FSTL3 is increased in renal dysfunction.
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.
Department of Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany.|IFB Adiposity Diseases, Leipzig University Medical Center, Leipzig, Germany.
Susan
S
Kralisch
Department of Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany.
Annett
A
Hoffmann
IFB Adiposity Diseases, Leipzig University Medical Center, Leipzig, Germany.
Nora
N
Klöting
Department of Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany.
Anette
A
Bachmann
Institute of Laboratory Medicine, University of Leipzig, Leipzig, Germany.
Jürgen
J
Kratzsch
Department of Urology, University of Leipzig, Leipzig, Germany.
Jens-Uwe
JU
Stolzenburg
Department of Urology, University of Leipzig, Leipzig, Germany.
Anja
A
Dietel
Division of Nephrology and KfH Renal Unit, Hospital St. Georg, Leipzig, Germany.
Joachim
J
Beige
Outpatient Nephrology Care Unit, Leipzig, Germany.
Matthias
M
Anders
Outpatient Nephrology Care Unit, Leipzig, Germany.
Ingolf
I
Bast
Department of Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany.
Matthias
M
Blüher
Department of Medicine, Division of Nephrology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.|Department of Medicine, Nashville Veterans Affairs Hospital, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Ming-Zhi
MZ
Zhang
Department of Medicine, Division of Nephrology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.|Department of Medicine, Nashville Veterans Affairs Hospital, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Raymond C
RC
Harris
Department of Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany.
Michael
M
Stumvoll
Department of Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany.|IFB Adiposity Diseases, Leipzig University Medical Center, Leipzig, Germany.
Mathias
M
Fasshauer
Department of Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany.|IFB Adiposity Diseases, Leipzig University Medical Center, Leipzig, Germany.
Thomas
T
Ebert
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D016022:Case-Control Studies; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D005260:Female; D038702:Follistatin-Related Proteins / Q000097:blood* / Q000235:genetics; D015870:Gene Expression; D005919:Glomerular Filtration Rate; D006801:Humans; D007333:Insulin Resistance; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000503:physiopathology; D015854:Up-Regulation
D038702:Follistatin-Related Proteins; C000606403:Fstl3 protein, human
AKI; CKD; FSTL3; cytokine; elimination