eMedicine Specialties > Pediatrics: General Medicine > Nephrology

Alport Syndrome: Treatment & Medication

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, Chief Executive Officer of Dialysis Unit, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine
Contributor Information and Disclosures

Updated: Oct 1, 2008

Treatment

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.9 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.

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.10,11
  • 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.

Consultations

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

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.

Activity

  • In general, no restriction of activity is indicated for individuals with Alport syndrome.

Medication

Immunosuppressive agents

Cyclosporine may reduce proteinuria and retard the progression of renal disease by inducing afferent arteriolar vasoconstriction, increasing glomerular permselectivity, and inhibiting proinflammatory lymphokines. Efficacy of this treatment in patients was documented only in small series, and further studies are required before this therapy can be recommended on a routine basis. Abstracts suggest that cyclosporine may accelerate the development of interstitial fibrosis.12,9 Therefore, such therapy should be approached with caution and with close monitoring.


Cyclosporine (Neoral, Sandimmune)

Cyclic polypeptide that suppresses some humoral immunity and, to greater extent, cell-mediated immune reactions. Available as cap and PO microemulsion liquid formulation.

Adult

3-5 mg/kg/d PO divided bid

Pediatric

5 mg/kg/d PO divided bid; adjust dose to provide trough levels of approximately 100 ng/ml

Cytochrome P450 (CYP) 3A4 inducers (eg, phenobarbital, phenytoin, rifampin, carbamazepine) decrease levels; CYP3A4 inhibitors (eg, erythromycin, antifungals, calcium channel blockers, grapefruit) increases levels; coadministration with nephrotoxic drugs (eg, aminoglycosides, acyclovir, amphotericin B) increase risk of nephrotoxicity; high-fat meals increase volume of distribution; rhabdomyolysis, myositis, and myalgias increase when taken concurrently with lovastatin

Documented hypersensitivity; relative contraindications include acute infections, acute renal insufficiency, and hypertension

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Adverse effects include renal dysfunction, hypertension, tremor, gingival hyperplasia, increased susceptibility to infections, and lymphoproliferative disorders; administer at same time each day; do not refrigerate; keep in original container; do not use plastic or plastic foam cup to administer microemulsion and use within 2 mo after opening

ACE inhibitors

These drugs may reduce proteinuria and retard the progression of renal disease by decreasing hydrostatic pressure across glomerular capillaries. Preliminary studies demonstrated effectiveness and relative safety of ACE inhibition in children with Alport syndrome, and its cautious use now is recommended.


Enalapril (Vasotec)

Prevents conversion of angiotensin I to angiotensin II, potent vasoconstrictor, increasing levels of plasma renin and reducing aldosterone secretion.

Adult

5 mg/d PO initially; may gradually increase until desired effect (ie, normalization of proteinuria); not to exceed 20 mg/d

Pediatric

2.5 mg/d PO initially; may increased by 2.5 mg until desired effect observed (ie, normalization of proteinuria); in general, not to exceed 10 mg/d PO in young children and 10 mg PO bid in adolescents

Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce hypotensive effects; ACE inhibitors may increase digoxin, lithium, and allopurinol levels; rifampin decreases l levels; probenecid may increase levels; concurrent diuretics may enhance hypotensive effects of ACE inhibitors

Documented hypersensitivity; pregnancy

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in renal impairment (adjust dose), valvular stenosis, or severe congestive heart failure; can cause hyperkalemia, hypotension, and neutropenia; titrate dose to effect as tolerated

More on Alport Syndrome

Overview: Alport Syndrome
Differential Diagnoses & Workup: Alport Syndrome
Treatment & Medication: Alport Syndrome
Follow-up: Alport Syndrome
Multimedia: Alport Syndrome
References
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References

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Further Reading

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Keywords

Alport syndrome, Alport's syndrome, hereditary nephritis, familial nephritis, hereditary nephritis with neurosensory deafness, Alport syndrome and mental retardation, ATS-MR, end-stage renal disease, ESRD, hematuria, glomerulosclerosis, proteinuria, hypertension, hearing loss, upper respiratory infection, renal insufficiency, nephrotic syndrome, chronic anemia, osteodystrophy, leiomyomatosis, bronchitis, megathrombocytopenia, Epstein syndrome, Fechtner syndrome, May-Hegglin syndrome, Sebastian syndrome, hypoalbuminemia, hypercholesterolemia, stone disease, cystic dysplasia

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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, Chief Executive Officer 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.

Medical Editor

Uri S Alon, MD, Director of Research and Education, Department of Pediatrics, Division of Pediatric Nephrology, Children's Mercy Hospital of Kansas City; Professor, University of Missouri at Kansas City
Uri S Alon, MD is a member of the following medical societies: American Federation for Medical Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Luther Travis, MD, William W Glauser Professor of Pediatrics and Pediatric Nephrology, Department of Pediatrics, Divisions of Nephrology and Diabetes, University of Texas Medical Branch and Children's Hospital
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.

CME Editor

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, Feinberg School of Medicine, Northwestern University; Division Head of Kidney Diseases, Children's Memorial Hospital, Chicago
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: Amgen Grant/research funds None; Abbott Honoraria Speaking and teaching; Altus Pharmaceuticals Grant/research funds None; Genzyme Grant/research funds None; Merck Grant/research funds None; NIH Grant/research funds None

 
 
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