Adipocitocinas, inflamación y resistencia insulínica en la insuficiencia renal crónica

: La insuficiencia renal crónica (IRC) condiciona disfunción del tejido adiposo y desequilibrio de las adipocitocinas relacionadas con la inflamación y metabolismo de la glicemia. Objetivo: describir la relación entre los marcadores de inflamación (IL6, TNFα, PCR, RIL2), las adipocitocinas (adiponectina, leptina) y las alteraciones de la glicemia en 336 pacientes con IRC en diferentes grupos de IRC (sin terapia renal sustitutiva, hemodiálisis, diálisis peritoneal). Conclusiones: Pacientes con IRC sin terapia renal sustitutiva, presentan menor estado inflamatorio y adipocitocinas que los pacientes en diálisis. Existe una relación inversa entre adiponectina, inflamación y filtrado glomerular. Las adipocitocinas son un factor de riesgo independiente de hiperglicemia

Lymphomatoid granulomatosis in a renal transplant patient.

Lymphomatoid granulomatosis is a rare angiocentric and angiodestructive pulmonary angiitis considered as a variant of the lymphoproliferative disorder group. Patients with organ transplantation are at an increased risk for post-transplant lymphoproliferative disorders secondary to their immunosuppression. However, lymphomatoid granulomatosis has rarely been described in patients with renal transplantation. It often presents with severe pulmonary signs. We describe a case whose initial presentation was an isolated VIth nerve palsy. We review the radiological and pathological findings and discuss the etiopathogenesis and therapeutic options of this particular lymphoproliferative disorder. With careful and stepwise reduction in her immunosuppression, our patient showed a complete disappearance of her lymphomatoid granulomatosis, and she is clinically well more than 3 years after the diagnosis, with good kidney function.

Evolución de la función renal en un grupo de pacientes con estenosis de la/s arterias renales sometidos a tratamiento medico.

: La elección del tratamiento adecuado para la estenosis aterosclerótica de arterias renales es controvertida. Los ensayos clínicos recientes demuestran que los resultados de la revascularización y el tratamiento farmacológico no son superiores a los del tratamiento con fármacos únicamente por lo que al final de un seguimiento promedio de 4 años, en 49 pacientes en el Servicio de Nefrología del Hospital Valle de Hebrón se consigue una estabilización de la función renal. A pesar de esta buena evolución la mortalidad global y las complicaciones CV siguen siendo muy elevadas.

Renal Services Review 2002

Renal Services Review 2002

Amniotic fluid insulin-like growth factor binding protein 3 concentration as early indicator of fetal growth restriction.

OBJECTIVE: Insulin-like growth factor-I (IGF-I) is an important regulator of fetal growth and its bioavailability depends on insulin-like growth factor binding proteins (IGFBPs). Genes coding for IGF-I and IGFBP3 are polymorphic. We hypothesized that either amniotic fluid protein concentration at the beginning of the second trimester or genotype of one of these two genes could be predictive of abnormal fetal growth. STUDY DESIGN: Amniotic fluid samples (14-18 weeks of pregnancy) from 123 patients with appropriate for gestational age (AGA) fetuses, 39 patients with small for gestational age (SGA) fetuses and 34 patients with large for gestational age (LGA) were analyzed. Protein concentrations were evaluated by ELISA and gene polymorphisms by PCR. RESULTS: Amniotic fluid IGFBP3 concentrations were significantly higher in SGA compared to AGA group (P=0.030), and this was even more significant when adjusted to gestational age at the time of amniocentesis and other covariates (ANCOVA analysis: P=0.009). Genotypic distribution of IGF-I variable number of tandem repeats (VNTR) polymorphism was significantly different in SGA compared to AGA group (P=0.029). 19CA/20CA genotype frequency was threefold decreased in SGA compared to AGA group and the risk of SGA occurrence of this genotype was decreased accordingly: OR=0.289, 95%CI=0.1-0.9, P=0.032. Genotype distribution of IGFBP3(A-202C) polymorphism was similar in all three groups. CONCLUSIONS: High IGFBP3 concentrations in amniotic fluid at the beginning of the second trimester are associated with increased risks of SGA while 19CA/20CA genotype at IGF-I VNTR polymorphism is associated with reduced risks of SGA. Neither IGFBP3 concentrations, nor IGF-I/IGFBP3 polymorphisms are associated with modified risks of LGA.

Role of MIF and glutathione, in association with fetal ovine globin chain (Hbgamma) and LPS, in induction of TNFalpha from cells of young and aged mice, and PBL from healthy human populations.

Previous reports from our group have established that the fetal ovine gamma globin chain (Hbgamma) and LPS can synergize in the induction of pro-inflammatory cytokines, especially TNFalpha, from mouse and human leukocytes. A fetal sheep liver extract (FSLE) which was observed to have marked immunoregulatory properties in vivo and in vitro had independently been observed to contain significant amounts of each of these molecules. However, the biological activity of this extract (hereafter FSLE) was not explained solely by its content of Hbgamma and LPS, and independent analysis confirmed also the presence of migration inhibitory factor, MIF, and glutathione in FSLE. We have investigated whether MIF and the cellular anti-oxidant glutathione can further synergize with Hbgamma and LPS in TNFalpha induction from human cells in vitro, and mouse cells activated in vivo/in vitro. Our data show that indeed there is evidence for such a synergy. Treatment or mouse cells with FSLE produced an enhanced TNFalpha production which could be inhibited independently both by anti-Hbgamma and by anti-MIF, and optimally by a combination of these reagents.

Prenatally engineered autologous amniotic fluid stem cell-based heart valves in the fetal circulation.

Prenatal heart valve interventions aiming at the early and systematic correction of congenital cardiac malformations represent a promising treatment option in maternal-fetal care. However, definite fetal valve replacements require growing implants adaptive to fetal and postnatal development. The presented study investigates the fetal implantation of prenatally engineered living autologous cell-based heart valves. Autologous amniotic fluid cells (AFCs) were isolated from pregnant sheep between 122 and 128 days of gestation via transuterine sonographic sampling. Stented trileaflet heart valves were fabricated from biodegradable PGA-P4HB composite matrices (n = 9) and seeded with AFCs in vitro. Within the same intervention, tissue engineered heart valves (TEHVs) and unseeded controls were implanted orthotopically into the pulmonary position using an in-utero closed-heart hybrid approach. The transapical valve deployments were successful in all animals with acute survival of 77.8% of fetuses. TEHV in-vivo functionality was assessed using echocardiography as well as angiography. Fetuses were harvested up to 1 week after implantation representing a birth-relevant gestational age. TEHVs showed in vivo functionality with intact valvular integrity and absence of thrombus formation. The presented approach may serve as an experimental basis for future human prenatal cardiac interventions using fully biodegradable autologous cell-based living materials.

Mycophenolic acid formulations in adult renal transplantation - update on efficacy and tolerability.

The description more than 30 years ago of the role of de novo purine synthesis in T and B lymphocytes clonal proliferation opened the possibility for selective immunosuppression by targeting specific enzymatic pathways. Mycophenolic acid (MPA) blocks the key enzyme inosine monophosphate dehydrogenase and the production of guanosine nucleotides required for DNA synthesis. Two MPA formulations are currently used in clinical transplantation as part of the maintenance immunosuppressive regimen. Mycophenolate mofetil (MMF) was the first MPA agent to be approved for the prevention of acute rejection following renal transplantation, in combination with cyclosporine and steroids. Enteric-coated mycophenolate sodium (EC-MPS) is an alternative MPA formulation available in clinical transplantation. In this review, we will discuss the clinical trials that have evaluated the efficacy and safety of MPA in adult kidney transplantation for the prevention of acute rejection and their use in new combination regimens aiming at minimizing calcineurin inhibitor toxicity and chronic allograft nephropathy. We will also discuss MPA pharmacokinetics and the rationale for therapeutic drug monitoring in optimizing the balance between efficacy and safety in individual patients.

Pacientes de edad avanzada con insuficiencia cardíaca ingresados en un servicio de medicina interna: valoración de la función renal.

Objectius: analitzar comorbiditats de pacients hospitalaris ≥65 anys amb Insuficiència Cardíaca (IC). Adequació tractament farmacològic. Impacte Insuficiència Renal (IR). Metodologia: estudi descriptiu transversal de 150 pacients ingressats en Medicina Interna Hospital Vall d'Hebron entre juny'2007-gener'2010. Resultats: hipertensió arterial: 84%; obesitat: 32,1%; cardiopatia isquèmica: 41,3%; fracció d'ejecció del ventricle esquerre (FEVI) conservada: 70%. 53 pacients sense antagonistes de l'enzim convertidor de l'angiotensina, 105 sense βBloquejants i 55 sense antialdosterònics. Prevalença IR: 70%. Factors de risc: HTA, sexe femení. IC+IR+anèmia: 66 pacients, 2 tractament amb eritropoetina. Conclusions: IC de causa hipertensiva, amb FEVI conservada. Mala adequació tractament. Elevada prevalença IR. Importància Síndrome cardiorenal.

Insuficiència renal i mortalitat dels pacients cirròtics amb peritonitis bacteriana espontània i baix risc de mortalitat no tractats amb albúmina

L’expansió amb albúmina disminueix la incidència d’insuficiència renal i la mortalitat dels pacients cirròtics amb peritonitis bacteriana espontània (PBE). Però no està ben establert si caldria administrar-la a tots aquests pacients. Aquest estudi determina la incidència i evolució de la insuficiència renal i mortalitat en una sèrie no seleccionada de pacients cirròtics amb PBE i baix risc de mortalitat (urea&11mmol/l i bilirrubina&68µmol/l) no tractats amb albúmina. La baixa mortalitat i la bona evolució de la funció renal observades en els pacients amb PBE i baix risc de mortalitat no tractats amb albúmina, suggereixen que en aquests pacients no caldria administrar albúmina.

Time course of in vitro maturation of intra-erythrocytic malaria parasite: a comparison between Plasmodium falciparum and Plasmodium knowlesi

The schizont maturation assay for in vitro drug sensitivity tests has been a standard method employed in the global baseline assessment and monitoring of drug response in Plasmodium falciparum. This test is limited in its application to synchronous plasmodial infections because it evaluates the effect of drug on the maturation of parasite especially from ring to schizont stage and therefore synchronized P. falciparum cultures are required. On the other hand, P. knowlesi, a simian malaria parasite has a unique 24-h periodicity and maintains high natural synchronicity in monkeys. The present report presents the results of a comparative study on the course of in vitro maturation of sorbitol synchronized P. falciparum and naturally synchronous P. knowlesi. Ring stage parasites were incubated in RPMI medium supplemented with 10-15% pooled homologous serum in flat-bottomed 96-well micro plates using a candle jar at 37°C. The results suggest that the ideal time for harvesting the micro-assay plates for in vitro drug sensitivity test for sorbitol-synchronized P. falciparum and naturally synchronous P. knowlesi are from 26 to 30 h and from 22 to 25 h, respectively. The advantages of using P. knowlesi in chemotherapeutic studies are discussed.

Efecto del cambio de posición de decúbito supino a decúbito prono en la presión intraabdominal y su relación con la función renal

Es tracta d’un estudi observacional prospectiu en 18 pacients afectats de la síndrome de destret respiratori agut que van requerir un canvi de posició de decúbit supí a decúbit pron per tal de millorar l’oxigenació. La hipòtesi de treball era que aquest canvi de posició podia augmentar la pressió intraabdominal i, en conseqüència, alterar la funció renal per causa prerrenal. Foren registrades variables hemodinàmiques, respiratòries i pressions intrabdominals, i valorada la funció renal. La posició en decúbit pron va produir un augment significatiu de la pressió intraabdominal, però no varem objectivar un descens del filtrat glomerular ni un empitjorament de l’aclariment de creatinina

Renograma 99mTc Post-Captoprilen la valoración de la hipertensión vásculo-renal en pacientes portadores de injerto renal.

Objectiu: Descripció de la metodologia del renograma isotòpic basal/postcaptopril (RIB/P) en pacients portadors de empelt renal amb sospita de malaltia vasculo-renal (MVR). Material i mètodes: Es va realitzar en 44 pacients trasplantats renals un renograma basal i 48 hores després un renograma postcaptopril administrant 25 mg de captopril v.o i realitzant una adquisició 30 minuts després. Resultats: Dels 44 estudis 6 van ser positius, constatant-se MVR per angio-TC i 38 van ser negatius tractats posteriorment amb IECAs o ARAII i no van mostrar alteracions significatives del funcionalisme renal. Conclusions: El RIB/P es una eina útil para determinar MVR en pacients amb empelt renal i hipertensió arterial.

Associació entre la malaltia renal crònica i la malaltia cardiovascular a la població general mediterrània

La malaltia renal crònica (MRC) inicial s’ha definit com un marcador de risc cardiovascular susceptible d’intervenció terapèutica preventiva. Aquesta relació ha estat poc estudiada al nostre entorn. Objectius: Determinar si la MRC s’associa a un increment de risc de morbiditat i mortalitat al nostre entorn. Disseny: Estudi observacional prospectiu d’una cohort poblacional de Girona de 31.612 individus de 35-74 anys. Resultats: La MRC estadi 3 sense albuminúria no incrementa el risc de malaltia cardiovascular en població general de baix risc cardiovascular. L’albuminúria&20mg/L i els estadis 4-5 de MRC s’associen a un increment de risc de morbiditat cardiovascular i mortalitat global.