Impact of transplantation on neutrophil extracellular trap formation in patients with end-stage renal disease: A single-center, prospective cohort study.

ABSTRACT: Increased neutrophil extracellular trap (NET) formation associates with high cardiovascular risk and mortality in patients with end-stage renal disease (ESRD). However, the effect of transplantation on NETs and its associated markers remains unclear. This study aimed to characterize circulating citrullinated Histone H3 (H3cit) and Peptidyl Arginase Deiminase 4 (PAD4) in ESRD patients undergoing transplantation and evaluate the ability of their neutrophils to release NETs.This prospective cohort study included 80 healthy donors and 105 ESRD patients, out of which 95 received a transplant. H3cit and PAD4 circulating concentration was determined by enzyme-linked immunosorbent assay in healthy donors and ESRD patients at the time of enrollment. An additional measurement was carried out within the first 6 months after transplant surgery. In vitro NET formation assays were performed in neutrophils isolated from healthy donors, ESRD patients, and transplant recipients.H3cit and PAD4 levels were significantly higher in ESRD patients (H3cit, 14.38 ng/mL [5.78-27.13]; PAD4, 3.22 ng/mL [1.21-6.82]) than healthy donors (H3cit, 6.45 ng/mL [3.30-11.65], P < .0001; PAD4, 2.0 ng/mL [0.90-3.18], P = .0076). H3cit, but not PAD4, increased after transplantation, with 44.2% of post-transplant patients exhibiting high levels (≥ 27.1 ng/mL). In contrast, NET release triggered by phorbol 12-myristate 13-acetate was higher in neutrophils from ESRD patients (70.0% [52.7-94.6]) than healthy donors (32.2% [24.9-54.9], P < .001) and transplant recipients (19.5% [3.5-65.7], P < .05).The restoration of renal function due to transplantation could not reduce circulating levels of H3cit and PAD4 in ESRD patients. Furthermore, circulating H3cit levels were significantly increased after transplantation. Neutrophils from transplant recipients exhibit a reduced ability to form NETs.

Patient and technique survival in continuous ambulatory peritoneal dialysis in a single center of the west of Mexico.

INTRODUCTION: In Mexico, CAPD survival has been analyzed in few studies from the center of the country. However, there are concerns that such results may not represent what occurs in other province centers of our country, particularly in our geographical area. AIM: To evaluate the patient and technique survival on CAPD of a single center of the west of Mexico, and compare them with other reported series. DESIGN: Retrospective cohort study. SETTING: Tertiary care, teaching hospital located in Guadalajara, Jalisco. PATIENTS: Patients from our CAPD program (1999-2002) were retrospectively studied. Interventions. Clinical and biochemical variables at the start of dialysis and at the end of the follow-up were recorded and considered in the analysis of risk factors. MAIN OUTCOME MEASURES: Endpoints were patient (alive, dead or lost to follow-up) and technique status at the end of the study (June 2002). RESULTS: 49 patients were included. Mean patient survival (+/- SE) was 3.32 +/- 0.22 years (CI 95%: 2.9-3.8 years). Patients in the present study were younger (39 +/- 17yrs), had larger body surface area (1.72 +/- 0.22 m2), lower hematocrit (25.4 +/- 5.2%), albumin (2.6 +/- 0.6g/dL), and cholesterol (173 +/- 44 mg/dL), and higher urea (300 +/- 93 mg/dL) and creatinine (14.9 +/- 5.6 mg/ dL) than those in other Mexican series. In univariate analysis, the following variables were associated (p < 0.05) to mortality: pre-dialysis age and creatinine clearance, and serum albumin and cholesterol at the end of follow-up. In multivariate analysis, only pre-dialysis creatinine clearance (RR 0.66, p = 0.03) and age (RR 1.08, p = 0.005) significantly predicted mortality. Mean technique survival was 2.83 +/- 0.24 years (CI 95%: 2.4-3.3). Pre-dialysis age (p < 0.05), peritonitis rate (p < 0.05), and serum phosphorus at the end of follow-up (p < 0.05) were associated with technique failure in univariate analysis, while in multivariate analysis, only pre-dialysis age (RR 1.07, p = 0.001) and peritonitis rate (RR 481, p < 0.0001) were technique failure predictors. CONCLUSIONS: Patients from this single center of the west of Mexico were younger, had higher body surface area and initiated peritoneal dialysis with a more deteriorated general status than patients reported in other Mexican series; in spite of the latter, patient and technique survival were not different. In our setting, pre-dialysis older age and lower CrCl significantly predicted mortality, while older predialysis age and higher peritonitis rate predicted technique failure.

Early steroid withdrawal in a renal transplant cohort treated with tacrolimus, mycophenolate mofetil and basiliximab.

BACKGROUND: Acute rejection and graft function have not been completely clarified in early-steroid-withdrawal (ESW) patients. The objective of this study was to compare the effect of early steroid withdrawal on GFR, graft survival/rejection in recipients in a cohort treated with tacrolimus/mycophenolate mofetil compared to a control cohort. MATERIAL AND METHOD: Retrospective cohort, in 60 low immunological risk recipients between December 2005 and July 2010. Study cohort (ESW-C N=32), steroid withdrawal was carried out after 5 days, while they were receiving tacrolimus/mycophenolate mofetil. The control cohort (C-C, N=28) received prednisone/tacrolimus/mycophenolate mofetil. Clinical, biochemical and histological variables were assessed at baseline and after 3, 6, and 12 months of follow-up. Kaplan-Meier and the Cox proportional hazards model were used to assess survival. Comparisons between cohorts were carried out by the Student's t and c2 tests. RESULTS: At follow-up, C-C displayed significantly higher systolic (125 ± 10 vs. 114 ± 8) and diastolic (81 ± 8 vs. 72 ± 7) blood pressure, serum glucose (96 ± 13 vs. 86 ± 10), triglycerides (177 ± 61 vs. 129 ± 34), total (183 ± 43 vs. 148 ± 34) and LDL-cholesterol (100 ± 22 vs. 87 ± 25). C-C had a higher proportion of antihypertensive (57 vs. 13%), and statins (27 vs. 9%) use. eGFR was better in ESW-C than in C-C (85.4 ± 20.6 vs. 70.6 ± 17.0, p=.004). AR frequency was lower in ESW-C. CONCLUSIONS: Graft survival, GFR, AR rate and metabolic profile were better in the ESW-C than in C-C.

The kidney transplant experience at Hospital de Especialidades, Centro Médico Nacional de Occidente, IMSS, Guadalajara México.

A total of 1,356 kidney transplants has been performed in the Hospital de Especialidades del Centro Médico Nacional de Occidente, IMSS, in Guadalajara Mexico, including 935 in the past 8 years. This represents an important increase of this activity in our country. Of the total transplants, 1,218 (90%) were from living donors and only 138 (10%) were from cadaveric donors, a number that we hope to increase. Most recipients were young adults, with an average age of 31 years old. The overall one-year graft and patient survival rates for living-donor kidney recipients were 90% and 82%, and for cadaveric kidney recipients they were 80% and 70%, respectively. Acute rejections occurred in 17% and chronic allograft nephropathy was diagnosed in 7% of our kidney transplant recipients. The main cause of patient death was infection, frequently invasive CMV. Cardiovascular complications were a relatively infrequent cause of death as has been seen in other international series. Hepatitis B and C have been widley studied. Hepatitis C is the most prevalent viral infection in our population. Both living and cadaveric donors in our series were young, which may explain the good results. We have had very few complications among living donors and no mortality. Two donors developed chronic renal insufficiency after the kidney donation (0.001%). This excellent safety record reflects the experience of our team. We hope to increase the number of cadaveric transplant donors with the renewed interest in enlarging the transplantation programs in Mexico while maintaining our high percentage of living donors in order to benefit more patients.