Angiotensin converting enzyme inhibition and calcium channel blockade in incipient diabetic nephropathy

Small increases in blood pressure are a feature of incipient diabetic nephropathy, and mean blood pressure often correlates with the degree of albuminuria in such patients. Antihypertensive therapy with angiotensin converting enzyme inhibitors (CEI) or calcium channel blockers (CCB) has been assessed in several studies to determine if either form of treatment modifies incipient diabetic nephropathy and its evolution to established nephropathy. The acute renal hemodynamic effects of CEI differ from those of CCB under certain circumstances. In incipient diabetic nephropathy, therapy with CEI but not CCB tends to reduce filtration fraction, especially in hyperfiltering patients. In hypertensive patients with incipient diabetic nephropathy, both treatments result in a decrease in albuminuria and the responses are mainly dependent on the lowering of systemic blood pressure. In normotensive patients with incipient diabetic nephropathy, a lowering of mean blood pressure with CEI or CCB is not found consistently while effects on albuminuria are difficult to interpret. Short- and long-term therapy with CEI lowers or stabilizes albuminuria. Short-term administration of CCB has at times been associated with increases in albuminuria, but a comparison of CEI and CCB over 12 months in the Melbourne Diabetic Nephropathy Study (MDNS) has shown that both drugs stabilize albuminuria with no significant differences in their effects. Serial analysis of urinary sodium excretion in the MDNS shows that the hypotensive response to CEI in incipient nephropathy is highly dependent on sodium intake, and that sodium intake may modulate albuminuria during both CEI and CCB therapy. In a subgroup of MDNS participants, examination of albumin excretion rates before and after treatment suggests that the natural history of evolution of albuminuria may have been ameliorated during CEI and CCB therapy. In patients with type II diabetes and albuminuria in the incipient nephropathy range, the responses of blood pressure and albuminuria to CEI and CCB have been similar and in general parallel to those observed in younger patients with type I diabetes and incipient nephropathy. Long-term studies are needed to determine whether a decrease in albuminuria induced by CEI or CCB in patients with incipient diabetic nephropathy delays or reduces the subsequent rate of decline in glomerular filtration rate and renal structural changes.