PubMed · 5278822
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J L Henry. 1971. Bridging the gap.. https://pubmed.ncbi.nlm.nih.gov/5278822/
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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.
CONTEXT: A home visitation program using nurses to improve maternal and child outcomes had favorable results in a randomized trial with a primarily white, semirural population. Many of the short-term findings have been replicated with urban blacks, but whether the program will continue to demonstrate effectiveness after its conclusion is uncertain. OBJECTIVE: To determine the effectiveness of a prenatal and infancy home visitation program on the maternal life course of women in an urban environment 3 years after the program ended. DESIGN AND SETTING: Three-year follow-up of a randomized controlled trial of women seen consecutively between June 1990 and August 1991 at an obstetrical clinic in Memphis, Tenn, who were enrolled in a visitation program for 2 years after the birth of their first child. PARTICIPANTS: A cohort of 743 women who were primarily black, were pregnant for less than 29 weeks, had no previous live births, and had at least 2 sociodemographic risk factors (unmarried, <12 years of education, or unemployed). INTERVENTION: An average of 7 (range, 0-18) home visits during pregnancy and 26 (range, 0-71) from birth to the child's second birthday. MAIN OUTCOME MEASURES: Rate of subsequent pregnancy, mean interval between first and second birth, and mean number of months of welfare use. RESULTS: Compared with the control group, women who received home visits by nurses had fewer subsequent pregnancies (1.15 vs 1.34; P=.03), fewer closely spaced subsequent pregnancies (0.22 vs 0.32; P=.03), longer intervals between the birth of the first and second child (30.25 vs 26.60 months; P=.004), and fewer months of using Aid to Families with Dependent Children (32.55 vs 36.19; P=.01) and food stamps (41.57 vs 45.04; P=.005). Compared with the effect of the program while the program was in operation, the effect after it ended was essentially equal for Aid to Families with Dependent Children, greater for food stamps, greater for rates of closely spaced subsequent pregnancies, and smaller for rates of subsequent pregnancy overall. CONCLUSIONS: We found enduring effects of a home visitation program on the lives of black women living in an urban setting. While these results were smaller in magnitude than those achieved in a previous trial with white women living in a semirural setting, the direction of the effects was consistent across the 2 studies.
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