Medications that worsen renal function in diabetes
Diabetic nephropathy is a microvascular complication of diabetes that requires preventive strategies focused on controlling blood pressure and reaching euglycemia. Additional preventive strategies related to avoidance of potentially nephrotoxic medications may be required for medications that have been shown to negatively affect renal function. The following is a summary of some medications that have the potential to worsen renal function and their mechanisms of drug-induced nephrotoxicity.
ACE inhibitors and others
These classes of medications, although known for their renal-protective effects, have the potential to reduce renal function. Reduction of angiotensin II through inhibition of angiotensin-converting enzyme or blockade of the angiotensin receptor results in a reduction in efferent renal artery tone and changes in intraglomerular pressure. In patients with renal artery stenosis, this translates to a reduction in transcapillary filtration pressure, potentially leading to either acute or chronic renal insufficiency. This effect is of particular concern in the presence of bilateral renal artery stenosis. An indication of the presence of renal artery stenosis is a rise in serum creatinine of >50% after initiation of these agents. The frequency of critical renal artery stenosis (>70%) may occur in up to 17% of people with type 2 diabetes.
Acute tubular necrosis can result from toxic or ischemic insults to the kidney. Certain antibiotics, such as those in the aminoglycoside or beta-lactam class, and the antifungal amphotericin B may cause acute tubular necrosis. This effect is a result of necrosis of the proximal tubule epithelium and basement membrane, decreased glomerular capillary permeability and backleak of glomerular filtrate into the venous circulation. Acute interstitial nephritis, an uncommon and usually reversible inflammatory renal disease affecting the interstitium and tubules, has been reported with the beta-lactam antibiotics in particular.
Patients who are dependent on renal adaptive mechanisms to maintain renal blood flow may develop functional acute renal failure when administered agents that compromise these adaptations. Patients with reduced cardiac output (heart failure, myocardial infarction) accommodate a decrease in renal blood flow through dilation of afferent arterioles, constriction of efferent arterioles and redistribution of blood flow to the adrenal medulla. The nonsteroidal anti-inflammatory drugs block production of prostaglandin required for dilation of afferent arterioles, thus impairing the adaption needed to maintain glomerular filtration rate. The onset of fluid retention or increased creatinine is evidence of NSAIDinduced declining renal function.
The use of radiocontrast agents in angiography may result in acute renal failure in as high as 35% of people with diabetes, particularly in the setting of pre-existing reduced renal function. The pathogenesis of the acute renal failure appears to be related to acute renal vasoconstriction and renal ischemia leading to generation of reactive oxygen species. The sensitivity of the diabetic kidney to renal vasoconstrictors and dysfunctional renal handling of reactive oxygen species impose a high risk on these patients for this complication. A consensus panel has recently published an executive summary of its findings and recommendations in preventing contrast-induced nephropathy. Prevention appears to be generally limited to IV hydration prior and administration of an iso-osmolar contrast media.
Other medications known to reduce renal function include the immunosuppressives cyclosporine and tacrolimus, especially when used in high doses. This effect is due to potent renal vasoconstriction that results in decreased intraglomerular pressure and a subsequent decrease in GFR. These medications are clinically indicated for patients with organ transplants, and close attention to dosing and monitoring of blood levels are needed to avoid adverse renal effects.
This is not an exhaustive list, and the clinician should review the renal effects of prescribed medications when used in people with diabetes, particularly those patients with pre-existing renal disease. Medications that have known potential for renal toxicity may be best avoided or used only in carefully selected patients with close monitoring.
June Felice Johnson, PharmD, is Associate Professor and Chair of the Department of Clinical Sciences at Drake University College of Pharmacy and Health Sciences, Des Moines, Iowa.
For more information:
- Chisholm-Burns MA. Pharmacotherapy: Principles & Practice. New York: McGraw-Hill Medical; 2007.
- Gross JL. Diabetes Care. 2005;28:176-188.
- McCullough PA. Rev Cardiovasc Med. 2006;7:177-1797.
- Pflueger A. Med Sci Monit. 2009;15:125-136.
- Plakogiannis R. Pharmacotherapy. 2007;27:1456-1461.