[Practical markers of renal function in cystinosis patients]. / Marcadores práticos de função renal em pacientes com cistinose.

BACKGROUND: Cystinosis is an autossomic recessive systemic disease that leads to renal insufficiency early in life unless cysteamine be started early. Unfortunately, even in this situation the patients will develop chronic renal disease with need of renal replacement therapy about second decade of life. Therefore, the renal function evaluation is essential to these patients. The aim of this study was to evaluate cystatin C, serum creatinine and creatinine clearance estimated by stature (Schwartz Formula) in cystinosis patients, with different degrees of renal function, and to correlate these parameters. METHODS: We studied cystinosis patients, aged lower than 18 years, with different degrees of renal function, classified according to KDOQI in Chronic Kidney Disease stage 1 to 4. No patient was under renal replacement therapy. In these patients we evaluate the serum creatinine, cystatin C and creatinine clearance according to Schwartz Formula. RESULTS: We analyzed 103 blood samples of 26 patients. We detected a significant statistical correlation between serum creatinine and cystatin C (r = 0.81, p < 0.0001), cystatin C and creatinine clearance estimated by stature (r = -0.84, p < 0.0001) and between serum creatinine and creatinine clearance estimated by stature (r = -0.97, p < 0.0001). CONCLUSIONS: The expensive measurement of cystatin C showed no advantage in relation to serum creatinine and creatinine clearance according to Schwartz Formula in cystinosis patients to estimate the glomerular filtration rate. This is the first report checking the value of serum creatinine, creatinine clearance estimated by stature and cystatin C in cystinosis patients.

Marcadores práticos de função renal em pacientes com cistinose / Practical markers of renal function in cystinosis patients

INTRODUÇÃO: Cistinose é uma doença sistêmica, autossômica recessiva, que leva à insuficiência renal crônica na infância, a não ser que o tratamento com cisteamina seja iniciado precocemente. Mesmo nestas condições, os pacientes evoluem para doença renal crônica terminal por volta da segunda década da vida. Portanto, a avaliação da função renal é essencial neste grupo de pacientes. OBJETIVO: Avaliar e correlacionar a cistatina C, creatinina sérica e o clearance de creatinina pela Fórmula de Schwartz em pacientes com cistinose, com diferentes graus de função renal. MÉTODOS: Foram incluídos pacientes com menos de 18 anos de idade, com diferentes níveis de função renal, de acordo com o KDOQI em estágios 1 a 4. Nenhum dos pacientes estava em terapia de substituição renal. Foram medidos os seguintes parâmetros: cistatina C, creatinina sérica e o clearance de creatinina pela fórmula de Schwartz. RESULTADOS: Foram analisadas 103 amostras de sangue de 26 pacientes. Foi detectada correlação significativa entre creatinina sérica e cistatina C (r = 0,81, p < 0,0001), cistatina C e o clearance de creatinina pela fórmula de Schwartz (r = -0,84, p < 0,0001) e creatinina sérica e clearance de creatinina (r = -0,97, p < 0,0001). CONCLUSÕES: A medida da cistatina não mostrou nenhuma vantagem sobre a creatinina sérica e o clearance de creatinina pela fórmula de Schwartz em pacientes com cistinose para avaliar o ritmo de filtração glomerular. Este é o primeiro relato sobre o valor da creatinina sérica, do clearance de creatinina pela fórmula de Schwartz e da cistatina C em pacientes com cistinose.

BACKGROUND: Cystinosis is an autossomic recessive systemic disease that leads to renal insufficiency early in life unless cysteamine be started early. Unfortunately, even in this situation the patients will develop chronic renal disease with need of renal replacement therapy about second decade of life. Therefore, the renal function evaluation is essential to these patients. The aim of this study was to evaluate cystatin C, serum creatinine and creatinine clearance estimated by stature (Schwartz Formula) in cystinosis patients, with different degrees of renal function, and to correlate these parameters. METHODS: We studied cystinosis patients, aged lower than 18 years, with different degrees of renal function, classified according to KDOQI in Chronic Kidney Disease stage 1 to 4. No patient was under renal replacement therapy. In these patients we evaluate the serum creatinine, cystatin C and creatinine clearance according to Schwartz Formula. RESULTS: We analyzed 103 blood samples of 26 patients. We detected a significant statistical correlation between serum creatinine and cystatin C (r = 0.81, p < 0.0001), cystatin C and creatinine clearance estimated by stature (r = -0.84, p < 0.0001) and between serum creatinine and creatinine clearance estimated by stature (r = -0.97, p < 0.0001). CONCLUSIONS: The expensive measurement of cystatin C showed no advantage in relation to serum creatinine and creatinine clearance according to Schwartz Formula in cystinosis patients to estimate the glomerular filtration rate. This is the first report checking the value of serum creatinine, creatinine clearance estimated by stature and cystatin C in cystinosis 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 AUC(0-12h) (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 / Cystatin C measurement as renal function marker

INTRODUÇÃO: A cistatina C sérica tem sido apontada como um marcador de filtração glomerular. OBJETIVO: Realizar a validação de um método específico e automatizado, a imunonefelometria, mensurando os níveis séricos de cistatina C por meio do nefelômetro da empresa Behring (BN II) e correlacionar resultados obtidos entre pacientes transplantados. O ensaio perfaz o intervalo de referência de 0,23-7,25 mg/l. A imprecisão intra e interensaio foi de 8,73 por cento e 5,38 por cento, respectivamente. A recuperação analítica da cistatina C após adição de controle foi entre 86,7 por cento e 98 por cento (média 92,3 por cento). A estabilidade da cistatina C à temperatura ambiente, sob refrigeração e sob congelamento foi testada. A perda mais significativa foi encontrada nas amostras armazenadas à temperatura ambiente, em que foram perdidos até 10 por cento da concentração inicial. Foi encontrado coeficiente de variação de 14,79 por cento para sensibilidade analítica. Durante todo o processo foram comparados os resultados com o controle de qualidade e obtivemos bons resultados. Depois desses testes, nós comparamos as correlações em três grupos de pacientes transplantados renais sob diferentes esquemas de imunossupressão (n = 197) - azatioprina (n = 36), micofenolato mofetil (n = 131) e sirolimus (n = 30) - entre as equações de estimativa de filtração glomerular (Cockroft Gault, Nankivell e Modification of Diet in Renal Disease) e cistatina C sérica ou creatinina sérica. CONCLUSÃO: O ensaio nefelométrico cistatina C pode perfeitamente ser adequado à nossa rotina laboratorial e as correlações entre creatinina sérica e as diferentes equações de estimativa de filtração glomerular são melhores do que quando comparamos as mesmas à cistatina C nos três grupos, independentemente da terapia imunossupressora utilizada.

INTRODUCTION: Serum cystatin C has been identified as a glomerular filtration marker. OBJECTIVE: To validate immunonephelometry, a specific and automated method, by measuring levels of serum cystatin C through Behring nephelometer (BN II) and correlate results among transplant patients. The assay comprises the reference range of 0:23 to 7:25 mg/l. The intra-assay and inter- assay imprecision rates were 8.73 percent and 5.38 percent, respectively. The analytical recovery of cystatin C after addition of control was between 86.7 percent and 98 percent (average 92.3 percent). The stability of cystatin C to room temperature, refrigerated or frozen was tested. The most significant loss was found in samples stored at room temperature, in which up to 10 percent of the initial concentration was lost. The coefficient of variation was 14.79 percent for analytical sensitivity. Throughout the process the results were compared with quality control and good results were achieved. After these tests, we compared the correlations between equations for estimating glomerular filtration rate (Cockroft Gault, Nankivell and MDRD) and serum cystatin C or serum creatinine in three groups of kidney transplant patients under different immunosuppressive regimens (n = 197) [azathioprine (n = 36), mycophenolate mofetil (n = 131) or sirolimus (n = 30)]. CONCLUSION: The nephelometric cystatin C assay may be perfectly suitable for our routine laboratory. The correlations between serum creatinine and the various equations for estimating glomerular filtration are better than those between cystatin C and equations for estimating glomerular filtration in the three groups irrespective of the immunosuppressive therapy used.