and Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function.

Genome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium (: 111,666; : 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea (, , and ; <3.

Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes.

Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.

Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: a collaborative meta-analysis of individual participant data.

Background: The usefulness of estimated glomerular filtration rate (eGFR) and albuminuria for prediction of cardiovascular outcomes is controversial. We aimed to assess the addition of creatinine-based eGFR and albuminuria to traditional risk factors for prediction of cardiovascular risk with a meta-analytic approach.

Methods: We meta-analysed individual-level data for 637 315 individuals without a history of cardiovascular disease from 24 cohorts (median follow-up 4·2-19·0 years) included in the Chronic Kidney Disease Prognosis Consortium.

The association between vitamin B12, albuminuria and reduced kidney function: an observational cohort study.

Background: Variants in CUBN, the gene encoding cubilin, a proximal tubular transport protein, have been associated with albuminuria and vitamin B12 (B12) deficiency. We hypothesized that low levels of B12 would be associated with albuminuria in a population-based cohort.

Methods: We analyzed participants from the Framingham Heart Study (n = 2965, mean age 58 years, 53% female) who provided samples for plasma B12.

Mid-adulthood risk factor profiles for CKD.

Early identification of CKD risk factors may allow risk factor modification and prevention of CKD progression. We investigated the hypothesis that risk factors are present ≥30 years before the diagnosis of CKD in a case-control study using data from the Framingham Offspring Study. Patients with incident CKD (eGFR≤60 ml/min per 1.

The association of a single-nucleotide polymorphism in CUBN and the risk of albuminuria and cardiovascular disease.

Background: Albuminuria is an important risk factor for cardiovascular disease (CVD). We have previously identified a missense single-nucleotide polymorphism (rs1801239) in the CUBN gene that is associated with albuminuria. Whether albuminuria is associated with CVD in the presence of the CUBN mutation is unknown.

Association of a cystatin C gene variant with cystatin C levels, CKD, and risk of incident cardiovascular disease and mortality.

Background: Carriers of the T allele of the single-nucleotide polymorphism rs13038305 tend to have lower cystatin C levels and higher cystatin C-based estimated glomerular filtration rate (eGFRcys). Adjusting for this genetic effect on cystatin C concentrations may improve GFR estimation, reclassify cases of chronic kidney disease (CKD), and strengthen risk estimates for cardiovascular disease (CVD) and mortality.

Study Design: Observational.

Genome-wide association studies of chronic kidney disease: what have we learned?

The past 3 years have witnessed a dramatic expansion in our knowledge of the genetic determinants of estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD). However, heritability estimates of eGFR indicate that we have only identified a small proportion of the total heritable contribution to the phenotypic variation. The majority of associations reported from genome-wide association studies identify genomic regions of interest and further work will be required to identify the causal variants responsible for a specific phenotype.

Association between parental history of diabetes and type 2 diabetes genetic risk scores in the PPP-Botnia and Framingham Offspring Studies.

Objective: Parental history of diabetes and specific gene variants are risk factors for type 2 diabetes, but the extent to which these factors are associated is unknown.

Methods: We examined the association between parental history of diabetes and a type 2 diabetes genetic risk score (GRS) in two cohort studies from Finland (population-based PPP-Botnia study) and the US (family-based Framingham Offspring Study).

Results: Mean (95% CI) GRS increased from 16.

Serum phosphorus predicts incident chronic kidney disease and end-stage renal disease.

Background: Elevations in serum phosphorus are associated with renal decline in animal models and progression of established chronic kidney disease (CKD) in human observational studies. We examined whether serum phosphorus levels increase the risk of incident CKD or end-stage renal disease (ESRD) in two population-based prospective cohort studies.

Methods: Overall, 2269 participants free of CKD [estimated glomerular filtration rate (eGFR) <60 mL/min/1.

Genetics of chronic kidney disease.

The current review collates what is already known of the genetics of chronic kidney disease (CKD), and focuses on new trends in genome-wide assessment of the inherited component of susceptibility to this condition. Early efforts to identify kidney disease susceptibility genetic loci using linkage and candidate gene strategies proved disappointing. More recently, genome-wide association studies have yielded highly promising results suggesting a number of potential candidate genes and genomic regions that may contribute to the pathogenesis of CKD.