CKD and Infection Risk: A CKD Prognosis Consortium Study

Background: Infectious disease is a major cause of hospitalization in people with CKD yet it has not been systematically studied across stages of CKD. Methods: We analyzed data on 2,958,633 individuals (mean age 49 yrs, 59% female, 19% diabetes, mean eGFRcr (CKD-EPI 2021), 93 ml/min/1.73m2) from 45 cohorts in the CKD Prognosis Consortium to examine the association of eGFRcr and ACR with the risk of hospitalization with infection. Outcomes were ascertained through ICD-9 and 10 codes on hospital discharge records relevant to acute infections (i.e., upper and lower respiratory tract, urinary tract, skin and soft tissue, musculoskeletal, gastrointestinal tract, genital, nervous system, cardiovascular system infections, and sepsis). Follow-up was censored at December 31, 2019, and therefore COVID-19 infection was not assessed. Multivariable Cox models were used to estimate HRs. Results: During follow-up, 195,040 had a hospitalization with infection (IR, 140.3 [89.4-202.5] per 10,000 person-yrs). In Cox models, compared to eGFRcr 90-105 and ACR <10, lower eGFRcr and higher ACR were each incrementally associated with an increased risk of infection, including in eGFRcr 45-59 and ACR 10-29 (adjusted HRs [95% CI], 1.46 [1.41-1.51] and 1.41 [1.35-1.47], respectively; far right column and bottom row in Figure). High eGFRcr ≥105 was also associated with the risk of hospitalization with infection (1.33 [1.27-1.39]). The cross-category analysis revealed that the association of eGFRcr and ACR was independent of each other, with the highest risk observed in eGFRcr <30 and ACR ≥300 (5.92 [5.37-6.53] vs. eGFRcr 90-105 and ACR <10). These findings were consistent across infection subtypes. Conclusion: Lower kidney function and higher albuminuria were independently associated with a higher risk of infection. The risk was substantially elevated even in mild to moderate CKD, with the highest risk seen in the most advanced stage of CKD. Infection prevention measures should target individuals across all CKD stages, and are particularly important for those with low eGFR and elevated ACR. Funding: NIDDK Support, Private Foundation Support