Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline

Abstract

M Gorski et al.: Rapid kidney function decline c l i n i c a l i n v e s t i g a t i o n

Distinct Mitochondrial Pathologies Caused by Mutations of the Proximal Tubular Enzymes EHHADH and GATM

“…It is also important not to consider mitochondria as isolated organelles: The crosstalk between mitochondria, cytosol, endoplasmic reticulum, and nucleus is of significant importance for understanding acute and chronic kidney diseases ( Mulay et al, 2016 ; Romagnani et al, 2017 ; Hill et al, 2018 ). This hypothesis is underlined by the pathophysiology of mitochondriopathies affecting the kidney ( O’Toole, 2014 ; Finsterer and Scorza, 2017 ; Lemaire, 2021 ; examples given in Table 1 ) and by gene loci of nuclear-encoded mitochondrial proteins 6 that are associated with kidney function in genome-wide association studies ( Wuttke et al, 2019 ; Gorski et al, 2021 ; examples given in Table 2 ).…”

“…Due to its strong dependence on oxidative energy production and specific metabolic pathways, the proximal tubule is susceptible for pathological mutations of genes encoding its specific subset of mitochondrial proteins; however, the same mutated proteins might be irrelevant in other kidney segments or other tissues. led to the identification of many gene loci associated with renal function (Teumer et al, 2019;Wuttke et al, 2019;Schlosser et al, 2020;Gorski et al, 2021). Some of these loci contain genes encoding proteins that are imported into mitochondria (Table 2).…”

“…Table 1 shows examples of mitochondrial diseases affecting the kidney. Moreover, in recent years, large-scale genome-wide association studies have led to the identification of many gene loci associated with renal function ( Teumer et al, 2019 ; Wuttke et al, 2019 ; Schlosser et al, 2020 ; Gorski et al, 2021 ). Some of these loci contain genes encoding proteins that are imported into mitochondria ( Table 2 ).…”

Nomogram to Predict Rapid Kidney Function Decline in Population at Risk of Cardiovascular Disease

“…And for the community primary care, proteinuria is often measured in patients with DM, so our nomogram maybe more available for the community health institution. Second, the nomogram developed in our study just incorporated routinely collected data, its predictive accuracy could be enhanced by adding newly identi ed biomarkers or genotype data of RKFD (30). Third, there was no external validation of our model, although it shows good Cindex and AUCs in the internal validation cohort.…”

Genetic kidney diseases as an underrecognized cause of chronic kidney disease: the key role of international registry reports

“…The heritability of the estimated glomerular filtration rate has been suggested to be somewhere between 6% and 30% in the general population [ 15–17 ], and several loci have been reported to be associated with kidney function [ 18 , 19 ]. Genetic variants related to the presence and degree of microalbuminuria and proteinuria have also been identified [ 20 ] and a meta-analysis revealed variants of significance for rapid decline in kidney function [ 21 ]. DNA variants in APOL1 have been shown to be associated with non-diabetic CKD in individuals of African origin [ 22 ].…”