Control of glomerular hyperfiltration and renal hypertrophy by an angiotensin converting enzyme inhibitor prevents the progression of renal damage inhypertensive diabetic rats

Objective Glomerular hyperfiltration and renal hypertrophy are both conside red important in the progression of diabetic nephropathy. The aim of this s tudy was to compare the effects of an equivalent reduction in blood pressur e produced by the angiotensin-converting enzyme (ACE) inhibitor spirapril ( SPI) and an antihypertensive triple drug combination of hydralazine, reserp ine and hydrochlorothiazide (HRH) on kidney function, proteinuria and renal structure in hypertensive diabetic rats. Design and methods Four groups of animals were evaluated in short-term and long-term studies. In both studies one group served as a non-diabetic hyper tensive control (H). The other three groups were rendered diabetic and were allocated to one of the following groups: the first diabetic group receive d no specific therapy (HD), the second diabetic group was treated with SPI (HD-SPI) and the third diabetic group was treated with HRH (HD-HRH). In eac h of the two studies the systolic blood pressure (SBP), 24 h urinary total protein, glomerular filtration rate (GFR), glomerular area, proximal tubula r area and glomerular sclerosis were evaluated. Results The blood pressure reduction was equal in rats receiving either SPI or HRH, The GFR, proteinuria, glomerular area and tubular area were signif icantly increased in the HD group, both in the short-term and the long-term study. In the HD-SPI group the diabetic hyperfiltration and renal hypertro phy responses were prevented. In the HD-HRH group the GFR and proteinuria w ere slightly reduced in the later phases of diabetes, while the glomerular area and tubular area were not affected. Semiquantitative analysis of renal lesions showed that SPI was more effective than HRH in the prevention of t he development of glomerulosclerosis. Conclusions The results of this study suggest that the control of early ada ptive hyperfiltration and renal hypertrophy by SPI may be relevant in the p revention of glomerulosclerosis. (C) Lippincott Williams & Wilkins.