Abstract
To understand the changes induced by uremia in the epiphyseal growth plate, two studies were performed in young rats. In study 1, the morphological features of the tibial growth cartilage of stunted rats with different degrees of reduction of renal function were analyzed 2 weeks after nephrectomy and compared with control rats. There was a negative (r=−0.549, P<0.05) correlation between serum urea nitrogen (SUN) concentrations and longitudinal growth rate. The heights (mean±SEM) of growth cartilage (564±32 vs. 366±9 µm) and its hypertrophic zone (321±25 vs. 157±6 µm) were greater (P<0.05) in uremic than control rats and were highly and positively correlated (r=0.604, P<0.03 and r=0.706, P<0.01) with SUN levels. In study 2, the time course of growth plate alterations was investigated in uremic rats sacrificed 1 (NX-1), 2 (NX-2), and 4 weeks (NX-4) after nephrectomy compared with their corresponding control animals (C-1, C-2, C-4). Growth cartilage and hypertrophic zone heights were greater in NX-2 (533±60 and 264±32 µm) than in C-2 (345±10 and 131±11 µm), with no significant differences in the other groups. This report shows that enlargement of the growth plate and its hypertrophic stratum is greatly, although not exclusively, influenced by the severity and duration of renal insufficiency.
Similar content being viewed by others
References
Mehls O, Ritz E, Gilli G, Schmidt-Gayk H, Krempien B, Kourist B, Wesch H, Prager P (1977) Skeletal changes and growth in experimental uremia. Nephron 18:288–300
Mehls O, Ritz E, Hunziker EB, Eggli P, Heinrich U, Zapf J (1988) Improvement of growth and food utilization by human recombinant growth hormone in uremia. Kidney Int 33:45–52
Kovacs G, Fine RN, Worgall S, Schaefer F, Hunziker EB, Skottner-Lindun A, Mehls O (1991) Growth hormone prevents steroid-induced growth depression in health and uremia. Kidney Int 40:1032–1040
Hanna JD, Santos F, Foreman JW, Chan JCM, Han VKM (1995) Insulin-like growth factor-I gene expression in the tibial epiphyseal growth plate of growth hormone-treated uremic rats. Kidney Int 47:1374–1382
Kovacs GT, Kovacs J, Oh J, Tönshoff B, Hunziker EB, Zapf J, Mehls O (1996) Growth promoting effects of growth hormone and IGF-I are additive in experimental uremia. Kidney Int 49:1413–1421
Cobo A, Carbajo E, Santos F, García E, López JM (1996) Morphometry of uremic rat growth plate. Miner Electrolyte Metab 22:192–195
Ureña P, Ferreira A, Morieux C, Drüeke TB, Vernejoul MC (1996) PTH/PTHrP receptor mRNA is down-regulated in epiphyseal cartilage growth plate of uraemic rats. Nephrol Dial Transplant 11:2008–2016
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 54:1879–1887
Cobo A, Lopez JM, Carbajo E, Santos F, Alvarez J, Fernandez M, Weruaga A (1999) Growth plate cartilage formation and resorption are differentially depressed in growth retarded uremic rats. J Am Soc Nephrol 10:971–979
Edmondson SR, Baker NL, Oh J, Kovacs G, Werther GA, Mehls O (2000) Growth hormone receptor abundance in tibial growth plates of uremic rats: GH/IGF-I treatment. Kidney Int 58:62–70
Sanchez CP, Kuizon BD, Abdella PA, Juppner H, Salusky IB, Goodman WG (2000) Impaired growth, delayed ossification, and reduced osteoclastic activity in the growth plate of calcium-supplemented rats with renal failure. Endocrinology 141:1536–1544
Alvarez J, Balbin M, Fernandez M, Lopez JM (2001) Collagen metabolism is markedly altered in the hypertrophic cartilage of growth plates from rats with growth impairment secondary to chronic renal failure. J Bone Miner Res 16:511–524
Sanchez CP, He YZ (2002) Alterations in the growth plate cartilage of rats with renal failure receiving corticosteroid therapy. Bone 30:692–698
Sanchez CP, He YZ (2003) Effects of thyroparathyroidectomy, exogenous calcium, and short-term calcitriol therapy on the growth plate in renal failure. J Am Soc Nephrol 14:148–158
Chantler C, Lieberman E, Holliday MA (1974) A rat model for the study of growth failure in uremia. Pediatr Res 8:109–113
Tönshoff B, Mehls O (1999) Growth retardation in children with chronic renal disease. Pathophysiology and treatment. In Hindmarsh PC (ed) Current indications for growth hormone therapy. Karger, Basel, pp 128–156
Santos F, Chan JCM, Hanna JD, Niimi K, Krieg RJ Jr, Wellons MD (1992) The effect of growth hormone on the growth failure of chronic renal failure. Pediatr Nephrol 6:262–266
Santos F, Cobo A, Orejas G, Martínez V, Rey C, Málaga S, Crespo M (1996) Analysis of growth in five-sixths-nephrectomized rats. Miner Electrolyte Metab 22:83–87
Trueta J, Amato VP (1960) The vascular contribution to osteogenesis. III. Changes in the growth cartilage caused by experimentally induced ischaemia. J Bone Joint Surg [Br] 42B:571–587
Amil B, Fernandez-Fuente M, Santos F, Rodriguez J, Diaz-Tejon L, García E (2003) Efecto de la hormona de crecimiento y del calcitriol sobre la placa de crecimiento de ratas urémicas. Nefrologia 23 [Suppl 2]:23–26
Hunziker EB, Schenk RK, Cruz-Orive LM (1987) Quantitation of chondrocyte performance in growth-plate cartilage during longitudinal bone growth. J Bone Joint Surg 69:162–173
Acknowledgements
Funding for this work was provided by grants PM 96–0110 from the Spanish Ministry of Science and Education, by grants FIS 97–0556, FIS 98/0611, FIS 00/0878, and FIS 00/0140 from the Spanish Ministry of Health, and by the Fundación Nutrición y Crecimiento. We are grateful to Teresa Usín and Vanessa Loredo for their expert technical assistance.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Fernández-Fuente, M., Santos, F., Carbajo-Pérez, E. et al. Growth plate height of uremic rats is influenced by severity and duration of renal failure. Pediatr Nephrol 19, 187–192 (2004). https://doi.org/10.1007/s00467-003-1326-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-003-1326-7