PubMed · 1990348
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I McMillan. Rough justice.. https://pubmed.ncbi.nlm.nih.gov/1990348/
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BACKGROUND: Glomerular filtration rate (GFR) is a heritable trait, and hyperfiltration (GFR increment in remnant nephrons) may accelerate renal functional decline in chronic kidney disease (CKD). Mesangial and vascular smooth myocytes control GFR by contraction, dependent on voltage-gated Ca(2+) influx, which is controlled by the regulatory β₁-subunit (KCNMB1) of large-conductance heteromeric K+ ('BK') channels. KCNMB1 gain-of-function variant Glu65Lys results in generalized vasorelaxation and thus protection against systemic hypertension. Here we asked whether the Glu65Lys variant influences GFR, in the basal state or during progressive renal decline. METHODS: We explored Glu65Lys effects on GFR in three populations spanning two ethnicities and two diseases (hypertension and nephrosclerosis). GFR was either estimated (eGFR from serum creatinine) or directly measured (iothalamate clearance). RESULTS: The 65Lys variant was relatively common, occurring on ∼5-10% of chromosomes in different biogeographic ancestry groups, and 65Lys carriers exhibited higher eGFR in two primary care populations: extreme BP values in Kaiser clinics (p = 0.029, accounting for ∼0.2% of trait variance), or treated hypertensives in VA clinics (p = 0.017, accounting for ∼0.9% of trait variance). In blacks with progressive renal disease (NIDDK AASK), 65Lys carriers displayed a steeper slope in GFR chronic decline (p = 0.030, accounting for ∼0.4% of trait variance), and Glu65Lys genotype also predicted time of onset of renal failure (log rank p = 0.019). CONCLUSIONS: Common KCNMB1 gain-of-function variant Glu65Lys influences GFR, and 65Lys carriers exhibit not only elevated baseline GFR, but also more rapid GFR decline (and consequent development of renal failure) in CKD. The results suggest that profiling patients at Glu65Lys can assist in gauging renal prognosis as well as selection of rational therapy in hypertension with progressive renal disease.
This study determined potential associations of sociodemographic, lifestyle, health, and drug use factors known to affect bone metabolism with incident nonvertebral fractures. The baseline sample consisted of 2,590 female, nonproxy subjects from the Duke Established Populations for Epidemiologic Studies of the Elderly, which focuses on five adjacent counties in the Piedmont area of North Carolina. Information about potential risk factors was collected during a baseline in-home interview during 1986-1987. Subsequent nonvertebral fractures were reported at follow-up interviews during the annual follow-up periods (1988-1993). The authors used multivariate analyses in which weighted data were adjusted for sampling design. After controlling for other potential confounding sociodemographic, lifestyle, health, and drug use factors, they found that African American race (adjusted odds ratio (OR) = 0.43, 95% confidence interval (CI) 0.31-0.58), age (adjusted OR = 1.04, 95% CI 1.01-1.06), alcohol consumption (adjusted OR = 1.61, 95% CI 1.01-2.57), being underweight (adjusted OR = 1.63, 95% CI 1.13-2.34), cognitive impairment (adjusted OR = 1.67, 95% CI 1.12-2.48), impaired mobility (adjusted OR = 1.15, 95% CI 1.03-1.29), and phenytoin use (adjusted OR = 2.93, 95% CI 1.04-8.30) were associated with first fracture occurrence. Similar findings were observed for nonhip, nonvertebral fractures. African Americans were less likely than Whites to have nonvertebral fractures, and these differences were not related to lifestyle or health factors examined in this study.
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