Kentaro Nishi1, Tomohiro Inoguchi2, Koichi Kamei1, Riku Hamada2, Hiroshi Hataya2, Masao Ogura1, Mai Sato1, Takako Yoshioka3, Kentaro Ogata4, Shuichi Ito5, Koichi Nakanishi6, Kandai Nozu7, Yuko Hamasaki2,8, Kenji Ishikura9,10. 1. Division of Nephrology and Rheumatology, National Center for Child Health and Development, Tokyo, Japan. 2. Department of Nephrology, Tokyo Metropolitan Children'S Medical Center, Tokyo, Japan. 3. Department of Pathology, National Center for Child Health and Development, Tokyo, Japan. 4. Department of Pathology, Federation of National Service Personnel Mutual Aid Associations, Tachikawa Hospital, Tokyo, Japan. 5. Department of Pediatrics, Yokohama City University Graduate School of Medicine, Kanagawa, Japan. 6. Department of Child Health and Welfare (Pediatrics), Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan. 7. Department of Pediatrics, Kobe University Graduate School of Medicine, Hyogo, Japan. 8. Department of Nephrology, Faculty of Medicine, Toho University, Tokyo, Japan. 9. Division of Nephrology and Rheumatology, National Center for Child Health and Development, Tokyo, Japan. kenzo@ii.e-mansion.com. 10. Department of Pediatrics, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, 252-0374, Kanagawa, Japan. kenzo@ii.e-mansion.com.
Abstract
BACKGROUND: Neonatal-onset Denys-Drash syndrome (NODDS) is a distinctive clinical entity and has a poor renal and life outcome. Early diagnosis of NODDS is important for managing disorders of sexual development and determining assigned gender. Although patients with NODDS and congenital nephrotic syndrome of the Finnish type (CNF) present with nephrotic syndrome in neonatal life or infancy, the clinical course of NODDS and factors distinguishing these diseases at onset is unknown. METHODS: We performed a retrospective cohort study of patients with NODDS and CNF between 1997 and 2017. Patients with nephrotic syndrome and WT1 or NPHS1 mutations with neonatal onset (within 30 days) were eligible. RESULTS: We studied eight patients with NODDS and 15 with CNF. The median serum creatinine level at onset in the NODDS group was significantly higher (1.85 mg/dL) than that in the CNF group (0.15 mg/dL; P = 0.002). The median placental/fetal weight ratio in the NODDS and CNF group was 41.8% and 21.0%, respectively (P = 0.001). Kaplan-Meier analysis showed that the median number of days for progression to ESRD from onset in the NODDS and CNF groups was 6 and 910 days, respectively (P < 0.001). All patients in the NODDS group were alive at follow-up. Only one patient in the CNF group died of cardiac complications during follow-up. CONCLUSION: CNS, renal dysfunction at onset, and a relatively large placenta are prominent signs of NODDS. Prognosis for patients with NODDS is satisfactory if appropriate and active management is performed.
BACKGROUND: Neonatal-onset Denys-Drash syndrome (NODDS) is a distinctive clinical entity and has a poor renal and life outcome. Early diagnosis of NODDS is important for managing disorders of sexual development and determining assigned gender. Although patients with NODDS and congenital nephrotic syndrome of the Finnish type (CNF) present with nephrotic syndrome in neonatal life or infancy, the clinical course of NODDS and factors distinguishing these diseases at onset is unknown. METHODS: We performed a retrospective cohort study of patients with NODDS and CNF between 1997 and 2017. Patients with nephrotic syndrome and WT1 or NPHS1 mutations with neonatal onset (within 30 days) were eligible. RESULTS: We studied eight patients with NODDS and 15 with CNF. The median serum creatinine level at onset in the NODDS group was significantly higher (1.85 mg/dL) than that in the CNF group (0.15 mg/dL; P = 0.002). The median placental/fetal weight ratio in the NODDS and CNF group was 41.8% and 21.0%, respectively (P = 0.001). Kaplan-Meier analysis showed that the median number of days for progression to ESRD from onset in the NODDS and CNF groups was 6 and 910 days, respectively (P < 0.001). All patients in the NODDS group were alive at follow-up. Only one patient in the CNF group died of cardiac complications during follow-up. CONCLUSION: CNS, renal dysfunction at onset, and a relatively large placenta are prominent signs of NODDS. Prognosis for patients with NODDS is satisfactory if appropriate and active management is performed.
Entities:
Keywords:
Congenital nephrotic syndrome; Congenital nephrotic syndrome of the Finnish type; Disorders of sexual development; NPHS1; Neonatal dialysis; WT1