PMID- 19776171
OWN - NLM
STAT- MEDLINE
DCOM- 20091228
LR  - 20211203
IS  - 1522-1466 (Electronic)
IS  - 1522-1466 (Linking)
VI  - 297
IP  - 6
DP  - 2009 Dec
TI  - Pulse mTOR inhibitor treatment effectively controls cyst growth but leads to 
      severe parenchymal and glomerular hypertrophy in rat polycystic kidney disease.
PG  - F1597-605
LID - 10.1152/ajprenal.00430.2009 [doi]
AB  - The efficacy of mammalian target of rapamycin (mTOR) inhibitors is currently 
      tested in patients affected by autosomal dominant polycystic kidney disease. 
      Treatment with mTOR inhibitors has been associated with numerous side effects. 
      However, the renal-specific effect of mTOR inhibitor treatment cessation in 
      polycystic kidney disease is currently unknown. Therefore, we compared pulse and 
      continuous everolimus treatment in Han:SPRD rats. Four-week-old male heterozygous 
      polycystic and wild-type rats were administered everolimus or vehicle by gavage 
      feeding for 5 wk, followed by 7 wk without treatment, or continuously for 12 wk. 
      Cessation of everolimus did not result in the appearance of renal cysts up to 7 
      wk postwithdrawal despite the reemergence of S6 kinase activity coupled with an 
      overall increase in cell proliferation. Pulse everolimus treatment resulted in 
      striking noncystic renal parenchymal enlargement and glomerular hypertrophy that 
      was not associated with compromised kidney function. Both treatment regimens 
      ameliorated kidney function, preserved the glomerular-tubular connection, and 
      reduced proteinuria. Pulse treatment at an early age delays cyst development but 
      leads to striking glomerular and parenchymal hypertrophy. Our data might have an 
      impact when long-term treatment using mTOR inhibitors in patients with autosomal 
      dominant polycystic kidney disease is being considered.
FAU - Wu, Ming
AU  - Wu M
AD  - Zurich Center for Integrative Human Physiology (ZIHP), Zurich, Switzerland.
FAU - Arcaro, Alexandre
AU  - Arcaro A
FAU - Varga, Zsuzsanna
AU  - Varga Z
FAU - Vogetseder, Alexander
AU  - Vogetseder A
FAU - Le Hir, Michel
AU  - Le Hir M
FAU - Wuthrich, Rudolf P
AU  - Wuthrich RP
FAU - Serra, Andreas L
AU  - Serra AL
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090923
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Emulsions)
RN  - 0 (Immunosuppressive Agents)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Drug Administration Schedule
MH  - Emulsions
MH  - Everolimus
MH  - Hypertrophy
MH  - Immunosuppressive Agents/*administration & dosage/*adverse effects
MH  - Kidney/*drug effects/*pathology/physiopathology
MH  - Kidney Glomerulus/pathology
MH  - Male
MH  - Polycystic Kidney Diseases/*drug therapy/pathology/physiopathology
MH  - Protein Kinases/*drug effects
MH  - Proteinuria/drug therapy
MH  - Pulse Therapy, Drug
MH  - Rats
MH  - Sirolimus/administration & dosage/adverse effects/*analogs & derivatives
MH  - TOR Serine-Threonine Kinases
EDAT- 2009/09/25 06:00
MHDA- 2009/12/29 06:00
CRDT- 2009/09/25 06:00
PHST- 2009/09/25 06:00 [entrez]
PHST- 2009/09/25 06:00 [pubmed]
PHST- 2009/12/29 06:00 [medline]
AID - 00430.2009 [pii]
AID - 10.1152/ajprenal.00430.2009 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2009 Dec;297(6):F1597-605. doi: 
      10.1152/ajprenal.00430.2009. Epub 2009 Sep 23.