Pediatric Alport Syndrome Treatment & Management

  • Author: Prasad Devarajan, MD; Chief Editor: Craig B Langman, MD   more...
 
Updated: Nov 29, 2011
 

Medical Care

  • No treatment prevents the progression to end-stage renal disease (ESRD) in male patients with X-linked Alport syndrome or in patients with autosomal recessive disease.
    • Some data suggests that cyclosporine therapy or ACE inhibitors decrease proteinuria and may slow the rate of progression.
    • Studies suggest that the response to cyclosporine can vary and that cyclosporine may accelerate the development of interstitial fibrosis due to calcineurin-induced nephrotoxicity.[13] Therefore, such therapy should be approached with caution and close monitoring.
  • Begin appropriate replacement therapy as renal failure advances. Therapy includes erythropoietin for chronic anemia, phosphate binders and vitamin D to manage osteodystrophy, alkali to correct acidosis, and antihypertensive therapy to control blood pressure.
  • Hemodialysis or peritoneal dialysis does not raise specific problems.
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Surgical Care

  • Renal transplantation is the treatment of choice for ESRD in individuals with Alport syndrome. The results of renal transplantation for patients with Alport syndrome compare favorably with results in persons with other diagnoses.[14, 15]
  • About 3-5% of male patients with transplants develop antiglomerular basement membrane glomerulonephritis. These individuals usually have early onset Alport syndrome with clinically significant hearing loss and ESRD by about age 20 years.
    • The pathogenesis is related to the donor glomerular basement membrane with antigens that the recipient lacked; therefore, the recipient never develops immune tolerance to these antigens. These antiglomerular basement membrane antibodies are directed against the NC1 domain of a5(IV) chain in patients with X-linked Alport syndrome and against the NC1 domain of a3(IV) chain in individuals with autosomal recessive disease.
    • Antiglomerular basement membrane disease generally begins within the first year after transplantation. Individuals with this disease develop a severe crescentic-type glomerulonephritis, and 75% of the allografts fail within a few weeks. Plasmapheresis and cytotoxic agents have been of limited value.
    • Antiglomerular basement membrane glomerulonephritis commonly recurs in patients who receive more than one transplant despite prolonged intervals between transplantations and despite an absence of circulating antiglomerular basement membrane antibodies before retransplantation.
  • Female patients with X-linked Alport syndrome and all patients with healthy hearing or late progression to ESRD have a low risk for antiglomerular basement membrane disease after transplantation.
  • Given the typically good rate of graft survival in patients with Alport syndrome and given the inability to predict rare antiglomerular basement membrane disease after transplantation, the use of living donor organs is generally recommended. The feasibility of using kidneys obtained from female donors who do not have symptoms of Alport syndrome and who are heterozygous for COL4A5 mutations is unresolved.
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Consultations

  • Pediatric nephrologist
  • Ophthalmologist
  • Audiologist
  • Transplant surgeon
  • Genetic counselor
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Diet

  • Asymptomatic patients require no dietary restrictions.
  • Individuals with hypertension benefit from a low-salt diet.
  • Protein restriction is routinely prescribed for adults with proteinuria and diminished renal function. The efficacy of restricting protein intake in a growing child with high protein requirements has not been established.
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Activity

  • In general, no restriction of activity is indicated for individuals with Alport syndrome.
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Contributor Information and Disclosures
Author

Prasad Devarajan, MD  Louise M Williams Endowed Chair in Pediatrics, Professor of Pediatrics and Developmental Biology, Director of Nephrology and Hypertension, Director of Clinical Nephrology Laboratories, CEO of Dialysis Unit, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine

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

Disclosure: Nothing to disclose.

Specialty Editor Board

Uri S Alon, MD  Director of Bone and Mineral Disorders Clinic and Renal Research Laboratory, Children's Mercy Hospital of Kansas City; Professor, Department of Pediatrics, Division of Pediatric Nephrology, University of Missouri-Kansas City School of Medicine

Uri S Alon, MD is a member of the following medical societies: American Federation for Medical Research

Disclosure: Nothing to disclose.

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.

Luther Travis, MD  Professor Emeritus, Departments of Pediatrics, Nephrology and Diabetes, University of Texas Medical Branch School of Medicine

Luther Travis, MD is a member of the following medical societies: Alpha Omega Alpha, American Federation for Medical Research, International Society of Nephrology, and Texas Pediatric Society

Disclosure: Nothing to disclose.

Howard Trachtman, MD  Program Director, Pediatrics Research, Schneider Children's Hospital, Department of Pediatrics, Division of Nephrology, Professor, Albert Einstein College of Medicine

Howard Trachtman, MD is a member of the following medical societies: American Society of Hypertension, American Society of Nephrology, American Society of Pediatric Nephrology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Chief Editor

Craig B Langman, MD  The Isaac A Abt, MD, Professor of Kidney Diseases, Northwestern University, The Feinberg School of Medicine; Division Head of Kidney Diseases, Children's Memorial Hospital

Craig B Langman, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Nephrology, and International Society of Nephrology

Disclosure: NIH Grant/research funds None; Raptor Pharmaceuticals, Inc Grant/research funds None; Alexion Pharmaceuticals, Inc. Grant/research funds None

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Electron micrograph from a patient with Alport syndrome revealing the typical splitting and splintering of the glomerular basement membrane (original magnification X3000). Courtesy of Glen S. Markowitz, MD, Department of Pathology, Columbia University College of Physicians and Surgeons, New York.
 
 
 
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