Abstract / Summary
Abstract Background Kidney function at the initiation of treatment for non-human immunodeficiency virus-associated (non-HIV) Pneumocystis jirovecii pneumonia (PCP) is of clinical concern because kidney dysfunction and hyperkalemia are well-known adverse effects of trimethoprim-sulfamethoxazole (TMP-SMX) use. However, the association between kidney function at treatment initiation and clinical outcomes remains unclear. This study aimed to clarify the association between kidney function at TMP-SMX initiation and clinical outcomes in patients with non-HIV PCP. Methods This multicenter, retrospective cohort study included patients with non-HIV PCP treated with TMP-SMX at three Japanese tertiary hospitals between January 2006 and March 2021. Patients were classified by estimated glomerular filtration rate (eGFR) at TMP-SMX initiation into reduced eGFR group (eGFR < 60 mL/min/1.73 m 2 ) and preserved eGFR group (eGFR ≥ 60 mL/min/1.73 m 2 ). The primary endpoint was 30-day mortality from treatment initiation, and the secondary endpoints were 180-day mortality, the incidence of each adverse event, and completion rate of initial treatment. Patient characteristics were adjusted using propensity score analysis with overlap weighting. A subgroup analysis was conducted of patients with respiratory failure. Results The study included 143 patients: 49 in the reduced eGFR group and 94 in the preserved eGFR group. After adjusting for patient background and established prognostic confounders, the 30-day mortality rate (12.2% vs. 15.2%; risk difference (RD), − 3.1%; 95% confidence interval (CI), − 13.1% to 8.7%) and the 180-day mortality rate (27.6% vs. 21.8%; RD, 5.8%; 95% CI, − 7.5% to 18.3%) were similar between the groups. Hyperkalemia was more frequent in the reduced eGFR group (19.3% vs. 5.8%; RD, 13.5%; 95% CI, 1.3% to 24.6%), whereas the treatment completion rate was similar between the groups (34.2% vs. 32.9%; RD, 1.3%; 95% CI, − 15.5% to 17.8%). Subgroup analysis showed no clear association between kidney function and clinical outcomes among patients with respiratory failure. Conclusions In patients with non-HIV PCP initially treated with TMP-SMX, we did not observe a clear association between reduced kidney function at treatment initiation and mortality. However, given the small sample size and wide confidence intervals, clinically meaningful differences cannot be excluded, and these findings should be interpreted cautiously. Clinical trial number Not applicable. The participants were retrospectively registered.