Alport syndrome refers to a hereditary disorder characterized by progressive renal disease and a multilaminar appearance to the glomerular basement membrane (GBM). In a small group of patients with
Alport syndrome,
cyclosporine A was reported to decrease
proteinuria and maintain stable renal function over 7 to 10 yr of follow-up. The present study examined the effect of
cyclosporine A on GBM structure and the progression to
renal failure in a canine model of
X-linked Alport syndrome. Affected male dogs and normal male dogs treated with
cyclosporine A underwent serial renal biopsies.
Body weight, serum concentrations of
creatinine and
albumin, and GFR were sequentially determined. Controls consisted of untreated dogs that developed
end-stage renal failure by 8 mo of age. Renal biopsies were assessed for glomerulosclerosis and the percent of multilaminar GBM as measured by image analysis. Significant differences were found between treated and untreated affected dogs for weight, serum
creatinine, and GFR. There was a significant delay in the progression of multilaminar change to the GBM, although treated affected dogs at termination had attained approximately 100% split GBM as did untreated affected dogs. A significant difference in the number of sclerotic glomeruli was also noted; treated dogs rarely developed obsolete glomeruli during the period studied. Interstitial
fibrosis was not significantly affected by
cyclosporine A treatment. These findings indicate that
cyclosporine A is beneficial in slowing, but not stopping, the clinical and pathologic progression of
Alport syndrome. At least part of this beneficial effect comes from a delayed deterioration of GBM structure, which in turn may be related to glomerular hemodynamics altered by
cyclosporine A.