Glomerular filtration and volume regulation in gravid animal models

The gestational increase in glomerular filtration rate (GFR) that occurs in the normal rat is the result exclusively of an increase in plasma flow rate, and there is no sustained increase in glomerular capillary blood pressure during a normal pregnancy. The factor or factors that initiate the gestational renal vasodilatation (and plasma volume expansion) are maternal, not fetoplacental in origin. Apart from ruling out prostaglandins as an initiating agent, animal studies have not yet defined the precise nature of the initiating factors; it is unlikely that the gestational plasma volume expansion can be the sole cause of the increased GFR seen in pregnancy. The normal kidney in pregnancy exhibits substantial renal reserve to amino acid infusion, despite being already vasodilated by the gestational stimulus. The renal volume-sensing and control system of tubuloglomerular feedback is fully operative in pregnancy, and appears to be 'reset' to perceive the expanded plasma volume of pregnancy as normal. This observation agrees with many other indications that the sensors perceiving and controlling intravascular volume are reset during a normal pregnancy to enable the mother to accommodate the increased plasma volume without provoking a natriuretic response. Multiple pregnancies do not have any cumulative, long-term deleterious effects on renal function, either when the underlying function is normal or when it has been compromised by removal of renal mass plus high-protein feeding. In the short-term, pregnancy does not worsen kidney function when underlying glomerulonephritis is present. Therefore, the hyperfiltration of pregnancy does not appear to be a damaging entity, unlike other hyperfiltration states studied in the male rat. Still unknown is the mechanism by which pregnancy does worsen underlying glomerular disease in some women. The preliminary data in the rat, presented above, suggest that the exacerbating influence may be something other than the glomerular haemodynamic changes of pregnancy.