Thiazide diuretics do not protect against changes that accompany renal aging

During the normal aging process, changes are produced in renal structure that are indistinguishable from those provoked by uncomplicated elevated arterial pressure. Our objective was to evaluate whether long-term treatment with thiazide diuretics (hydrochlorothiazide [HCT]) prevented the changes that occur during kidney aging.

Fifty CF1 female mice were divided into 2 groups: control group without treatment and HCT group which received 25 mg/L HCT in their drinking water, after weaning and during their entire existence. Mean arterial pressure (MAP) was evaluated per semester, and proteinuria at end of study. At months 6, 12, 18 and 24 of treatment, 5 animals were sacrificed per group. Aortic blood samples were taken to measure plasma creatinine and urea concentrations. Morphometric analysis of glomeruli measured number per mm(2), diameter, percentage of mesangial area and percentage glomerulosclerosis (%GS). Using immunolabeling with anti- alpha-SM-actin percentage, we evaluated percentage glomerular alpha-SM-actin as a marker for early GS. Through electron microscopy we evaluated podocytes and thickness of the glomerular basement membrane.

MAP was lower in the HCT group in all periods, while proteinuria was higher in the HCT group during month 24. Progressive decline in number of glomeruli and %GS was not modified by treatment. Expansion of mesangial matrix and alpha-SM-actin immunolabeling was greater in the HCT group.

GS and loss of renal function are changes produced during aging. Although thiazide diuretics do help reduce arterial pressure, they do not prevent and, furthermore, appear to favor these changes in the normal CF1 mouse.