Glomerular Ultrafiltration in Normal and Preeclamptic Pregnancy

Abstract

Abstract. GFR and renal plasma flow (RPF) decrease in preeclampsia, a serious hypertensive complication of pregnancy. Serial data derived in late pregnancy (LP) and Ͼ5 mo postpartum (PP) in 13 healthy controls and 10 preeclamptic women (13 and 5, respectively) returning PP for theoretical analysis of neutral dextran sieving curves ( D ), are presented and are used to calculate the key determinants of glomerular ultrafiltration. Normal LP hyperfiltration was associated with increases in RPF and the ultrafiltration coefficient (K f ), as well as in the nondiscriminatory shunt pathway ( 0 ) and the SD of pore size (S). Preeclamptic LP showed the largest 0 and S values, indicating a loss of size-selectivity, accompanying reduced K f and RPF, both of which are implicated in the relative hypofiltration. Despite a 100-fold increase in urinary albumin excretion (UAE), LP preeclamptic D values were reduced for the equivalent neutral dextran (36Å), providing indirect evidence for a loss of glomerular barrier charge-selectivity. All the determinants of GFR and all modeled parameters were comparable across both groups PP, strong evidence that preeclamptic glomerular dysfunction resolves.Preeclampsia, a major cause of maternal and fetal morbidity and mortality, is a multisystem disorder affecting, among others, the hepatic, hematologic, and renal systems. The latter include decreases in renal plasma flow (RPF) and GFR as well as proteinuria that may be in the nephrotic range. Impaired RPF and disordered glomerular barrier integrity could both contribute to hypofiltration (1). One goal of our study was to determine the relative contributions of each in preeclampsia; the other being the quantification of glomerular barrier parameters in relation to proteinuria. Renal hemodynamics were analyzed using clearance of PAH and inulin, while fractional dextran clearances ( D ), combined with mathematical modeling, provided glomerular sieving data, including estimation of the ultrafiltration coefficient (K f ) and glomerular porosity. Preeclamptic and healthy women were studied in late pregnancy (LP) and again 5 mo postpartum (PP). Materials and Methods SubjectsThirteen normotensive, healthy white women with no family history or evidence of renal or cardiovascular disease were studied during LP (36 to 38 wk) and again at least 5 mo PP. Ten untreated preeclamptic primigravidae were also studied in LP, of which 5 returned PP. All met the criteria of the International Society for the Study of Hypertension in Pregnancy (ISSHP) for preeclampsia (de novo hypertension Ͼ140/90 mmHg; proteinuria Ͼ500 mg/24 h) (2). When PP, none were hypertensive, ingesting oral contraceptives, taking medication or breast-feeding. All gave informed written consent to protocols approved by the Joint Ethics Committee of Newcastle and North Tyneside Health Authority and the Universities of Newcastle upon Tyne and Northumbria at Newcastle. ProtocolsOn the study morning, each subject ate a light carbohydrate breakfast but avoided tea and coffee. A 24-h urine collecti...

Course of preeclamptic glomerular injury after delivery

“…Restoration of the normal balance of angiogenic factors that occurs after delivery of the placenta likely promotes rapid endothelial cell healing, as noted in our patients with preeclampsia. A previous study inferred from sieving curves of uncharged dextran macromolecules of graded size that K f was restored to normal after the fifth postpartum month (18).…”

“…with persistent postpartum hypertension, GFR and proteinuria also normalize over several months (18,(32)(33)(34).…”

“…Although complete recovery can occasionally require in excess of 6 mo, the majority of cases demonstrate complete resolution of the renal pathology within 3 mo (25). With the exception of those women with persistent postpartum hypertension, GFR and proteinuria also normalize over several months (18,(32)(33)(34).…”

“…Although complete recovery can occasionally require in excess of 6 mo, the majority of cases demonstrate complete resolution of the renal pathology within 3 mo (25). With the exception of those women with persistent postpartum hypertension, GFR and proteinuria also normalize over several months (18,(32)(33)(34).In the present study, we have employed precise physiological techniques to evaluate the postpartum course of the GFR and its determinants in women with preeclampsia. We combined our physiological findings with mathematical modeling to estimate glomerular ultrafiltration capacity.…”

Effect of pre-eclampsia on glomerular filtration rate in Sudanese women

“…A decrease in the ultrafiltration coefficient (K f ), in the order of 50% either alone or in combination with reduced RBF, is presented as the most likely mechanism for the decrease of GFR. 9 Creatinine is a breakdown product of creatinine phosphate in muscle, and is usually produced at a fairly constant rate by the body (depending on muscle mass). Its molar mass is 113.12g/mol (molecular weight is 163.2).…”