The nature of glomerular dysfunction in preeclampsia
thesisposted on 15.12.2014, 10:30 by Justine Norman
Normal pregnancy was compared to preeclamptic (PE) pregnancy with respect to glomerular ultrafiltration nitric oxide (NO) activity, derived from the metabolism of L-arginine (L-arg) to citrulline. Two biomathematical models, the "isoporous plus shunt" (mean pore size ro, shunt component wo) and "lognormal" (mean pore size U, standard deviation S), together with fractional dextran clearance (betaD) enabled estimation of glomerular ultrafiltration parameters (Kf~ ultrafiltration coefficient, DP-transglomerular pressure). NO activity was assed from plasma and 24hr urinary NOx (nitrate and nitrite), second messenger cyclic GMP (cGMP) and NO synthase inhibitor asymmetric-D-methyl-arginine 9ADMA). Late pregnant (LP) and post partum (PP) data are presented. As NO might mediate gestational renal vasodilatation, the effects of infused L-arginine (NO precursor) compared to glycine, on ultrafiltration were examined, testing the hypothesis that NO deficiency is important in renal vasoconstriction and hypofiltration of PE.;Normal pregnancy is associated with increased GFR, ERPF, wo and S (p<0.05). PE pregnancy is associated with reduced Kf but increased ro, wo U and S. PE values PP approach controls. From the indices that were utilised, there was no evidence of significant NO deficiency in Preeclampsia and even if there was a relative deficiency the infusion of the NO precursor L-arginine failed to augment the decreased renal haemodynamics of Preeclampsia. In PE the hypofiltration therefore has both a haemodynamic and a structural basis, it recovers PP and L-arg has no ameliorating effect in LP, or PP.