Medical Care

Cornerstones of Denys-Drash syndrome (DDS) medical therapy include management of fluid and electrolyte balance, treatment of hypertension, renal replacement therapy for patients with end-stage renal disease (ESRD) or after bilateral nephrectomy, and chemotherapy for patients with Wilms tumor.

Surgical Care

The management of Denys-Drash syndrome is challenging, and optimal management strategies have not been established. The plan must be guided by the typical early progression of diffuse mesangial sclerosis to end-stage renal disease (ESRD), high risk of Wilms tumor development, and highly variable clinical course.^[10]

In patients without Wilms tumor at the time of Denys-Drash syndrome diagnosis, two management strategies have been proposed: radical and conservative. The radical approach involves prophylactic bilateral nephrectomy prior to ESRD progression in order to avoid development of Wilms tumor and shortened total duration of renal replacement therapy prior to transplantation.^[11]The conservative approach involves close monitoring for Wilms tumor development using serial imaging studies.^{[12, 13]}In patients who develop Wilms tumor, radical bilateral nephrectomy is advocated over nephron-sparing surgery to preserve renal function as long as possible.^[14]

A 2018 survey of the international pediatric nephrology community described management of 21 confirmed cases of Denys-Drash syndrome.^[15]The authors concluded that, based on the known risks associated with ESRD, the variable course of Denys-Drash syndrome, and the relatively good prognosis associated with Wilms tumor, the guiding principle of renal function preservation is most logical. Most surveyed would advocate bilateral prophylactic nephrectomy after ESRD is reached owing to the high tumor risk, which is likely further heightened after transplantation.

Surgical treatment of Wilms tumor should follow the guidelines of the National Wilms Tumor Study-4 and -5 Protocols.^{[16, 17]}

Denys-Drash syndrome manifests as gonadal dysgenesis and increased risk of gonadal malignancy. According to the Chicago consensus and other published data, the incidence of gonadoblastoma in patients with 46-XY Denys-Drash is 40%.^{[18, 19]}Gonadectomy versus close observation has been debated, although data supporting each approach are limited. In 2019, two patients who were managed conservatively experience delayed puberty owing to primary hypogonadism.^[19]Hence, gonadal preservation does not provide endocrinological benefit while risking the development of gonadal malignancy.

Kidney transplantation is the treatment of choice after bilateral nephrectomy. For patients with Wilms tumor, a 2-year period free of chemotherapy and tumor is recommended prior to renal transplantation.

Consultations

Consultations may be indicated with the following specialists:

Pediatric nephrologist - For managing the nephropathy, ESRD, hypertension, and medical aspects of transplantation
Pediatric oncologist - For diagnosis and treatment of Wilms tumor and gonadoblastoma
Pediatric surgeon - For managing Wilms tumor, access in renal replacement therapy and surgical aspects of renal transplantation, and evaluation and possible removal of abnormal gonads
Pediatric endocrinologist - For evaluation and management of intersex disorders
Geneticist - For chromosomal analysis, molecular diagnosis, and genetic counseling

Diet

A low-sodium diet is important to manage hypertension and edema. Patients with renal insufficiency require a low-potassium, low-phosphate diet.

Further Outpatient Care

In patients with Denys-Drash syndrome (DDS), arrange for follow-up with a pediatric nephrologist for renal transplantation and for ongoing management of nephrotic syndrome, hypertension, and renal insufficiency.

Arrange for follow-up with a pediatric oncologist for ongoing management of Wilms tumor. The Children's Oncology Group has released guidelines for long-term follow-up.^[20]

Arrange for follow-up with a pediatric endocrinologist for management of intersex disorders.

Transfer

Children with Denys-Drash syndrome require integrated interdisciplinary care, including such pediatric subspecialty services as nephrology, surgery, oncology, endocrinology, and genetics.

Medication

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Media Gallery

Gross nephrectomy specimen shows a Wilms tumor pushing the normal renal parenchyma to the side.

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Author

Agnieszka Swiatecka-Urban, MD, FASN, FAAP Professor of Pediatrics, Chief of Pediatric Nephrology, UVA Children's Hospital, University of Virginia School of Medicine

Agnieszka Swiatecka-Urban, MD, FASN, FAAP is a member of the following medical societies: American Heart Association, American Society for Biochemistry and Molecular Biology, American Society of Nephrology, American Society of Pediatric Nephrology, International Pediatric Nephrology Association, International Society of Nephrology, Society for Pediatric Research, Women in Nephrology

Disclosure: Nothing to disclose.

Coauthor(s)

Prasad Devarajan, MD, FAAP Louise M Williams Endowed Chair in Pediatrics, Professor of Pediatrics and Developmental Biology, Director of Nephrology and Hypertension, Director of the Nephrology Fellowship Program, Medical Director of the Kidney Stone Center, Co-Director of the Institutional Office of Pediatric Clinical Fellowships, Director of Clinical Nephrology Laboratory, CEO of Dialysis Unit, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine

Prasad Devarajan, MD, FAAP is a member of the following medical societies: American Heart Association, American Society of Nephrology, American Society of Pediatric Nephrology, National Kidney Foundation, Society for Pediatric Research

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Consultant for Reata, Dicerna, Alnylam<br/>Received none from Coinventor on patents submitted for the use of NGAL as a biomarker of kidney injury for none.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Maria Descartes, MD Professor, Department of Human Genetics and Department of Pediatrics, University of Alabama at Birmingham School of Medicine

Maria Descartes, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics, Society for Inherited Metabolic Disorders, International Skeletal Dysplasia Society, Southeastern Regional Genetics Group

Disclosure: Nothing to disclose.