Persistent Increased Risk of Renal Replacement Therapy Following COVID-19: A Two-Year Follow-Up Study in Japan using propensity score matching and inverse probability censoring weighting

Although COVID-19 has been associated with multi-organ complications, growing evidence from Western populations suggests an increased risk of chronic kidney disease progression and end-stage renal disease (ESRD) following infection. However, data from Asian populations remain insufficiently characterized despite potential differences in comorbidity profiles and healthcare systems. Given the profound burden of ESRD on patients, families, and healthcare systems, elucidating whether COVID-19 increases this risk in the Asian context is of major clinical and public health importance. We investigated the association between COVID-19 and ESRD using a nationwide claims database encompassing all insurance types and age groups in Japan, providing a comprehensive population-based assessment.

We conducted a retrospective cohort study using nationwide claims data from 2020 to 2022. For each calendar month, patients with confirmed COVID-19 were matched 1:1 with individuals who had not been infected with COVID-19 as of that month, using propensity scores incorporating age, sex, Charlson comorbidity index, comorbidities, and medication use (fig1). Follow-up was continued until the earliest of the following: occurrence of the outcome, subsequent COVID-19 infection in controls, 24 months after the index month, or the end of the observation period. Outcomes were strictly defined by procedure codes, including the initiation of hemodialysis, peritoneal dialysis, and kidney transplantation. After matching, inverse probability of censoring weighting was applied to account for differential follow-up and for censoring. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Subgroup analyses were conducted by demographics and comorbidities, with p-values for interaction to assess effect modification. For COVID-19 severity, subgroup results were presented descriptively.

A total of 6,149,118 individuals were analyzed, including 3,074,559 patients with COVID-19 and matched controls (Fig2). The median age was 50–54 years, and 56% were female. After matching, all baseline covariates achieved excellent balance (absolute standardized differences <0.1). The median follow-up duration was seven months. During this period, 1573.2 weighted events of the primary composite outcomes were observed. COVID-19 infection was significantly associated with an increased risk of ESRD (HR 2.70, 95% CI 2.43–3.01). When analyzed separately, the HRs were 2.70 (95% CI 2.42–3.01) for hemodialysis, 2.94 (95% CI 1.16–7.44) for peritoneal dialysis, and 3.51 (95% CI 0.69–17.92) for kidney transplantation. As a negative control, the risk of acquired cataract surgery was not elevated (HR 1.01, 95% CI 0.98–1.03) (Fig3). Subgroup analyses demonstrated increased ESRD risk across all severity levels (HR 2.77, 95% CI 1.95-3.94 for hospitalized cases; HR 2.70, 95% CI 2.41-3.03 for outpatient cases). No significant interaction was observed by demographic and comorbidity subgroups.

In this nationwide matched cohort study, COVID-19 was associated with a markedly increased risk of ESRD during follow-up. Elevated risks were even observed in mild COVID-19. These findings underscore the need for proactive renal monitoring and preventive strategies in COVID-19 survivors in the post-COVID era.