American journal of kidney diseases : the official journal of the National Kidney Foundation · 2026
Associations of Pre-Pandemic CKD With Acute and Post-Acute COVID-19: The C4R Study.
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Choi Yuni, Jacobs David R, Kramer Holly J, Coresh Josef, Cushman Mary, Reiner Alexander P, Demmer Ryan T, Tracy Russell P, Sun Yifei, Balte Pallavi P, Raffield Laura M, Min Yuan-I, Vasan Ramachandran S, Xanthakis Vanessa, Regan Elizabeth A, Kanaya Alka M, Lash James P, Umans Jason G, Oelsner Elizabeth C
Аннотация
RATIONALE & OBJECTIVE: Kidney failure is associated with severe COVID-19, but data on early stage chronic kidney disease (CKD) and its relationship to acute and post-acute COVID-19 as well as postvaccination antibody responses are limited. We evaluated pre-pandemic CKD stage in relation to these outcomes.
STUDY DESIGN: Prospective cohort.
SETTING & PARTICIPANTS: Adults in 9 US population-based studies established since 1971, with pre-pandemic CKD measurements and follow-up for COVID-19 outcomes.
EXPOSURE: CKD stages (low CKD stage [reference], moderate CKD stage, high CKD stage, and very high CKD stage) defined by creatinine-based eGFR and urinary albumin-creatinine ratio.
OUTCOME: (1) COVID-19 hospitalization or death (self-report/medical records, 2020-2023); (2) RECOVER Long COVID Research Index score ≥11 (LCRI-positivity by questionnaires, 2023-2024); (3) post-vaccination anti-spike 1 (S1) IgG levels (dried blood spots, 2021‒2022).
ANALYTICAL APPROACH: Cause-specific hazards for severe COVID-19, logistic regression for LCRI positivity, and generalized additive models for anti-S1 IgG.
RESULTS: Among 26,039 participants, CKD stage was low in 81.7%, moderate in 13.0%, high in 3.6%, and very high in 1.7%. Over a median 550-day follow-up period (IQR, 314-636), 734 had severe COVID-19; 12.1% of infected patients (669 of 5,527) were classified as LCRI positive; and 3.1% (82 of 2,679) were anti-S1 IgG antibody nonreactive. A more severe CKD stage was associated with a greater risk for severe COVID-19: the HR for moderate stage CKD was 1.27 (95% CI, 1.03-1.56), for high stage CKD, 2.33 (1.77-3.06), and for very high stage CKD, 2.72 (1.88-3.92). Higher CKD stages were associated with lower anti-S1 IgG levels: -12.00% (95% CI, -21.14% to -1.78%) for moderate stage CKD, -27.03% (95% CI, -40.00% to -11.25%) for high stage CKD, and -48.9% (95% CI, -61.60% to -32.01%) for very high stage CKD. A higher prevalence of LCRI positivity was observed only among infected individuals with very high stage CKD (odds ratio, 2.20 [95% CI, 1.16-4.18]).
LIMITATIONS: Some outcomes were self-reported.
CONCLUSIONS: Higher CKD stages were associated with a greater risk for severe COVID-19 and a lower anti-S1 antibody response. No consistent association was observed between CKD stage and LCRI positivity except in individuals with very high stage CKD.
PLAIN-LANGUAGE SUMMARY: Chronic kidney disease (CKD) affects approximately 1 in 7 US adults, yet its impact on COVID-19 outcomes, particularly in early stage CKD, remains incompletely understood. We analyzed pre-pandemic CKD stage data from 9 population-based US cohorts to assess their associations with the risk of severe COVID-19, symptom-defined long COVID, and postvaccination anti-spike 1 IgG levels. More advanced stages of CKD had a stronger relationship with severe COVID-19 and a lower anti-S1 antibody response. No consistent association was observed with symptom-defined long COVID, although its prevalence was higher among individuals with very high stage CKD. These findings suggest an altered vaccine-induced immunity and increased susceptibility to both acute and post-acute COVID-19 outcomes among persons with advanced CKD. Adults with advanced CKD may benefit from targeted preventive measures.
STUDY DESIGN: Prospective cohort.
SETTING & PARTICIPANTS: Adults in 9 US population-based studies established since 1971, with pre-pandemic CKD measurements and follow-up for COVID-19 outcomes.
EXPOSURE: CKD stages (low CKD stage [reference], moderate CKD stage, high CKD stage, and very high CKD stage) defined by creatinine-based eGFR and urinary albumin-creatinine ratio.
OUTCOME: (1) COVID-19 hospitalization or death (self-report/medical records, 2020-2023); (2) RECOVER Long COVID Research Index score ≥11 (LCRI-positivity by questionnaires, 2023-2024); (3) post-vaccination anti-spike 1 (S1) IgG levels (dried blood spots, 2021‒2022).
ANALYTICAL APPROACH: Cause-specific hazards for severe COVID-19, logistic regression for LCRI positivity, and generalized additive models for anti-S1 IgG.
RESULTS: Among 26,039 participants, CKD stage was low in 81.7%, moderate in 13.0%, high in 3.6%, and very high in 1.7%. Over a median 550-day follow-up period (IQR, 314-636), 734 had severe COVID-19; 12.1% of infected patients (669 of 5,527) were classified as LCRI positive; and 3.1% (82 of 2,679) were anti-S1 IgG antibody nonreactive. A more severe CKD stage was associated with a greater risk for severe COVID-19: the HR for moderate stage CKD was 1.27 (95% CI, 1.03-1.56), for high stage CKD, 2.33 (1.77-3.06), and for very high stage CKD, 2.72 (1.88-3.92). Higher CKD stages were associated with lower anti-S1 IgG levels: -12.00% (95% CI, -21.14% to -1.78%) for moderate stage CKD, -27.03% (95% CI, -40.00% to -11.25%) for high stage CKD, and -48.9% (95% CI, -61.60% to -32.01%) for very high stage CKD. A higher prevalence of LCRI positivity was observed only among infected individuals with very high stage CKD (odds ratio, 2.20 [95% CI, 1.16-4.18]).
LIMITATIONS: Some outcomes were self-reported.
CONCLUSIONS: Higher CKD stages were associated with a greater risk for severe COVID-19 and a lower anti-S1 antibody response. No consistent association was observed between CKD stage and LCRI positivity except in individuals with very high stage CKD.
PLAIN-LANGUAGE SUMMARY: Chronic kidney disease (CKD) affects approximately 1 in 7 US adults, yet its impact on COVID-19 outcomes, particularly in early stage CKD, remains incompletely understood. We analyzed pre-pandemic CKD stage data from 9 population-based US cohorts to assess their associations with the risk of severe COVID-19, symptom-defined long COVID, and postvaccination anti-spike 1 IgG levels. More advanced stages of CKD had a stronger relationship with severe COVID-19 and a lower anti-S1 antibody response. No consistent association was observed with symptom-defined long COVID, although its prevalence was higher among individuals with very high stage CKD. These findings suggest an altered vaccine-induced immunity and increased susceptibility to both acute and post-acute COVID-19 outcomes among persons with advanced CKD. Adults with advanced CKD may benefit from targeted preventive measures.