Study Underscores Need for Long-term Follow-up After AKI

Acute kidney injury (AKI) is common and is associated with poor short-term and long-term clinical consequences.^[1] Specifically, studies^[2] report a strong association of AKI and decline in estimated glomerular filtration rate (eGFR) and progression to end-stage renal disease. But eGFR is only one clinical measure of kidney function. Less is known about the association of AKI with subsequent development of proteinuria.

Preclinical studies have suggested a mechanistic link between AKI and residual damage in the tubules, which could lead to proteinuria; however, data from clinical trials are limited. One large study^[3] of more than 90,000 US veterans reported that the odds of having 1+ or greater dipstick proteinuria in the 12 months after hospitalization were significantly higher in patients who had AKI compared with those who had not had AKI. While informative, this study was limited by dipstick detection of proteinuria and clinical measures of proteinuria (which may have been ascertained for cause and thus may bias the quantification of proteinuria).

A New Prospective Study

A July 2019 study^[4] published in the Journal of the American Society of Nephrology extends this previous work to examine the association of AKI and the subsequent development of proteinuria among 2048 individuals from two prospective research cohorts: the ASSESS-AKI study and a subset of the CRIC study. The AKI episodes in hospitalized patients occurred after enrollment in each study and were based on measurements of inpatient serum creatinine. AKI was defined as at least a 50% relative difference between the peak and nadir inpatient serum creatinine concentrations during a single hospitalization. Proteinuria was quantified by either spot or 24-hour urine samples collected at annual study visits.

In all, 324 individuals were hospitalized with AKI after enrollment. Among the first episodes of patients hospitalized with AKI, 50.3% were KDIGO stage 1 in severity, 23.8% were stage 2, and 25.9% were stage 3. In multivariable models, the authors report a 9% increase in urine protein-to-creatinine ratio in those hospitalized with AKI compared with those without AKI. Furthermore, greater severity of AKI was associated with greater risk for proteinuria; for example, stage 3 AKI was associated with a 24% increase in urine protein-to-creatinine ratio. When individuals receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) were excluded, the associations were similar to the primary analysis.

The Takeaways

The findings of this study have important clinical implications. First, they underscore the long-term sequela of AKI and the need for post-AKI medical care; many patients who experience AKI are lost to follow-up care. Second, they highlight the importance of a comprehensive kidney assessment in high-risk individuals, such as those with previous AKI. In addition to eGFR, this assessment should include a systematic analysis of proteinuria. Sole focus on eGFR may underestimate or miss long-term kidney damage in some individuals. Third, the findings stress the need for further studies to investigate the use and timing of currently available therapies (eg, RAAS inhibitors) as well as novel therapies to mitigate the kidney and systemic downstream consequences of AKI.

Withholding ACE inhibitors and ARBs around an episode of AKI has become common practice. When and whether to reinitiate these therapies remains unclear, but the known kidney and cardiac protective effects of these drugs are particularly important for high-risk individuals, such as those with AKI. Thus, current practice should consider routine monitoring for AKI and treatment for proteinuria.

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