Glucocorticoid pharmacokinetics and growth retardation in children with renal transplants

Authors: Chavatte, Claire¹; Guest, Geneviève²; Proust, Virginie¹; Le Bihan, Christine³; Gimenez, François⁴; Maisin, Anne⁵; Loirat, Chantal⁵; Mogenet, Agnès⁶; Bresson, Jean-Louis⁶; Hankard, Régis⁷; Broyer, Michel²; Niaudet, Patrick²; Singlas, Eric¹

Source: Pediatric Nephrology, Volume 19, Number 8, August 2004 , pp. 898-904(7)

Publisher: Springer

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Abstract:

Long-term glucocorticoid treatment contributes to the growth retardation in children after renal transplantation. We investigated whether determination of prednisone (PN) and prednisolone (PL) in plasma and PN, PL, and 6-β-hydroxyprednisolone (βOH-PL) in urine could help to predict growth. PN and PL pharmacokinetics were studied in 36 children, from 5 to 15 years of age, receiving daily (D) or alternate-day (AD) oral PN treatment. Statural growth velocity was evaluated over a 1-year period. We compared three groups of children according to the growth kinetics during the study year (catch-up, stable, or decline) for clinical and pharmacokinetic parameters. A multiple linear regression analysis was performed in order to determine pharmacokinetic parameters able to explain height 1 year after inclusion. Height at the beginning of the study, creatinine clearance, and type of D or AD treatment explained 94.2% of height variance 1 year after inclusion. Only PL clearance was associated with growth evolution, but introduction of PL clearance in the multivariate model did not improve the variance of height accounted for by the previous model. We, therefore, do not recommend using glucocorticoid pharmacokinetics to predict growth retardation in children with renal transplantation.

Keywords: Glucocorticoid; Growth; Renal transplantation; Pharmacokinetics

Document Type: Research article

DOI: 10.1007/s00467-004-1497-x

Affiliations: 1: Service Pharmacie, Hôpital Necker Enfants Malades, 149 rue de Sèvres, 75015 Paris, France, 2: Néphrologie Pédiatrique, Hôpital Necker Enfants Malades, 149 rue de Sèvres, 75015 Paris, France, 3: Biostatistique et Informatique Médicale, Hôpital Necker Enfants Malades, 149 rue de Sèvres, 75015 Paris, France, 4: Service Pharmacie, Hôpital Necker Enfants Malades, 149 rue de Sèvres, 75015 Paris, France, Email: francois.gimenez@nck.ap-hop-paris.fr 5: Néphrologie Pédiatrique, Hôpital Robert Debré, Paris, France, 6: Centre d'Investigation Clinique, Hôpital Necker Enfants Malades, 149 rue de Sèvres, 75015 Paris, France, 7: Centre d'Investigation Clinique, Hôpital Robert Debré, Paris, France,

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