Disease recurrence in paediatric renal transplantation

Renal transplantation (Tx) is the treatment of choice for end-stage renal disease. The incidence of acute rejection after renal Tx has decreased because of improving early immunosuppression, but the risk of disease recurrence (DR) is becoming relatively high, with a greater prevalence in children than in adults, thereby increasing patient morbidity, graft loss (GL) and, sometimes, mortality rate. The current overall graft loss to DR is 7–8%, mainly due to primary glomerulonephritis (70–80%) and inherited metabolic diseases. The more typical presentation is a recurrence of the full disease, either with a high risk of GL (focal and segmental glomerulosclerosis 14–50% DR, 40–60% GL; atypical haemolytic uraemic syndrome 20–80% DR, 10–83% GL; membranoproliferative glomerulonephritis 30–100% DR, 17–61% GL; membranous nephropathy ∼30% DR, ∼50% GL; lipoprotein glomerulopathy ∼100% DR and GL; primary hyperoxaluria type 1 80–100% DR and GL) or with a low risk of GL [immunoglobulin (Ig)A nephropathy 36–60% DR, 7–10% GL; systemic lupus erythematosus 0–30% DR, 0–5% GL; anti-neutrophilic cytoplasmic antibody (ANCA)-associated glomerulonephritis]. Recurrence may also occur with a delayed risk of GL, such as insulin-dependent diabetes mellitus, sickle cell disease, endemic nephropathy, and sarcoidosis. In other primary diseases, the post-Tx course may be complicated by specific events that are different from overt recurrence: proteinuria or cancer in some genetic forms of nephrotic syndrome, anti-glomerular basement membrane antibodies-associated glomerulonephritis (Alport syndrome, Goodpasture syndrome), and graft involvement as a consequence of lower urinary tract abnormality or human immunodeficiency virus (HIV) nephropathy. Some other post-Tx conditions may mimic recurrence, such as de novo membranous glomerulonephritis, IgA nephropathy, microangiopathy, or isolated specific deposits (cystinosis, Fabry disease). Adequate strategies should therefore be added to kidney Tx, such as donor selection, associated liver Tx, plasmatherapy, specific immunosuppression protocols. In such conditions, very few patients may be excluded from kidney Tx only because of a major risk of DR and repeated GL. In the near future the issue of DR after kidney Tx may benefit from alternatives to organ Tx, such as recombinant proteins, specific monoclonal antibodies, cell/gene therapy, and chaperone molecules

Preparo do intestino grosso para a coloscopia: usos, abusos e idéias controversas Bowel preparation for colonoscopy: myths and misconceptions

O uso rotineiro do exame coloscópico para avaliação, diagnóstico e procedimentos terapêutico das doenças dos cólons e do reto, bem como para rastreamento e prevenção do câncer colorretal, seja em pessoas jovens portadores de doenças reconhecidamente pré-malignas ou em pessoas acima do 50 anos de idade, tem sido considerado um dos mais bem sucedidos projetos de saúde pública de extensão mundial. A fácil aceitação se deve a três principais fatores: primeiro, à adequação técnica e evolução dos aparelhos e a segurança do exame; segundo, ao desenvolvimento prático das habilidades do examinador e, terceiro, a magnificência da imagem revelando amplo acesso às finas características da mucosa, com critérios abrangentes para o diagnóstico. Nesse contexto, o preparo necessário para o resultado expressivo que se intenta tornou-se a parte pior ou menos tolerável da coloscopia, razão pela qual o que está em discussão atualmente é a necessária busca com o objetivo de se encontrar um método de preparo, rápido, eficiente, barato, agradável e, principalmente seguro. Nos últimos 40 anos, entre as várias fórmulas - mecânicas e farmacológicas - com diferentes associações de drogas laxativas, tem sido possível destacar três produtos que, pelo menos por algum tempo, foram referências mundiais na limpeza dos cólons que antecede a coloscopia. São eles: primeiro, a solução de manitol a 10% - descartado por causa de acidentes explosivos; segundo, as soluções de polietileno glicol (PEG), depreciado por conta da exigência da ingestão oral de grandes volumes, pelos consequentes distúrbios do equilíbrio hidroeletrolítico e pela rejeição por parte do paciente; e, o terceiro, o fosfato de sódio (NaP) que poderia parecer ideal, mas vem recebendo críticas veementes por causa de seus efeitos colaterais, mormente os nefrotóxicos. Não está em jogo a eficácia desses três produtos, mas a segurança que deveria determinar seus usos indiscriminados para propiciar as melhores condições para os mais adequados exames. Estamos diante de um impasse: o manitol, mundialmente proscrito, continua sendo indicado entre nós, sem causar problemas, num esquema posológico diferente do que foi usado no passado e que influenciou os acidentes. Por outro lado, a industria farmacêutica não conseguiu popularizar o PEG; o NaP, fabricado para uso retal, substituiu os antecessores com limpeza eficiente, mas com ações lesivas significativas, principalmente renais. Assim, o que nos resta é resgatar o manitol - demonstrar por meio de um estudo prospectivo, casualizado, que o manitol a 10% ingerido pelo menos até 4 horas antes da coloscopia é totalmente inócuo para o procedimento de diagnóstico e de terapêutica.<br>The routine of the colonoscopic examination for therapeutic evaluation, for diagnosis, and management of the diseases of the colon and of the rectum, as well as for screening and prevention of the colorectal cancer in young patients bearing premalignant diseases or in those above 50 years of age, as well as for screening and prevention of the colorectal cancer in young patients bearing premalignant diseases or in those above 50 years of age, "has been one of the most successful public health projects worldwide71". The easy acceptance is due to three principal factors: first, to the technical adaptation and evolution of the instruments, and the safety of the examination; second one, to the practical development of the examiner skills, and, thirdly, to the magnificence of the image revealing broad access to the fine structures of the mucous membrane, with a large criteria for the diagnosis. In this context, the necessary preparation became the worst part or less tolerable of the colonoscopy. For this reason, it is necessary to look for a method of preparation, quick, efficient, cheap, pleasant, and safe. In the last 40 years, between the commentaries on mechanical and pharmacological methods - with different associations of laxative drugs - it was possible to find three products that, at least during some time, were world-wide references on large bowel cleaning for colonoscopy. They are: first, a 10% mannitol solution - it was dropped because of explosives accidents -; second, the polyethylene glycol (PEG) solutions, it was depreciated due to the requirement of large volumes for oral ingestion, due to electrolytic balance disturbance and rejection by the patient, and the third, the sodium phosphate (NaP) that would seem ideal, but that has received criticism because of its side effects, especially the nephrotoxicity. There is no the discussion on the efficiency of these three products, but on the safety with which we might promote their indiscriminate uses to offer the best conditions on performance of the colonoscopy. However, we have an impasse: the mannitol was abandoned, but it keeps on indicated among us, without causing problems, in a scheme that is different from which was used in the past when it influenced the accidents. On the other hand, the pharmaceutical industry did not manage to popularize PEG; the NaP is manufactured for rectal use, it substituted the predecessors with efficient cleaning, but with significantly harmful lesions. So, which remains for us is to rescue the mannitol - for that, we must evidence through a randomized trial that a oral ingestion of 10% mannitol solution, at least up to 4 hours before the colonoscopy, is totally harmless on diagnosis and therapeutic procedures