ABSTRACT
Objectives: At normal doses of trimethoprim-sulfamethoxazole (TMP/SMX), trimethoprim inhibits tubular creatinine secretion, leading to a rapid but reversible increase in serum creatinine (SCr). Although patients with connective tissue diseases are often in the state of immunosuppression and TMP/SMX is an important prophylactic drug, clinicians often have to stop or reduce the dosage due to concerns regarding its effect on renal function. This study aimed to evaluate the effect of a prophylactic dose of TMP/SMX on SCr in Japanese patients with connective tissue diseases, the extent of SCr level elevation and the independent risk factors for creatinine elevation. Methods: A retrospective cohort study was undertaken. Participants included patients with connective tissue diseases who were treated with a prophylactic dose of TMP/SMX between 2004 and 2018. Using single and multiple regression analyses, the risk factors that affected SCr elevation were evaluated. Results: A total of 262 patients, females, n = 181; age, median (range) = 59 (19-89) years, were included. The median baseline SCr level before treatment was 0.62 (0.16-2.1) mg/dL. The median SCr elevation value was 0.07 (-0.54 to 0.84) mg/dL in 4 weeks after TMP/SMX initiation. Five (2%) participants had ⩾0.3 mg/dL SCr elevation. Multiple regression analyses, including age, baseline SCr, diuretic use, nonsteroidal anti-inflammatory drug use and diabetes mellitus, indicated that baseline SCr and advanced age were independent risk factors of SCr elevation. Conclusions: These results demonstrated that baseline SCr and advanced age were associated with SCr elevation by a prophylactic dose of TMP/SMX. However, a prophylactic dose of TMP/SMX rarely elevated the SCr level significantly. Therefore, other causes can be considered if patients show an SCr elevation ⩾0.3 mg/dL.
ABSTRACT
A 72-year-old woman with a history of type 2 diabetes mellitus was brought to the ER with metformin-associated lactic acidosis. She received continuous hemofiltration and hemodialysis, but the laboratory analyses showed no improvement. She died 11 hours after admission. Metformin is minimally bound to proteins and is readily dialyzable, but a prolonged period of dialysis is required, because metformin has a very large distribution volume and is distributed to multiple compartments. The peak blood metformin level was 432 mg/L in this case, which is one of the highest metformin concentrations ever reported, and eight hours of hemodialysis were not sufficient to reduce the serum level.
