DEVELOPMENT OF HUMAN FETAL KIDNEY IN OBSTRUCTIVE UROPATHY - CORRELATIONS WITH ULTRASONOGRAPHY AND URINE BIOCHEMISTRY

In utero urethral obstruction results in bilateral hydronephrosis and severe fetal and post-natal morbidity and mortality. Obstetrical manag ement depends on the indirect evaluation of fetal renal function by ul trasonography and biochemical analysis. No direct evaluation of the se verity and possible reversibility of renal lesions is available. In th is paper we analyzed kidneys from 34 fetuses (14 to 37 gestational wee ks) in which (1) isolated bilateral urinary tract obstruction had been detected in utero by sonography, and (2) the severity of sonographic and biochemical prognostic indicators led to the indication of termina tion of pregnancy or to perinatal death. Pure hydronephrosis was obser ved in two young fetuses [14 and 20 gestational weeks (GW)] and was as sociated with regressive changes in two others. In contrast, a wide sp ectrum of dysplastic renal lesions was present in 30 fetuses and was c lassified into four subgroups according to the association of dysplasi a, hypoplasia and cysts. They had the following characteristics in com mon: (1) premature cessation of nephrogenesis assessed by the medullar y ray counting method; (2) early disappearance or myofibroblastic diff erentiation of metanephric blastema; (3) early increase in interstitia l mesenchyme with widespread expression of alpha-smooth muscle actin b y mesenchymal cells; (4) frequent absence of classical criteria of dys plasia (nests of cartilage were observed in only 5 fetuses); (5) an id entification, based upon the detection of alpha-smooth muscle actin ex pression, of the muscular phenotype of mesenchymal cells encircling pr imitive ducts. In conclusion, (1) the value of prognostic markers in f etuses less than 20 GW should be reconsidered; (2) after 20 GW there i s a good correlation between markers predicting poor prognosis and the severity of renal lesions; (3) hypoplasia with disappearance of blast ema cells, dysplasia and early interstitial fibrosis are evidence of t he irreversibility of renal lesions and preclude any possibility of ne w nephron formation; (4) these findings suggest that most surgical in utero procedures are performed when irreversible renal lesions have de veloped.