Refractory Hypertension in Infantile-Onset Denys-Drash Syndrome

Refractory Hypertension in Infantile-Onset Denys-Drash Syndrome

KENTARO NISHI,¹ KOICHI KAMEI,¹ MASAO OGURA,¹ MAI SATO,¹ MIKI MURAKOSHI,¹ CHIKAKO KAMAE,¹ RYUTARO SUZUKI,¹ TORU KANAMORI,¹ CHINA NAGANO,² KANDAI NOZU,² KENJI ISHIKURA³ and SHUICHI ITO⁴

¹Division of Nephrology and Rheumatology, National Center for Child Health and Development, Tokyo, Japan
²Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan
³Department of Pediatrics, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan
⁴Department of Pediatrics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan

Denys-Drash syndrome is characterized by progressive nephropathy, gonadal dysgenesis, and Wilms tumor caused by a WT1 gene mutation. Infants with Denys-Drash syndrome frequently experience severe hypertension, but detailed clinical manifestations have yet to be clarified. Cases of infantile-onset Denys-Drash syndrome with severe hypertension at our hospital were retrospectively analyzed and the pathogenesis of hypertension was investigated. Six infants who received the diagnosis of Denys-Drash syndrome at the median age of 10 days (range: 2-182 days) were enrolled. Five infants had the complication of severe hypertension within a few days of diagnosis. All the patients showed rapid progression to end-stage renal disease and urgently required dialysis due to anuria/oliguria and hypervolemia with a median duration of 7.5 days (range: 0-17 days) on the day after diagnosis. Even under dialysis, all the patients continued to need antihypertensive treatment. Five patients underwent a preventive nephrectomy for Wilms tumor, and one patient underwent a nephrectomy due to progression to Wilms tumor. Two patients developed hypotension after a nephrectomy. The main causes of hypertension were hypervolemia in the predialysis stage, renin-associated hypertension in the dialysis stage, and multiple factors, including increased plasma catecholamine-associated hypertension in the postnephrectomy dialysis stage. At last the follow-up after bilateral nephrectomy, four of the five patients required antihypertensive treatment. Not all the patients showed target organ complications caused by hypertension. Severe hypertension is a common complication of infantile-onset Denys-Drash syndrome. The possibility of hypotension after nephrectomy should be considered in patients with Denys-Drash syndrome.

Keywords —— Denys-Drash syndrome; hypertension; hypotension after nephrectomy; renin; WT1

===============================

Tohoku J. Exp. Med., 2020 , 252, 45-51.

Correspondence: Koichi Kamei, Division of Nephrology and Rheumatology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan.

e-mail: kamei-k@ncchd.go.jp