Advanced CKD Risk Doubles After COVID-19 Infection, Even Without Initial AKI

Compared with the flu, COVID-19 infection was linked with significant risks of kidney dysfunction.

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Compared with influenza, COVID-19 infection demonstrated a significantly higher long-term risk of kidney dysfunction, even when acute kidney injury (AKI) was absent in the early stages of infection, recent research reveals.¹ Individuals aged at least 45 years showed significantly higher rates of all kidney-related outcomes, including more than a twofold increase in advanced chronic kidney disease (CKD), and a threefold increase in the risk of reduced estimated glomerular filtration rate (eGFR).

With the emergence of SARS-CoV-2, there have been unprecedented challenges for health care systems globally, with extensive impacts beyond the acute phases.² Therefore, this matched cohort study, published in Scientific Reports, used data from more than 280,000 patients across the TriNetX nationwide network of 133 health care organizations.¹ This included 141,587 COVID-19 patients and an equal number of influenza patients. Researchers matched the cohorts by age, sex, race, comorbidities, and baseline lab values. Importantly, all patients with AKI in the first month post-infection were excluded to isolate the long-term effects of the viruses on kidney health.

The study's primary outcome, incidence of advanced CKD (stages 3–5) at 12 months compared with influenza, was significantly higher among those who had COVID-19 (HR, 2.02; 95% CI, 1.69-2.42; P < .0001). COVID-19 infection was also 3 times more likely than influenza to be associated with AKI development (HR, 3.04; 95%CI, 2.61-3.55; P < .0001) or reduced eGFR (< 60 mL/min/1.73 m²; HR, 3.01; 95%CI, 2.74-3.30; P < .0001) within 1 year.

Disparities Persist Across Subgroups

The risks of renal dysfunction after COVID-19 were consistently elevated across both men and women and particularly pronounced among individuals older than 45.

• Older adults (>45 years) experienced significantly higher rates of all kidney-related outcomes, including a more than twofold increase in advanced CKD (0.56% vs 0.29%; HR, 2.09; 95% CI, 1.74-2.53; P < .0001), and a tripled risk of reduced eGFR (2.79% vs 1.00%; HR, 3.08; 95% CI, 2.80–3.40; P < .0001).
• Younger patients (18–45 years) also had higher risks of AKI (0.16% vs 0.07%; HR, 2.29; 95% CI, 1.62-3.24, P < .0001) and reduced eGFR (0.23% vs 0.05%; HR, 4.47; 95% CI, 3.09-6.49, P < .0001), but the difference in advanced CKD between COVID-19 and influenza was not statistically significant (0.03% vs 0.02%; HR, 1.53; 95% CI, 0.76-3.07, P = .2311).
• Males showed greater vulnerability than females to AKI and eGFR decline (HR 3.78 vs 2.27).

COVID-19 Effects Persist Without Severe Disease

The researchers conducted several sensitivity analyses to probe whether the observed kidney risks were limited to patients with obvious complications like AKI or severe illness. Even after removing patients who developed AKI within one year of infection, the risk of advanced CKD remained significantly higher among those with COVID-19 (HR, 1.88; 95% CI, 1.59-2.22; P < .0001).

COVID-19 patients also exhibited greater kidney risk when compared to those hospitalized with influenza or who experienced severe outcomes. However, early hospitalization for COVID-19—often a marker of more severe disease—was not associated with increased risk of advanced CKD, suggesting that some chronic kidney effects may develop independently of initial disease severity.

Key Risk Factors for Advanced CKD

A Cox proportional hazards analysis identified several predictors of advanced CKD at 12 months:

• Diabetes mellitus (HR, 2.42; 95% CI, 2.24-2.62)
• Essential hypertension (HR, 2.14; 95% CI, 1.97-2.33)
• Older age (HR, 1.07; 95% CI, 1.07-1.08)
• Male sex (HR, 1.18; 95% CI, 1.10-1.26)

Public Health Implications

With over 1.4 million COVID-19 and 666,000 influenza cases identified in the study’s initial data pool, the researchers emphasized that this large-scale analysis adds critical insight into the long-term health consequences of SARS-CoV-2 infection.

"Our findings of increased CKD risk in COVID-19 patients without initial AKI suggest mechanisms distinct from acute damage pathways," they wrote. "This phenomenon can be explained by several pathophysiological processes."

The study concluded by acknowledging the increased association between COVID-19 and the risk of long-term kidney dysfunction compared with influenza. Monitoring should focus on high-risk groups, such as those with diabetes or hypertension, to better allocate care. They called for further research to guide targeted interventions and understand underlying causes.

References

1. Chen IW, Chang LC, Ho CN, et al. Association between COVID-19 and the development of chronic kidney disease in patients without initial acute kidney injury. Sci Rep 15, 10924 (2025). https://doi.org/10.1038/s41598-025-96032-4

2. Katz GM, Bach K, Bobos P, Cheung A, Décary S, Goulding S, Herridge MS, McNaughton CD, Palmer KS, Razak FA, Zhang B, Quinn KL. Understanding how post-COVID-19 condition affects adults and health care systems. JAMA Health Forum. 4(7):e231933. doi:10.1001/jamahealthforum.2023.1933.