Search

More than 800 million people in the world suffer from chronic kidney disease (CKD). Genome-wide association studies (GWAS) have identified hundreds of loci where genetic variants are associated with kidney function; however, causal genes and pathways for CKD remain unknown. Here, we performed integration of kidney function GWAS and human kidney–specific expression quantitative trait analysis and identified that the expression of beta-mannosidase (MANBA) was lower in kidneys of subjects with CKD risk genotype. We also show an increased incidence of renal failure in subjects with rare heterozygous loss-of-function coding variants in MANBA using phenome-wide association analysis of 40,963 subjects with exome sequencing data. MANBA is a lysosomal gene highly expressed in kidney tubule cells. Deep phenotyping revealed structural and functional lysosomal alterations in human kidneys from subjects with CKD risk alleles and mice with genetic deletion of Manba. Manba heterozygous and knockout mice developed more severe kidney fibrosis when subjected to toxic injury induced by cisplatin or folic acid. Manba loss altered multiple pathways, including endocytosis and autophagy. In the absence of Manba, toxic acute tubule injury induced inflammasome activation and fibrosis. Together, these results illustrate the convergence of common noncoding and rare coding variants in MANBA in kidney disease development and demonstrate the role of the endolysosomal system in kidney disease development.

Poor sleep shows potential causal relationship with risk of developing chronic kidney disease.

Does SARS-CoV-2 infection have long-term effects on the kidney? SARS-CoV2 infection and the associated clinical disease, coronavirus disease-19 (COVID-19), have resulted in more than 20 million infections worldwide with an overall mortality rate of 3 9% Initially thought to be a disease of the respiratory system, the clinical syndrome of COVID-19 is actually multifaceted, also affecting the heart, vasculature, and neurological system Acute kidney injury (AKI) is a common complication, affecting up to 40% of patients hospitalized with COVID-19, with 20% of these patients needing acute hemodialysis Along with the shortage of ventilators that has been amply discussed, hospitals suffered from an acute shortage of dialysis machines during case surges Although the epidemiology of in-hospital AKI has been shown before in reports from China, Europe, and the United States of America, Fisher et al delved deeper into the effects of COVID-19 on the kidney They retrospectively evaluated AKI incidence, risk factors, and outcomes for hospitalized adult patients with and without COVID-19 in a large New York City health system They showed increased AKI incidence, greater need for acute dialysis, and higher mortality in those with COVID-19 They also identified several factors that were significantly associated with AKI, regardless of COVID-19 status Critically, they also assessed how many individuals recovered kidney function during hospitalization after an AKI episode Only 42% of patients with COVID-19 and AKI recovered baseline kidney function compared to 70% without COVID-19 Considering the substantial evidence linking in-hospital AKI, and more importantly, non-recovery of kidney function after an acute episode, with long-term mortality and worse kidney function, this may herald the onset of a coming post-COVID kidney disease epidemic This may be worsened by the fact that regular physician visits have decreased during this pandemic, and as a result, many patients with chronic disease may not be monitored regularly Although the research and medical community's focus has been on the acute care of patients with COVID-19, the long-term effects of infection are slowly coming into focus Integrated research and clinical care approaches are urgently needed to better understand and address what is likely to be a growing at-risk population

Multimodal measurements and machine learning provide evidence for personalized dietary advice.

Multifaceted nonpharmaceutical interventions supported by data restricted spread of COVID-19 in China.

suPAR might serve as a biomarker for prediction of acute kidney injury with possible therapeutic implications.