Nephrology Dialysis Transplantation最新文献

{"title":"Protocol and rationale for a randomized controlled SGLT2 inhibitor trial in paediatric and young adult populations with chronic kidney disease: DOUBLE PRO-TECT Alport.","authors":"Oliver Gross, Jan Boeckhaus, Lutz T Weber, Hiddo J L Heerspink, James F Simon, Rees Ahmed, Christoph Gerst, Ulrike Duerr, Florian Walker, Ralf Tostmann, Jürgen Helm, Thomas Asendorf, Tim Friede","doi":"10.1093/ndt/gfae180","DOIUrl":"10.1093/ndt/gfae180","url":null,"abstract":"<p><strong>Background: </strong>Clinical trials have demonstrated positive cardiovascular and kidney outcomes of sodium-glucose co-transporter 2 (SGLT2) inhibitors in adult patients with diabetic and other chronic kidney diseases (CKDs). Whether benefits extend to children, teenagers and young adults with early-stage CKD is unknown. For this reason, the DOUBLE PRO-TECT Alport trial (NCT05944016) will study the progression of albuminuria in young patients with Alport syndrome (AS), the most common hereditary CKD, to assess the safety and efficacy of the SGLT2 inhibitor dapagliflozin. Patients living with AS and chronically elevated albuminuria have a high risk of kidney failure before the age of 50 years.</p><p><strong>Methods: </strong>DOUBLE PRO-TECT Alport is a multicentre, randomized, double-blind, placebo-controlled trial. Participants (ages 10-39 years) must have a diagnosis of AS by genetic testing or kidney biopsy, be on a stable (>3 months) maximum tolerated dose of a renin-angiotensin system inhibitor and have a urinary albumin:creatinine ratio (UACR) of >300 mg/g (paediatric) or >500 mg/g (adult).Eligible participants will be randomly assigned at a 2:1 ratio to 48 weeks of treatment with dapaglifozin 10 mg/day or matched placebo. Most participants are expected to be children with a normal estimated glomerular filtration rate (eGFR). In addition to safety, the primary (change in UACR from baseline to week 48) and key secondary (eGFR change from baseline to week 52) efficacy outcomes will be analysed with a mixed model repeated measures approach. Efficacy analyses will be performed primarily in the full analysis set according to the intention-to-treat principle. A sensitivity analysis will be performed using reference-based multiple imputation.</p><p><strong>Conclusion: </strong>DOUBLE PRO-TECT Alport will assess whether SGLT2 inhibitors can safely reduce the UACR change from baseline as a marker for progression of CKD in young patients living with AS.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"679-687"},"PeriodicalIF":4.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The gut microbiome as a potential therapeutic target in IgA nephropathy.","authors":"Inês Miguel Pereira, Marta Pereira, José António Lopes, Joana Gameiro","doi":"10.1093/ndt/gfae274","DOIUrl":"10.1093/ndt/gfae274","url":null,"abstract":"<p><p>Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis and a leading cause of kidney failure, with limited treatment options available. The pathophysiology of IgAN remains unclear; however, recent studies suggest that genetic, epigenetic and environmental factors play significant roles. There is also strong evidence linking the gut microbiome to the development of IgAN. In this review, we will examine the relationship between the microbiome and the pathogenesis of IgAN, as well as its potential as a target for future therapeutic interventions.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"641-650"},"PeriodicalIF":4.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813697","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}

{"title":"Kidney thrombotic microangiopathy with concurrent monoclonal gammopathy.","authors":"Meng Tan, Changhao Jia, Xiaotian Liu, Daoxu Wu, Xiaojuan Yu, Minghui Zhao, Ying Tan","doi":"10.1093/ndt/gfae191","DOIUrl":"10.1093/ndt/gfae191","url":null,"abstract":"<p><strong>Background: </strong>The concurrence of monoclonal gammopathy and thrombotic microangiopathy (TMA) has been suggested in a few studies. However, the complement activation was not fully studied in previous cases. In this study, we aimed to determine the complement activation in these group of patients and the association with clinical, laboratory and pathological features.</p><p><strong>Methods: </strong>Between 2007 and 2020, 20 patients with biopsy-proven renal TMA and monoclonal gammopathy in Peking University First Hospital were included in the study. Complement activation was tested by enzyme-linked immunosorbent assay. Associations with clinical features, pathological data and laboratory findings were further investigated.</p><p><strong>Results: </strong>Among renal TMA patients beyond 50 years of age, the prevalence of monoclonal gammopathy was 16.51% (18/109) which is almost 4-fold greater than the expected rate in population (4.2%). Eleven patients had acute kidney injury, and two patients required dialysis. Hematological diagnosis was consistent with monoclonal gammopathy of undetermined significance (MGUS) (n = 10), unconfirmed MGUS (n = 3), POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) syndromes (n = 4), Castleman's disease (n = 2) and chronic lymphocytic leukemia (n = 1). A majority of patients (84.2%) showed the activation of complement classical pathway. Fifteen percent (3/20) of patients received conservative therapy, 5% (1/20) received steroid only, 30% (6/20) with immunosuppression and 50% (10/20) received clone-targeted chemotherapy. During a median 56 months of follow-up, end-stage renal disease developed in two patients, and five patients died mainly because of hematological progression.</p><p><strong>Conclusion: </strong>This study found the dysregulation of complement activation, especially the classical pathway, involved in the pathogenesis of biopsy-proven renal TMA and monoclonal gammopathy.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"781-787"},"PeriodicalIF":4.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081115","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}

{"title":"Adult outcomes of childhood kidney replacement therapy in Europe from 2008 to 2019: an ERA Registry study.","authors":"Iris R Montez de Sousa, Marjolein Bonthuis, Anneke Kramer, Flor Angel Ordoñez, Francisco de la Cerda Ojeda, Helena Rydell, Jaakko Helve, Jaap W Groothoff, Kristine Hommel, Lukas Buchwinkler, Mårten Segelmark, Mustafa Arici, Runolfur Palsson, Samira Bell, Sara Trujillo-Alemán, Sevcan A Bakkaloglu, Søren S Sørensen, Anna Vila, Alberto Ortiz, Vianda S Stel, Kitty J Jager","doi":"10.1093/ndt/gfae189","DOIUrl":"10.1093/ndt/gfae189","url":null,"abstract":"<p><strong>Background: </strong>Young adults starting kidney replacement therapy (KRT) during childhood and reaching their 18th birthday (i.e. adult survivors of childhood KRT) form a challenging population of interest to nephrologists treating adults, as during this period there will be a transition to adult renal centres. Nonetheless, few studies have focused on the epidemiology of KRT in this group. We aimed to provide an update on these patients' characteristics, treatment history, and graft and patient survival, to report their 5-year prognosis and expected remaining lifetime.</p><p><strong>Methods: </strong>Data on KRT patients reaching their 18th birthday in 2008-19 were collected from 21 European countries/regions providing individual patient data to the European Renal Association (ERA) Registry. Patient characteristics and treatment trajectories were examined before and after turning 18 years old. Kaplan-Meier and Cox proportional hazards regression were used for patient and graft survival analyses.</p><p><strong>Results: </strong>In total, 2944 patients were included. The proportion of adult survivors initiating KRT at a very young age (0-4 years) and undergoing pre-emptive kidney transplantation increased. Unadjusted 5-year patient survival was 96.9% [95% confidence interval (CI) 96.2-97.5]. Dialysis patients had a higher risk of death than kidney transplant recipients [adjusted hazard ratio 5.44 (95% CI 3.34-8.86)]. Between ages 18 and 23 years, about 21% of the adult survivors lost their kidney transplant and 34% of the dialysis patients continued this treatment. Compared with the general population, life expectancy for 18-year-old kidney transplant and dialysis patients was 17 and 40 years shorter, respectively.</p><p><strong>Conclusion: </strong>Life expectancy of 18-year-old kidney transplant recipients was lower compared with the general population, yet having a functioning kidney graft at age 18 years resulted in better outcomes than being on dialysis. Nevertheless, between ages 18 and 23 years, about one-fifth of the kidney grafts failed and one-third of the patients remained on dialysis.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"707-719"},"PeriodicalIF":4.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056148","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}

{"title":"Translational research on cognitive impairment in chronic kidney disease.","authors":"Carsten A Wagner, Ziad A Massy, Giovambattista Capasso, Francesco Mattace-Raso, Marion Pepin, Mickaël Bobot, Carmine Zoccali, Ana C Ferreira, Ewout J Hoorn, Pedro H Imenez Silva, Robert J Unwin, Vesna Pesic","doi":"10.1093/ndt/gfae229","DOIUrl":"10.1093/ndt/gfae229","url":null,"abstract":"<p><p>Cognitive decline is common in patients with acute or chronic kidney disease. Several areas of brain function can be affected, including short- and long-term memory, attention and inhibitory control, sleep, mood, eating control and motor function. Cognitive decline in kidney disease shares risk factors with cognitive dysfunction in people without kidney disease, such as diabetes, high blood pressure, sedentary lifestyle and unhealthy diet. However, additional kidney-specific risk factors may contribute, such as uremic toxins, electrolyte imbalances, chronic inflammation, acid-base disorders or endocrine dysregulation. Traditional and kidney-specific risk factors may interact to cause damage to the blood-brain barrier, induce vascular damage in the brain and cause neurotoxicity or neuroinflammation. Here, we discuss recent insights into the pathomechanisms of cognitive decline from animal models and novel avenues for prevention and therapy. We focus on a several areas that influence cognition: blood-brain barrier disruption, the role of skeletal muscle, physical activity and the endocrine factor irisin, and the emerging therapeutic role of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists. Taken together, these studies demonstrate the importance of animal models in providing a mechanistic understanding of this complex condition and their potential to explain the mechanisms of novel therapies.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"621-631"},"PeriodicalIF":4.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470749","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}

{"title":"Dietary protein intake and the tubular handling of indoxyl sulfate.","authors":"Mara Lauriola, Ricard Farré, Sander Dejongh, Henriette de Loor, Pieter Evenepoel, Rosalinde Masereeuw, Ward Zadora, Björn Meijers","doi":"10.1093/ndt/gfae220","DOIUrl":"10.1093/ndt/gfae220","url":null,"abstract":"<p><strong>Background: </strong>Chronic kidney disease (CKD) patients are advised to limit their protein intake. A high protein diet is known to induce glomerular hyperfiltration, as well as hypertrophy of the remnant kidney, and glomerulosclerosis. Whether the diet causes changes in kidney tubule transport via gut microbiome metabolites is still unknown. We hypothesized that protein intake affects not only the intestinal generation and absorption, but also the kidney disposal of microbial amino acid metabolites.</p><p><strong>Methods: </strong>We combined data from animal models and human studies. 5/6th nephrectomy rats were administered a high (HP) or low-protein (LP) diet for 7 weeks. Plasma and urine concentration of the uremic toxins (UTs) indoxyl sulfate (IS), p-cresyl sulfate (PCS) and p-cresyl glucuronide (PCG) were measured. Their fractional excretion (FE) was calculated. The expression of kidney membrane transporters organic anion transporter 1 (OAT1), OAT3, BCRP, OCT2 and MRP4 was analyzed. Differences in FE of UTs between individuals with higher and lower protein intake in two CKD cohorts were sought.</p><p><strong>Results: </strong>CKD rats on an HP diet showed increased plasma levels of PCS and PCG but not IS compared with rats on an LP diet. Conversely, urinary excretion and FE of IS were higher in the HP CKD group. BCRP, MRP4 and OCT2 were not influenced by the diet. OAT1 and OAT3 were upregulated in the HP CKD group. In two independent cohorts of CKD patients, individuals with a high dietary protein intake showed a significantly higher FE of IS.</p><p><strong>Conclusions: </strong>A HP diet leads to a higher generation and/or absorption of amino acid-derived UT precursors in CKD rodent models and humans, most likely via gut microbiome modulation. We demonstrate that dietary protein intake modulates transcription and expression of OAT1 and OAT3, corroborating the existence of the remote sensing and signaling hypothesis. Dietary protein intake influences kidney physiology beyond glomerular filtration.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"739-750"},"PeriodicalIF":4.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361842","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}

{"title":"Intravenous methylprednisolone for nephrotic syndrome with minimal change lesions in adults: a randomized controlled trial.","authors":"Jinxia Chen, Ruting Li, Hua Guo, Tianyu Zhu, Yongzhi Xu, Cuiwei Yao, Huafeng Liu","doi":"10.1093/ndt/gfae208","DOIUrl":"10.1093/ndt/gfae208","url":null,"abstract":"<p><strong>Background: </strong>Patients with minimal change nephrotic syndrome (MCNS) usually experience severe oedema, which can affect the absorption of oral corticosteroid during the first 2 weeks. We conducted a randomized controlled trial (RCT) to compare the efficacy of intravenous (IV) isovalent methylprednisolone induction followed by oral prednisone therapy with conventional oral prednisone therapy in highly oedematous MCNS patients, aiming to provide a better therapy for MCNS patients.</p><p><strong>Methods: </strong>A single-centre, open-label, parallel-arm RCT was performed in the Nephrology Department of the Affiliated Hospital of Guangdong Medical University. Patients who met the inclusion criteria were enrolled in our study from May 2015 to October 2020 and were randomized to receive conventional oral steroid or 2 weeks of IV methylprednisolone followed by oral prednisone.</p><p><strong>Results: </strong>A total of 117 patients were enrolled and randomly assigned to either the sequential group (n = 57) or the oral group (n = 60). The total remission rate in the sequential group was higher than in the oral group after treatment for 2 weeks and 4 weeks (P = .032, P = .027). The complete remission (CR) rate was higher in the sequential group than in the oral group (63.3% versus 41.5%; P = .031) after treatment for 2 weeks. The time to achieve CR was shorter in the sequential group than in the oral group, with a statistically significant difference {14.0 days [95% confidence interval (CI) 13.5-14.5] versus 16.0 days [95% CI 12.7-19.3], P = .024}. There were no significant differences in relapse rate (24.5% versus 28.3%; P = .823) and time to relapse (155 ± 103 days versus 150.7 ± 103.7 days; P = .916) between two groups.</p><p><strong>Conclusion: </strong>This study suggested that highly oedematous MCNS patients who received IV isovalent methylprednisolone induction therapy followed by oral prednisone achieved earlier remission than the conventional oral prednisone regimen without differences in relapse rates or adverse effects. Short-term IV methylprednisolone followed by oral prednisone may be a better choice for MCNS patients with severe oedema.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"731-738"},"PeriodicalIF":4.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SELECT: a 10% reduction in body weight with GLP-1 receptor agonists improves kidney outcomes in overweight and obese patients without diabetes.","authors":"Marieta Theodorakopoulou, Marius Miglinas, Morten Buus Jørgensen","doi":"10.1093/ndt/gfae207","DOIUrl":"10.1093/ndt/gfae207","url":null,"abstract":"","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"617-620"},"PeriodicalIF":4.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292077","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}

{"title":"SGLT2 inhibitors and nephrolithiasis risk: a meta-analysis.","authors":"Mehmet Kanbay, Crischentian Brinza, Sidar Copur, Ozge Sekreter, Alexandru Burlacu, Katherine R Tuttle, Peter Rossing, Adrian Covic","doi":"10.1093/ndt/gfae179","DOIUrl":"10.1093/ndt/gfae179","url":null,"abstract":"<p><strong>Background: </strong>Sodium-glucose co-transporter 2 (SGLT2) inhibitors are novel anti-diabetic medications with potential beneficial effects on cardiovascular and renal outcomes, metabolic parameters and body weight. In addition to the beneficial effects on renal function, including estimated glomerular filtration rate and reduction in proteinuria, recent studies have investigated the potential role of SGLT2 inhibitor (SGLT2i) therapy on nephrolithiasis development. Nephrolithiasis, a condition affecting almost 10% of the general population at least once during a lifetime, is a common disorder with considerable risk for acute and chronic kidney injury and relatively few effective therapeutic options.</p><p><strong>Methods: </strong>We performed a literature search through multiple databases, including PubMed, Ovid MEDLINE, Web of Science, Scopus and Cochrane Library. We followed the systematic review and meta-analysis guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. We included a total of 11 635 698 patients who experienced nephrolithiasis from six clinical trials in this meta-analysis study.</p><p><strong>Results: </strong>In the pooled analysis, nephrolithiasis occurred in 1.27% of patients in the SGLT2i group (n = 739 197), compared with 1.56% of patients (n = 10 896 501) in the control arm (active control, placebo or no therapy). SGLT-2 inhibitor therapy has been associated with a lower risk for nephrolithiasis compared with placebo {odds ratio [OR] 0.61 [95% confidence interval (CI) 0.53-0.70], P < .00001} or active therapy such as glucagon-like peptide 1 and dipeptidyl peptidase 4 inhibitors [OR 0.66 (95% CI 0.47-0.93), P = .02].</p><p><strong>Conclusion: </strong>We demonstrated a lower risk of nephrolithiasis with SGLT2i therapy compared with placebo or active control. Potential underlying mechanisms include osmotic diuresis leading to a reduction in the concentration of lithogenic substances, anti-inflammatory and anti-fibrotic effects and an increase in urine pH. There is a clear need for future large-scale randomized clinical trials evaluating such associations for better understanding.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"671-678"},"PeriodicalIF":4.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902470","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}

{"title":"How complement inhibitors are transforming the management of complement-mediated disorders.","authors":"Pedro H Prata, Régis Peffault de Latour","doi":"10.1093/ndt/gfae231","DOIUrl":"10.1093/ndt/gfae231","url":null,"abstract":"","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":"614-616"},"PeriodicalIF":4.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576542","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}