Do Oral Contraceptives Pose a Risk to Diabetic Kidneys?

During the past decade or so, a multitude of weapons have emerged in the battle against the complications of diabetes mellitus. Here are a few examples:

• Patients with diabetes benefit from treatment of elevated low-density lipoprotein (LDL) cholesterol levels (secondary prevention LDL target of less than 100 mg/dL [less than 70 mg/dL in some consensus panel recommendations]).
• Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) can decrease proteinuria and slow the progression of diabetic renal disease.
• Tight glucose control has repeatedly been demonstrated to retard microvascular complications.

But the expansion of the therapeutic armamentarium raises the question: Are we giving our patients with diabetes any medications that make them more susceptible to complications?

The benefits of ACEIs and ARBs in diabetic renal disease are consistent with a critical pathophysiology. An activated renin-angiotensin system leads to deleterious effects on the kidneys of patients with diabetes. If the renin-angiotensin system is inhibited or blocked by ACEIs and ARBs, the kidneys are protected.

In contrast, oral contraceptives (OCs) can activate the renin-angiotensin system in healthy women. Could they have potential adverse effects on the kidneys of women with diabetes?

Renal blood flow (as measured by paraaminohippurate) was chosen as a marker of renin-angiotensin system activation. It was measured after administration of an ACEI (captopril) and later an ARB (either irbesartan( or candesartan) in the following groups of women: nondiabetic OC users, nondiabetic nonusers, diabetic OC users, and diabetic nonusers. Women with diabetes who were taking an OC had the largest increase in renal blood flow after ACEI and ARB administration.¹

This increase in blood flow suggests that through activation of the renin-angiotensin system, OCs could have negative effects on the kidneys of women with diabetes. In fact, macroalbuminuria developed in 18% of diabetic OC users in the study compared with 2% of nonusers.¹ A previous study demonstrated that OCs can increase the risk of microalbuminuria in women with type 2 diabetes.²

The authors concluded that OC use in women with diabetes may be a risk factor for diabetic nephropathy.¹ This is cause for concern because an earlier study showed that at least 20% of women with diabetes use OCs.³ This percentage may well be higher, given that more than a decade has elapsed since the results of this study were published.

A large prospective trial is required to determine definitively whether the risk of renal disease is real enough to lead to a change in the manner in which OCs are prescribed for women with diabetes. Until then, use caution in these patients. Blood pressure control, close follow-up of all risk factors (such as hemoglobin A_1c levels and urinary protein excretion), and smoking cessation counseling are essential. Make every effort, if possible, to avoid OCs in women with diabetes who have established proteinuria.