PMID- 20466742
OWN - NLM
STAT- MEDLINE
DCOM- 20100621
LR  - 20220316
IS  - 1533-3450 (Electronic)
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 21
IP  - 6
DP  - 2010 Jun
TI  - Sirolimus therapy to halt the progression of ADPKD.
PG  - 1031-40
LID - 10.1681/ASN.2009121302 [doi]
AB  - Activation of mammalian target of rapamycin (mTOR) pathways may contribute to 
      uncontrolled cell proliferation and secondary cyst growth in patients with 
      autosomal dominant polycystic kidney disease (ADPKD). To assess the effects of 
      mTOR inhibition on disease progression, we performed a randomized, crossover 
      study (The SIRENA Study) comparing a 6-month treatment with sirolimus or 
      conventional therapy alone on the growth of kidney volume and its compartments in 
      21 patients with ADPKD and GFR>or=40 ml/min per 1.73 m2. In 10 of the 15 patients 
      who completed the study, aphthous stomatitis complicated sirolimus treatment but 
      was effectively controlled by topical therapy. Compared with pretreatment, 
      posttreatment mean total kidney volume increased less on sirolimus (46+/-81 ml; 
      P=0.047) than on conventional therapy (70+/-72 ml; P=0.002), but we did not 
      detect a difference between the two treatments (P=0.45). Cyst volume was stable 
      on sirolimus and increased by 55+/-75 ml (P=0.013) on conventional therapy, 
      whereas parenchymal volume increased by 26+/-30 ml (P=0.005) on sirolimus and was 
      stable on conventional therapy. Percentage changes in cyst and parenchyma volumes 
      were significantly different between the two treatment periods. Sirolimus had no 
      appreciable effects on intermediate volume and GFR. Albuminuria and proteinuria 
      marginally but significantly increased during sirolimus treatment. In summary, 
      sirolimus halted cyst growth and increased parenchymal volume in patients with 
      ADPKD. Whether these effects translate into improved long-term outcomes requires 
      further investigation.
FAU - Perico, Norberto
AU  - Perico N
AD  - Clinical Research Center for Rare Diseases, Aldo e Cele Dacco, Mario Negri 
      Institute for Pharmacological Research, Bergamo, Italy.
FAU - Antiga, Luca
AU  - Antiga L
FAU - Caroli, Anna
AU  - Caroli A
FAU - Ruggenenti, Piero
AU  - Ruggenenti P
FAU - Fasolini, Giorgio
AU  - Fasolini G
FAU - Cafaro, Mariateresa
AU  - Cafaro M
FAU - Ondei, Patrizia
AU  - Ondei P
FAU - Rubis, Nadia
AU  - Rubis N
FAU - Diadei, Olimpia
AU  - Diadei O
FAU - Gherardi, Giulia
AU  - Gherardi G
FAU - Prandini, Silvia
AU  - Prandini S
FAU - Panozo, Andrea
AU  - Panozo A
FAU - Bravo, Rodolfo Flores
AU  - Bravo RF
FAU - Carminati, Sergio
AU  - Carminati S
FAU - De Leon, Felipe Rodriguez
AU  - De Leon FR
FAU - Gaspari, Flavio
AU  - Gaspari F
FAU - Cortinovis, Monica
AU  - Cortinovis M
FAU - Motterlini, Nicola
AU  - Motterlini N
FAU - Ene-Iordache, Bogdan
AU  - Ene-Iordache B
FAU - Remuzzi, Andrea
AU  - Remuzzi A
FAU - Remuzzi, Giuseppe
AU  - Remuzzi G
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20100513
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
CIN - J Am Soc Nephrol. 2010 Jun;21(6):891-3. PMID: 20431043
CIN - Nat Rev Nephrol. 2010 Aug;6(8):443. PMID: 20690198
MH  - Adult
MH  - Cell Proliferation/drug effects
MH  - Cross-Over Studies
MH  - *Disease Progression
MH  - Female
MH  - Glomerular Filtration Rate/drug effects/physiology
MH  - Humans
MH  - Immunosuppressive Agents/adverse effects/pharmacology/*therapeutic use
MH  - Intracellular Signaling Peptides and Proteins/metabolism
MH  - Kidney/drug effects/pathology
MH  - Male
MH  - Middle Aged
MH  - Polycystic Kidney, Autosomal Dominant/*drug therapy/pathology/physiopathology
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Signal Transduction/drug effects/physiology
MH  - Sirolimus/adverse effects/pharmacology/*therapeutic use
MH  - TOR Serine-Threonine Kinases
MH  - Treatment Outcome
PMC - PMC2900967
EDAT- 2010/05/15 06:00
MHDA- 2010/06/22 06:00
PMCR- 2011/06/01
CRDT- 2010/05/15 06:00
PHST- 2010/05/15 06:00 [entrez]
PHST- 2010/05/15 06:00 [pubmed]
PHST- 2010/06/22 06:00 [medline]
PHST- 2011/06/01 00:00 [pmc-release]
AID - ASN.2009121302 [pii]
AID - 2009121302 [pii]
AID - 10.1681/ASN.2009121302 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2010 Jun;21(6):1031-40. doi: 10.1681/ASN.2009121302. Epub 2010 
      May 13.