PMID- 28491859
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2251-8363 (Print)
IS  - 2251-8819 (Electronic)
IS  - 2251-8363 (Linking)
VI  - 6
IP  - 2
DP  - 2017 Mar
TI  - Autophagy in kidney transplants of sirolimus treated recipients.
PG  - 90-96
LID - 10.15171/jnp.2017.15 [doi]
AB  - BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors are increasingly used 
      as immunosuppressive agents in kidney transplantation. In the experimental 
      setting it has been shown that mTOR inhibitors promote autophagy, but the concept 
      that this might also occur in transplant patients has not been addressed. 
      OBJECTIVES: This study was designed to investigate the association between mTOR 
      inhibition and autophagy in renal transplants under routine clinical conditions. 
      MATERIALS AND METHODS: Protocol transplant biopsies of patients receiving 
      sirolimus were compared to biopsies of patients treated without mTOR inhibitor. 
      Electron microscopy was used for quantitative stereological analysis of 
      autophagosomal volume fractions. Ultrastructural analysis was focused on 
      podocytes to avoid cell type bias. Autophagy-related gene products were profiled 
      by QPCR from laser assisted microdissected glomeruli and by immunohistochemistry 
      for semiquantitative evaluation. RESULTS: By electron microscopy, we observed a 
      significant > 50% increase in podocytic autophagosomal volume fractions in 
      patients treated with sirolimus. Evaluation of biopsy material from the same 
      patients using transcriptional profiling of laser capture microdissected 
      glomeruli revealed no differences in autophagy-related gene expressions. 
      Immunohistochemical evaluation of autophagic degradation product p62 was also 
      unaltered whereas a significant increase was observed in podocytic LC3 positivity 
      in biopsies of sirolimus treated patients. CONCLUSIONS: These results indicate an 
      association of sirolimus treatment and autophagosome formation in transplant 
      patients. However, they might reflect autophagosomal buildup rather than 
      increased autophagic flux. Further research is needed to investigate the 
      potential functional consequences in short- and long-term outcome of patients 
      treated with mTOR inhibitors.
FAU - Bhayana, Sagar
AU  - Bhayana S
AD  - Department of Nephrology and Hypertension, Hannover Medical School, Hannover, 
      Germany.
FAU - Baisantry, Arpita
AU  - Baisantry A
AD  - Department of Nephrology and Hypertension, Hannover Medical School, Hannover, 
      Germany.
AD  - Department of Paediatric Nephrology and Gastroenterology, Hannover Medical 
      School, Hannover, Germany.
FAU - Kraemer, Thomas D
AU  - Kraemer TD
AD  - Department of Nephrology and Hypertension, Hannover Medical School, Hannover, 
      Germany.
FAU - Wrede, Christoph
AU  - Wrede C
AD  - Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, 
      Germany.
AD  - REBIRTH Cluster of Excellence, Hannover, Germany.
FAU - Hegermann, Jan
AU  - Hegermann J
AD  - Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, 
      Germany.
AD  - REBIRTH Cluster of Excellence, Hannover, Germany.
FAU - Brasen, Jan-Hinrich
AU  - Brasen JH
AD  - Institute of Pathology, Medical School Hannover, Hannover, Germany.
FAU - Bockmeyer, Clemens
AU  - Bockmeyer C
AD  - Institute of Pathology, Medical School Hannover, Hannover, Germany.
FAU - Ulrich Becker, Jan
AU  - Ulrich Becker J
AD  - Institute of Pathology, Medical School Hannover, Hannover, Germany.
FAU - Ochs, Matthias
AU  - Ochs M
AD  - Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, 
      Germany.
AD  - REBIRTH Cluster of Excellence, Hannover, Germany.
FAU - Gwinner, Wilfried
AU  - Gwinner W
AD  - Department of Nephrology and Hypertension, Hannover Medical School, Hannover, 
      Germany.
FAU - Haller, Hermann
AU  - Haller H
AD  - Department of Nephrology and Hypertension, Hannover Medical School, Hannover, 
      Germany.
FAU - Melk, Anette
AU  - Melk A
AD  - Department of Paediatric Nephrology and Gastroenterology, Hannover Medical 
      School, Hannover, Germany.
FAU - Schmitt, Roland
AU  - Schmitt R
AD  - Department of Nephrology and Hypertension, Hannover Medical School, Hannover, 
      Germany.
LA  - eng
PT  - Journal Article
DEP - 20161022
PL  - Iran
TA  - J Nephropathol
JT  - Journal of nephropathology
JID - 101611182
PMC - PMC5418076
OTO - NOTNLM
OT  - Autophagy
OT  - Electron microscopy
OT  - Kidney transplant biopsy
OT  - Sirolimus
OT  - mTOR inhibitors
EDAT- 2017/05/12 06:00
MHDA- 2017/05/12 06:01
PMCR- 2017/03/01
CRDT- 2017/05/12 06:00
PHST- 2016/07/30 00:00 [received]
PHST- 2016/10/10 00:00 [accepted]
PHST- 2017/05/12 06:00 [entrez]
PHST- 2017/05/12 06:00 [pubmed]
PHST- 2017/05/12 06:01 [medline]
PHST- 2017/03/01 00:00 [pmc-release]
AID - 10.15171/jnp.2017.15 [doi]
PST - ppublish
SO  - J Nephropathol. 2017 Mar;6(2):90-96. doi: 10.15171/jnp.2017.15. Epub 2016 Oct 22.