AKI during Hospitalization for COVID-19 and Kidney Function at Discharge

Patients hospitalized with severe COVID-19 infection commonly develop acute kidney injury (AKI). There are wide variations in the reported incidence of AKI among that patient population; results of recent studies from the United States suggest an incidence rate of as high as 37% to 40%. Patients hospitalized with COVID-19 who experience AKI face poor prognosis, increased length of stay, and increases in healthcare costs. Further, patients with COVID-19 who survive AKI appear to be at increased risk of death and incident chronic kidney disease (CKD).

Researchers, led by Jia H. Ng, MD, MSCE, updated results from a previous study on AKI in COVID-19 among 5449 patients. The current study, reported in the American Journal of Kidney Diseases [2021; 77(2):204-215], included 9657 patients with COVID-19, >99% of whom have completed outcomes. The study was designed to provide analysis of in-hospital mortality and kidney outcomes among patients with COVID-19 and AKI.

The primary outcome of interest in the retrospective observational cohort study was in-hospital death. Secondary outcomes were requiring dialysis at discharge and recovery of kidney function. The study was conducted in a large New York health system. Data were obtained from 13 hospitals using the enterprise inpatient electronic health record Sunrise Clinical Manager (Allscripts).

The cohort included all adult patients ≥18 years of age with positive results by polymerase chain reaction testing of a nasopharyngeal sample for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who were hospitalized from March 1, 2020, to April 27, 2020. AKI was defined according to Kidney Disease: Improving Global Outcomes criteria as an increase in serum creatinine level by 0.3 mg/dL within 48 hours or 1.5 to 1.9 times increase in serum creatinine level from baseline within 7 days (stage 1); 2 to 2.9 times increase in serum creatinine level within 7 days (stage 2); and 3 or more times increase in serum creatinine level within 7 days or initiation of dialysis (stage 3).

During the study period, 11,635 patients were admitted to 13 health system hospitals with a diagnosis of COVID-19. Of those patients, 9657 patients were included in the final cohort. Follow-up continued until June 4, 2020, the day of death, or the day of discharge, whichever came earlier. A total of 2409 patients were admitted to an intensive care unit (ICU), 2033 were treated with mechanical ventilation, and 2075 required vasopressor support during the hospital stay. Within the study cohort, 2418 patients died (25.0%), 7149 (74.0%) were discharged home, and 90 (0.9%) were still admitted at study end. Complete hospital disposition data were available for 99.6% of patients without AKI, 98.1% of patients with AKI stage 1 to 3, and 96.2% of patients with AKI stage 3 requiring dialysis (AKI 3D).

Of the 9657 patients in the study cohort, 39.9% (n=3854) developed AKI: 33.3% (n=3216) had AKI stages 1 to 3 (1644 with stage 1, 840 with stage 2, and 732 with stage 3) and 6.6% (n=638) had AKI 3D. Following accounting for follow-up time, the incidence rate of AKI was 38.3 per 1000 patient-days (32.0 per 1000 patient-days for AKI 1-3 and 6.3 per 1000 patient-days for AKI 3D). The group of patients who developed AKI had a higher proportion with comorbid conditions (diabetes mellitus, coronary artery disease, heart failure, and chronic kidney disease [CKD]). The AKI 3D group had the highest levels of inflammatory markers (D-dimer, C-reactive protein, and serum ferritin), followed by the AKI stage 1-3 group and the non-AKI group.

Of the 3216 patients in the AKI 1-3 group, 40.8% (n=1313) required mechanical ventilation and 42.1% (n=1354) required vasopressors. In the group with AKI 3D (n=638), 91.0% (n=581) required mechanical ventilation and 91.5% (n=584) required vasopressors.

Median time to AKI diagnosis was 10.3 hours following initiation of mechanical ventilation and 7.3 hours after initiation of vasopressor therapy. Among patients who required mechanical ventilation and had AKI, 74.7% (n=1415/1894) developed AKI following initiation of mechanical ventilation; among patients with AKI who required vasopressor therapy, 70% (n=1357/1938) developed AKI following vasopressor therapy initiation.

Among patients without AKI (n=5801), 7.3% (n=421) experienced in-hospital death, a rate of 10.8 deaths per 1000 patient-days. Among the 3216 patients with AKI 1-3, 46.4% (n=1491) died, for a rate of 31.1 deaths per 1000 patient-days. Using the non-AKI group as reference, the unadjusted hazard rate (HR) for in-hospital mortality was 5.6 (95% confidence interval [CI], 5.0-6.3) among patients with AKI 1-3. Following adjustment for baseline demographics, comorbidity, and severity of illness, the risk for in-hospital mortality remained significant. Of the patients with AKI 3D, 79.3% (n=506) died (37.5 deaths per 1000  patient-days). Using the non-AKI group as reference, the unadjusted HR for in-hospital mortality was 11.3 (95% CI, 9.6-13.1).

There were significant differences based on AKI status in median length of stay in patients who survived to discharge. Patients with AKI 3D had the longest median length of stay (29.2 days), followed by patients with AKI 1-3 (11.6 days), and those in the non-AKI group (5.2 days).

Among the 3854 patients who developed AKI, 83.4% (n=3216) developed AKI 1-3 during their admission; of those, 51.7% (n=1663) survived and 74.1% (n=1233/1663) regained kidney function. Median serum creatinine level on discharge was lower than median admission and peak serum creatinine levels across all stages of AKI.

For patients with AKI 3D, 16.9% (n=108/638) survived and 3.7% (n=24) remained hospitalized at the end of the study period. Among the survivors, 66.7% (n=72) had recovery of kidney function (not requiring dialysis at discharge) and a minimum of 33% decline in discharge serum creatinine from peak serum creatinine level. Among the patients who recovered kidney function, 75% (n=54) had a discharge serum creatinine level lower than the admission and peak levels. Among patients with AKI 3D who survived, the remaining 33.3% (n=36/108) did not achieve recovery of kidney function. Of those patients, 33 required dialysis at discharge and three were discharged off dialysis but did not have at least 33% decline in discharge serum creatinine level from peak level. Median time off dialysis prior to hospital discharge was 17.0 days.

Prehospitalization chronic kidney disease was the only independent risk factor associated with needing dialysis at discharge (odds ratio, 9.3; 95 % CI, 2.3-37.8).

Limitations to the study cited by the researchers were the observational retrospective design and limiting the cohort to patients admitted to centers in the New York metropolitan area during the initial peak of the pandemic.

In conclusion, the researchers said, “We found that the development of AKI during hospitalization with COVID-19 was associated with a substantial increase in risk for death. This risk was amplified when AKI resulted in dialysis. Most surviving patients with COVID-19 and AKI experienced substantial kidney recovery before discharge. In contrast, among those who had AKI 3D and survived, 30.6% still needed dialysis at discharge, a group of patients whose subsequent outcomes will require further study.”

Takeaway Points

1. Researchers conducted an observational retrospective cohort study in patients in 13 hospitals in metropolitan New York who were hospitalized with COVID-19 between March and April 2020 to examine outcomes of patients who developed acute kidney injury (AKI) while hospitalized.
2. The AKI incidence rate was 38.4 per 1000 patient-days. Incidence rates of in-hospital mortality for patients without AKI, those with AKI stages 1-3, and those with AKI requiring dialysis (AKI 3D) were 10.8, 31.1, and 37.5 per 1000 patient-days, respectively.
3. Among patients with AKI 1-3 who survived to discharge, 74.1% recovered kidney function. Among those with AKI 3D who survived to discharge, 30.6% remained on dialysis at discharge.