Early initiation of ACE inhibitor therapy once patients exhibit proteinuria is becoming the standard of care for Alport syndrome.
Treatment of renal failure in Alport patients is the same as in patients with other kidney diseases. Therapy includes erythropoietin for anemia, phosphate binders and vitamin D analogues to manage osteodystrophy, and antihypertensive therapy to control blood pressure. Hemodialysis or peritoneal dialysis does not raise specific problems.
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.
About 3-5% of male patients with transplants develop anti-glomerular basement membrane glomerulonephritis. These individuals usually have early-onset Alport syndrome with clinically significant hearing loss and ESRD before 30 years of age.
- The pathogenesis is related to the presence in donor glomerular basement membrane of antigens that the recipient lacks; therefore, the recipient never develops immune tolerance to these antigens. These anti-GBM antibodies are directed against the NC1 domain of the a5(IV) chain in patients with X-linked Alport syndrome and against the NC1 domain of the a3(IV) chain in individuals with autosomal recessive disease.
- Anti-GBM disease generally begins within the first year after transplantation. Individuals with this disease develop a severe crescentic glomerulonephritis, and 75% of the allografts fail within a few weeks. Plasmapheresis and cytotoxic agents have been of limited value.
- Anti-GBM nephritis commonly recurs in patients who receive more than one transplant despite prolonged intervals between transplants and despite absence of circulating anti-GBM antibodies at the time of retransplantation.
Female patients with X-linked Alport syndrome and patients with late progression to ESRD have a low risk for anti-GBM disease after transplantation.
Given the typically good rate of graft survival in patients with Alport syndrome and the inability to predict which patients will develop anti-GBM disease after transplant, the use of living donor organs is generally recommended. Females with X-linked Alport syndrome should be discouraged from being kidney donors, because of the risk of chronic renal failure in these patients.