Effect of cyclosporin a on proteinuria in patients with Alport's syndrome

Callı́s, L; Vila, Amparo Marquina; Nieto, Juliana Serrano; Fortuny, G.

doi:10.1007/bf00866293

Cited by 33 publications

(18 citation statements)

References 8 publications

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“…One of the most striking results in human Alport patients receiving cyclosporine A was a marked reduction or elimination of proteinuria (20,21). Protein balance in the present study was assessed by determining serum protein concentrations and the urinary protein/creatinine ratio.…”

Section: Discussionmentioning

confidence: 88%

“…Cyclosporine A has been used in transplantation and immune-mediated disease for many years; however, its therapeutic effects in the treatment of Alport syndrome has only recently been examined (20,21). In a small and uncontrolled study, cyclosporine A decreased or eliminated proteinuria and halted the progression of renal disease.…”

Section: Discussionmentioning

confidence: 99%

“…Beneficial effects have been reported for human Alport patients and in animal models using low-protein diets (17) and angiotensin-converting enzyme inhibitors (18,19). More recently, cyclosporine A was reported to be beneficial to patients with Alport syndrome in a small noncontrolled study (20,21). Massive proteinuria decreased or disappeared, whereas creatinine clearance remained stable throughout treatment.…”

Section: Mutations Have Been Identified In the Col4a3mentioning

confidence: 99%

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Cyclosporine A Slows the Progressive Renal Disease of Alport Syndrome (X-Linked Hereditary Nephritis)

Chen¹,

Jefferson²,

Harvey³

et al. 2003

Journal of the American Society of Nephrology

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Abstract. 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.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Mutations Have Been Identified In the Col4a3mentioning

confidence: 99%

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Cyclosporine A Slows the Progressive Renal Disease of Alport Syndrome (X-Linked Hereditary Nephritis)

Chen¹,

Jefferson²,

Harvey³

et al. 2003

Journal of the American Society of Nephrology

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“…Callis et al reported on eight male patients with Alport syndrome treated with CyA for 7-10 years. These patients showed a slower progression to renal failure than their affected but untreated siblings [7,8]. Repeat renal biopsies did not show any signs of CyA nephrotoxicity after 5 years of treatment.…”

Section: Introductionmentioning

confidence: 78%

Non-immunologic mechanisms of calcineurin inhibitors explain its antiproteinuric effects in genetic glomerulopathies

Bensman

Niaudet

2010

Pediatr Nephrol

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It has been reported (this issue Pediatric Nephrology) that cyclosporine A (CyA) therapy in combination with corticosteroids, angiotensin-converting enzyme inhibitor, and an angiotensin receptor blocker decreased proteinuria in three patients with nephrotic syndrome (NS) due to WT1 mutations. Treatment with calcineurin inhibitors were found to induce a partial remission of proteinuria in several other children with genetic forms of NS, such as mutation in the podocine and in the phospholipase C epsilon gene. CyA therapy has also been reported to be beneficial to patients with Alport syndrome. Recent data have shown that the antiproteinuric effect of CyA in these cases may be due to a non-immunologic mechanism. CyA exerts an antiproteinuria effect by preventing the degradation of the actin organizing protein synaptodpodin and by a downregulation of TRPC6. This mechanism leads to the stabilization of the actin cytoskeleton in the kidney podocytes. This beneficial effect of CyA is interesting, but long-term results regarding function and nephrotoxicity are still missing.

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“…Callis and colleagues found, in an uncontrolled study of eight Alport males, that cyclosporine appeared to suppress proteinuria and stabilize renal function, over several years of observation [75,76]. There has yet to be a published report that contradicts these findings.…”

Section: Examination Of Type IV Collagen Expression By Immunohistochementioning

confidence: 84%

Familial hematurias: what we know and what we don’t

Kashtan

2005

Pediatr Nephrol

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Over the past 30 years we have learned a great deal about the molecular genetics and natural history of familial forms of hematuria. Our enhanced understanding of these conditions has yet to generate effective therapies for Alport syndrome, the form of familial hematuria associated with end-stage renal disease. This review briefly presents the current state of knowledge about familial hematuria and argues for the organization of clinical therapeutic trials in Alport syndrome.

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Effect of cyclosporin a on proteinuria in patients with Alport's syndrome

Cited by 33 publications

References 8 publications

Cyclosporine A Slows the Progressive Renal Disease of Alport Syndrome (X-Linked Hereditary Nephritis)

Cyclosporine A Slows the Progressive Renal Disease of Alport Syndrome (X-Linked Hereditary Nephritis)

Non-immunologic mechanisms of calcineurin inhibitors explain its antiproteinuric effects in genetic glomerulopathies

Familial hematurias: what we know and what we don’t

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