Proton pump inhibitors and the risk of acute kidney injury in cancer patients receiving immune checkpoint inhibitors: A Danish population-based cohort study.

Previous studies have suggested that the use of proton pump inhibitors (PPIs) more than doubles the risk of acute kidney injury (AKI) in cancer patients receiving immune checkpoint inhibitors (ICIs). However, this association may be confounded. Therefore, we conducted a register-based cohort study to examine the risk of AKI in users and nonusers of PPIs among cancer patients treated with ICIs in Denmark from 2011 through 2021 while accounting for a comprehensive range of potential confounders. PPI use was determined based on redeemed prescriptions of PPIs before ICI initiation. We identified laboratory-recorded AKI events within the first year after ICI initiation. We estimated the risks and hazard ratios (HRs) of AKI while accounting for a comprehensive range of confounders (including comorbidities and comedication) by propensity score weighting. Furthermore, we performed an additional per-protocol analysis while accounting for informative censoring by weighting. We identified 10 200 cancer patients including 2749 (27%) users, 6214 (61%) nonusers, and 1237 (12%) former users of PPIs. PPI users had an increased risk of AKI compared to nonusers (1-year risk, 24.7% vs 19.9%; HR, 1.42 [95% confidence interval (CI), 1.29-1.56]); however, this association attenuated when accounting for confounders (weighted 1-year risk, 24.2% vs 23.8%; weighted HR, 1.06 [95% CI, 0.93-1.21]). In the per-protocol analysis, the crude HR was 1.86 (95% CI, 1.63-2.12), while the weighted HR was 1.24 (95% CI, 1.03-1.49). Thus, the association between PPI use and AKI could largely be explained by confounding, suggesting that previous studies may have overestimated the association.

Performance of the race-free CKD-EPI creatinine-based eGFR equation in a Danish cohort with measured GFR.

Background: In 2021, an updated Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for estimated glomerular filtration rate (eGFR) without a coefficient for race (CKD-EPI21) was developed. The performance of this new equation has yet to be examined among specific patient groups. Methods: We compared the performances of the new CKD-EPI21 equation and the 2009 equation assuming non-Black race (CKD-EPI09-NB) in patients with GFR measured by chromium-51-EDTA plasma clearance at Aarhus University Hospital in Denmark during 2010-18. We examined bias, accuracy, precision and correct classification of chronic kidney disease (CKD) stage using chromium-51-EDTA clearance as the reference standard. We assessed the performance in the total cohort, cancer patients and potential living kidney donors. We also assessed the performance stratified by CKD stage in the total cohort. Results: In this predominantly white population, the CKD-EPI21 equation performed slightly better than the CKD-EPI09-NB equation in both the total cohort (N = 4668), and in cancer patients (N = 3313) and potential living kidney donors (N = 239). In the total cohort, the CKD-EPI21 equation demonstrated a slightly lower median absolute bias (-0.2 versus -4.4 mL/min/1.73 m2), and a similar accuracy, precision and correct classification of CKD stage compared with the CKD-EPI09-NB equation. When stratified by CKD stage, the CKD-EPI09-NB equation performed slightly better than the CKD-EPI21 equation among patients with a measured GFR (mGFR) <60 mL/min/1.73 m2. Conclusions: In a selected cohort of Danish patients with mGFR, the CKD-EPI21 equation performed slightly better than the CKD-EPI09-NB equation except for patients with a mGFR <60 mL/min/1.73 m2, where CKD-EPI09-NB performed slightly better although the differences were considered clinically insignificant.