Whole body resistance training on functional outcomes of patients with Stage 4 or 5 chronic kidney disease: A systematic review.

Chronic kidney disease (CKD) causes skeletal muscle wasting, resulting in reduced function and inability to live independently. This systematic review critically appraised the scientific literature regarding the effects of full-body resistance training on clinically-relevant functional capacity measures in CKD. The study population included studies of people with Stage 4 or 5 CKD and a mean age of 40+ years old.

Clonal hematopoiesis of indeterminate potential contributes to accelerated chronic kidney disease progression.

Background: Clonal hematopoiesis of indeterminate potential (CHIP) is a common inflammatory condition of aging that causes myriad end-organ damage. We have recently shown associations for CHIP with acute kidney injury and with kidney function decline in the general population, with stronger associations for CHIP driven by mutations in genes other than (non- CHIP). Longitudinal kidney function endpoints in individuals with pre-existing chronic kidney disease (CKD) and CHIP have been examined in two previous studies, which reported conflicting findings and were limited by small sample sizes.

Kidney Volume and Risk of Incident Kidney Outcomes.

Background: Low total kidney volume (TKV) is a risk factor for chronic kidney disease (CKD). However, evaluations of nonlinear relationships, incident events, causal inference, and prognostic utility beyond traditional biomarkers are lacking.

Methods: TKV, height-adjusted TKV, and body surface area-adjusted TKV (BSA-TKV) of 34,595 White British ancestry participants were derived from the UK Biobank.

How Does ADPKD Severity Differ Between Family Members?

Thousands of pathogenic variants in more than 100 genes can cause kidney cysts with substantial variability in phenotype and risk of subsequent kidney failure. Despite an established genotype-phenotype correlation in cystic kidney diseases, incomplete penetrance and variable disease expressivity are present as is the case in all monogenic diseases. In family members with autosomal dominant polycystic kidney disease (ADPKD), the same causal variant is responsible in all affected family members; however, there can still be striking discordance in phenotype severity.

Clonal hematopoiesis of indeterminate potential is associated with acute kidney injury.

Age is a predominant risk factor for acute kidney injury (AKI), yet the biological mechanisms underlying this risk are largely unknown. Clonal hematopoiesis of indeterminate potential (CHIP) confers increased risk for several chronic diseases associated with aging. Here we sought to test whether CHIP increases the risk of AKI.

Clonal hematopoiesis of indeterminate potential-associated non-small cell lung cancer risk is potentiated by small particulate matter air pollution among non-smokers: a novel somatic variant-environment interaction.

Small particulate matter air pollution (PM ) is a recognized driver of non-small cell lung cancer (NSCLC) among non-smoking individuals. Inhaled PM recruits pro-inflammatory macrophages to the air-lung interface, which promotes malignant lung epithelial cell growth and progression to overt cancer. We sought to determine whether clonal hematopoiesis of indeterminate potential (CHIP), a common age-related condition characterized by hyperinflammatory macrophages, exacerbates PM -associated NSCLC in non-smokers using genetic, environmental, and phenotypic data from 413,901 individuals in the UK Biobank.

The Good and the Bad of SHROOM3 in Kidney Development and Disease: A Narrative Review.

Purpose Of Review: Multiple large-scale genome-wide association meta-analyses studies have reliably identified an association between genetic variants within the gene and chronic kidney disease. This association extends to alterations in known markers of kidney disease including baseline estimated glomerular filtration rate, urinary albumin-to-creatinine ratio, and blood urea nitrogen. Yet, an understanding of the molecular mechanisms behind the association of SHROOM3 and kidney disease remains poorly communicated.

Assessing the Risk of Progression to Kidney Failure in Patients With Autosomal Dominant Polycystic Kidney Disease.

While autosomal dominant polycystic kidney disease (ADPKD) is a dichotomous diagnosis, substantial variability in disease severity exists. Identification of inherited risk through family history, genetic testing, and environmental risk factors through clinical assessment are important components of risk assessment for optimal management of patients with ADPKD. Genetic testing is especially helpful in cases with diagnostic uncertainty, particularly in cases with no apparent family history, in young cases (age less than 25 years) where a definitive diagnosis is sought, or in atypical presentations with early, severe, or discordant findings.

Clonal haematopoiesis, ageing and kidney disease.

Clonal haematopoiesis of indeterminate potential (CHIP) is a preclinical condition wherein a sizeable proportion of an individual's circulating blood cells are derived from a single mutated haematopoietic stem cell. CHIP occurs frequently with ageing - more than 10% of individuals over 65 years of age are affected - and is associated with an increased risk of disease across several organ systems and premature death. Emerging evidence suggests that CHIP has a role in kidney health, including associations with predisposition to acute kidney injury, impaired recovery from acute kidney injury and kidney function decline, both in the general population and among those with chronic kidney disease.

A novel multi-ancestry proteome-wide Mendelian randomization study implicates extracellular proteins, tubular cells, and fibroblasts in estimated glomerular filtration rate regulation.

Estimated glomerular filtration rate (eGFR) impacts the concentration of plasma biomarkers confounding biomarker association studies of eGFR with reverse causation. To identify biomarkers causally associated with eGFR, we performed a proteome-wide Mendelian randomization study. Genetic variants nearby biomarker coding genes were tested for association with plasma concentration of 1,161 biomarkers in a multi-ancestry sample of 12,066 participants from the Prospective Urban and Rural Epidemiological (PURE) study.

Basic Research Protocol: Exome Sequencing in Adults With Loin Pain Hematuria Syndrome: A Pilot Study.

Background: Loin pain hematuria syndrome (LPHS) is a poorly understood clinical syndrome characterized by hematuria and either unilateral or bilateral severe kidney pain in the absence of identifiable urological disease. Loin pain hematuria syndrome imposes a significant health and economic impact with a loss of productivity and quality of life in a young population. Owing to an incomplete understanding of its pathophysiology, treatment has been limited to nonspecific pain management.

Clonal Hematopoiesis of Indeterminate Potential is Associated with Acute Kidney Injury.

Age is a predominant risk factor for acute kidney injury (AKI), yet the biological mechanisms underlying this risk are largely unknown and to date no genetic mechanisms for AKI have been established. Clonal hematopoiesis of indeterminate potential (CHIP) is a recently recognized biological mechanism conferring risk of several chronic aging diseases including cardiovascular disease, pulmonary disease and liver disease. In CHIP, blood stem cells acquire mutations in myeloid cancer driver genes such as and and the myeloid progeny of these mutated cells contribute to end-organ damage through inflammatory dysregulation.

Atypical Polycystic Kidney Disease as defined by Imaging.

Using age- and height-adjusted total kidney volume, the Mayo Clinic Imaging Classification provides a validated approach to assess the risk of chronic kidney disease (CKD) progression in autosomal dominant polycystic kidney disease (ADPKD), but requires excluding patients with atypical imaging patterns, whose clinical characteristics have been poorly defined. We report an analysis of the prevalence, clinical and genetic characteristics of patients with atypical polycystic kidney disease by imaging. Patients from the extended Toronto Genetic Epidemiology Study of Polycystic Kidney Disease recruited between 2016 and 2018 completed a standardized clinical questionnaire, kidney function assessment, genetic testing, and kidney imaging by magnetic resonance or computed tomography.

A practical approach to curate clonal hematopoiesis of indeterminate potential in human genetic data sets.

Clonal hematopoiesis of indeterminate potential (CHIP) is a common form of age-related somatic mosaicism that is associated with significant morbidity and mortality. CHIP mutations can be identified in peripheral blood samples that are sequenced using approaches that cover the whole genome, the whole exome, or targeted genetic regions; however, differentiating true CHIP mutations from sequencing artifacts and germ line variants is a considerable bioinformatic challenge. We present a stepwise method that combines filtering based on sequencing metrics, variant annotation, and population-based associations to increase the accuracy of CHIP calls.