测定法（足细胞计数、密度和核体积）检查非肿瘤肾脏区域的组织学切片。采用线性回归评估肾切除术后第一年的肾代偿（肾小球滤过率的变化[ΔeGFR]）。结果52例BMI正常或超重的患者中，35例诊断为VO，肾小球体积较大（2.6±0.7 vs 2.0±0.5 ×106 μm3, P = 0.004），足细胞密度较低（194±50 vs 243±59 / 106 μm3, P = 0.003），足细胞核肥大（226±27 vs 195±22 μm3, P = 0.001）。非肾切除术后，VO与eGFR代偿受损相关（ΔeGFR:−24±15 vs - 12±12 ml/min / 1.73 m2, P = 0.03）。结构改变，包括肾小球增大（P = 0.005）、足细胞密度（P = 0.01）和核肥大（P = 0.003），与ΔeGFR降低显著相关。结论在BMI正常和超重人群中，vo与肾切除术后肾小球和足细胞的改变以及肾功能代偿受损有关。这些数据表明，VAT量化可以指导计划进行肾切除术的受试者的个人决策。
{"title":"Visceral Adipose Tissue Alters Podometrics and Renal Compensation After Uninephrectomy","authors":"Christopher Paschen , Maximilian C. Koeller , Juliane Hennenberg , Johannes Kläger , Maja Nackenhorst , Andre Oszwald , Michael Kammer , Nicolas Kozakowski , Dietmar Tamandl , Heinz Regele , Rainer Oberbauer","doi":"10.1016/j.ekir.2025.103739","DOIUrl":"10.1016/j.ekir.2025.103739","url":null,"abstract":"<div><h3>Introduction</h3><div>Obesity is an established risk factor for chronic kidney disease (CKD). However, excess visceral adipose tissue (VAT) termed visceral obesity (VO) can occur in individuals with normal body mass index (BMI) or overweight. VO is associated with impaired kidney function but its effect on kidney morphology remains unclear. This study aimed to examine the association of VO with glomerular ultrastructure, podocyte morphometry (podometrics), and the kidneys’ ability for compensation after uninephrectomy in normal BMI and overweight individuals.</div></div><div><h3>Methods</h3><div>VAT was retrospectively quantified in computed tomography (CT) of 52 patients (BMI < 30 kg/m<sup>2</sup>) who underwent nephrectomy for nonmetastatic renal tumor without previous chemotherapy or immunotherapy. VO was defined as VAT area ≥ 100 cm<sup>2</sup>. Histological sections from nontumorous kidney regions were examined using deep learning–supported glomerular morphometry and podometrics (podocyte count, density, and nuclear volume). Renal compensation in the first year after nephrectomy (change in estimated glomerular filtration rate [ΔeGFR]) was assessed using linear regression.</div></div><div><h3>Results</h3><div>Of the 52 subjects with normal BMI or overweight, 35 were diagnosed with VO and exhibited a larger glomerular volume (2.6 ± 0.7 vs. 2.0 ± 0.5 ×10<sup>6</sup> μm<sup>3</sup>; <em>P</em> = 0.004), lower podocyte density (194 ± 50 vs. 243 ± 59 per 10<sup>6</sup> μm<sup>3</sup>; <em>P</em> = 0.003), and podocyte nuclear hypertrophy (226 ± 27 vs. 195 ± 22 μm<sup>3</sup>; <em>P</em> < 0.001). VO was associated with impaired eGFR compensation after uninephrectomy (ΔeGFR: −24 ± 15 vs. −12 ± 12 ml/min per 1.73 m<sup>2</sup>, <em>P</em> = 0.03). Structural changes, including glomerular enlargement (<em>P</em> = 0.005), podocyte density (<em>P</em> = 0.01), and nuclear hypertrophy (<em>P</em> = 0.003), were significantly associated with reduced ΔeGFR.</div></div><div><h3>Conclusion</h3><div>VO was associated with glomerular and podocyte changes, and impaired kidney function compensation after nephrectomy in normal BMI and overweight individuals. These data suggest that VAT quantification could guide individual decision making in subjects planned for nephrectomy.</div></div>","PeriodicalId":17761,"journal":{"name":"Kidney International Reports","volume":"11 3","pages":"Article 103739"},"PeriodicalIF":5.7,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146189538","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}
Pub Date : 2025-12-23DOI: 10.1016/j.ekir.2025.103737
Gwénaëlle Begue , Armin Ahmadi , Christopher MT. Hayden , Alec Foster , Usman Rehman , Jennifer E. Norman , Chenoa Vargas , Brian J. Bennett , Craig McDonald , T. Alp Ikizler , Hiba Hamdan , Lucas Smith , Tae Youn Kim , Thomas Jue , Jorge Gamboa , Baback Roshanravan
Introduction
Muscle impairment in chronic kidney disease (CKD) contributes to decreased physical performance, frailty, and increased mortality. This proof-of-concept randomized controlled study evaluated the efficacy of a 12-week home-based, video-supervised exercise program on muscle endurance in moderate-to-severe nondialysis CKD.
Methods
Thirty-two sedentary adults with CKD (estimated glomerular filtration rate [eGFR] < 60 ml/min per 1.73 m2) were randomized (3:1) to a home exercise group (EX, n = 23) or usual care group (UC, n = 9). The primary outcome was in vivo muscle mitochondrial bioenergetics (rate of phosphocreatine recovery, kPCr) measured using phosphorus-31 magnetic resonance spectroscopy. Secondary outcomes included 6-minute walk test (6MWT) distance (6MWD), total work, peak oxygen consumption (VO2peak), and work efficiency obtained from cardiopulmonary exercise testing (CPET). Other outcomes were body composition and plasma cytokines. Within- and between-group differences were analyzed using linear mixed models (LMMs).
Results
Mean (SD) ages were 62.6 (10.8) years in EX and 67.2 (8.2) in UC. Mean eGFRs were 35.0 (12.6) and 32.3 (12.0) ml/min per 1.73 m2, respectively. No serious adverse events occurred; 90.5% of EX completed ≥ 75% of sessions. Compared with UC, EX significantly increased kPCr (0.20/min, 95% confidence interval [CI]: 0.05–0.35, P = 0.01), total work (5.03 kJ, 95% CI: 1.25–8.80, P = 0.007), and 6MWD (39.1 m, 95% CI: 7.1–71.1, P = 0.014) while preserving fat-free mass (2.3 kg, 95% CI: 0.49–4.1, P = 0.024) and marginally decreasing fat mass (−2.22 kg, 95% CI: −4.7 to 0.27, P = 0.1) . Interleukin (IL)-8 concentration differed between groups (effect size: −1.16, 95% CI: −2.4 to −0.04, P = 0.016). Work efficiency, VO2peak, and other cytokines showed no significant differences between groups.
Conclusion
Home-based, video-supervised exercise is feasible, improves muscle oxidative capacity and endurance, offering a strategy to mitigate functional decline in moderate-to-severe nondialysis CKD.
慢性肾脏疾病（CKD）的肌肉损伤会导致身体机能下降、虚弱和死亡率增加。这项概念验证的随机对照研究评估了一项为期12周、以家庭为基础、视频监督的锻炼计划对中重度非透析慢性肾病患者肌肉耐力的疗效。方法将32名久坐不动的CKD成年患者（估计肾小球滤过率[eGFR] <； 60 ml/min / 1.73 m2）随机（3:1）分为家庭运动组（EX, n = 23）和常规护理组（UC, n = 9）。主要结果是使用磷-31磁共振波谱测量体内肌肉线粒体生物能量（磷酸肌酸回收率，kPCr）。次要结果包括6分钟步行测试（6MWT）距离（6MWD）、总工作量、峰值耗氧量（vo2峰值）和心肺运动测试（CPET）获得的工作效率。其他结果包括身体成分和血浆细胞因子。使用线性混合模型（lmm）分析组内和组间差异。结果EX患者平均（SD）年龄为62.6（10.8）岁，UC患者平均（SD）年龄为67.2（8.2）岁。平均egfr分别为35.0（12.6）和32.3 (12.0)ml/min / 1.73 m2。未发生严重不良事件；90.5%的EX完成≥75%的疗程。与UC相比，EX显著增加了kPCr （0.20/min， 95%可信区间[CI]: 0.05-0.35, P = 0.01）、总功（5.03 kJ, 95% CI: 1.25-8.80, P = 0.007）和6MWD (39.1 m, 95% CI: 7.1-71.1, P = 0.014)，同时保持了无脂质量（2.3 kg, 95% CI: 0.49-4.1, P = 0.024），并略微减少了脂肪质量（- 2.22 kg, 95% CI: - 4.7 - 0.27, P = 0.1）。两组间白细胞介素(IL)-8浓度存在差异（效应值：−1.16,95% CI:−2.4 ~−0.04,P = 0.016）。工作效率、VO2peak等细胞因子组间差异无统计学意义。结论：以家庭为基础的视频指导运动是可行的，可以提高肌肉的氧化能力和耐力，为减轻中重度非透析性CKD的功能下降提供了一种策略。
{"title":"Home-Based Exercise Improves Muscle Oxidative Capacity in Kidney Disease","authors":"Gwénaëlle Begue , Armin Ahmadi , Christopher MT. Hayden , Alec Foster , Usman Rehman , Jennifer E. Norman , Chenoa Vargas , Brian J. Bennett , Craig McDonald , T. Alp Ikizler , Hiba Hamdan , Lucas Smith , Tae Youn Kim , Thomas Jue , Jorge Gamboa , Baback Roshanravan","doi":"10.1016/j.ekir.2025.103737","DOIUrl":"10.1016/j.ekir.2025.103737","url":null,"abstract":"<div><h3>Introduction</h3><div>Muscle impairment in chronic kidney disease (CKD) contributes to decreased physical performance, frailty, and increased mortality. This proof-of-concept randomized controlled study evaluated the efficacy of a 12-week home-based, video-supervised exercise program on muscle endurance in moderate-to-severe nondialysis CKD.</div></div><div><h3>Methods</h3><div>Thirty-two sedentary adults with CKD (estimated glomerular filtration rate [eGFR] < 60 ml/min per 1.73 m<sup>2</sup>) were randomized (3:1) to a home exercise group (EX, <em>n</em> = 23) or usual care group (UC, <em>n</em> = 9). The primary outcome was <em>in vivo</em> muscle mitochondrial bioenergetics (rate of phosphocreatine recovery, k<sub>PCr</sub>) measured using phosphorus-31 magnetic resonance spectroscopy. Secondary outcomes included 6-minute walk test (6MWT) distance (6MWD), total work, peak oxygen consumption (VO<sub>2</sub>peak), and work efficiency obtained from cardiopulmonary exercise testing (CPET). Other outcomes were body composition and plasma cytokines. Within- and between-group differences were analyzed using linear mixed models (LMMs).</div></div><div><h3>Results</h3><div>Mean (SD) ages were 62.6 (10.8) years in EX and 67.2 (8.2) in UC. Mean eGFRs were 35.0 (12.6) and 32.3 (12.0) ml/min per 1.73 m<sup>2</sup>, respectively. No serious adverse events occurred; 90.5% of EX completed ≥ 75% of sessions. Compared with UC, EX significantly increased k<sub>PCr</sub> (0.20/min, 95% confidence interval [CI]: 0.05–0.35, <em>P</em> = 0.01), total work (5.03 kJ, 95% CI: 1.25–8.80, <em>P</em> = 0.007), and 6MWD (39.1 m, 95% CI: 7.1–71.1, <em>P</em> = 0.014) while preserving fat-free mass (2.3 kg, 95% CI: 0.49–4.1, <em>P</em> = 0.024) and marginally decreasing fat mass (−2.22 kg, 95% CI: −4.7 to 0.27, <em>P</em> = 0.1) . Interleukin (IL)-8 concentration differed between groups (effect size: −1.16, 95% CI: −2.4 to −0.04, <em>P</em> = 0.016). Work efficiency, VO<sub>2</sub>peak, and other cytokines showed no significant differences between groups.</div></div><div><h3>Conclusion</h3><div>Home-based, video-supervised exercise is feasible, improves muscle oxidative capacity and endurance, offering a strategy to mitigate functional decline in moderate-to-severe nondialysis CKD.</div></div>","PeriodicalId":17761,"journal":{"name":"Kidney International Reports","volume":"11 3","pages":"Article 103737"},"PeriodicalIF":5.7,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035553","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}
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been demonstrated to reduce proteinuria and disease progression in people with chronic kidney disease (CKD), but data in Fabry disease (FD) are scant. This prospective, multicenter study evaluated the 12-month effects of dapagliflozin 10 mg/dL on albuminuria, proteinuria, and renal function in patients with FD and albuminuric CKD.
Methods
Adults with FD and albuminuric CKD (estimated glomerular filtration rate [eGFR] ≥ 25 ml/min) despite stable enzyme replacement therapy (ERT) or migalastat and maximally tolerated dose of renin-angiotensin system inhibitors (RAS-i) were included. Proteinuria, urinary albumin-to-creatinine ratio (UACR), eGFR, and blood pressure were assessed 12 months before dapagliflozin initiation (T0), at treatment initiation (T1), and at 12-month follow-up (T2).
Results
Sixteen patients were enrolled. After 12 months of dapagliflozin, UACR and 24-hour proteinuria decreased by 47.6% (300.1 [interquartile range, IQR: 106.5–856.1] mg/g [T1] vs. 142.5 [IQR: 60.7–415.7) mg/g [T2]; P = 0.01) and 22.2% (0.45 [IQR: 0.31–1.67] g/d [T1] vs. 0.35 [IQR: 0.18–1.42] g/d [T2]; P < 0.001), respectively. Mixed-effects model analysis confirmed the effect of dapagliflozin on reducing 24-hour proteinuria (P < 0.001), after adjustment for age, sex, eGFR, FD phenotype and ERT/migalastat treatments. eGFR remained stable (63.50 [SD: 25.13] ml/min per 1.73 m2 [T1] vs. 64.31 [SD: 26.40] ml/min per 1.73 m2 [T2]; P = 0.65), contrasting with annual decline (−5.63 [SE: 1.78] ml/min per 1.73 m2) during T0 to T1 period, adjusting for sex, age, FD phenotype, ERT/migalastat treatments and 24-hour proteinuria. Eight out of 9 fast renal progressor patients achieved an annual eGFR slope ≤ 3 ml/min during the T1 to T2 period.
Conclusion
this preliminary evidence shows that dapagliflozin was associated with reduction in albuminuria, proteinuria, and eGFR decline in patients with FD and albuminuric CKD receiving ERT or migalastat and RAS-i over 12 months.
{"title":"Dapagliflozin in Patients With CKD With Fabry Disease","authors":"Yuri Battaglia , Nicola Vitturi , Giacomo Marchi , Federica Baciga , Federica Caccia , Giorgia Gugelmo , Loris Martinetti , Lucia Federica Stefanelli , Sara Torresani , Antonio Pisani , Eleonora Riccio , Pasquale Esposito , Francesca Viazzi , Cristina Chimenti , Francesca Katiana Martino , Livia Lenzini , Annalisa Sechi , Luca Zanoli , Domenico Girelli , Gian Paolo Fadini , Gianni Carraro","doi":"10.1016/j.ekir.2025.103742","DOIUrl":"10.1016/j.ekir.2025.103742","url":null,"abstract":"<div><h3>Introduction</h3><div>Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been demonstrated to reduce proteinuria and disease progression in people with chronic kidney disease (CKD), but data in Fabry disease (FD) are scant. This prospective, multicenter study evaluated the 12-month effects of dapagliflozin 10 mg/dL on albuminuria, proteinuria, and renal function in patients with FD and albuminuric CKD.</div></div><div><h3>Methods</h3><div>Adults with FD and albuminuric CKD (estimated glomerular filtration rate [eGFR] ≥ 25 ml/min) despite stable enzyme replacement therapy (ERT) or migalastat and maximally tolerated dose of renin-angiotensin system inhibitors (RAS-i) were included. Proteinuria, urinary albumin-to-creatinine ratio (UACR), eGFR, and blood pressure were assessed 12 months before dapagliflozin initiation (T0), at treatment initiation (T1), and at 12-month follow-up (T2).</div></div><div><h3>Results</h3><div>Sixteen patients were enrolled. After 12 months of dapagliflozin, UACR and 24-hour proteinuria decreased by 47.6% (300.1 [interquartile range, IQR: 106.5–856.1] mg/g [T1] vs. 142.5 [IQR: 60.7–415.7) mg/g [T2]; <em>P</em> = 0.01) and 22.2% (0.45 [IQR: 0.31–1.67] g/d [T1] vs. 0.35 [IQR: 0.18–1.42] g/d [T2]; <em>P</em> < 0.001), respectively. Mixed-effects model analysis confirmed the effect of dapagliflozin on reducing 24-hour proteinuria (<em>P</em> < 0.001), after adjustment for age, sex, eGFR, FD phenotype and ERT/migalastat treatments. eGFR remained stable (63.50 [SD: 25.13] ml/min per 1.73 m<sup>2</sup> [T1] vs. 64.31 [SD: 26.40] ml/min per 1.73 m<sup>2</sup> [T2]; <em>P</em> = 0.65), contrasting with annual decline (−5.63 [SE: 1.78] ml/min per 1.73 m<sup>2</sup>) during T0 to T1 period, adjusting for sex, age, FD phenotype, ERT/migalastat treatments and 24-hour proteinuria. Eight out of 9 fast renal progressor patients achieved an annual eGFR slope ≤ 3 ml/min during the T1 to T2 period.</div></div><div><h3>Conclusion</h3><div>this preliminary evidence shows that dapagliflozin was associated with reduction in albuminuria, proteinuria, and eGFR decline in patients with FD and albuminuric CKD receiving ERT or migalastat and RAS-i over 12 months.</div></div>","PeriodicalId":17761,"journal":{"name":"Kidney International Reports","volume":"11 3","pages":"Article 103742"},"PeriodicalIF":5.7,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146189615","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}
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