Crioglobulinemia mixta no relacionada con virus de la hepatitis C, glomerulonefritis mesangiocapilar y linfoma linfoplasmocitario / Mixed cryoglobulinaemia not related to hepatitis C virus, mesangiocapillary glomerulonephritis and lymphoplasmocytic lymphoma

La afectación renal asociada a linfoma es un fenómeno conocido pero frecuentemente no caracterizado debido a la baja frecuencia con que se realizan biopsias en estos pacientes. Varios patrones histológicos pueden coexistir y pasar desapercibidos sin un estudio histopatológico. La infiltración parenquimatosa renal por linfoma no es infrecuente, y se ha encontrado hasta en un 34% (post mortem) y 14% (pre mortem), aunque tiene una baja incidencia de manifestaciones clínicas. Existen diferentes patrones de lesión renal asociados a linfoma y destaca la asociación de enfermedad de cambios mínimos con linfoma de Hodgkin. La afectación renal asociada a paraproteínas sintetizadas por un linfoma linfoplasmocitario es una asociación excepcional pese a que existen un 20% de pacientes afectados por dichos linfomas que presentan crioglobulinemia. En la literatura se han publicado casos de enfermedad de cadenas ligeras, amiloidosis, glomerulonefritis inmunotactoide como causas de paraproteinemia, proteinuria e insuficiencia renal en pacientes con linfoma. Presentamos un caso de asociación entre paraproteinemia, glomerulonefritis membrano-proliferativa y la aparición clínicamente evidente de un linfoma linfoplasmocitario en ausencia de infección por virus de la hepatitis C. Esto demuestra la afectación polimorfa que pueden presentar los linfomas en el riñón y el valor de la nefropatología en el diagnóstico y pronóstico de las enfermedades hematológicas que cursan con paraproteinemia (AU)

Kidney involvement associated to lymphoma is a known phenomenon but frequently not characterized due to the low frequency with which biopsies are realized in these patients. Several histological patterns can co-exist and happen unnoticed without a biopsy. Parenchyma infiltration in kidney for lymphoma has been found in 34% (post-mortem) and 14% (pre-mortem) and have low incident of clinical manifestations. Other patterns of renal injury are associated to lymphomaand minimal changes disease is especially related with Hodgkin's lymphoma. Renal lesions associated to paraprotein in lymphoplasmocitic lymphoma are an exceptional association, in spite of in 20% of them, appear cryoglobulinemia. There are a few cases reported in the literature with different histological patterns: light-chain disease, amyloidosis, and immuotactoid glomerulopathy related with kidney injury in patients with lymphoma. A 39-year-old male presented an association among paraproteinemia, membrano-proliferative glomerulonephritis no hepatitis C virus related and lymphoplasmocitic lymphoma with renal infiltration. This case emphasized the variety of renal lesions that lymphomas could trigger and the value of the nephropatology in the diagnosis and outcome of the hematologic diseases with paraproteinemia (AU)

¿Cuánto tiempo es necesario aumentar la prescripción de hemodiálisis con la utilización de catéteres? / No disponible

En los últimos años hemos observado un aumento progresivo en el porcentaje de pacientes de hemodiálisis que utilizan catéteres centrales tunelizados como acceso vascular permanente, situándose las tasas de prevalencia e incidencia entorno al 7 y 25%, respectivamente. A pesar de que los catéteres actuales permiten la obtención de mayores flujos sanguíneos y menores complicaciones infecciosas, las dosis de diálisis obtenidas resultan inferiores a las alcanzadas mediante la utilización de fístulas arterio-venosas nativas (FAV) y prótesis vasculares. El objetivo principal del presente estudio fue valorar el tiempo adicional para obtener una dosis óptima de diálisis mediante la utilización de catéteres centrales venosos tunelizados. Dicha premisa se basa en la obtención de menores flujos sanguíneos (Qb) así como de posibles disfunciones vasculares que en diferentes ocasiones obligan a invertir las líneas arterio-venosas. Se analizaron un total de 48 pacientes (31 varones/17 mujeres) con una edad media de 61,6 ± 14 años (rango: 28-83); 20 con catéteres centrales tunelizados y 28 con FAV nativas. Todos los pacientes incluidos en el estudio se dializaron con la modalidad de hemodiálisis de alto flujo, con polisulfona de 1,9 m2, con una duración de 240 minutos, con flujo baño a 500 ml/min y monitores equipados con dialisancia iónica (DI). El objetivo principal de análisis fue la obtención de un Kt de 45 litros con cada uno de los diferentes accesos vasculares. Los pacientes portadores de una FAV recibieron 3 sesiones con variaciones de Qb a 300, 350 y 400 ml/min. Los pacientes con catéteres tunelizados recibieron dos sesiones de diálisis al máximo Qb, una con conexión de líneas normales y otra con líneas invertidas. Entre los resultados obtenidos cabe destacar que sólo los pacientes portadores de una FAV con un Qb de 400 ml/min alcanzaron el objetivo de Kt de 45 litros. Los sujetos con FAV precisaron incrementar 12 minutos de hemodiálisis con Qb de 350 ml/min y 28 minutos con Qb de 300 ml/min; los catéteres tunelizados en posición normal 24 minutos y los invertidos un total de 59 minutos. Concluimos que los pacientes dializados con catéteres centrales venosos tunelizados necesitan para alcanzar una dosis mínima de diálisis (Kt de 45 litros), incrementar por término medio 30 minutos el tiempo de la sesión si funciona en posición normal y 60 minutos en posición invertida de líneas arterio-venosas (AU)

The use of central catheters in hemodialysis patients as a permanent vascular access has increased during the last years, reaching numbers of around 7% of prevalent patients and between 25% of incident patients. Although the current catheters allow higher sanguineous flows with smaller incidence of infectious complications and dysfunction, the dose of dialysis that is reached is still inferior to that obtained with native arterio-venous fistula (AVF) and grafts. The aim of the present study was to evaluate the possible additional time supposed by dialysis using central venous catheters with respect to habitual vascular access as a consequence of the lesser blood flow (Qb) and the irregularity of its function (frequent lowering of the Qb and necessity of inverting the lines on many occasions). A total of 48 patients (31 men/17 women) with an average age of 61.6 ± 14 years old (rank: 28-83), 20 with tunnelled catheter and the remaining with AVF, were included in the study. All the patients were dialyzed in the modality of high flux hemodialysis with a polisulphone of 1.9 m2 dialyzer, dialysis time of 240 minutes, dialysate flow 500 ml/min and monitors equipped with ionic dialysance (ID) with the objective of obtaining a Kt of 45 litres with each one of the different vascular accesses. The patients with AVF received 3 sessions, with variations of Qb to 300, 350 and 400 ml/min. The patients with tunnelled catheter received two sessions, to the maximum Qb, one with normal connection and other with inverted one. In the results obtained it is possible to emphasize that only the patients with AVF and 400 ml/min reached the objective of 45 L of Kt. The patients with AVF needed to increase 12 minutes of hemodialysis with a Qb of 350 ml/min and 28 minutes with a Qb of 300 ml/min; the catheters on normal position needed to increase 24 minutes and finally in the inverted catheters an increase of 59 minutes was necessary to reach the same Kt objective. We concluded that the patients dialyzed with central catheters on average needed to increase by 30 minutes the time of dialysis if the catheter worked in a normal position but 60 minutes if the arterio-venous lines were inverted so as to reach the minimum dose of dialysis (AU)

Kt como control y seguimiento de la dosis en una unidad de hemodiálisis / Kt as control and follow-up of the dose at a hemodialysis unit

Asegurar que el paciente recibe la dosis adecuada en cada sesión de diálisis debe ser un objetivo a conseguir a corto o medio plazo. La incorporación de la dialisancia iónica (DI) en los monitores durante los últimos años ha permitido monitorizar la dosis de hemodiálisis en tiempo real y en cada sesión. Lowrie y cols., recomiendan el seguimiento de la dosis con el Kt, recomendando un mínimo de 40 L en mujeres y 45 en hombres o individualizar la dosis por área de superficie corporal. El objetivo del presente estudio era hacer un seguimiento de la dosis con el Kt en cada sesión durante 3 meses, y comparar con la analítica mensual habitual. 51 pacientes (58% de la Unidad de hemodiálisis), 32 varones y 19 mujeres, de 60,7 ± 14 años de edad, en programa de hemodiálisis durante 37,7 ± 52 meses, se dializaron con monitor con DI de forma rutinaria. La etiología de su IRC era de 3 NTI, 9 GNC, 12 nefroangiosclerosis, 7 poliquistosis renal, 7 diabetes mellitus y 13 no filiada. Se analizaron 1.606 sesiones durante 3 meses. Cada paciente recibió la pauta habitual de HD, con dializadores de diacetato de celulosa de 2,1 m2 (33,3%), polisulfona de 1,9 m2 (33,3%) y helixona de 1,8 m2, con duración de 263 ± 32 minutos, con un flujo sanguíneo de 405 ± 66, con flujo baño a 712 ± 138 ml/min, peso seco de 66,7 ± 14 kg. Se valoró la DI inicial, la DI final y el Kt en cada sesión y el PRU y el Kt/V mediante la analítica mensual. La DI inicial fue de 232 ± 41 ml/min, la DI final de 197 ± 44 ml/min, la dosis media de Kt fue de 56,6 ± 14 L, el Kt/V medio de 1,98 ± 0,5 y el PRU de 79,2 ± 7%. Todos los pacientes recibieron una dosis mínima de Kt/V y PRU de 1,3 y 70%, respectivamente. No obstante, si utilizamos el Kt según el sexo, observamos que el 31% de los pacientes no alcanzaban la dosis mínima prescrita (48,1 ± 2,4 L), 34,4% de los hombres y el 26,3% de las mujeres. Si utilizamos el Kt individualizado por su superficie corporal, (49,1 ± 4 L), observamos que el 43.1% de los pacientes no alcanzaban la dosis mínima prescrita, con 4,6 ± 3,4 L menos de dosis. Concluimos que el seguimiento de la dosis de diálisis con el Kt, permite una mejor discriminación de la adecuación de diálisis, identificando entre el 30 y el 40% de pacientes que quizá no alcanzasen una dosis adecuada para su género o para su superficie corporal (AU)

To ensure our patients are receiving an adequate dose in every dialysis session there must be a target to achieve this in the short or medium term. The incorporation during the last years of the ionic dialysance (ID) in the monitors, has provided monitoring of the dialysis dose in real time and in every dialysis session. Lowrie y cols., recommend monitoring the dose with Kt, recommending at least 40 L in women and 45 L in men or individualizing the dose according to the body surface area. The target of this study was to monitor the dose with Kt in every dialysis session for 3 months,and to compare it with the monthly blood test. 51 patients (58%of our hemodialysis unit), 32 men and 19 women, 60.7 ± 14 years old, in the hemodialysis program me for 37.7 ± 52 months, were dialysed with a monitor with IC. The etiology of their chronic renalfailure was: 3 tubulo-interstitial nephropathy, 9 glomerulonephritis,12 vascular disease, 7 polycystic kidney disease, 7 diabetic nephropathy and 13 unknown. 1,606 sessions were analysed during a 3 month period. Every patient was treated with the usual parameters of dialysis with 2.1 m2 cellulose diacetate (33.3%), 1.9m2 polisulfone (33.3%) or 1.8 m2 helixone, dialysis time of 263 ±32 minutes, blood flow of 405 ± 66, with dialysate flow of 712 ±138 and body weight of 66.7 ± 14 kg. ITo ensure our patients are receiving an adequate dose in every dialysis session there must be a target to achieve this in the short or medium term. The incorporation during the last years of the ionic dialysance (ID) in the monitors, has provided monitoring of the dialysis dose in real time and in every dialysis session. Lowrie y cols., recommend monitoring the dose with Kt, recommending at least 40 L in women and 45 L in men or individualizing the dose according to the body surface area. The target of this study was to monitor the dose with Kt in every dialysis session for 3 months, and to compare it with the monthly blood test. 51 patients (58% of our hemodialysis unit), 32 men and 19 women, 60.7 ± 14 years old, in the hemodialysis programme for 37.7 ± 52 months, were dialysed with a monitor with IC. The etiology of their chronic renal failure was: 3 tubulo-interstitial nephropathy, 9 glomerulonephritis, 12 vascular disease, 7 polycystic kidney disease, 7 diabetic nephropathy and 13 unknown. 1,606 sessions were analysed during a 3 month period. Every patient was treated with the usual parameters of dialysis with 2.1 m2 cellulose diacetate (33.3%), 1.9 m2 polisulfone (33.3%) or 1.8 m2 helixone, dialysis time of 263 ± 32 minutes, blood flow of 405 ± 66, with dialysate flow of 712 ± 138 and body weight of 66.7 ± 14 kg. Initial ID, final ID and Kt were measured in each session. URR and Kt/V were obtained by means of a monthly blood test. The initial ID was 232 ± 41 ml/min, the final ID was 197 ± 44 ml/min, the mean of Kt determinations was 56.6 ± 14 L, the mean of Kt/V was 1.98 ± 0.5 and the mean of URR was 79.2 ± 7%. Although all patients were treated with a minimum recommended dose of Kt/V and URR when we used the Kt according to gender, we observed that 31% of patients do not get the minimum dose prescribed (48.1 ± 2.4 L), 34.4% of the men and 26.3% of the women. If we use the Kt individualized for the body surface area, we observe that 43.1% of the patients do not get the minimum dose prescribed with 4.6 ± 3.4 L less than the dose prescribed. We conclude that the monitoring of dialysis dose with the Kt provides a better discrimination detecting that between 30 and 40% of the patients perhaps do not get an adequate dose for their gender or body surface areanitial ID, final ID and Kt (..) (AU)

Conversion from tacrolimus to cyclosporine could improve control of posttransplant diabetes mellitus after renal transplantation.

Posttransplant diabetes mellitus (PTDM) occurs in approximately 15% to 20% of renal transplant patients. It has important clinical implications for graft function and survival. Anticalcineurin drugs are associated with an increased risk of developing PTDM. There is a little evidence that conversion from tacrolimus to cyclosporine (CsA)-based immunosuppression improves glucose metabolism and reverses diabetes. This prospective study included nine renal transplant patients (mean age of 34 +/- 20) with PTDM under immunosuppression with tacrolimus. Five were switched directly to CsA and the other four (glycemia > 250 mg/dL) required insulin and were simultaneously switched to CsA. Basal blood levels of tacrolimus were 7.9 +/- 1.9 ng/dL. Conversion was associated with an early, significant improvement of glycemia and HbA1c blood levels (P < .01). At the end of the follow-up, the glycemia (105 +/- 20 mg/dL) and Hb1Ac (5.1 +/- 0.4 mg/dL) were normal. Insulin was discontinued between 3 and 6 months in all patients who required it at the beginning. Cholesterol did not change significantly and triglycerides decreased significantly (basal 210 +/- 85 mg/dL, at 12 months 125 +/- 29, P < .01). Graft function was stable with a mean serum creatinine of 1.7 +/- 0.2 mg/dL. CsA blood levels remained stable during all follow-up periods (P = NS). There were neither episodes of acute rejection nor secondary effects related to the medication. In summary, renal transplant patients receiving tacrolimus who develop PTDM may display better control of hyperglycemia by a switch to CsA.

Increased anandamide induced relaxation in mesenteric arteries of cirrhotic rats: role of cannabinoid and vanilloid receptors.

BACKGROUND AND AIMS: Anandamide is an endocannabinoid that evokes hypotension by interaction with peripheral cannabinoid CB1 receptors and with the perivascular transient receptor potential vanilloid type 1 protein (TRPV1). As anandamide has been implicated in the vasodilated state in advanced cirrhosis, the study investigated whether the mesenteric bed from cirrhotic rats has an altered and selective vasodilator response to anandamide. METHODS: We assessed vascular sensitivity to anandamide, mRNA and protein expression of cannabinoid CB1 receptor and TRPV1 receptor, and the topographical distribution of cannabinoid CB1 receptors in resistance mesenteric arteries of cirrhotic and control rats. RESULTS: Mesenteric vessels of cirrhotic animals displayed greater sensitivity to anandamide than control vessels. This vasodilator response was reverted by CB1 or TRPV1 receptor blockade, but not after endothelium denudation or nitric oxide inhibition. Anandamide had no effect on distal femoral arteries. CB1 and TRPV1 receptor protein was higher in cirrhotic than in control vessels. Neither CB1 mRNA nor protein was detected in femoral arteries. Immunochemistry showed that CB1 receptors were mainly in the adventitia and in the endothelial monolayer, with higher expression observed in vessels of cirrhotic rats than in controls. CONCLUSIONS: These results indicate that anandamide is a selective splanchnic vasodilator in cirrhosis which predominantly acts via interaction with two different types of receptors, CB1 and TRPV1 receptors, which are mainly located in perivascular sensory nerve terminals of the mesenteric resistance arteries of these animals.

Effect of calcineurin inhibitors on low-density lipoprotein oxidation.

INTRODUCTION: Low-density lipoprotein (LDL) oxidation is considered a key factor in the biological processes that trigger and accelerate atherosclerosis. Reported data suggest that tacrolimus improves the lipid profile in renal transplant recipients. OBJECTIVE: The objective of this study was to analyze the effect of converting from cyclosporine to tacrolimus on lipoprotein oxidation in renal transplant recipients. METHODS: We studied a group of 12 recipients (6 men and 6 women of mean age 55 +/- 11 years) treated with a cyclosporine-mycophenolate mofetil (MMF)-prednisone combination that was converted to tacrolimus-MMF-prednisone because of gingival hyperplasia. The LDL fraction was isolated by density-gradient ultracentrifugation. Oxidative stress was studied before converting (baseline) and at 6 and 12 weeks, thereafter by in vivo oxidation analysis of LDL, a direct assay of oxidized LDL (oxLDL) and oxLDL autoantibodies (Ab-oxLDL) using enzyme-immunoassay techniques. We measured total cholesterol (TC), triglyceride, LDL-cholesterol, high-density lipoprotein (HDL)-cholesterol, ApoA1, ApoB, and Lp(a) levels. RESULTS: The change to tacrolimus resulted in significant decreases in TC levels, 213 +/- 30 (B) versus 185 +/- 27 (12s) (P < .01); LDL, 129 +/- 24 (B) versus 104 +/- 14 (12s) (P = .002); and ApoB 98 +/- 15 (B) versus 85 +/- 10 (12s) (P < .01). HDL levels significantly increased (45 +/- 10 vs 48 +/- 10 [12s]; P = .018), whereas oxLDL concentrations decreased significantly after conversion (B) (55.42 +/- 10.61 vs 12s 45.76 +/- 10.21; P < .01). Converting to tacrolimus produced a nonsignificant decrease in Ab-oxLDL (baseline 204.88 +/- 134.49 vs 12s 179.51 +/- 143.54). A correlation was observed between LDL and oxLDL (r = 65, P = .02 [B] and r = 0.7, P = .01 [12s]) but not between oxLDL levels and Ab-oxLDL concentration (r = -0.05, P = .87 [3] and r = -0.1, P = .77 [12s]). CONCLUSIONS: In renal transplantation, tacrolimus therapy was associated with a better lipid profile and lower in vivo LDL oxidation when compared with cyclosporine treatment.

IV. Nuevos métodos diagnósticos en el trasplante renal: a) Análisis de factores de riesgo genéticos asociados a la nefropatía crónica del trasplante renal: polimorfismos genéticos de citoquinas, moléculas de adhesión, sistema de coagulación-plaquetar y marcadores de riesgo cardiovascular / No disponible

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Disfunción endotelial en trasplante renal / Endothelial dysfunction in renal transplantation

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Trasplante renal en pacientes virus de la hepatitis C positivos / Kidney transplantation in HCV patients

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Riesgo cardiovascular en el paciente trasplantado renal / Cardiovascular risk in the renal transplanted patient

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Prevención del riesgo cardiovascular en el trasplante renal. Documento de consenso / Prevention of cardiovascular risk in renal transplantation: a consensus document

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Citomegalovirus atípico en el trasplante renal: una nueva forma de presentación / Atypical cytomegalovirus in renal transplantation: a new form of presentation

La infección por citomegalovirus (CMV) es la infección oportunista más frecuente en el trasplante renal (TR). La infección asintomática es la forma más común de manifestarse. La enfermedad por CMV (ECMV) se manifiesta habitualmente en forma de fiebre, leucopenia, trombopenia y leve aumento de transaminasas. Actualmente, el desarrollo de formas invasivas severas es poco frecuente con la monitorización post-trasplante del CMV, las pautas de profilaxis o tratamiento anticipado en pacientes de alto riesgo y el tratamiento precoz con ganciclovir. Se describen dos pacientes trasplantados renales de edad avanzada en tratamiento con tacrolimus, micofenolato y prednisona que debutaron con una hemorragia digestiva severa como forma de presentación de la ECMV a las 9 y 14 semanas post-TR. En ambos pacientes la monitorización post-trasplante mediante antigenemia pp65 fue negativa. Un paciente debutó en forma de shock hipovolémico por rectorragias severas detectando una úlcera sangrante atípica en la válvula ileocecal. El otro paciente presentó una hemorragia digestiva alta con una úlcera duodenal sangrante. El estudio histológico e inmunohistoquímico confirmó el diagnóstico. Se discute la influencia del micofenolato-mofetil y los nuevos fármacos inmunosupresores en el desarrollo de la infección por CMV (AU)

Riesgo cardiovascular en el paciente trasplantado renal / Cardiovascular risk in the kidney transplant patient

El trasplante renal ha experimentado en los últimos años un avance espectacular, mejorando de manera significativa la calidad y las expectativas de vida del enfermo renal. No obstante, la mortalidad cardiovascular se ha constituido en los últimos años como la primera causa de muerte del trasplantado renal, por delante de las infecciones y de los procesos neoplásicos. Las razones que han motivado este incremento de la mortalidad cardiovascular son: 1) Un cambio profundo en las características del donante y del receptor renal. 2) Un descenso significativo en la mortalidad en el post-trasplante inmediato, y 3) Una elevada prevalencia de factores de riesgo cardiovascular en el post-trasplante renal a largo plazo (AU)

Renal transplants have experienced a spectacular development in recent years, significantly improving the quality of life and life expectancy of patients. However, mortality due to cardiovascular disease in recent years has become the first cause of death in renal transplant patients, ahead of infections and neoplasic disorders. The causes of this increase are due to the following reasons: 1) Important changes in the characteristics of the donor and the renal receptor. 2) A significant decrease in the immediate post-transplant mortality rates, and 3) increase in the incidence of cardiovascular risk factors in transplant patients (AU)

Trasplante renal utilizando riñones de donantes con serología positiva para el virus de la hepatitis C / Renal transplantation using kidneys from donors with hepatitis C virus positive serology

La infección por el virus de la hepatitis C (VHC) se transmite con el trasplante de órganos. La mayoría de los autores coincide en la opinión de no utilizar riñones procedentes de donantes VHC positivos en receptores con serología negativa para el VHC. Sin embargo, su uso en receptores VHC positivos sigue siendo controvertida. Revisamos a continuación la experiencia existente en este campo, experiencia que avala la seguridad de este procedimiento a corto y largo plazo cuando se limita el uso de estos riñones a receptores con serología positiva para el VHC y, especialmente, cuando estos receptores presentan a su vez positividad para el RNA viral antes del trasplante. Conseguir emparejar donante y receptor en función del genotipo viral implicado sería el próximo paso a considerar con vistas a proporcionar una mayor seguridad a esta política. Dada la alta prevalencia que la infección por el VHC alcanza en determinadas poblaciones, esta estrategia podría ampliar considerablemente el número de donantes disponibles para trasplante (AU)

Hepatitis C virus (HCV) infection is transmitted by organ transplantation. The majority of the groups agree with the no utilization of kidneys from HCV positive donors into HCV negative recipients. However, it is still a controversial issue wether to use these organs in patients with a positive serology for HCV. We review the actual experience in this field of kidney transplantation. There are clinical studies that demonstrate that the use of HCV positive kidneys into HCV positive recipients is a safe strategy in the short and the long term, specially when these organs are limited to those patients with a positive HCV RNA before transplantation. Efforts to make this policy even safer should be made, such as matching donors and recipients in terms of the genotype of the HCV. Given the high prevalence that HCV infection has in some populations, the donor pool could considerably increase if these strategies were universally applied (AU)