Pathogenesis of human renal dysplasia: an alternative scenario to the major theories.
Among the various congenital anomalies of the kidney and urinary tract (CAKUT), renal dysplasia may deserve the closest attention due to its frequency and clinical severity. However, the pathogenesis of this disease is still not well known. It is believed that renal dysplasia is caused by a nephron induction deficit due to ampullary inactivity, or an abnormal budding of the ureteric bud from the mesonephric duct. Renal dysplasia is frequently associated with urinary tract obstruction, suggesting an alternative mechanism whereby urinary retention causes abnormal kidney development. Multicystic dysplastic kidney (MCDK) and obstructive renal dysplasia (ORD) are two different phenotypes of dysplasia associated with urinary tract obstruction. From detailed morphological studies using fetal dysplastic kidneys, nephron induction with filtrating function occurs before cysts are formed. Moreover, three-dimensional reconstruction of dysplastic nephrons showed that cysts developed in the once-induced nephrons as the result of fluid retention in both MCDK and ORD. In utero urinary tract obstruction may cause urine retention in functioning nephrons and lead to multiple cyst formation in the nephrogenic zone. These findings are common to MCDK and ORD, although there may be a difference in the obstruction site. Expansion of cysts with tubular dilatation (cysts) disturbs the subsequent nephrogenesis by the deregulated expression of growth and transcription factors, and may contribute to the misdevelopment of fetal kidneys.
Shibata
Sawako
S
Department of Pediatrics, Moriya Daiichi General Hospital, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Nagata
Michio
M
D004268:DNA-Binding Proteins / Q000235:genetics; D006801:Humans; D007668:Kidney / Q000002:abnormalities* / Q000196:embryology; D021782:Multicystic Dysplastic Kidney / Q000196:embryology; D051762:PAX2 Transcription Factor; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors / Q000235:genetics
D004268:DNA-Binding Proteins; D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors