Factores asociados a insuficiencia renal postoperatoria en cirugía de revascularización miocárdica

Introducción: La insuficiencia renal postoperatoria (IRP) es una complicación de alta prevalencia y de importancia en la cirugía cardiaca. Se estima que más del 30% de los pacientes sometidos a cirugía cardiaca desarrollan IRP clínicamente importante. Una estrategia razonable a realizar es la identificación de factores de riesgo modificables para intervenir sobre ellos. Objetivos: Determinar cuáles de los antecedentes clínicos del paciente y factores relacionados con el procedimiento quirúrgico se asocian a la aparición de IRP en pacientes sometidos a cirugía de –revascularización miocárdica (RVM). Métodos: Estudio de casos y controles. Casos fueron pacientes sometidos a cirugía de revascularización miocárdica electiva que presentaron insuficiencia renal postoperatoria durante el postoperatorio inmediato hasta el egreso. Controles pacientes sometidos a cirugía de revascularización miocárdica electiva que no presentaron insuficiencia renal postoperatoria durante el postoperatorio inmediato hasta el egreso. Estudio realizado entre enero de 2005 y diciembre de 2013. Se realizó un modelo de regresión logística para determinar los factores asociados a insuficiencia renal posoperatoria. Las asociaciones se expresan en OR con sus respectivos intervalos de confianza. Resultados: Edad avanzada OR 1.03 IC 95% (1.01-1.04), presencia preoperatoria de diabetes mellitus OR 1.8 IC 95% (1.9-3.4), enfermedad pulmonar OR 1.3 IC 95% (1.1-1.6), dislipidemia OR 3.5 IC 95% (1.7-7.1), insuficiencia cardiaca OR 2.7 IC 95% (1.1-6.7) y mayor tiempo de perfusión OR 1.02 IC 95% (1.01-1.03) se asociaron a mayor riesgo de IRP. Mayor hematocrito OR 0.86 IC95% (0.82-0.91) y mayor fracción de eyección OR 0.94 IC 95% (0.92-0.96) se asociaron disminuyendo el riesgo de IRP. Conclusiones: En pacientes sometidos a RVM los factores asociados a la presentación de IRP fueron comorbilidades que se asocian a daño renal progresivo dentro y fuera del contexto de la cirugía. Esto implica que las estrategias para minimizar este evento estarán enfocadas a identificar tempranamente los pacientes y realizar una adecuada nefroprotección.

Supervivencia en pacientes con trasplante hepático realizado en la Fundación Cardioinfantil entre 2005 y 2013

Introducción: El trasplante hepático es la terapia de elección para los pacientes con enfermedad hepática terminal, logrando mejorar su expectativa y calidad de vida, de acuerdo a estudios realizados en otros países. En la Fundación Cardioinfantil – Instituto de Cardiología (FCI-IC) se han realizado 332 trasplantes hepáticos hasta el 2014, pero no se conoce la supervivencia y los factores pronósticos propios de los pacientes intervenidos. Objetivo Principal: Estimar la supervivencia a 1, 3 y 5 años e identificar los principales factores pronósticos de los pacientes a quienes se les realizó trasplante hepático en el periodo 2005-2013 en la FCI-IC. Método: Estudio observacional y retrospectivo, basado en revisión de historias clínicas de los pacientes adultos a quienes se les realizó trasplante hepático en el periodo 2005-2013 en la FCI-IC. Resultados: La supervivencia al año fue de 90.91% (IC95% 86.40-93.98), a los 3 años 83.64% (IC95% 77.89-88.01) y a los 5 años de 79.18% (IC95% 72.54-84.39). Los principales factores pronósticos fueron el antecedente de ascitis (HR 2.449, IC 1.252 – 4.792), la edad del donante (HR 1.040, IC 1.009 – 1.071) y el receptor (HR 1.037, IC 1.014 – 1.060). Se encontró una mayor supervivencia en los pacientes con cirrosis alcohólica (HR 0.099, IC 0.021 – 0.467). Conclusiones: El estudio mostró una supervivencia mayor a la reportada en estudios realizados en Estados Unidos (67.4-73.0% a los 5 años) y España (73,3% a los 3 años) y similar a la de Chile (80.0% a los 5 años). Cabe resaltar que estos estudios incluyeron series más grandes de pacientes.

Respuesta inflamatoria sistémica en el donante como predictor de infección en el primer mes del trasplante renal

Introducción: El objetivo principal de la selección del donante es disminuir la posibilidad de transmisión de enfermedades infecciosas o neoplásicas en el receptor. De forma cruda se calcula que aproximadamente el 50% de los potenciales donantes son contraindicados, la mayoría por infección. La alta demanda de órganos obliga a revalorar las contraindicaciones que hasta hace poco eran absolutas, el reto es diferenciar el SIRS del donante por Muerte Encefálica con el SIRS por infecciones. Método: Estudio de cohorte retrospectivo; que busca evaluar la respuesta inflamatoria sistémica (SIRS) como predictor de infección en pacientes con trasplante renal en el primer mes pos trasplante. Resultados: El contraste de hipótesis proporciono una significancia bilateral (P= 0,071). La pruebas de hipótesis aceptaron la hipótesis nula (P= 0,071), que no existe asociación entre la presencia de SIRS en el donante con la incidencia de infección en el primer mes del pos trasplante renal. La estimación del riesgo de no reingreso por infección al primer mes pos trasplante renal es de 0.881 veces para los donantes con SIRS (IC 0.757 – 1.025). Conclusión: A pesar de no encontrar significancia estadística: el SIRS en el donante no se asocia con un aumento en la incidencia de infección en el primer mes postrasplante. Para encontrar la significancia se propone un estudio con un tamaño de muestra mayor.

A system for studying epithelial-stromal interactions reveals distinct inductive abilities of stromal cells from benign prostatic hyperplasia and prostate cancer

The development of normal and abnormal glandular structures in the prostate is controlled at the endocrine and paracrine levels by reciprocal interactions between epithelium and stroma. To study these processes it is useful to have an efficient method of tissue acquisition for reproducible isolation of cells from defined histologies. Here we assessed the utility of a standardized system for acquisition and growth of prostatic cells from different regions of the prostate with different pathologies, and we compared the abilities of stromal cells from normal peripheral zone (PZ-S), benign prostatic hyperplasia (BPH-S), and cancer (CA-S) to induce the growth of a human prostatic epithelial cell line (BPH-1) in vivo. Using the tissue recombination method, we showed that grafting stromal cells (from any histology) alone, or BPH-1 epithelial cells alone produced no visible grafts. Recombining PZ-S with BPH-1 cells also produced no visible grafts (n = 15). Recombining BPH-S with BPH-1 cells generated small, well-organized and sharply demarcated grafts approximately 3-4 mm in diameter (n = 9), demonstrating a moderate inductive ability of BPH-S. Recombining CA-S with BPH-1 cells generated highly disorganized grafts that completely surrounded the host kidney and invaded into adjacent renal tissue, demonstrating induction of an aggressive phenotype. We conclude that acquisition of tissue from toluidine blue dye stained specimens is an efficient method to generate high quality epithelial and/or stromal cultures. Stromal cells derived by this method from areas of BPH and cancer induce epithelial cell growth in vivo which mimics the natural history of these diseases.

Expression of TLR-4 and -2 in peripheral mononuclear cells in renal transplant patients with TLR-4 gene polymorphism

Introduction: TLR-4 has also been identified as a receptor for endogenous alarmins, which are increased post transplantation. TLR-4 has also been associated with a polymorphism that could impact graft outcome. Objective: To assess the expression of TLR-4 in kidney transplant patients carrying or not a polymorphism. Methods: TLR-4 polymorphism (A299G/T399I) was studied in 200 renal transplant patients. Healthy volunteers were also enrolled as control group. The polymorphism analysis was performed using restriction enzymes technique (RFLP). Functionality of TLR-4 polymorphism was assessed in samples from controls by quantification of TNF-alpha after LPS stimulus. TLR-4 and -2 expressions were also analyzed by flow cytometry. Results: TLR-4 polymorphism was present in 8.5% of renal transplant patients. This polymorphism was associated with impairment in TNF-alpha secretion. In general, in renal transplant patients, TLR-4 expression in monocytes and in neutrophils was lower than in health volunteers. TLR-2 and TLR-4 expressions in healthy volunteers with A299G/T399I TLR-4 polymorphism was higher than in wild-type genotype healthy volunteers (p<0.01 and p<0.05, respectively), and also higher than A299G/T399I TLR-4 polymorphism renal transplant patients (p<0.05). TLR-2 expression on neutrophils in wild-type genotype renal transplant patients was higher compared to wild-type genotype healthy volunteers, and was also higher in relation to A299G/T399I kidney transplanted patients (p<0.01). Conclusion: Stable renal transplant patients with TLR-4 polymorphism have a lower expression of TLR-4 and TLR-2 receptors in peripheral mononuclear cells, which ultimately indicate a less responsiveness for alarmins. (C) 2010 Elsevier B.V. All rights reserved.

Vimentin Expression and Myofibroblast Infiltration Are Early Markers of Renal Dysfunction in Kidney Transplantation: An Early Stage of Chronic Allograft Dysfunction?

Introduction. The objective of this study was to show the morphologic characteristics of allograft renal biopsies in renal transplant patients with stable renal function, which can potentially be early markers of allograft dysfunction, after 5 years of follow-up. Methods. Forty-nine renal transplant patients with stable renal function were submitted to renal biopsies and simultaneous measurement of serum creatinine (Cr). Histology was evaluated using Banff scores, determination of interstitial fibrosis by Sirius red staining and immunohistochemical study of proximal tubule and interstitial compartment (using cytokeratin, vimentin, and myofibroblasts as markers). Biopsies were evaluated according to the presence or absence of the epitheliomesenchymal transition (EMT). The interstitial presence of myofibroblasts and tubular presence of vimentin was also analyzed simultaneously. Renal function was measured over the follow-up period to estimate the reduction of graft function. Results. Median posttransplant time at enrollment was 105 days. Patients were followed for 64.3 +/- 8.5 months. The mean Cr at biopsy time was 1.44 +/- 0.33 mg/dL, and after the follow-up it was 1.29 +/- 0.27 mg/dL. Nine patients (19%) had a reduction of their graft function. Eleven biopsies (22%) had tubulointerstitial alterations according to Banff score. Seventeen biopsies (34%) presented EMT. Fifteen biopsies (32%) had high interstitial expression of myofibroblasts and tubular vimentin. Using Cox multivariate analysis, HLA and high expression of interstitial myofibroblasts and tubular vimentin were associated with reduction of graft function, yielding a risk of 3.3 (P = .033) and 9.8 (P = .015), respectively. Conclusion. Fibrogenesis mechanisms occur very early after transplantation and are risk factors for long-term renal function deterioration.

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

P>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 +/- 7.8 months. At biopsy time, mean serum creatinine was 1.43 +/- 0.33 mg/dl. Twelve patients (24.5%) had uRBP >= 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 >= 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.

Maximal inflammatory response benefits syngeneic skin graft acceptance

Objective: We investigated the influence of acute inflammation in skin isograft acceptance. Methods: Two mouse lines selected for maximal (AIR(MAX)) or minimal inflammatory response (AIR(MIN)) were transplanted with syngeneic skin. Cellular infiltrates and cytokine production were measured 1, 3, 7 or 14 days post-transplantation. The percentage of CD4(+) CD25(+) Foxp3(+) cells in the lymph nodes was also evaluated. Results: Grafts were totally accepted in 100% of AIR(MAX) and in 26% of AIR(MIN) mice. In the latter, partial acceptance was observed in 74% of the animals. Emigrated cells were basically PMN and were enhanced in AIR(MAX) transplants. IL-10 production by graft infiltrating cells showed no interline differences. IFN-gamma was increased in AIR(MIN) grafts at day 14 and lower percentages of CD4(+)CD25(+)Foxp3(+) cells in the lymph nodes were observed in these mice. Conclusions: Our data suggest that differences in graft acceptance might be due to a lack of appropriate regulation of the inflammatory response in AIR(MIN) mice compromising the self/non-self recognition.

Identification of protein-coding and intronic noncoding RNAs down-regulated in clear cell renal carcinoma

The clear cell subtype of renal cell carcinoma (RCC) is the most lethal and prevalent cancer of the urinary system. To investigate the molecular changes associated with malignant transformation in clear cell RCC, the gene expression profiles of matched samples of tumor and adjacent non-neoplastic tissue were obtained from six patients. A custom-built cDNA microarray platform was used, comprising 2292 probes that map to exons of genes and 822 probes for noncoding RNAs mapping to intronic regions. Intronic transcription was detected in all normal and neoplastic renal tissues. A subset of 55 transcripts was significantly down-regulated in clear cell RCC relative to the matched nontumor tissue as determined by a combination of two statistical tests and leave-one-out patient cross-validation. Among the down-regulated transcripts, 49 mapped to untranslated or coding exons and 6 were intronic relative to known exons of protein-coding genes. Lower levels of expression of SIN3B, TRIP3, SYNJ2BP and NDE1 (P<0.02), and of intronic transcripts derived from SND1 and ACTN4 loci (P<0.05), were confirmed in clear cell RCC by Real-time RT-PCR. A subset of 25 transcripts was deregulated in additional six nonclear cell RCC samples, pointing to common transcriptional alterations in RCC irrespective of the histological subtype or differentiation state of the tumor. Our results indicate a novel set of tumor suppressor gene candidates, including noncoding intronic RNAs, which may play a significant role in malignant transformations of normal renal cells. (C) 2008 Wiley-Liss, Inc.

Repair of lamellar scleral lesions in dogs with preserved equine renal capsule: short report

OBJETIVO: Avaliar o uso da cápsula renal de eqüino preservada em glicerina 98% no reparo de lesões lamelares esclerais em cães. MÉTODOS: Foram utilizados 12 cães, machos e fêmeas, com peso médio de 12kg. Foram realizadas avaliações clínica e morfológica aos 1, 3, 7, 15, 30 e 60 dias de pós-operatório. Após anestesia geral e procedimentos padrões de preparo do campo operatório, foi realizada cantotomia temporal, seguida de incisão conjutival e escleral com área de 0,5x0,5 cm na posição de 1hora, próxima ao limbo. em seguida, um fragmento de mesma dimensão de cápsula renal de eqüino preservada em glicerina, previamente hidratado em solução salina, foi aplicado ao defeito escleral criado sendo fixado com pontos simples isolados com vicryl 7-0®. RESULTADOS: A avaliação clínica revelou blefaroespasmo/fotofobia até o sétimo dia de pós-operatório. Foi observado edema conjuntival até o quinto dia, acompanhado de secreção ocular mucóide, que persistiu até o décimo dia de pós-operatório. Não foram observados sinais clínicos de rejeição do enxerto em todos os animais, em todos os períodos avaliados. Os segmentos anterior e posterior do bulbo ocular não apresentaram sinais de inflamação. A análise morfológica revelou exsudação inflamatória aguda nos períodos precoces e intermediários da avaliação e inflamação crônica nos períodos tardios da observação. Houve incorporação do enxerto ao leito receptor. CONCLUSÃO: Os resultados sugerem que a cápsula renal de eqüino preservada pode ser mais uma alternativa de membrana biológica para o reparo de lesões esclerais lamelares em cães e no homem.

Amastigotes forms of Trypanosoma cruzi detected in a renal allograft

Detecção de formas amastigotas do Trypanosoma cruziem enxerto renalA doença de Chagas é zoonose transmitida pelo Trypanosoma cruzi, o qual apresenta duas formas distintas no hospedeiro vertebrado, a tripomastigota circulante e a amastigota tecidual. Esta última parasita freqüentemente os tecidos musculares cardíaco, liso e estriado, e o tecido nervoso. Até o presente momento nunca foram detectados formas amastigotas em parênquima renal. O presente relato descreve, pela primeira vez, a detecção de formas amastigotas do T. cruzi em parênquima renal em receptor de enxerto de rim, com testes sorológicos negativos para a doença de Chagas e ausência de transfusões prévias, observado 1 mês após o transplante renal com doador cadáver proveniente de região endêmica. O paciente desenvolveu doença de Chagas aguda com detecção de formas tripomastigotas circulantes. Como a única forma de transmissão desta zoonose pelo enxerto é através de órgão parasitado com formas amastigotas, sugere-se fortemente que o rim transplantado foi o responsável pela transmissão da doença de Chagas, no presente caso. Esta é a via de infecção que deve ser levada em consideração em transplantes nas áreas endêmicas

Hyperlipidemia as a risk factor of renal allograft function impairment

In this study, the graft outcome in renal allograft recipients with [high cholesterol group (HCG), n = 30] or without [normal cholesterol group (NCG), n = 42] hypercholesterolemia and with [high triglyceride group (HTG), n = 33] or without [normal triglyceride group (NTG), n = 36] hypertriglyceridemia were prospectively compared. At 6 months post-transplantation, no significant difference was observed between the groups (NTG compared with HTG, and NCG compared with HCG) regarding age, presence of arterial hypertension, kind of donor (living related or cadaveric), immunosuppressive therapy, number of rejection episodes per patient, frequency of patients with acute cellular rejection, prevalence of patients with diabetes mellitus or proteinuria > 3 g/24 h, and mean serum creatinine. The probability of doubling serum creatinine during follow-up was statistically different between NTG and HTG (12 months: NTG = 0.03, HTG = 0.15; 36 months: NTG = 0.08, HTG = 0.33; 60 months: NTG = 0.08, HTG = 0.48; and 120 months: NTG = 0.18, HTG = 0.48), but not between NCG and HCG (12 months: NCG = 0.05, HCG = 0.13; 36 months: NCG = 0.13, HCG = 0.24; 60 months: NCG = 0.19, HCG = 0.31; 84 months: NCG = 0.27, HCG = 0.31). There was no significant difference in actuarial graft survival between HCG and NCG or between NTG and HTG. Hypertriglyceridemia, but not hypercholesterolemia, was associated with loss of graft function.

FTY720 in combination with cyclosporine - an analysis of skin allograft survival and renal function

Acute and chronic nephrotoxicity caused by CsA Continuous administration impair kidney allograft survival. Several clinical and experimental protocols have shown benefits to the kidney after decreasing CsA dose, withdrawing the drug or delaying its introduction after transplantation.FTY720 is a new Compound that has immunosuppressive characteristics and increase allograft survival in animal models without causing the side effects of calcineurin inhibitors (CNIs). FTY720 described mechanism of action that consists to alter the lymphocyte migration pattern without impairment of the immune system response against pathogens.In our mice model, FTY720 administered alone or in combination with CsA during 21 days increased skin allograft survival in a fully mismatched strain combination and did not cause significant changes in renal function. Moreover, renal structure was normal in all groups suggesting that at low doses (10 mg/kg/day) CsA can be associated during short-term period to other immunosuppressive drugs, i.e. FTY720 without affecting the kidney.Combination of immunosuppressive compounds with FTY720 and/or delayed introduction of low cyclosporine dose Could prevent graft rejection and avoid nephrotoxicity. (c) 2006 Elsevier B.V. All rights reserved.

Oral health in renal transplant recipients administered cyclosporin A or tacrolimus

OBJECTIVE: the aim of this study was to determine the oral status of renal transplant recipients receiving cyclosporin A (CsA) or tacrolimus (FK-506) as immunosuppressant.SUBJECTS AND METHODS: A total of 88 renal transplant recipients receiving CsA (63 men and 25 women, mean age 51.4 years) and 67 receiving FK-506 (57 men and 10 women, mean age 33.5 years) were included in the study. Donor type, histocompatibility, cold ischemia time and prior delayed graft function were similar between the two groups. Demographics and pharmacological data were recorded for all subjects.RESULTS: the results demonstrated that CsA caused a greater number of oral diseases. A greater number of gingival overgrowth was present in patients treated with CsA. However, the combined use with calcium channel blockers increased the gingival overgrowth number. The occurrence of candida in saliva was observed in 80 renal recipients treated with CsA and 20 treated with FK-506. The presence of squamous oral carcinoma (n = 3) and herpes simplex (n = 10) was observed in patients treated with CsA. These alterations were not observed in renal recipients treated with FK-506.CONCLUSIONS: Renal recipients constitute a high-risk group for oral diseases, as they are immunocompromised. However, the FK-506 regime appears to ameliorate this effect, compared with CsA. Adequate pre- and post-transplant oral health care is recommended for these subjects, irrespective of the time interval for which the drug is administered.