Glucocorticoid pharmacokinetics and growth retardation in children with renal transplants

Chavatte, Claire; Proust, Virginie; Bihan-Benjamin, Christine Le; Gimenez, François; Maisin, Anne; Loirat, Chantal; Mogenet, Agnès; Bresson, Jean‐Louis; Hankard, R.; Broyer, M.; Niaudet, Patrick; Singlas, E

doi:10.1007/s00467-004-1497-x

Cited by 14 publications

(11 citation statements)

References 21 publications

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“…Whereas, Chavatte et al [14] attributed that corticosteroid therapy is probably the main factor inducing stunted growth in pediatric renal transplant recipients. Meanwhile, abnormalities of growth hormone/insulin-like growth factor (IGF) axis have been reported in children with CRF and post transplant and thought to contribute to poor growth [15].…”

Section: Discussionmentioning

confidence: 97%

Growth in children with chronic renal failure and after renal transplantation

et al. 2007

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Growth retardation is a major problem for many children with chronic renal failure (CRF) and transplantation. The aim of this study is to assess the relation between height, glomerular filtration rate (GFR), hormonal alterations in children with CRF on regular haemodialysis (HD), and the impact of functioning graft after kidney transplantation.Thirty-six hemodialysed children were included in the study beside 32 pediatric transplants. Mean duration on HD was 14.72 +/- 7.73 months for the CRF group, while the mean interval after transplantation was 1.97 +/- 0.9 years for the second group. Moreover, twenty healthy children of matched age and sex served as controls. Assessment of growth parameters included height, expressed as standard deviation scores (Ht SDS) for chronological age, serum levels of growth hormone (hGH), and parathormone (PTH). Growth performance was evaluated twice: at the start of the study and one year later. Children with CRF and transplantation had significantly higher levels of both serum hGH and PTH compared to their controls, while CRF children experienced significantly higher serum levels of both hGH and PTH compared to those with functioning graft. Furthermore, analysis of our results by non-parametric Kendall's correlation at the start and one year later revealed negative correlation concerning dialysis duration, serum creatinine, and PTH. On the other hand, positive correlation was achieved for serum calcium and GFR.

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Section: Discussionmentioning

confidence: 97%

Growth in children with chronic renal failure and after renal transplantation

et al. 2007

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“…[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. In our study, all but 2 patients were on low-dose daily steroid treatment (2 to 7 mg/m 2 /d) and pharmacokinetics studies of prednisolone or methylprednisolone were not available.…”

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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“…Reduced allograft function has been considered a risk factor for growth impairment after renal TX in children (20,27,28). In a previous study from our center, GC exposure, rather than dose, was related to adrenal suppression and growth retardation in pediatric TX patients (9).…”

Section: Discussionmentioning

confidence: 99%

“…The higher S-MP and GBA values observed in the obese patients in the present study may be partially explained by reduced clearance of MP (8), thus suggesting dosing of MP according to ideal body weight or body surface area. Pharmacokinetic parameters have been reported to relate to the immunosuppressive efficacy (7,18) and to clinical side effects (9,19) of GCs, although with one contradiction (20). To investigate the GC milieu in pediatric TX patients receiving chronic GC therapy, we used two different analytical methods and correlated the results with the adverse effects of MP.…”

Section: Discussionmentioning

confidence: 99%

Methylprednisolone Exposure in Pediatric Renal Transplant Patients

Seikku

Raivio

Jänne

et al. 2006

American Journal of Transplantation

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Glucocorticoid (GC) dosing is commonly based on body mass or surface area in children, although the drug effects appear to correlate with steroid exposure, rather than dose. We compared the area under the serum concentration-time curve (AUC) of methylprednisolone (MP) with a recombinant cell bioassay measuring serum glucocorticoid bioactivity (GBA), in prediction of side effects in 16 pediatric patients (5.4-18.4 years of age) 2.0-14.9 years after renal transplantation (TX). They received 0.3 mg/kg of MP orally and timed blood samples were drawn up to 8 h postdose. Serum MP concentrations correlated moderately with GBA (r = 0.65, p < 0.0001) with best linear fit at 6 and 8 h (r = 0.72, 0.79, respectively, p < 0.001). MP-AUC t=0-8 and GBA t=6 were significantly greater in patients who gained excessive weight soon after TX. Change in growth after TX was inversely correlated with MP-AUC (r = 0.73, p < 0.05) and GBA t=6 (r = 0.62, p < 0.05). No correlation of MP-AUC or GBA was found with blood glucose or serum lipid concentrations, glomerular filtration rate, bone mineral density or graft histology. In conclusion, GC exposure varies individually and dosing should be adjusted accordingly to control the adverse effects. GBA might provide a complementary tool for monitoring GC exposure but further studies are needed.

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Glucocorticoid pharmacokinetics and growth retardation in children with renal transplants

Cited by 14 publications

References 21 publications

Growth in children with chronic renal failure and after renal transplantation

Growth in children with chronic renal failure and after renal transplantation

Effect of Renal Graft on Longitudinal Growth in Prepubertal Children

Methylprednisolone Exposure in Pediatric Renal Transplant Patients

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