Kidney Outcomes in Long COVID

Abstract

Background: COVID-19 is associated with increased risk of post-acute sequelae involving pulmonary and extrapulmonary organ systems-referred to as long COVID. However, a detailed assessment of kidney outcomes in long COVID is not yet available.

Methods: We built a cohort of 1,726,683 US Veterans identified from March 1, 2020 to March 15, 2021, including 89,216 patients who were 30-day survivors of COVID-19 and 1,637,467 non-infected controls. We examined risks of AKI, eGFR decline, ESKD, and major adverse kidney events (MAKE). MAKE was defined as eGFR decline ≥50%, ESKD, or all-cause mortality. We used inverse probability-weighted survival regression, adjusting for predefined demographic and health characteristics, and algorithmically selected high-dimensional covariates, including diagnoses, medications, and laboratory tests. Linear mixed models characterized intra-individual eGFR trajectory.

Results: Beyond the acute illness, 30-day survivors of COVID-19 exhibited a higher risk of AKI (aHR, 1.94; 95% CI, 1.86 to 2.04), eGFR decline ≥30% (aHR, 1.25; 95% CI, 1.14 to 1.37), eGFR decline ≥40% (aHR, 1.44; 95% CI, 1.37 to 1.51), eGFR decline ≥50% (aHR, 1.62; 95% CI, 1.51 to 1.74), ESKD (aHR, 2.96; 95% CI, 2.49 to 3.51), and MAKE (aHR, 1.66; 95% CI, 1.58 to 1.74). Increase in risks of post-acute kidney outcomes was graded according to the severity of the acute infection (whether patients were non-hospitalized, hospitalized, or admitted to intensive care). Compared with non-infected controls, 30-day survivors of COVID-19 exhibited excess eGFR decline (95% CI) of -3.26 (-3.58 to -2.94), -5.20 (-6.24 to -4.16), and -7.69 (-8.27 to -7.12) ml/min per 1.73 m² per year, respectively, in non-hospitalized, hospitalized, and those admitted to intensive care during the acute phase of COVID-19 infection.

Conclusions: Patients who survived COVID-19 exhibited increased risk of kidney outcomes in the post-acute phase of the disease. Post-acute COVID-19 care should include attention to kidney disease.

Keywords: COVID-19; ESKD; ESRD; PASC; acute kidney injury; eGFR decline; kidney function; long COVID; post-acute COVID; post-acute sequelae of SARS-CoV-2 infection.

Figure 1.

Risk and excess burden of post-acute COVID-19 kidney outcomes at 6 months. Participants who had COVID-19 were compared with users of the VHA healthcare system who had no record of a positive COVID-19 test (control group). Outcomes were ascertained starting from 30 days after the participant’s positive COVID-19 test through end of follow-up. Unadjusted incident rates in the COVID-19 and VHA users groups per 1000 person-years, HRs, and excess burden per 1000 persons at 6 months are provided. HRs and corresponding 95% CIs are plotted. MAKE was defined as a composite of eGFR decline ≥50%, ESKD, or all-cause mortality. All models were adjusted for a set of 29 predefined variables and 100 variables selected by a high-dimensional variable selection algorithm.

Figure 2.

Risk and excess burden of postacute COVID-19 kidney outcomes at 6 months in mutually exclusive cohorts of veterans with non-hospitalized COVID-19, those hospitalized with COVID-19, and those admitted to intensive care with COVID-19 during the first 30 days (acute phase) of the infection. Participants who had COVID-19 were compared with users of the VHA healthcare system who had no record of a positive COVID-19 test (control group). Outcomes were ascertained starting from 30 days after the participant’s positive COVID-19 test through end of follow-up. Unadjusted incident rates per 1000 person-years, HRs, and excess burden per 1000 persons at 6 months are provided for each COVID-19 group (non-hospitalized, hospitalized, and those admitted to intensive care during the acute phase of the infection). HRs and corresponding 95% CIs are plotted. MAKE was defined as a composite of eGFR decline ≥50%, ESKD, or all-cause mortality. All models were adjusted for a set of 29 predefined variables and 100 variables selected by a high-dimensional variable selection algorithm.

Figure 3.

and excess burden of post-acute COVID-19 kidney outcomes at 6 months in mutually exclusive cohorts of Veterans with non-hospitalized COVID-19, those hospitalized with COVID-19 with no evidence of an AKI, and those hospitalized with COVID-19 with an AKI during the first 30 days (acute phase) of the infection. Participants who had COVID-19 were compared with users of the VHA healthcare system who had no record of a positive COVID-19 test (control group). Outcomes were ascertained starting from 30 days after the participant’s positive COVID-19 test through end of follow-up. Unadjusted incident rates per 1000 person-years, HRs, and excess burden per 1000 persons at 6 months are provided for each COVID-19 group (non-hospitalized, hospitalized without an AKI, and hospitalized with an AKI during the acute phase of the infection). HRs and corresponding 95% CIs are plotted. MAKE was defined as a composite of eGFR decline ≥50%, ESKD, or all-cause mortality. All models were adjusted for a set of 29 predefined variables and 100 variables selected by a high-dimensional variable selection algorithm.

Figure 4.

Excess decline in eGFR in post-acute COVID-19 by care setting of the acute phase of the illness. Differences in the trajectory of eGFR by day of follow-up compared with users of the VHA healthcare system with no record of a positive COVID-19 test (control group), estimated after adjustment for baseline characteristics. Changes are estimated starting from 30 days after a COVID-19 positive test. Bands represent the 95% CI.

Figure 5.

Excess decline in eGFR in postacute COVID-19 by AKI status during the acute phase of the illness. Differences in the trajectory of eGFR by day of follow-up compared with users of the VHA healthcare system with no record of a positive COVID-19 test (control group), estimated after adjustment for baseline characteristics. Changes are estimated starting from 30 days after a COVID-19 positive test. Bands represent the 95% CI.