title: The effect of nephrectomy on Klotho, FGF-23 and bone metabolism.
abstract: BACKGROUND
  Increased concentration of fibroblast growth factor 23 (FGF-23) and decreased levels of soluble Klotho (sKL) are linked to negative clinical outcomes among patients with chronic kidney disease and acute kidney injury. Therefore, it is reasonable to hypothesize that GFR reduction caused by nephrectomy might alter mineral metabolism and induces adverse consequences. Whether nephrectomy due to urological indications causes derangements in FGF-23 and sKL has not been studied. The aim of the study was to evaluate the effect of acute GFR decline due to unilateral nephrectomy on bone metabolism, FGF-23 and sKL levels.
  
  
  METHODS
  This is a prospective, single-centre observational study of patients undergoing nephrectomy due to urological indications. Levels of C-terminal FGF-23 (c-FGF-23), sKL and bone turnover markers [β-crosslaps (CTX), bone-specific alkaline phosphatase (bALP) and tartrate-resistant acid phosphatase 5b (TRAP 5b)] were measured before and after surgery (5 ± 2 days).
  
  
  RESULTS
  Twenty-nine patients were studied (14 females, age 63.0 ± 11.6, eGFR 87.3 ± 19.2 ml/min/1.73 m2). After surgery, eGFR significantly declined (p < 0.0001). Nephrectomy significantly decreased sKL level [709.8 (599.9-831.2) vs. 583.0 (411.7-752.6) pg/ml, p < 0.001] and did not change c-FGF-23 concentration [70.5 (49.8-103.3) vs. 77.1 (60.5-109.1) RU/ml, p = 0.9]. Simultaneously, alterations in bone turnover markers were observed. Serum concentration of CTX increased [0.49 (0.4-0.64) vs. 0.59 (0.46-0.85) ng/ml, p = 0.001], while bALP and TRAP 5b decreased [23.6 (18.8-31.4) vs. 17.9 (15.0-22.0) U/l, p < 0.0001 and 3.3 (3.0-3.7) vs. 2.8 (2.3-3.2) U/l, p < 0.001, respectively].
  
  
  CONCLUSIONS
  Nephrectomy among patients with preserved renal function before surgery does not increase c-FGF-23 but reduces sKL. Moreover, nephrectomy results in derangements in bone turnover markers in short-term follow-up. These changes may participate in pathogenesis of bone disease after nephrectomy.
authors.affiliation: I Department of Nephrology and Transplantation with Dialysis Unit, Medical University of Bialystok, Ul. Zurawia 14, 15-540, Białystok, Poland. kponikwicka@o2.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kakareko
authors.affiliation: I Department of Nephrology and Transplantation with Dialysis Unit, Medical University of Bialystok, Ul. Zurawia 14, 15-540, Białystok, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Rydzewska-Rosolowska
authors.affiliation: I Department of Nephrology and Transplantation with Dialysis Unit, Medical University of Bialystok, Ul. Zurawia 14, 15-540, Białystok, Poland.
authors.forename: Szymon
authors.initials: S
authors.lastname: Brzosko
authors.affiliation: II Department of Nephrology and Hypertension with Dialysis Unit, Medical University of Bialystok, Białystok, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Gozdzikiewicz-Lapinska
authors.affiliation: II Department of Nephrology and Hypertension with Dialysis Unit, Medical University of Bialystok, Białystok, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Koc-Zorawska
authors.affiliation: Department of Oncological and General Urology, J. Sniadecki Provincial Hospital, Białystok, Poland.
authors.forename: Pawel
authors.initials: P
authors.lastname: Samocik
authors.affiliation: Department of Oncological and General Urology, J. Sniadecki Provincial Hospital, Białystok, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Kozlowski
authors.affiliation: I Department of Nephrology and Transplantation with Dialysis Unit, Medical University of Bialystok, Ul. Zurawia 14, 15-540, Białystok, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Mysliwiec
authors.affiliation: I Department of Nephrology and Transplantation with Dialysis Unit, Medical University of Bialystok, Ul. Zurawia 14, 15-540, Białystok, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Naumnik
authors.affiliation: I Department of Nephrology and Transplantation with Dialysis Unit, Medical University of Bialystok, Ul. Zurawia 14, 15-540, Białystok, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Hryszko
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D016723:Bone Remodeling; D024042:Collagen Type I / Q000097:blood; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005919:Glomerular Filtration Rate; D005966:Glucuronidase / Q000097:blood*; D006801:Humans; D007674:Kidney Diseases / Q000097:blood / Q000601:surgery; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy; D010281:Parathyroid Hormone / Q000097:blood; D010455:Peptides / Q000097:blood; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood; D000071681:Tartrate-Resistant Acid Phosphatase / Q000097:blood
chemical_list: D024042:Collagen Type I; C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D000469:Alkaline Phosphatase; C000605510:ACP5 protein, human; D000071681:Tartrate-Resistant Acid Phosphatase; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: Acute GFR decline; Bone metabolism; FGF-23; Klotho; Nephrectomy