Predictive value of amniotic fluid cystatin C levels for the early identification of fetuses with obstructive uropathies Michele Mussap a , Vassilios Fanos b , Carla Pizzini b , Alma Marcolongo c , Graziella Chiaffoni b , Mario Plebani a,d, * Objective To compare the diagnostic accuracy of cystatin C with that of creatinine in discriminating renal function in fetuses without ultrasononographic evidence of renal malformations from those with obstructive uropathies. Design Prospective, observational cohort study. Setting Prenatal morphologic and functional evaluation of fetal obstructive uropathies throughout pregnancy. Population A total of 96 healthy pregnant women at different stages of pregnancy, without any pregnancy- related maternal disease. Eighty-one pregnant women without clinical and ultrasonographic evidence of any fetal anomaly, confirmed at birth, were defined as controls; 15 pregnant women with various fetal obstructive uropathies, evidenced by repeated ultrasound examinations and confirmed at birth, were defined as cases. Methods Creatinine was measured by a kinetic Jaffe picric acid method and cystatin C by a nephelometric immunoassay. Variables were analysed by applying conventional statistical tests; the non-parametric receiver operating curves (ROC) analysis was used to evaluate the diagnostic efficiencies of the biochemical markers. Main outcome measures Incidence of confirmed, diagnosed, neonatal obstructive uropathy by measuring baseline levels of cystatin C and creatinine in amniotic fluid. Results Baseline levels of cystatin C in amniotic fluid were significantly higher ( P ¼ 0.0015) among cases than in controls with comparable gestational age; no significant difference was found for creatinine levels ( P ¼ n.s.). The maximum diagnostic accuracy of serum cystatin C in discriminating controls from fetal uropathies was 96%, while that of creatinine was 62%. Conclusion Cystatin C may be considered a sensitive biochemical marker for the early identification of fetuses with obstructive uropathies. INTRODUCTION For the past two decades, the increasingly widespread and sophisticated use of ultrasonography during pregnancy has led to a significant number of reports on the prenatal diagnosis of fetal renal malformations and obstructive nephro-uropathy 1,2 . The early identification of fetuses with obstructive nephro-uropathy appropriate for in utero intervention allows a rational approach to fetal surgery and in utero percutaneous catheter drainage 3–5 . Unfortu- nately, the most important limitation is the identification of fetuses with renal anomalies appropriate for in utero intervention, because of our inability at present to evalu- ate fetal renal functions and maturation 6 . No definitive method has been identified for an accurate selection of fetuses with concomitantly high risk for further advancing pregnancy and potentially salvageable renal function; these fetuses might benefit from either in utero interven- tion or delivery before term 7 . In addition, most cases of acute renal failure in the newborn may be considered a consequence of intrauterine events, being dependent on fetal renal maturation and dysfunction 8 . Clinicians have long recognised that assessment of amniotic fluid status is an integral part of fetal testing 9 , because it is produced by chorion and the umbilical cord, with a contribution from fetal urine and fetal tracheo- bronchial fluid 10 . Fetal urine is the most important com- ponent of the amniotic fluid 11,12 ; at first, a normal amount of amniotic fluid was considered the only index of fetal renal development 13 . Later, it was demonstrated that BJOG: an International Journal of Obstetrics and Gynaecology July 2002, Vol. 109, pp. 778–783 D RCOG 2002 BJOG: an International Journal of Obstetrics and Gynaecology PII:S1470-0328(02)01430-1 www.bjog-elsevier.com a Department of Laboratory Medicine, University-Hospital of Padova, Padua, Italy b Department of Pediatrics, University of Verona, Verona, Italy c Department of Obstetrics and Gynecology, University of Verona, Verona, Italy d Centre of Biomedical Research, Veneto Region, Castelfranco Veneto (TV), Italy * Correspondence: Dr M. Plebani, Azienda Ospedaliera di Padova, Servizio di Medicina di Laboratorio, Via N. Giustiniani, 2, 35128 Padua, Italy.