Trapianto di polmone ed ex-vivo. Esperienza iniziale in due centri trapianti di polmone

Background Il trapianto polmonare rappresenta l'unica soluzione percorribile per l'insufficienza respiratoria end-stage. La principale limitante ad un suo impiego è rappresentata dalla scarsità di polmoni idonei. In questo contesto si colloca il progetto di ricondizionamento ex-vivo. L'implementazione risulta possibile attraverso il ricondizionamento di organi cosiddetti “marginali” o giudicati inizialmente non idonei al trapianto e da donatori a cuore fermo (Donor after Cardiac Death – DCD). Scopo Lo scopo principale del progetto è quello di analizzare i risultati a breve e medio termine del trapianto polmonare effettuato impiegando polmoni sottoposti a procedura di ricondizionamento ex-vivo in due centri trapianti di polmone a basso volume. Materiali e Metodi I dati sono stati raccolti retrospettivamente (da Giugno 2013 per quanto riguarda l’ISMETT e dal 2014 quelli dell’ Ospedale S. Orsola-Malpighi) e in maniera prospettica dal 2019. Risultati Sommando i dati relativi ad entrambi i centri, dal 2013 sono stati eseguiti un totale di 26 procedure di riperfusione. Sei volte i polmoni sono stati giudicati idonei al trapianto al termine con 5 trapianti doppi e un trapianto singolo sinistro. I risultati in termine di sopravvivenza a medio termine sono risultati sovrapponibili a quelli disponibili in letteratura, tuttavia è stato registrato un alto tasso di PGD (Primary Graft Disfunction) di grado 3, da imputare alla patologia di base del ricevente (ipertensione polmonare), che per protocollo di istituto rimane con supporto cardio-respiratorio (ECMO) dopo il trapianto. Conclusioni L’EVLP si conferma in centri di piccolo e medio volume un metodo sicuro ed efficace per implementare in numero di polmoni idonei al trapianto.

The role of myocardial scintigraphy in the assessment of cardiovascular risk in patients with end-stage chronic kidney disease on the waiting list for renal transplantation

The usefulness of stress myocardial perfusion scintigraphy for cardiovascular (CV) risk stratification in chronic kidney disease remains controversial. We tested the hypothesis that different clinical risk profiles influence the test. We assessed the prognostic value of myocardial scintigraphy in 892 consecutive renal transplant candidates classified into four risk groups: very high (aged epsilon 50 years, diabetes and CV disease), high (two factors), intermediate (one factor) and low (no factor). The incidence of CV events and death was 20 and 18, respectively (median follow-up 22 months). Altered stress testing was associated with an increased probability of cardiovascular events only in intermediate-risk (one risk factor) patients [30.3 versus 10, hazard ratio (HR) 2.37, confidence interval (CI) 1.693.33, P 0.0001]. Low-risk patients did well regardless of scan results. In patients with two or three risk factors, an altered stress test did not add to the already increased CV risk. Myocardial scintigraphy was related to overall mortality only in intermediate-risk patients (HR 2.8, CI 1.55.1, P 0.007). CV risk stratification based on myocardial stress testing is useful only in patients with just one risk factor. Screening may avoid unnecessary testing in 60 of patients, help stratifying for risk of events and provide an explanation for the inconsistent performance of myocardial scintigraphy.

Common variants in mendelian kidney disease genes and their association with renal function.

Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.

Scoring system for renal pathology in Fabry disease: report of the international study group of fabry nephropathy (ISGFN).

BACKGROUND: In Fabry nephropathy, alpha-galactosidase deficiency leads to accumulation of glycosphingolipids in all kidney cell types, proteinuria and progressive loss of kidney function. METHODS: An international working group of nephrologists from 11 Fabry centres identified adult Fabry patients, and pathologists scored histologic changes on renal biopsies. A standardized scoring system was developed with a modified Delphi technique assessing 59 Fabry nephropathy cases. Each case was scored independently of clinical information by at least three pathologists with an average final score reported. RESULTS: We assessed 35 males (mean age 36.4 years) and 24 females (43.9 years) who mostly had clinically mild Fabry nephropathy. The average serum creatinine was 1.3 mg/dl (114.9 micromol/l); estimated glomerular filtration rate was 81.7 ml/min/1.73 m(2) and urine protein to creatinine ratio was 1.08 g/g (122.0 mg/mmol). Males had greater podocyte vacuolization on light microscopy (mean score) and glycosphingolipid inclusions on semi-thin sections than females. Males also had significantly more proximal tubule, peritubular capillary and vascular intimal inclusions. Arteriolar hyalinosis was similar, but females had significantly more arterial hyalinosis. Chronic kidney disease stage correlated with arterial and glomerular sclerosis scores. Significant changes, including segmental and global sclerosis, and interstitial fibrosis were seen even in patients with stage 1-2 chronic kidney disease with minimal proteinuria. CONCLUSIONS: The development of a standardized scoring system of both disease-specific lesions, i.e. lipid deposition related, and general lesions of progression, i.e. fibrosis and sclerosis, showed a spectrum of histologic appearances even in early clinical stage of Fabry nephropathy. These findings support the role of kidney biopsy in the baseline evaluation of Fabry nephropathy, even with mild clinical disease. The scoring system will be useful for longitudinal assessment of prognosis and responses to therapy for Fabry nephropathy.

Nutritional evaluation of stage 5 chronic kidney disease patients on dialysis

CONTEXTO E OBJETIVO: Portadores de insuficiência renal crônica em diálise apresentam alta prevalência de desnutrição proteico-energética. Não existe ainda um método uniforme para avaliar o estado nutricional desses pacientes. Recomenda-se a aplicação de um conjunto de métodos subjetivos e objetivos para se chegar aos diagnósticos nutricionais adequados. O objetivo deste estudo é traçar o perfil nutricional de pacientes submetidos a hemodiálise. TIPO DE ESTUDO E LOCAL: Estudo transversal descritivo realizado na Unidade de Tratamento Dialítico de Araraquara, São Paulo, Brasil, em 2008. MÉTODOS: 48 pacientes tiveram seus indicadores antropométricos e bioquímicos caracterizados, sendo também submetidos ao questionário Avaliação Global Subjetiva modificada (SGAm), verificando-se possíveis correlações entre esses indicadores. RESULTADOS: A frequência de desnutrição moderada e grave variou de 22% a 54%, de acordo com o parâmetro utilizado. Com relação à adequação do peso ideal, 29% da amostra estavam com porcentagem de adequação abaixo do percentil 75, classificados como portadores de desnutrição moderada e grave. As correlações mais significativas foram observadas entre índice de massa corporal (IMC) e adequações de prega triciptal (PCT), circunferência do braço (CB) e circunferência muscular do braço (CMB); e entre o SGAm e adequações de CB e CMB. CONCLUSÃO: A desnutrição apresentou grande variabilidade de frequência entre os pacientes de acordo com o critério escolhido para avaliação. O acompanhamento nutricional de rotina e a validação de métodos que avaliem a composição corporal desses pacientes são de extrema importância para diagnosticar precocemente a desnutrição e assim prevenir complicações e reduzir as taxas de morbimortalidade nesta população.

Periodontal disease characterization in dogs with normal renal function or chronic renal failure

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Classificação em estágios da doença renal crônica em cães e gatos: abordagem clínica, laboratorial e terapêutica

Foi proposta uma revisão das terminologias empregadas para a descrição das alterações renais e também sugerida uma classificação em estágios para a doença renal crônica à semelhança da medicina humana pela IRIS (International Renal Interest Society). Essa classificação considera os estágios da doença de acordo com o tempo de evolução e a presença de marcadores de lesão renal. O objetivo principal é auxiliar no estabelecimento do diagnóstico, do prognóstico e da terapia adequada conforme cada estágio e, assim, retardar a perda da função dos rins e a evolução da doença renal e, dessa forma, propiciar melhor qualidade de vida ao paciente.

Variation in the Distribution of Trace Elements in Renal Cell Carcinoma

The development of cancer is a complex, multistage process during which a normal cell undergoes genetic changes that result in phenotypic alterations and in the acquisition of the ability to invade other sites. Inductively coupled plasma optical emission spectroscopy was used to estimate the contents of Al, Ca, Cd, Cr, Cu, Fe, K, Mg, Mn, Na, P, Pb, and Zn in healthy kidney and renal cell carcinoma (RCC), and significant differences were found for all elements. Along with the progression of the malignant disease, a progressive decrease of Cd and K was observed. In fact, for Cd, the concentration in stage T4 was 263.9 times lower than in stage T1, and for K, the concentration in stage T4 was 1.73 times lower than in stage T1. Progressive accumulation was detected for P, Pb, and Zn in stage T4. For P, the concentration in stage T4 was 11.1 times higher than in stage T1; for Pb, the concentration in stage T4 was 232.7 times higher than in T1; and for Zn, the concentration in T4 was 8.452 times higher than in T1. This study highlights the marked differences in the concentrations of selected trace metals in different malignant tumor stages. These findings indicate that some trace metals may play important roles in the pathogenesis of RCC.

K/DOQI-recommended intact PTH levels do not prevent low-turnover bone disease in hemodialysis patients

The guidelines proposed by the Kidney Disease Outcomes Quality Initiative (K/DOQI) suggested that intact parathyroid hormone (iPTH) should be maintained in a target range between 150 and 300 pg ml(-1) for patients with stage 5 chronic kidney disease. Our study sought to verify the effectiveness of that range in preventing bone remodeling problems in hemodialysis patients. We measured serum ionized calcium and phosphorus while iPTH was measured by a second-generation assay. Transiliac bone biopsies were performed at the onset of the study and after completing 1 year follow-up. The PTH levels decreased within the target range in about one-fourth of the patients at baseline and at the end of the study. The bone biopsies of two-thirds of the patients were classified as showing low turnover and a one-fourth showed high turnover, the remainder having normal turnover. In the group achieving the target levels of iPTH 88% had low turnover. Intact PTH levels less than 150 pg ml(-1) for identifying low turnover and greater than 300 pg ml(-1) for high turnover presented a positive predictive value of 83 and 62%, respectively. Our study suggests that the iPTH target recommended by the K/DOQI guidelines was associated with a high incidence of low-turnover bone disease, suggesting that other biochemical markers may be required to accurately measure bone-remodeling status in hemodialysis patients.

Validation of a strategy to diagnose coronary artery disease and predict cardiac events in high-risk renal transplant candidates

Background We validated a strategy for diagnosis of coronary artery disease ( CAD) and prediction of cardiac events in high-risk renal transplant candidates ( at least one of the following: age >= 50 years, diabetes, cardiovascular disease). Methods A diagnosis and risk assessment strategy was used in 228 renal transplant candidates to validate an algorithm. Patients underwent dipyridamole myocardial stress testing and coronary angiography and were followed up until death, renal transplantation, or cardiac events. Results The prevalence of CAD was 47%. Stress testing did not detect significant CAD in 1/3 of patients. The sensitivity, specificity, and positive and negative predictive values of the stress test for detecting CAD were 70, 74, 69, and 71%, respectively. CAD, defined by angiography, was associated with increased probability of cardiac events [log-rank: 0.001; hazard ratio: 1.90, 95% confidence interval (CI): 1.29-2.92]. Diabetes (P=0.03; hazard ratio: 1.58, 95% CI: 1.06-2.45) and angiographically defined CAD (P=0.03; hazard ratio: 1.69, 95% CI: 1.08-2.78) were the independent predictors of events. Conclusion The results validate our observations in a smaller number of high-risk transplant candidates and indicate that stress testing is not appropriate for the diagnosis of CAD or prediction of cardiac events in this group of patients. Coronary angiography was correlated with events but, because less than 50% of patients had significant disease, it seems premature to recommend the test to all high-risk renal transplant candidates. The results suggest that angiography is necessary in many high-risk renal transplant candidates and that better noninvasive methods are still lacking to identify with precision patients who will benefit from invasive procedures. Coron Artery Dis 21: 164-167 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Influence of coronary artery disease assessment and treatment in the incidence of cardiac events in renal transplant recipients

Background: The best strategy for pre-transplant investigation and treatment of coronary artery disease (CAD) is controversial. Methods: We evaluated 167 renal transplant recipients before transplantation to determine the incidence of cardiac events and death. We performed clinical evaluations and myocardial scans in all patients and coronary angiography in select patients. Results: Asymptomatic patients with normal myocardial scans (n = 57) had significantly fewer cardiac events (log-rank = 0.0002) and deaths (log-rank = 0.0005) than did patients with abnormal scans but no angiographic evidence of CAD (n = 76) and individuals with CAD (n = 34) documented angiographically. CAD increased the probability of events (HR = 2.27, % CI 1.007-5.11; p = 0.04). The incidence of cardiac events (log-rank = 0.349) and deaths (log-rank = 0.588) was similar among patients treated medically (n = 23) or by intervention (n = 11). Conclusion: Asymptomatic patients with normal myocardial scans had a better cardiac prognosis than did patients with or without CAD and positive for myocardial ischemia. Patients with altered scan and CAD had the poorer outcome. Guideline-oriented medical treatment is safe and yields results comparable to coronary intervention in renal transplant patients with CAD. The data do not support pre-emptive myocardial revascularization for renal transplant candidates.

Comparative study of Botox (R) injection treatment for upper eyelid retraction with 6-month follow-up in patients with thyroid eye disease in the congestive or fibrotic stage

Aim To compare morphometric data of the eyelid fissure and the levator muscle function (LF) before and up to 6 months after transcutaneous injection with five units of Botox (R) in patients with upper lid retraction (ULR) from congestive or fibrotic thyroid eye disease (TED). Methods Twenty-four patients with ULR from TED were submitted to transcutaneous injection of 5 units (0.1 ml) of Botox in one eye only. Patients were divided into two groups: 12 with congestive-stage TED (CG), and 12 with fibrotic-stage TED (FG). Bilateral lid fissure measurements using digital imaging and computer-aided analysis were taken at baseline and at regular intervals 2 weeks, 1 month, 3 months and 6 months after unilateral Botox injection. Mean values taken at different follow-up points were compared for the two groups. Results Most patients experienced marked improvement in ULR, with a mean reduction of 3.81 mm in FG and 3.05 mm in CG. The upper eyelid margin reflex distance, fissure height and total area of exposed interpalpebral fissure were significantly smaller during 1 month in CG and during 3 months in FG. Reduction in LF and in the difference between lateral and medial lid fissure measurements was observed in both groups. The treatment lasted significantly longer in FG than in CG. Conclusions A single 5-unit Botox injection improved ULR, reduced LF and produced an adequate lid contour in patients with congestive or fibrotic TED. The effect lasts longer in patients with fibrotic orbitopathy than in patients with congestive orbitopathy.

Peritoneal cytology: impact on disease-free survival in clinical stage I endometrioid adenocarcinoma of the uterus

The prognostic significance of positive peritoneal cytology in endometrial carcinoma has led to the incorporation of peritoneal cytology into the current FIGO staging system, While cytology was shown to be prognostically relevant in patients with stage II and III disease, conflicting data exists about its significance in patients who would have been stage I but were classified as stage III solely and exclusively on the basis of positive peritoneal cytology (clinical stage I). Analysis was based on the data of 369 consecutive patients with clinical stage I endometrioid adenocarcinoma of the endometrium. Standard treatment consisted of an abdominal total hysterectomy, bilateral salpingo-oophorectomy with or without pelvic lymph node dissection. Peritoneal cytology was obtained at laparotomy by peritoneal washing of the pouch of Douglas and was considered positive if malignant cells could be detected regardless of the number of malignant cells present. Disease-free survival (DFS) was considered the primary statistical endpoint. In 13/369 (3.5%) patients, positive peritoneal cytology was found. The median follow-up was 29 months and 15 recurrences occurred. Peritoneal cytology was independent of the depth of myometrial invasion and the grade of tumour differentiation, Patients with negative washings had a DFS of 96'7e at 36 months compared with 67% for patients with positive washings (log-rank P < 0.001). The presence of positive peritoneal cytology in patients with clinically stage I endometrioid adenocarcinoma of the endometrium is considered an adverse prognostic factor. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Renal pathology of polycystic kidney disease and concurrent hereditary nephritis in Bull Terriers

Objective To describe the renal lesions in Bull Terrier polycystic kidney disease (BTPKD), to confirm that the renal cysts in BTPKD arise from the nephron or collecting tubule, an to identify lesions consistent with concurrent BTPKD and Bull Terrier hereditary nephritis (BTHN). Design Renal tissue from five Bull Terriers with BTPKD and eight control dogs was examined by light and transmission electron microscopy. Clinical data were collected from all dogs, and family history of BTPKD and BTHN for all Bull Terriers. Results In BTPKD the renal cysts were lined by epithelial cells of nephron or collecting duct origin that were usually squamous or cuboidal, with few organelles. They had normal junctional complexes, and basal laminae of varying thicknesses. Glomeruli with small, atrophic tufts and dilated Bowman's capsules, tubular loss and dilation, and interstitial inflammation and fibrosis were common. Whereas the lesions seen in BTHN by light microscope were nonspecific, the presence of characteristic ultrastructural glomerular basement membrane (GMB) lesions and a family history of this disease indicated concurrent BTHN was likely in three of five cases of BTPKD. Conclusion This paper provides evidence that renal cysts in BTPKD are of nephron or collecting duct origin. In addition, GBM lesions are described that strongly suggest that BTPKD and BTHN may occur simultaneously.

Legionnaires' disease in the renal transplant unit of "Hospital das Clinicas, FMUSP": during a five year period (1988-1993)

Several reports have related Legionella pneumophila with pneumonia in renal transplant patients, however this association has not been systematically documented in Brazil. Therefore this paper reports the incidence, by serologycal assays, of Legionella pneumophila serogroup 1 in these patients during a five year period. For this purpose sera from blood samples of 70 hospitalized patients with pneumonia from the Renal Transplant Unit of Hospital das Clinicas, FMUSP collected at the acute and convalescent phase of infection were submitted to indirect immunofluorescence assay (IFA) to demonstrate anti-Legionella pneumophila serogroup 1 antibodies. Of these 70 patients studied during the period of 1988 to 1993,18 (25.71 %) had significant rises in specific antibody titers for Legionella pneumophila serogroup 1. Incidence was interrupted following Hospital water decontamination procedures, with recurrence of infections after treatment interruption. In this study, the high susceptibility (25.71%) of immunodepressed renal transplant patients to Legionella pneumophila serogroup 1 nosocomial infections is documented. The importance of the implementation and maintenance of water decontamination measures for prophylaxis of the infection is also clearly evident.