A systematic review and meta-analysis indicates long-term risk of chronic and end-stage kidney disease after preeclampsia

Preeclampsia is a pregnancy-related syndrome of variable severity, classically characterized by acute kidney involvement, with hypertension and/or proteinuria and reduced kidney function. Once considered a self-limited disease healed by delivery, it is now acknowledged that preeclampsia can affect cardiovascular and kidney health in the long term. The entity of risk has not been established and consequently follow-up policies have not been defined. Here we undertook a systematic review to gain better insights into the need for post–preeclampsia follow-up. Articles published between January 2000 and March 2018 were selected, dealing with at least 20 preeclampsia patients, with follow-up of 4 years or more (MEDLINE, Embase, and Cochrane Library). No quality selection or language restriction was performed. Of the 10,510 titles and abstracts originally considered, 21 papers were selected, providing information on 110,803 cases with and 2,680,929 controls without preeclampsia, with partial overlap between studies on the same databases. Heterogeneity was high, and a random meta-analytic model selected. The increase in risk of end stage renal disease after preeclampsia was significant (meta-analytic risk ratios (95% confidence interval) 6.35 (2.73-14.79)); the risk of albuminuria and chronic kidney disease increased but statistical significance was not reached (4.31 (0.95-19.58) and 2.03 (0.58-7.32), respectively). Translating meta-analytic risk into the number of patients who need follow-up to detect one adverse event, 310 patients with preeclampsia are needed to identify one woman with end stage renal disease or four to identify one woman with albuminuria. Heterogeneity in definitions, insufficient follow-up and incomplete recruitment may account for discrepancies. Thus, preeclampsia significantly increases the risk of end stage renal disease. However, there is lack of sufficient data to show a relationship between preeclampsia, albuminuria and chronic kidney disease, underlining the need for further prospective studies

A core outcome set for pre‐eclampsia research: an international consensus development study

Objective To develop a core outcome set for pre‐eclampsia. Design Consensus development study. Setting International. Population Two hundred and eight‐one healthcare professionals, 41 researchers and 110 patients, representing 56 countries, participated. Methods Modified Delphi method and Modified Nominal Group Technique. Results A long‐list of 116 potential core outcomes was developed by combining the outcomes reported in 79 pre‐eclampsia trials with those derived from thematic analysis of 30 in‐depth interviews of women with lived experience of pre‐eclampsia. Forty‐seven consensus outcomes were identified from the Delphi process following which 14 maternal and eight offspring core outcomes were agreed at the consensus development meeting. Maternal core outcomes: death, eclampsia, stroke, cortical blindness, retinal detachment, pulmonary oedema, acute kidney injury, liver haematoma or rupture, abruption, postpartum haemorrhage, raised liver enzymes, low platelets, admission to intensive care required, and intubation and ventilation. Offspring core outcomes: stillbirth, gestational age at delivery, birthweight, small‐for‐gestational‐age, neonatal mortality, seizures, admission to neonatal unit required and respiratory support. Conclusions The core outcome set for pre‐eclampsia should underpin future randomised trials and systematic reviews. Such implementation should ensure that future research holds the necessary reach and relevance to inform clinical practice, enhance women's care and improve the outcomes of pregnant women and their babies

S-Nitrosoglutathione Reductase Underlies the Dysfunctional Relaxation to Nitric Oxide in Preterm Labor

Abstract Tocolytics show limited efficacy to prevent preterm delivery. In uterine smooth muscle cGMP accumulation following addition of nitric oxide (NO) has little effect on relaxation suggesting a role for protein S-nitrosation. In human myometrial tissues from women in labor at term (TL), or spontaneously in labor preterm (sPTL), direct stimulation of soluble guanylyl cyclase (sGC) fails to relax myometrium, while the same treatment relaxes vascular smooth muscle completely. Unlike term myometrium, effects of NO are not only blunted in sPTL, but global protein S-nitrosation is also diminished, suggesting a dysfunctional response to NO-mediated protein S-nitrosation. Examination of the enzymatic regulator of endogenous S-nitrosoglutathione availability, S-nitrosoglutathione reductase, reveals increased expression of the reductase in preterm myometrium associated with decreased total protein S-nitrosation. Blockade of S-nitrosoglutathione reductase relaxes sPTL tissue. Addition of NO donor to the actin motility assay attenuates force. Failure of sGC activation to mediate relaxation in sPTL tissues, together with the ability of NO to relax TL, but not sPTL myometrium, suggests a unique pathway for NO-mediated relaxation in myometrium. Our results suggest that examining the action of S-nitrosation on critical contraction associated proteins central to the regulation of uterine smooth muscle contraction can reveal new tocolytic targets