Cyclosporine A slows the progressive renal disease of Alport syndrome (X-linked hereditary nephritis): Results from a canine model

被引:64
作者
Chen, D
Jefferson, B
Harvey, SJ
Zheng, KQ
Gartley, CJ
Jacobs, RM
Thorner, PS
机构
[1] Hosp Sick Children, Div Pathol, Toronto, ON M5G 1X8, Canada
[2] Hosp Sick Children, Div Struct Biol & Biochem, Toronto, ON M5G 1X8, Canada
[3] Univ Guelph, Dept Pathobiol, Guelph, ON N1G 2W1, Canada
[4] Univ Guelph, Dept Populat Med, Guelph, ON N1G 2W1, Canada
[5] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2003年 / 14卷 / 03期
关键词
D O I
10.1097/01.ASN.0000046964.15831.16
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:690 / 698
页数:9
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