Abstract

Background: High global incidence of acute kidney injury (AKI) is an observable complication in critically ill patients. Long-term disease and medication complexity contribute to devastating chronic kidney disease (CKD), diminishing quality of life.

Objectives: To establish new biomarkers to guide patient care and facilitate novel therapeutics development.

Methods: Serum and urinary levels of creatinine, CysC, and NGAL were estimated in 86 renal patients and compared with healthy controls for AKI and CKD categorization. Creatinine and CysC measurements were used to estimate GFR. Kidney biopsies were prepared for light microscopy for further characterization. Patients’ demographic data were used in group association studies.

Results: Thirty-six patients met the criteria for AKI and 50 for CKD. Both mean serum and urine creatinine levels were significantly elevated by 2.8 and 2.6, respectively, from baseline in 48 h in the AKI group but not CKD group. Mean serum Cystatin C (CysC) values were higher than controls but similar in both disease states, while urine levels were slightly higher in CKD patients, and remained steady by the end of the follow-up (EF-Up). Further, a significant 2.9-fold and 5.5-fold (p=0.001) increase in serum NGAL in AKI and CKD, respectively, and a dramatic 7.1-factor reduction in AKI group, but no appreciable change in the CKD group from admission to EF-Up were observed. Similarly, urine NGAL level for AKI and CKD increased 3.2-fold and 6-fold respectively, on admission, which decreased moderately with the AKI group (2.5-fold) but increased by a factor of 1-8 (10.7- fold; p=0.001) at EF-Up. ROC assessment curve revealed relatively higher NGAL performance at good predictive values than CysC (p < 0.009).

Conclusion: Our data demonstrated creatinine elevation by a factor > 2 in 48 h in AKI group but not CKD group, which returned close to normal levels by the EF-Up, an indication of abrupt renal injury in AKI, compared with a persistent effect in the CKD group. Both serum and urine NGAL sensitivity and specificity provided powerful discriminative tool between AKI and CKD by reduction in the AKI group and an increase in the CKD group by the EF-UP, thus, contributing in establishing the basis for AKI and CKD classification. CysC, however, displayed less sensitivity than NGAL, indicating effects by enigmatic non-specific factors.

Keywords: Acute kidney injury (AKI), chronic kidney disease (CKD), biomarkers, cystatin C (CysC), NGAL, estimated glomerular filtration rate (eGFR).