Alternate-Day Steroid Dosing Improves Growth Without Adversely Affecting Graft Survival or Long-Term Graft Function

Jabs, Kathy; Sullivan, Emily; Avner, Ellis D.; Harmon, William

doi:10.1097/00007890-199601150-00008

Cited by 123 publications

(66 citation statements)

References 16 publications

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“…Studies in children suggest that growth retardation following a short period of systemic exposure to GC may be followed by a period of catch-up growth and that alternate day therapy may be less adverse for growth (Jabs et al 1996, Ahmed et al 1999. Catch-up growth has also been observed following direct injection of GC into the growth plate of rabbits .…”

Section: Introductionmentioning

confidence: 99%

Glucocorticoid effects on chondrogenesis, differentiation and apoptosis in the murine ATDC5 chondrocyte cell line

Mushtaq¹,

Farquharson²,

Seawright³

et al. 2002

Journal of Endocrinology

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Glucocorticoids (GC) are used extensively in children and may cause growth retardation, which is in part due to the direct effects of GC on the growth plate. We characterised the ATDC5 chondrocyte cell line, which mimics the in vivo process of longitudinal bone growth, to examine the effects of dexamethasone (Dex) and prednisolone (Pred) during two key time points in the chondrocyte life cyclechondrogenesis and terminal differentiation. Additionally, we studied the potential for recovery following Dex exposure. During chondrogenesis, Dex and Pred exposure at 10 -8 M, 10 -7 M and 10 -6 M resulted in a significant mean reduction in cell number (28% vs 20%), cell proliferation (27% vs 24%) and proteoglycan synthesis (47% vs 43%) and increased alkaline phosphatase (ALP) activity (106% vs 62%), whereas the incidence of apoptosis was unaltered. Minimal effects were noted during terminal differentiation with both GC although all concentrations of Dex lowered apoptotic cell number. To assess catch-up growth the cells were incubated for a total of 14 days which included 1, 3, 7, 10 or 14 days exposure to 10 -6 M Dex, prior to the recovery period. Recovery of proteoglycan synthesis was irreversibly impaired following just one day exposure to Dex. Although cell number showed a similar pattern, significant impairment was only achieved following 14 days exposure. Irreversible changes in ALP activity were only noticed following 10 days exposure to Dex.In conclusion, GC have maximal effects during chondrogenesis; Dex is more potent than Pred and cells exposed to Dex recover but this may be restricted due to differential effects of GC on specific chondrocyte phenotypes.

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Section: Introductionmentioning

confidence: 99%

Glucocorticoid effects on chondrogenesis, differentiation and apoptosis in the murine ATDC5 chondrocyte cell line

Mushtaq¹,

Farquharson²,

Seawright³

et al. 2002

Journal of Endocrinology

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“…During the first week, a high dose of DEXA (0.5 mg/kg) for 3 d was given, followed by a dose of 0.3 mg/kg for 3 d and 0.25 mg/kg for 3 d. When the daily DEXA dose was decreased to Ͻ0.25 or 0.20 mg · kg Ϫ1 · d Ϫ1 , the growth of head circumference and weight was similar to the growth rate after discontinuation of DEXA. Apparently, there was a dose-effect relationship of DEXA as described in older children (29). Because the present studies show an association between DEXA treatment in the neonatal period and a decrease in cortical gray matter and neurologic impairment, the fact that we did find stunted growth of head circumference with the use of high-dose DEXA (0.5 to 0.25 mg · kg Ϫ1 · d Ϫ1 ) might have major implications for future use of DEXA in very preterm infants.…”

Section: Discussionmentioning

confidence: 94%

A Randomized, Placebo-Controlled GH Trial in Very Preterm Infants Who Were at Risk for Bronchopulmonary Dysplasia and Were Treated with Dexamethasone

et al. 2005

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Very preterm infants who develop bronchopulmonary dysplasia are often treated with dexamethasone (DEXA) to wean them from the ventilator. As DEXA has growth-suppressive and catabolic effects, which might have long-term consequences on growth and organ development, we investigated whether high-dose GH treatment could overcome these effects. In a randomized, double-blind, placebo-controlled trial, 30 ventilated very low birth weight infants were assigned to receive either GH or placebo treatment after start of DEXA. DEXA was given for 24 d (starting dose 0.5 mg · kg, tapering off every third day). Simultaneously, high-dose GH (0.3 mg · kg Ϫ1 · d Ϫ1) or placebo was administered during 6 wk. During high-dose DEXA treatment (dose 0.5-0.3 mg · kg Ϫ1 · d Ϫ1), no gain in head circumference, weight, crown-heel length, and knee-heel length occurred in the GH and placebo groups. Growth during the 6-wk study period was not different between the GH and the placebo groups. Two patients in the placebo group died, but the number and the severity of adverse effects was not statistically different between the GH and placebo groups. In conclusion, highdose GH treatment did not improve growth in DEXA-treated very preterm infants and thus cannot be recommended to prevent growth failure in these infants. During high-dose DEXA, a complete growth arrest occurred, including stunting of head growth. Growth in head circumference and weight with lower dose DEXA was comparable to growth after discontinuation of DEXA. In very preterm infants, the development of bronchopulmonary dysplasia (BPD) is a major problem. According to the latest classification, BPD is evaluated at 36 wk postmenstrual age or at discharge from the neonatal intensive care unit (NICU), whichever comes first, and is defined as a persistent need for supplemental oxygen for at least 28 d with a persistence of respiratory features, such as retractions, tachypnea, and rales as a result of respiratory disease (1). The incidence of BPD increases from 12% in infants with a gestational age of 30 wk to 30 -40% in those who are born after a gestational age of 25-26 wk (2,3).In NICUs, systemic corticosteroids are often given to wean very preterm infants with severe and prolonged respiratory problems from the ventilator (4 -6). Many infants who are at risk for development of BPD are treated with dexamethasone (DEXA). DEXA treatment in preterm infants is known to have an inhibiting effect on weight gain as well as linear growth and head circumference (7-11). Follow-up studies suggest impairment in brain growth and persisting growth retardation into childhood (12-16).

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“…Reduction in the daily administered dosage of steroids, use of alternate day dosing regimens, steroid withdrawal after transplant, and complete steroid avoidance have been used to minimize their adverse effects. [15][16][17] Seikku and associates and Sarna and associates 18,19 demonstrated that the area under the serum concentration-time curve of methylprednisolone, rather than dosage-was related to growth inhibition in pediatric liver and renal transplant recipients. However, Chavatte and associates 20 reported that pharmacokinetics studies of prednisone and prednisolone were not predictive of growth retardation in children with RTx.…”

Section: Discussionmentioning

confidence: 99%

Effect of Renal Graft on Longitudinal Growth in Prepubertal Children

Doğan¹,

Durmaz²,

Çomak³

et al. 2013

Exp Clin Transplant

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Objectives: Linear growth impairment frequently accompanies chronic kidney disease in children. Despite successful renal transplant, growth retardation may persist in renal allograft recipients. Materials and Methods:We recorded the longitudinal growth and biochemical data of prepubertal children during the first 2 years after renal transplant in 34 children (18 boys [52.9%]; mean age at renal transplant, 7.3 ± 2.5 y; range, 1.4 to 9.8 y). Height standard deviation scores were calculated. The patients were divided into 2 groups according to the increase in height standard deviation scores over the first 2 years after renal transplant: group 1 (increases in height standard deviation scores < 1) and group 2 (increases in height standard deviation scores > 1). Results: Increases in height standard deviation scores were 0.12 ± 0.34 and 1.62 ± 0.52 for group 1 and group 2 (P < .001). The number of acute rejection episodes was significantly different between groups (P = .04). At renal transplant, increases in height standard deviation scores were negatively correlated with mean age (r: -0.354; P = .04) and height standard deviation scores (r: -0.353; P = .04). In the multivariate model, mean age and height standard deviation scores at renal transplant remained significantly associated with increases in height standard deviation scores (P = .018; β coefficient: -0.341, 95% CI: -0.17; -0.002; and P = .005; β coefficient: -0.431, 95% CI: -0.519; -0.101). Conclusions:Renal transplant improves linear growth by providing moderate or accelerated growth in prepubertal children.

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Alternate-Day Steroid Dosing Improves Growth Without Adversely Affecting Graft Survival or Long-Term Graft Function

Cited by 123 publications

References 16 publications

Glucocorticoid effects on chondrogenesis, differentiation and apoptosis in the murine ATDC5 chondrocyte cell line

Glucocorticoid effects on chondrogenesis, differentiation and apoptosis in the murine ATDC5 chondrocyte cell line

A Randomized, Placebo-Controlled GH Trial in Very Preterm Infants Who Were at Risk for Bronchopulmonary Dysplasia and Were Treated with Dexamethasone

Effect of Renal Graft on Longitudinal Growth in Prepubertal Children

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