title: Renal Handling of Sclerostin in Response to Acute Glomerular Filtration Decline.
abstract: Deterioration of glomerular filtration rate (GFR) is associated with alterations of bone metabolism. It translates clinically to bone fragility and increased fractures rate among patients with impaired GFR. Recently, sclerostin (SCL) gained much attention as an important factor in pathogenesis of mineral and bone disturbances in patients with renal diseases. There is no data about SCL behaviour in patients with acute GFR decline. The aim of this study was to evaluate the renal handling of SCL. This is a prospective, single-centre observational study in patients undergoing nephrectomy due to urological indications. Serum and urinary SCL levels were measured prior and after nephrectomy. 25 patients were enrolled. After surgery, eGFR significantly declined (from 87.4±19.7 to 67.7±25.7 ml/min/1.73 m(2), p<0.0001). Nephrectomy caused more than 20 times higher renal fractional excretion of SCL [0.15 (interquartile range, IQR 0.09-0.40) vs. 2.78 (IQR 1.51-4.02)%, p<0.001], while its serum level remained intact [0.69 (IQR 0.57-0.90 vs. 0.65 (IQR 0.53-0.88) ng/ml, p=0.4]. The magnitude of eGFR reduction was associated inversely with change in urinary SCL fractional excretion (r=-0.6, p=0.001) and with alteration in serum SCL level (r=-0.5, p=0.01). Our results suggest that increased serum SCL concentrations at moderately reduced GFR are not due to diminished renal clearance. At more severely decreased GFR, elevated SCL concentration results from both increased production and reduced renal elimination.
authors.affiliation: I Department of Nephrology and Transplantation with Dialysis Unit, Medical University of Bialystok, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Kakareko
authors.affiliation: I Department of Nephrology and Transplantation with Dialysis Unit, Medical University of Bialystok, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Rydzewska-Rosolowska
authors.affiliation: I Department of Nephrology and Transplantation with Dialysis Unit, Medical University of Bialystok, Poland.
authors.forename: S
authors.initials: S
authors.lastname: Brzosko
authors.affiliation: II Department of Nephrology and Hypertension with Dialysis Unit, Medical University of Bialystok, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Gozdzikiewicz-Lapinska
authors.affiliation: I Department of Nephrology and Transplantation with Dialysis Unit, Medical University of Bialystok, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Koc-Zorawska
authors.affiliation: Department of Oncological and General Urology, J. Sniadecki Provincial Hospital, Bialystok, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Samocik
authors.affiliation: Department of Oncological and General Urology, J. Sniadecki Provincial Hospital, Bialystok, Poland.
authors.forename: R
authors.initials: R
authors.lastname: Kozlowski
authors.affiliation: I Department of Nephrology and Transplantation with Dialysis Unit, Medical University of Bialystok, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Mysliwiec
authors.affiliation: I Department of Nephrology and Transplantation with Dialysis Unit, Medical University of Bialystok, Poland.
authors.forename: B
authors.initials: B
authors.lastname: Naumnik
authors.affiliation: I Department of Nephrology and Transplantation with Dialysis Unit, Medical University of Bialystok, Poland.
authors.forename: T
authors.initials: T
authors.lastname: Hryszko
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins / Q000097:blood* / Q000652:urine; D002118:Calcium / Q000097:blood; D005260:Female; D005819:Genetic Markers; D005919:Glomerular Filtration Rate; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; D010281:Parathyroid Hormone; D010710:Phosphates; C422903:SOST protein, human; D002118:Calcium