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.
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
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.
- Pflueger A. Med Sci Monit. 2009;15:125-136.
- Plakogiannis R. Pharmacotherapy.