RESUMEN
Many of the potential effects of antihypertensive therapy, including renal function, have been inadequately investigated in clinical trials in older adults. In an observational study, we examined the association between treatment with various classes of antihypertensive agents and 3-year changes in serum creatinine in 1296 older adults with treated hypertension and without prior renal disease (mean age 72.2 years; 60% female; 30% diabetic; 42% with cardiovascular disease (CVD)) from the Cardiovascular Health Study. Baseline antihypertensive medications included thiazides (HCT), beta-adrenergic blockers, angiotensin converting enzyme inhibitors (ACE-I), calcium channel blockers (CCB), vasodilators (VAS), HCT + BB, HCT + ACE-I, HCT + CCB, HCT + VAS, loop diuretics (LOOP), and other combinations. Unadjusted results indicated that minimal changes in mean serum creatinine occurred over time for all therapies and only a few changes were statistically significant (HCT: +0.02 mg/dL, ACE-I: +0.04, CCB: +0.04; all P < .05; LOOP: +0.06 mg/dL; P < .001). In multivariate analyses with HCT users as the reference group and adjusting for baseline serum creatinine, age, sex, smoking, diabetes mellitus, CVD, height, weight, common carotid intima-media thickness, and use of allopurinol, phenytoin, cimetidine, and nonsteroidal antiinflammatory drugs, all of the relative changes were small and statistically nonsignificant except for HCT + VAS users (+0.07 mg/dL; P < .05). When users of the same therapy at baseline and follow-up were restricted, only LOOP users had significant albeit small changes in serum creatinine (+0.05 mg/dL; P < .05). Although results from clinical trials are needed to confirm these findings, these observational data suggest no major differences between specific antihypertensive therapies in 3-year serum creatinine changes in older adults without prior renal disease.
Asunto(s)
Antihipertensivos/farmacología , Creatinina/sangre , Anciano , Estudios de Cohortes , Femenino , Humanos , MasculinoRESUMEN
There has been controversy regarding the initial pathogenic events involved with the hyperparathyroidism of chronic renal failure (CRF). Low serum levels of 1,25-dihydroxyvitamin D in uremic patients are postulated by some as having a role in permitting higher parathyroid hormone (PTH) secretion. However, recent animal and in vitro studies strongly suggest that phosphate has a direct effect on parathyroid cells to enhance PTH secretion. To evaluate the relationships among serum phosphate, calcium, PTH, and 1,25-dihydroxyvitamin D in uremic humans, we performed a cross-sectional analysis of 84 patients with varying levels of CRF. Using stepwise regression analysis after adjusting for multiple comparisons, we found that serum phosphate correlated directly with serum PTH (r = 0.62, P < 0.01) in patients with mild to moderate CRF (creatinine < or = 3.0 mg/dL), independent of serum calcium and 1,25-dihydroxyvitamin D levels. In patients with more severe renal failure (creatinine > 3.0 mg/dL), only the serum calcium correlated with serum PTH (r = -0.47, P < 0.01). While serum 1 ,25-dihydroxyvitamin D showed no correlations with PTH, phosphate, or calcium at any stage of renal failure, the mean 1,25-dihydroxyvitamin D level in patients with mild CRF was lower than that in age-matched controls (24 +/- 3 pg/mL v 37 +/- 2 pg/mL; P < 0.01), suggesting that low 1,25-dihydroxyvitamin D was permissive for enhanced PTH secretion. These data demonstrate an independent association of serum phosphate with PTH in patients with CRF and suggest that phosphate may directly enhance PTH secretion in this setting. This study supports recent animal studies showing a direct parathyroid cell effect of phosphate on PTH secretion.