Circulating NT-proBNP but not soluble corin levels were associated with preeclampsia in pregnancy-associated hypertension.

BACKGROUND: Corin is a serine protease known to convert B-type natriuretic peptide (BNP) prohormone into BNP and its amino-terminal fragment (NT-proBNP). In mice lacking corin, high blood pressure and proteinuria were found at late gestational stages, with associated delayed trophoblast invasion and impaired spiral artery remodeling in the uterus. We hypothesize that both NT-proBNP and soluble corin elevation predict the presence of preeclampsia in pregnant patients with hypertension. METHODS: We prospectively enrolled 149 pregnant women with a history of chronic hypertension or gestational hypertension presenting at a tertiary-care hospital. We compared plasma NT-proBNP and soluble corin concentrations based on their preeclamptic status. RESULTS: In our study cohort, 62 patients with preeclampsia had lower gestational age than 87 patients without preeclampsia (33.3 ±â€¯3 versus 36.6 ±â€¯3 weeks; P < .001), otherwise the baseline characteristics were similar. We observed higher NT-proBNP concentrations in patients with preeclampsia compared to those without preeclampsia (304.3 [96.34, 570.4] vs. 60.8 [35.61, 136.8] ng/L, P < .001), with no differences between chronic and gestational hypertension. However, the concentration of corin was not statistically different between the two groups (1756 [1214, 2133] vs. 1571 [1171, 1961] ng/L, P = .1087). ROC curve analysis demonstrated stronger predictive value of NT-proBNP compared to soluble corin in predicting the presence of preeclampsia in our study population (AUC 0.7406 vs. 0.5789, P < .0001). CONCLUSION: While corin may contribute to mechanistic underpinnings of the development of preeclampsia in animal models, soluble corin likely has no diagnostic role in human pregnancies for preeclampsia beyond natriuretic peptide levels.

Natriuretic peptide testing in high-risk pregnancy: a preventive opportunity?

Natriuretic peptide testing has been widely utilized in the heart failure and cardiac patient population, but there is limited utilization during pregnancy. Patients with hypertensive diseases of pregnancy have been shown to experience elevation of circulating natriuretic peptide levels compared to normal pregnancies, especially in the setting of preeclampsia. Natriuretic peptide testing can be utilized in patients presenting with signs and symptoms suspicious of heart failure in order to rule out underlying cardiac causes. Meanwhile, monitoring natriuretic peptide levels in those with established heart diseases (both congenital and acquired) may facilitate careful management of cardiac status during the course of pregnancy. Further investigations in the judicious use of selected medications (particularly loop diuretics) in the setting of elevated natriuretic peptide levels are warranted.

Lack of significant renal tubular injury despite acute kidney injury in acute decompensated heart failure.

AIMS: Acute kidney injury (AKI) is a strong predictor of adverse events with an incompletely understood pathophysiology. Neutrophil gelatinase-associated lipocalin (NGAL) is proposed as an early marker of renal tubular injury. Our aim is to determine whether AKI during treatment of acute decompensated heart failure (ADHF) is accompanied by renal tubular injury. METHODS AND RESULTS: Urinary NGAL (uNGAL) and urinary creatinine (uCreat) levels were measured in 141 consecutive patients hospitalized for ADHF and followed for 180 days for death or re-hospitalization. AKI was defined as a rise in serum creatinine ≥0.3 mg/dl in a 48 h period. Median uNGAL/uCreat levels on Day 1 (baseline) were similar between patients who did and did not develop AKI [22.8 (12.5-106.8) µg/g vs. 20.6 (12.4-52.0) µg/g, P = 0.55]. On Day 2 and beyond, the difference between the AKI and no AKI cohorts increased, but was only significant on Day 3 [36.2 (21.7-131.8) µg/g vs. 29.4 (11.4-54.6) µg/g, P = 0.02]. The area under the receiver operating characteristic curve for Day 2 uNGAL/uCreat (≥ or <32 µg/g) to predict AKI was 0.61. There was no difference in diuretic response between 'uNGAL/uCreat + ' (≥ 27 µg/g) and 'uNGAL/uCreat-' (<27 µg/g) patients. However 'uNGAL/uCreat + ' patients had more adverse events after 180 days (66% vs. 52%, P = 0.02). CONCLUSIONS: In patients with ADHF who develop AKI following diuretic therapy, a minor rise in uNGAL precedes AKI. However, the degree of renal tubular insult was much lower than that observed in other forms of AKI.

Aldosterone receptor antagonists in the medical management of chronic heart failure.

The benefits of aldosterone receptor antagonists (spironolactone and eplerenone) for patients with heart failure were shown in 2 recent randomized controlled trials. Some of the proposed mechanisms of action of aldosterone antagonists are (1) inhibition of myocardial and vascular remodeling, (2) blood pressure reduction, (3) decreased collagen deposition, (4) decreased myocardial stiffness, (5) prevention of hypokalemia and arrhythmia, (6) modulation of nitric oxide synthesis, and (7) immunomodulation. Like many hormone receptors, the aldosterone receptor can be either nuclear or membrane bound. Most of the activities of the aldosterone receptor are subserved by the nuclear receptors and often lead to alterations in gene transcription. Although these agents are well tolerated in carefully selected patient populations that meet the inclusion criteria of large clinical trials, their use in unselected elderly patients with heart failure and multiple comorbidities has been associated with a significant risk of hyperkalemia and renal failure. Although no convincing data exist to predict which individual patients will respond to aldosterone inhibition, patients with more severe heart failure and those with acute myocardial infarction with concomitant heart failure or left ventricular dysfunction are most likely to respond. Theoretically, aldosterone receptor antagonists may also be beneficial in patients with more mild to moderate systolic heart failure or even in those with diastolic heart failure, although direct evidence is still lacking.