Effect of CYP3A51/3 polymorphism on blood pressure in renal transplant recipients.

BACKGROUND: The cytochrome P450 3A5 (CYP3A5) enzyme has been implicated to determine blood pressure (BP) in humans. Different results have been reported concerning CYP3A5 gene polymorphisms and posttransplantation hypertension in kidney recipients. Our objective was to investigate whether CYP3A5 1/3 polymorphism was associated with ambulatory BP among a population of renal transplant recipients receiving the calcineurin inhibitor tacrolimus for immunosuppression. METHODS: Sixty primary kidney transplant recipients undergoing treatment with tacrolimus were genotyped for the CYP3A5 1/3 polymorphism. We analysed the association of the CYP3A5 alleles with ambulatory systolic and diastolic BP measured at 6 and 24 months posttransplantation. RESULTS: We observed that 23.3% of the patients were CYP3A5 1 carriers and 76.7% were homozygous for CYP3A5 3. CYP3A5 1 carriers showed higher adjusted systolic BP and diastolic BP at 6 and 24 months posttransplantation, and they were prescribed more antihypertensive drugs compared with non CYP3A5 1 carrier patients, albeit not significant. No significant differences were found comparing the distribution of the hypertension classes. CONCLUSION: We did not observe a significant association of CYP3A5 1/3 polymorphism with posttransplantation hypertension, although there were some differences in BP associated with the presence of the CYP3A5 1 allele.

Lack of association of immune cell function test with rejection in kidney transplantation.

BACKGROUND: The Cylex Immuknow assay provides a rapid assessment of global immune function in immunocompromised patients by measuring the global immune responses of CD4 T cells from a whole-blood sample. It may help to monitor the immune status of immunosuppressed transplant patients. However, earlier studies have shown that there is no consensus on the utility of the Immuknow assay in renal transplant rejection. METHODS: T-cell activation was determined by measuring an increase of intracellular adenosine triphosphate (iATP) from CD4 cells in 227 samples from 116 kidney transplant patients. The results were analyzed regarding patient clinical status, namely, rejection, infection, or stability. In addition, we measured the immunologic response of 108 healthy control subjects. RESULTS: There were 24 infectious and 36 rejection episodes. iATP concentrations differed significantly between stable and infected patients (180.5 ± 55.2 vs 375.3 ± 140.1 ng/mL; P < .001) and between infected patients and control subjects (180.5 ± 55.2 vs 436.5 ± 112 ng/mL; P < .001). No correlation was observed between patients suffering an acute rejection episode with this response. CONCLUSIONS: Our results confirmed that the Immuknow assay identified transplant patients at risk for infection. It may provide information to guide immunosuppressive therapy, but the assay did not seem to have the potential to differentiate subjects experiencing rejection.

Medida del grosor foveolar mediante tomografía de coherencia óptica en pacientes adultos con nefropatía diabética en hemodiálisis / Measurement of foveal thickness by optical coherence tomography in adult haemodialysis patients with diabetic nephropathy

Antecedentes: Diversos estudios han demostrado la eficacia de la hemodiálisis (HD) sobre el edema macular de los pacientes diabéticos. Objetivo: Estudiar los efectos de una sesión de HD sobre el grosor foveolar, mediante tomografía de coherencia óptica (OCT), en pacientes adultos con diabetes mellitus tipo 2 con insuficiencia renal crónica (IRC)estadio 5 secundaria a nefropatía diabética en HD. Pacientes y métodos: Se estudiaron 25 ojos de 14 pacientes a los cuales se les realizó analítica y OCT pre-HD y post-HD. Resultados: Como grupo, el grosor foveolar no se modificaba tras una sesión de HD en los 25 ojos estudiados (245,28± 52,21 µ frente a 240,40 ± 40,25 µ) (p = 0,428) (2% de reducción) ni se correlacionaba con ninguno de los parámetros clínicos o analíticos analizados. Al comparar el subgrupo de 13 ojos en los que el grosor foveolar no se modificaba o disminuía respecto al subgrupo de 12 ojos en los que el grosor foveolar aumentaba se encontró que en el primer subgrupo la temperatura del baño era significativamente mayor (37,00 ± 0,00 frente a 36,29 ºC, p = 0,008) y la conductividad significativamente menor (14,00 ± 0,00 frente a 14,29 ± 0,10 mS/cm, p = 0,030). Conclusión: La HD podría modificar el grosor foveolar retiniano en función de la modificación de parámetros como la temperatura del baño yl a conductividad (AU)

Background: Several studies have demonstrated the efficacy of hemodialysis (HD) on macular edema in diabetic patients. Objective: To study the effects of a HD session on foveal thickness by optical coherence tomography (OCT) in adult patients with type 2 diabetes mellitus with chronic renal failure (CRF)secondary to stage 5 diabetic nephropathy in HD. Patients and methods: We studied 25 eyes of 14 patients who underwent analytical studies and pre-HD and post-HD OCT. Results: As a group, the foveal thickness did not change afterone session of HD in the 25 eyes studied (245.28 ± 52.21 Ì versus 240.40 ± 40.25 µ) (p = 0.428) (2% reduction) or correlated with any clinical or laboratory parameters analyzed. When comparing the subgroup of 13 eyes in which the foveal thickness did not change or decreased compared to the subgroup of 12 eyes in which the foveal thickness increased we found that in the first subgroup the bath temperature was significantly higher (37.00 ± 0.00 versus 36.29 °C, p = 0.008) and the conductivity was significantly lower (14.00 ± 0.00 versus 14.29± 0.10 mS/cm, p = 0.030). Conclusion: HD may modify the foveal retinal thickness as a function of changing parameters such as bath temperature and conductivity. Conclusion: HD may modify the foveal retinal thickness as a function of changing parameters such as bath temperature and conductivity (AU)

Measurement of foveal thickness by optical coherence tomography in adult haemodialysis patients with diabetic nephropathy.

BACKGROUND: Several studies have demonstrated the efficacy of hemodialysis (HD) on macular edema in diabetic patients. OBJECTIVE: To study the effects of a HD session on foveal thickness by optical coherence tomography (OCT) in adult patients with type 2 diabetes mellitus with chronic renal failure (CRF) secondary to stage 5 diabetic nephropathy in HD. PATIENTS AND METHODS: We studied 25 eyes of 14 patients who underwent analytical studies and pre-HD and post-HD OCT. RESULTS: As a group, the foveal thickness did not change after one session of HD in the 25 eyes studied (245.28 ± 52.21 µ versus 240.40 ± 40.25 µ) (p = 0.428) (2% reduction) or correlated with any clinical or laboratory parameters analyzed.When comparing the subgroup of 13 eyes in which the foveal thickness did not change or decreased compared to the subgroup of 12 eyes in which the foveal thickness increased we found that in the first subgroup the bath temperature was significantly higher (37.00 ± 0.00 versus 36.29 ° C, p = 0.008) and the conductivity was significantly lower (14.00 ± 0.00 versus 14.29 ± 0.10 mS / cm, p = 0.030). CONCLUSION: HD may modify the foveal retinal thickness as a function of changing parameters such as bath temperature and conductivity.

Niveles de 25 hidroxivitamina D y riesgo cardiovascular en una cohorte de pacientes con enfermedad renal crónica avanzada / 25 hydroxyvitamin D levels and cardiovascular risk in a cohort of patients with chronic kidney disease

Introducción: Los niveles bajos de 25 hidroxivitamina D han sido relacionados con un aumento de la morbimortalidad de origen cardiovascular en la población general y en pacientes con enfermedad renal crónica. Objetivo: Nuestro objetivo fue estudiar los niveles de 25 hidroxivitamina D en un grupo de pacientes con enfermedad renal crónica estadios 4 y 5 prediálisis, y relacionarlos con los antecedentes de enferme- dad cardiovascular y con factores conocidos de riesgo cardiovascular. Material y métodos: Se trata de un estudio observacional transversal de una cohorte de 171 pacientes seguidos en la consulta prediálisis de nuestro hospital, me- dia de edad 64,16 ± 13 años, el 59,6% hombres, el 64,3% diabéticos, el 47,3% obesos y el 46,8% con antecedentes de enfermedad cardiovascular. A todos los pacientes se les mi- dieron los niveles séricos de 25 hidroxivitamina D y de 1-25 dihidroxivitamina D, se recogieron datos clínicos y analíticos de función renal, anemia, perfil lipídico y metabolismo óseo-mineral; también se evaluó la presión arterial mediante registro ambulatorio de 24 horas (MAPA) y se realizó estudio ecocardiográfico. Resultados: La media de los niveles de 25 hidroxivitamina D fue de 22,1 ± 13 ng/ml, sólo un 18,7% de los pacientes presentaban niveles normales, un 58,5% presentaban niveles insuficientes o bajos y un 22,8% niveles deficientes o muy bajos. Las variables que se asociaron con los niveles bajos de vitamina D fueron la edad, la diabetes, el sexo femenino, la obesidad, el filtrado glomerular y el antecedente de enfermedad cardiovascular. Dentro de los parámetros asociados a la presión arterial, la presión del pulso fue la que más se relacionó con los niveles de vitamina D. No se encontró asociación entre los niveles de 25 hidroxivitamina D con otros parámetros del metabolismo óseo mineral ni con los valores ecográficos de hipertrofia ventricular izquierda. En el análisis multivariante las variables que más se asociaron al déficit de 25 hidroxivitamina D fueron el sexo femenino, el antecedente de enfermedad cardiovascular, el filtrado glomerular y la presión del pulso del MAPA. Conclusiones: Nuestro estudio confirma una alta prevalencia de insuficiencia y deficiencia de 25 hidroxivitamina D en la población con enfermedad renal crónica avanzada; este déficit se asocia con la presencia de factores de riesgo cardiovascular y con el antecedente de enfermedad cardiovascular. Sin embargo, no se encontró ninguna asociación con uno de los principales predictores de eventos cardiovasculares como es la hipertrofia ventricular izquierda (AU)

Background: Decreased 25 hydroxyvitamin D serum levels have been related to an increase in cardiovascular morbility and mortality in both general population and chronic kidney disease patients. The aim of this study was to evaluate the relationship between 25 hydroxy vitamin D serum level, cardiovascular risk factors and previouses tablished cardiovascular disease in a group of patients with advanced chronic kidney disease. Material and methods: We performed a cross-sectional observational study in a cohort of 171 stage 4 and 5 chronic kidney disease out patients seen in our predialysis clinic, mean age64.16 ± 13 years, 59.6% were men, 64.3% had diabetes,47.3% had obesity, 46.8% had previous cardiovascular disease. 25 hydroxy vitamin D and 1-25 dihydroxy vitamin D were measured, we also determine other routine biochemical parameters. All subjects underwent anechocardiogram and 24 hours ambulatory blood pressure monitoring was also performed. Results: Mean 25hydroxyvitamin D levels were 22.1 ± 13 ng/ml, only 18.7%of the patients had adecuate levels, levels were insufficient in 58.5% of the patients and deficient in 22.8% of them. Low 25 hydroxyvitamin D levels were significatively related with age, diabetes, female gender, obesity, MDRD glomerular filtration rate and previous cardiovascular disease. Pulse pressure was the Ambulatory Blood Pressure Monitoring parameter that was better correlated with 25 hydroxyvitamin D levels. We could not find any association between vitamin D levels and other bone and mineral metabolism parameters. No relationship was seen between low vitamin D levels and left ventricular hypertrophy. On multivariate analysis lower levels of 25 hydroxyvitamin D were independently associated with female gender, previous cardiovascular disease, MDRD4-GFR and higher pulse pressure. Conclusions: Our study confirm a high prevalence of 25 hydroxyvitamin D insufficiency and deficiency in advanced chronic kidney disease patiens, this was associated with the presence of cardiovascular risk markers and previous established cardiovascular disease. However we could not see any relationship with left ventricular hypertrophy which is an known predictor of future cardiovascular events in this population (AU)

¿Minimiza el carvedilol los requerimientos de fotocoagulación láser en la retinopatía diabética? / No disponible

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Regional differences in the prevalence of someg lomerulopathies on the Canary Islands

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[Mycophenolate mofetil in the treatment of lupus nephritis, in patients with failure, intolerance or relapses after treatment with steroids and cyclophosphamide]. / Micofenolato mofetil en el tratamiento de la nefritis lúpica en pacientes con fracaso, intolerancia o recidivas tras tratamiento con esteroides y ciclofosfamida.

Intravenous cyclophosphamide (IVCP) in combination with oral steroids (ST) is the most widely accepted therapy for severe lupus nephritis (LN); however, its side effects, lack of response and relapses, have led to other treatment alternatives. being sought. Mycophenolate mofetil (MMF) has been shown to be effective in these cases. We studied the course over 12 months of 28 patients with LN WHO class III(n=3), IV(n=22) or V(n=3), with 38,1 +/- 11,4 tears of age, proteinuria 4,2 +/- 2,6 g /24 hours and serum creatinine 1,4 +/- 0,8 mg/dL, who, after being initially treated with ST and IVCP, showed no response(n=21), frequent relapses(n=6), or adverse side effects(n=1). All patients were treated with MMF in doses of 1000 to 2000 mg/day combined with ST or cyclosporine for one year. Four patients withdrew from treatment before the end of the follow-up. None of the patients who completed the study showed changes in hematologic parameters. Creatinine and creatinine clearance remained stable. Resulted in a significant improvement; serum albumine (3 +/- 0,8 vs 3,9 +/- 0,5 g/dL) p<0.01, and decreased of proteinuria (4,2 +/- 2,6 vs 1,8 +/- 2,2 g/ 24 hours) p<0.05, complement fractions improvement significantly, C3 and CH50 p<0.05, C4 p<0.01. Antinuclear antibodies (ANA) and anti-DNA antibodies decreased significantly (p<0.05). During follow-up, a reduction in the ST dose was achieved: 18.3 +/- 10,5 vs 10,1 +/- 4,1 mg/24h (p<0.01). Three mild side effects related to MMF were observed and only 1 case required discontinuation of treatment. We concluded that MMF is a useful drug in the treatment and control of lupus nephritis, which also allows for a significant reduction in the dose of ST, with minimal side effects.

The PlA2 polymorphism of the platelet glycoprotein IIIA gene as a risk factor for acute renal allograft rejection.

Glycoprotein IIIa/IIb is a membrane receptor for fibrinogen and von Willebrand factor that plays an important role in platelet aggregation. The beta integrin chain of this receptor, GPIIIa, is polymorphic, and the allele known as PlA2 has been associated with coronary thrombosis. The GPIIIa genotype of a cohort of 119 consecutive renal allograft recipients (46.3 +/- 13 yr; 85 M/34 F; 24.4% diabetic patients) was determined by PCR-restriction fragment length polymorphism, and those patients were followed for at least 12 mo. From 119 patients with at least 1 yr of follow-up, those who suffered an acute rejection (n = 52) showed a lower proportion of HLA-DR beta1 identity with the donor (7.7% versus 23.9%; P = 0.03), a higher proportion of cytomegalovirus-positive (CMV+) donors/CMV- recipients (21% versus 7.5%; P = 0.05), and the PlA2 allele was more frequent (48.1% versus 26.9%; P = 0.02) compared with patients free of acute rejection (n = 67). No other variable was associated with acute rejection in the univariate analysis. The impact of the three above-mentioned significant variables on acute rejection was analyzed by stepwise logistic regression. The presence of the PlA2 allele yielded an odds ratio of 2.75 (95% confidence interval, 1.01 to 7.93) and an HLA-DR beta1 identity of 0.2 (95% confidence interval, 0.06 to 0.99) for suffering an acute rejection episode. In addition, the serum creatinine at discharge was higher in PlA2-positive versus PlA2-negative patients (2.2 +/- 1.6 versus 1.5 +/- 0.6 mg/dl, respectively; P = 0.01), and the prevalence of proteinuria >1.5 g/d 1 yr after transplantation was significantly higher among patients showing the PlA2 allele (16% versus 3%; P = 0.02). Finally, in the entire cohort of patients, the 2-yr graft survival was significantly lower in PlA2-positive (n = 43) compared with PlA2-negative (n = 76) patients (85.7% versus 97.2%; P = 0.015). No differences were found in patient survival (95.2% versus 98.7%, respectively). Proportional hazards regression analysis (Cox regression model) confirmed that serum creatinine level at discharge is the best predictor of allograft survival, followed by CMV status, delayed graft function, and the glycoprotein IIIa/IIb genotype. The PlA2 polymorphism is an independent risk factor for acute renal graft rejection, affecting short-term graft survival. Future studies aimed at preventing the hemostatic imbalance favoring platelet aggregation associated with this polymorphism may be important in preventing acute rejection and its impact on chronic rejection.