Focal segmental glomerulosclerosis in association with neurofibromatosis type 1: a case report and proposed molecular pathways
Open accessAbstract
A 42-year-old Caucasian female with history of neurofibromatosis type 1 presented with nephrotic range proteinuria and focal segmental glomerulosclerosis (FSGS). On final dose of lisinopril 20 mg/day, protein-creatinine ratio declined to 0.33 within 10 months. We propose the hypothesis that development of FSGS in NF1 may be mediated by activation of mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling pathways secondary to up-regulation of ras proteins due to deficient neurofibromin. Since mTOR signaling pathway is partially mediated through angiotensin-II activation, angiotensin-converting enzyme (ACE) inhibition may serve as an effective initial treatment beyond anti-proteinuric properties of ACE-inhibitors.
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Decreased neurofibromin activity in NF1 might be associated with LPG and contribute to its development as an additional factor.
“The decrease in activity of neurofibromin in NF1 might also be associated with LPG which is a glomerular disease, and contribute to the development of LPG as an additional factor.”
From A case of lipoprotein glomerulopathy with a rare apolipoprotein E isoform combined with neurofibromatosis type I (2018) · cites this paper as [14]
The Discussion (page unavailable) says NF1 can diminish neurofibromin activity and proposes that deficient neurofibromin may contribute to focal segmental glomerulosclerosis (FSGS). It does not address LPG or propose a role for neurofibromin in its development; a search for LPG and lipoprotein glomerulopathy found no matching passage. (LLM, conf=0.88)
Experimental — accuracy not yet measuredNF1 is associated with glomerular diseases.
“These findings suggest the association of NF1 with glomerular diseases.”
From A case of lipoprotein glomerulopathy with a rare apolipoprotein E isoform combined with neurofibromatosis type I (2018) · cites this paper as [14]
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Cites
The neurofibromatosis type 1 gene encodes a protein related to GAP
Xu, G., O'Connell, P., Viskochil, D., Cawthon, R., Robertson, M., Culver, M., Dunn, D., Stevens, J., Gesteland, R., White, R., et al. (1990) · Cell · doi:10.1016/0092-8674(90)90024-9 · Cited by 1,095 · cited 1× · see citing works
“The p21-ras protein binds to guanine nucleotides, possesses intrinsic GTPase activity and functions as an important regulator of cell growth [15, 16].”
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Takasaki, S., Matsunaga, A., Joh, K., & Saito, T. (2018) · CEN Case Reports · doi:10.1007/s13730-018-0309-2 · Cited by 7 · see citing works
- Authors
- Afshinnia, F., Vega-Warner, V., & Killen, P.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Afshinnia, F.
- Venue
- Clinical Kidney Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-03-27
- Volume
- 6
- Issue
- 2
- Pages
- 208-210
- ISSN
- 2048-8505 (ISSN-L)
- 2048-8513
- PMC
- PMC3693487
- OpenAlex
- W2110266123
- Cited by
- 12
- References
- 2
- Citations by year
- 2024: 1 · 2021: 2 · 2019: 2 · 2018: 2 · 2016: 2 · 2015: 1 · 2014: 2
- FWCI
- 1.26
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Clinical Kidney Journal (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007378)
- Topics
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Health Sciences › Medicine › Neurology › Neurofibromatosis and Schwannoma Cases
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Keywords
- focal segmental glomerulosclerosis, neurofibromatosis type 1, nephrotic-range proteinuria, lisinopril, ACE inhibitors, MAPK signaling, mTOR signaling, neurofibromin, Ras proteins, angiotensin II, proteinuria
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