J. J. Walshe

Haemostatic, fibrinolytic and endothelial variables in normal pregnancies and pre‐eclampsia

Objective To determine the behaviour of the coagulation variables antithrombin III (ATIII), protein C, thrombin/antithrombin III (TATIII); fibrinolytic activity, tissue plasminogen activator antigen (t‐PA), plasminogen activator inhibitors (PAI) 1 and 2, and endothelial involvement by fibronectin assay in normal and pre‐eclamptic pregnancies.

Nitric oxide in the uteroplacental, fetoplacental, and peripheral circulations in preeclampsia

OBJECTIVE Altered production of nitric oxide by the vascular endothelium may influence the pathogenesis of preeclampsia. The aim of this study was to measure circulating levels of nitric oxide metabolites (nitrites) in the uteroplacental, fetoplacental, and peripheral circulation of preeclamptic pregnancies compared with normotensive controls. METHODS Fifteen women with preeclampsia were compared with 16 women with normotensive pregnancies. At cesarean, blood samples were taken from the uterine vein draining the placental site, the umbilical vein, and the antecubital vein after delivery of the baby but before delivery of the placenta. Plasma nitrites were measured using the Greiss reaction after conversion of plasma nitrates to nitrites using nitrate reductase. RESULTS Nitric oxide metabolites were higher in the uteroplacental (P < .01), fetoplacental (P < .001), and peripheral (P < .02) circulations in samples from preeclamptic pregnancies compared with control pregnancies. In samples from the fetoplacental circulation only, nitric oxide metabolite levels were negatively correlated with gestational age (r = -.489, P < .01) and birth weight (r = -.544, P < .004). Nitric oxide metabolite levels were not significantly correlated with blood pressure, placental weight, or maternal age. CONCLUSION In established preeclampsia, production of nitric oxide was higher in the uteroplacental, fetoplacental, and peripheral circulation than in normotensive pregnancies. This increase may be part of a compensatory mechanism to offset the pathologic effects of preeclampsia.

Can 24-hour ambulatory blood pressure measurement predict the development of hypertension in primigravidae?

Objective To assess the role of 24‐hour ambulatory blood pressure measurement in the mid‐second trimester as a predictive test for the development of hypertension in pregnancy.

Hemostasis in the uteroplacental and peripheral circulations in normotensive and pre-eclamptic pregnancies

OBJECTIVE Our purpose was to determine the hemostatic changes in the uteroplacental and peripheral circulations in normotensive and pre-eclamptic pregnancies. STUDY DESIGN This prospective, observational study involved 2 patient groups. Group 1 consisted of 30 normotensive women and 22 women with pre-eclampsia who were followed up longitudinally through pregnancy and post partum. Group 2 consisted of 20 women with established pre-eclampsia and 19 normotensive control subjects, all undergoing cesarean section. Plasma levels of thrombin-antithrombin III complex, soluble fibrin, plasmin-alpha2-antiplasmin complex, and fibrin-degradation product (D-dimer) were measured in blood drawn from the antecubital vein (group 1) and from both the antecubital and uterine veins (group 2). Data were analyzed by analysis of variance. RESULTS In group 1 levels of thrombin-antithrombin III complex, soluble fibrin, and fibrin-degradation product were significantly higher during normal pregnancy than at 6 weeks post partum. Plasmin-alpha2-antiplasmin complex levels did not change. No differences between the pre-eclamptic and normotensive pregnancy groups were found for any of the hemostatic markers. In group 2 normotensive women undergoing cesarean section, thrombin-antithrombin III complex and soluble fibrin levels were significantly higher in the uterine vein than in the antecubital vein. In group 2 women with pre-eclampsia, thrombin-antithrombin III complex and fibrin-degradation product levels were significantly higher in the uterine vein than in the antecubital vein. In addition, plasmin-alpha2-antiplasmin complex and fibrin-degradation product levels were higher and soluble fibrin levels were lower in the uterine vein in the pre-eclamptic group than in the normotensive group. CONCLUSION Both the coagulation and fibrinolytic systems are activated during normal pregnancy. Activation of these systems is more marked in the uteroplacental circulation than in the systemic circulation in both normotensive and pre-eclamptic pregnancies. An abnormal pattern of hemostasis occurs in the uteroplacental circulation in pre-eclampsia.

Circulating vascular cell adhesion molecule–1 in pre-eclampsia, gestational hypertension, and normal pregnancy: Evidence of selective dysregulation of vascular cell adhesion molecule–1 homeostasis in pre-eclampsia

OBJECTIVE Our purpose was to investigate circulating levels of vascular cell adhesion molecule-1 in the peripheral and uteroplacental circulations during normotensive and hypertensive pregnancies. STUDY DESIGN This prospective observational study involved 2 patient groups. Group 1 consisted of 22 women with pre-eclampsia and 30 normotensive women followed up longitudinally through pregnancy and post partum. There were an additional 13 women with established gestational hypertension. Group 2 consisted of 20 women with established pre-eclampsia and 19 normotensive control subjects undergoing cesarean delivery. Plasma levels of vascular cell adhesion molecule-1 were measured in blood drawn from the antecubital vein (group 1) and from both the antecubital and uterine veins (group 2). Data were analyzed by analysis of variance. RESULTS In group 1 vascular cell adhesion molecule-1 levels did not change significantly throughout normal pregnancy and post partum. Women with established pre-eclampsia had increased vascular cell adhesion molecule-1 levels compared with the normotensive pregnancy group (P = .01). Vascular cell adhesion molecule-1 levels were not elevated in women with established gestational hypertension. In group 2 significantly higher levels of vascular cell adhesion molecule-1 were detected in the uteroplacental (P < .0001) and peripheral (P < .0001) circulations of pre-eclamptic women by comparison with normotensive women. In the pre-eclamptic group there was a tendency toward higher vascular cell adhesion molecule-1 levels in the peripheral circulation than in the uteroplacental circulation (P = .06). In contrast to vascular cell adhesion molecule-1, circulating levels of E-selectin and intercellular adhesion molecule-1, other major leukocyte adhesion molecules expressed by the endothelium, were not different in pre-eclamptic and normotensive pregnancies. CONCLUSION Established pre-eclampsia is characterized by selective dysregulation of vascular cell adhesion molecule-1 homeostasis. This event is not an early preclinical feature of pre-eclampsia, does not persist post partum, is not a feature of nonproteinuric gestational hypertension, and is not observed with other major leukocyte adhesion molecules. Induction of vascular cell adhesion molecule-1 expression in pre-eclampsia may contribute to leukocyte-mediated tissue injury in this condition or may reflect perturbation of other, previously unrecognized, functions of this molecule in pregnancy.

Characteristics and Outcome of Anti-Glomerular Basement Membrane Disease: A Single-Center Experience

Over the last 16 years we have treated 40 patients with a renal pathological diagnosis of anti-glomerular basement membrane (anti-GBM) disease. The age of presentation ranged from 18 years to 76. Males and females were equally affected. The most common presenting symptoms were anorexia and uremia. Fifty percent of the patients were oliguric at presentation and required dialysis within 24 h, while the mean serum creatinine (Cr) at presentation was 5.1 +/- 6.8 mg/dL. Sixty-two percent of the patients demonstrated evidence of pulmonary involvement. Hematuria was universally present and was macroscopic in 35% of cases. Eight-two percent of the biopsies demonstrated greater than 80% crescents. Eight patients retained independent renal function after immunosuppression with cyclophosphamide, prednisone, and plasmapheresis. No patient who presented with a Cr greater than 5 mg/dL retained renal function. Using a logistic regression model the only clinical, biochemical, or pathological factors at presentation that significantly predicted eventual need for dialysis were the serum creatinine and percentage of glomeruli with crescents. Ten patients underwent cadaveric renal transplantation, and 7 have a functioning graft for a mean of 8.2 years. None have shown evidence of recurrence of anti-GBM disease in the graft. We conclude that anti-GBM disease is an important cause of renal failure and that its prognosis is directly related to the degree of renal failure at presentation. Efforts need to be made to diagnose this condition earlier in its natural history if its prognosis is to be improved.

Improved patient survival in recipients of simultaneous pancreas-kidney transplant compared with kidney transplant alone in patients with type 1 diabetes mellitus and end-stage renal disease

There are emerging data that simultaneous pancreas–kidney transplant (SPK) prolongs life compared with kidney transplant alone (KTA) in type 1 diabetics with end‐stage renal disease. This study was a retrospective comparison of SPK with KTA in patients with type 1 diabetes.

A Comparison of Long‐Term Graft Survival Rates Between the First and Second Donor Kidney Transplanted—The Effect of a Longer Cold Ischaemic Time for the Second Kidney

Prolonged cold ischaemic time (CIT) is associated with delayed initial graft function and may also have a negative impact on long‐term graft outcome. We carried out a study comparing the long‐term graft survival rates between those recipients who received the first of a pair of donor kidneys versus the recipient of the second graft.

Pathogenesis of acute renal failure associated with the HELLP syndrome: a case report and review of the literature

Acute renal failure is a rare but serious complication of pregnancy. We describe a 31-year-old woman with haemolytic anemia, elevated liver enzymes, low platelets (HELLP syndrome) who developed acute peripartum renal failure. Renal biopsy performed 2 weeks later because of persistent oliguria revealed thrombotic microangiopathy and acute tubular necrosis. This case highlights the probable pathogenesis of acute renal failure in HELLP patients and explains why it resolves in the majority of cases. A review of the literature that describes renal histology in HELLP patients is presented.

MDRD-Estimated GFR at One Year Post-Renal Transplant Is a Predictor of Long-Term Graft Function

Renal transplantation is the optimal mode of renal replacement. Improvements in graft survival and acute rejection rates have made these outcomes less useful for prognostication and as end-points in clinical trials; accurate surrogate markers of long-term graft outcome are therefore increasingly important. This study examines the relationship between both serum creatinine (SCr1yr) and MDRD estimated glomerular filtration rate measured at one year (eGFRMDRD1yr) as predictors of graft survival. Data on 1,110 patients who received a renal transplant between 1989 and 2005 were extracted from the Irish Renal Transplant Registry. The study group was divided into quartiles of patient numbers according to SCr1yr and eGFRMDRD1yr. Kaplan-Meier estimates of the primary end-point graft survival were constructed for each quartile. Additionally, a Cox Regression restricted cubic spline model was performed for both eGFRMDRD1yr and SCr1yr. Both overall graft outcome and outcome censored for death with a functioning graft (CDWFG) were used as endpoints. Cox regression analysis was performed along with tests for the proportionality assumption to compare the predictive value of eGFRMDRD1yrand SCr1yr. Both eGFRMDRD1yr and SCr1yr were independently associated with long-term renal transplant survival. eGFRMDRD1yr and SCr1yr had similarly strong associations with long-term outcome when the quartile variables were compared using the Bayesian Information Criterion method. The Cox regression restricted cubic spline modeling demonstrated that an eGFRMDRD1yr value < 27 mLs/min/1.73m2 and a SCr1yr value > 229 μmol/L were associated with poor graft survival.