# P-869. Acute Kidney Injury Related to Trimethoprim-Sulfamethoxazole Treatment of Pneumocystis jirovecii Pneumonia: A Retrospective Cohort Analysis

## TL;DR

High-dose trimethoprim-sulfamethoxazole treatment for Pneumocystis pneumonia causes frequent kidney injury and electrolyte issues, leading to high readmission rates.

## Contribution

This study provides new evidence on the high risk of acute kidney injury and electrolyte disturbances from high-dose TMP/SMX in non-HIV patients.

## Key findings

- 24 out of 91 patients were readmitted for AKI or electrolyte disorders during TMP/SMX therapy.
- Hyperkalemia occurred in 50% of readmitted patients, and hyponatremia in 100%.
- A number needed to harm of 4 indicates significant risk with current treatment protocols.

## Abstract

High-dose oral trimethoprim-sulfamethoxazole (TMP/SMX) for 21 days is the standard dose to treat Pneumocystis jirovecii pneumonia (PJP). There has been scant data assessing morbidity due to adverse renal events from TMP/SMX after hospital discharge, despite known adverse effects of TMP on renal function. We evaluated renal function outcomes and health care utilization in a cohort of non-bone marrow transplant, non-HIV (NTNH) patients with PJP.

Electrolyte (Na, K, CO3) values for patients on discharge from initial hospitalizations, readmission, and day 3 of readmission

We conducted a retrospective chart review of NTNH patients diagnosed with PJP at the University of Colorado Hospital (UCH) system over 2016-25 who were admitted for PJP and discharged on high-dose oral TMP/SMX ( >10 mg/kg/day of TMP). We assessed readmission rates due to acute kidney injury (AKI), hyperkalemia, or hyponatremia and compared lab values from discharge, readmission, and 3 days after re-admission by paired t-tests. We used the TriNetX database for national validation with linear mixed models applied to creatinine, sodium, and potassium trajectories by readmission status.
Renal function markers (sCr, eGFR, BUN) for patients on discharge from initial hospitalizations, readmission, and day 3 of readmissionPotassium Trajectory for Patients Who Were Re-admitted and not Re-admitted p <0.001Change in Potassium for patients who were and were not re-admitted for AKI following TMP-SMX treatment

Renal function markers (sCr, eGFR, BUN) for patients on discharge from initial hospitalizations, readmission, and day 3 of readmission

Potassium Trajectory for Patients Who Were Re-admitted and not Re-admitted p <0.001

Change in Potassium for patients who were and were not re-admitted for AKI following TMP-SMX treatment

24 out of 91 UCH patients discharged on TMP/SMX were readmitted for AKI and/or electrolyte disorders during therapy (Figures 1-3). All presented with a KDIGO AKI of stage 1-3 (p< 0.001). Hyperkalemia was observed in 50% of patients (p< 0.001), 42% of whom received shifting therapies. Hyponatremia occurred in 100% (p< 0.001). Symptoms at readmission included weakness (50%), nausea (41.7%), falls (33.3%), and altered mental status (20.8%). One patient died of cardiac arrest attributed to hyperkalemia. We then analyzed 547 NHNT PJP patients in the TriNetX data over 2013-23; 37% were readmitted within 21 days of discharge after PJP diagnosis on TMP/SMX - these patients had similar changes as the UCH cohort with significant impairments in the trajectories of creatinine, potassium, and sodium (p< 0.001) compared to those not readmitted (Figure 4).

High-dose oral consolidation TMP/SMX treatment for PJP results in significant adverse events and healthcare utilization due to a high rate of readmission for AKI - with a number needed to harm of 4. Such outpatient PJP therapy needs closer monitoring than appears to be the current standard-of-care. Clinical trials evaluating efficacy and renal safety of lower-dose TMP/SMX for treating PJP are needed.

Andrés F. Henao Martínez, MD, MPH, F2: Grant/Research Support|Scynexis: Grant/Research Support