Correlation of serum neutrophil gelatinase associated lipocalin with disease severity in hypertensive disorders of pregnancy

Sachan, Rekha; Patel, ML; Gaurav, Amrita; Gangwar, Radheshyam; Sachan, Pushpalata

Correlation of serum neutrophil gelatinase associated lipocalin with disease severity in hypertensive disorders of pregnancy

Authors

¹ Departments of Obstetrics and Gynaecology, King George Medical University, Lucknow, Uttar Pradesh, India

² Department of Medicine, King George Medical University, Lucknow, Uttar Pradesh, India

³ Department of Critical Care, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

⁴ Department of Physiology, King George Medical University, Lucknow, Uttar Pradesh, India

Abstract

Background: Vascular endothelial dysfunction is considered central to the pathogenesis of hypertensive disorders of pregnancy (HDP). Serum level of neutrophil gelatinase-associated lipocalin (NGAL) is closely related to endothelial injury. The aim of this study was to examine the correlation of serum NGAL with disease severity in HDP.
Materials and Methods: This prospective case-control study was carried out for one year. After informed consent, ethical clearance, total 1,850 pregnant women were screened. Analysis was performed on 142 cases of HDP and 31 healthy controls. Quantitative measurement of serum NGAL levels was done by the enzyme linked immunosorbent assay (ELISA) technique, by using sandwich ELISA kit.
Results: Mean serum NGAL value in patients with oliguria was significantly higher when compared with non-oliguric patients (P < 0.001). Serum NGAL had a positive correlation with systolic blood pressure (r ~ 0.5973), diastolic blood pressure (r ~ 0.6195), blood urea (r ~ 0.4392), serum creatinine (r ~ 0.6112), serum uric acid (r ~ 0.3878). Sensitivity and specificity of serum NGAL using a cut-off value of 545 pg/ml, for the diagnosis of HDP, was 97.89% and 93.55% respectively, using 95% confidence interval.
Conclusion: Between the two groups, we found that serum NGAL had a positive correlation with disease severity and better sensitivity and specificity in the evaluation of HDP.

Keywords

References

1.	Khan KS, Wojdyla D, Say L, Gülmezoglu AM, Van Look PF. WHO analysis of causes of maternal death: A systematic review. Lancet 2006;367:1066-74.
2.	Montan S, Sjoberg NO, Svenningsen N. Hypertension in pregnancy-Fetal and infant outcome. A cohort study. Clin Exp Hypertens B 1987;6:337-48.
3.	ACOG technical bulletin. Hypertension in pregnancy. Number 219 - January 1996 (replaces no. 91, February 1986). Committee on Technical Bulletins of the American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet 1996;53:175-83.
4.	Roberts JM, Pearson G, Cutler J, Lindheimer M, NHLBI Working Group on Research on Hypertension During Pregnancy. Summary of the NHLBI Working Group on research on hypertension during pregnancy. Hypertension 2003;41:437-45.
5.	Norwitz ER, Hsu CD, Repke JT. Acute complications of preeclampsia. Clin Obstet Gynecol 2002;45:308-29.
6.	Arora R, Ganguli RP, Swain S, Oumachigui A, Rajaram P. Determinants of maternal mortality in eclampsia in India. Aust N Z J Obstet Gynaecol 1994;34:537-9.
7.	Rawal A. Trend in maternal mortality and some policy concerns. Indian J Community Med 2003;28:43-6.
8.	Uttenthal LO. NGAL; Marker molecule for distressed kidney. Clinical Laboratory International; November 1, 2005.
9.	Kjeldsen L, Johnsen AH, Sengeløv H, Borregaard N. Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase. J BiolChem 1993;268:10425-32.
10.	Kjeldsen L, Bainton DF, Sengeløv H, Borregaard N. Identification of neutrophil gelatinase-associated lipocalin as a novel matrix protein of specific granules in human neutrophils. Blood 1994;83:799-807.
11.	Kuwabara T, Mori K, Mukoyama M, Kasahara M, Yokoi H, Saito Y, et al. Urinary neutrophil gelatinase-associated lipocalin levels reflect damage to glomeruli, proximal tubules, and distal nephrons. Kidney Int 2009;75:285-94.
12.	Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, et al. Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am SocNephrol 2003;14:2534-43.
13.	Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 2005;365:1231-8.
14.	D'Anna R, Baviera G, Giordano D, Todarello G, Russo S, Recupero S, et al. Neutrophil gelatinase-associated lipocalin serum evaluation through normal pregnancy and in pregnancies complicated by preeclampsia. Acta Obstet Gynecol Scand 2010;89:275-8.
15.	Yan J, Zeng X, Liu Q. Expression and significance of MMP-9 and NGAL in maternal serum and placental tissue in preeclampsia. J Pract Obstet Gynaecol 2011;06:244.
16.	Strevens H, Wide-Swensson D, Hansen A, Horn T, Ingemarsson I, Larsen S, et al. Glomerular endotheliosis in normal pregnancy and pre-eclampsia. BJOG 2003;110:831-6.
17.	Var A, Yildirim Y, Onur E, Kuscu NK, Uyanik BS, Goktalay K, et al. Endothelial dysfunction in preeclampsia. Increased homocysteine and decreased nitric oxide levels. Gynecol Obstet Invest 2003;56:221-4.
18.	Report of the National High Blood Pressure Education Program Working Group on high blood pressure in pregnancy. Am J Obstet Gynecol 2000;183:S1-22.
19.	Menon MK. The evaluation of treatment of eclampsia. Br J Obstet Gynaecol 1961;68:417.
20.	Prakash J, Vohra R, Pandey LK, Niwas SS, Behura SK, Singh U. Spectrum of kidney diseases in patients with preeclampsia-eclampsia. J Assoc Physicians India 2010;58:543-6.
21.	Elneihoum AM, Falke P, Hedblad B, Lindgärde F, Ohlsson K. Leukocyte activation in atherosclerosis: Correlation with risk factors. Atherosclerosis 1997;131:79-84.
22.	D'Anna R, Baviera G, Giordano D, Todarello G, Corrado F, Buemi M. Second trimester neutrophil gelatinase-associated lipocalin as a potential prediagnostic marker of preeclampsia. ActaObstetGynecolScand 2008;87:1370-3.
23.	Kang DH, Finch J, Nakagawa T, Karumanchi SA, Kanellis J, Granger J, et al. Uric acid, endothelial dysfunction and pre-eclampsia: Searching for a pathogenetic link. J Hypertens 2004;22:229-35.
24.	Bainbridge SA, Roberts JM. Uric acid as a pathogenic factor in preeclampsia. Placenta 2008;29 Suppl A: S67-72.
25.	Sagen N, Haram K, Nilsen ST. Serum urate as a predictor of fetal outcome in severe pre-eclampsia. Acta Obstet Gynecol Scand 1984;63:71-5.
26.	Redman CW, Beilin LJ, Bonnar J, Wilkinson RH. Plasma-urate measurements in predicting fetal death in hypertensive pregnancy. Lancet 1976;1:1370-3.
27.	Wagener G, Minhaz M, Mattis FA, Kim M, Emond JC, Lee HT. Urinary neutrophil gelatinase-associated lipocalin as a marker of acute kidney injury after orthotopic liver transplantation. Nephrol Dial Transplant 2011;26:1717-23.
28.	Thangaratinam S, Coomarasamy A, O'Mahony F, Sharp S, Zamora J, Khan KS,et al. Estimation of proteinuria as a predictor of complications of pre-eclampsia: A systematic review. BMC Med 2009;7:10.
29.	Qublan HS, Ammarin V, Bataineh O, Al-Shraideh Z, Tahat Y, Awamleh I, et al. Lactic dehydrogenase as a biochemical marker of adverse pregnancy outcome in severe pre-eclampsia. Med Sci Monit 2005;11:CR393-7.
30.	Beyer C. Lactate dehydrogenase isoenzymes in serum of patients with preeclampsia/eclampsia complicated by the HELLP syndrome. Clin Chim Acta 1991;202:119-20.
31.	Williams KP, Galerneau F. The role of serum uric acid as a prognostic indicator of the severity of maternal and fetal complications in hypertensive pregnancies. J Obstet Gynaecol Can 2002;24:628-32.
32.	Cnossen JS, de Ruyter-Hanhijärvi H, van der Post JA, Mol BW, Khan KS, terRiet G. Accuracy of serum uric acid determination in predicting pre-eclampsia: A systematic review. Acta Obstet Gynecol Scand 2006;85:519-25.
33.	Thangaratinam S, Ismail KM, Sharp S, Coomarasamy A, Khan KS, Tests in Prediction of Pre-eclampsia Severity review group. Accuracy of serum uric acid in predicting complications of pre-eclampsia: A systematic review. BJOG 2006;113:369-78.
34.	Bellomo G, Venanzi S, Saronio P, Verdura C, Narducci PL. Prognostic significance of serum uric acid in women with gestational hypertension. Hypertension 2011;58:704-8.
35.	Roberts JM, Gammill HS. Preeclampsia: Recent insights. Hypertension 2005;46:1243-9.

Advanced Biomedical Research