CAKUT subtypes determine the rate of progression to kidney failure - an adult patient cohort study.

Background And Hypothesis: Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) are the leading cause of pediatric kidney failure (KF) and a significant contributor to KF in adults. Progression to KF varies widely. Early renal risk stratification is challenging, due to a lack of data on long-term kidney outcomes during adulthood.

In vivo base editing reduces liver cysts in autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent genetic kidney disorder, affecting over 10 million individuals worldwide. Cystic expansion typically progresses to kidney failure and also involves the liver with limited treatment options. Pathogenic variants in PKD1 or PKD2 account for 85%-90% of cases.

Structure-Activity Analysis Reveals Perturbed Cilia-Jun N-Terminal Kinase Signaling in MAPKBP1-Associated Kidney Disease.

Introduction: Nephronophthisis (NPH) is a renal ciliopathy characterized by chronic tubulointerstitial fibrosis. Despite discovery of multiple disease genes, mechanisms of NPH-associated kidney degeneration remain poorly understood. In this study, we present details of clinical and molecular mechanisms of () loss-of-function.

Polygenic prediction of body mass index and obesity through the life course and across ancestries.

Polygenic scores (PGSs) for body mass index (BMI) may guide early prevention and targeted treatment of obesity. Using genetic data from up to 5.1 million people (4.

Valosin-containing protein in ciliary morphology: a novel target in ADPKD.

Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary disorder leading to kidney cyst formation and loss of kidney function. The major causative genes and encode for the ciliary proteins polycystin-1 (PC1) and polycystin-2 (PC2), respectively, which are involved in ciliary functions. Within -defective cells, the accumulation of misfolded PC1 proteins triggers the unfolded protein response (UPR).

-p.Gly624Asp is the Predominant Variant in Europe Associated With a Mild Alport Syndrome Phenotype.

Introduction: Pathogenic variants in are common causes of inherited kidney disease. The clinical presentation extends from classical Alport syndrome (AS) to focal segmental glomerulosclerosis (FSGS) without extrarenal manifestation. In this study, we aimed to assess the genetic and phenotypic spectrum, along with the associated natural histories, in a cohort of patients with AS from 3 tertiary centers in Central Europe.

Multicentre pragmatic embedded stepped wedge cluster randomised trial comparing glucose 5% with sodium chloride 0.9% as the default drug diluent in the ICU: the sweet-water trial protocol.

Introduction: Hypernatraemia, defined as a plasma sodium concentration >145 mmol/L, is a frequent complication in critically ill patients treated in the intensive care unit (ICU) (= ICU-acquired hypernatraemia), with reported prevalence ranging from 4% to 26%. Hypernatraemia adversely affects various physiological functions and is associated with delirium, prolonged length of stay and increased ICU and post-discharge mortality. The sodium load from intravenous drug diluents significantly contributes to ICU-acquired hypernatraemia, with drug infusions comprising about 30% of the daily fluid volume of an average ICU patient.

Vascular Access Thrombosis Events in Patients With Dialysis-Dependent CKD Treated With Vadadustat or Darbepoetin Alfa: The INNOVATE Trial Program.

Rationale & Objective: In the global phase 3 INNOVATE program of patients with dialysis-dependent chronic kidney disease (DD-CKD) and CKD-related anemia (2 trials: patients new to [NCT02865850] and established on maintenance dialysis [NCT02892149]), vadadustat was noninferior to the erythropoiesis-stimulating agent darbepoetin alfa for cardiovascular safety and hemoglobin efficacy. Here, we investigated between-group differences in positively adjudicated vascular access thrombosis (VAT) events.

Study Design: Phase 3, global, open-label, randomized, active-controlled clinical trials.

base editing reduces liver cysts in autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent genetic kidney disorder, affecting over 10 million individuals worldwide. Cystic expansion typically progresses to kidney failure and also involves the liver with limited treatment options. Pathogenic variants in or account for 85-90% of cases.

Coupling metabolomics and exome sequencing reveals graded effects of rare damaging heterozygous variants on gene function and human traits.

Genetic studies of the metabolome can uncover enzymatic and transport processes shaping human metabolism. Using rare variant aggregation testing based on whole-exome sequencing data to detect genes associated with levels of 1,294 plasma and 1,396 urine metabolites, we discovered 235 gene-metabolite associations, many previously unreported. Complementary approaches (genetic, computational (in silico gene knockouts in whole-body models of human metabolism) and one experimental proof of principle) provided orthogonal evidence that studies of rare, damaging variants in the heterozygous state permit inferences concordant with those from inborn errors of metabolism.

Association of Serum Afamin Concentrations With Kidney Failure in Patients With CKD: Findings From the German CKD Cohort Study.

Rationale & Objective: Afamin is a vitamin E-binding glycoprotein primarily expressed in the liver and kidney. This study investigated whether serum afamin concentrations are associated with kidney function and incident kidney failure.

Study Design: Prospective cohort study with 6.

Integrated Use of Autosomal Dominant Polycystic Kidney Disease Prediction Tools for Risk Prognostication.

Key Points: The Mayo clinic imaging classification and the predicting renal outcome in polycystic kidney disease score are used to assess the risk of progression to kidney failure in autosomal dominant polycystic kidney disease. Mayo imaging classification and predicting renal outcome in polycystic kidney disease show little concordance; combined use increased the ability to identify rapid progression especially among intermediate risk patients. Accurate risk prediction is key for determining indication for specific treatment.

Donor-derived cell-free DNA monitoring for early diagnosis of antibody-mediated rejection after kidney transplantation: a randomized trial.

Background: Donor-derived cell-free DNA (dd-cfDNA) shows good diagnostic performance for the detection of antibody-mediated rejection (AMR) in kidney transplant recipients (KTR). However, the clinical benefits of dd-cfDNA monitoring need to be established. Early diagnosis of AMR at potentially reversible stages may be increasingly important due to emerging treatment options for AMR.

Kidney transplantation in patients with polycystic kidney disease: increased risk of infection does not compromise graft and patient survival.

Background: Patients with autosomal dominant polycystic kidney disease (ADPKD) represent >10% of patients awaiting kidney transplantation. These patients are prone to potentially severe urinary tract (UTI) and liver cyst infections after transplantation. Whether such infections compromise outcome is unclear.

Lipoprotein(a) concentrations and cardiovascular disease in patients with chronic kidney disease: Results from the German Chronic Kidney Disease study.

Background: Lipoprotein(a) (Lp(a)) is a causal, genetically determined risk factor for cardiovascular disease (CVD) in the general population. Patients with chronic kidney disease (CKD) have an increased CVD risk and elevated Lp(a) concentrations. Only a few studies on Lp(a) were performed in persons with mild-to-moderate CKD; none of them used genetic variants to explore potential causal associations.

Long-term outcomes of patients with IgA nephropathy in the German CKD cohort.

Background: The importance of albuminuria as opposed to proteinuria in predicting kidney outcomes in primary immunoglobulin A nephropathy (IgAN) is not well established.

Methods: From 2010 to 2012, 421 patients with biopsy-proven IgAN have been enrolled into the German Chronic Kidney Disease (GCKD) cohort, a prospective observational cohort study ( = 5217). Adjudicated endpoints include a composite kidney endpoint (CKE) consisting of eGFR decline >40%, eGFR <15 ml/min/1.