PubMed · 5412196
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C V Cimmino. 1970-02-19. On not being upper class.. https://pubmed.ncbi.nlm.nih.gov/5412196/
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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: We aimed to compare the prevalence of abnormal glucose tolerance identified by the 1985 WHO and the 1997 American Diabetes Association (ADA) diagnostic categories based on information collected in the Cardiovascular Health Study, an epidemiological study of elderly people. METHODS: We measured glucose concentrations during fasting and 2 h after a 75 g oral glucose-tolerance test in participants aged 65-100 years in the Cardiovascular Health Study. From a 1989 cohort, we analysed the glucose measurements of 4515 individuals without a previous diagnosis of diabetes and of 262 additional measurements from an African-American cohort recruited in 1992-93. FINDINGS: In the 1989 cohort, the prevalence of untreated diabetes with ADA diagnostic fasting criteria was 7.7% versus a prevalence of 14.8% by the WHO criteria. In the African-American cohort, the prevalence of untreated diabetes was 2.7% with ADA criteria and 11.8% with WHO criteria. 3509 (77.7%) of the 4515 participants in the 1989 cohort had normal glucose concentrations according to ADA fasting criteria, compared with 2401 (53.2%) according to WHO criteria. In the African-American cohort, the corresponding numbers were 239 (91.2%) versus 153 (58.4%). All differences in prevalence of abnormal glucose tolerance between ADA and WHO classifications were significant (p<0.0001). INTERPRETATION: Among elderly individuals, there was a significant difference in the prevalence of diabetes identified by the WHO diagnostic criteria based on oral glucose-tolerance test and the ADA fasting criteria. Consequently, many individuals currently classified as non-diabetic according to ADA criteria would previously have had a diagnosis of diabetes according to WHO criteria. Longitudinal studies are needed to assess the value of the criteria in the identification of individuals at increased risk of diabetes-associated chronic complications.
BACKGROUND: Prostate carcinoma is one of the leading causes of death in men. Although the mortality rate is high, it still may underestimate the number of deaths associated with the disease. This study was conducted to compare causes of death among men previously diagnosed with prostate carcinoma and to examine the extent to which differences in cause of death (death from prostate carcinoma vs. death from other causes) varied by age, race, clinical factors, and comorbid conditions. METHODS: A review was conducted of the medical records of decedent members of the Kaiser Permanente Medical Care program who previously were diagnosed with prostate carcinoma between January 1980 and December 1984 (n=584). The review focused on demographic factors, symptoms, diagnostic tests, stage of disease, and treatment. Data on comorbidity were obtained from a computerized discharge summary. Logistic regression analysis was used to estimate odds ratios. RESULTS: Approximately 54% of the decedent prostate carcinoma patients died of their prostate carcinoma. Decedents who were black, age < or = 65 years, diagnosed with more advanced disease stage, recipients of hormonal therapy, and whose death occurred > 6 months after diagnosis were more likely than others to die of prostate carcinoma. In contrast, the likelihood of dying of some other cause was associated with concurrent cardiovascular disease, after adjustment for the effects of race, age, and disease stage. There also were significant two-way age-race and age-time-to-death interactions. CONCLUSIONS: The prognostic significance of cardiovascular disease in prostate carcinoma patients should be investigated in subsequent survival studies. A number of questions need to be addressed delineating the complex relations between coexisting diseases and their treatment.