Urinary Calcium Is Associated with Serum Sclerostin among Stone Formers.

BACKGROUND: Sclerostin plays an important role in bone metabolism and adipose tissue. Animal studies suggest that sclerostin influences urinary calcium (UCa), but this relationship has not been evaluated in stone formers (SFs). We aimed to investigate the association of UCa with serum sclerostin, bone mineral density (BMD), and body composition among SFs. METHODS: Clinical and laboratorial data were retrieved from medical records. Determinants of UCa were studied using linear regression. RESULTS: A total of 107 SFs (35.8 ± 9.3 years, 54% male) with eGFR 99.8 ± 14.5 mL/min/1.73 were studied. Subjects were split by sex and grouped into tertiles of UCa levels. Men in the highest UCa tertile had higher body mass index (BMI) and serum sclerostin, lower lean mass, and a trend towards higher fat mass. Women in the highest tertile had higher BMI and a trend towards higher serum sclerostin. Hypertension and metabolic syndrome, but not lower BMD, were more prevalent in the highest UCa tertile for both sexes. Sclerostin was positively correlated with fat mass and inversely correlated with lean mass among men, but not among women. BMD corrected for BMI at lumbar spine was inversely associated with UCa in a univariate analysis, but only serum sclerostin, hypertension, and NaCl intake were independent determinants of UCa in the multivariate model. CONCLUSION: The present findings disclose that in addition to hypertension and salt intake, serum sclerostin is associated with urinary calcium in stone formers, suggesting that in addition to the hormones traditionally thought to alter calcium reabsorption in the kidney, sclerostin may play a significant additional role, warranting further investigation.

Increased Body Fat and Organic Acid Anions Production Are Associated with Larger Kidney Size in ADPKD.

Background and Objectives: A high body mass index (BMI) is associated with the progression of autosomal dominant polycystic kidney disease (ADPKD). However, body fat (BF), which is another adiposity marker, has not yet been studied. Excessive weight may promote elevation in the endogenous synthesis of organic acid (OA) anions. Accordingly, we aimed to investigate the possible association of the aforementioned markers with kidney volume and renal function in patients with ADPKD. Materials and Methods: We conducted a retrospective cohort study of adult ADPKD outpatients involving clinical, serum, and urinary laboratorial data and body composition assessments retrieved from their medical records. BF was estimated by skinfold thickness (mm) on the non-dominant arm and was considered as normal or high for each sex. Total kidney volume (TKV) and height-adjusted volume (htTKV) were measured by magnetic resonance imaging. The annual estimated glomerular filtration rate (eGFR) slope was analyzed during a median follow-up time of 6 (5.0-7.0) years to calculate rapid progression (decline in renal function ≥2.5 mL/min/year over 5 years). Results: A total of 104 patients were included (41.9 ± 11.9 years old, 38.5% men), with 62.5% of the patients classified as high BF. The High BF group presented higher levels of OA, glycosylated hemoglobin (HbA1c), C-reactive protein (CRP), 24 h urinary sodium (UNa), and htTKV, and lower eGFR than those with a normal BF. In the multivariate linear regression, the associated variables with TKV were high BF, OA and BMI (std. ß 0.47, p < 0.05; std. ß 0.36, p = 0.001; std. ß 0.25, p = 0.01, respectively). In the binary logistic regression, when adjusted for potential confounders, UNa was the only parameter associated with an increased risk of eGFR decline ≥2.5 mL/min/year (OR 1.02, 95% CI 1.01-1.03, p = 0.02). Conclusions: Increased body fat and endogenous production of organic acid anions are associated with larger kidney size in ADPKD but not with a decline in renal function.

Exploring the causes of the high incidence of delayed graft function after kidney transplantation in Brazil: a multicenter study.

This retrospective multicenter (n = 18) cohort study evaluated the incidence, risk factors, and the impact of delayed graft function (DGF) on 1-year kidney transplant (KT) outcomes. Of 3992 deceased donor KT performed in 2014-2015, the incidence of DGF was 54%, ranging from 29.9% to 87.7% among centers. Risk factors (lower-bound-95%CI OR upper-bound-95%CI ) were male gender (1.066 1.2491.463 ), diabetic kidney disease (1.053 1.2961.595 ), time on dialysis (1.005 1.0071.009 ), retransplantation (1.035 1.3971.885 ), preformed anti-HLA antibodies (1.011 1.3831.892 ), HLA mismatches (1.006 1.0661.130 ), donor age (1.011 1.0171.023 ), donor final serum creatinine (sCr) (1.239 1.3171.399 ), cold ischemia time (CIT) (1.031 1.0431.056 ), machine perfusion (0.401 0.5420.733 ), and induction therapy with rabbit antithymocyte globulin (rATG) (0.658 0.8000.973 ). Duration of DGF > 4 days was associated with inferior renal function and DGF > 14 days with the higher incidences of acute rejection, graft loss, and death. In conclusion, the incidence and duration of DGF were high and associated with inferior graft outcomes. While late referral and poor donor maintenance account for the high overall incidence of DGF, variability in donor and recipient selection, organ preservation method, and type of induction agent may account for the wide variation observed among transplant centers.

Intragraft transcriptional profiling of renal transplant patients with tubular dysfunction reveals mechanisms underlying graft injury and recovery.

BACKGROUND: Proximal tubular dysfunction (PTD) is associated with a decreased long-term graft survival in renal transplant patients and can be detected by the elevation of urinary tubular proteins. This study investigated transcriptional changes in biopsies from renal transplant patients with PTD to disclose molecular mechanisms underlying graft injury and functional recovery. METHODS: Thirty-three renal transplant patients with high urinary levels of retinol-binding protein, a biomarker of PTD, were enrolled in the study. The initial immunosuppressive scheme included azathioprine, cyclosporine, and steroids. After randomization, 18 patients (group 2) had their treatment modified by reducing cyclosporine dosage and substituting azathioprine for mycophenolate mofetil, while the other 15 patients (group 1) remained under the initial scheme. Patients were biopsied at enrollment and after 12 months of follow-up, and paired comparisons were performed between their intragraft gene expression profiles. The differential transcriptome profiles were analyzed by constructing gene co-expression networks and identifying enriched functions and central nodes in each network. RESULTS: Only the alternative immunosuppressive scheme used in group 2 ameliorated renal function and tubular proteinuria after 12 months of follow-up. Intragraft molecular changes observed in group 2 were linked to autophagy, extracellular matrix, and adaptive immunity. Conversely, gene expression changes in group 1 were related to fibrosis, endocytosis, ubiquitination, and endoplasmic reticulum stress. CONCLUSION: These results suggest that molecular networks associated with the control of endocytosis, autophagy, protein overload, fibrosis, and adaptive immunity may be involved in improvement of graft function.

An analysis of the quality indicators of the organ donation process in São Paulo, Brazil.

BACKGROUND: Few studies have investigated whether quality initiatives in the process of organ donation yield better results of the organ donation process. OBJECTIVE: To analyze whether the indicators of the organ donation process in Brazilian hospitals meet the standards established by the Organ Donation European Quality System (ODEQUS). DESIGN: We evaluated the quality of the organ donation in a selected group of Brazilian hospitals served by the Nucleus of Organ Procurement (NOP) using standards of the ODEQUS. RESULTS: Structural and process indicators had 100% conformity. Indicators of results showed a family consent rate of 61% (29% lower than ODEQUS goal); a conversion rate of potential donors to effective donors of 47% (28% below the goal); and a 12% rate of sudden cardiac arrest (higher than the quality limit). CONCLUSIONS: Our findings highlight the importance for the development of quality initiatives in identifying gaps and weaknesses in the process that should be corrected or even restructured, therefore maximizing the number of donors and organs transplanted. Hospitals that participate in the NOP process met 61% of the quality indicators proposed by ODEQUS. Identification of potential donors, family consent, conversion, and sudden cardiac arrest rates are areas that did not conform to ODEQUS standard and revealed a great opportunity for improvement.

Expanding the pool of kidney donors: use of kidneys with acute renal dysfunction.

Given the shortage of organs transplantation, some strategies have been adopted by the transplant community to increase the supply of organs. One strategy is the use of expanded criteria for donors, that is, donors aged >60 years or 50 and 59 years, and meeting two or more of the following criteria: history of hypertension, terminal serum creatinine >1.5mg/dL, and stroke as the donor´s cause of death. In this review, emphasis was placed on the use of donors with acute renal failure, a condition considered by many as a contraindication for organ acceptance and therefore one of the main causes for kidney discard. Since these are well-selected donors and with no chronic diseases, such as hypertension, renal disease, or diabetes, many studies showed that the use of donors with acute renal failure should be encouraged, because, in general, acute renal dysfunction is reversible. Although most studies demonstrated these grafts have more delayed function, the results of graft and patient survival after transplant are very similar to those with the use of standard donors. Clinical and morphological findings of donors, the use of machine perfusion, and analysis of its parameters, especially intrarenal resistance, are important tools to support decision-making when considering the supply of organs with renal dysfunction.

Expanding the pool of kidney donors: use of kidneys with acute renal dysfunction / Ampliando o pool de doadores de rim: utilização de órgãos com disfunção renal aguda

ABSTRACT Given the shortage of organs transplantation, some strategies have been adopted by the transplant community to increase the supply of organs. One strategy is the use of expanded criteria for donors, that is, donors aged >60 years or 50 and 59 years, and meeting two or more of the following criteria: history of hypertension, terminal serum creatinine >1.5mg/dL, and stroke as the donor´s cause of death. In this review, emphasis was placed on the use of donors with acute renal failure, a condition considered by many as a contraindication for organ acceptance and therefore one of the main causes for kidney discard. Since these are well-selected donors and with no chronic diseases, such as hypertension, renal disease, or diabetes, many studies showed that the use of donors with acute renal failure should be encouraged, because, in general, acute renal dysfunction is reversible. Although most studies demonstrated these grafts have more delayed function, the results of graft and patient survival after transplant are very similar to those with the use of standard donors. Clinical and morphological findings of donors, the use of machine perfusion, and analysis of its parameters, especially intrarenal resistance, are important tools to support decision-making when considering the supply of organs with renal dysfunction.

RESUMO Diante da escassez de órgãos para transplante, algumas estratégias têm sido adotadas pela comunidade transplantadora, no sentido de ampliar a oferta de órgãos. Uma delas é a utilização de rins de doadores com critérios expandidos, ou seja, doadores com idade >60 anos ou entre 50 e 59 anos, e que atendem a dois ou mais dos seguintes critérios: história de hipertensão, creatinina sérica terminal >1,5mg/dL e acidente vascular cerebral como causa de morte do doador. Nesta revisão, foi dada ênfase à utilização de doadores com disfunção renal aguda, condição considerada por muitos uma contraindicação para a aceitação de órgãos e, portanto, uma das principais causas de descarte de órgãos. Desde que sejam doadores bem selecionados e que não tenham doença renal crônica, como hipertensão ou diabetes, muitos trabalhos mostraram que o uso de doadores com disfunção renal aguda deve ser encorajado, pois, em geral, a disfunção renal aguda é de caráter reversível. Embora, a maioria dos estudos tenha demonstrado que há uma maior taxa de função retardada do enxerto com a utilização desses órgãos, os resultados de sobrevida do enxerto e do paciente após o transplante são muito semelhantes aos resultados obtidos da utilização de doadores padrão. Os achados clínicos e morfológicos do doador, a utilização da máquina de perfusão e a análise de seus parâmetros, principalmente a resistência intrarrenal, são importantes ferramentas de apoio para tomada de decisão no momento da oferta de órgãos com disfunção renal.

Ischemia and reperfusion injury in renal transplantation: hemodynamic and immunological paradigms.

Ischemia and reperfusion injury is an inevitable event in renal transplantation. The most important consequences are delayed graft function, longer length of stay, higher hospital costs, high risk of acute rejection, and negative impact of long-term follow-up. Currently, many factors are involved in their pathophysiology and could be classified into two different paradigms for education purposes: hemodynamic and immune. The hemodynamic paradigm is described as the reduction of oxygen delivery due to blood flow interruption, involving many hormone systems, and oxygen-free radicals produced after reperfusion. The immune paradigm has been recently described and involves immune system cells, especially T cells, with a central role in this injury. According to these concepts, new strategies to prevent ischemia and reperfusion injury have been studied, particularly the more physiological forms of storing the kidney, such as the pump machine and the use of antilymphocyte antibody therapy before reperfusion. Pump machine perfusion reduces delayed graft function prevalence and length of stay at hospital, and increases long-term graft survival. The use of antilymphocyte antibody therapy before reperfusion, such as Thymoglobulin™, can reduce the prevalence of delayed graft function and chronic graft dysfunction.

Ischemia and reperfusion injury in renal transplantation: hemodynamic and immunological paradigms / Lesão de isquemia e reperfusão no transplante renal: paradigmas hemodinâmico e imunológico

Ischemia and reperfusion injury is an inevitable event in renal transplantation. The most important consequences are delayed graft function, longer length of stay, higher hospital costs, high risk of acute rejection, and negative impact of long-term follow-up. Currently, many factors are involved in their pathophysiology and could be classified into two different paradigms for education purposes: hemodynamic and immune. The hemodynamic paradigm is described as the reduction of oxygen delivery due to blood flow interruption, involving many hormone systems, and oxygen-free radicals produced after reperfusion. The immune paradigm has been recently described and involves immune system cells, especially T cells, with a central role in this injury. According to these concepts, new strategies to prevent ischemia and reperfusion injury have been studied, particularly the more physiological forms of storing the kidney, such as the pump machine and the use of antilymphocyte antibody therapy before reperfusion. Pump machine perfusion reduces delayed graft function prevalence and length of stay at hospital, and increases long-term graft survival. The use of antilymphocyte antibody therapy before reperfusion, such as Thymoglobulin™, can reduce the prevalence of delayed graft function and chronic graft dysfunction.

A lesão de isquemia e reperfusão é um evento inevitável no transplante de rim, tendo como consequências retardo na função do enxerto, aumento no tempo de hospitalização e dos custos, aumento no risco de rejeição aguda e potencial impacto negativo na evolução a longo prazo. Atualmente, vários fatores estão implicados na fisiopatologia da lesão de isquemia e reperfusão, podendo ser didaticamente divididos em dois paradigmas: hemodinâmico e imunológico. O paradigma hemodinâmico é classicamente descrito como a privação de oxigênio pela interrupção do fluxo sanguíneo, envolvendo diversos sistemas hormonais e pela produção de radicais livres de oxigênio após a reperfusão. O paradigma imunológico tem sido descrito mais recentemente e envolve as células do sistema imune, sobretudo as células T, como papel fundamental na lesão. De acordo com esses conceitos, novas estratégias de prevenção dos impactos da lesão de isquemia e reperfusão têm sido estudadas, especialmente formas mais fisiológicas de preservação do órgão, como a preservação em máquina de perfusão e o uso de anticorpos depletores de linfócitos antes da reperfusão. A perfusão em máquina reduz a prevalência de retardo na função do enxerto e o tempo de hospitalização, além de melhorar a sobrevida do enxerto a longo prazo. Já o uso de anticorpos depletores de linfócitos, como Timoglobulina®, antes da reperfusão, pode diminuir a prevalência de retardo na função do enxerto e a disfunção crônica do mesmo.

Cytomegalovirus infection in renal transplantation: clinical aspects, management and the perspectives / Infecção pelo citomegalovírus no transplante de rim: aspectos clínicos, manejo e perspectivas

Cytomegalovirus infection is one of most frequent infectious complications after renal transplantation, and can be classified as primo-infection, when the transmission occurs through the graft, or reactivation, when the recipient is cytomegalovirus seropositive. After transplantation, cytomegalovirus can appear as an infection, when the patient presents with evidence of viral replication without symptoms or disease, which has two clinical spectra: typical viral syndrome or invasive disease, which is a less common form. Their effects can be classified as direct, while the disease is developed, or indirect, with an increase of acute rejection and chronic allograft dysfunction risks. Diagnosis must be made based on viremia by one of the standardized methods: antigenemia or PCR, which is more sensitive. The risk factors related to infection after transplantation are the serologic matching (positive donor and negative recipient) and anti-lymphocyte antibody drugs. One of the strategies to reduce risk of disease should be chosen for patients at high risk: preemptive treatment or universal prophylaxis. Recent clinical research has described ganciclovir resistance as an emergent problem in management of cytomegalovirus infection. Two types of mutation that cause resistance were described: UL97 (most frequent) and UL54. Today, sophisticated methods of immunologic monitoring to detect specific T-cell clones against cytomegalovirus are used in clinical practice to improve the management of high-risk patients after renal transplantation.

A infecção pelo citomegalovírus é uma das principais complicações após o transplante de rim, podendo ser classificada em primoinfecção, quando a transmissão ocorre por meio do enxerto, ou em reativação, quando o receptor é soropositivo. Do ponto de vista clínico, pode se apresentar como infecção, na ausência de sintomas, ou como doença, com dois diferentes espectros: a síndrome viral típica ou, menos comumente, a doença invasiva. Os efeitos podem ser diretos, que é o desenvolvimento da doença, ou indiretos, como aumento no risco de rejeição aguda e de disfunção crônica do enxerto. O diagnóstico deve ser feito por pesquisa de viremia por meio de um dos dois métodos padronizados: antigenemia ou PCR − sendo essa última a mais sensível. Os fatores de risco relacionados com a infecção após o transplante são o match sorológico (doador positivo e receptor negativo) e o uso de anticorpos antilinfócitos. Uma das estratégias de redução de risco de doença deve ser escolhida após o transplante nos pacientes de alto risco: tratamento preemptivo ou profilaxia. Recentemente, linhas de pesquisa clínica têm apontado a resistência ao ganciclovir como um problema emergente no manejo da infecção pelo citomegalovírus. Duas formas de mutação que causam resistência são descritas: UL97, que é a mais frequente, e a UL54. Atualmente, sofisticados métodos de monitorização imunológica, como a detecção de clones específicos de células T contra o citomegalovírus podem ser utilizados na prática clínica para o melhor manejo após o transplante renal dos pacientes de alto risco.

Immunological induction with thymoglobulin: reduction in the number of doses in renal transplant from deceased donor / Indução imunológica com timoglobulina: redução no número de doses em transplante de rim com doador falecido

ABSTRACT Objective: To compare three different regimens of thymoglobulin induction. Methods: One hundred seventy two patients submitted to renal transplantation from a dead donor were divided into three groups according to the total number of thymoglobulin doses used in the post-transplantation surgery: Group 1, until 14 doses - May 2002 to June 2004 (n = 48); Group 2, until 7 doses - July 2004 to December 2006 (n = 57); Group 3, until 4 doses - January 2007 to July 2009 (n = 67). The three groups were compared according to the main outcomes. Results: The main demographic differences among the groups were: greater dialysis time in Group 3 (p < 0.001 for Group 1; and p = 0.04 for Group 2); donor age, greater in Groups 2 and 3 (p = 0.02; p = 0.01, respectively); and cold ischemia time progressively greater from Group 1 to 3: 19.5 ± 5.1 to 24.6 ± 5.7 hours (p < 0.001). In relation to the inhibitor of calcineurin, the relation Tac/Csa was 14.6/66.7% in Group 1, 78.9/12.3% in Group 2 and 100/0% in Group 3. Reflecting the increase in cold ischemia time, the incidence of delayed graft function was 64.6%, 68.4% e 82.1% in Groups 1, 2 and 3, respectively (p = ns). The incidence of acute rejection was similar in the three groups: 16.7% (1); 16.3% (2) and 16.4 (3) - p = ns. The prevalence of viremia for cytomegalovirus was 61.7% in Group 1, 66.1% in Group 2 and 83.3% in Group 3 (p = ns). There were no difference related to the number of infected cells with cytomegalovirus in antigenemia, according to the groups, however, patients in Group 3 had an earlier diagnosis: from 64.3 ± 28.5 days in Grup 2, to 47.1 ± 22.5 days, in Group 3, p < 0.001. Survival of the graft in one year was 89.6%, 92.9% and 91.0%, in Groups 1, 2 and 3, respectively (p = ns). The graft function was much better with the lower doses of thymoglobulin: Group 1: 57.0 ± 20.0 mL/min; Group 2: 67.0 ± 18.4 mL/min (p = 0.008); Group 3: 71.2 ± 18.4 mL/min (p < 0.001, Group 1 versus Group 3; p = 0.06, Group 1 versus Group 2). There was a significant reduction in the costs of induction protocol from U$ 7,567.02 to U$ 3,485.56 (p < 0.001). Conclusions: The total number of thymoglobulin doses for immunologic induction could be reduced in a safe and effective way, without a negative impact in graft rejection or survival, preserving renal function and being significantly cheaper.

RESUMO Objetivo: Comparar três regimes diferentes de indução com timoglobulina. Métodos: Cento e setenta e dois pacientes submetidos a transplante de rim com doador falecido foram divididos em três grupos, de acordo com o número total de doses de timoglobulina utilizada no pós-operatório: Grupo 1, até 14 doses - Maio de 2002 a Junho de 2004 (n = 48); Grupo 2, até 7 doses - Julho de 2004 a Dezembro de 2006 (n = 57); Grupo 3, até 4 doses - Janeiro de 2007 a Julho de 2009 (n = 67). Os três grupos foram comparados de acordo com os principais desfechos. Resultados: As principais diferenças demográficas entre os três grupos foram: tempo em diálise, que foi maior no Grupo 3 (p < 0,001 para o Grupo 1; p = 0,04 para o Grupo 2); idade do doador, maior nos Grupos 2 e 3 (p = 0,02; p = 0,01, respectivamente); e o tempo de isquemia fria, progressivamente maior do Grupo 1 ao 3: 19,5 ± 5,1 para 24,6 ± 5,7 horas (p < 0,001). Em relação ao inibidor de calcineurina utilizado, a relação entre Tac/Csa foi de 14,6/66,7% no Grupo 1, 78,9/12,3% no Grupo 2 e de 100/0% no Grupo 3. Refletindo o aumento no tempo de isquemia fria, a incidência de delayed graft function foi de 64,6%, 68,4% e 82,1% nos Grupos 1, 2 e 3, respectivamente (p = ns). A incidência de rejeição aguda foi semelhante nos três grupos: 16,7% (1), 16,3% (2) e 16,4% (3) - p = ns. A prevalência de viremia para citomegalovírus foi de 61.7% no Grupo 1; 66,1% no Grupo 2; e 83,3% no Grupo 3 (p = ns). Não houve diferenças quanto ao número de células infectadas com o citomegalovírus na antigenemia, de acordo com os grupos; entretanto, os pacientes do Grupo 3 tiveram diagnostico mais precoce: de 64,3 ± 28,5 dias no Grupo 2, para 47,1 ± 22,5 dias no Grupo 3 (p < 0,001). A sobrevida do enxerto em um ano foi de 89,6%, 92,9% e 91,0%, nos Grupos 1, 2 e 3, respectivamente (p = ns). A função do enxerto foi substancialmente melhor com menor número de doses de timoglobulina: Grupo 1: 57,0 ± 20,0 mL/min; Grupo 2: 67,0 ± 18,4 mL/min (p = 0,008); Grupo 3: 71,2 ± 18,4 mL/min (p < 0,001, Grupo 1 versus Grupo 3; p = 0,06, Grupo 1 versus Grupo 2). Houve uma redução significativa no custo do protocolo de indução de U$ 7.567,02 para U$ 3.485,56 (p < 0,001). Conclusão: O número total de doses de timoglobulina para indução imunológica pôde ser reduzido de forma segura e eficaz, sem impacto negativo na incidência de rejeição ou sobrevida do enxerto, com preservação da função renal, sendo significativamente mais barato.

A new spectrophotometric method to detect residual amounts of peroxide after reprocessing hemodialysis filters / Um novo método espectrofotométrico para detectar níveis residuais de peróxido após o reprocessamento de filtros de hemodiálise

ABSTRACT Objective: Reuse of hemodialysis filters is a standard practice and the sterilizing chemical most often employed is peracetic acid. Before starting the dialysis session, filters and lines are checked for residual levels of peracetic acid by means of a non-quantitative colorimetric test that is visually interpreted. The objective of this study was to investigate a new quantitative spectrophotometric test for detection of peracetic acid residues. Methods: Peracetic acid solutions were prepared in concentrations ranging from 0.01 to 10 ppm. A reagent (potassium-titanium oxide + sulfuric acid) was added to each sample in proportions varying from 0.08 to 2.00 drops/mL of solution. Optical densities were determined in a spectrophotometer using a 405-nm filter and subjected to visual qualitative test by different observers. Results: A relation between peroxide concentrations and respective optical densities was observed and it was linear with R2 > 0.90 for all reagent/substrate proportions. The peak optical densities were obtained with the reagent/substrate ratio of 0.33 drops/mL, which was later standardized for all further experiments. Both qualitative and quantitative tests yielded a specificity of 100%. The quantitative test was more sensitive than the qualitative test and resulted in higher positive and negative predictive values. There was a difference between observers in the qualitative test and some samples with significant amounts of peroxide were not detected. Conclusion: A quantitative spectrophotometric test may improve detection of residues of peracetic acid when compared to the standard visual qualitative test. This innovation may contribute to the development of safer standards for reuse of hemodialysis filters.

RESUMO Objetivo: A reutilização de filtros de hemodiálise é uma prática disseminada e a substância química esterilizante mais empregada é o ácido peracético. Antes de iniciar a sessão de diálise, os filtros e as linhas são verificados em relação a níveis residuais de ácido peracético por meio de teste colorimétrico não quantitativo, com interpretação visual. O objetivo deste trabalho foi investigar um novo teste espectrofotométrico quantitativo para detecção de resíduos de ácido peracético. Métodos: As soluções de ácido peracético foram preparadas em concentrações que variam de 0,01 a 10 ppm. O reagente (óxido de potássio-titânio + ácido sulfúrico) foi acrescentado a cada amostra em proporções que variaram de 0,08 a 2,00 gotas/mL de solução. As densidades ópticas foram determinadas em um espectrofotômetro com filtro de 405 nm e submetidas a um teste visual qualitativo por diferentes observadores. Resultados: Observou-se a relação linear entre as concentrações de peróxido e as respectivas densidades ópticas com R2 > 0,90 para todas as proporções de reagente/substrato. As maiores densidades ópticas foram obtidas com a proporção reagente/substrato de 0,33 gotas/mL, que foi padronizada para todos os experimentos posteriores. Os testes qualitativos e quantitativos apresentaram especificidade de 100%. O teste quantitativo foi mais sensível do que o qualitativo e apresentou maiores valores preditivos positivos e negativos. Houve uma diferença entre os observadores no teste qualitativo e algumas amostras com quantidade significativa de peróxido não foram detectadas. Conclusão: O teste espectrofotométrico quantitativo pode melhorar a detecção de resíduos de ácido peracético em comparação ao teste visual qualitativo padrão. Essa inovação pode contribuir para o desenvolvimento de padrões mais seguros na reutilização de filtros de hemodiálise.

Immunological induction with thymoglobulin: reduction in the number of doses in renal transplant from deceased donor.

OBJECTIVE: To compare three different regimens of thymoglobulin induction. METHODS: One hundred seventy two patients submitted to renal transplantation from a dead donor were divided into three groups according to the total number of thymoglobulin doses used in the post-transplantation surgery: Group 1, until 14 doses - May 2002 to June 2004 (n = 48); Group 2, until 7 doses - July 2004 to December 2006 (n = 57); Group 3, until 4 doses - January 2007 to July 2009 (n = 67). The three groups were compared according to the main outcomes. RESULTS: The main demographic differences among the groups were: greater dialysis time in Group 3 (p < 0.001 for Group 1; and p = 0.04 for Group 2); donor age, greater in Groups 2 and 3 (p = 0.02; p = 0.01, respectively); and cold ischemia time progressively greater from Group 1 to 3: 19.5 ± 5.1 to 24.6 ± 5.7 hours (p < 0.001). In relation to the inhibitor of calcineurin, the relation Tac/Csa was 14.6/66.7% in Group 1, 78.9/12.3% in Group 2 and 100/0% in Group 3. Reflecting the increase in cold ischemia time, the incidence of delayed graft function was 64.6%, 68.4% e 82.1% in Groups 1, 2 and 3, respectively (p = ns). The incidence of acute rejection was similar in the three groups: 16.7% (1); 16.3% (2) and 16.4 (3) - p = ns. The prevalence of viremia for cytomegalovirus was 61.7% in Group 1, 66.1% in Group 2 and 83.3% in Group 3 (p = ns). There were no difference related to the number of infected cells with cytomegalovirus in antigenemia, according to the groups, however, patients in Group 3 had an earlier diagnosis: from 64.3 ± 28.5 days in Grup 2, to 47.1 ± 22.5 days, in Group 3, p < 0.001. Survival of the graft in one year was 89.6%, 92.9% and 91.0%, in Groups 1, 2 and 3, respectively (p = ns). The graft function was much better with the lower doses of thymoglobulin: Group 1: 57.0 ± 20.0 mL/min; Group 2: 67.0 ± 18.4 mL/min (p = 0.008); Group 3: 71.2 ± 18.4 mL/min (p < 0.001, Group 1 versus Group 3; p = 0.06, Group 1 versus Group 2). There was a significant reduction in the costs of induction protocol from U$ 7,567.02 to U$ 3,485.56 (p < 0.001). CONCLUSIONS: The total number of thymoglobulin doses for immunologic induction could be reduced in a safe and effective way, without a negative impact in graft rejection or survival, preserving renal function and being significantly cheaper.

A new spectrophotometric method to detect residual amounts of peroxide after reprocessing hemodialysis filters.

OBJECTIVE: Reuse of hemodialysis filters is a standard practice and the sterilizing chemical most often employed is peracetic acid. Before starting the dialysis session, filters and lines are checked for residual levels of peracetic acid by means of a non-quantitative colorimetric test that is visually interpreted. The objective of this study was to investigate a new quantitative spectrophotometric test for detection of peracetic acid residues. METHODS: Peracetic acid solutions were prepared in concentrations ranging from 0.01 to 10 ppm. A reagent (potassium-titanium oxide + sulfuric acid) was added to each sample in proportions varying from 0.08 to 2.00 drops/mL of solution. Optical densities were determined in a spectrophotometer using a 405-nm filter and subjected to visual qualitative test by different observers. RESULTS: A relation between peroxide concentrations and respective optical densities was observed and it was linear with R2 > 0.90 for all reagent/substrate proportions. The peak optical densities were obtained with the reagent/substrate ratio of 0.33 drops/mL, which was later standardized for all further experiments. Both qualitative and quantitative tests yielded a specificity of 100%. The quantitative test was more sensitive than the qualitative test and resulted in higher positive and negative predictive values. There was a difference between observers in the qualitative test and some samples with significant amounts of peroxide were not detected. CONCLUSION: A quantitative spectrophotometric test may improve detection of residues of peracetic acid when compared to the standard visual qualitative test. This innovation may contribute to the development of safer standards for reuse of hemodialysis filters.

Functional and morphologic evaluation of kidney proximal tubuli and correlation with renal allograft prognosis.

Renal transplant patients with stable graft function and proximal tubular dysfunction (PTD) have an increased risk for chronic allograft nephropathy (CAN). In this study, we investigated the histologic pattern associated with PTD and its correlation with graft outcome. Forty-nine transplant patients with stable graft function were submitted to a biopsy. Simultaneously, urinary retinol-binding protein (uRBP) was measured and creatinine clearance was also determined. Banff's score and semi-quantitative histologic analyses were performed to assess tubulointerstitial alterations. Patients were followed for 24.0 + or - 7.8 months. At biopsy time, mean serum creatinine was 1.43 + or - 0.33 mg/dl. Twelve patients (24.5%) had uRBP > or = 1 mg/l, indicating PTD and 67% of biopsies had some degree of tubulointerstitial injury. At the end of the study period, 18 (36.7%) patients had lost renal function. uRBP levels were not associated with morphologic findings of interstitial fibrosis and tubular atrophy (IF/TA), interstitial fibrosis measured by Sirius red or tubulointerstitial damage. However, in multivariate analysis, the only variable associated with the loss of renal function was uRBP level > or = 1 mg/l, determining a risk of 5.290 of loss of renal function (P = 0.003). Renal transplant patients who present PTD have functional alteration, which is not associated with morphologic alteration. This functional alteration is associated to progressive decrease in renal function.

A expressão de vimentina é um preditor de disfunção renal após o transplante renal / Vimentin expression is a predictor of renal dysfunction after kidney transplantation

Identificar em pacientes transplantados renais, com função renal normal e estável, marcadores prognósticos da função renal alongo prazo. Realizamos biópsias renais protocolares em 32 pacientes após um tempo mediano de 180 dias após o transplante renal. Conforme a classificação de Banff-1997,as biópsias foram classificadas de acordo com a presença ou não denefropatia crônica do enxerto e foi calculada a soma de cada alteração crônica, obtendo-se a soma dos escores crônicos. Todas as biópsias foram coradas com Picro-sirius, observado sob luz polarizada e o tecido fibrótico encontrado foi quantificado por meio de histomorfometria. Por meio de imunoistoquímica, foram avaliados os marcadores envolvidos no fenômeno de transdiferenciação epiteliomesenquimal: vimentina alfa-SMA e citoceratina. A função renal foi avaliada por meio da creatinina sérica, no momento da biópsia, após um e dois anos do transplante e atual (após 36,5 ±8,42 meses da realização da biópsia). Os testes estatísticos utilizados foram: Mann-Whitney, Kruskal-Wallis, Spearman e o teste exato de Fisher. A expressão tubular de vimentina correlacionou-se à creatinina da biópsia (r = 0,390 p = 0,033), de um ano (r = 0,405 p = 0,026), dois anos (r = 0,474 p = 0,008) e atual (r = 0,415 p= 0,028). A expressão intersticial de alfa-SMA, correlacionou-se à creatinina da biópsia (r = 0,442 p = 0,014), de dois anos (r = 0,364 p= 0,047) e atual (r = 0,376 p = 0,048). A expressão intersticial de alfa-SMA esteve associada às alterações crônicas (r = 0,412 p = 0,029), à expressão de vimentina (r = 0,502 p = 0,004), à fibrose estimada pelo Picro-Sirius (r = 0,402 p = 0,003) e à presença de nefropatia crônica do enxerto (p = 0,04). A expressão tubular de vimentina associou-se à nefropatia crônica do enxerto (p = 0,001) e foi o marcador que se associou mais fortemente às alterações tubulointersticiais crônicas(r = 0,513 p = 0,003).

Índice de doenças coexistentes e idade avançada como preditores desobrevida em pacientes em diálise / Index of coexisting disease and old age as predictors of survival in hemodialysis patients

Identificar os fatores que podem influenciar a sobrevida dos pacientes em programa crônico de hemodiálise em um hospital privado do Brasil. Neste estudo, foram avaliados, retrospectivamente, 99 pacientes do Centro de Diálise Einstein (CDE), Unidade de Hemodiálise do Hospital Israelita Albert Einstein, que estiveram em programa crônico de hemodiálise por pelo menos três meses, no período de fev. de 2000 a out. de 2006. As características dos pacientes que foram avaliadas quanto à possível influência na sobrevida foram: causa da insuficiência renal cardíaca (IRC) (com e sem diabetes mellitus), sexo, idade, níveis de albumina, proteína C reativa (PCR), hemoglobina e o Índice de Doença Coexistenteou Index of Coexisting Disease(instrumento que avalia a presença e a severidade das comorbidades) da admissão. As curvas de sobrevida foram calculadas segundo o método de Kaplan-Meier e as diferenças entre as curvas foram avaliadas pelo teste log-rank. A média de idade dos pacientes foi de 63,14 ± 16,18 anos, 34% deles eram do sexo feminino e 40% apresentavam DM como causa da IRC. Os níveis médios de albumina e hemoglobina na admissão foram 3,44 ± 0,58 g/dl e 10,55 ± 1,51 g/dl respectivamente, e a mediana dos níveis de PCR foi 9,55 g/dl. A distribuição dos pacientes de acordo com o nível de ICED na admissão foi: 25(25%) pacientes apresentavam ICED leve, 36(36%) apresentavam ICED moderado e 38(38%) apresentavam ICED grave. 33 pacientes (33%) foram a óbito, 24(24%) foram submetidos a transplante renal, 5(5%) foram transferidos para outra unidade de diálise, 36(36%) continuaram em hemodiálise e 1 (1%) paciente recuperou a função renal. A sobrevida em um ano foi de 80% e a mediana da sobrevida dos pacientes foi de 42,34 meses(IC 95%: 28,06-54,84). Na...

Tratamento MARS (Molecular Adsorbent Recirculating System) em pacientes com cirrose biliar primária: relato da primeira expectativa ambulatorial no Brasil / The MARS (Molecular Adsorbent Recirculating System): patient with primary biliary cirrhosis: first experience report in Brazil

O tratamento MARS (Molecular Adsorbent Recirculating System) permite a remoção de toxinas hepáticas ligadas à albumina. Dentre estas substâncias estão os ácidos biliares, que têm importante papel no prurido nas síndromes colestáticas. Relato do Caso: Descrição da primeira experiência brasileira ambulatorial de diálise MARS em paciente de 39 anos, sexo feminino, com diagnóstico de cirrose biliar primária e prurido recorrente após transplante de fígado e refratário às medidas clínicas, havendo também importante comprometimento na qualidade de vida. Após a realização de 2 sessões consecutivas do tratamento MARS, houve controle do prurido por pelo menos 7 meses. Procedimento bem tolerado e sem intercorrências Conclusão: O tratamento MARS é uma opção para pacientes com prurido intratável secundário a síndromes colestáticas e está associado à reduzida taxa de complicações

Timoglobulina como terapia de indução: proteção contra a lesão de isquemia e reperfusão / Thymoglobulin as an induction therapy: protection against ischemia and reperfusion injury

O objetivo deste trabalho foi avaliar a função e a sobrevida do enxerto em pacientes com alto risco para NTA (necrose tubular aguda) e determinar o impacto dessa lesão na função do enxerto renal em pacientes utilizando protocolo de indução com timoglobulina. Timo foi usado com monitoramento da contagem de células CD3+. Avaliaram-se a sobrevida e a função do enxerto ao final de um ano. Setenta e oito pacientes que receberam rim de doador cadáver com o referido protocolo foram avaliados em dois anos de acompanhamento. Tempo de isquemia fria foi de 19,9 ± 4,89 horas. O total de doses de timoglobulina foi 7,48 ± 3,79. Contagem de CD3+: 19,3 ± 22,5. Ocorreu rejeição aguda em 14,1% dos casos, NTA em 66,6% e infecção pelo CMV em 55,1%. A sobrevida do enxerto em um ano foi de 95,9%, com creatinina de 1,56 ± 0,53 mg/dl. Pacientes que apresentaram NTA tiveram maior tempo de hospitalização (18,8 ± 6,1 x 10,4 ± 4,3dias p = < 0,001) e pior creatinina sérica ao fim de um ano (1,66 ±0,47 x 1,39 ± 0,6 mg/dl, p = 0,003). A única variável relacionada com a função do enxerto foi a idade do doador (> 38 anos, RR = 3,43 p <0,001). A indução com timoglobulina conferiu excelente sobrevida ao enxerto, com baixo índice de rejeição aguda e preservação da função do enxerto até o segundo ano após o transplante, a despeito da elevada prevalência de NTA.

Alterações funcionais e morfológicas da célula epitelial tubular no transplante renal e sua repercussão na função renal / Functional and morphologic changes of tubular epithelial cell in renal transplantation and its impact on renal function

A nefropatia crônica do enxerto (NCE) é urna das principais causas de perda do enxerto após o primeiro ano do transplante. Estudo prévio demonstrou que altos níveis urinários de proteína transportadora do retinol (RBP) se associaram à NCE. Corn o objetivo de identificar em pacientes transplantados renais com função renal boa e estável, as características morfológicas que se correlacionam aos altos níveis de RBPu e potenciais marcadores laboratoriais e histológicos da função do enxerto renal a longo prazo, realizamos 74 biópsias protocolares em 50 transplantados renais assintomáticos após uma média de 1 19 dias do transplante (30-690 dias). A histopatologia foi avaliada pela Classificação de Banff-1997, com análise semi-quantitativa das alterações tubulares (atrofia, degeneração epitelial tubular e tubulite) e intersticiais (inflamação e fibrose), calculando-se os escores de lesão tubular, intersticial e total (0- I 5). As biópsias foram coradas com Picro Sirius (PS), observadas sob luz polarizada e a fibrose foi quantificada das imagens digitalizadas. Realizou-se imuno-histoquímica para vimentina (marcador mesenquimal ), -SMA (marcador de miofibroblastos) e citoceratina (marcador epitelial). A função tubular proximal foi avaliada pela medida da RBPu no momento da biópsia. A função renal foi avaliada por meio da creatinina (Cr) e do clearance de creatinina (CICr) calculado em diferentes tempos. A alteração da função renal foi calculada pela diferença do CICr atual e o da época da biópsia ou pela diferença do CICr atual e o da época da biópsia dividido pelo CICr da biópsia. Na maioria dos pacientes encontramos alterações tubulointersticiais leves, sendo que 30 por cento dos pacientes estavam livres qualquer lesão tubulintersticial. A média da fibrose estimada pelo PS estava dentro da faixa considerada normal. Encontramos a expressão tubular de vimentina e1n 60 por cento das amostras, principalmente em biópsias que apresentavam mais dano tubulointersticial (inflamação, fibrose e atrofia)...