Reduced guanidinoacetate in plasma of patients with autosomal dominant Fanconi syndrome due to heterozygous P341L variant and study of organoids towards treatment.

Autosomal dominant Fanconi syndrome due to a variant (GATM-FS), causes accumulation of misfolded arginine-glycine amidinotransferase (AGAT) in proximal renal tubules leading to cellular injury. GATM-FS presents during childhood and progresses to end-stage kidney disease (ESKD) in adults. We study creatine metabolism in two individuals of unrelated families with a known variant and the effect of creatine supplementation in kidney organoids.

A pragmatic approach to selective genetic testing in kidney transplant candidates.

Introduction: Advances in the field of genetic testing have spurred its use in transplantation. Potential benefits of genetic testing in transplant nephrology include diagnosis, treatment, risk stratification of recurrent disease, and risk stratification in potential donors. However, it is unclear how to best apply genetic testing in this population to maximize its yield.

Video Images about Decisions for Ethical Outcomes in Kidney Disease (VIDEO-KD): the study protocol for a multi-centre randomised controlled trial.

Introduction: Older patients with advanced chronic kidney disease (CKD) often are inadequately prepared to make informed decisions about treatments including dialysis and cardiopulmonary resuscitation. Further, evidence shows that patients with advanced CKD do not commonly engage in advance care planning (ACP), may suffer from poor quality of life, and may be exposed to end-of-life care that is not concordant with their goals. We aim to study the effectiveness of a video intervention on ACP, treatment preferences and other patient-reported outcomes.

Filter clotting with continuous renal replacement therapy in COVID-19.

Coronavirus disease 2019 (COVID-19) appears to be associated with increased arterial and venous thromboembolic disease. These presumed abnormalities in hemostasis have been associated with filter clotting during continuous renal replacement therapy (CRRT). We aimed to characterize the burden of CRRT filter clotting in COVID-19 infection and to describe a CRRT anticoagulation protocol that used anti-factor Xa levels for systemic heparin dosing.

Assessment of Interobserver Reliability of Nephrologist Examination of Urine Sediment.

Importance: Urine sediment microscopy is commonly performed during the evaluation of kidney disease. Interobserver reliability of nephrologists' urine sediment examination has not been well studied.

Objective: Assess interobserver reliability of the urine sediment examination.

From Theory to Reality: Establishing a Successful Kidney Genetics Clinic in the Outpatient Setting.

Background: Genetic testing in nephrology is increasingly described in the literature and several groups have suggested significant clinical benefit. However, studies to date have described experience from established genetic testing centers or from externally funded research programs.

Methods: We established a kidney genetics clinic within an academic adult general nephrology practice.

Ectopic germinal center and megalin defect in primary Sjogren syndrome with renal Fanconi syndrome.

Background: This study reports the clinical and pathological features of 12 cases of primary Sjogren syndrome (pSS) with renal involvement presenting with proximal tubular dysfunction in a single center, and investigates the possible correlation of ectopic germinal center formation and megalin/cubilin down-expression.

Method: Clinical and pathological records were reviewed. Immunohistochemistry was carried out to detect megalin, cubilin, CD21 and IL-17 expression.

Lupus-like Immune Complex-mediated Glomerulonephritis in Patients with Hepatitis C Virus Infection Treated with Oral, Interferon-free, Direct-acting Antiviral Therapy.

Novel, all-oral interferon-free direct-acting antiviral agents have revolutionized the management of hepatitis C virus (HCV) infection by producing exceptional cure rates with minimal adverse events. While provocation or exacerbation of autoimmunity has been reported in HCV-infected patients receiving interferon, this phenomenon has not been reported in patients receiving interferon-free HCV therapy. We report the occurrence of three cases of lupus-like immune complex-mediated glomerulonephritis occurring shortly after exposure to sofosbuvir-based direct-acting antiviral therapies.

Optimal management of bone mineral disorders in chronic kidney disease and end stage renal disease.

Purpose Of Review: The review summarizes recent studies on chronic kidney disease-mineral bone disorders, with a focus on new developments in disease management.

Recent Findings: The term chronic kidney disease-mineral bone disorder has come to describe an increasingly complex network of alterations in minerals and skeletal disorders that contribute to the significant cardiovascular morbidity and mortality seen in patients with chronic kidney disease and end stage renal disease. Clinical studies continue to suggest associations with clinical outcomes, yet current clinical trials have failed to support causality.

Treatment of hepatitis C virus-associated mixed cryoglobulinemia with direct-acting antiviral agents.

Unlabelled: Hepatitis C virus (HCV) is the most common cause of mixed cryoglobulinemia syndrome (MCS). The efficacy and safety of all-oral direct-acting antiviral (DAA) therapy in HCV-associated MCS (HCV-MCS) is largely unknown. The authors studied case series of patients with HCV-MCS who were treated with sofosbuvir-based regimens and historical controls treated with pegylated interferon and ribavirin in a single health care network.

Reduced expression of Kir6.2/SUR2A subunits explains KATP deficiency in K+-depleted rats.

We investigated on the mechanism responsible for the reduced ATP-sensitive K(+)(K(ATP)) channel activity recorded from skeletal muscle of K(+)-depleted rats. Patch-clamp and gene expression measurements of K(ATP) channel subunits were performed. A down-regulation of the K(ATP) channel subunits Kir6.

Serum sickness following rabbit antithymocyte-globulin induction in a liver transplant recipient: case report and literature review.

Thymoglobulin (Genzyme, Cambridge, MA) is an antithymocyte globulin preparation used for induction immunosuppression therapy in solid organ transplantation. It is being utilized with increasing frequency in orthotopic liver transplantation (OLT) in an effort to minimize or delay the use of calcineurin inhibitors due to their inherent nephrotoxicity. Experience with thymoglobulin in OLT remains limited.

Hybrid assemblies of ATP-sensitive K+ channels determine their muscle-type-dependent biophysical and pharmacological properties.

ATP-sensitive K(+) channels (K(ATP)) are an octameric complex of inwardly rectifying K(+) channels (Kir6.1 and Kir6.2) and sulfonylurea receptors (SUR1 and SUR2A/B), which are involved in several diseases.

Expression and transcriptional control of human KCNE genes.

Potassium channels are essential for a variety of cellular processes ranging from membrane excitability to cellular proliferation. The KCNE genes (KCNE1-5) encode a family of single-transmembrane-domain proteins that modulate the properties of several potassium channels, suggesting a physiologic role for these accessory subunits in many human tissues. To investigate the expression and transcriptional control of KCNE genes we mapped transcription start sites, delineated 5' genomic structure, and characterized functional promoter elements for each gene.

Phenotypic variability and unusual clinical severity of congenital long-QT syndrome in a founder population.

Background: In the congenital long-QT syndrome (LQTS), there can be a marked phenotypic heterogeneity. Founder effects, by which many individuals share a mutation identical by descent, represent a powerful tool to further understand the underlying mechanisms and to predict the natural history of mutation-associated effects. We are investigating one such founder effect, originating in South Africa in approximately ad 1700 and segregating the same KCNQ1 mutation (A341V).

KCNH2-K897T is a genetic modifier of latent congenital long-QT syndrome.

Background: Clinical heterogeneity among patients with long-QT syndrome (LQTS) sharing the same disease-causing mutation is usually attributed to variable penetrance. One potential explanation for this phenomenon is the coexistence of modifier gene alleles, possibly common single nucleotide polymorphisms, altering arrhythmia susceptibility. We demonstrate this concept in a family segregating a novel, low-penetrant KCNH2 mutation along with a common single nucleotide polymorphism in the same gene.

Expression of multiple KCNE genes in human heart may enable variable modulation of I(Ks).

Voltage-gated potassium (K(V)) channels are modulated by at least three distinct classes of proteins including the KCNE family of single transmembrane accessory subunits. In the human genome, KCNE proteins are encoded by five genes designated KCNE1 through KCNE5. KCNE1 associates with KCNQ1 in vitro to generate a potassium current closely resembling the slowly activating delayed rectifier (I(Ks)).