Lysosomal enzymuria in preeclampsia.

We hypothesize that the preeclamptic patient has proximal tubule epithelial injury, which leads to the release of lysosomal enzymes, and that the excretion of these enzymes might serve as a diagnostic or predictive marker in preeclamptic women. The study group consisted of 14 women with preeclampsia (10 severe and 4 mild, as defined by The American College of Obstetricians and Gynecologists criteria) and 28 normotensive controls with singleton pregnancies at 27 to 41 weeks. There were no significant differences between the two groups for gestational age, maternal age, or race. Maternal serum and urine specimens were prospectively obtained and analyzed for beta-glucuronidase, beta-hexosaminidase, alpha-galactosidase, beta-galactosidase, and alpha-mannosidase using fluorometric assays. Median serum and urine activities and fractional excretions of each of the five hydrolases were compared between the two study groups using the Mann-Whitney two-sample rank test. The serum enzyme activities of beta-hexosaminidase (P = 0.002), alpha-galactosidase (P = 0.0001), and alpha-mannosidase (P = 0.02) were significantly lower in preeclamptic patients than in controls. The urine enzyme activities of beta-glucuronidase (P = 0.001), alpha-galactosidase (P = 0.002), beta-galactosidase (P 0.0003), and alpha-mannosidase (P = 0.003) were significantly higher in the preeclamptic patients. The fractional enzyme excretions of all five lysosomal hydrolases were higher in preeclamptic patients than in controls with P < or = 0.0003 for each enzyme. Preeclampsia is associated with a significant decrease in serum activities of three of the five hydrolases studied, a significant increase in urine enzyme activities in four of the five hydrolases studied, and a significant increase in the fractional excretion of all five lysosomal hydrolases.

Altered urinary excretion of lysosomal hydrolases in pregnancy.

Creatinine concentrations and the activities of five lysosomal hydrolases were measured in the serum and urine of 14 healthy nonpregnant control women and 19 healthy pregnant women. Fractional enzyme excretion (FEE) values for beta-glucuronidase, beta-hexosaminidase, alpha-galactosidase, beta-galactosidase, and alpha-mannosidase were calculated and compared between the two groups of subjects. Fractional enzyme excretion was calculated as the ratio of enzyme clearance to creatinine clearance. The FEE values for beta-galactosidase and alpha-mannosidase between the nonpregnant and pregnant populations were not statistically different; however, relative to the nonpregnant control group, the median FEE values for beta-glucuronidase (P < 0.03), beta-hexosaminidase (P < 0.06), and alpha-galactosidase (P < 0.02) were decreased approximately 1.5-, 1.8-, and 2.7-fold, respectively, in the pregnant population. The median urinary beta-galactosidase activity for the pregnant population, when expressed on the basis of creatinine, was twofold higher than that of the control group (P < 0.0005). These data indicate that with pregnancy there are marked changes in the urinary excretion of selected lysosomal enzymes, particularly alpha-galactosidase and beta-glucuronidase. When the molecular weights of these five hydrolases were compared between kidney homogenate and control urine, a correlation of 0.96 was observed, while the correlation between control serum and control urine was 0.69. This suggests that the FEE value differences between the pregnant and control groups are most likely due to changes in tubule cell metabolism, either decreased secretion or increased reabsorption. These biochemical changes may provide a means of assessing changes in renal function during pregnancy.