Renal function in preeclampsia.

Preeclampsia (pregnancy-induced hypertension) is a disorder specific to pregnancy and the pathological changes it causes regress after delivery. Reversible hyperuricaemia is the most characteristic biochemical feature of preeclampsia, first noted nearly 60 years ago by Slemons and Bogert (1917). More recently, Chesley and Williams have shown that the high plasma urate is the result of renal tubular urate retention occurring independently of decreases in the glomerular filtration rate (GFR). Why renal tubular function should alter is not known but clinical and pathological studies clearly demonstrate that the degree of hyperuricaemia in preeclampsia reflects the severity of the disorder (Redman et al, 1976), as well as being the best correlate of renal biopsy changes (Pollak and Nettles, 1960). Of the many possible causes of urate retention, lactate acidosis has received most attention. In non-pregnant subjects, it explains the urate retention of starvation (Murphy and Shipman, 1963) and the hyperuricaemia following grand-mal convulsions (Warren et al, 1975). Previously it was thought that the hyperuricaemia of eclampsia was a consequence of convulsions; many investigators have shown that this is not so, and our own studies confirm that evidence of urate retention may be present weeks or months before there is any likelihood of eclamptic fits. It is possible that an ischaemic placenta may generate enough lactate to account for the changes, a view supported by the observations of Handler (1960) who showed a marked negative correlation between arterial lactate levels and urate clearance in preeclamptic and eclamptic women. Circulatory changes in the kidney may provide an alternative explanation of urate retention. Angiotensin H is known to depress urate clearance without lowering GFR (Ferris and Gorden, 1968) although it is not thought to be the cause of the intense vasoconstriction of preeclampsia. The undiscovered factor, or factors, that causes preeclamptic vasospasm may exert an effect on renal tubular function similar to that of angiotensin II. A falling GFR, and progressive uraemia, are late features of preeclampsia, usually associated with proteinuria. At this stage circulating fibrin degrada91 tion products may appear (Bonnar et al, 1971), and the disease enters a final fulminating stage which, without intervention, ends either with eclampsia, a fetal death, or spontaneous labour and delivery. The poor fetal prognosis, once proteinuria develops, has been amply documented in the first British Perinatal Mortality Survey (Butler and Bonham, 1963). Preeclamptic uraemia is ischaemic in origin. Arterial constriction, glomerular endothelial swelling and intravascular fibrin deposition are all developed sufficiently to explain the deterioration in renal function. One of the major problems in studying preeclampsia has been the lack of observations in the earliest stages of the disease. By managing selected high-risk patients in a combined antenatal hypertension clinic, we have been able to document the renal changes occurring throughout the evolution of preeclampsia.