Kidney Function Recovery in COVID-19-Related AKI

Of patients hospitalized with COVID-19, 17% to 46% experience acute kidney failure (AKI); of those patients, 14% to 20% are treated with kidney replacement therapy (KRT). Critically ill patients with COVID-19-related AKI who were treated with dialysis had high rates of mortality. Dialysis requires intense resource use and patients on long-term dialysis experience adverse impacts on their quality of life as well as adverse clinical outcomes.

At present, there are no widely accepted tools for prediction of kidney recovery from AKI associated with COVID-19, particularly among patients with COVID-19-related AKI treated with KRT (AKI-KRT). In previous studies, mortality as a competing outcome has been difficult to account for; studies have also been limited by variation in patterns of recovery and lack of detailed data on clinical status at the time of AKI or initiation of KRT.

AKI associated with COVID-19, while occurring via multiple possible mechanisms, has less heterogeneity regarding timing and underlying cause. Caroline M. Hsu, MD, and colleagues conducted a multicenter cohort study to examine the association of severity of AKI with kidney function at the time of hospital discharge. Using baseline characteristics and measures of clinical status at the time of initiation of dialysis among those with AKI-KRT, the researchers examined clinical factors that may predict kidney recovery. Results were reported in the American Journal of Kidney Diseases [2022; 79(3):404-416].

The analysis utilized data from STOP-COVID (Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19), a multicenter cohort study that enrolled consecutive adult patients ≥18 years of age with laboratory-confirmed COVID-19 who were admitted to intensive care units (ICUs) at 68 hospitals across the United States. Patients admitted to an ICU between March 1 and June 22, 2020, were included.

Exposures were demographics (age, sex, race, ethnicity), baseline medical status (history of diabetes mellitus, estimated glomerular filtration rate [eGFR] using the CKD-EPI equation with a race coefficient), initial modality of dialysis (continuous KRT [CKRT], intermittent hemodialysis, or peritoneal dialysis), markers of severity of illness on KRT day (serum albumin, arterial pH, 24-hour urine output, maximum number of vasopressors or inotropes received that day), and occurrence of a major cardiac event (ventricular tachycardia, ventricular fibrillation, or cardiac arrest) on or preceding day 1 of KRT.

Patients were followed until hospital discharge or death. Kidney recovery was defined as independence from dialysis at discharge. Among survivors discharged with kidney recovery, serum creatinine at the time of discharge was used to calculate discharge eGFR, which was then compared with baseline eGFR in a series of descriptive analyses.

Of the 5154 patients enrolled in STOP-COVID, 741 had incomplete data and 192 were receiving maintenance dialysis at admission; the remaining 4221 patients were included in the current analysis. Of those, 63% (n=2681) were male, mean age was 61 years, and 26% (n=1085) had a baseline eGFR of ≤60 mL/min/1.73 m2.

A total of 2361 patients (56%) developed AKI within the first 14 days after admission to the ICU. Of those, 527 (12%) had stage 1 AKI, 468 (11%) had stage 2 AKI, 490 (12%) had stage 3 without KRT AKI, and 876 (21%) received KRT. There was an association between more severe AKI and greater mortality: among those with no AKI, AKI stage 1, AKI stage 2, AKI stage 3 without dialysis, and AKI-KRT, 26%, 44%, 60%, 73%, and 67% died, respectively. Among the patients with AKI-KRT, 11% were discharged dependent on dialysis. Of the patients with other stages of AKI, discharge with dialysis occurred in less than 0.5%.

Among the patients who survived to discharge, there was an association between more severe AKI and a higher likelihood of nonrecovery of kidney function at discharge. There was also an association between more severe AKI and higher serum creatinine at discharge. Percentages of those with a discharge Scr ≥1.5 times their baseline Scr or were continuing to receive KRT at discharge among those with no AKI, AKI stage 1, AKI stage 2, AKI stage 3 without dialysis, and AKI-KRT were 1%, 7%, 11%, 41%, and 52%, respectively.

Outcomes in the AKI-KRT Subcohort

In the subcohort with AKI-KRT (n=876), mean age was 61 years, 71.5% (n=626) were male, 41.3% (n=362) were Black, and 20.2% (n=177) were Hispanic or Latino. Forty-one percent (n=362) had baseline eGFR ≤60 mL/min/1.73 m2. The most common dialysis modality at initiation of KRT was CKRT (76.4%, n=590). Most patients required at least one vasopressor/isotope on the day of initiation of KRT (75.9%, n=665). In 521 patients (59.5%), urine output was <500 mL/day and <50 mL/day in 149 patients (17.0%) on day 1 of KRT.

Median serum albumin was 2.5 g/dL, and median arterial pH was 7.27. Prior to initiation of KRT, 32.8% of the patients (n=287) had received steroids, 17.1% (n=155) received tocilizumab, and 6.2% (n=54) received remdesivir. Median time elapsed from admission to the ICU to day 1 of KRT was 3 days.

In the AKI-KRT subcohort, 67% (n=588) died, 11% (n=95) were discharged alive and were continuing to receive dialysis at discharge, and 22% (n=193) had recovery of kidney function by the time of discharge. In multinomial logistic regression models, there were associations between both lower baseline kidney function and lower urine output on day 1 of KRT and nonrecovery of kidney function.

The odds of nonrecovery approximately doubled with each more severe baseline eGFR category, with odds ratios of 2.09 (95% confidence interval [CI], 1.09-4.04), 4.27 (95%CI, 1.99-9.17), and 8.69 (95% CI, 3.07-24.55) for patients with eGFR of 31-60, 16-30, and ≤15 mL/min/1.73 m2, respectively, compared with patients with eGFR >60 mL/min/1.73 m2. Compared with patients with urine output ≥500 mL/day, urine output 50-499 mL/day (oliguria) was associated with a 2.10-fold increased odds of nonrecovery (95% CI, 1.14-3.88). Urine output <50 mL/day was associated with a 4.2-fold increased odds of nonrecovery (95% CI, 1.72-9.39).

Limitations to the findings cited by the authors included only collecting data on Scr and KRT for the first 14 days following admission to the ICU and on hospital discharge, lack of postdischarge data, and the challenge associated with addressing death as a competing outcome.

In summary, the researchers said, “In this large cohort study of critically ill patients with COVID-19, decreased eGFR, and oliguria at the time of dialysis initiation were each significantly associated with a lower likelihood of kidney recover. The magnitude of the associations presented here may assist prognostication of long-term dialysis treatment, which carries implications for patients’ physical health and quality of life.”

Takeaway Points

  1. Results of a multicenter cohort study to examine clinical factors associated with kidney recovery in critically ill patients with COVID-19-related AKI who were treated with dialysis.
  2. The odds of nonrecovery of kidney function were greater for patients with lower eGFR at baseline.
  3. There was also an association between oliguria at the time of kidney replacement therapy initiation and nonrecovery of kidney function.