J. Strehlau

Prophylactic oral ganciclovir after renal transplantation-dosing and pharmacokinetics

Abstract. Ganciclovir alone or in combination with hyperimmunoglobulin is replacing other treatment modalities for the prophylactic treatment of cytomegalovirus (CMV) infections. No dose recommendations are available for oral ganciclovir therapy in children with impaired renal function after renal transplantation of a kidney from a CMV IgG-positive donor. We undertook a pharmacokinetic study in 14 pediatric renal transplant recipients who were CMV IgG negative and had received a graft from a CMV IgG-positive donor. We estimated the daily dosage of oral ganciclovir in relation to the glomerular filtration rate (GFR). Oral ganciclovir was administered at a starting dose of 3 × 1 g for children with a weight above 50 kg, 3 × 750 mg for children between 50 and 37.5 kg, and 3 × 500 mg for children between 37.5 and 24 kg. The starting dose was reduced by 50% for GFR values ≤50 ml/min per 1.73 m2 and by 75% for GFR values ≤25 ml/min per 1.73 m2. The daily dose was divided into three daily doses unless GFR was <40 ml/min per 1.73 m2, when only two daily doses were given. Doses were adjusted according to the measured plasma trough concentrations (c) using the simple formula: cganciclovir(measured)/cganciclovir(desired) = dosage rate(used)/dosage rate(adjusted). Mean stable plasma trough concentration was 0.91±0.68 μg/ml. The dosage rate, adjusted to a trough concentration of 1.0 μg/ml, correlated with the GFR. The dose per day could be calculated according to a simple equation for a GFR <100 ml/min per 1.73 m2: dosage per day (mg/kg per day) = GFR. No CMV disease developed in any of the patients during oral ganciclovir, but 1 patient developed an acute rejection episode and a positive pp65 antigen 5 weeks after discontinuation of ganciclovir. The drug was well tolerated and without side effects.

Alterations of cyclosporin A metabolism induced by mycophenolate mofetil

Unexpectedly lower CsA 2‐h levels were found in patients who received additional immunosuppression by MMF in our center. The aim of this study is to prove whether there are differences in CsA metabolization when MMF is added to treatment. In 33 children who received an immunosuppression of prednisolone and CsA as well as in 15 children who were treated with additional MMF, C2 and C0 were taken. In 11 children, full AUC of CsA were obtained. C2 levelsdiffered significantly (p < 0.05) between patients treated with (617 ± 230 ng/mL) and without MMF (750 ± 271 ng/mL) but with similar CsA dosages. C2 correlated better with the AUC than CsA levels at other time points with r = 0.95. The equation AUC = 139 + 6.17 × C2 was calculated to match best in a C2‐limited sampling strategy. This formula proved to be safer than equations that had been published before. According to our findings, we suspect that MMF alters the CsA metabolism. When MMF is used in pediatric transplant recipients, either target values of CsA have to be changed or patients may require higher doses of CsA.

ABO-incompatible kidney transplantation of an 8-yr-old girl with donor/recipient-constellation A1B/B

Abstract: Background: Antigen‐specific immunoadsorption combined with rituximab offers the possibility for ABO‐incompatible kidney transplantation without splenectomy.

Dosing of MMF in combination with tacrolimus for steroiD‐resistant vascular rejection in pediatric renal allografts

Abstract SteroiD‐resistant vascular rejection was treated in seven adolescent renal allograft recipients using the combination of mycopheno‐late mofetil (MMF) and tacrolimus (FK506). Since there are no published pediatric dose recommendations for MMF using this combination, trough concentrations and pharmacokinetic profiles were used for therapeutic drug monitoring. In order to keep the mycophenolic acid (MPA) concentrations between 2–5 μg/ml, mean MMF doses were reduced from 600 to 250 mg/m2 b. i. d. Apparent clearance of MPA decreased from 5 to 1 ml/min per kg within 2 weeks. Pharmacokinetic monitoring revealed substantial variability among patients of both MMF and FK506. The MPA dose ranged from 178 to 1008 mg/m2 per day to achieve an area under the curve (AUC) of 59.9 μg × h/ml ± 10.5 SD (range 49–65 μg). FK506 dose ranged from 1.3 to 8.8 mg/m2 per day to achieve an AUC of 116 ng × h/ml ± 27 SD (range 83–145). We recommend adjusting MMF doses using therapeutic drug monitoring.

Impfungen bei nierenkranken Kindern

Nierenkranke Kinder profitieren von einer zeitgerechten Grundimmunisierung entsprechend den STIKO-Empfehlungen. Oberstes Ziel ist eine vollstandige Grundimmunisierung vor Transplantation. Neben der Grundimmunisierung sind Indikationsimpfungen wie Pneumokokken, Influenza sinnvoll. Da die Impfantwort gegenuber einzelnen Impfstoffen (z. B. Hepatitis B, Varicella) reduziert sein kann, sind Antikorperbestimmungen und Boosterimpfungen haufiger erforderlich. Sie dienen zur Beurteilung des Impferfolges sowie der Schutzdauer. Im ersten Jahr nach einer Organtransplantation sind Impfungen aufgrund der verstarkten Immunsuppression meist nicht erfolgreich. Bei Lebendimpfungen ist Zuruckhaltung angebracht, im Einzelfall muss jedoch bei der Varizellenimpfung das Risiko der Infektion gegen das Impfrisiko abgewogen werden.

Immunsuppressive Behandlung des nephrotischen Syndroms im Kindesalter – Was kommt nach der Steroidtherapie?

Die Behandlung des idiopathischen nephrotischen Syndroms (NS) im Kindesalter erfordert bei Steroidtoxizitat oder fehlender Remission weitere immunsuppressive Masnahmen, vorausgesetzt dass keine nachgewiesene Mutation im Podocin, Nephrin oder α-Actinin vorliegt und die Nephrose nicht durch eine syndromale Erkrankung verursacht wird. Die klare Zuordnung des Verlaufes unter/nach Steroidtherapie in haufig rezidivierend – steroidabhangig – steroidresistent entscheidet uber das therapeutische Vorgehen. Bei haufig rezidivierenden und steroidabhangigen Patienten kommen Monotherapien mit Levamisol, Cyclophosphamid oder Cyclosporin A zum Einsatz. Beim steroidresistenten nephrotischen Syndrom im Rahmen einer glomerularen Minimallasion oder fokal-segmentalen Glomerusklerose sollten Kombinationstherapien mit intravenosen Prednisolonpulsen und Cyclosporin A oder Cyclophosphamid, Tacrolimus und Mycophenolsaure zum Erzielen einer kompletten Remission eingesetzt werden. Eine enge Zusammenarbeit zwischen Eltern, Kinderarzt und Kindernephrologen ist Voraussetzung fur anhaltende Remissionen und niedrige Medikamententoxizitat.