Fine R N
Department of Pediatrics, Children's Medical Center, State University of New York, Stony Brook 11794-8111.
J Am Soc Nephrol. 1991 Apr;1(10):1136-45. doi: 10.1681/ASN.V1101136.
Hypothalamic production of growth hormone releasing hormone stimulates the anterior pituitary gland to release growth hormone (GH). The clinical manifestations of GH on tissues are either direct or are mediated by insulin-like growth factors (IGF). Both the somatic effects of GH and the renal manifestations of an increase in glomerular filtration rate and renal plasma flow are mediated by IGF. The increase in glomerular filtration rate/renal plasma flow that occurs with either exogenous or endogenous GH is not apparent in patients with chronic renal failure (CRF); therefore, it is unlikely that recombinant human growth hormone (rhGH) treatment of patients with CRF will result in glomerular hyperfiltration. Longitudinal studies are required to determine if the glomerulosclerosis and renal functional impairment occurring in GH and growth hormone releasing hormone transgenic mice occurs after rhGH treatment of growth-retarded uremic rats with GH resulted in an improvement in growth velocity. This led to preliminary studies in growth-retarded children with CRF by using rhGH. The acceleration of growth velocity was dramatic despite the fact that GH levels are elevated in uremia. The elevated IGF carrier proteins in uremic children may contribute to the growth retardation. Treatment with rhGH may be efficacious by stimulating a net increase in the free (unbound) IGF levels. Hyposecretion of GH may contribute to the failure to achieve optimal growth after successful renal transplantation. Treatment with rhGH may be efficacious in improving the growth velocity of renal allograft recipients.
下丘脑分泌的生长激素释放激素刺激垂体前叶释放生长激素(GH)。GH对组织的临床表现要么是直接的,要么是由胰岛素样生长因子(IGF)介导的。GH的躯体效应以及肾小球滤过率和肾血浆流量增加的肾脏表现均由IGF介导。外源性或内源性GH引起的肾小球滤过率/肾血浆流量增加在慢性肾衰竭(CRF)患者中并不明显;因此,用重组人生长激素(rhGH)治疗CRF患者不太可能导致肾小球高滤过。需要进行纵向研究,以确定在对生长迟缓的尿毒症大鼠用GH进行rhGH治疗导致生长速度改善后,GH和生长激素释放激素转基因小鼠中发生的肾小球硬化和肾功能损害是否会出现。这导致了对生长迟缓的CRF儿童使用rhGH的初步研究。尽管尿毒症患者的GH水平升高,但生长速度的加快却很显著。尿毒症儿童中升高的IGF载体蛋白可能导致生长迟缓。通过刺激游离(未结合)IGF水平的净增加,rhGH治疗可能有效。GH分泌不足可能导致肾移植成功后无法实现最佳生长。用rhGH治疗可能有效改善肾移植受者的生长速度。