Diferencias en los marcadores de estrés oxidativo entre pacientes con enfermedad pulmonar obstructiva crónica según fenotipo agudizador y no agudizador / Differences in biomarkers of oxidative stress between patients with chronic obstructuve pulmonary disease according to the exacerbator and non-exacerbator phenotypes

Objetivo: en las agudizaciones de los pacientes con EPOC los marcadores de estrés oxidativo suelen estar elevados. Nuestro objetivo fue analizar si existen diferencias en estos marcadores entre pacientes con EPOC estable según fenotipo agudizador y no agudizador y la influencia de factores de confusión como la edad y el sexo. Método: se analizaron pacientes remitidos a una consulta monográfica de EPOC. Tras realizar una historia clínica detallada se clasificaron como agudizadores los que habían presentado dos o más agudizaciones en el año previo o habían tenido ingreso hospitalario. Se realizaron una espirometria y una extracción de sangre, cuantificando el estado total antioxidante del suero y los grupos tioles totales (sistemas antioxidantes no enzimáticos), la actividad superóxido dismutasa (sistema antioxidante enzimático) y las especies reactivas del ácido tiobarbitúrico(TBARS), los hidroperóxidos lipídicos, los productos avanzados de oxidación proteica y los productos finales de glicosilación avanzada como productos de oxidación. Resultados: se incluyeron 50 pacientes con fenotipo agudizador y 57 no agudizadores (edad media de 63 ± 7 años; 73% hombres). Se observaron valores superiores de TBARS en el fenotipo no agudizador, con significación estadística, a expensas de los pacientes mayores de 65 años y de sexo masculino. También se observó una tendencia a valores superiores de superóxido dismutasas en el fenotipo no agudizador. Conclusiones: existen pocas diferencias en los parámetros relacionados con el estrés oxidativo entre pacientes agudizadores y no agudizadores en fase estable. Encontramos valores más elevados de TBARSen pacientes no agudizadores, probablemente por causas no directamente relacionadas con la EPOC

Objective: In exacerbations of patients with COPD, the biomarkers of oxidative stress are often high. Our objective was to analyze whether there are any differences between these biomarkers in patients with stable COPD according to the exacerbator and non-exacerbator phenotypes and the influence of confounding factors such as age and gender. Method: Patients referred to a COPD consultation unit were analyzed. After taking a detailed clinical history, those who had two or more exacerbations in the previous year or hospital admission were classified as the exacerbator phenotype. Spirometry was performed and blood drawn, quantifying the total antioxidant status of serum and total thiol groups (non-enzymatic antioxidant systems), superoxide dismutase activity (enzymatic antioxidant system) and thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides, advanced oxidation protein products and advanced glycation end products as oxidation products. Results: Fifty patients with the exacerbator phenotype and 57 with the non-exacerbator phenotype were included (mean age of 63 ± 7 years; 73% male). Statistically significantly higher TBARS values were observed in the group with the nonexacerbated phenotype, at the expense of male patients over 65 years of age. A trend towards higher superoxide dismutase values was also observed in the non-exacerbated phenotype. Conclusions: There are few differences in oxidative stressrelated parameters between exacerbated and non-exacerbated patients at a stable stage. We found higher TBARS values in non-exacerbated patients, probably due to causes not directly related to COPD

CXCR3+ Monocytes Increase Significantly in Graft Blood Compared to Peripheral Blood in Patients With Stable Kidney Graft Function.

INTRODUCTION: We have recently reported that some lymphocyte populations do not maintain the same proportion in kidney graft blood as in peripheral blood, despite a stable function of the transplanted kidney. These results suggest that a comparative study between leukocyte cells from graft blood and those obtained from peripheral blood could provide information about the inflammatory state of the transplanted organ. In this work we selected the population of CD4+ lymphocytes and monocytes expressing CXCR3 to test this hypothesis. MATERIAL AND METHODS: The study was performed by flow cytometry during month 3, 6, and 12 after transplantation in 58 patients who received an isolated kidney transplant and the same immunosuppressive regimen. The peripheral blood sample was obtained by venipuncture and the graft blood by fine needle aspiration. RESULTS: We found a significant percentage decrease in CXCR3+ monocytes throughout the first year of transplantation in peripheral blood (15.9 ± 20.7 vs. 12.6 ± 12.4 vs. 6.3 ± 9.0, at 3, 6, and 12 months, respectively; P = .001), whereas the percentage of CXCR3+ monocytes in graft blood did not change over this period. This situation resulted in a significant percentage difference between the CXCR3+ monocytes from the graft blood and those from the peripheral blood at the sixth (15.8 ± 8.1 vs. 12.6 ± 12.4, respectively; P = .008) and 12th months (12.9 ± 8.1 vs. 6.3 ± 9.0, respectively; P < .001). CONCLUSIONS: Therefore, we can conclude that the significant percentage increase of CXCR3+ monocytes in graft blood with respect to peripheral blood suggests the presence of inflammatory activity despite renal function being stable during the second half of the first year post-transplantation.

Pancreas Preservation With Viaspan, Celsior, and Custodiol Solutions: An Initial Experience.

BACKGROUND: There is still controversy about which preservation solution in pancreas transplantation could be the best. The aim of this study was to analyze our initial experience with Custodiol solution (CuS) compared with Viaspan solution (VS) and Celsior solution (CS) in pancreas transplantation. METHODS: A retrospective study included 94 consecutive pancreatic transplants, from 2007 until 2015. We compared 3 groups, depending on preservation solution: Viaspan (n = 41), Celsior (n = 40), or Custodiol (n = 13). The primary end point was patient and pancreas survival at 1 year after pancreas transplantation. RESULTS: The recipient and donor characteristics were similar except in cold ischemia time; it was higher with Celsior. No differences were found in postoperative complications and pancreas graft function at 3 months, 6 months, and 1 year (glucose, HbA1c, C-peptide, creatinine). The pancreas and patient survival at 1 year was comparable (pancreas survival: VS, 80%; CS, 90%; CuS, 92%; log-rank, 0.875; and patient survival: VS, 92%; CS, 97%; CuS, 100%; log-rank, 0.9). CONCLUSIONS: In our institution, the Custodiol solution in pancreas transplantation presented similar outcomes in terms of postoperative complications, pancreas graft function, and 1-year survival.

Impact of Asystolic Donations in Kidney Transplant Activity From Cadaveric Donors in Andalusia.

BACKGROUND: Kidneys from donors after brain death (DBD) cannot meet the demand for renal transplants in Andalusia. METHODS: We analyzed the impact of using non-heart-beating donors (NHBD) in Andalusia from the start of this program to the present. RESULTS: From 2010 to 2014, brain-death kidney donations remained at a standstill (1,635 in total) although NHBD increased from 2.4% to 16% annually, to 5% of the total (n = 164: 83 type II Maastricht [NHBD-T2] and 81 type III Maastricht [NHBD-T3]). The donors were more frequently men (T2 80.5% and T3 76.5% vs DBD 58.2%; P < .001). NHBD were younger (48.9 ± 10.8 y vs DBD 53.3 ± 16 y; P < .001); 11.6% of NHBD were >60 and 0% >70 years old, versus 39.4% and 15.2% of DBD, respectively; this is mostly explained by NHBD-T2 (48.9 ± 10.8 y vs DBD 53.3 ± 16 y). NHBD were used much less frequently than DBD in recipients over the age of 65 years or for retransplanted or hyperimmunized patients and never on priority recipients (children and combined transplant patients). Blood groups differed significantly among different donor types (A, O, B, AB): NHBD-T2 65.1%, 27.7%, 7.2%, and 0%, respectively; NHBD-T3 45.7%, 45.7%, 8.6%, and 0%; and DBD 46.5%, 39.4%, 10.2 %, and 3.9% (P = .01). The immediate output of the graft also differed in the proportion of primary nonfunction and delayed graft function: NHBD-T2 9.8% and 70.7%, respectively; NHBD-T3 5.0% and 65.0%; and DBD 5.9% and 28.7%. CONCLUSIONS: The development of an NHBD program allows us to maintain and even increase transplants in our region. The impact on transplant access for O group recipients without priority will depend on the type of NHBD (low proportion of O group in NHBD-T2).

Impact of Early Low-Grade Proteinuria and Allograft Dysfunction on Survival in Expanded Criteria Donor Kidney Transplant Recipients.

INTRODUCTION: Recent studies have demonstrated a relationship between low-grade proteinuria and worse graft survival, but this has not been fully studied in expanded criteria donor (ECD) kidney transplant recipients. AIM: The aim of this study was to assess whether the combination of early low-grade proteinuria (<1 g/d) and allograft dysfunction at the third month post-transplantation predicts outcomes in terms of survival in ECD kidney transplant recipients. MATERIAL AND METHODS: We studied a cohort of 269 ECD kidney transplant recipients subdivided into 4 groups according to clinically relevant proteinuria (300 mg/d) and median creatinine (Cr; 1.7 mg/dL; interquartile range, 1.4-2.1 mg/dL) at the third month post-transplantation: Group A (Cr <1.7 mg/dL and proteinuria <300 mg/24 h; n = 97), Group B (Cr <1.7 mg/dL and proteinuria ≥300 mg/24 h; n = 38), Group C (Cr ≥1.7 mg/dL and proteinuria <300 mg/24 h; n = 79), and Group D (Cr ≥1.7 mg/dL and proteinuria ≥300 mg/24 h; n = 55). RESULTS: Death-censored graft survival was significantly lower in Group D compared with the rest (P < .007). Multivariate Cox regression analysis using fixed covariates showed that the combination of low-grade proteinuria and a lower estimated glomerular filtration rate (eGFR) as associated with graft failure (hazard rate [HR] 2.5, 95% confidence interval [CI], 1.09-5.97; P = .03). CONCLUSIONS: The early association of low-grade proteinuria and allograft dysfunction represents an important risk factor for graft loss in ECD kidney transplant recipients. Strategies to optimize renal function could improve the outcome in this specific population.

Associated characteristics and impact on survival of post renal-transplantation lymphoproliferative disease: case-control study from a regional registry.

BACKGROUND: Lymphoproliferative disease (LPD) after renal transplantation (RT) is an unusual complication but one that impacts greatly on survival. We examined possible predisposing factors and their effect on survival using data from the Andalusian Transplant Co-ordination Information System (SICATA) regional computerized database of patients on renal replacement therapy due to chronic kidney disease (CKD). METHODS: The study population comprised all RT undertaken at adult centers in Andalusia from January 1, 1990 to December 31, 2009 (N = 5577). We retrospectively analyzed cases at December 31, 2011 (N = 60). A control group comprised the 2 closest RT in time done at the same center and with equal or greater graft survival at the time of diagnosis of LPD in the associated case (N = 120). The basic variables were obtained from the general register (1990-2009) and widened from the specific register (2000-2009). Case-control comparison of survival was done with Kaplan-Meier from diagnosis to death or organ loss censored for death. Cox univariate and multivariate (LPD plus available covariables of demonstrated effect) analyses were done. RESULTS: We found no significant differences between cases and controls regarding the characteristics of the recipient or of the donor/organ, initial immunosuppression by intention to treat, or post-RT course. The impact on recipient survival 5 years after diagnosis was as follows: LPD, 35%; controls, 90% (P < .000). Cox univariate analysis showed the relative risk (RR) of death for LPD was 11.36 (95% confidence interval [CI], 6.2-20.9; P < .000) and the multivariate analysis showed relative risk (RR) = 13.87 (7.45-25.3; P < .000). The impact on death-censored graft survival 5 years after diagnosis was as follows: LPD, 65%; controls, 87% (P = .007). Cox univariate analysis was as follows: RR of failure for LPD, 2.70 (95% CI, 1.3-5.7; P = .009). CONCLUSIONS: We found no significant differences between LPD cases and contemporary controls regarding the basic characteristics of the recipient, donor/organ, initial immunosuppression, or initial graft evolution. There was an enormous impact on both patient and graft survival.

Rate of long-term graft loss has fallen among kidney transplants from cadaveric donors.

First-year renal allograft survival has increased, but whether this is associated with improvement in the long term is controversial. We analyzed 1045 consecutive adult deceased donor kidney transplant recipients from 1986 to 2001, with a follow-up to 2011. The aim of this study was to compare the graft half-life and attrition rates stratified by year of transplant in patients who received the graft in the periods 1986 to 1995 versus 1996 to 2001. The graft half-life increased significantly in the second period (P = .000) and the rate of graft loss stratified per year of evolution fell in all the study periods (P = .0000). In addition, the study period 1996 to 2001 was significantly associated with a reduction in graft failure risk compared with 1986 to 1995 in the multivariate analysis (P = .005). In conclusion, both short- and long-term graft survival increased significantly at our center.

Concordance of estimated glomerular filtration rates using Cockcroft-Gault modification of diet in renal disease, and chronic kidney disease epidemiology in renal transplant recipients.

INTRODUCTION: Various equations have been used to estimate the glomerular filtration rate (GFR) in renal patients, including kidney transplant recipients. Controversy exists concerning which equation is more precise to determine kidney failure. AIM: The aim of this study was to analyze the concordance (bias, variability, and exactness) of GFR estimated by the Modification of Diet in Renal Disease (MDRD4) and the Chronic Kidney Disease Epidemiology (CKD-EPI) equations using the Cockcroft-Gault (CG) method as the reference. MATERIAL AND METHODS: This observational, cross-sectional study included 153 clinically stable patients who underwent kidney transplantation between 2007 and 2009. The GFR was estimated at 12 months after the transplantation using the MDRD and CKP-EPI formula, using CG as the reference. RESULTS: The mean GFR for the various methods was as follows: CG = 65.6 ± 23.3 mL/min/1.73 m(2), MDRD4 = 54.9 ± 19.3 mL/min/1.73 m(2), and CKD-EPI = 55.8 ± 19.6 mL/min/1.73 m(2). Good correlations were found between CG-MDRD4 (r = 0.84; P < .001), CG-CKD-EPI (r = 0.87; P < .001), and MDRD4-CKD-EPI (r = 0.98; P < .001). The analysis of concordance detected a bias (normal difference) of -10.6 ± 12.7 versus -9.8 ± 11.3 mL/min/1.73 m(2) (P = .006), a variability (percent difference) of 14.5 ± 15.4% versus 13.6 ± 14.5% (P = .031), and an exactness (P30) of 81.7% versus 86.9% (P < .001) of CG-MDRD4 versus CG-CKD-EPI, respectively. For a GFR >60 mL/min/1.73 m(2) the exactness was 75.3% versus 83.5% (P < .001) for CG-MDRD4 versus CG-CKD-EPI, and for a GFR ≤ 60 mL/min/1.73 m(2) it was 89.7% versus 91.2% (P < .001). CONCLUSIONS: In our population the CKD-EPI method most approached the CG values, particularly when the GFR was >60 mL/min/1.73 m(2).

Mycophenolate mofetil and tacrolimus reduce mortality after deceased donor kidney transplantation.

A study of mortality in renal transplantation recipients showed that the combination of mycophenolate mofetil (MMF) and tacrolimus (TaC) reduced the mortality rate. We studied 1045 consecutive adult deceased donor kidney transplant recipients from 1986-2001, where follow-up to 2011 was a minimum of 10 years, to analyze the impact of these immunosuppressive drugs on patient survival. Cox multivariate analysis showed that treatment with MMF and the use of TaC instead of cyclosporine reduced the risk of death by 43%. In conclusion, both immunosuppressive drugs reduced the risk of death of patients receiving from renal transplants deceased donors.