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Clinical proof-of-concept trial to assess the therapeutic effect of sirolimus in patients with autosomal dominant polycystic kidney disease: SUISSE ADPKD study


Serra, A L; Kistler, A D; Poster, D; Struker, M; Wüthrich, R P; Weishaupt, D; Tschirch, F (2007). Clinical proof-of-concept trial to assess the therapeutic effect of sirolimus in patients with autosomal dominant polycystic kidney disease: SUISSE ADPKD study. BMC Nephrology, 8:13.

Abstract

BACKGROUND: Currently there is no effective treatment available to retard cyst growth and to prevent the progression to end-stage renal failure in patients with autosomal dominant polycystic kidney disease (ADPKD). Evidence has recently been obtained from animal experiments that activation of the mammalian target of rapamycin (mTOR) signaling pathway plays a crucial role in cyst growth and renal volume expansion, and that the inhibition of mTOR with rapamycin (sirolimus) markedly slows cyst development and renal functional deterioration. Based on these promising results in animals we have designed and initiated the first randomized controlled trial (RCT) to examine the effectiveness, safety and tolerability of sirolimus to retard disease progression in ADPKD. METHOD/DESIGN: This single center, randomised controlled, open label trial assesses the therapeutic effect, safety and tolerability of the mTOR inhibitor sirolimus (Rapamune) in patients with autosomal dominant polycystic kidney disease and preserved renal function. The primary outcome will be the inhibition of kidney volume growth measured by magnetic resonance imaging (MRI) volumetry. Secondary outcome parameters will be preservation of renal function, safety and tolerability of sirolimus. DISCUSSION: The results from this proof-of-concept RCT will for the first time show whether treatment with sirolimus effectively retards cyst growth in patients with ADPKD.

Abstract

BACKGROUND: Currently there is no effective treatment available to retard cyst growth and to prevent the progression to end-stage renal failure in patients with autosomal dominant polycystic kidney disease (ADPKD). Evidence has recently been obtained from animal experiments that activation of the mammalian target of rapamycin (mTOR) signaling pathway plays a crucial role in cyst growth and renal volume expansion, and that the inhibition of mTOR with rapamycin (sirolimus) markedly slows cyst development and renal functional deterioration. Based on these promising results in animals we have designed and initiated the first randomized controlled trial (RCT) to examine the effectiveness, safety and tolerability of sirolimus to retard disease progression in ADPKD. METHOD/DESIGN: This single center, randomised controlled, open label trial assesses the therapeutic effect, safety and tolerability of the mTOR inhibitor sirolimus (Rapamune) in patients with autosomal dominant polycystic kidney disease and preserved renal function. The primary outcome will be the inhibition of kidney volume growth measured by magnetic resonance imaging (MRI) volumetry. Secondary outcome parameters will be preservation of renal function, safety and tolerability of sirolimus. DISCUSSION: The results from this proof-of-concept RCT will for the first time show whether treatment with sirolimus effectively retards cyst growth in patients with ADPKD.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Nephrology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2007
Deposited On:11 Jan 2010 15:49
Last Modified:28 Aug 2017 11:42
Publisher:BioMed Central
ISSN:1471-2369
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1186/1471-2369-8-13
PubMed ID:17868472

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