Urinary biomarkers and renal recovery in critically ill patients with renal support

Abstract

Background and objectives: Despite significant advances in the epidemiology of acute kidney injury (AKI), prognostication remains a major clinical challenge. Unfortunately, no reliable method to predict renal recovery exists. The discovery of biomarkers to aid in clinical risk prediction for recovery after AKI would represent a significant advance over current practice.

Design, setting, participants, & measurements: We conducted the Biological Markers of Recovery for the Kidney study as an ancillary to the Acute Renal Failure Trial Network study. Urine samples were collected on days 1, 7, and 14 from 76 patients who developed AKI and received renal replacement therapy (RRT) in the intensive care unit. We explored whether levels of urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary hepatocyte growth factor (uHGF), urinary cystatin C (uCystatin C), IL-18, neutrophil gelatinase-associated lipocalin/matrix metalloproteinase-9, and urine creatinine could predict subsequent renal recovery.

Results: We defined renal recovery as alive and free of dialysis at 60 days from the start of RRT. Patients who recovered had higher uCystatin C on day 1 (7.27 versus 6.60 ng/mg·creatinine) and lower uHGF on days 7 and 14 (2.97 versus 3.48 ng/mg·creatinine; 2.24 versus 3.40 ng/mg·creatinine). For predicting recovery, decreasing uNGAL and uHGF in the first 14 days was associated with greater odds of renal recovery. The most predictive model combined relative changes in biomarkers with clinical variables and resulted in an area under the receiver-operator characteristic curve of 0.94.

Conclusions: We showed that a panel of urine biomarkers can augment clinical risk prediction for recovery after AKI.

Figure 1.

Subject disposition for the Biologic Markers of Recovery for the Kidney (BioMaRK) study cohort.

Figure 2.

Box plots for the six biomarkers evaluated. The vertical box represents the 25th percentile (bottom line), median (middle line), and 75th percentile (top line) values whereas the vertical bars represent the intervals between maximum and minimum values: (A) urinary neutrophil gelatinase associated lipocalin (uNGAL) levels, (B) uNGAL/matrix metalloproteinase-9 (MMP-9), (C) urinary IL-18 (uIL-18), (D) urine hepatocyte growth factor (uHGF), (E) urinary cystatin C (uCystatinC), and (F) urinary creatinine (uCreatinine). *P < 0.05, **P < 0.01. The mean (SD) of the largest relative change of uNGAL for recovery and nonrecovery were −1.1 (1.5) and + 4.8 (10.0), P = 0.01, respectively. The mean (SD) of the largest relative change of uHGF for recovery and nonrecovery were −1.0 (1.5) and + 5.8 (12.8), P = 0.003, respectively.

Figure 3.

Receiver-operating characteristic (ROC) curves for the best prediction model for renal recovery. Shown are best combination biomarker model alone (thin dashed line), clinical prediction model alone (solid line), and best combined clinical model and best combination biomarker model (thick dashed line): (A) day 1, (B) day 14, and (C) the largest relative change. The clinical risk prediction model included age and Charlson comorbidity index. The area under the ROC curve (AUC) values and 95% confidence intervals (CIs) are also shown.