Circulatory Maternal Endothelin 1 and Matrix Metalloproteinase-9 Gene Expression in PREECLAMPSIA: A Study in Western Uttar Pradesh, India.

Introduction: Preeclampsia (PE) is a multiorgan disease of pregnant women. The main pathophysiology of PE is a trophoblastic invasion into maternal circulation leading to alterations in circulatory levels of matrix metalloproteinases (MMPs), inflammatory markers, and endothelin 1(ET1) levels. Therefore, the present study has explored the role of MMP-9 and ET1 and their association in PE. The advantage of the study is to provide insight into the pathology of PE. These markers may help in the early diagnosis and prognosis of PE. Objective: To investigate MMP-9 gene expression, ET1 level in PE cases and their correlation with blood pressure (BP), gestational age, weight, and height. Methods: The study design was a case-control observational study, which included 70 subjects in each case (PE) and controls (normal pregnant women (NPW)). Whole blood (250 ul) was utilized for RNA extraction (Trizol method) and synthesized cDNA as per manufacturer protocol. MMP-9 gene expression was analyzed by real-time PCR. Serum was utilized for ET1 estimation by sandwich ELISA. Results: The ET1 levels and MMP-9 gene expression were significantly increased in preeclamptic women as compared to controls. There was no significant correlation between MMP-9 gene expression and serum ET1 levels. However, a significant moderate association between systolic BP and diastolic BP with ET1 levels and MMP9 gene expression was seen in both PE and NPW. Conclusion: A significantly increased circulatory concentration of ET1 and MMP-9 gene expression in PE might be used as an early diagnostic as well as a prognostic marker of PE.

Serum neutrophil gelatinase associated lipocalin (NGAL) and cystatin C as early predictors of contrast-induced acute kidney injury in patients undergoing percutaneous coronary intervention.

BACKGROUND: Contrast-induced acute kidney injury (AKI) is diagnosed by estimating serum creatinine at 48-72h after diagnostic or interventional coronary angiography. It is too late for an early intervention. Neutrophil gelatinase associated lipocalin (NGAL) and cystatin C are novel markers of AKI. We determined the optimum cut-off level of NGAL and cystatin C in early diagnosis and prediction of AKI in patients undergoing coronary angiography followed by angioplasty. METHODS: In a nested case control study, serum NGAL, cystatin C by ELISA and serum creatinine by Jaffe's kinetic method were estimated at 0, 4, 24 and 48h of coronary angiography followed by angioplasty in 30 cases who developed contrast-induced AKI and 30 subjects who did not develop AKI. eGFR was estimated for both cases and controls by the MDRD equation. ROC was used to determine the optimum cut-off. RESULTS: Serum NGAL increased sharply at 4h after the procedure and then gradually declined to near normal level at 48h in AKI cases. The rise in cystatin C peaked at 24h and then declined but remained high till 48h. In controls, they remained static. The optimum cut-off of serum NGAL and cystatin C was 155.2ng/ml and 0.517mg/l respectively at 4h and 89.5ng/ml and 0.99mg/l respectively at 24h of angiography. Odds ratio for hypertensives to develop AKI was 3.57 (CI: 1.2-11.1, p=0.03). CONCLUSION: Serum NGAL and cystatin C may act as early markers of contrast-induced AKI in patients undergoing percutaneous coronary intervention. Patients with hypertension are susceptible to develop contrast-induced AKI.