الفهرس 
CHRONIC KIDNEY DISEASEOnly 14 pages are availabe for public view
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Abstract
The incidence of chronic kidney disease (CKD) is reaching an epidemic proportion worldwide. Early identification of CKD and timely detection of progression are truly global challenges facing the nephrology community. Neutrophil gelatinase-associated lipocalin (NGAL) is a member of the lipocalin family of proteins. It is most robustly expressed in the kidney following acute renal injury, with a concomitant increase in its serum and urinary levels.
Objective: To evaluate the clinical utility of urinary NGAL in patients with different stages of chronic kidney disease, in a trial to assess its diagnostic significance as an early marker of chronic kidney damage and its value in assessment of disease severity.
Subjects and methods: The study included 60 adult patients with CKD and 20 age- and sex- matched healthy individuals serving as a control group. According to the modification of diet in renal disease (MDRD) study equation, 12 patients were in stage 2 CKD, 16 in stage 3, 17 in stage 4 and 15 in stage 5. All studied individuals were subjected to assessment of their urinary NGAL, serum creatinine, BUN, ESR, complete blood picture and complete urine analysis. Urinary NGAL was measured by ELISA, and expressed as ng/mL and ng/g creatinine. Subjects with urinary tract infection, as evidenced by urine culture, were excluded from the study.
Results: Data of the present study are expressed as mean ± standard deviation or meadian [interquartile rang] in case of skewness. Urinary NGAL showed a highly significant increase starting as early as stage 2 CKD (20.7±7.7 ng/mL, 48.8 [26.1-88.9 ng/g creatinine]) as compared to healthy controls (7.2±1.8 ng/mL; 9.7 [8.4-17.3 ng/g creatinine]), p<0.001, respectively). A highly significant stepwise progressive increase in the marker level was recorded through stages 2 to 5 (stage 2: 20.7±7.7 ng/mL; stage 3: 44.3±8.9 ng/mL, p< 0.001; stage 4: 100.1±12.4 ng/mL, p<0.001; stage 5: 114.6±14.7 ng/mL, p<0.05). This increase was almost doubled, especially between stages 2-4 when the marker was expressed as ng/ g creatinine (stage 2: 48.8 [26.1-88.9]; stage 3: 200.0 [105.7-277.5]; stage 4: 828.2±280.9; stage 5: 1,218.6±145.7). Urinary NGAL levels (ng/mL) of the studied patients collectively were inversely correlated with the eGFR (rs= –0.84, p<0.05), and positively correlated with BUN, creatinine and urinary albumin (rs=0.60, 0.88 & 0.57, p<0.05, respectively). When expressed as ng/g creatinine rsvalues were –0.87, 0.62, 0.89 and 0.58, respectively. However, this correlation was more prominent in patients with GFR ≥ 30 mL/min (stage 2 & 3) as compared to those with GFR < 30 mL/min (stage 4 & 5). It was even lost in case of albumin (rs=0.20, p>0.05). ROC curve analysis revealed an outstanding performance of the marker in CKD patients collectively versus healthy controls. The optimum cut-off level was 10.1 ng/mL (AUC 0.983, sensitivity 100% & efficacy 98.8%). The only false-negative case was in stage 2 (sensitivity 91.7%). When expressed as ng/g creatinine, the optimum cut-off level was 17.9 ng/g creatinine (AUC 0.953, sensitivity 100%, specificity 85% & efficacy 96.3%). Finally, urinary NGAL could clearly discriminate between patients in stages 4 & 5 and those at earlier stages of the disease. Whether expressed as ng/mL or ng/g creatinine, the AUC was 1.0, sensitivity, specificity, and efficacy were 100%, respectively at cut-off levels of 62 ng/mL and 387.5 ng/g creatinine, respectively.
Conclusion: Urinary NGAL is a promising non-invasive early indicator of renal pathology and a reliable marker of disease progression.