Objectives. To determine predictors of renal relapse and end-stage renal failure (ESRF) in patients with ANCA-associated vasculitis.Methods. Data from four European Vasculitis Society randomized... Show moreObjectives. To determine predictors of renal relapse and end-stage renal failure (ESRF) in patients with ANCA-associated vasculitis.Methods. Data from four European Vasculitis Society randomized controlled trials, conducted roughly simultaneously between 15 March 1995 and 30 September 2002, was pooled to determine predictors of long-term renal outcome. The respective trial inclusion criteria covered the entire spectrum of disease severity. Baseline predictors of time to first renal relapse and time to ESRF were assessed by competing events analysis and Cox proportional hazards regression. The effect of renal relapse on time to ESRF was assessed by adding renal relapses to the competing events analysis as a time-varying covariate.Results. The number of patients participating was 535; mean serum creatinine (+/- S.D.) at entry was 341 +/- 321 mu mol/l and 19.7% developed ESRF. One or more renal relapse(s) was experienced by 101 patients. Multivariable regression analysis demonstrated that, in addition to impaired baseline renal function, developing >= 1 renal relapse was an independent risk factor for ESRF (subhazard ratio 9; 95% CI 4, 19; P < 0.001). No predictive factors for renal relapse were found.Conclusion. In addition to baseline renal function, the occurrence of renal relapses is an important determinant of ESRF in patients with ANCA-associated vasculitis. We did not find any clinical predictors for renal relapse itself, including disease activity elsewhere. In light of the silent nature of renal relapse in ANCA-associated vasculitis, we stress the need for long-term vigilant monitoring for early signs of renal relapse and propose performing 3-monthly urinalysis. This will enable timely treatment and help further improve renal outcome. Show less
ABSTRACTObjectiveWomen pregnant after oocyte donation (OD) are prone to develop preeclampsia, a syndrome characterised by an aberrant immunologic response, hypercoagulability and endothelial... Show moreABSTRACTObjectiveWomen pregnant after oocyte donation (OD) are prone to develop preeclampsia, a syndrome characterised by an aberrant immunologic response, hypercoagulability and endothelial dysfunction. A mediator of inflammation and coagulation is thrombomodulin; a possible role player in this syndrome. Our objective is to investigate whether thrombomodulin dysregulation is involved in the development of preeclampsia after OD. DesignCase-control study. SettingWomen who received OD in the LUMC or in the nearby teaching hospitals between 2004 and 2013. Patient(s)A total of 109 placentas of uncomplicated pregnancies (48 naturally conceived, 21 IVF and 40 OD pregnancies) and 16 placentas of OD pregnancies complicated by preeclampsia. Intervention(s)NoneMeasurementsAbundance of thrombomodulin protein and vitamin D receptor (VDR) were determined using immunohistochemistry. mRNA expression was determined using qPCR. Result(s)Placental thrombomodulin protein abundance was lower in OD pregnancies(diffuse pattern in 45%) than in controls(diffuse pattern in 96%;p<0.001). Placental thrombomodulin mRNA expression was lower in OD pregnancies complicated by preeclampsia(0.72±0.47) compared with uncomplicated OD pregnancies(0.43±0.18;p<0.001). Thrombomodulin expression correlated with inflammation and coagulation. VDR expression was decreased in OD pregnancies complicated by preeclampsia and correlated with thrombomodulin mRNA.Conclusion(s) Pregnancies conceived through OD lose placental thrombomodulin expression. This loss is associated with an increased coagulation and inflammation, and indicates that endothelial protection is diminished in OD pregnancies, which might be an explanation for the increased risk for preeclampsia. The vitamin D metabolism is dysregulated in OD pregnancies and might be a target for therapy. Show less
