Placebo-controlled, double-blind, cross-over trial of growth hormone treatment in prepubertal children with chronic renal failure

Hokken-Koelega, Anita; Keizer‐Schrama, Sabine M.P.F. de Muinck; Drop, Stenvert L. S.; Wolff, E; Stijnen, Theo; Bot, A.; Wit, Jan M.; Donckerwolcke, R. A.; Jong, M. C. J. W. de; Abbad, N. C. B.; Blum, Werner

doi:10.1016/0140-6736(91)90604-n

Cited by 213 publications

(120 citation statements)

References 28 publications

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“…However, during recent years, it has been convincingly shown that biosynthetic growth hormone treatment accelerates pretransplant growth significantly without adverse effects. Growth hormone treatment did not accelerate epiphyseal maturation, although it improved hSDScA at first RTx, thus promising a better FH (3,4). In view of these positive findings, we prefer biosynthetic growth hormone treatment and do not advocate preemptive RTx for severe growth retardation in these children.…”

Section: Discussionmentioning

confidence: 96%

“…T h e psychosocial consequences of short stature are profound in both children and adults. Recent studies have convincingly shown that recombinant h G H therapy will accelerate growth significantly both before (3,4) and after RTx (5,6). For a true evaluation of this therapy, it is essential t o assess FH and pinpoint its predictive factors in patients not so treated.…”

Section: Fh Final Heightmentioning

confidence: 99%

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Final Height and Its Predictive Factors after Renal Transplantation in Childhood

et al. 1994

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Erasmus University Rotterdam, The NetherIand.7 1M.A. J.d. R., T. S. 1A retrospective study is reported assessing final height (FH) and its predictive factors in 52 patients (31 male, 21 female) who underwent renal transplantation (RTx) before the age of 15 y. They received prednisone daily or on alternate days as well as azathioprine. The study period covered 20 y. FH remained below the third height percentile [height standard deviation score for chronologic age (hSDS,,) < -1.881 for most of these patients (77% males, 71% females). Median (range) FH was 165.0 (143.0-176.8) cm in males and 153.0 (135.0-168.4) cm in females. Median difference between FH and target height was 15.0 and 15.4 cm for males and females, respectively. For both sexes, the median hSDS,, was already below -1.88 at the start of the first hemodialysis, after which it decreased significantly until the first RTx. After RTx, there was no significant improvement of hSDS,,.The predictive factors for FH were determined by evaluating various factors simultaneously in a multiple regression analysis. This analysis provided a regression equation for predicting FH. A higher hSDS,, at the time of the first RTx and alternate-day versus daily prednisone therapy both had a significantly positive influence on FH, whereas a longer duration of reduced GFR ( 4 0 mLlminl1.73 m') had a significantly negative effect on FH. Other factors such as age or bone age at first RTx, primary renal disease, duration of initial dialysis, repeat RTx, and the cumulative dose of prednisone did not influence FH significantly. In conclusion, 71-77% of patients that received their first renal transplant before the age of 15 ended up with severely short adult stature. Optimization of the hSDS,., at first RTx appears very important. Long-term administration of prcdnisone on alternate days would then result in optimal FH, particularly if the GFR remains above 50 mL/min/1.73 m2. (Pediatr Res 36: 323-328, 1994) Abbreviations FH, final heightRTx, renal transplantation hSDS,,, height standard deviation score for chronologic age HD, hemodialysis AD, alternate-day Growth failure is a common and serious consequence of chronic renal failure in childhood. The majority of these children now survive thanks t o advances in hemodialysis and RTx, but successful transplantation rarely results in full growth rehabilitation. Some children show an appreciable improvement in growth after RTx, but the initially increased growth rate may not be sustained during the ensuing years of immunosuppressive drug administration (1). reported that the F H of o n e third of patients w h o underwent RTx

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Section: Discussionmentioning

confidence: 96%

Section: Fh Final Heightmentioning

confidence: 99%

Final Height and Its Predictive Factors after Renal Transplantation in Childhood

et al. 1994

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“…GH stimulates growth in children with CKF, including those undergoing maintenance dialysis therapy and kidney transplant recipients (33,34). Studies in adults with ESRD indicate that GH may stimulate anabolism and improve indicators of body composition known to be associated with increased survival.…”

Section: Effects Of Gh In Normal Individuals and People With Advancedmentioning

confidence: 99%

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Kopple¹,

Cheung²,

Christiansen³

et al. 2008

Clinical Journal of the American Society of Nephrology

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Background: The mortality rate of maintenance hemodialysis (MHD) patients remains high. Measures of protein-energy wasting, including hypoalbuminemia, are strongly associated with their high mortality. Growth hormone (GH) may improve lean body mass (LBM) and serum albumin levels, and health-related quality of life (HRQoL), which are significantly and positively associated with survival in MHD patients. The OPPORTUNITY TM Trial will examine whether GH reduces mortality and morbidity and improves overall health in hypoalbuminemic MHD patients.Hypothesis: The primary hypothesis is that daily recombinant human GH injections, compared with placebo, improve survival in hypoalbuminemic MHD patients. Secondary hypotheses are that GH improves morbidity and health, including number of hospitalized days, time to cardiovascular events, LBM, serum protein and inflammatory marker levels, exercise capacity, and HRQoL, and has a favorable safety profile.Design/Measurements: This is a prospective, double-blind, multicenter, randomized clinical trial involving 2500 MHD patients, up to 50% with diabetes mellitus, from 22 countries. Patients are randomized in a 1:1 ratio to receive daily injections of GH (20 g/kg per day) or placebo for 104 weeks. Key inclusion criteria include clinically stable and well-dialyzed (Kt/V >1.2) adult MHD patients with serum albumin <4.0 g/dl. Exclusion criteria include active malignancy, active proliferative or severe nonproliferative diabetic retinopathy, uncontrolled hypertension, chronic use of high-dose glucocorticoids, or immunosuppressive agents and pregnancy.Conclusions: The OPPORTUNITY TM Trial is the first large-scale randomized clinical trial in adult MHD patients evaluating the response to GH of such clinical endpoints as mortality, morbidity, markers of body protein mass, inflammation, exercise capacity, and HRQoL.

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“…Consequently, optimization of the hSDScA at RTx is very important. Recent studies have demonstrated that biosynthetic growth hormone therapy accelerates growth significantly in children with chronic renal insufficiency, resulting in an improved hSDScA at RTx (24,25). After RTx, maximum catch-up growth may then be achieved provided the following conditions are met: alternateday instead of daily prednisone administration, a minimal cumulative dose of prednisone, CsA instead of Aza treatment, and a GFR above 50 mL/min/1.73 m2.…”

Section: Discussionmentioning

confidence: 99%

Growth after Renal Transplantation in Prepubertal Children: Impact of Various Treatment Modalities

et al. 1994

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ABSTRACT. A retrospective study evaluated posttransplant growth of 70 prepubertal children during the first 2 y after renal transplantation (RTx). Immunosuppressive treatment consisted of prednisone administered either daily or on alternate days in combination with either azathioprine or cyclosporin A. The increment in height standard deviation score for chronologic age during the first 2 y after RTx was less than 0.5 S D for 70% of the study population. The predictive factors for posttransplant growth were determined by evaluating several factors and treatment modalities singly and simultaneously in a multiple regression analysis. Patients with the most severe growth retardation at RTx appeared to have the most pronounced growth spurt after RTx, but even they never had complete catchup growth, and 2 y after RTx they were still shorter than those with less severe growth retardation a t RTx. Alternate-day instead of daily prednisone administration had a significantly positive influence, whereas a high cumulative dose of prednisone, azathioprine instead of cyclosporin A therapy, and a persistently reduced GFR (GFR < 50 mL/ min/1.73 m2) had a significantly negative influence on catch-up growth during the 2 y after RTx. Other factors, such a s gender, chronologic and bone age at RTx, primary renal disease, duration of initial dialysis, repeat RTx, and target height S D score for chronologic age, whether evaluated singly or simultaneously with other significant factors, appeared to have no significant influence on post-RTx growth. Thus, 70% of the prepubertal children do not experience appreciable catch-up growth during the first 2 y after RTx. Optimization of pretransplant height appears very important. Immunosuppressive treatment with cyclosporin therapy in combination with a minimal dose of alternate-day prednisone would then result in optimal posttransplant growth, particularly if the GFR remains above 50 mL/min/1.73 m2). (Pediatr Res 35: 367-371, 1994) Abbreviations RTx, renal transplantation hSDSca, height standard deviation score for chronologic age CsA, cyclosporin A Aza, azathioprine

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Placebo-controlled, double-blind, cross-over trial of growth hormone treatment in prepubertal children with chronic renal failure

Cited by 213 publications

References 28 publications

Final Height and Its Predictive Factors after Renal Transplantation in Childhood

Final Height and Its Predictive Factors after Renal Transplantation in Childhood

Opportunity™

Growth after Renal Transplantation in Prepubertal Children: Impact of Various Treatment Modalities

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