Progranulin and Its Receptor Predict Kidney Function Decline in Patients With Type 2 Diabetes

Progranulin (PGRN), a growth factor, is abundantly expressed in a broad range of tissues and cell types with pleiotropic functions including inflammation, neurodegeneration, and facilitating lysosome acidification. PGRN binds to TNF receptors (TNFR) and inhibits downstream inflammatory signaling pat...

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Published in:Frontiers in endocrinology (Lausanne) 2022-04, Vol.13, p.849457-849457
Main Authors: Murakoshi, Maki, Gohda, Tomohito, Sakuma, Hiroko, Shibata, Terumi, Adachi, Eri, Kishida, Chiaki, Ichikawa, Saki, Koshida, Takeo, Kamei, Nozomu, Suzuki, Yusuke
Format: Article
Language:English
Subjects:
biomarker
Diabetes Mellitus, Type 2 - complications
diabetic kidney disease
Endocrinology
Female
Humans
Kidney - metabolism
Male
progranulin (GRN)
Progranulins
Receptors, Tumor Necrosis Factor - metabolism
Receptors, Tumor Necrosis Factor, Type I - metabolism
renal outcome
tumor necrosis factor receptor (TNFR)
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Summary:Progranulin (PGRN), a growth factor, is abundantly expressed in a broad range of tissues and cell types with pleiotropic functions including inflammation, neurodegeneration, and facilitating lysosome acidification. PGRN binds to TNF receptors (TNFR) and inhibits downstream inflammatory signaling pathways. TNFR is a well-known predictor of glomerular filtration rate (GFR) decline in a variety of diseases. Therefore, we measured circulating PGRN in addition to TNFR using an enzyme-linked immunosorbent assay and explored whether it predicted renal prognosis in 201 Japanese patients with type 2 diabetes. During a median follow-up of 7.6 years, 21 participants reached primary renal endpoint, which involves a decline of at least 57% in eGFR from baseline, or the onset of end-stage renal disease. Univariate Cox regression analysis revealed that classical renal measures (GFR and albuminuria), two TNF-related biomarkers (PGRN and TNFR), and BMI were associated with this outcome. Multivariate analysis demonstrated that high levels of PGRN [HR 2.50 (95%CI 2.47-2.52)] or TNFR1 [HR 5.38 (95%CI 5.26-5.50)] were associated with this outcome after adjusting for relevant covariates. The high levels of PGRN as well as TNFR1 were associated with a risk of primary renal outcome in patients with type 2 diabetes after adjusting for established risk factors.
ISSN:1664-2392
1664-2392
DOI:10.3389/fendo.2022.849457