Pharmacologic management of diabetic nephropathy

Diabetes mellitus and hypertension are leading causes of end stage renal disease in the United States. Drug therapy that focuses on tight glycemic control and blood pressure control reduces the progression of nephropathy and cardiovascular complications. Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce the progression of renal disease in patients with diabetes. The angiotensin II receptor blockers (ARBs) losartan and irbesartan have also been shown to reduce microalbuminuria compared with placebo. The nondihydropyridine calcium channel blockers (CCBs) verapamil and diltiazem have been shown to be as effective as an ACE inhibitor in reducing urinary albumin excretion.

This paper reviews the pathophysiology and diagnosis of diabetic nephropathy and recent clinical trials assessing the most appropriate therapeutic options for delaying the progression of nephropathy in patients with diabetes.

Primary and review articles that addressed the pathophysiology, diagnosis, and therapeutic options for attenuating the progression of diabetic nephropathy were retrieved through a MEDLINE search (January 1990 to August 2002) and the bibliographies of identified articles were reviewed. English-language sources were searched using the following search terms: diabetes mellitus, nephropathy, proteinuria, ACE inhibitors, and ARBs. Studies published in peer-reviewed journals that were determined to be methodologically sound, with appropriate statistical analysis of the results, were selected for inclusion in this review.

Patients with type 1 diabetes mellitus and evidence of nephropathy should be started on an ACE inhibitor unless contraindicated. The ARBs and ACE inhibitors are viable choices for patients with type 2 diabetes mellitus and evidence of proteinuria. Patients who experience adverse events such as dry cough with ACE inhibitors can be switched to ARBs. Clinical literature suggests that if monotherapy with an ACE inhibitor or ARB does not provide an adequate response, a nondihydropyridine CCB should be added to the regimen. Nondihydropyridine CCBs should also be considered when ACE inhibitors and ARBs are contraindicated.

ACE inhibitors and ARBs should be considered first-line therapy for patients with type 2 diabetes mellitus and nephropathy. The ACE inhibitors are still the drug of choice for patients with type 1 diabetes mellitus and evidence of incipient or overt nephropathy. If therapeutic goals are not achieved with an ACE inhibitor or ARB, then the addition of a nondihydropyridine CCB should be considered.