Maria E. Mendes

The need of mycophenolic acid monitoring in long-term renal transplants.

Abstract:  Background:  There is little information regarding the 12‐h mycophenolic acid (MPA) pharmacokinetics (PK), a way to monitor the drug and the need of frequent monitoring, in stable patients.

Diminished mycophenolic acid exposure caused by omeprazole may be clinically relevant in the first week posttransplantation.

Background: Some studies have reported a decreased absorption of mycophenolic acid (MPA) from mycophenolate mofetil (MMF) in renal transplanted (RTx) patients under proton-pump inhibitors (PPIs). There is still a lack of information regarding (1) whether this effect occurs when MMF is administered with either tacrolimus or cyclosporine A [calcineurin inhibitors (CNIs)], (2) whether the effect has the same amplitude during the first year after RTx, and finally (3) whether this decrease in exposure is clinically relevant. Methods: We retrospectively analyzed the omeprazole effect in 348 12-hour pharmacokinetic samplings [area under the curve (AUC)0–12h] performed on days 7, 14, 30, 60, 180, and 360 after RTx in 77 patients who participated in previous trials. Results: For all periods, the groups with and without PPI did not differ in all variables. By mixed-model analysis of variance, PPI reduced the MPA AUC0–12h (P < 0.0008) in the patients under both CNIs mainly due to decreased absorption (P = 0.049). In the tacrolimus group, a lower exposure seemed also due to a decreased MPA reabsorption at 10–12 hours. The PPI effect remains throughout the first year but was clinically more important on day 7. By Cox analysis, the use of PPI was associated with a 25% less chance of being adequately exposed to MPA (95% confidence interval 0.58–0.99, P = 0.04). Similarly, the number of patients underexposed to MPA (AUC < 30 ng·h/mL) was higher at most periods in the PPI group but again not statistically significant. Conclusions: These data indicate that PPI decreases the MPA exposure when associated with both CNIs but particularly in the first week after RTx. In this period, the MMF dose should be increased. This effect lasts throughout the first year but does not seem to be clinically relevant after the first week.

Determinação de cistatina C como marcador de função renal

INTRODUCAO: A cistatina C serica tem sido apontada como um marcador de filtracao glomerular. OBJETIVO: Realizar a validacao de um metodo especifico e automatizado, a imunonefelometria, mensurando os niveis sericos de cistatina C por meio do nefelometro da empresa Behring (BN II) e correlacionar resultados obtidos entre pacientes transplantados. O ensaio perfaz o intervalo de referencia de 0,23-7,25 mg/l. A imprecisao intra e interensaio foi de 8,73% e 5,38%, respectivamente. A recuperacao analitica da cistatina C apos adicao de controle foi entre 86,7 % e 98% (media 92,3%). A estabilidade da cistatina C a temperatura ambiente, sob refrigeracao e sob congelamento foi testada. A perda mais significativa foi encontrada nas amostras armazenadas a temperatura ambiente, em que foram perdidos ate 10% da concentracao inicial. Foi encontrado coeficiente de variacao de 14,79% para sensibilidade analitica. Durante todo o processo foram comparados os resultados com o controle de qualidade e obtivemos bons resultados. Depois desses testes, nos comparamos as correlacoes em tres grupos de pacientes transplantados renais sob diferentes esquemas de imunossupressao (n = 197) - azatioprina (n = 36), micofenolato mofetil (n = 131) e sirolimus (n = 30) - entre as equacoes de estimativa de filtracao glomerular (Cockroft Gault, Nankivell e Modification of Diet in Renal Disease) e cistatina C serica ou creatinina serica. CONCLUSAO: O ensaio nefelometrico cistatina C pode perfeitamente ser adequado a nossa rotina laboratorial e as correlacoes entre creatinina serica e as diferentes equacoes de estimativa de filtracao glomerular sao melhores do que quando comparamos as mesmas a cistatina C nos tres grupos, independentemente da terapia imunossupressora utilizada.