Abstract
Background: Infections are a major cause of hospitalization in people with chronic kidney disease (CKD), with incidence similar to cardiovascular disease, yet the risk of infection has not been systematically studied across stages of CKD.
Methods: We analyzed data on 1,246,912 individuals across 47 cohorts in the CKD Prognosis Consortium, with information on estimated glomerular filtration rate based on serum creatinine (eGFRcr) and urinary albuminuria (ACR) (or proteinuria converted to ACR), to examine the association of eGFR and ACR with the risk of hospitalization with infection. Outcomes were ascertained through diagnostic 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, and cardiovascular system infections, and sepsis). Follow-up was censored on December 31, 2019 or on the last date of cohort follow-up, whichever was earlier. Multivariable Cox models were used to estimate hazard ratios (HRs).
Findings: During follow-up, 170,864 (13.7%) individuals had a hospitalization with infection (IR, 22.0 [ IQI, 16.2 – 31.0] per 1,000 person-yrs). In Cox models, compared to eGFRcr 90-105 ml/min/1.73m2 and ACR <10 mg/g, lower eGFRcr and higher ACR were each independently associated with an increased hazard of infection in a graded manner, including in eGFRcr 60-89 and 45-59 ml/min/1.73m2 (adjusted HRs [95% CI], 1.09 [1.06-1.13] and 1.39 [1.34-1.45]) and ACR 10-29 and 30-299 mg/g (1.40 [1.33-1.47] and 1.82 [1.72-1.92]). High eGFRcr ≥105 ml/min/1.73m2 was also associated with the risk of infection (1.22 [1.17-1.26]). Combined, eGFRcr <30 ml/min/1.73m2 and ACR ≥300 mg/g were associated with more than 6-fold higher hazard of infections (6.27 [5.70-6.90]). These findings were consistent across infection subtypes (e.g., HRs for lower respiratory tract infections, 1.26 [1.22-1.30] per -15 ml/min/1.73m2 in eGFR and 1.48 [1.44-1.53] per 8-fold increase in ACR).
Interpretation: Lower kidney function and higher albuminuria were independently associated with higher risk of infection. The risk was 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.
Methods: We analyzed data on 1,246,912 individuals across 47 cohorts in the CKD Prognosis Consortium, with information on estimated glomerular filtration rate based on serum creatinine (eGFRcr) and urinary albuminuria (ACR) (or proteinuria converted to ACR), to examine the association of eGFR and ACR with the risk of hospitalization with infection. Outcomes were ascertained through diagnostic 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, and cardiovascular system infections, and sepsis). Follow-up was censored on December 31, 2019 or on the last date of cohort follow-up, whichever was earlier. Multivariable Cox models were used to estimate hazard ratios (HRs).
Findings: During follow-up, 170,864 (13.7%) individuals had a hospitalization with infection (IR, 22.0 [ IQI, 16.2 – 31.0] per 1,000 person-yrs). In Cox models, compared to eGFRcr 90-105 ml/min/1.73m2 and ACR <10 mg/g, lower eGFRcr and higher ACR were each independently associated with an increased hazard of infection in a graded manner, including in eGFRcr 60-89 and 45-59 ml/min/1.73m2 (adjusted HRs [95% CI], 1.09 [1.06-1.13] and 1.39 [1.34-1.45]) and ACR 10-29 and 30-299 mg/g (1.40 [1.33-1.47] and 1.82 [1.72-1.92]). High eGFRcr ≥105 ml/min/1.73m2 was also associated with the risk of infection (1.22 [1.17-1.26]). Combined, eGFRcr <30 ml/min/1.73m2 and ACR ≥300 mg/g were associated with more than 6-fold higher hazard of infections (6.27 [5.70-6.90]). These findings were consistent across infection subtypes (e.g., HRs for lower respiratory tract infections, 1.26 [1.22-1.30] per -15 ml/min/1.73m2 in eGFR and 1.48 [1.44-1.53] per 8-fold increase in ACR).
Interpretation: Lower kidney function and higher albuminuria were independently associated with higher risk of infection. The risk was 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.
| Original language | English |
|---|---|
| Article number | 103372 |
| Journal | eClinicalMedicine |
| Early online date | 31 Jul 2025 |
| DOIs | |
| Publication status | Published - 31 Jul 2025 |
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The CKD Prognosis Consortium (CKD-PC) Data Coordinating Center is funded in part by a program grant from the US National Kidney Foundation and the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK100446). A variety of sources have supported enrollment and data collection including laboratory measurements, and follow-up in the collaborating cohorts of the CKD-PC. These funding sources include government agencies such as national institutes of health and medical research councils as well as foundations and industry sponsors listed in Supplemental Appendix S3.