Timing of Recovery from AKI Predictor of Subsequent Loss of Kidney Function

The rates of acute kidney injury (AKI) are growing, resulting in an increase in the number of survivors requiring ongoing medical care. AKI, particularly severe AKI, is associated with increased risk for incident and progressive chronic kidney disease (CKD), cardiovascular disease, future hospitalizations, recurrent AKI, and death.

Available data suggest that few patients with AKI receive nephrology care after hospital discharge. Identification of which patients would benefit from post-discharge specialist care and which elements of nephrology-based care would be helpful has not been established. The majority of studies designed to examine risk factors for poor outcomes after AKI have concentrated on the severity of AKI or the degree of recovery. Results of these studies indicate an association between more severe injury and less recovery of kidney function and higher risk of death or development of CKD or kidney failure.

Another indicator of future risk may be the timing of recovery. Edward D. Siew, MD, MSCI, and colleagues conducted a retrospective cohort study to test the hypothesis that recovery from moderate to severe AKI may last weeks or months and that there would be an association between duration of recovery and a hastened rate of future loss of kidney function. The study was designed to examine the association between timing of recovery and future loss of kidney function among patients who survived moderate to severe AKI. Study results were reported in the American Journal of Kidney Diseases [2020;75(2):204-213].

The study was conducted among a national cohort of US veterans ≥18 years of age who were hospitalized with moderate to severe AKI. Data were collected from January 1, 2002, to December 31, 2014. Baseline data were obtained from 730 days prior to hospital admission to 90 days following hospital discharge. The cohort included 4,169,266 adults hospitalized in 116 Veterans Affairs hospitals between January 1, 2004, and December 31, 2011.

Exclusion criteria were non-VA follow-up, baseline estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m², kidney transplantation, or registry within the US Renal Data System prior to the index hospitalization. In-hospital exclusions were stage 1 AKI and an uncertain diagnosis of AKI. Post-hospital exclusions were patients who did not recover to within 120% of baseline serum creatinine and patients for whom the timing of recovery could not be well characterized. Other exclusions were patients with evidence of recurrent AKI or those whose final eGFR during the recovery window was <15 mL/,min/1.73 m².

The primary outcome of interest was a composite outcome of time to a sustained 40% decline in eGFR or kidney failure from the most recent serum creatinine/eGFR value prior to the end of the 90-day recovery window. Kidney failure was defined as having two outpatient eGFRs of <15 mL/min/1.73 m² greater than 90 days apart, receipt of two dialysis procedures more than 90 days apart, kidney transplantation, or registry in the USDRD, whichever came first.

The final cohort included 47,903 unique patient hospitalizations in which the patient experienced Kidney Disease Improving Global Outcomes stages 2 to 3 AKI, recovered to within 120% of baseline serum creatinine within 90 days, and survived to 90 days without an episode of recurrent AKI or receiving dialysis.

Of the 47,903 patients, 61% (n=29,316) recovered by 1 to 4 days following the peak serum creatinine level, 22% (n=10.360) recovered by 5 to 10 days, 9% (n=4520) recovered by 11 to 30 days, and 8% (n=3707) recovered in the 31- to 90-day period. During a median follow-up time of 42 months, the unadjusted incidence rates per 100 person-years for the primary outcome were 2.01 in the 1- to 4-day group, 3.55 in the 5- to 10-day group, 3.86 in the 11- to 30-day groups, and 3.68 in the 31- to 90-day group. Median times until the primary outcome were 721, 506, 425, and 445 days in the 1- to 4-day group, 5- to 10-day group, 11- to 30-day group, and 31- to 90-day group, respectively.

Following risk adjustment, the overall hazard ratios (HRs) were estimated per patient group identified by time to recovery using 1- to 4-day recovery as the referent group. The risk adjusted HRs were: for patients in the 5- to 10-day recovery group, 1.33 (95% confidence interval [CI], 1.24-1.43); for patients in the 11- to 30-day recovery group, 1.41 (95% CI, 1.28-1.54); and for patients in the 31- to 90-day recovery group, 1.58 (95% CI, 1.43-1.75). The same results were found in straight covariate-adjusted models.

In analysis of subgroups stratified by baseline CKD, there were similar associations between the risk-adjusted HRs and the overall cohort analysis. The greatest absolute increase in incidence rates associated with longer recovery was seen in the highest risk quintiles (81%-100%), with an increase in incidence from approximately six per 100 person-years to 10 to 13 per 100 person-years.

The predominately male study population and the potential for residual confounding were cited by the authors as limitations to the study findings. Also cited was the inability to make causal inferences due to the retrospective design of the study.

In conclusion, the researchers said, “Recovery from moderate to severe AKI is heterogeneous and can take up to several months. The timing of recovery is an independent predictor of future loss of kidney function and may be useful information to help further risk stratify survivors of AKI. Future studies to identify whether the trajectory of recovery can be modified to improve outcomes are warranted.”

Takeaway Points

1. A retrospective cohort study was designed to examine the independent association between the timing of recovery from moderate to severe acute kidney injury (AKI) and subsequent loss of kidney function.
2. In a large cohort of US veterans, 61% of patients with AKI recovered within 1 to 4 days, 22% within 5 to 10 days, 9% within 11 to 30 days, and 8% within 31 to 90 days.
3. With the 1- to 4-day group as referent, recovery within 5 to 10, 11 to 30, and 31 to 90 days was associated with increased rates of a sustained 40% decline in estimated glomerular filtration rate during the 90-day recovery period or kidney failure.