Parent-to-Child Transplantation With Cyclosporine Immunosuppression

Kahan, E; Conley, Susan B.; Portman, Ronald J.; Lemaire, R; Wideman, C.; Flechner, Stuart M.; Buren, C. Van

doi:10.1016/s0022-5347(17)42942-9

Cited by 4 publications

(10 citation statements)

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“…recently reported that the clearance (4.932 L/h/kg) and apparent volume of distribution (V ss = 34.4 L/kg) of cyclosporine in children < 10 years of age was significantly greater than that observed in patients 11 to 40 years of age (CL = 2.58 L/h/kg and Vss = 20.6 L/kg). Kahan et al (1987) have also described increased cyclosporine clearance and F = 29 ± 24%). In this study, trough cyclosporine concentrations> 100 JLg/L could not be achieved in 57% of patients during the first month of treatment despite daily doses of 20 mg/kg.…”

Section: Cyclosporine Immunosuppressionmentioning

confidence: 84%

“…At present, the mechanisms of action for cyclosporine appear to include inhibition of T -cell-dependent B cell activation, expansion ofunprimed T helper and cytotoxic T cell subsets, clonal expansion of alloreactive cells and induction of 'Y-interferon secretion (Gerson 1987). The primary therapeutic uses of cyclosporine in paediatric patients have been to prevent or ameliorate rejection of kidney (Conley et al 1985;Geary et al 1987;Kahan et al 1987;Salaman et al 1987;Sheldon et al 1985;So et al 1987;Tejani et al 1986), liver (Esquivel et al 1987), cardiac (Addonizio & Rose 1987) and bone marrow allografts (Beveridge et al 1982;Deeg et al 1985;Kay 1982;Yee et al 1986). Recently, how-43 ever, the use of this agent in infants and children has been broadened with successful therapeutic trials for autoimmune enteropathy (Roth et al 1987;Siedman et al 1987), autoimmune chronic active hepatitis (Hyams et al 1987), systemic lupus erythematosus (Feutren et al 1987), relapsing nephrotic syndrome (Tejani et al 1987), dermatomyositis (Girardin et al 1988) and type I diabetes mellitus (Bach 1987;Stiller et al 1987).…”

Section: Cyclosporine Immunosuppressionmentioning

confidence: 99%

“…It appears, therefore, that many of the same development,tl factors that contribute to enhanced biotransformation and distribution of drugs in infants and children may also affect cydosporine. Indeed, the developmental pharmacokinetics of cyclosporine appear to underscore the recommendations for higher doses and shorter dosing intervals in paediatric patients (Conley et al 1985;Kahan et al 1987). …”

Section: Cyclosporine Immunosuppressionmentioning

confidence: 99%

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Clinical Pharmacokinetics in Infants and Children A Reappraisal

Kearns

Reed

1989

Clinical Pharmacokinetics

174

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A significant increase in the knowledge base in paediatric clinical pharmacology has occurred over the past 2 decades and has largely been the result of important scientific and sociological advancements pertaining to paediatric therapeutics. Although the data on drug disposition in infants and children have increased considerably over the past few years, pharmacokinetic-pharmacodynamic interactions, particularly the effect of development on pharmacodynamics, remain poorly understood.The impact of developmental physiology on drug absorption, distribution, metabolism and elimination in infants and children is reviewed and contrasted to the determinants of clinical pharmacokinetics in neonates. The most notable differences in drug disposition between in/ants and children when compared with neonates and young adults centre around alterations in body water and serum protein composition and the affinity/capacity for hepatic biotransformation of xenobiotics.As opposed to examining the effect of age on the disposition of specific compounds, the differences in developmental pharmacology are highlighted by the review of important and/or emerging pharmacokinetic-pharmacodynamic controversies in infants and children. These include the issues of altered drug distribution and metabolism in cysticjibrosis, pharmacokinetic determinants of successful antimicrobial therapy in bacterial meningitis and the pharmacokinetic determinants of immunosuppression treatment with cyclosporin. The pharmacological differences which are characteristic of development in both infants and children are also reviewed by examination of considerations for clinical pharmacokinetic evaluations such as specific routes and techniques for both drug administration and determination of sampling strategies.Clinical pharmacokinetics will continue to function as a bridge between the generation of new information and the practical application of this knowledge. Consequently, pharmacokinetics provides a pharmacological tool for use in research and clinical care. The clinical application of this tool is examined by a review of the pertinent assumptions and limitations, as well as useful mathematical techniques for use in paediatric patients. Additionally, 'non-traditional' uses of clinical pharmacokinetics (forensic application and use to evaluate organ function) in infants and children are discussed as are considerations for research use of clinical pharmacokinetic data.

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Section: Cyclosporine Immunosuppressionmentioning

confidence: 84%

Section: Cyclosporine Immunosuppressionmentioning

confidence: 99%

Section: Cyclosporine Immunosuppressionmentioning

confidence: 99%

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Clinical Pharmacokinetics in Infants and Children A Reappraisal

Kearns

Reed

1989

Clinical Pharmacokinetics

174

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“…In the early years of transplantation only a few centers performed this procedure in children and then mostly from a living‐related source ( 2). As immunosuppression became safer and more stable ( 3, 4) pediatric renal transplant activity increased markedly; however, with 73 pediatric centers across the country, the volume at each center is too small to derive meaningful information regarding outcome and the quality of life of children, post‐transplantation.…”

mentioning

confidence: 99%

The 1997 Annual Renal Transplantation in Children Report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS)

Benfield

McDonald

Sullivan

et al. 1999

Pediatric Transplantation

150

108

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This report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS), covering the years 1987-96 (January 15, 1997), analyzed data on 4898 patients who received 5362 transplants. Over the 10 yr of the study, 21.3% of the patients were under the age of 6 yr. Of the disorders that lead to end-stage renal disease (ESRD), structural and developmental anomalies of aplasia, dysplasia, and obstructive uropathy accounted for over 1500 patients. Despite the potential therapies for focal segmental glomerulosclerosis (FSGS), there has been little change in its incidence and this lesion continues to be the most common cause of renal failure and transplantation among acquired diseases. Eighty-nine per cent of patients with a functioning graft continue to receive cyclosporin A (CsA) 5 yr post-transplantation, and 84% of patients continue to receive azathioprine (AZA), whereas 26% of patients receive alternate-day steroid therapy at 4 yr post-transplant. Thirty-seven per cent of the living donor (LD) recipients and 47% of cadaver donor (CD) recipients were treated with the polyclonal T-cell antibody ATG/ALG for induction, and the monoclonal T-cell antibody, OKT3, was utilized for induction in 12% of LD patients and in 19% of CD patients. Twenty-five per cent of the 5362 transplants (1333) have failed over the 10-yr period. Graft survival is 90% at 1 yr and 74% at 6 yr for LD kidneys, and is 80% at 1 yr and 58% at 6 yr for CD patients. The most common cause for graft failure (30%) is chronic rejection. For recipients of LD grafts, relative risk (RR) factors for graft survival are African-American race (RR = 2.1, p < 0.001) and greater than five prior transfusions (RR = 1.6, p < 0.001). Prophylactic anti-T-cell antibody reduces the risk of graft failure (RR = 0.76, p = 0.009). For recipients of cadaver kidneys, risk factors are: recipient age < 2 yr (RR = 2, p < 0.001), donor age < 6 yr (RR = 1.3, p = 0.005), and absence of induction T-cell antibody (RR = 1.31, p < 0.001).

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“…A recent report of the European Dialysis and Transplantation Association indicates that 2-4 years post-transplantation, increased serum creatinine levels are found about twice as often in pediatric patients receiving CyA as in those not receiving this drug [8]. In addition, a number of untoward effects have been noted from high-dose CyA therapy: hypertension [5], hirsutism, gingival hyperplasia, and seizures [12,13,291. Subsequently, attempts to avoid nephrotoxic and other side effects of CyA, either by reducing the dose rapidly or limiting use of the drug to a short period after grafting [16] or by delaying the start of CyA therapy, have been proposed [3].…”

Section: Discussionmentioning

confidence: 99%

Low-dose cyclosporin A therapy in cadaver renal transplantation in children

et al. 1989

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Fifty-one pediatric patients undergoing a first cadaveric kidney transplantation were followed for at least 2 years after grafting. They were divided into two groups: those treated with methylprednisolone plus azathioprine (AZA) and those treated with methylprednisolone plus low-dose cyclosporin A (CyA; median dose 109 mg/m2 per day = 3.4 mg/kg per day after 1 year). The steroid dosage given was significantly lower in the second group. The 4-year graft survival rate was 68% for the AZA group and 78% for the CyA group. Renal function did not differ significantly in the two groups; after 1, 2, and 3 years, the median 24-h creatinine clearance was 79, 69, and 51 ml/min/1.73 m2, respectively, for the AZA group and 78, 63, and 68 ml/min/1.73 m2, respectively, for the CyA group. Linear growth was similar in the two groups. We conclude that in pediatric patients the results of low-dose CyA immunosuppression do not differ significantly from those obtained with AZA in terms of graft survival, renal function, or growth.

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Parent-to-Child Transplantation With Cyclosporine Immunosuppression

Cited by 4 publications

References 0 publications

Clinical Pharmacokinetics in Infants and Children A Reappraisal

Clinical Pharmacokinetics in Infants and Children A Reappraisal

The 1997 Annual Renal Transplantation in Children Report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS)

Low-dose cyclosporin A therapy in cadaver renal transplantation in children

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