Horm Metab Res 2016; 48(07): 457-461
DOI: 10.1055/s-0042-107791
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Renal Handling of Sclerostin in Response to Acute Glomerular Filtration Decline

K. Kakareko
1   I Department of Nephrology and Transplantation with Dialysis Unit, Medical University of Bialystok, Poland
,
A. Rydzewska-Rosolowska
1   I Department of Nephrology and Transplantation with Dialysis Unit, Medical University of Bialystok, Poland
,
S. Brzosko
1   I Department of Nephrology and Transplantation with Dialysis Unit, Medical University of Bialystok, Poland
,
J. Gozdzikiewicz-Lapinska
2   II Department of Nephrology and Hypertension with Dialysis Unit, Medical University of Bialystok, Poland
,
E. Koc-Zorawska
1   I Department of Nephrology and Transplantation with Dialysis Unit, Medical University of Bialystok, Poland
,
P. Samocik
3   Department of Oncological and General Urology, J. Sniadecki Provincial Hospital, Bialystok, Poland
,
R. Kozlowski
3   Department of Oncological and General Urology, J. Sniadecki Provincial Hospital, Bialystok, Poland
,
M. Mysliwiec
1   I Department of Nephrology and Transplantation with Dialysis Unit, Medical University of Bialystok, Poland
,
B. Naumnik
1   I Department of Nephrology and Transplantation with Dialysis Unit, Medical University of Bialystok, Poland
,
T. Hryszko
1   I Department of Nephrology and Transplantation with Dialysis Unit, Medical University of Bialystok, Poland
› Author Affiliations
Further Information

Publication History

received 02 November 2015

accepted 27 April 2016

Publication Date:
23 May 2016 (online)

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 m2, 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.

 
  • References

  • 1 Naylor KL, McArthur E, Leslie WD, Fraser LA, Jamal SA, Cadarette SM, Pouget JG, Lok CE, Hodsman AB, Adachi JD, Garg AX. The three-year incidence of fracture in chronic kidney disease. Kidney Int 2014; 86: 810-818
  • 2 Jadoul M, Albert JM, Akiba T, Akizawa T, Arab L, Bragg-Gresham JL, Mason N, Prutz KG, Young EW, Pisoni RL. Incidence and risk factors for hip or other bone fractures among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study. Kidney Int 2006; 70: 1358-1366
  • 3 Tentori F, McCullough K, Kilpatrick RD, Bradbury BD, Robinson BM, Kerr PG, Pisoni RL. High rates of death and hospitalization follow bone fracture among hemodialysis patients. Kidney Int 2014; 85: 166-173
  • 4 Baron R, Kneissel M. WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nat Med 2013; 19: 179-192
  • 5 Brandenburg VM, Kramann R, Koos R, Kruger T, Schurgers L, Muhlenbruch G, Hubner S, Gladziwa U, Drechsler C, Ketteler M. Relationship between sclerostin and cardiovascular calcification in hemodialysis patients: a cross-sectional study. BMC Nephrol 2013; 14: 219
  • 6 Kramann R, Brandenburg VM, Schurgers LJ, Ketteler M, Westphal S, Leisten I, Bovi M, Jahnen-Dechent W, Knuchel R, Floege J, Schneider RK. Novel insights into osteogenesis and matrix remodelling associated with calcific uraemic arteriolopathy. Nephrol Dial Transplant 2013; 28: 856-868
  • 7 Qureshi AR, Olauson H, Witasp A, Haarhaus M, Brandenburg V, Wernerson A, Lindholm B, Soderberg M, Wennberg L, Nordfors L, Ripsweden J, Barany P, Stenvinkel P. Increased circulating sclerostin levels in end-stage renal disease predict biopsy-verified vascular medial calcification and coronary artery calcification. Kidney Int 2015; 88: 1356-1364
  • 8 Cejka D, Marculescu R, Kozakowski N, Plischke M, Reiter T, Gessl A, Haas M. Renal elimination of sclerostin increases with declining kidney function. J Clin Endocrinol Metab 2014; 99: 248-255
  • 9 Arasu A, Cawthon PM, Lui LY, Do TP, Arora PS, Cauley JA, Ensrud KE, Cummings SR. Study of Osteoporotic Fractures Research G. Serum sclerostin and risk of hip fracture in older Caucasian women. J Clin Endocrinol Metab 2012; 97: 2027-2032
  • 10 Ardawi MS, Akhbar DH, Alshaikh A, Ahmed MM, Qari MH, Rouzi AA, Ali AY, Abdulrafee AA, Saeda MY. Increased serum sclerostin and decreased serum IGF-1 are associated with vertebral fractures among postmenopausal women with type-2 diabetes. Bone 2013; 56: 355-362
  • 11 McClung MR, Grauer A, Boonen S, Bolognese MA, Brown JP, Diez-Perez A, Langdahl BL, Reginster JY, Zanchetta JR, Wasserman SM, Katz L, Maddox J, Yang YC, Libanati C, Bone HG. Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med 2014; 370: 412-420
  • 12 Cejka D, Herberth J, Branscum AJ, Fardo DW, Monier-Faugere MC, Diarra D, Haas M, Malluche HH. Sclerostin and Dickkopf-1 in renal osteodystrophy. Clin J Am Soc Nephrol 2011; 6: 877-882
  • 13 Pelletier S, Dubourg L, Carlier MC, Hadj-Aissa A, Fouque D. The relation between renal function and serum sclerostin in adult patients with CKD. Clin J Am Soc Nephrol 2013; 8: 819-823
  • 14 Ponte B, Trombetti A, Hadaya K, Ernandez T, Fumeaux D, Iselin C, Martin PY. de Seigneux S. Acute and long term mineral metabolism adaptation in living kidney donors: a prospective study. Bone 2014; 62: 36-42
  • 15 Young A, Hodsman AB, Boudville N, Geddes C, Gill J, Goltzman D, Jassal SV, Klarenbach S, Knoll G, Muirhead N, Prasad GV, Treleaven D, Garg AX. Donor Nephrectomy Outcomes Research N. Bone and mineral metabolism and fibroblast growth factor 23 levels after kidney donation. Am J Kidney Dis 2012; 59: 761-769
  • 16 Bagrodia A, Mehrazin R, Bazzi WM, Silberstein J, Malcolm JB, Stroup SP, Raheem O, Wake RW, Kane CJ, Patterson AL, Wan JY, Derweesh IH. Comparison of rates and risk factors for development of osteoporosis and fractures after radical or partial nephrectomy. Urology 2011; 78: 614-619
  • 17 Bijvoet OL, Morgan DB, Fourman P. The assessment of phosphate reabsorption. Clin Chim Acta 1969; 26: 15-24
  • 18 Walton RJ, Bijvoet OL. Nomogram for derivation of renal threshold phosphate concentration. Lancet 1975; 2: 309-310
  • 19 Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro 3rd AF, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J. Ckd EPI. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009; 150: 604-612
  • 20 Bonani M, Rodriguez D, Fehr T, Mohebbi N, Brockmann J, Blum M, Graf N, Frey D, Wuthrich RP. Sclerostin blood levels before and after kidney transplantation. Kidney Blood Press Res 2014; 39: 230-239
  • 21 Goncalves FL, Elias RM, dos Reis LM, Graciolli FG, Zampieri FG, Oliveira RB, Jorgetti V, Moyses RM. Serum sclerostin is an independent predictor of mortality in hemodialysis patients. BMC Nephrol 2014; 15: 190
  • 22 Ferreira JC, Ferrari GO, Neves KR, Cavallari RT, Dominguez WV, Dos Reis LM, Graciolli FG, Oliveira EC, Liu S, Sabbagh Y, Jorgetti V, Schiavi S, Moyses RM. Effects of dietary phosphate on adynamic bone disease in rats with chronic kidney disease – role of sclerostin?. PLoS One 2013; 8: e79721
  • 23 Register TC, Hruska KA, Divers J, Bowden DW, Palmer ND, Carr JJ, Wagenknecht LE, Hightower RC, Xu J, Smith SC, Dietzen DJ, Langefeld CD, Freedman BI. Sclerostin is positively associated with bone mineral density in men and women and negatively associated with carotid calcified atherosclerotic plaque in men from the African American-Diabetes Heart Study. J Clin Endocrinol Metab 2014; 99: 315-321
  • 24 Evenepoel P, D’Haese P, Brandenburg V. Sclerostin and DKK1: new players in renal bone and vascular disease. Kidney Int 2015; 88: 235-240
  • 25 Viaene L, Behets GJ, Claes K, Meijers B, Blocki F, Brandenburg V, Evenepoel P, D’Haese PC. Sclerostin: another bone-related protein related to all-cause mortality in haemodialysis?. Nephrol Dial Transplant 2013; 28: 3024-3030
  • 26 Delanaye P, Krzesinski JM, Warling X, Moonen M, Smelten N, Medart L, Bruyere O, Reginster JY, Pottel H, Cavalier E. Clinical and biological determinants of sclerostin plasma concentration in hemodialysis patients. Nephron Clin Pract. 2014 128. 127-134