Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jul 31:86:103372.
doi: 10.1016/j.eclinm.2025.103372. eCollection 2025 Aug.

Estimated glomerular filtration rate, albuminuria, and risk of infection: a collaborative meta-analysis of individual participant data

Junichi Ishigami  1   2 , Aditya Surapaneni  3 , Kunihiro Matsushita  1   2 , Josef Coresh  4 , Morgan E Grams  3 , Shoshana H Ballew  4 , Yingying Sang  4 , Benedicte Stengel  5 , Johan Ärnlöv  6 , Samira Bell  7 , Juan-Jesus Carrero  8   9 , Alexander R Chang  10 , Elizabeth L Ciemins  11 , Richard Haynes  12 , Joachim Ix  13   14 , Fruzsina Kotsis  15 , Jennifer S Lees  16   17 , Krutika Pandit  3 , Panduranga Rao  18 , Cassianne Robinson-Cohen  19 , Natalia Alencar de Pinho  5 , Keiichi Sumida  20 ; CKD Prognosis Consortium
Collaborators, Affiliations

Estimated glomerular filtration rate, albuminuria, and risk of infection: a collaborative meta-analysis of individual participant data

Junichi Ishigami et al. EClinicalMedicine. .

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 conducted a meta-analysis of individual participant data including 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 1000 person-yrs). In Cox models, compared to eGFRcr 90-104 ml/min/1.73 m2 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/1.73 m2 (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/1.73 m2 was also associated with the risk of infection (1.22 [1.17-1.26]). Combined, eGFRcr <30 ml/min/1.73 m2 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/1.73 m2 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.

Funding: US National Kidney Foundation and the National Institute of Diabetes and Digestive and Kidney Diseases.

Keywords: Albuminuria; Chronic kidney disease; Estimated glomerular filtration rate; Infection; Risk.

PubMed Disclaimer

Conflict of interest statement

Drs. Alencar de Pinho and Stengel have received financial support of the Agence Nationale de la Recherche (France) through the 2010 «Cohortes-Investissements d’Avenir» program (ANR-IA-COH-2012/3731), the 2010 national Programme Hospitalier de Recherche Clinique, and through a public-private partnership with GlaxoSmithKline (GSK) since 2012, Boehringer Ingelheim France since 2022, Novo Nordisk since 2024, Fresenius Medical Care from 2012 to 2024, Vifor France from 2018 to 2023, Sanofi-Genzyme from 2012 to 2015, Baxter and Merck Sharp & Dohme-Chibret (MSD France) from 2012 to 2017, Amgen from 2012 to 2020, Lilly France from 2013 to 2018, Otsuka Pharmaceutical from 2015 to 2020, and AstraZeneca from 2018 to 2021. All grants are made to Paris-Saclay University. Dr. Ärnlöv has served on advisory boards for Astella, AstraZeneca, and Boehringer Ingelheim, and has received lecturing fees from AstraZeneca and Boehringer Ingelheim, all of which are unrelated to the present work. Dr. Bell has received consultancy fees from Astra Zeneca, GSK and Bayer and participated on the Stada UK unrelated to present work. Dr. Carrero received grants to Karolinska Institutet from AstraZeneca, Boehringer, MSD, Astellas, Novonordisk, ViforPharma as well as honoraria from Fresenuis Kabi. Dr. Chang has received grant funding from Novartis, Boehringer-Ingelheim, Bayer, Novo Nordisk, National Kidney Foundation; consulting fees from Amgen serving on the advisory board. Dr. Coresh received grants from NIH. Dr. Grams has received grants from NIH and honoraria from University of Pennsylvania, Columbia University Medical Center, and NephSAP; she also receives support to attend meetings from KDIGO, European Renal Association, University of Pennsylvania, Korean Society of Nephrology, Hong Kong Society of Nephrology, and the Kidney Research Institute; and she has a leadership role in the American Society of Nephrology Publication Committee, Kidney Disease: Improving Global Outcomes (Co-Chair), National Kidney Foundation Scientific Advisory Committee, United States Renal Data System Scientific Advisory Board, Kidney Institute Executive Committee, Clinical Journal of American Society of Nephrology. American Journal of Kidney Diseases, and the Journal of American Society of Nephrology. Dr. Haynes received an institutional grant to support the SHARP trial from Merck Sharp & Dohme and grants from Boehringer Ingelheim, Roche, and Regeneron; he has also served as an unpaid member of the DMC at Eli Lilly. Dr. Lees has received personal lectureship honoraria from Astra Zeneca and consulting fees from Boehringer Ingelheim outside the submitted work. Dr. Matsushita received grants from the NIH and Resolve to Save Lives as well as consulting fees from RhythmX AI, and honoraria from Fukuda Denshi. Dr. Rao received a grant from NIDDK. Dr. Robinson-Cohen received grants from NIDDK. Dr. Ix received grants from NIDDK, NHLBI, and Breakthrough T1D; consulting fees from Bayer and AstraZeneca; and support to attend meetings by the American Society of Nephrology and Kidney Disease: Improving Global Outcomes; and has a leadership role in AlphaYoung; and received equipment or materials from Genentech. All other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The association of categorical (A) and continuous (B) eGFRcr and (C) ACR with risk of hospitalization with all-cause infection in the ACR/PCR population. The analysis included participants of cohorts with data on both eGFRcr and ACR or PCR (47 cohorts; N = 1,246,912). The models were adjusted for age, sex, body mass index, hypertension, diabetes, total cholesterol, use of aspirin or glucocorticoids, history of cardiovascular disease, cancer, or chronic obstructive pulmonary disease, current and former smoking. In the cross-category analysis, the model for the colored heatmap also includes interaction terms between eGFR and ACR categories. Cells are colored in green if HR < 1.1; yellow if HR < 2.0, orange if HR < 3.0, and red if HR ≥ 3.0. In the linear spline models, the model was further adjusted for ACR (for eGFRcr analysis) or eGFRcr (for ACR analysis). Abbreviations: eGFRcr, estimated glomerular filtration rate based on serum creatinine; ACR, albumin-to-creatinine ratio; HR, hazard ratio; CKD, chronic kidney disease.
Fig. 2
Fig. 2
Adjusted for hazard ratios of site-specific infections by eGFRcr (A) and ACR (B) in the ACR/PCR population. (A) Hazard ratio per 15 ml/min/m2 decrease in eGFRcr in eGFRcr <60 ml/min/1.73 m2 and (B) Hazard ratios per 8-fold increase in ACR. Models were adjusted for age, sex, body mass index, hypertension, diabetes, total cholesterol, use of aspirin or glucocorticoids, history of cardiovascular disease, cancer, and chronic obstructive pulmonary disease, current and former smoking. eGFRcr and ACR models adjusted for each other. Abbreviations: ACR, urinary albumin-to-creatinine ratio; PCR, urinary protein-to-creatinine ratio; eGFRcr, estimated glomerular filtration rate based on serum creatinine.
Fig. 3
Fig. 3
Predicted 5-year probability of hospitalization with infection by eGFRcr (A) and ACR (B) categories in the ACR/PCR population. Models were adjusted for age, sex, body mass index, hypertension, diabetes, total cholesterol, use of aspirin or glucocorticoids, history of cardiovascular disease, cancer, and chronic obstructive pulmonary disease, current and former smoking. eGFRcr and ACR models adjusted for each other. Baseline risk was derived from the Geisinger cohort with median overall infection risk. Abbreviations: ACR, urinary albumin-to-creatinine ratio; PCR, urinary protein-to-creatinine ratio; eGFRcr, estimated glomerular filtration rate based on serum creatinine.
See this image and copyright information in PMC

References

    1. Johansen K.L., Gilbertson D.T., Li S., et al. US renal data system 2023 annual data report: epidemiology of kidney disease in the United States. Am J Kidney Dis. 2024;83(4S1):A8–A13. - PubMed
    1. Bouchard J., Acharya A., Cerda J., et al. A prospective international multicenter study of AKI in the intensive care unit. Clin J Am Soc Nephrol. 2015;10(8):1324–1331. - PMC - PubMed
    1. Cowan L.T., Lutsey P.L., Pankow J.S., Matsushita K., Ishigami J., Lakshminarayan K. Inpatient and outpatient infection as a trigger of cardiovascular disease: the ARIC study. J Am Heart Assoc. 2018;7(22) - PMC - PubMed
    1. Ishigami J., Cowan L.T., Demmer R.T., et al. Hospitalization with major infection and incidence of end-stage renal disease: the Atherosclerosis risk in Communities (ARIC) study. Mayo Clin Proc. 2020;95(9):1928–1939. - PMC - PubMed
    1. James M.T., Laupland K.B., Tonelli M., et al. Risk of bloodstream infection in patients with chronic kidney disease not treated with dialysis. Arch Intern Med. 2008;168(21):2333–2339. - PubMed

LinkOut - more resources