Alport Syndrome Follow-up

  • Author: Ramesh Saxena, MD, PhD; Chief Editor: Vecihi Batuman, MD, FACP, FASN   more...
 
Updated: Nov 21, 2011
 

Further Outpatient Care

  • Control the patient's blood pressure.
  • Administer ACE inhibitors or ARBs to control proteinuria.
  • Monitor renal function test results and proteinuria (24-h urinary protein and creatinine). Check 24-hour urinary protein, creatinine, and serum chemistry on an annual basis in those patients without renal insufficiency or those with mild renal insufficiency, every 6 months in those patients with moderate renal insufficiency, and every 1-3 months in those patients with advanced renal failure.
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Inpatient & Outpatient Medications

  • Administer ACE inhibitors or ARBs to control proteinuria and hypertension.
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Transfer

  • Transfer to a dialysis facility when the patient develops ESRD.
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Complications

  • Progression of renal failure
    • The risk of progression of renal failure is highest among males with XLAS and in both males and females with ARAS. ESRD develops in virtually all males with XLAS. Approximately 90% of patients develop ESRD by age 40 years. According to the age at ESRD, XLAS arbitrarily is either the juvenile type or the adult type with a cut off at age 30 years. The juvenile type is encountered in 75% of kindreds. Renal prognosis depends on the kind of mutation. The probability of ESRD in people younger than 30 years is significantly higher (90%) in patients with large rearrangement of the COL4A5 gene compared to those with minor mutations (50-70%). Furthermore, the rate of progression of renal disease is fairly constant among patients within a particular family but shows significant variability between different families.
    • The prognosis in females with XLAS is usually benign, and they rarely develop ESRD. The reported probability of developing ESRD in these patients is 12% by age 40 years and 30% by age 60 years. Risk factors for progression to ESRD are episodes of gross hematuria in childhood, nephrotic range proteinuria, and diffuse GBM thickening on examination with an electron microscope.
  • Hematologic disorders: Several reports describe families with hereditary nephritis associated with deafness, megathrombocytopenia (giant platelets), and, in some families, granulocyte abnormalities. Clinical features include bleeding tendency, macrothrombocytopenia, abnormalities of platelet aggregation (ie, Epstein-Barr syndrome), and, occasionally, neutrophil inclusions that resemble Dohle bodies (ie, May-Hegglin anomaly, Fechner syndrome). In most patients, the autosomal dominant pattern of inheritance is observed. In only 2 reports, focal thickening, splitting, or lamellation of the GBM was identified. The basement membrane of these patients showed normal expression of a chain of type IV collagen. So far, the genetic loci involved remain unknown.
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Prognosis

  • Renal prognosis depends on the kind of mutation. Approximately 90% of patients with Alport syndrome develop ESRD by age 40 years. The probability of ESRD in people younger than 30 years is significantly higher in patients with a large rearrangement of the COL4A5 gene compared to those with minor mutations. Prognosis in females with XLAS is usually benign, with only 12% developing ESRD by age 40 years and 30% by age 60 years.
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Patient Education

  • Provide pre-ESRD education to discuss various options and issues regarding renal replacement therapy (eg, dialysis, transplantation).
  • Arrange dietary counseling for patients approaching ESRD.
  • Avoid administering nephrotoxins in these patients, including over-the-counter nonsteroidal analgesic agents.
  • For excellent patient education resources, visit eMedicine's Kidneys and Urinary System Center. Also, see eMedicine's patient education article Blood in the Urine.
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Contributor Information and Disclosures
Author

Ramesh Saxena, MD, PhD  Associate Professor, Department of Internal Medicine, Division of Nephrology, University of Texas Southwestern Medical Center

Ramesh Saxena, MD, PhD is a member of the following medical societies: American Medical Association, American Society of Nephrology, International Society of Nephrology, and National Kidney Foundation

Disclosure: e-medicine Honoraria authoring review articles

Specialty Editor Board

Frank C Brosius III, MD  Nephrology Program Director, Professor of Internal Medicine and Physiology, Department of Internal Medicine, Division of Nephrology, University of Michigan School of Medicine

Frank C Brosius III, MD is a member of the following medical societies: Alpha Omega Alpha, American Diabetes Association, American Society of Nephrology, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Eleanor Lederer, MD  Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine; Consulting Staff, Louisville Veterans Affairs Hospital

Eleanor Lederer, MD is a member of the following medical societies: American Association for the Advancement of Science, American Federation for Medical Research, American Society for Biochemistry and Molecular Biology, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney Foundation, and Phi Beta Kappa

Disclosure: Dept of Veterans Affairs Grant/research funds Research

Rebecca J Schmidt, DO, FACP, FASN  Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine

Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association

Disclosure: Renal Ventures Ownership interest Other

Chief Editor

Vecihi Batuman, MD, FACP, FASN  Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, and International Society of Nephrology

Disclosure: Nothing to disclose.

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Electron micrograph of kidney biopsy from a patient with Alport syndrome. Note the splitting and lamellation of the glomerular basement membrane (see arrows).
Table 1. Location and Mutations of the Genes Coding for Alpha (IV) Chains of Type IV Collagen in Alport Syndrome
Alpha (IV) ChainGenesChromosomal LocationMutation
Alpha-1 (IV)COL4A113Unknown
Alpha-2 (IV)COL4A213Unknown
Alpha-3 (IV)COL4A32ARAS*
Alpha-4 (IV)COL4A42ARAS
Alpha-5 (IV)COL4A5xXLAS †
Alpha-6 (IV)COL4A6xLeiomyomatosis ‡
* Autosomal recessive Alport syndrome (mutations spanning 5' regions of COL4A5 and COL4A6 genes)



† X-linked Alport syndrome



‡ Autosomal recessive Alport syndrome



Table 2. Tissue Distribution of Alpha (IV) Chains
Alpha (IV) ChainTissue Distribution
Alpha-1 (IV)Ubiquitous
Alpha-2 (IV)Ubiquitous
Alpha-3 (IV)GBM, distal TBM*, Descemet membrane, Bruch membrane, anterior lens capsule, lungs, cochlea
Alpha-4 (IV)GBM, distal TBM, Descemet membrane, Bruch membrane, anterior lens capsule, lungs, cochlea
Alpha-5 (IV)GBM, distal TBM, Descemet membrane, Bruch membrane, anterior lens capsule, lungs, cochlea
Alpha-6 (IV)Distal TBM, epidermal basement membrane
* Tubular basement membrane
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