Abstract
Renal osteodystrophy (ROD) develops early in the course of chronic kidney disease (CKD). With improving patient survival it’s importance and relevance has increased. The last published bone biopsy data in children prior to renal replacement therapy (RRT) was in 1982, which demonstrated abnormal histology in all patients with a glomerular filtration rate (GFR) <20 ml/min per 1.73 m2. Studies investigating the relationship between bone histology and parathyroid hormone levels (PTH) and/or growth in children with CKD are few (seven). These were mostly undertaken in patients already initiated on RRT–dialysis. We investigated the presence of ROD in children at the commencement of RRT and to investigate any relationship between histology, growth and PTH levels. Following double tetracycline labelling, bone biopsies were taken from patients at the time of RRT surgery. Histological classification was based on the newly proposed turnover/mineralisation/volume (TMV) system. Eleven patients underwent bone biopsy. Patients were followed for an average of 1.1 years (0.5–1.8) prior to biopsy over an average of eight clinic visits (3–14), when routine biochemical data were collected. Time-integrated median calcium, phosphate and PTH levels were calculated. PTH levels were within the normal range in two patients with low turnover, 1.1–1.4 times the upper limit of normal (ULN) in three with mixed osteodystrophy and >2.9 times the ULN in four patients with high bone turnover. There was no relationship between bone turnover and growth. The presence of ROD was universal in these children with severe CKD. Low bone turnover was associated with normal-range mean PTH levels, and high bone turnover occurred at lower PTH levels than current guidelines would suggest.
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Block GA, Cunningham J (2006) Morbidity and mortality associated with abnormalities in bone and mineral metabolism in CKD. In: Olgaard K (ed) Clinical guideline to the basics of bone and mineral metabolism in CKD. 1st edn. National Kidney Foundation, New York, pp 77–92
Hodson EM, Evans RA, Dunstan CR, Hills EE, Shaw PF (1982) Quantitative bone histology in children with chronic renal failure. Kidney Int 21(6):833–839
Hutchison AJ, Whitehouse RW, Boulton HF, Adams JE, Mawer EB, Freemont TJ, Gokal R (1993) Correlation of bone histology with parathyroid hormone, vitamin D3, and radiology in end-stage renal disease. Kidney Int 44(5):1071–1077
Torres A, Lorenzo V, Hernandez D, Rodriguez JC, Concepcion MT, Rodriguez AP, Hernandez A, de BE, Darias E, Gonzalez-Posada JM (1995) Bone disease in predialysis, hemodialysis, and CAPD patients: evidence of a better bone response to PTH. Kidney Int 47(5):1434–1442
Mathias R, Salusky I, Harman W, Paredes A, Emans J, Segre G, Goodman W (1993) Renal bone disease in pediatric and young adult patients on hemodialysis in a children’s hospital. J Am Soc Nephrol 3(12):1938–1946
Salusky IB, Ramirez JA, Oppenheim W, Gales B, Segre GV, Goodman WG (1994) Biochemical markers of renal osteodystrophy in pediatric patients undergoing CAPD/CCPD. Kidney Int 45(1):253–258
Rees L (2008) What parathyroid hormone levels should we aim for in children with stage 5 chronic kidney disease; what is the evidence? Pediatr Nephrol 23(2):179–184
Goodman WG, Ramirez JA, Belin TR, Chon Y, Gales B, Segre GV, Salusky IB (1994) Development of adynamic bone in patients with secondary hyperparathyroidism after intermittent calcitriol therapy. Kidney Int 46(4):1160–1166
Kuizon BD, Goodman WG, Juppner H, Boechat I, Nelson P, Gales B, Salusky IB (1998) Diminished linear growth during intermittent calcitriol therapy in children undergoing CCPD. Kidney Int 53(1):205–211
Ziolkowska H, Paniczyk-Tomaszewska M, Debinski A, Polowiec Z, Sawicki A, Sieniawska M (2000) Bone biopsy results and serum bone turnover parameters in uremic children. Acta Paediatr 89(6):666–671
Yalcinkaya F, Ince E, Tumer N, Ensari A, Ozkaya N (2000) Spectrum of renal osteodystrophy in children on continuous ambulatory peritoneal dialysis. Pediatr Int 42(1):53–57
Salusky IB, Coburn JW, Brill J, Foley J, Slatopolsky E, Fine RN, Goodman WG (1988) Bone disease in pediatric patients undergoing dialysis with CAPD or CCPD. Kidney Int 33(5):975–982
Rehman MT, Hoyland JA, Denton J, Freemont AJ (1994) Age related histomorphometric changes in bone in normal British men and women. J Clin Pathol 47(6):529–534
Parker CR, Freemont AJ, Blackwell PJ, Grainge MJ, Hosking DJ (1999) Cross-sectional analysis of renal transplantation osteoporosis. J Bone Miner Res 14(11):1943–1951
Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR (1987) Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 2(6):595–610
Glorieux FH, Travers R, Taylor A, Bowen JR, Rauch F, Norman M, Parfitt AM (2000) Normative data for iliac bone histomorphometry in growing children. Bone 26(2):103–109
Moe S, Drueke T, Cunningham J, Goodman W, Martin K, Olgaard K, Ott S, Sprague S, Lameire N, Eknoyan G (2006) Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 69(11):1945–1953
Potter DE, Broyer M, Chantler C, Gruskin A, Holliday MA, Roche A, Scharer K, Thissen D (1978) Measurement of growth in children with renal insufficiency. Kidney Int 14(4):378–382
Cole TJ (2002) A chart to link child centiles of body mass index, weight and height. Eur J Clin Nutr 56(12):1194–1199
Souberbielle JC, Boutten A, Carlier MC, Chevenne D, Coumaros G, Lawson-Body E, Massart C, Monge M, Myara J, Parent X, Plouvier E, Houillier P (2006) Inter-method variability in PTH measurement: implication for the care of CKD patients. Kidney Int 70(2):345–350
Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58(2):259–263
Martin KJ, Gonzalez EA (2001) The evolution of assays for parathyroid hormone. Curr Opin Nephrol Hypertens 10(5):569–574
Klaus G, Watson A, Edefonti A, Fischbach M, Ronnholm K, Schaefer F, Simkova E, Stefanidis CJ, Strazdins V, Vande Walle J, Schroder C, Zurowska A, Ekim M, European Pediatric Dialysis Working Group (EPDWG) (2006) Prevention and treatment of renal osteodystrophy in children on chronic renal failure: European guidelines. Pediatr Nephrol 21(2):151–159
NKF K/DOQI (2005) K/DOQI clinical practice guidelines for bone metabolism and disease in children with chronic kidney disease. Accessed at https://doi.org/www.kidney.org/professionals/KDOGI/guidelines-pedbone/index.htm
Waller S, Ledermann S, Trompeter R, van’t Hoff W, Ridout D, Rees L (2003) Catch-up growth with normal parathyroid hormone levels in chronic renal failure. Pediatr Nephrol 18(12):1236–1241
Waller SC, Ridout D, Cantor T, Rees L (2005) Parathyroid hormone and growth in children with chronic renal failure. Kidney Int 67(6):2338–2345
Cansick J, Waller S, Ridout D, Rees L (2007) Growth and PTH in prepubertal children on long-term dialysis. Pediatr Nephrol 22(9):1349–1354
Shroff RC, Donald AE, Hiorns MP, Watson A, Feather S, Milford D, Ellins EA, Storry C, Ridout D, Deanfield J, Rees L (2007) Mineral metabolism and vascular damage in children on dialysis. J Am Soc Nephrol 18(11):2996–3003
Baron R (1999) Anatomy and ultrastructure of bone. In: Favus M (ed) Primer on the metabolic bone diseases and disorders of mineral metabolism. 4th edn. Lippincott Williams and Wilkins, Philadelphia, pp 3–10
French CB, Genel M (1986) Pathophysiology of growth failure in chronic renal insufficiency. Kidney Int Suppl 19:S59–S64
Schmitt CP, Ardissino G, Testa S, Claris-Appiani A, Mehls O (2003) Growth in children with chronic renal failure on intermittent versus daily calcitriol. Pediatr Nephrol 18(5):440–444
Watson AR, Kooh SW, Tam CS, Reilly BJ, Balfe JW, Vieth R (1988) Renal osteodystrophy in children on CAPD: a prospective trial of 1-alpha-hydroxycholecalciferol therapy. Child Nephrol Urol 9(4):220–227
Sanchez CP, Salusky IB, Kuizon BD, Abdella P, Juppner H, Goodman WG (1998) Growth of long bones in renal failure: roles of hyperparathyroidism, growth hormone and calcitriol. Kidney Int 54(6):1879–1887
Brown AJ, Dusso A, Slatopolsky E (1999) Vitamin D. Am J Physiol 277(2 Pt 2):F157–F175
Lepage R, Roy L, Brossard JH, Rousseau L, Dorais C, Lazure C, D’Amour P (1998) A non-(1–84) circulating parathyroid hormone (PTH) fragment interferes significantly with intact PTH commercial assay measurements in uremic samples. Clin Chem 44(4):805–809
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This work was supported by grants from the National Kidney Research Fund (R 18/2/2001) and the Special Trustees of Great Ormond Street Hospital.
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Waller, S., Shroff, R., Freemont, A.J. et al. Bone histomorphometry in children prior to commencing renal replacement therapy. Pediatr Nephrol 23, 1523–1529 (2008). https://doi.org/10.1007/s00467-008-0838-6
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DOI: https://doi.org/10.1007/s00467-008-0838-6