Growth hormone therapy influences endothelial function in children with renal failure

Abstract

Endothelial dysfunction, an early step in atherogenesis, is prevalent in children with renal insufficiency. Endothelial dysfunction in growth hormone deficiency is reversed by growth hormone (rhGH) therapy. Renal failure induces growth hormone resistance at the receptor and post-receptor level, which can be overcome by rhGH therapy. This study investigates the influence of rhGH therapy in children with renal failure on flow-mediated dilation (FMD) of the brachial artery, a marker of endothelial function. We studied 8 patients, who were on rhGH for at least 6 months, and 8 healthy children for comparison. FMD of the brachial artery was measured non-invasively as the percentage increase in diameter during post-ischemic hyperemia. Patients were studied at baseline, after 4 weeks interruption of rhGH therapy, and 4 weeks after resumption of therapy. FMD was significantly lower in patients (4.7%) than healthy controls (13.8%) ( P=0.01). During the administration of rhGH, FMD was significantly higher (3.9%) than during interruption of the treatment (1.4%) ( P=0.04). Our data support the theory that a disturbance in the GH-IGF axis contributes to the endothelial dysfunction of renal failure. Treatment with rhGH not only improves growth but may also favorably influence the risk for atherogenesis.

Flow-mediated vasodilatation of the brachial artery in children with chronic kidney disease

“…Future studies should utilize these techniques in evaluation of FMD in children with CKD. As in previous FMD studies of children with CKD, dialysis and transplantation [14][15][16][17], our study did not identify significant factors associated with lower FMD. There was no significant difference in any of the studied demographic, clinical or laboratory parameters between children with normal and abnormal FMD (Table 2), except, paradoxically, significantly lower serum triglyceride level in children with low FMD.…”

“…Previously published studies evaluating endothelial function in CKD children demonstrated decreased peak FMD in renal patients compared to healthy controls [14][15][16][17]. Kari et al [14] studied 23 normotensive children with advanced CKD (mean GFR=17.5 ml/min per 1.73 m 2 ) and showed decreased mean FMD compared with that of healthy controls.…”

“…Despite its relative simplicity, there have been few studies evaluating brachial artery FMD in children with CKD [14][15][16][17]. The above studies, all rather small, concluded that children with advanced chronic renal failure, those on hemodialysis, and those with kidney transplants had decreased FMD.…”

Assessment and treatment of short stature in pediatric patients with chronic kidney disease: a consensus statement

“…A study of ten pre-pubertal patients with CRI showed that GH therapy for 1 year produced a significant increase in lumbar spine and total body bone mineral content and bone mineral density [59]. Whereas GH therapy may be associated with neurodevelopmental and cardiovascular improvements, more research is needed to elucidate these benefits in the CRI population [60,61]. Several studies have already documented the important role of GH in maintaining cardiovascular health in children and adolescents with GHD [62][63][64].…”

Report of an NIH task force on research priorities in chronic kidney disease in children

“…Risk factors for growth retardation include age at onset of CRI, primary diagnosis (those with structural disease have more growth retardation than those with acquired disease), concomitant acidosis, inadequate nutritional (caloric) intake, renal osteodystrophy (with secondary hyperparathyroidism), perturbations of the GH (growth hormone)/IGF (insulin growth factor) axis [36,37], and genetic potential (mid-parental height). The genetic potential of patients in interventions undertaken to improve height or examine risk factors is not usually studied.…”