The effect of nephrectomy on Klotho, FGF-23 and bone metabolism

Int Urol Nephrol. 2017 Apr;49(4):681-688. doi: 10.1007/s11255-017-1519-9. Epub 2017 Jan 27.

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.

Keywords: Acute GFR decline; Bone metabolism; FGF-23; Klotho; Nephrectomy.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Alkaline Phosphatase / blood
  • Bone Remodeling*
  • Collagen Type I / blood
  • Female
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / blood*
  • Glomerular Filtration Rate*
  • Glucuronidase / blood*
  • Humans
  • Kidney Diseases / blood
  • Kidney Diseases / surgery
  • Klotho Proteins
  • Male
  • Middle Aged
  • Nephrectomy*
  • Parathyroid Hormone / blood
  • Peptides / blood
  • Prospective Studies
  • Renal Insufficiency, Chronic / blood
  • Tartrate-Resistant Acid Phosphatase / blood

Substances

  • Collagen Type I
  • FGF23 protein, human
  • Parathyroid Hormone
  • Peptides
  • collagen type I trimeric cross-linked peptide
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23
  • Alkaline Phosphatase
  • ACP5 protein, human
  • Tartrate-Resistant Acid Phosphatase
  • Glucuronidase
  • Klotho Proteins