Recovery after Acute Kidney Injury

John A Kellum, Florentina E Sileanu, Azra Bihorac, Eric A J Hoste, Lakhmir S Chawla, John A Kellum, Florentina E Sileanu, Azra Bihorac, Eric A J Hoste, Lakhmir S Chawla

Abstract

Rationale: Little is known about how acute kidney injury (AKI) resolves, and whether patterns of reversal of renal dysfunction differ among patients with respect to ultimate recovery.

Objectives: We sought to examine different patterns for AKI reversal that are found in patients and assess how they relate to postdischarge outcomes.

Methods: We studied 16,968 critically ill patients with Kidney Disease Improving Global Outcomes stage 2 or 3 AKI, using an electronic database. Reversal of AKI was defined as alive and no longer meeting criteria for even stage 1. Recovery was defined as reversal at hospital discharge.

Measurements and main results: We observed five patterns. The most common (4,508; 26.6%) was early reversal that was sustained through discharge, but almost as many patients (4,496; 26.5%) had no reversal at all. The remaining patients had late reversal after Day 7 (9.7%); early reversal with one or more relapses, but with ultimate recovery (22.5%); and relapsing without recovery (14.7%). Outcomes for patients with these phenotypes were quite different, with age-adjusted 1-year survival varying from more than 90% for early reversal to less than 40% for patients never reversing. Relapses are common (37.3%), especially in the first 72 hours after reversal, and are associated with a fivefold increased risk for death by 1 year compared with early sustained reversal.

Conclusions: We have identified five distinct recovery phenotypes on the basis of the clinical course over the first week after AKI manifestation. These phenotypes may identify patients amenable to therapeutic intervention. Long-term outcomes are associated with recovery status at hospital discharge.

Keywords: critical care; dialysis; outcomes; renal failure; survival.

Figures

Figure 1.
Figure 1.
Conceptual model. Acute kidney injury (AKI) is an abrupt loss of renal function developing over the course of 7 days or less (1). Although the actual start of AKI may not be identified (more than half of AKI cases are community acquired), and many cases may not resolve rapidly, we defined “early reversal” as absence of AKI for at least 24 hours within 7 days of first documented AKI. *Recovery status was determined at hospital discharge, but we recognize that recovery may proceed out further, and a true final status would be better assessed at 90 days or longer.
Figure 2.
Figure 2.
Study flow. Source population included all patients admitted to the intensive care unit (ICU). *Exclusions: not stage 2 or 3 acute kidney injury (23,587); end-stage kidney disease, creatinine >3.5 or receiving dialysis before ICU admission (3,839); massive blood transfusion (1,174); ICU stay

Figure 3.

Age-adjusted survival by recovery patterns.…

Figure 3.

Age-adjusted survival by recovery patterns. Survival differences are highly significant overall ( P…

Figure 3.
Age-adjusted survival by recovery patterns. Survival differences are highly significant overall (P < 0.001). All pairwise comparisons are also significant. For example, late sustained reversal versus relapse recovery hazard ratio (95% confidence interval): 0.86 (0.77–0.96), P = 0.005; relapse with no recovery versus never reversed hazard ratio (95% confidence interval): 0.81 (0.76–0.86), P < 0.001. ICU = intensive care unit; RRT = renal replacement therapy.
Figure 3.
Figure 3.
Age-adjusted survival by recovery patterns. Survival differences are highly significant overall (P < 0.001). All pairwise comparisons are also significant. For example, late sustained reversal versus relapse recovery hazard ratio (95% confidence interval): 0.86 (0.77–0.96), P = 0.005; relapse with no recovery versus never reversed hazard ratio (95% confidence interval): 0.81 (0.76–0.86), P < 0.001. ICU = intensive care unit; RRT = renal replacement therapy.

References

    1. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P Acute Dialysis Quality Initiative workgroup. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004;8:R204–R212.
    1. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A Acute Kidney Injury Network. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11:R31.
    1. Akcan-Arikan A, Zappitelli M, Loftis LL, Washburn KK, Jefferson LS, Goldstein SL. Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Int. 2007;71:1028–1035.
    1. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012;2:1–138.
    1. Kellum JA, Sileanu FE, Murugan R, Lucko N, Shaw AD, Clermont G. Classifying AKI by Urine Output versus Serum Creatinine Level. J Am Soc Nephrol. 2015;26:2231–2238.
    1. Hoste EAJ, Bagshaw SM, Bellomo R, Cely CM, Colman R, Cruz DN, Edipidis K, Forni LG, Gomersall CD, Govil D, et al. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med. 2015;41:1411–1423.
    1. Kashani K, Al-Khafaji A, Ardiles T, Artigas A, Bagshaw SM, Bell M, Bihorac A, Birkhahn R, Cely CM, Chawla LS, et al. Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Crit Care. 2013;17:R25.
    1. Bihorac A, Chawla LS, Shaw AD, Al-Khafaji A, Davison DL, Demuth GE, Fitzgerald R, Gong MN, Graham DD, Gunnerson K, et al. Validation of cell-cycle arrest biomarkers for acute kidney injury using clinical adjudication. Am J Respir Crit Care Med. 2014;189:932–939.
    1. Murray PT, Mehta RL, Shaw A, Ronco C, Endre Z, Kellum JA, Chawla LS, Cruz D, Ince C, Okusa MD ADQI 10 workgroup. Potential use of biomarkers in acute kidney injury: report and summary of recommendations from the 10th Acute Dialysis Quality Initiative consensus conference. Kidney Int. 2014;85:513–521.
    1. Kellum JA, Chawla LS, Keener C, Singbartl K, Palevsky PM, Pike FL, Yealy DM, Huang DT, Angus DC. ProCESS and ProGReSS-AKI investigators: the effects of alternative resuscitation strategies on acute kidney injury in patients with septic shock. Am J Respir Crit Care Med. 2016;193:281–287.
    1. Kellum JA. How can we define recovery after acute kidney injury? Considerations from epidemiology and clinical trial design. Nephron Clin Pract. 2014;127:81–88.
    1. Korenkevych D, Ozrazgat-Baslanti T, Thottakkara P, Hobson CE, Pardalos P, Momcilovic P, Bihorac A. The pattern of longitudinal change in serum creatinine and 90-day mortality after major surgery. Ann Surg. 2016;263:1219–1227.
    1. Bihorac A, Yavas S, Subbiah S, Hobson CE, Schold JD, Gabrielli A, Layon AJ, Segal MS. Long-term risk of mortality and acute kidney injury during hospitalization after major surgery. Ann Surg. 2009;249:851–858.
    1. Palevsky PM, Molitoris BA, Okusa MD, Levin A, Waikar SS, Wald R, Chertow GM, Murray PT, Parikh CR, Shaw AD, et al. Design of clinical trials in acute kidney injury: report from an NIDDK workshop on trial methodology. Clin J Am Soc Nephrol. 2012;7:844–850.
    1. Knaus WA, Wagner DP, Draper EA, Zimmerman JE, Bergner M, Bastos PG, Sirio CA, Murphy DJ, Lotring T, Damiano A, et al. The APACHE III prognostic system. Risk prediction of hospital mortality for critically ill hospitalized adults. Chest. 1991;100:1619–1636.
    1. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, et al. Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41:580–637.
    1. Hoste EAJ, Clermont G, Kersten A, Venkataraman R, Angus DC, De Bacquer D, Kellum JA. RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis. Crit Care. 2006;10:R73.
    1. Závada J, Hoste E, Cartin-Ceba R, Calzavacca P, Gajic O, Clermont G, Bellomo R, Kellum JA AKI6 investigators. A comparison of three methods to estimate baseline creatinine for RIFLE classification. Nephrol Dial Transplant. 2010;25:3911–3918.
    1. Mehta RL, Pascual MT, Gruta CG, Zhuang S, Chertow GM. Refining predictive models in critically ill patients with acute renal failure. J Am Soc Nephrol. 2002;13:1350–1357.
    1. Goldstein SL, Chawla L, Ronco C, Kellum JA. Renal recovery. Crit Care. 2014;18:301.
    1. Chawla LS, Davison DL, Brasha-Mitchell E, Koyner JL, Arthur JM, Shaw AD, Tumlin JA, Trevino SA, Kimmel PL, Seneff MG. Development and standardization of a furosemide stress test to predict the severity of acute kidney injury. Crit Care. 2013;17:R207.
    1. Fuhrman DY, Kellum JA. Biomarkers for diagnosis, prognosis and intervention in acute kidney injury. Contrib Nephrol. 2016;187:47–54.

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