PubMed · 9874989
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C Wedderburn-Tate. 1998. Backs to the future.. https://doi.org/10.7748/nm.5.4.5.s7
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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.
OBJECTIVE: To describe the 6-year probability of survival for older adults after their first hospitalization for heart failure. SETTING: National Medicare hospital claims records for 1984 through 1986 and Medicare enrollment records from 1986 through 1992. DESIGN: We identified a national cohort of 170 239 (9% black patients) Medicare patients, 67 years or older, with no evidence of heart failure in 1984 or 1985, who were hospitalized and discharged for the first time in 1986 with a principal diagnosis of heart failure. For groups defined by race, sex, age, Medicaid eligibility, and comorbid conditions, we compared the probability of survival with Cox proportional hazards regression. RESULTS: Only 19% of black men, 16% of white men, 25% of black women, and 23% of white women survived 6 years. One third died within the first year. Men had lower median survival and 38% greater risk of mortality than did women (P<.05). White men had 10% greater risk of mortality than did black men (P<.05). Medicaid eligibility (white adults only) and diabetes were associated with increased mortality (P<.05). CONCLUSIONS: The prognosis for older adults with heart failure underscores the importance of prevention strategies and early detection and treatment modalities that can prevent, improve, or reverse myocardial dysfunction, particularly for the growing number of adults who are at increased risk for developing heart failure because of hypertension, diabetes, or myocardial infarction.
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