Chronic kidney disease (CKD), impairment of kidney function, is a serious public health problem, and the assessment of genetic factors influencing kidney function has substantial clinical relevance. Here, we report a meta-analysis of genome-wide association studies for kidney function–related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital- or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN). Our meta-analysis identified 17 loci newly associated with kidney function–related traits, including the concentrations of blood urea nitrogen, uric acid and serum creatinine and estimated glomerular filtration rate based on serum creatinine levels (eGFRcrea) (P < 5.0 × 10−8). We further examined these loci with in silico replication in individuals of European ancestry from the KidneyGen, CKDGen and GUGC consortia, including a combined total of ~110,347 individuals. We identify pleiotropic associations among these loci with kidney function–related traits and risk of CKD. These findings provide new insights into the genetics of kidney function.

Chronic kidney disease (CKD), the result of permanent loss of kidney function, is a major global problem. We identify common genetic variants at chr2p12-p13, chr6q26, chr17q23 and chr19q13 associated with serum creatinine, a marker of kidney function (P=10−10 to 10−15). SNPs rs10206899 (near NAT8, chr2p12-p13) and rs4805834 (near SLC7A9, chr19q13) were also associated with CKD. Our findings provide new insight into metabolic, solute and drug-transport pathways underlying susceptibility to CKD.

BACKGROUND: Vascular calcification independently predicts cardiovascular disease, the major cause of death in kidney transplant recipients (KTRs). Longitudinal studies of vascular calcification in KTRs are few and small and have short follow-up. We assessed the evolution of coronary artery (CAC) and thoracic aorta calcification and their determinants in a cohort of prevalent KTRs. STUDY DESIGN: Longitudinal. SETTING PARTICIPANTS: The Agatston score of coronary arteries and thoracic aorta was measured by 16-slice spiral computed tomography in 281 KTRs. PREDICTORS: Demographic, clinical, and biochemical parameters were recorded simultaneously. OUTCOMES MEASUREMENTS: The Agatston score was measured again 3.5 or more years later. RESULTS: Repeated analyzable computed tomographic scans were available for 197 (70%) KTRs after 4.40 ± 0.28 years; they were not available for the rest of patients because of death (n = 40), atrial fibrillation (n = 1), other arrhythmias (n = 4), refusal (n = 35), or technical problems precluding confident calcium scoring (n = 4). CAC and aorta calcification scores increased significantly (by a median of 11% and 4% per year, respectively) during follow-up. By multivariable linear regression, higher baseline CAC score, history of cardiovascular event, use of a statin, and lower 25-hydroxyvitamin D(3) level were independent determinants of CAC progression. Independent determinants of aorta calcification progression were higher baseline aorta calcification score, higher pulse pressure, use of a statin, older age, higher serum phosphate level, use of aspirin, and male sex. Significant regression of CAC or aorta calcification was not observed in this cohort. LIMITATIONS: Cohort of prevalent KTRs with potential survival bias; few patients with diabetes and nonwhites, limiting the generalizability of results. CONCLUSION: In contrast to previous small short-term studies, we show that vascular calcification progression is substantial within 4 years in prevalent KTRs and is associated with several traditional and nontraditional cardiovascular risk factors, some of which are modifiable.

Abstract-Although renal transplantation improves survival, cardiovascular morbidity and mortality remain significantly elevated compared with nonrenal populations. The negative impact of traditional, uremia-related, and transplantationrelated risk factors in this process remains, however, largely unexplored. Surrogate markers such as aortic stiffness and central wave reflections may lead to more accurate cardiovascular risk stratification, but outcome data in renal transplant recipients are scarce. We aimed to establish the prognostic significance of these markers for fatal and nonfatal cardiovascular events in renal transplant recipients. Carotid-femoral pulse wave velocity, central augmentation pressure, and central augmentation index were measured in a cohort of 512 renal transplant recipients using the SphygmoCor system. After a mean follow-up of 5 years, 20 fatal and 75 nonfatal cardiovascular events were recorded. Using receiver operating characteristic curves, the area under the curve for predicting cardiovascular events was 0. Key Words: cardiovascular events Ⅲ mortality Ⅲ pulse wave velocity Ⅲ augmentation pressure Ⅲ augmentation index Ⅲ transplantation Ⅲ kidney A lthough the survival advantage offered by successful renal transplantation 1 in large part can be attributed to a long-term reduction of the cardiovascular (CV) disease progression and mortality, 2 the annual risk of CV death still remains Ϸ50-fold higher than in the general population. 3 Nevertheless, CV death rates in transplanted patients are reduced by approximately 75% compared with wait-listed patients remaining on dialysis. 4 This decrease in CV risk by partial restoration of kidney function can be offset by the emergence or worsening of other risk factors due to transplant-specific causes, such as acute rejection, infection, or side effects of immunosuppressive drugs, including newonset diabetes after transplantation (tacrolimus, steroids), dyslipidemia (calcineurin inhibitors, mammalian target of rapamycin inhibitors), and anemia (mammalian target of rapamycin inhibitors). Part of the CV risk after transplantation may also relate to irreversible vascular damage accrued during the pretransplantation period.These numerous potential risk factors, together with the small number of randomized trials, render the management of CV risk in renal transplant recipients (RTRs) particularly difficult, whereas this population represents one of the largest groups of patients with chronic kidney disease regularly seen by the nephrologist. Therefore, surrogate markers of arterial damage, such as aortic stiffness and central wave reflections, have gained increasing interest for the assessment of overall CV risk in this heterogeneous population. Patient and donor characteristics that have been related to measures of arterial stiffness or wave reflection include donor age, 5 graft function, 6,7 microinflammation, 7 new-onset diabetes after transplantation, 8 hypomagnesemia, 9 and use of cyclosporine. 10 However, these cross-sectional relationships are on...