Experiencia del Hospital Universitario de Canarias con pacientes tratados con plasmaféresis / Patients treated with plasmapheresis: a case review from University Hospital of the Canary Islands

Introducción: La plasmaféresis (PF) es una técnica de aféresis terapéutica utilizada en el tratamiento de diversas enfermedades renales y sistémicas con distintos grados de eficacia clínica demostrada. Objetivo: Analizar los resultados globales de la indicación de PF en el Hospital Universitario de Canarias, enfocados a resultados de su efectividad y seguridad en diversos grupos de enfermedades. Material y métodos: Se trata de un análisis descriptivo retrospectivo de una serie de casos que analiza los resultados de la indicación de PF desde el uno de enero de 2006 hasta el 31 de diciembre de 2009 en nuestro centro. Se revisaron las historias clínicas y se recogieron datos demográficas (sexo y edad), parámetros bioquímicos, enfermedad de base, volumen y tipo de reposición utilizado en la sesión de PF (albúmina humana al 5% y/o plasma fresco congelado), complicaciones asociadas con la técnica, días transcurridos desde la sospecha clínica diagnóstica hasta el inicio de la técnica de aféresis, número de sesiones de PF recibidas, mortalidad del paciente, grado de afectación renal y evolución de la función renal. Resultados: Estudiamos a 51 pacientes, de 50 ± 18 años, el 60% eran hombres, 331 sesiones de PF. Las enfermedades tratadas se agruparon como: 11 vasculitis, 15 inmunoactivaciones del trasplante renal, cinco síndromes hemolítico urémicos, siete casos de púrpura trombótica trombocitopénica o idiopática, dos inmunizaciones Rh fetal, dos enfermedades hematológicas y cuatro casos de enfermedades neurológicas, entre otras. La mortalidad global fue del 19,6 % (n = 10); en seis de los casos, secundaria a shock séptico y en el resto como resultado de la evolución de la enfermedad de base y uno por shock hemorrágico en el área de la biopsia renal. No hubo fallecimientos en el grupo de inmunoactivación del trasplante. En el grupo de vasculitis se produjeron tres fallecimientos (dos de ellos secundarios a un shock séptico). Nueve de los 10 pacientes que fallecieron lo hicieron dentro de los tres primeros meses tras el diagnóstico. De las 26 biopsias renales realizadas, las indicaciones más frecuentes fueron: vasculitis (23%), rechazos humorales (42%), rechazo humoral más toxicidad por anticalcineurínicos (12%) y síndrome hemolítico-urémico (8%), entre otros. Veinticuatro pacientes precisaron hemodiálisis al inicio del cuadro clínico, nueve de los 11 pacientes con vasculitis, cuatro de los cinco pacientes con síndrome hemolítico-urémico y cinco de los 15 pacientes con inmunoactivación del trasplante. Al final de la evolución, 14 de ellos permanecieron en programa de hemodiálisis. Concretamente, cinco de 11 pacientes con vasculitis, dos de 15 pacientes sometidos a trasplante y tres de cinco pacientes con síndrome hemolítico-urémico. De forma significativa, los pacientes que evolucionaron hacia enfermedad renal terminal en el grupo de las vasculitis eran de mayor edad y tenían una mayor creatinina en el comienzo de la enfermedad. En los pacientes sometidos a trasplante en quienes se monitorizaron anticuerpos anti-HLA de clases I o II medidos por luminex pre y post-PF se objetivó una media de descenso del título de anticuerpos en todos excepto en un caso; el descenso medio fue del 51 al 31%. En general, la técnica de PF transcurrió prácticamente libre de complicaciones. Se constataron cinco reacciones al plasma fresco (3%) de carácter leve-moderado (hormigueo peribucal y reacciones urticariformes) que requirieron premedicación con esteroides y no supusieron la interrupción del tratamiento. Conclusión: Teniendo en cuenta la gran variedad de enfermedades que pueden beneficiarse de la PF y el carácter esporádico de algunas de ellas, la publicación de la experiencia con esta modalidad terapéutica cobra gran importancia, ya que si incrementamos la descripción de series de casos por centros, podemos ayudar a ampliar el nivel de evidencia en términos de supervivencia y función renal en múltiples patologías infrecuentes. Nuestro estudio aporta una información útil y valiosa para la práctica clínica habitual y, sin duda, nos hace reflexionar sobre estrategias futuras que optimicen el pronóstico en nuestros enfermos (AU)

Introduction: Plasmapheresis (PP) is a therapeutic apheresis technique used in the treatment of various renal and systemic diseases with varying degrees of proven clinical efficacy. Objective: To review our experience with PP at the Hospital Universitario de Canarias, focused on effectiveness and safety results in different disease groups. Material and methods: A retrospective-descriptive study of patients treated with PP from 01/01/2006 to 31/12/2009 at the hospital. We analysed medical histories and demographic data (sex, age), biochemical parameters, underlying disease, volume and type of replacement used in the PP sessions (5% human albumin and/or fresh frozen plasma), complications with the technique, delay in starting PP treatment after suspected clinical diagnosis, number of PP sessions received, patient mortality, degree of renal impairment and evolution of renal function. Results: There were 51 patients studied, aged 50±18 years, of whom 60% were male; 331 PP sessions were performed. The diseases treated were grouped as: 11 vasculitis, 15 transplant immune activation, 5 haemolytic-uraemic syndrome (HUS), 7 idiopathic or thrombotic thrombocytopaenic purpura, 2 foetal Rh immunisations, 2 haematological diseases, 4 neurological diseases, among others. Overall mortality was 19.6% (n=10): 6 cases secondary to septic shock and the rest as a result of the evolution of the underlying disease, with 1 due to haemorrhagic shock in the renal biopsy area. There were no deaths in the transplant immune activation group. In the vasculitis group, there were 3 deaths (2 secondary to septic shock). Of the 10 patients who died, 9 did so within the first three months after diagnosis. Of the 26 renal biopsies performed, the most frequent indications were: vasculitis (23%), humoral rejection (42%), humoral rejection with calcineurin-inhibitor toxicity (12%) and HUS (8%), among others. Haemodialysis (HD) was required by 24 patients at the start of clinical symptoms: 9 of the 11 patients with vasculitis, 4 of the 5 patients with HUS and 5 of the 15 patients with transplant immune activation. At the end of evolution, 14 of them remained on the HD programme: 5 of the 11 patients with vasculitis, 2 of the 15 transplant patients and 3 of the 5 HUS patients. Significantly, patients who developed end kiney disease (EKD) in the vasculitis group were older and had higher creatinine at the onset of the disease. The transplant patients were monitored for anti-HLA class I or II before and after PP; there was a mean decrease of antibody titres in all but one patient; with an average decrease of 51% to 31%. In general, the PP technique was virtually free of complications. There were only 5 (3%) mild-moderate reactions to fresh plasma (perioral tingling and urticarial reactions) requiring pre-medication with steroids, but which did not lead to discontinuation of the treatment. Conclusion: Taking into account the wide variety of diseases that can benefit from PP and the nature of some of them, publishing our experience with this therapeutic method is of great importance. By increasing the description of case series by centre, we can add survival and renal function evidence in many uncommon diseases. Our study provides useful information for clinical practice and has also led us to reflect on future strategies to optimise outcomes in our patients (AU)

Tratamiento de inducción combinando inmunoglobulinas, plasmaféresis y rituximaben pacientes hipersensibilizados que reciben trasplante renal de cadáver / Induction treatment by combining immunoglobulins, plasmapheresis and rituximab in hypersensitive patients receiving cadaveric renal allograft

En el Hospital Universitario de Canarias pusimos en marcha, en mayo de 2008, un protocolo de tratamiento de inducción para pacientes hipersensibilizados que reciben injerto renal de cadáver utilizando inmunoglobulinas intravenosas, plasmaféresis y rituximab más una inmunosupresión triple con prednisona, tacrolimus y micofenolatomofetil. Presentamos los resultados de 4 pacientes. Todo sellos presentaban una tasa de anticuerpos anti-HLA (PARA por CDC) superior al 75%, llevaban en lista de espera de 4a 17 años, el tiempo de seguimiento posterior al trasplante fue de 10-14 meses y la supervivencia de paciente y del injerto en este período fue del 100%. Sólo un paciente sufrió un rechazo agudo mediado por anticuerpos y otro uno celular, en ambos casos reversibles con el tratamiento. En la evolución no se objetivó aparición de novo de anticuerpos donante-específicos. Todos los pacientes habían reducido significativamente el número de células CD19+ después de la infusión de rituximab. No se han detectado síntomas neurológicos indicativos de leucoencefalopatía multifocal progresiva ni infecciones virales graves después del trasplante y tampoco se han observado efectos secundarios inmediatos tras la administración de la medicación. En resumen, el tratamiento de inducción combinado con inmunoglobulinas, plasmaféresis y rituximab en pacientes (..) (AU)

In our Universitary Hospital of Canarias we iniciated in May2008 a induction therapy protocol for sensitized patients receiving cadaveric renal graft using intravenous immunoglobulins, plasmapheresis and rituximab plusimmuno suppression with prednisone, tacrolimus and mycophenolate mofetil. We present the results of four patients. Everyone had anti-HLA antibodies rate (PRA by CDC) more than 75%, were on a waiting list during 4 to 17 years and follow-up time was 10-14 months after transplantation. Patient and graft survival in this period was 100%. Only one patient suffered a humoral acute rejection and another one cellular rejection, in both cases reversible with treatment. During the first year, no evidence of de novo donor-specific antibodies was detected. All patients had significantly reduced the CD19+ cells percentage after infusion of rituximab. Neurological symptoms suggestive of progressive multifocal leukoencephalopathy or serious viral infections after transplantation have not been observed. Additionally, no immediate side effects were observed after administration of medication. In summary, induction therapy by combining immunoglobulin, plasmapheresis and rituximab in hypersensitive patients allows the realization of deceased kidney transplantation with good results in the short and medium-term without serious side effects. It remains to know whether this success will continue in the long term (AU)

[Induction treatment by combining immunoglobulins, plasmapheresis and rituximab in hypersensitive patients receiving cadaveric renal allograft]. / Tratamiento de inducción combinando inmunoglobulinas, plasmaféresis y rituximab en pacientes hipersensibilizados que reciben trasplante renal de cadáver.

In our Universitary Hospital of Canarias we iniciated in May 2008 a induction therapy protocol for sensitized patients receiving cadaveric renal graft using intravenous immunoglobulins, plasmapheresis and rituximab plus immunosuppression with prednisone, tacrolimus and mycophenolate mofetil. We present the results of four patients. Everyone had anti-HLA antibodies rate (PRA by CDC) more than 75%, were on a waiting list during 4 to 17 years and follow-up time was 10-14 months after transplantation. Patient and graft survival in this period was 100%. Only one patient suffered a humoral acute rejection and another one cellular rejection, in both cases reversible with treatment. During the first year, no evidence of de novo donor-specific antibodies was detected. All patients had significantly reduced the CD19+ cells percentage after infusion of rituximab. Neurological symptoms suggestive of progressive multifocal leukoencephalopathy or serious viral infections after transplantation have not been observed. Additionally, no immediate side effects were observed after administration of medication. In summary, induction therapy by combining immunoglobulin, plasmapheresis and rituximab in hypersensitive patients allows the realization of deceased kidney transplantation with good results in the short and medium-term without serious side effects. It remains to know whether this success will continue in the long term.

[A study using nondecalcified bone biopsy of the incidence and presentation forms of renal osteodystrophy]. / Estudio con biopsia ósea sin descalcificar de la incidencia y formas de presentación de la osteodistrofia renal.

BACKGROUND: Renal osteodystrophy (ROD) is a common complication of chronic renal failure. Fibrous osteitis and, to a lesser extent, osteomalacia are the predominant lesions. The aim of the present study was to evaluate the prevalence of the different forms of ROD. METHODS: Nondecalcified bone biopsies were evaluated in 100 patients with end-stage renal disease (57 in pre-dialysis and 43 on hemodialysis) in whom biochemical (calcium, phosphorus, alkaline phosphatase, parathyroid hormone) and histomorphometric studies were carried out. Bone biopsies were classified in four histological groups: mild, fibrous osteitis (FO), osteomalacia (OM) and mixed type (FO + OM). RESULTS: 96% of patients had histological findings of ROD with the following distribution: 41% mild; 30% FO; 14% OM; and 11% mixed. The most advanced types of ROD were seen in interstitial renal diseases. Pre-dialysis OM was associated with metabolic acidosis, a low phosphocalcic product and relative hypophosphoremia. Chronic aluminium poisoning was uncommon (7%) and was basically associated with OM. No instance of aluminium poisoning with osteodystrophy and bone fractures was seen. CONCLUSIONS: The most severe histological forms of OM were found in hemodialysis patients with persistent hypophosphoremia and associated with osteosclerosis.

[Recovery of kidney function in a female patient with severe lupus nephropathy]. / Recuperación de la función renal en una paciente con nefropatía lúpica severa.

The evolution of Lupus Nephritis to end-stage chronic renal failure is a frequent event. We report the case of a 28 years old patient with diffuse proliferative lupus nephritis with crescents formation and rapid decline of renal function without response to steroids, immunosuppressors and plasmapheresis. After 10 weeks of continued hemodialysis, during which the patient received 30 mg of prednisone in alternate days, renal function recovered spontaneously, and after 1 year of follow-up plasma creatinine is maintained in 2.5 mg/dl.