Treatment of Microalbuminuria in Patients with Type 2 Diabetes in the Absence of Hypertension

Case

RT is a 54-year-old woman seen in the internal medicine clinic for management of type 2 diabetes. Her hemoglobin A1C (6.7%) and lipid levels (low-density lipoprotein = 86; high-density lipoprotein = 52) are currently at goal. All blood pressure readings over the past year have been less than 130/80 mm Hg, with systolics ranging from 90 to 100 and diastolics 65 to 70. Her most recent microalbumin-to-creatinine (M/C) ratio results were 66 mcg/mg and 81 mcg/mg. RT’s primary care provider seeks your opinion on whether to initiate an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) for renal protection.

Answer

The American Diabetes Association guidelines currently state that all patients with diabetes mellitus and micro- or macroalbuminuria should be prescribed an ACE inhibitor or ARB to mitigate nephropathy.

^1,2

Three main trials were cited as evidence supporting this recommendation, 2 of which included only patients with microalbuminuria (M/C ratio of 30 to 300 mcg/mg).

^3-5

Although the data from these studies support the treatment of microalbuminuria in patients with diabetes, it is important to note that the mean baseline blood pressure readings from all 3 trials were greater than 150/80 mm Hg.^3-5 As such, it is difficult to extrapolate these results to RT’s case given her normotensive status.

Few studies have investigated the treatment of diabetic nephropathy in the absence of hypertension, possibly due to the fact that this combination of characteristics is relatively uncommon.² One small, prospective trial published in 1996 reported a 42% absolute risk reduction in the progression of microalbuminuria to proteinuria with the addition of enalapril; however, this percentage was based on a difference of only 6 patients.⁶ In addition, a 2005 metaanalysis including this trial reported no significant benefit of ACE inhibitor or ARB therapy in patients with microalbuminuria, leading the authors to conclude that the renoprotective benefits of these agents are a result of their blood pressure—lowering effects alone.⁷

Despite substantial evidence to support the use of ACE inhibitors and ARBs in patients with diabetes, it remains unclear whether RT would receive a significant benefit from these agents. In addition to increasing pill burden, monthly medication expenses, and the need for laboratory monitoring, starting an antihypertensive agent could increase RT’s risk for developing symptomatic hypotension considering her low baseline blood pressures. Weighing these risks against the available evidence, you recommend to RT’s provider that therapy be withheld at this time. If in the future her M/C ratio rises above 300 mcg/mg (macroalbuminuria) or her blood pressures increase to greater than 130/80 mm Hg, initiation of an ACE inhibitor or ARB should be reconsidered.

Dr. Holler is a clinical assistant professor at the Wayne State University Eugene Applebaum College of Pharmacy and Health Sciences and a clinical pharmacist at Henry Ford Hospital in Detroit, Michigan.

References:

• Standards of medical care in diabetes — 2012. Diabetes Care. 2012;35(1):S11-S63.
• Williams CD. Is microalbuminuria a disease? Pharmacotherapy. 2012;32(9):781-783.
• Parving HH, Lehnert H, Brochner-Mortensen J, Gomis R, Andersen S, Arner P. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 2001;345:870-878.
• Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345:851-860.
• Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345:861-869.
• Ravid M, Lang R, Rachmani R, Lishner M. Long-term renoprotective effect of angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus: a 7-year follow-up study. Arch Intern Med. 1996;156:286-289.
• Casas JP, Chua W, Loukogeorgakis S, et al. Effect of inhibitors of the renin-angiotensin system and other antihypertensive drugs on renal outcomes: systematic review and meta-analysis. Lancet. 2005;366:2026-2033.