Kynurenine Concentrations During Pregnancy in Women With or Without Chronic Kidney Disease - A Prospective Multicenter Study

Official title

Concentrations of Kynurenine During Pregnancy in Women With or Without Chronic Kidney Disease: A Prospective Multicenter Study

Overview

Chronic kidney disease (CKD) affects more than 10% of the population worldwide and represents the second most important risk factor for preeclampsia, a life-threatening complication of pregnancy responsible for approximately 80,000 maternal and 500,000 perinatal deaths each year. Experimental studies have suggested a causal link between CKD, relative kynurenine deficiency during pregnancy, and preeclampsia development. Kynurenine, a tryptophan metabolite, plays a central role at the materno-fetal interface, supporting placental energy production, maternal-fetal immune tolerance, and placental perfusion. This study will prospectively assess and compare longitudinal kynurenine concentrations in pregnant women with and without CKD, and evaluate their associations with maternal and fetal outcomes.

Detailed description

This is a multicenter, prospective cohort study including 204 pregnant women, with or without chronic kidney disease (CKD stages 2 to 4). Participants will be enrolled before 14 weeks of gestation. Blood samples (14 mL) will be collected at the 1st, 2nd, and 3rd trimesters and 2 months postpartum for kynurenine measurement, centrally analyzed at CHU Reims using LC-MS/MS. Additional data include maternal demographics, medical and obstetric history, anthropometry, laboratory data (creatinine, hemoglobin, hematocrit, proteinuria), blood pressure, ultrasound (growth parameters, umbilical artery Doppler), and maternal-fetal outcomes (preeclampsia, gestational hypertension, HELLP, hemorrhage, SGA, prematurity, mortality). The primary objective is to compare kynurenine concentrations in the 3rd trimester between women with and without CKD. Secondary objectives include describing longitudinal kynurenine evolution, its association with maternal-fetal outcomes, and modeling kynurenine needs during pregnancy in CKD.

Interventions

• Other Blood sampling
  A 14ml blood sample will be collected during the first second and third trimesters of pregnancy and at 2 months (+ 1 month post partum)

Primary outcome measures

• Kynurenine concentration at the 3rd trimester (32±1 weeks) in women with and without CKD [Time frame: 32±1 weeks]

Secondary outcome measures (9)

• Kynurenine concentrations at 1st, 2nd, 3rd trimesters and 2 months postpartum in women with and without CKD [Time frame: at 9 months]
• preeclampsia [Time frame: at 6 months]
• gestational hypertension [Time frame: at 6 months]
• HELLP syndrome [Time frame: at 6 months]
• postpartum hemorrhage [Time frame: at 6 months]
• small-for-gestational-age [Time frame: at 6 months]
• prematurity [Time frame: at 6 months]
• fetal/neonatal mortality [Time frame: at 6 months]
• Modeling of kynurenine needs across pregnancy in CKD women mean kynurenine concentration [Time frame: at 6 months]

Eligibility criteria

Inclusion criteria

• Adult pregnant women <14 weeks of amenorrhea
• With or without CKD stage 2-4 (eGFR 15-89 mL/min/1.73m², diagnosed before pregnancy)
• Written informed consent
• Affiliation to a social security system

Exclusion criteria

• Multiple pregnancy
• Kidney transplantation
• Persons under guardianship or legal protection

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

France · 1 center

• Marie MULLER — Reims

Identifiers

NCT: NCT07411937 · PR26006

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗