Acute kidney injury associated with trimethoprim/sulfamethoxazole

Abstract

Objectives: Trimethoprim/sulfamethoxazole effectively treats community-acquired soft tissue infections and urinary tract infections, both of which occur in patients with risk factors for renal impairment. We systematically studied the adverse renal effects of trimethoprim/sulfamethoxazole in a middle-aged veteran population.

Methods: We reviewed complete electronic records for all patients who, during a 3 year period, had received ≥6 days of treatment with trimethoprim/sulfamethoxazole and for whom a baseline and follow-up determination of serum creatinine and blood urea nitrogen (BUN) were available.

Results: Of 573 patients who met inclusion criteria, 64 (11.2%) had increases in both serum creatinine and BUN that met predetermined criteria for acute kidney injury (AKI): in 33 (5.8%), AKI was judged likely due to trimethoprim/sulfamethoxazole; in 28 (4.9%), possibly due to trimethoprim/sulfamethoxazole; and in 3 (0.52%), unrelated to trimethoprim/sulfamethoxazole. Five additional patients (0.9%) had elevations only in serum creatinine. In nearly all cases likely due to trimethoprim/sulfamethoxazole, AKI resolved promptly after discontinuation of therapy, but one patient required dialysis. Pyuria appeared in only 2 of 37 patients who had urinalyses; eosinophiluria was not observed. In a multivariate model, patients with hypertension and diabetes mellitus had increased risk for renal insufficiency, especially if these conditions were considered poorly controlled.

Conclusions: In a middle-aged male inpatient population treated for a minimum of 6 days, AKI is much more common with trimethoprim/sulfamethoxazole therapy than previously reported. Intrinsic renal impairment rather than interstitial nephritis or competition for creatinine clearance appears responsible for the great majority of cases, and neither an effect of dose nor duration was detected in a univariate analysis. Impairment is transient if therapy is discontinued.