PubMed · 5581040
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R Williams. 1971. No small thing.. https://pubmed.ncbi.nlm.nih.gov/5581040/
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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: Immunization rates in the inner city remain lower than in the general US population, but efforts to raise immunization levels in inner-city areas have been largely untested. OBJECTIVE: To assess the effectiveness of case management in raising immunization levels among infants of inner-city, African American families. DESIGN: Randomized controlled trial with follow-up through 1 year of life. SETTING: Low-income areas of inner-city Los Angeles, Calif. PATIENTS: A representative sample of 419 African American infants and their families. INTERVENTIONS: In-depth assessment by case managers before infants were 6 weeks of age, with home visits 2 weeks prior to when immunizations were scheduled and additional follow-up visits as needed. MAIN OUTCOME MEASURES: Percentage of children with up-to-date immunizations at age 1 year, characteristics associated with improved immunization rates, and cost-effectiveness of case management intervention. RESULTS: A total of 365 newborns were followed up to age 1 year. Overall, the immunization completion for the case management group was 13.2 percentage points higher than the control group (63.8% vs 50.6%; P=.01). In a logistic model, the case management effect was limited to the 25% of the sample who reported 3 or fewer well-child visits (odds ratio, 3.43; 95% confidence interval, 1.26-9.35); for them, immunization levels increased by 28 percentage points. Although for the case management group intervention was not cost-effective ($12022 per additional child immunized), it was better ($4546) for the 25% of the sample identified retrospectively to have inadequate utilization of preventive health visits. CONCLUSIONS: A case management intervention in the first year of life was effective but not cost-effective at raising immunization levels in inner-city, African American infants. The intervention was demonstrated to be particularly effective for subpopulations that do not access well-child care; however, currently there are no means to identify these groups prospectively. For case management to be a useful tool to raise immunizations levels among high-risk populations, better methods of tracking and targeting, such as immunization registries, need to be developed.
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