PMID- 37532078
OWN - NLM
STAT- MEDLINE
DCOM- 20231124
LR  - 20231213
IS  - 1523-6838 (Electronic)
IS  - 0272-6386 (Linking)
VI  - 82
IP  - 6
DP  - 2023 Dec
TI  - Microscopic Kidney Disease in Tuberous Sclerosis Complex and Treatment With mTOR 
      Inhibition.
PG  - 772-775
LID - S0272-6386(23)00744-8 [pii]
LID - 10.1053/j.ajkd.2023.04.016 [doi]
AB  - Declining kidney function in tuberous sclerosis complex (TSC) is often attributed 
      to large lesions, including angiomyolipomas (AMLs) and cysts, that encroach on 
      the normal parenchyma or that require intervention and loss of parenchyma from 
      surgical debulking or embolization. Consequently, research on inhibitors of the 
      mammalian target of rapamycin (mTOR), a protein complex implicated in TSC 
      pathophysiology for its role in promoting cell growth and proliferation, has 
      largely focused on their ability to reduce AML size. Clinical guidelines 
      distilled from this research limit mTOR inhibition as a first-line treatment to 
      patients with large AMLs. However, chronic kidney disease (CKD) occurs in 
      patients without large AMLs or a history of renal intervention. Alternate 
      mechanisms postulated for CKD in TSC may suggest a role for mTOR inhibition in 
      this population. In this report, we present 2 cases of a microscopic variant of 
      TSC kidney disease causing declining kidney function, as well as anecdotal 
      evidence for the use of mTOR inhibition to improve kidney function in the absence 
      of large AMLs. We highlight the importance of annual kidney function assessment 
      in patients with TSC and suggest a low threshold for kidney biopsy in patients 
      with declining glomerular filtration rate without a clear etiology clinically or 
      radiographically.
CI  - Copyright (c) 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All 
      rights reserved.
FAU - Kronick, Jami
AU  - Kronick J
AD  - Schulich School of Medicine and Dentistry, Western University, London, Ontario, 
      Canada.
FAU - Gabril, Manal Y
AU  - Gabril MY
AD  - Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry, 
      Western University, London, Ontario, Canada.
FAU - House, Andrew A
AU  - House AA
AD  - Division of Nephrology, Department of Medicine, Western University and London 
      Health Sciences Centre, London, Ontario, Canada. Electronic address: 
      Andrew.House@lhsc.on.ca.
LA  - eng
PT  - Case Reports
DEP - 20230731
PL  - United States
TA  - Am J Kidney Dis
JT  - American journal of kidney diseases : the official journal of the National Kidney 
      Foundation
JID - 8110075
RN  - W36ZG6FT64 (Sirolimus)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Humans
MH  - *Tuberous Sclerosis/complications/drug therapy/pathology
MH  - *Kidney Neoplasms/drug therapy/complications
MH  - Sirolimus/therapeutic use
MH  - Kidney/pathology
MH  - *Angiomyolipoma/drug therapy/etiology/pathology
MH  - TOR Serine-Threonine Kinases
MH  - *Renal Insufficiency, Chronic/complications
OTO - NOTNLM
OT  - Angiomyolipomas
OT  - Chronic kidney disease: mTOR inhibitor
OT  - Everolimus
OT  - Sirolimus
OT  - TSC
OT  - Tuberous sclerosis complex
EDAT- 2023/08/03 01:06
MHDA- 2023/11/24 06:43
CRDT- 2023/08/02 19:14
PHST- 2022/10/31 00:00 [received]
PHST- 2023/03/02 00:00 [revised]
PHST- 2023/04/27 00:00 [accepted]
PHST- 2023/11/24 06:43 [medline]
PHST- 2023/08/03 01:06 [pubmed]
PHST- 2023/08/02 19:14 [entrez]
AID - S0272-6386(23)00744-8 [pii]
AID - 10.1053/j.ajkd.2023.04.016 [doi]
PST - ppublish
SO  - Am J Kidney Dis. 2023 Dec;82(6):772-775. doi: 10.1053/j.ajkd.2023.04.016. Epub 
      2023 Jul 31.