FSTL3 is increased in renal dysfunction.

Kralisch S, Hoffmann A, Klöting N, Bachmann A, Kratzsch J, Stolzenburg JU, Dietel A, Beige J, Anders M, Bast I, Blüher M, Zhang MZ, Harris RC, Stumvoll M, Fasshauer M, Ebert T
Nephrol Dial Transplant. 2017 32 (10): 1637-1644

PMID: 28339962 · DOI:10.1093/ndt/gfw472

Background - Follistatin-like 3 (FSTL3) is a novel cytokine that regulates insulin sensitivity and counteracts activin/myostatin signalling. In the present study, regulation of FSTL3 in renal dysfunction was investigated in both human chronic kidney disease (CKD) and acute kidney dysfunction (AKD). Furthermore, mFSTL3 expression was analysed in insulin-sensitive tissues in a mouse model of CKD.

Methods - Circulating FSTL3 was quantified by enzyme-linked immunosorbent assay in 581 patients with CKD covering the whole spectrum of estimated glomerular filtration rate (eGFR) categories from G1 to G5. Furthermore, FSTL3 was measured in 61 patients before and within 30 h after elective unilateral nephrectomy, an established model of AKD. Moreover, mFSTL3 mRNA expression was investigated in an animal CKD model, that is, eNOS-/-db/db mice, and compared with littermate controls.

Results - Median circulating FSTL3 levels significantly and continuously increased with deteriorating renal function (eGFR category G1: 6.1; G2: 8.2; G3: 12.7; G4: 18.5; G5: 32.1 µg/L; P < 0.001). In both human CKD and AKD, renal dysfunction remained the strongest independent predictor of FSTL3 serum concentrations in multivariate analyses. FSTL3 was independently associated with an adverse cardiometabolic profile. In CKD mice, hepatic mFSTL3 mRNA expression was increased more than 6-fold as compared with controls.

Conclusions - Circulating FSTL3 is significantly and independently associated with renal function in both patients with CKD and AKD. Hepatic mFSTL3 mRNA upregulation might contribute to increased FSTL3 levels in CKD. Our results are in agreement with the hypothesis that FSTL3 is eliminated by the kidneys and might counteract adverse activin/myostatin signalling observed in renal dysfunction.

© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

MeSH Terms (21)

Aged Aged, 80 and over Animals Case-Control Studies Cells, Cultured Cross-Sectional Studies Female Follistatin-Related Proteins Gene Expression Glomerular Filtration Rate Humans Insulin Resistance Kidney Liver Male Mice Mice, Inbred C57BL Mice, Knockout Middle Aged Renal Insufficiency, Chronic Up-Regulation

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