Follow-Up Renal Assessment of Injury Long-Term After Acute Kidney Injury (FRAIL-AKI)

Abstract

Background and objectives: Novel urinary kidney damage biomarkers detect AKI after cardiac surgery using cardiopulmonary bypass (CPB-AKI). Although there is growing focus on whether AKI leads to CKD, no studies have assessed whether novel urinary biomarkers remain elevated long term after CPB-AKI. We assessed whether there was clinical or biomarker evidence of long-term kidney injury in patients with CPB-AKI.

Design, setting, participants, & measurements: We performed a cross-sectional evaluation for signs of chronic kidney injury using both traditional measures and novel urinary biomarkers in a population of 372 potentially eligible children (119 AKI positive and 253 AKI negative) who underwent surgery using cardiopulmonary bypass for congenital heart disease at Cincinnati Children's Hospital Medical Center between 2004 and 2007. A total of 51 patients (33 AKI positive and 18 AKI negative) agreed to long-term assessment. We also compared the urinary biomarker levels in these 51 patients with those in healthy controls of similar age.

Results: At long-term follow-up (mean duration±SD, 7±0.98 years), AKI-positive and AKI-negative patients had similarly normal assessments of kidney function by eGFR, proteinuria, and BP measurement. However, AKI-positive patients had higher urine concentrations of IL-18 (48.5 pg/ml versus 20.3 pg/ml [P=0.01] and 20.5 pg/ml [P<0.001]) and liver-type fatty acid-binding protein (L-FABP) (5.9 ng/ml versus 3.9 ng/ml [P=0.001] and 3.2 ng/ml [P<0.001]) than did AKI-negative patients and healthy controls.

Conclusions: Novel urinary biomarkers remain elevated 7 years after an episode of CPB-AKI in children. However, there is no conventional evidence of CKD in these children. These biomarkers may be a more sensitive marker of chronic kidney injury after CPB-AKI. Future studies are needed to understand the clinical relevance of persistent elevations in IL-18, kidney injury molecule-1, and L-FABP in assessments for potential long-term kidney consequences of CPB-AKI.

Keywords: acute kidney injury; biomarkers; children; chronic kidney disease; follow-up studies; humans; kidney; proteinuria; renal insufficiency, chronic.

Figure 1.

Patient selection flow diagram. Children enrolled in prior cardiopulmonary bypass surgery (CPB)–related studies of novel AKI biomarkers who did and did not have AKI at the time of their initial CPB were identified and invited back for long-term follow-up. AKI was determined by increase in serum creatinine and novel urinary biomarkers. CCHMC, Cincinnati Children’s Hospital Medical Center.

Figure 2.

Novel urinary biomarkers are elevated in previously AKI-positive patients at long-term follow-up. Median biomarker concentrations at the time of longitudinal follow-up are displayed for AKI-positive (n=30 except for liver fatty acid–binding protein [L-FABP], for which n=29) compared with AKI-negative (n=18) patients. Error bars represent 25th and 75th percentiles. Cr, creatinine; KIM-1, kidney injury molecule-1; NGAL, neutrophil gelatinase-associated lipocalin.

Figure 3.

Biomarkers are elevated post-cardiopulmonary bypass surgery (CPB) in AKI-positive patients and remain elevated at long-term follow-up (F/U) compared to healthy age-matched patients. Median biomarker concentrations at pre-CPB baseline were compared with those 24 hours after CPB (*P<0.05). Median biomarker concentrations at long-term follow-up were compared with those 24 hours after CPB (#P<0.05). Median biomarker concentrations at long-term follow-up were compared with pre-CPB baseline values ($P<0.05). Finally, median biomarker concentrations at long-term follow-up were compared with those of healthy age-matched controls (+P<0.05). Error bars represent 25th and 75th percentiles. * denotes P value for comparison between baseline pre-CPB and 24-hour post-CPB biomarker concentrations; # denotes P value for comparison between long-term and 24-hour post-CPB biomarker concentrations; $ denotes P value for comparison between long-term and pre-CPB biomarker concentrations; + denotes P value for comparison between long-term and healthy age-matched control biomarker concentrations. Cr, creatinine; KIM-1, kidney injury molecule-1; L-FABP, liver fatty acid–binding protein; NGAL, neutrophil gelatinase-associated lipocalin.