COVID-19 vs. Flu: Higher Long-Term Kidney Disease Risk with COVID-19

COVID-19’s Lingering Impact: Increased Kidney Disease Risk Compared to Influenza

New research published in Communications Medicine suggests that a COVID-19 infection carries a significantly higher risk of developing kidney disease – both in the short and long term – compared to an influenza infection. The study, analyzing data from over 3 million commercially insured adults in the United States, found that while both viruses posed a short-term risk of acute kidney injury (AKI), only COVID-19 was linked to a sustained increase in the risk of chronic kidney disease (CKD) and complete-stage kidney disease (ESKD). This finding adds to a growing body of evidence highlighting the potentially long-lasting health consequences of COVID-19, even beyond the acute phase of the illness.

Previous studies have indicated a connection between COVID-19 and a range of adverse health outcomes, including increased risks of cardiovascular disease, mental health disorders, and neurological issues. Research published earlier in 2025, for example, demonstrated a greater risk of rapid kidney decline following a COVID-19 infection compared to pneumonia. However, a direct comparison of kidney-related risks between COVID-19 and influenza had been lacking, prompting this latest investigation by researchers at Johns Hopkins Bloomberg School of Public Health and Penn State College of Medicine.

Understanding the Study Design and Findings

The researchers utilized a large retrospective cohort study, leveraging data from the MarketScan commercial health insurance database spanning 2020 to 2021. This allowed them to compare three distinct groups: individuals diagnosed with COVID-19 (over 939,000 participants with an average age of 41.3 years), a control group with influenza (nearly 1.9 million participants, also averaging 41.3 years), and a negative control group with neither infection (approximately 200,000 participants, with an average age of 39.7 years). The primary outcomes assessed were the onset of AKI, CKD, ESKD (requiring dialysis or transplantation), and glomerular disease.

The results revealed a substantial increase in risk for individuals who had contracted COVID-19. Compared to the influenza group, those with COVID-19 had a nearly twofold higher risk of developing any kidney disease (adjusted hazard ratio [aHR] of 1.93). Specifically, the risk of AKI was more than 2.7 times higher (aHR = 2.74), CKD was 38% higher (aHR = 1.38), ESKD was over three times higher (aHR = 3.22), and glomerular disease was 28% higher (aHR = 1.28).

While influenza was also associated with an increased risk of any kidney disease (aHR = 1.1) and AKI (aHR = 1.24) compared to the negative control group, it did not demonstrate a significant association with CKD, ESKD, or glomerular disease. Importantly, the study highlighted that the increased risks associated with COVID-19 persisted over time, while the risks associated with influenza diminished after the initial acute phase.

Acute vs. Long-Term Kidney Risks

The study further examined the timing of kidney injury following infection. The risk of AKI peaked within the first 180 days after both COVID-19 and influenza infection, with a particularly pronounced increase following COVID-19 (aHR = 4.35) compared to influenza (aHR = 1.51). However, while the AKI risk declined after 540 days for both viruses, the increased risk of CKD associated with COVID-19 remained significant at 180, 360, and 540 days post-infection. This sustained risk was not observed with influenza.

“In terms of timing, the risk of AKI was highest shortly after infection, while the increased risk of CKD persisted over a longer follow-up period,” explained Yue Zhang, PhD, MPH, a postdoctoral scholar at Johns Hopkins Bloomberg School of Public Health and one of the study’s authors. This distinction suggests that COVID-19 may trigger a different, more prolonged inflammatory or direct damaging process within the kidneys compared to influenza.

Why Might COVID-19 Pose a Greater Threat to Kidney Health?

The kidneys’ vulnerability to COVID-19 may stem from the virus’s ability to directly target these organs. SARS-CoV-2, the virus that causes COVID-19, enters cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor. Kidney cells express high levels of ACE2, making them susceptible to direct viral infection. Kidney cells produce transmembrane serine protease 2 (TMPRSS2), another enzyme that facilitates viral entry. Research published in the American Journal of Physiology-Renal Physiology details the mechanisms of SARS-CoV-2 entry into kidney cells.

Beyond direct viral damage, COVID-19 can also induce systemic inflammation and blood clotting abnormalities, both of which can contribute to kidney injury. Acute tubular necrosis, a common cause of AKI, can result from prolonged reduced blood flow to the kidneys. The immune response triggered by COVID-19 can sometimes lead to inflammation within the kidneys themselves (interstitial nephritis) or affect the filtering units (glomeruli).

Implications for Clinical Practice and Public Health

According to Nasrollah Ghahramani, MD, MS, J. Lloyd Huck Chair in Medicine and professor of medicine and of public health sciences at Penn State College of Medicine, clinicians should be aware of the potential for long-term kidney complications following COVID-19 infection. “Individuals with a history of COVID-19 infection may benefit from more frequent and longer-term monitoring of kidney function to allow earlier detection of kidney injury and potential preventive interventions,” he stated.

This proactive approach is particularly crucial for individuals with pre-existing risk factors for kidney disease, such as diabetes, hypertension, and obesity. Regular check-ups, including blood and urine tests to assess kidney function, can help identify early signs of damage and allow for timely intervention. The Centers for Disease Control and Prevention (CDC) provides comprehensive information on kidney disease, including risk factors, symptoms, and treatment options.

Future Research Directions

The researchers emphasize the need for further investigation to better understand the mechanisms underlying COVID-19-associated kidney disease and to develop strategies for prevention and treatment. Future studies could focus on identifying biomarkers that predict which individuals are at highest risk of developing CKD after COVID-19, as well as evaluating the effectiveness of different interventions to protect kidney function. Zhang and colleagues have already begun exploring the use of machine learning models to predict CKD and AKI risk in the post-COVID-19 period, aiming to create more personalized risk assessment tools for clinicians.

Ongoing surveillance of kidney disease incidence following COVID-19 is also crucial. As the pandemic evolves and new variants emerge, it will be important to monitor whether the risk of kidney complications changes over time. This information will be essential for informing public health recommendations and ensuring that individuals receive appropriate care.

this research underscores the importance of continued vigilance regarding the long-term health consequences of COVID-19. While the acute phase of the pandemic may be waning, the potential for lasting health impacts, particularly on vulnerable organs like the kidneys, remains a significant concern.