RESUMO
Anti-HLA alloantibodies are the main barrier in kidney transplantation. Lack of appropriate donors for highly sensitized (HS) recipients makes access to transplantation very difficult and results in a significant increase in both the time on the waiting list and the number of post-transplant complications in these patients. The transplantation itself is also associated with higher risk in the HS. There are many programs aimed at increasing access to renal transplantation for this group of recipients. It is noteworthy that new acceptable HLA-mismatches allowed significant progress in programs for HS recipients. Currently implemented programs (ET-AMP, UNOS, Emory algorithm) proved useful as they increased access to transplantation and graft survival in HS patients. Nevertheless, even with these programs there is still the problem of humoral rejection in these patients. The strong correlation between donor-specific antibodies (DSA) and graft rejection seen both immediately after transplantation and in long-term complications such as CAN (chronic allograft nephropathy) may be the simplest explanation for this effect. Hence the assessment of alloantibodies limited to the pre-transplant period, which is nowadays routine, seems insufficient. Current evidence suggests that early detection of post-transplant DSA may be an excellent prognostic marker of graft function and may allow implementing the necessary treatment prior to rejection.
Assuntos
Rejeição de Enxerto/imunologia , Antígenos HLA/imunologia , Isoanticorpos/imunologia , Transplante de Rim/imunologia , HumanosRESUMO
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common causes of end stage renal failure (ESRF). Nevertheless, until now the standard therapy of ADPKD consists merely of nephroprotection and treatment of complications. In the sixth decade of life in about 50% of patients renal replacement therapy is initiated. Surgery procedures such as nephrectomy and renal contraction therapy are performed in some patients. In 21st century numerous studies concerning patophysiology of the disease (role of polycystins, intracellular calcium, cAMP) were published and gave an impulse for searching new drugs that could slower progression of ADPKD. Somatostatin receptor agonists, vasopressin V2 receptor antagonists, rapamycin, and tyrosine kinase inhibitors are among medications that are thought to be effective. Although it is unclear if any of these drugs will be really effective there are strong theoretical backgrounds and promising results of experimental studies on animals. Nephrologists and their patients are waiting for the results of clinical trials that are performed now.
Assuntos
Rim Policístico Autossômico Dominante/terapia , Humanos , Pessoa de Meia-Idade , Nefrectomia , Rim Policístico Autossômico Dominante/tratamento farmacológico , Resultado do TratamentoRESUMO
Despite changing epidemiology of chronic kidney disease, autosomal dominant polycystic kidney disease (ADPKD) is one of the most prevalent causes of end stage renal disease. The first symptoms of the disease occur usually in the 3rd or 4th decade of life, however, it can often be diagnosed much earlier. Advances in the understanding of the disease may lead, in the near future, to slowing the progression of ADPKD in asymptomatic individuals. ADPKD is diagnosed on the basis of family history (autosomal dominant inheritance) and radiological imaging. Ultrasound examination (US) of the kidneys is the most important imaging diagnostic method. US is highly sensitive and specific in patients >30 years of age. In US, Ravine criteria are applied and their modifications with other imaging techniques (computed tomography [CT], magnetic resonance [MR]). In all cases, however, there are multiple cysts in both kidneys and, importantly, concomitant renal enlargement can be observed, which is typical of ADPKD. High expectations for early ADPKD diagnosis are risen by genetics and proteomics. However, these methods are not used routinely. The most sensitive parameter in the evaluation of the disease progression is total renal volume. This parameter is presently used in clinical studies, but its utility in monitoring an individual patient has not been fully proven. Unfortunately, MR and CT are expensive and in case of significantly enlarged kidneys US does not yield accurate assessment of their size and is not sensitive enough for monitoring the disease progression. The rate of glomerular filtration rate (GFR) decline is usually constant. Therefore, it is important to monitor GFR in individuals who have developed renal insufficiency. Other tests, including markers of kidney injury, e.g. albuminuria, or vascular flow parameters, are used mainly in clinical studies. Thus, before more efficient therapeutic approaches have been developed, an early diagnosis and prevention of the disease complications are most essential.