Complement alternative pathway determines disease susceptibility and severity in antineutrophil cytoplasmic antibody (ANCA) –associated vasculitis.
Activation of the alternative pathway (AP) of complement is involved in the pathogenesis of antineutrophil cytoplasmic antibody (ANCA) –associated vasculitis (AAV), although the underlying molecular mechanisms are unclear. To gain insight into the role of the AP, common gene variants in CFH/CFHR1-5, CFB, C3 and MCP, and longitudinal determinations of plasma C3, C4, FH, FHR-1, FHR-2, FHR-5, FB, properdin and sC5b-9 levels were ana lyzed in a Spanish AAV cohort consisting of 102 patients; 54 with active AAV (active cohort) and 48 in remission not receiving immunosuppressants or dialysis therapy (remission cohort). (Source:...
Source: Kidney International - November 1, 2023 Category: Urology & Nephrology Authors: Laura Lucientes-Continente, Gema Fern ández-Juárez, Bárbara Márquez-Tirado, Laura Jiménez-Villegas, Mercedes Acevedo, Teresa Cavero, Luís Sánchez Cámara, Juliana Draibe, Paula Anton-Pampols, Fernando Caravaca-Fontán, Manuel Praga, Javier Villacor Tags: clinical investigation Source Type: research
Unveiling a new era with liquid chromatography coupled with mass spectrometry to enhance parathyroid hormone measurement in patients with chronic kidney disease.
Precise determination of circulating parathyroid hormone (PTH) concentration is crucial to diagnose and manage various disease conditions, including the chronic kidney diseases-mineral and bone disorder. However, the lack of standardization in PTH assays is challenging for clinicians, potentially leading to medical errors because the different assays do not provide equivalent results and use different reference ranges. Here, we aimed to evaluate the impact of recalibrating PTH immunoassays by means of a recently developed LC-MS/MS method as the reference. (Source: Kidney International)
Source: Kidney International - October 31, 2023 Category: Urology & Nephrology Authors: Etienne Cavalier, Jordi Farr é-Segura, Pierre Lukas, Anne-Sophie Gendebien, Stéphanie Peeters, Philippe Massonnet, Caroline Le Goff, Antoine Bouquegneau, Jean-Claude Souberbielle, Vincent Delatour, Pierre Delanaye Tags: clinical investigation Source Type: research
Pretransplant screening for coronary artery disease: data are required before practice change
Declining rates of peritransplant cardiovascular death, an increasing burden of pretransplant tests, and concerns about the effectiveness of screening candidates for coronary artery disease have led many transplant programs to de-escalate screening protocols. Recent Kidney Disease: Improving Global Outcomes and American Heart Association scientific statements and guidelines neatly summarize current evidence, but also identify areas of need. Here, we argue that key questions should be addressed by adequately powered clinical trials before our long-held screening paradigms are completely rewritten. (Source: Kidney International)
Source: Kidney International - October 30, 2023 Category: Urology & Nephrology Authors: John S. Gill, Steven J. Chadban Tags: Mini Review Source Type: research
Pre-transplant screening for coronary artery disease: data are required before practice change.
Declining rates of peri-transplant cardiovascular death, an increasing burden of pre-transplant tests and concerns over the effectiveness of screening candidates for coronary artery disease have led many transplant programs to de-escalate screening protocols. Recent KDIGO and American Heart Association scientific statements and guidelines neatly summarize current evidence, but also identify areas of need. Here, we argue that key questions should be addressed by adequately powered clinical trials before our long-held screening paradigms are completely re-written. (Source: Kidney International)
Source: Kidney International - October 30, 2023 Category: Urology & Nephrology Authors: John S. Gill, Steven J. Chadban, John S. Gill Tags: mini review Source Type: research
Results of a randomized double-blind placebo-controlled Phase 2 study propose iptacopan as an alternative complement pathway inhibitor for IgA nephropathy.
Targeting the alternative complement pathway is an attractive therapeutic strategy given its role in the pathogenesis of immunoglobulin A nephropathy (IgAN). Iptacopan (LNP023) is an oral, proximal alternative complement inhibitor that specifically binds to Factor B. Our randomized, double-blind, parallel-group adaptive Phase 2 study (NCT03373461) enrolled patients with biopsy-confirmed IgAN (within previous three years) with estimated glomerular filtration rates of 30 mL/min/1.73 m2 and over and urine protein 0.75 g/24 hours and over on stable doses of renin angiotensin system inhibitors. (Source: Kidney International)
Source: Kidney International - October 30, 2023 Category: Urology & Nephrology Authors: Hong Zhang, Dana V. Rizk, Vlado Perkovic, Bart Maes, Naoki Kashihara, Brad Rovin, Hern án Trimarchi, Ben Sprangers, Matthias Meier, Dmitrij Kollins, Olympia Papachristofi, Julie Milojevic, Guido Junge, Prasanna Kumar Nidamarthy, Alan Charney, Jonathan Ba Tags: clinical trial Source Type: research
The transcription factor GATA6 accelerates vascular smooth muscle cell senescence-related arterial calcification by counteracting the role of anti-aging factor SIRT6 and impeding DNA damage repair
Arterial calcification is a hallmark of vascular pathology in the elderly and in individuals with chronic kidney disease (CKD). Vascular smooth muscle cells (VSMCs), after attaining a senescent phenotype, are implicated in the calcifying process. However, the underlying mechanism remains to be elucidated. Here, we reveal an aberrant upregulation of transcriptional factor GATA6 in the calcified aortas of humans, mice with CKD and mice subjected to vitamin D3 injection. Knockdown of GATA6, via recombinant adeno-associated virus carrying GATA6 shRNA, inhibited the development of arterial calcification in mice with CKD. (Sourc...
Source: Kidney International - October 30, 2023 Category: Urology & Nephrology Authors: Xiaoxue Li, Aiting Liu, Chen Xie, Yanlian Chen, Kuan Zeng, Changming Xie, Zhengzhipeng Zhang, Pei Luo, Hui Huang Tags: basic research Source Type: research
A pragmatic, open-label, randomized controlled trial of Plasma-Lyte-148 versus standard intravenous fluids in children receiving kidney transplants (PLUTO).
Acute electrolyte and acid-base imbalance is experienced by many children following kidney transplant. This is partly because doctors give very large volumes of artificial fluids to keep the new kidney working. When severe, fluid imbalance can lead to seizures, cerebral edema and death. In this pragmatic, open-label, randomized controlled trial, we randomly assigned (1:1) pediatric kidney transplant recipients to Plasma-Lyte-148 or standard of care perioperative intravenous fluids (predominantly 0.45% sodium chloride and 0.9% sodium chloride solutions). (Source: Kidney International)
Source: Kidney International - October 30, 2023 Category: Urology & Nephrology Authors: Wesley N. Hayes, Emma Laing, Rosemary Brown, Laura Silsby, Laura Smith, Helen Thomas, Fotini Kaloyirou, Rupa Sharma, James Griffiths, Helen Hume-Smith, Stephen D. Marks, Nicos Kessaris, Martin Christian, Jan Dudley, Mohan Shenoy, Michal Malina, Mordi Muor Tags: clinical trial Source Type: research
Exploiting the neonatal crystallizable fragment receptor to treat kidney disease
The neonatal crystallizable fragment receptor (FcRn) was initially discovered as the receptor that allowed passive immunity in newborns by transporting maternal IgG through the placenta and enterocytes. Since its initial discovery, FcRn has been found to exist throughout all stages of life and in many different cell types. Beyond passive immunity, FcRn is necessary for intrinsic albumin and IgG recycling and is important for antigen processing and presentation. Given its multiple important roles, FcRn has been used in many disease treatments including a new class of agents that were developed to inhibit FcRn for the treatm...
Source: Kidney International - October 27, 2023 Category: Urology & Nephrology Authors: James F. Dylewski, George Haddad, Judith Blaine Tags: Review Source Type: research
Exploiting the neonatal Fc receptor to treat kidney disease
The neonatal Fc receptor (FcRn) was initially discovered as the receptor that allowed passive immunity in newborns by transporting maternal IgG through the placenta and enterocytes. Since its initial discovery, FcRn has been found to exist throughout all stages of life and in many different cell types. Beyond passive immunity, FcRn is necessary for intrinsic albumin and IgG recycling and is important for antigen processing and presentation. Given its multiple important roles, FcRn has been utilized in many disease treatments including a new class of agents that were developed to inhibit FcRn for treatment of a variety of a...
Source: Kidney International - October 27, 2023 Category: Urology & Nephrology Authors: James F. Dylewski, George Haddad, Judith Blaine Tags: review Source Type: research
A central role for mesangial cells in the initiation of diabetic nephropathy
More than 35 years ago, it was postulated that mesangial cells represent a special form of microvascular pericytes that “not only occupy a central anatomical position in the glomerulus but may also deserve this role functionally.”1 Accumulating clinical and experimental evidence has since demonstrated the important functional properties of mesangial cells in kidney homeostasis, as they provide key structural supp ort for glomerular capillary loops, regulate capillary flow, and play an essential role in mediating glomerular crosstalk. (Source: Kidney International)
Source: Kidney International - October 18, 2023 Category: Urology & Nephrology Authors: Zhengying Fang, Kyung Lee, John Cijiang He Tags: Nephrology Digest Source Type: research
“Nailing” chronicity in kidney disease
An 80-year-old woman presented with a 2-week history of vomiting and failure to thrive. The results of laboratory testing revealed a serum creatinine level of 10 mg/dl. The patient was not known to the hospital, and no previous serum creatinine level was available. The presence of distinctive nail changes on physical examination (Figure 1) guided the diagnosis toward a chronic progressive kidney disease, confirmed later by the presence of bilateral atrophic kidneys on abdomen ultrasound. (Source: Kidney International)
Source: Kidney International - October 18, 2023 Category: Urology & Nephrology Authors: Najat I. Joubran, Helena P. Salem Tags: Nephrology Image Source Type: research
A rare combination of hydronephrosis, megaureter, and hyperphosphatasia
A female term-born infant presented with muscular hypotonia, brachydactyly, and dysmorphic features, such as deep-seated ears, submucosal cleft palate, and hypertelorism (Supplementary Figure S1). She developed acute kidney injury and abdominal distention, without meconium evacuation for 48 hours. Moreover, laboratory findings showed a 5-fold increase in alkaline phosphatase levels (normal range, 1.61–5.3 μkat/l), without liver or bone metabolism disorder. Abdominal magnetic resonan ce imaging revealed bilateral dysplastic multicystic kidneys with right-sided massive hydronephrosis and bilateral megaureters with ectop...
Source: Kidney International - October 18, 2023 Category: Urology & Nephrology Authors: Lea Maria Merz, Julia Hentschel, Christian Roth, Manuela Siekmeyer, Katalin Dittrich, Friederike Petzold Tags: Nephrology Image Source Type: research
The Case | Acute kidney injury after a party
A 34-year-old patient (Mahoran) with no medical history presented to the emergency department with diffuse abdominal and lumbar pain, myalgia, and nausea. Recent history revealed only the consumption of alcohol and soft drinks 2 days before the onset of symptoms. He was exposed to still water and trash in his job. He never traveled out of France since he migrated 10 years ago. (Source: Kidney International)
Source: Kidney International - October 18, 2023 Category: Urology & Nephrology Authors: Thibault Letellier, Jeremy Debraux, Jimmy Grellier, Romain Collot, Gr égoire Couvrat-Desvergnes, Anne Moreau, Awena Le Fur Tags: Make Your Diagnosis Source Type: research
Is hemodiafiltration superior to hemodialysis in patients with kidney failure?
Hemodiafiltration and hemodialysis are 2 accepted therapies for patients with end-stage kidney disease (ESKD), although the former is more commonly favored in Europe, whereas the latter is the primary treatment available in the United States. A prior pooled analysis of participant-level data from 4 randomized, controlled trials involving 2793 participants suggested a survival benefit for hemodiafiltration compared with hemodialysis, especially when a convection volume was delivered at a high dose, with a putative threshold of at least 23 L per session in postdilution mode. (Source: Kidney International)
Source: Kidney International - October 18, 2023 Category: Urology & Nephrology Authors: Tilman B. Dr üeke, T. Alp Ikizler Tags: Nephrology Digest Source Type: research
The authors reply
We thank Szili-Torok et al.1 for their interest in our study, in which we showed that a set of machine learning (ML) models does not outperform a validated Cox-based prediction system (CBPS) in predicting kidney-allograft failure. (Source: Kidney International)
Source: Kidney International - October 18, 2023 Category: Urology & Nephrology Authors: Agathe Truchot, Marc Raynaud, Alexandre Loupy Tags: Letter to the Editor Source Type: research
