PubMed · 9165909
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R Porter. The double-glazed ceiling.. https://pubmed.ncbi.nlm.nih.gov/9165909/
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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.
BACKGROUND: Results of previous studies of white older adults suggest that antihypertensive medications preserve cognition. We assessed the long-term effect of antihypertensive medications on cognitive function in a community sample of African American older adults. METHODS: We conducted longitudinal surveys and clinical assessment of cognitive function in a random sample of 2212 community-dwelling African Americans 65 years and older. We identified 1900 participants without evidence of cognitive impairment at baseline, 1617 of whom had subsequent follow-up information, and 946 of whom had blood pressure measurements. Cognitive function was measured at baseline and at 2 and 5 years by means of scores on the Community Screening Instrument for Dementia and neuropsychological and clinical assessment for dementia and cognitive impairment. Prescription and nonprescription medication use was derived from in-home inspection of medications and participant and informant reports. RESULTS: Of 1900 participants, 288 (15.2%) developed incident cognitive impairment. Using logistic regression to control for the effects of age, sex, education, baseline cognitive scores, and hypertension and angina or myocardial infarction, we found that antihypertensive medications reduced the odds of incident cognitive impairment by 38% (odds ratio, 0.62; 95% confidence interval, 0.45-0.84). Corresponding analysis using blood pressure measurements on the subset of participants was inconclusive. CONCLUSION: Antihypertensive medication use is associated with preservation of cognitive function in older African American adults.
CONTEXT: Child maltreatment is a significant problem within US society, and minority children have higher rates of substantiated maltreatment than do white children. However, it is unclear whether minority children are abused more frequently than whites or whether their cases are more likely to be reported. OBJECTIVES: To determine whether there are racial differences in the evaluation and Child Protective Services (CPS) reporting of young children hospitalized for fractures. DESIGN, SETTING, AND PATIENTS: Retrospective chart review conducted at an urban US academic children's hospital among 388 children younger than 3 years hospitalized for treatment of an acute primary skull or long-bone fracture between 1994 and 2000. Children with perpetrator-admitted child abuse, metabolic bone disease, birth trauma, or injury caused by vehicular crash were excluded. MAIN OUTCOME MEASURES: Ordering of skeletal surveys and filing reports of suspected abuse. RESULTS: Reports of suspected abuse were filed for 22.5% of white and 52.9% of minority children (P<.001). Abusive injuries, as determined by expert review, were more common among minority children than among white children (27.6% vs 12.5%; P<.001). Minority children aged at least 12 months to 3 years (toddlers) were significantly more likely to have a skeletal survey performed compared with their white counterparts, even after controlling for insurance status, independent expert determination of likelihood of abuse, and appropriateness of performing a skeletal survey (adjusted odds ratio [OR], 8.75; 95% confidence interval [CI], 3.48-22.03; P<.001). This group of children was also more likely to be reported to CPS compared with white toddlers, even after controlling for insurance status and likelihood of abuse (adjusted OR, 4.32; 95% CI, 1.63-11.43; P =.003). By likelihood of abuse, differential ordering of skeletal surveys and reporting of suspected abuse were most pronounced for children at least 12 months old with accidental injuries; however, differences were also noted among toddlers with indeterminate injuries but not among infants or toddlers with abusive injuries. Minority children at least 12 months old with accidental injuries were more than 3 times more likely than their white counterparts to be reported for suspected abuse (for children with Medicaid or no insurance, relative risk [RR], 3.08; 95% CI, 1.37-4.80; for children with private insurance, RR, 3.74; 95% CI, 1.46-6.01). CONCLUSION: While minority children had higher rates of abusive fractures in our sample, they were also more likely to be evaluated and reported for suspected abuse, even after controlling for the likelihood of abusive injury. This suggests that racial differences do exist in the evaluation and reporting of pediatric fractures for child abuse, particularly in toddlers with accidental injuries.