Elevated serum urate as a marker of pre-eclampsia: evidence for impaired renal tubular urate secretion

Pre-eclampsia is a common disorder of pregnancy, characterized by high bloo d pressure and proteinuria, and posing a serious health risk to both mother and foetus. Elevation of uric acid levels in the blood has long been recog nized In this disorder, and found to correlate with its severity, in partic ular with a poor foetal outcome. While this relative hyperuricaemia Is wide ly used diagnostically, its biochemical mechanism remains poorly understood . In this study we examined 85 Individuals admitted to hospital in their th ird trimester of pregnancy for gestational hypertension, and 75 control sub jects, admitted for unrelated obstetric disorders not known to affect serum urate levels. Thirty-two subjects in both categories were also studied at their 6-week post-natal visit. Prenatal serum urate showed a 50% elevation in hypertensive patients, compared to non-hypertensive controls [315 +/- 9 muM vs 212 +/- 8 muM (mean s.e.m.), respectively], whereas post-delivery ur ate was indistinguishable between the two groups (257 +/- 16 muM vs 267 +/- 12 muM, respectively). Changes in serum creatinine were insufficient to as cribe the difference in serum urate to renal impairment. Fractional excreti on of urate (F(ox)urate) was determined, and shown to increase by approxima tely 40% in normal pregnancy, compared to post-natal values (F(ox)urate 8.1 +/- 0.4% vs 5.7 +/- 0.6%). This increase was totally abolished when pregna ncy was complicated by hypertension (F(ox)urate pre- and post-natal: 4.6 +/ - 0.5% vs 4.5 +/- 0.5%, respectively). Receiver-operated characteristic cur ves were constructed to optimize the use of serum urate and F(ox)urate to d istinguish pre-eclampsia from normal pregnancy. We conclude that hyperurica emia of pre-eclampsia is due to failure of the normal increase in urate sec retion by the kidney in pregnancy.