Impact of cotrimoxazole prophylaxis on serum creatinine and potassium levels in renal transplant recipients

Details

Supervisors

Jadoul, Michel

Faculty

Faculté de médecine et médecine dentaire

Degree label

Master [180] en médecine

Abstract

Administration of cotrimoxazole (CTX) 800/160 mg 3 times a week is the standard prophylaxis of pneumocystis pneumonia in renal transplant recipients as per KDIGO guidelines. The impact of CTX on serum creatinine and potassium is well quantified when used in doses of 800/160 mg daily and more. Whether the prophylactic regimen significantly influences serum creatinine and potassium is unknown, and our hypothesis is that it does. The objective of this study is thus to assess and quantify the impact of CTX prophylaxis on creatinine and potassium levels. The medical records of two hundred and eighteen consecutive recipients of a kidney transplant at CUSL between June 2012 until December 2015 were analyzed retrospectively. This cohort received a standard CTX prophylaxis during 6 months. With time of CTX discontinuation as the time-point of reference, monthly lab results - before and after stop - were compared. Continuous variables were compared using a t-test with unequal variances. Multivariate analysis was conducted with a panel data linear fixed effects model for periods and robust cluster variance estimation. Between period 6 (last intake of CTX) and 7 (1 month after last intake of CTX) serum creatinine decreased significantly (-0.111 mg/dl.) This 8% decrease in serum creatinine contrasts with the absence of significant change of serum creatinine in the months before 6 or after 7. By multivariate statistical analysis we found that impact of CTX on serum creatinine was dependent on baseline serum creatinine (p-value <0.001), which is consistent with the fact that tubular secretion of creatinine (blocked by CTX at higher doses) is known to increase as serum creatinine increases. In addition, serum urea did not drop at the time of CTX discontinuation, a finding further supporting the causal link between CTX discontinuation and serum creatinine decrease. Serum potassium decreased significantly by -0.093 mmol/L (CI95% -0.173 to -0.014 mmol/L) after CTX discontinuation. For clinicians, the significant reversible impact of low dose CTX prophylaxis on serum creatinine should be considered when interpreting the evolution of serum creatinine over time. The absence of such a drop at the time of CTX discontinuation or a seemingly mild increase should trigger the suspicion of a problem. As to the potassium results, clinicians facing hyperkalemia in KTRs should seriously consider stopping low dose CTX prophylaxis, as it reversibly contributes to hyperkalemia. For registries, and large databases, the main implication is that comparisons of creatinine based eGFR between studies or registries are not completely reliable if some units continue low dose CTX prophylaxis indefinitely whereas others stop after 3 or 6 months (like at CUSL).