The Emerging Role of Serum Neutrophil Gelatinase-Associated Lipocalin (Ngal) in Renal Failure and Malignancy,MAHMOUD MAHFOUZ and SHEREEN MAHMOUD
Abstract
Neutrophil gelatinase-associated lipocalin (NGAL) is a small protein expressed in neutrophils and certain epithelia, including the renal tubules. NGAL is a lipocalin that is well known for its functions as a shuttle for both iron and sidero-phores. It comprises a critical component of innate immunity to exogenous bacterial infections. However, recent reports have added new dimensions of functionality that have attracted the interest of oncologists and nephrologists. Renal expression of NGAL is dramatically increased in injury from a variety of causes and is released into both urine and plasma. NGAL levels rise within 2 hours of the insult, making, NGAL an early and sensitive biomarker of kidney injury. Moreover, NGAL plays a critical role in breast cancer development and progression, and thus NGAL has potential to be a new thera-peutic target in breast cancer.
The aim of this study: Was to highlight the emerging role of NGAL in human cancers and renal failure (and to evaluate how specific diagnoses affect serum NGAL levels). Study was conducted on 64 patients, (26 patients with end stage renal disease 12 patients after renal transplantation, 26 patients with various tumours).
Results: In patients with renal transplantation, the mean serum NGAL was statistically higher in patients than control subjects with a mean value of 236.27±257 and 42.80±36.9 ng/ml respectively (p=0.000). There was a negative correlation between serum NGAL and serum phosphate(r-1.000, p=0.000). Serum NGAL had a negative correlation with mean hemoglo-bin(r-498, p=0.09) and a positive correlation with serum uric acid(r-0.646, p=0.002). No significant correlations were detected between serum NGAL and the duration of renal transplantation surgery, the age of recipients and the serum creatinine.
In patients with renal failure, the mean serum NGAL was 1349.23±645.8ng/ml compared to its level in normal controls 42.8±36.9ng/ml. It was higher in females than males with a mean value of 1784.00±754.9 and 1288.50±571ng/ml respec-tively. There was insignificant correlation between serum NGAL and the presence of hypertension, the presence of volume overload, the type of renal failure(end stage, AKI) and the mean Hb, but it was positively correlated with BUN (r=0.459, p=0.018) and serum potassium 505, p=0.017. In patients with various tumors, the mean serum NGAL was 285.77±44.2ng/ml compared to its level in normal controls 42.8±36.9ng/ml. The value of serum NGAL was higher in males than females but the difference was insignificant. There were insignificant correlations between serum NGAL and any of the tumor markers, histopathological examination. The mean value of serum NGAL was 2220ng/ml in bladder carci-noma, 130ng/ml in breast cancer, 335ng/ml in CML, 350ng/ml in cancer colon, 405ng/ml in hepatocellular carcinoma and 300ng/ml in prostate cancer (p=0.086). Hypertension was significantly higher in patients with serum NGAL >500ng/ml (p=0.025).
Conclusion: Serum NGAL is higher in patients with end stage renal failure, renal transplantation (even with normal serum creatinine) and various tumours (regardless the tumour type) than control subjects. Serial measurements may be more valuable than a single measurement in both diagnosis and prognosis.