AB1217 THE EFFECT OF PROPHYLACTIC DOSE OF TRIMETHOPRIM-SULFAMETHOXAZOLE ON SERUM CREATININE IN JAPANESE PATIENTS WITH CONNECTIVE TISSUE DISEASES

Abstract

Background:Trimethoprim-sulfamethoxazole (TMP/SMX) is an effective antibiotic for prevention of pneumocystis pneumonia (PCP) in immunocompromised patients with various connective tissue diseases (CTD).1)At the normal dose of TMP/SMX, trimethoprim (TMP) component inhibits tubular creatinine secretion, leading to a rapid, but ultimately reversible, increase in serum creatinine.2)However, at prophylactic dose, the effect of TMP/SMX on creatinine in patients with CTD is not clear.Objectives:We conducted this study to evaluate the effect of prophylactic dose of TMP/SMX on serum creatinine in patients with CTD.Methods:This was a retrospective cohort study in which all patients with CTD, treated with prophylactic dose of TMP/SMX during the period between 2004 and 2018, were included, while patients with acute kidney injury due to other causes, were excluded. Retrospective medical chart review was performed to collect the following data, from the baseline through 12 weeks: baseline patient characteristics, serum creatinine (SCr), creatinine clearance (CCr), urine test, serum electrolytes, and level of SCr elevation after initiation of prophylactic dose of TMP/SMX from baseline, within 12 weeks. Using single and multiple regression analyses, we explored the risk factors that affected the SCr elevation value.Results:A total of 272 patients, comprising 186 females, at an average age of 56±18 years, were included in the present study. Based on the medical chart review, this cohort was scored under the following categories: rheumatoid arthritis (RA) n=78, systemic lupus erythematosus (SLE) n=76, Vasculitis n=39, polymyalgia rheumatica/ giant cell arteritis (PMR/GCA) n=29, systemic sclerosis (SSc) n=32, polymyositis/dermatomyositis (PM/DM) n=10, mixed CTD (MCTD) n=5, and others n=56. Their average baseline creatinine level before treatment was 0.67 ± 0.25 mg/dL. They were administered with a mean dose of TMP comprising 99.2 ± 34.4 mg/day, which elevated the mean SCr level by 0.07 ± 0.12 mg/dL. Approximately 85% of the patients continued with the TMP/SMX treatment for 12 weeks, and only 5 (2%) showed creatinine elevation by more than 0.3 mg/dL. They were also administered with prednisolone at an average dose of 36.9 ± 92.3 mg/day.For multiple regression analyses, the following variables were included: age, baseline CCr, use of loop diuretics, use of spironolactone, dose of TMP/SMX, use of non-steroidal anti-inflammatory drugs, and past history of diabetes mellitus. Baseline CCr and advanced age were independent risk factors. Regression coefficients and p values for age and CCr were 0.0018 (95% CI; 0.00083 – 0.0027) and p=0.00028; and 0.0007 (95% CI; 0.0003 – 0.0010) and p=0.00038, respectively.Conclusion:In this study, we demonstrated that prophylactic dose of TMP/SMX elevates SCr by 0.07 ± 0.12 mg/dL on an average. Prophylactic dose of TMP/SMX rarely elevated the creatinine level significantly. Thus, based on our findings, other causes of renal impairment may be considered, if the patients administered with low-dose TMP/SMX show creatinine elevation by more than 0.3 mg/dL.