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Deterioration in maternal kidney function is associated with adverse pregnancy outcomes and long-term morbidity and mortality for mother and baby. Lack of accurate assessment of kidney function, accounting for physiological adaptation across gestations, makes personalised care in pregnancy challenging. Serum creatinine is recommended to assess kidney function in pregnancy. Urea guides commencement of dialysis. Cystatin C provides an estimate glomerular filtration rate (GFR) and beta-2-microglobulin is a marker of tubular injury. This study aims to define normal centile ranges in pregnancy for serum creatinine, urea, cystatin c and beta-2-microglobulin.
Prospective cohort study of women receiving antenatal care at two UK tertiary hospitals (2018-2021) recruited to Pregnancy Adaptations in Renal disease study (REC15/WA/0009) and Prediction of pregnancy complications study (REC02-03-033).
Inclusion criteria:6 weeks gestation to postpartum discharge, singleton pregnancy, blood pressure before 20 weeks below 130/80mmHg without antihypertensive medication, no proteinuria, haematuria, or urinary tract infection.
Venous serum samples were taken at recruitment and routine ultrasound appointments and stored at -80’C prior to analysis. Serum creatinine (enzymatic), cystatin C, beta-2-microglobulin (Siemens ADVIA 1800) and urea (Clinical Chemistry Analyser) were quantified according to manufacturer’s instructions.
Centile reference ranges for each biomarker were created for the following groups:
1) No known risk factors for chronic kidney disease (CKD)
2) Existing risk for CKD: pre-pregnancy eGFR<90mls/min/1.73m2, haematuria, proteinuria, or structural abnormalities; previous acute kidney injury (AKI); connective tissues disease; thrombophilia; cardiovascular disease; assisted conception; or previous pregnancy complications to assess the impact of known risk factors for CKD
3) No risk factor at time of samples but subsequently developed new risk for acute kidney injury: e.g., hypertensive disorder, gestational diabetes, placental insufficiency, or neonatal complications.
Xrigls command was used in Stata 18.0 to allow reference interval estimation using generalized least squares.
549 participants were included. 193(35.2%) had no known risk factors, 178(32.4%) a new risk factor and 178(32.4%) a known risk factor(Table 1). Table 2 describes means for all biomarkers at each gestational window by sub-group.
In this ethnically diverse population, mean and median serum creatinine values were lower than previous reports in population cohorts. Serum creatinine above 63umol/l at any gestation of pregnancy is above the 97th centile and may represent pathology. Urea values above 5.5umol/l in the first and third trimester, and 4.6mmol/l in the second warrant further assessment. Cystatin C and beta-2-microglobulin vary increasingly towards term, even in women with no risk factors, thus are unlikely to be useful markers of kidney impairment in pregnancy.