Pub Date : 2025-01-01DOI: 10.1016/j.kint.2024.10.020
Zewu Zhu , Clemens Bergwitz
Pathogenic variants in the SLC34A1 and SLC34A3 genes, encoding sodium-phosphate cotransporters 2a (NPT2a) and 2c (NPT2c), are linked to rare phosphate-wasting disorders. In this issue, Brunkhorst et al. explore the clinical presentations, biochemical profiles, and treatment outcomes associated with these genetic variants in 113 individuals. The study highlights distinct phenotypes, potential treatment challenges, and the need for further research to optimize therapeutic strategies and understand long-term outcomes for affected individuals.
{"title":"Phenotypic variability in phosphate transport disorders highlights need for individualized treatment strategies","authors":"Zewu Zhu , Clemens Bergwitz","doi":"10.1016/j.kint.2024.10.020","DOIUrl":"10.1016/j.kint.2024.10.020","url":null,"abstract":"<div><div>Pathogenic variants in the <em>SLC34A1</em> and <em>SLC34A3</em> genes, encoding sodium-phosphate cotransporters 2a (NPT2a) and 2c (NPT2c), are linked to rare phosphate-wasting disorders. In this issue, Brunkhorst <em>et al.</em> explore the clinical presentations, biochemical profiles, and treatment outcomes associated with these genetic variants in 113 individuals. The study highlights distinct phenotypes, potential treatment challenges, and the need for further research to optimize therapeutic strategies and understand long-term outcomes for affected individuals.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"107 1","pages":"Pages 12-15"},"PeriodicalIF":14.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.kint.2024.10.017
Lanette M. Christensen , Matthew H. Levine
A current study by Kitai et al. found that ovariectomy before estrogen/female sex hormone sensitization at puberty provided protection against kidney ischemia reperfusion injury, challenging the general consensus within the field that estrogen provides renoprotective function. These results are intriguing and could have important clinical implications, while requiring some clarification and substantiation of the conclusions reported.
{"title":"Potential nuances in renoprotective properties of estrogen in females","authors":"Lanette M. Christensen , Matthew H. Levine","doi":"10.1016/j.kint.2024.10.017","DOIUrl":"10.1016/j.kint.2024.10.017","url":null,"abstract":"<div><div>A current study by Kitai <em>et al.</em> found that ovariectomy before estrogen/female sex hormone sensitization at puberty provided protection against kidney ischemia reperfusion injury, challenging the general consensus within the field that estrogen provides renoprotective function. These results are intriguing and could have important clinical implications, while requiring some clarification and substantiation of the conclusions reported.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"107 1","pages":"Pages 10-12"},"PeriodicalIF":14.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.kint.2024.10.015
Mark Canney , Mohammad Atiquzzaman , Yuyan Zheng , Dilshani Induruwage , Yinshan Zhao , Lee Er , Christopher B. Fordyce , Sean J. Barbour
Patients with glomerular disease are at high risk of cardiovascular disease but the contribution of immunosuppression to this risk is unclear. In this retrospective cohort study of 1912 patients (comprised of 759 with IgA nephropathy, 540 with focal segmental glomerulosclerosis, 387 with membranous nephropathy and 226 with minimal change disease) from British Columbia, Canada, we evaluated the association between exposure to specific immunosuppressive medications and a composite outcome including coronary artery, cerebrovascular and peripheral arterial events. Survival models were adjusted for baseline cardiovascular risk factors, type of glomerular disease, estimated glomerular filtration rate (eGFR) and proteinuria over time. During a median follow-up of 6.8 years, 212 patients (11.1%) experienced the primary outcome. Corticosteroid exposure was not significantly associated with the primary outcome after adjusting for cardiovascular risk factors. In fully adjusted models, cumulative calcineurin inhibitor exposure at modest (150-300 defined daily doses [DDD]) and higher (300 or more DDD) doses were associated with a 2-fold higher risk of cardiovascular events (hazard ratio 2.98, 95% confidence interval 1.27-6.95) and (2.78, 1.32-5.84), respectively. A peak daily dose of antimetabolite (azathioprine, mycophenolate mofetil and mycophenolate sodium) of 0.5 or more DDD was associated with higher risk of cardiovascular events after adjustment for baseline risk factors and type of glomerular disease, but not after adjusting for time-varying eGFR and proteinuria (1.70, 0.91-3.20). Each 10 grams of cumulative cyclophosphamide exposure was associated with a 1.5-fold higher risk of cardiovascular events in a fully adjusted model (1.46, 1.22-1.75) Thus, our findings suggest that immunosuppressive therapies used in the treatment of glomerular disease may have different cardiovascular risk profiles, which should be considered when deciding on immunosuppression for individual patients and as a safety endpoint in future clinical trials.
{"title":"Evaluating the risk of cardiovascular events associated with different immunosuppression treatments for glomerular diseases","authors":"Mark Canney , Mohammad Atiquzzaman , Yuyan Zheng , Dilshani Induruwage , Yinshan Zhao , Lee Er , Christopher B. Fordyce , Sean J. Barbour","doi":"10.1016/j.kint.2024.10.015","DOIUrl":"10.1016/j.kint.2024.10.015","url":null,"abstract":"<div><div>Patients with glomerular disease are at high risk of cardiovascular disease but the contribution of immunosuppression to this risk is unclear. In this retrospective cohort study of 1912 patients (comprised of 759 with IgA nephropathy, 540 with focal segmental glomerulosclerosis, 387 with membranous nephropathy and 226 with minimal change disease) from British Columbia, Canada, we evaluated the association between exposure to specific immunosuppressive medications and a composite outcome including coronary artery, cerebrovascular and peripheral arterial events. Survival models were adjusted for baseline cardiovascular risk factors, type of glomerular disease, estimated glomerular filtration rate (eGFR) and proteinuria over time. During a median follow-up of 6.8 years, 212 patients (11.1%) experienced the primary outcome. Corticosteroid exposure was not significantly associated with the primary outcome after adjusting for cardiovascular risk factors. In fully adjusted models, cumulative calcineurin inhibitor exposure at modest (150-300 defined daily doses [DDD]) and higher (300 or more DDD) doses were associated with a 2-fold higher risk of cardiovascular events (hazard ratio 2.98, 95% confidence interval 1.27-6.95) and (2.78, 1.32-5.84), respectively. A peak daily dose of antimetabolite (azathioprine, mycophenolate mofetil and mycophenolate sodium) of 0.5 or more DDD was associated with higher risk of cardiovascular events after adjustment for baseline risk factors and type of glomerular disease, but not after adjusting for time-varying eGFR and proteinuria (1.70, 0.91-3.20). Each 10 grams of cumulative cyclophosphamide exposure was associated with a 1.5-fold higher risk of cardiovascular events in a fully adjusted model (1.46, 1.22-1.75) Thus, our findings suggest that immunosuppressive therapies used in the treatment of glomerular disease may have different cardiovascular risk profiles, which should be considered when deciding on immunosuppression for individual patients and as a safety endpoint in future clinical trials.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"107 1","pages":"Pages 143-154"},"PeriodicalIF":14.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.kint.2024.10.011
Nicholas M. Selby , Lui G. Forni
Hypotension is a common cause of acute kidney injury (AKI), with strong associations between the duration and magnitude of hypotension seen across a range of situations including major surgery. However, it is less clear whether targeting higher intraoperative MAP results in lower rates of AKI. In a prespecified analysis of the Perioperative Ischemic Evaluation-3 (POISE-3) randomized controlled trial, this question is addressed for noncardiac major surgery. Despite an increase in cessation of antihypertensive medications and higher intraoperative mean arterial blood pressure in the intervention arm, no differences were seen in the rates of postoperative AKI. This commentary discusses the strengths and weaknesses of the trial, as well as providing some interpretation of results and their relevance to clinical practice.
低血压是导致急性肾损伤（AKI）的常见原因，在包括大手术在内的各种情况下，低血压的持续时间和程度之间都存在密切联系。然而，针对术中更高的血压是否能降低 AKI 的发生率还不太清楚。在围术期缺血评估-3（POISE-3）随机对照试验的预设分析中，非心脏大手术中的这一问题得到了解决。尽管干预组中停用降压药物的人数增加，术中平均动脉血压升高，但术后 AKI 的发生率没有差异。本评论讨论了该试验的优缺点，并对结果及其与临床实践的相关性进行了一些解读。
{"title":"Higher intraoperative blood pressure does not reduce acute kidney injury in noncardiac surgery: what do the results of the POISE-3 trial tell us?","authors":"Nicholas M. Selby , Lui G. Forni","doi":"10.1016/j.kint.2024.10.011","DOIUrl":"10.1016/j.kint.2024.10.011","url":null,"abstract":"<div><div>Hypotension is a common cause of acute kidney injury (AKI), with strong associations between the duration and magnitude of hypotension seen across a range of situations including major surgery. However, it is less clear whether targeting higher intraoperative MAP results in lower rates of AKI. In a prespecified analysis of the Perioperative Ischemic Evaluation-3 (POISE-3) randomized controlled trial, this question is addressed for noncardiac major surgery. Despite an increase in cessation of antihypertensive medications and higher intraoperative mean arterial blood pressure in the intervention arm, no differences were seen in the rates of postoperative AKI. This commentary discusses the strengths and weaknesses of the trial, as well as providing some interpretation of results and their relevance to clinical practice.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"107 1","pages":"Pages 15-17"},"PeriodicalIF":14.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amoxicillin crystalluria (AC) refers to the precipitation of amoxicillin in the urine as amoxicillin trihydrate crystals. Amoxicillin-induced crystal nephropathy (AICN) refers to the obstruction of kidney tubules by amoxicillin trihydrate crystals, resulting in acute kidney injury. Usually considered rare and not serious, AC and AICN would be more frequent in patients receiving high-dose i.v. amoxicillin (≥150 mg/kg per day) than previously reported. AC prevalence ranges from 24% to 41%. AICN prevalence remains unclear. AC is generally asymptomatic, but sudden macroscopic hematuria with cloudy urine suggests the diagnosis. AC is diagnosed by detecting amoxicillin trihydrate crystals in urine. AC is a risk factor for acute kidney injury. Diagnosing AICN is more challenging in the absence of noninvasive diagnostic tools. It is suspected in high-dose i.v. amoxicillin–treated patients who develop acute kidney injury and AC, and after excluding other causes of acute kidney injury (mainly sepsis and acute interstitial nephritis). When testing for AC is unavailable, the presence of demonstrated (high blood amoxicillin levels and low urinary pH) or suspected (rapid i.v. amoxicillin administration and hypovolemia) risk factors for AC suggests its diagnosis. AICN management includes discontinuation/reduction of amoxicillin doses and volume resuscitation to improve tubular flow and urine output and decrease amoxicillin supersaturation. Patients generally recover normal kidney function rapidly after stopping amoxicillin, but renal replacement therapy is required in 10%-40% of patients. No deaths have been directly attributed to AICN. Future studies are needed to assess the exact prevalence of AC/AICN and to define optimal therapeutic options.
阿莫西林结晶尿（AC）是指阿莫西林在尿液中沉淀为三水阿莫西林晶体。阿莫西林诱发晶体肾病（AICN）是指三水合阿莫西林晶体阻塞肾小管，导致急性肾损伤（AKI）。AC 和 AICN 通常被认为罕见且不严重，但在接受大剂量静脉注射阿莫西林（HDIVA ≥150 毫克/千克/天）的患者中，AC 和 AICN 的发生率会比以往报道的更高。AC 患病率从 24% 到 41% 不等。AICN 患病率仍不清楚。AC 一般无症状，但突然出现的大镜下血尿和尿液混浊可提示诊断。通过检测尿液中的三水阿莫西林结晶可确诊 AC。AC 是 AKI 的危险因素。由于缺乏无创诊断工具，诊断 AICN 更具挑战性。接受 HDIVA 治疗的患者如果出现 AKI 和 AC，在排除其他 AKI 病因（主要是败血症和急性间质性肾炎）后，就会被怀疑为 AICN。在无法进行 AC 检测的情况下，如果存在已证实（血液中阿莫西林含量高、尿液 pH 值低）或疑似（快速静脉注射阿莫西林、低血容量）的 AC 危险因素，则可提示其诊断。AICN 的治疗包括停用/减少阿莫西林剂量和容量复苏，以改善肾小管流量和尿量，降低阿莫西林的过饱和度。停用阿莫西林后，患者的肾功能一般会迅速恢复正常，但有 10%-40% 的患者需要进行肾脏替代治疗。目前还没有死亡直接归因于 AICN。今后还需要进行研究，以评估 AC/AICN 的确切发病率，并确定最佳治疗方案。
{"title":"Amoxicillin crystalluria and amoxicillin-induced crystal nephropathy: a narrative review","authors":"Dominique Vodovar , Cyril Mousseaux , Michel Daudon , Matthieu Jamme , Emmanuel Letavernier","doi":"10.1016/j.kint.2024.09.019","DOIUrl":"10.1016/j.kint.2024.09.019","url":null,"abstract":"<div><div>Amoxicillin crystalluria (AC) refers to the precipitation of amoxicillin in the urine as amoxicillin trihydrate crystals. Amoxicillin-induced crystal nephropathy (AICN) refers to the obstruction of kidney tubules by amoxicillin trihydrate crystals, resulting in acute kidney injury. Usually considered rare and not serious, AC and AICN would be more frequent in patients receiving high-dose i.v. amoxicillin (≥150 mg/kg per day) than previously reported. AC prevalence ranges from 24% to 41%. AICN prevalence remains unclear. AC is generally asymptomatic, but sudden macroscopic hematuria with cloudy urine suggests the diagnosis. AC is diagnosed by detecting amoxicillin trihydrate crystals in urine. AC is a risk factor for acute kidney injury. Diagnosing AICN is more challenging in the absence of noninvasive diagnostic tools. It is suspected in high-dose i.v. amoxicillin–treated patients who develop acute kidney injury and AC, and after excluding other causes of acute kidney injury (mainly sepsis and acute interstitial nephritis). When testing for AC is unavailable, the presence of demonstrated (high blood amoxicillin levels and low urinary pH) or suspected (rapid i.v. amoxicillin administration and hypovolemia) risk factors for AC suggests its diagnosis. AICN management includes discontinuation/reduction of amoxicillin doses and volume resuscitation to improve tubular flow and urine output and decrease amoxicillin supersaturation. Patients generally recover normal kidney function rapidly after stopping amoxicillin, but renal replacement therapy is required in 10%-40% of patients. No deaths have been directly attributed to AICN. Future studies are needed to assess the exact prevalence of AC/AICN and to define optimal therapeutic options.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"107 1","pages":"Pages 33-43"},"PeriodicalIF":14.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.kint.2024.10.009
T. Alp Ikizler , Tilman B. Drueke , Jürgen Floege , Germaine Wong
Cardiac arrythmias are common in patients undergoing maintenance hemodialysis. In this issue, Charytan et al. showed that in patients with hyperkalemia (serum potassium concentration 5.10–6.50 mmol/l [5.1–6.5 mEq/l]) on hemodialysis, a dialysate concentration of 3 mEq/l combined with sodium zirconium cyclosilicate on dialysis-free days is associated with a lower frequency of atrial fibrillation compared with a dialysate concentration of 2 mEq/l over 8 weeks. Despite the obvious limitations such as small sample size, short treatment period, and lack of information on longer-term impact on important patient outcomes such as sudden death, this well-conceived pilot study provided impetus for larger prospective trials to test whether this personalized approach reduces major cardiovascular events and mortality.
{"title":"Avoiding arrythmias by personalizing the dialysate concentration: a case for precision medicine in patients on dialysis","authors":"T. Alp Ikizler , Tilman B. Drueke , Jürgen Floege , Germaine Wong","doi":"10.1016/j.kint.2024.10.009","DOIUrl":"10.1016/j.kint.2024.10.009","url":null,"abstract":"<div><div>Cardiac arrythmias are common in patients undergoing maintenance hemodialysis. In this issue, Charytan <em>et al</em>. showed that in patients with hyperkalemia (serum potassium concentration 5.10–6.50 mmol/l [5.1–6.5 mEq/l]) on hemodialysis, a dialysate concentration of 3 mEq/l combined with sodium zirconium cyclosilicate on dialysis-free days is associated with a lower frequency of atrial fibrillation compared with a dialysate concentration of 2 mEq/l over 8 weeks. Despite the obvious limitations such as small sample size, short treatment period, and lack of information on longer-term impact on important patient outcomes such as sudden death, this well-conceived pilot study provided impetus for larger prospective trials to test whether this personalized approach reduces major cardiovascular events and mortality.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"107 1","pages":"Pages 18-20"},"PeriodicalIF":14.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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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