Decline in Estimated Glomerular Filtration Rate After Acute Kidney Injury: A Surrogate Endpoint?

• Background: Often a transient condition, acute kidney injury (AKI) is not currently accepted as an endpoint for drug registration trials by the US FDA. We sought to determine whether an intermediate-term change in eGFR after AKI has a sufficiently strong relationship with subsequent ESRD to serve as an alternative endpoint in clinical trials of AKI preventionand/or treatment.Methods: We evaluated 161,185 US veterans who underwent major surgery between2004-2011. Post-surgical AKI was defined by the KDIGO creatinine criteria;decline in eGFR was calculated from pre-hospitalization value to two time-points post-discharge (60-days, 90-days) and related to ESRD and mortality using Cox proportional hazards regression.Results: In-hospital mortality varied by AKI status, ranging from 1% for patients without AKI to 35% for those with dialysis-requiring AKI. An eGFR decline of ³30% at 60-days was relatively frequent: 2.5%, 9.7%, 17.2%, and 28.6% in those with no AKI, Stage 1 AKI, Stage 2 AKI, and Stage 3 AKI, respectively. There was a graded relationship between eGFR decline at 60-days and risk of ESRD in persons both with and without AKI (Figure). Compared to stable eGFR/no in-hospital AKI, the adjusted hazard ratio (HR) of ESRD associated with a 30% decline at 60-days after AKI was 6.42 (95% CI: 4.8-8.7). Risks for mortality associated with eGFR decline were smaller: the HR for 30% decline 60-days after in-hospital AKI was 1.59 (95% CI: 1.46-1.73). Risk relationships were similar at 90-days.Conclusions: A 30% decline in eGFR from pre-hospitalization baseline to 60-days or 90-days after an episode of AKI may be an acceptable surrogate endpoint in trials of AKI prevention and/or treatment.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

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