Changes in urinary tissue kallikrein excretion in black African women with hypertensive disorders of pregnancy

Abstract

The aim of this study was firstly to establish whether tissue kallikrein (TK) was involved in the aetiology of hypertensive disorders of pregnancy. Secondly, to assess whether tissue kallikrein:creatinine ratios may differentiate normotensive pregnant women from those with hypertensive disorders of pregnancy and have a predictive value. Random untimed urine samples were collected from all women (n=264) recruited to this study. Urine specimens were analyzed for urinary tissue kallikrein using a selective, synthetic chromogenic tripeptide substrate (H-D-Val-Leu-Arg-pNA). Urinary creatinine levels were measured using standard methods. There was a significant difference in the excretion of urinary tissue kallikrein between normotensive pregnant women (2.91 ng TK/μg protein) and women with mild (2.52 ng TK/μg protein; p<0.0001) and severe (1.53 ng TK/μg protein; p<0.0001) hypertension in pregnancy. No statistical difference was observed with regard to urinary tissue kallikrein excretion between normotensive pregnant and normotensive non-pregnant women (2.87 ng TK/μg protein; p=0.16). A positive correlation was observed between the diastolic blood pressure and urinary tissue kallikrein excretion in women with hypertensive disorders of pregnancy. When compared to the normotensive pregnant group, the urinary kallikrein: creatinine ratios were significantly lower in the mild (0.6 versus 0.3; p<0.0001) and severe (0.6 versus 0.12; p<0.0001) hypertensive groups. The urinary creatinine excretion was significantly higher in the mild (9.55±2.6 mmol/l; p<0.0001) and in severe (15.62±5.48 mmol/l; p<0.0001) hypertensives when compared to normotensive pregnant values (5.65±2.6 mmol/l). The reduced urinary tissue kallikrein excretion in hypertensive disorders of pregnancy may be a significant factor in the development of the hypertension in pregnancy. Measurement of urinary tissue kallikrein: creatinine ratios may represent a simple and practical predictive test to differentiate women with hypertensive disorders of pregnancy from normotensive pregnant women.