{"title":"Elevated phosphate levels in CKD - a direct threat for the heart.","authors":"Isaac Campos, Christian Faul","doi":"10.1093/ndt/gfaf001","DOIUrl":"https://doi.org/10.1093/ndt/gfaf001","url":null,"abstract":"<p><p>Elevations in systemic phosphate levels, also called hyperphosphatemia, occur in chronic kidney disease (CKD) and during the normal aging process and are associated with various pathologies, such as cardiovascular injury. Experimental studies suggest that at high serum concentrations, phosphate can induce osteogenic differentiation of vascular smooth muscle cells and contribute to vascular calcification. However, the precise underlying mechanism leading to cardiovascular injury is not well understood. Here we discuss how elevations in extracellular phosphate levels could potentially affect cells and intracellular reactions and functions in general. We then zoom in on the heart to discuss whether hyperphosphatemia can have direct pathologic actions beyond inducing vascular calcification. Furthermore, we discuss myocardial calcification as a pathologic event that has not been described and studied in greater detail, but that seems to occur in the context of hyperphosphatemia-induced pathologic cardiac remodeling, as observed in dialysis patients.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984203","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}
Marie-Sophie Pagniez, Victor Fages, Clémence Gatinois, Romain Larrue, Nicolas Pottier, Timothée Laboux, Rémi Lenain, Olivier Grunewald, Thomas Robert, Claire Rigothier, Laurent Mesnard, François Glowacki
{"title":"Exon location of glycine substitutions impacts kidney survival in autosomal dominant Alport Syndrome.","authors":"Marie-Sophie Pagniez, Victor Fages, Clémence Gatinois, Romain Larrue, Nicolas Pottier, Timothée Laboux, Rémi Lenain, Olivier Grunewald, Thomas Robert, Claire Rigothier, Laurent Mesnard, François Glowacki","doi":"10.1093/ndt/gfaf011","DOIUrl":"https://doi.org/10.1093/ndt/gfaf011","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>Unlike X-linked or autosomal recessive Alport Syndrome, no clear genotype/phenotype correlation has yet been demonstrated in patients carrying a single variant of COL4A3 or COL4A4.</p><p><strong>Methods: </strong>We carried out a multicenter retrospective study to assess the risk factors involved in renal survival in patients presenting a single pathogenic variant on COL4A3 or COL4A4.</p><p><strong>Results: </strong>97 patients presenting a single pathogenic variant of COL4A3 or COL4A4 were included. The prevalence of end-stage kidney disease (ESKD) during follow-up was 28.7% (median age 47.5 years [IQR, 39.1-55.8]). 23 patients carried a 'severe' mutation (frameshift, stop gain, extensive deletion, impacting splicing), and 60 patients presented a glycine substitution in a collagenous domain. In patients with glycine missense variants, the location of the mutation in the distal exons was associated with worse renal survival with a more pronounced decline in eGFR compared to variants in proximal exons. Conversely, the presence of a severe mutation did not impact renal survival.</p><p><strong>Conclusion: </strong>Our results confirm that ADAS can lead to ESKD. We demonstrated that a glycine substitution involving the distal exons had a negative impact on renal survival in ADAS patients, probably due to a trimerization defect. This could help improve personalized follow-up in ADAS patients with glycine substitution and could be integrated to a future prognostic score to accurately predict renal outcomes.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984207","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}
Abhi Dutta, Sanchari Chakraborty, Antara Roy, Anupam Mittal, Trayambak Basak
{"title":"Tissue fibrosis in cardiorenal syndrome: crosstalk between heart and kidneys.","authors":"Abhi Dutta, Sanchari Chakraborty, Antara Roy, Anupam Mittal, Trayambak Basak","doi":"10.1093/ndt/gfaf009","DOIUrl":"https://doi.org/10.1093/ndt/gfaf009","url":null,"abstract":"<p><p>Cardiorenal syndrome (CRS) is represented as an intricate dysfunctional interplay between the heart and kidneys, marked by cardiorenal inflammation and fibrosis. Unlike other organs, the repair process in cardiorenal injury involves a regenerative phase characterized by proliferation and polyploidization, followed by a subsequent pathogenic phase of fibrosis. In CRS, acute or chronic cardiorenal injury leads to hyperactive inflammation and fibrotic remodeling, associated with injury-mediated immune cell (Macrophages, Monocytes, and T-cells) infiltration and myofibroblast activation. An inflammatory to fibrotic transition corresponds with macrophage transition (M1-M2) associated with increased TGF-β response. Chronic inflammation disrupts hemodynamic pathways, leading to imbalanced oxidative stress and the production of cytokines and growth factors that promote fibrotic stimulation, contributing to pathological cardiorenal remodeling. The inflammatory response paves the pre-fibrotic cardiorenal niche and drives subsequent fibrotic remodeling by activated myofibroblasts. A fibrotic cardiorenal response in CRS is characterized by increased and degradation-resistant deposition of extracellular proteins especially fibrillar Collagen -I, -III, -V, and non-fibrillar Collagen-IV by active myofibroblasts. Recent advances in basic research animal models of CRS have advanced the knowledge of cardiorenal fibrosis. However, a significant need for clinical applications, trials, and evaluation is still needed. Circulating biomarkers like procollagen peptides and TGF-β have clinically been associated with cardiorenal fibrosis diagnosis in CRS. Treatments targeting the fibrotic pathways have also shown efficacy in amelioration of cardiorenal fibrosis in preclinical models. Recent combination therapies targeting multiple fibrotic pathways have been shown to offer promising results. Understanding the heterogenic pathological progression and fibrogenesis could identify novel therapeutic approaches for clinical CRS diagnosis and treatment.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979322","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}
Beatriz Fernandez-Fernandez, Jose M Valdivielso, Liffert Vogt, Pantelis Sarafidis, Alberto Ortiz
{"title":"Stratified medicine for blood pressure targets in type 2 diabetes mellitus.","authors":"Beatriz Fernandez-Fernandez, Jose M Valdivielso, Liffert Vogt, Pantelis Sarafidis, Alberto Ortiz","doi":"10.1093/ndt/gfaf007","DOIUrl":"https://doi.org/10.1093/ndt/gfaf007","url":null,"abstract":"","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979318","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":"IL-12/23 Blockers Ustekinumab for the Treatment of ANCA-associated Glomerulonephritis.","authors":"Jonas Engesser, Christian F Krebs, Ulf Panzer","doi":"10.1093/ndt/gfaf005","DOIUrl":"https://doi.org/10.1093/ndt/gfaf005","url":null,"abstract":"","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mariam Charkviani, Maria Jose Vargas Brochero, Arjunmohan Mohan, Lisa E Vaughan, Tyler B Sandahl, Andre De Menezes Silva Corrae, Yi Lin, Nelson Leung, Sandra M Herrmann
{"title":"Incidence of Acute Kidney Injury in Relapsed and Refractory Multiple Myeloma treated with Teclistamab versus CAR T-cells.","authors":"Mariam Charkviani, Maria Jose Vargas Brochero, Arjunmohan Mohan, Lisa E Vaughan, Tyler B Sandahl, Andre De Menezes Silva Corrae, Yi Lin, Nelson Leung, Sandra M Herrmann","doi":"10.1093/ndt/gfaf004","DOIUrl":"https://doi.org/10.1093/ndt/gfaf004","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>Teclistamab, a novel bispecific monoclonal antibody targeting CD3 and B-cell maturation antigen (BCMA), and chimeric antigen receptor T-cell (CAR-T) therapy are promising options for treating relapsed/refractory multiple myeloma (MM). However, the rates of acute kidney injury (AKI) associated with teclistamab remain inadequately characterized. This study aims to compare the incidence, severity, and outcomes of AKI between patients receiving teclistamab and CAR-T therapy.</p><p><strong>Methods: </strong>This was a retrospective study involving 64 patients with relapsed/refractory MM treated with either teclistamab or CAR-T therapy. All patients had previously received at least four lines of chemotherapy before being treated with either teclistamab or CAR-T. The primary outcome was the incidence of AKI, and secondary outcomes included AKI severity, kidney recovery rates, and mortality. Kaplan-Meier estimates for AKI-free survival were calculated, and hazard ratios (HRs) for AKI risk were determined using Cox proportional hazards models.</p><p><strong>Results: </strong>Sixty-four patients met inclusion criteria for this study (30 received CAR-T and 34 received teclistamab therapy). Among these patients, 14 AKI events occurred in total (22%), with 10 events (29%) in the teclistamab group and 4 events (13%) in the CAR-T group. AKI-free survival estimates at 180 days after treatment initiation were 68% (95% confidence interval [CI]: 53%-87%) for teclistamab patients and 90% (95% CI: 79%-100%) for CAR-T patients. While patients receiving teclistamab were found to have an increased risk of an AKI event compared to those receiving CAR-T therapy, the results were not statistically significant (HR [95% CI]: 3.38 [0.93-12.31], P = 0.065).</p><p><strong>Conclusions: </strong>This study suggests that patients treated with teclistamab may experience a higher incidence of AKI compared to those receiving CAR-T therapy. However, further research is required to determine whether this increased risk is attributable to disease progression or teclistamab itself. These results highlight the need for close kidney function monitoring in patients receiving teclistamab.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979341","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}
Arend Bökenkamp, Gema Ariceta, Detlef Böckenhauer, Olivier Devuyst, Francesco Emma, David van Bennekom, Elena Levtchenko, John Sayer, Aude Servais, Rosa Vargas, Marcin Zaniew, Larisa Prikhodina
{"title":"Dent disease: Clinical Practice Recommendations.","authors":"Arend Bökenkamp, Gema Ariceta, Detlef Böckenhauer, Olivier Devuyst, Francesco Emma, David van Bennekom, Elena Levtchenko, John Sayer, Aude Servais, Rosa Vargas, Marcin Zaniew, Larisa Prikhodina","doi":"10.1093/ndt/gfaf003","DOIUrl":"https://doi.org/10.1093/ndt/gfaf003","url":null,"abstract":"<p><p>Dent disease is a rare X-linked tubulopathy that is characterized by low-molecular-weight (LMW) proteinuria associated with hypercalciuria, which may lead to nephrolithiasis, nephrocalcinosis, and kidney failure between the 3rd and the 5th decades of life in 30-80% of affected males. The disease is most often associated with various manifestations of proximal tubular dysfunction. Affected individuals may present nephrotic range proteinuria which may be misinterpreted and cause diagnostic delay. Due to its rarity, there is limited evidence to guide diagnosis and management. This clinical practice recommendations summarize the current knowledge on Dent disease and provide guidance for diagnosis and management. The recommendations are based on a systematic search of the literature and were endorsed by a Delphi procedure among stakeholders in the field as well as the respective ERA and ESPN working groups.</p>","PeriodicalId":19078,"journal":{"name":"Nephrology Dialysis Transplantation","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142966097","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}