Benjamín Gómez-Navarro

Pentoxifylline decreases serum levels of tumor necrosis factor alpha, interleukin 6 and C-reactive protein in hemodialysis patients: results of a randomized double-blind, controlled clinical trial

AIM The aim of this study was to compare the effect of pentoxifylline versus placebo on serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) and C-reactive protein (CRP) of hemodialysis (HD) patients. METHODS This is a randomized double-blind, controlled clinical trial. HD patients without infection or drugs with anti-inflammatory effect were randomly allocated to a study (n = 18, pentoxifylline 400 mg/day) or control (n = 18, placebo) group; all patients had arteriovenous fistula. Besides clinical and laboratory monthly assessments, serum TNF-α and IL-6 (ELISA) and CRP (nephelometry) were measured at 0, 2 and 4 months. RESULTS All the inflammation markers significantly (P < 0.05) decreased in the pentoxifylline group: TNF-α [baseline 0.4 (0-2) versus final 0 (0-0) pg/mL], IL-6 [baseline 9.4 (5-14) versus final 2.9 (2-5) pg/mL] and CRP [baseline 7.1 (3-20) versus final 2.6 (1-8) mg/L], whereas no significant changes were observed in the placebo group: TNF-α [baseline 0 (0-0) versus final 1.2 (0-4) pg/mL], IL-6 [baseline 8.0 (5-11) versus final 8.7 (4-11) pg/mL] and CRP [baseline 4.5 (2-9) versus final 3.8 (3-23) mg/L]. CONCLUSIONS Pentoxifylline significantly decreased serum concentrations of TNF-α, IL-6 and CRP compared to placebo. Pentoxifylline could be a promising and useful strategy to reduce the systemic inflammation frequently observed in patients on HD.

Early Steroid Withdrawal in Recipients of a Kidney Transplant From a Living Donor: Experience of a Single Mexican Center.

BACKGROUND Early steroid withdrawal (ESW) can improve lipid and hemodynamic profiles without severe acute rejection (AR) events in renal transplant patients. Our objective was to evaluate the effects of ESW on the frequency and severity of AR. METHODS A randomized, open-label, controlled clinical trial was performed on renal transplant recipients with a follow-up of 12 months. In the ESW group, patients were selected for corticosteroid treatment withdrawal on the fifth day post transplantation. In the Control group, patients continued with steroid treatment. All patients were over 18 years of age with panel reactive antibody (PRA) class I and II HLA <20%. RESULTS In total, 71 patients, 37 in the ESW group (52.1%) and 34 in the Control group (47.9%), had comparable AR incidences at the end of the follow-up (16% vs 15%) (NS) (RR = 1.20, 95% CI = 0.32-3.33). Although renal graft survival was similar between the ESW and Control groups (87% vs 94%), renal function was superior in the ESW group (85 vs 75 mL/min). Additionally, hypertension was less frequent in the ESW group (3% vs 35%), requiring the use of fewer antihypertensives (8% vs 50%). CONCLUSIONS ESW was also associated with better blood pressure control and similar AR risk. The ESW group exhibited stable renal function.

The Oxidative and Inflammatory State in Patients with Acute Renal Graft Dysfunction Treated with Tacrolimus

Objective. To determine the oxidative stress/inflammation behavior in patients with/without acute graft dysfunction (AGD) with Tacrolimus. Methods. Cross-sectional study, in renal transplant (RT) recipients (1-yr follow-up). Patients with AGD and without AGD were included. Serum IL-6, TNF-α, 8-isoprostanes (8-IP), and Nitric Oxide (NO) were determined by ELISA; C-reactive protein (CRP) was determined by nephelometry; lipid peroxidation products (LPO) and superoxide dismutase (SOD) were determined by colorimetry. Results. The AGD presentation was at 5.09 ± 3.07 versus 8.27 ± 3.78 months (p < 0.001); CRP >3.19 mg/L was found in 21 versus 19 in the N-AGD group (p = 0.83); TNF-α 145.53 ± 18.87 pg/mL versus 125.54 ± 15.92 pg/mL in N-AGD (p = 0.64); IL-6 2110.69 ± 350.97 pg/mL versus 1933.42 ± 235.38 pg/mL in N-AGD (p = 0.13). The LPO were higher in AGD (p = 0.014): 4.10 ± 0.69 µM versus 2.41 ± 0.29 µM; also levels of 8-IP were higher in AGD 27.47 ± 9.28 pg/mL versus 8.64 ± 1.54 pg/mL (p = 0.01). Serum levels of NO in AGD were lower 138.44 ± 19.20 µmol/L versus 190.57 ± 22.04 µmol/L in N-AGD (p = 0.042); antioxidant enzyme SOD activity was significantly diminished in AGD with 9.75 ± 0.52 U/mL versus 11.69 ± 0.55 U/mL in N-AGD (p = 0.012). Discussion. Patients with RT present with a similar state of the proinflammatory cytokines whether or not they have AGD. The patients with AGD showed deregulation of the oxidative state with increased LPO and 8-IP and decreased NO and SOD.

The Beneficial Effects of Renal Transplantation on Altered Oxidative Status of ESRD Patients

Renal transplantation (RT), has been considered the best therapeutic option for end stage renal disease (ESRD). Objective. To determine the effect of RT on the evolution of oxidative DNA status. Methods. Prospective cohort (N = 50 receptors of RT); genotoxic damage, 8-hydroxy-2′-deoxyguanosine (8-OHdG), and DNA repair enzyme, human 8-oxoguanine-DNA-N- glycosylase-1 (hOGG1); and antioxidants, superoxide dismutase (SOD) and glutathione peroxidase (GPx), were evaluated. Results. Before RT, 8-OHdG were significantly elevated (11.04 ± 0.90 versus 4.73 ± 0.34 ng/mL) compared to healthy controls (p = 0.001), with normalization after 6 months of 4.78 ± 0.34 ng/mL (p < 0.001). The same phenomenon was observed with hOGG1 enzyme before RT with 2.14 ± 0.36 ng/mL (p = 0.01) and decreased significantly at the end of the study to 1.20 ng/mL (p < 0.001) but was higher than controls, 0.51 ± 0.07 ng/mL (p < 0.03). Antioxidant SOD was elevated at 24.09 ± 1.6 IU/mL versus healthy controls (p = 0.001) before RT; however, 6 months after RT it decreased significantly to 16.9 ± 1.6 IU/mL (p = 0.002), without achieving the levels of healthy controls (p = 0.01). The GPx, before RT, was significantly diminished with 24.09 ± 1.6 IU/mL versus healthy controls (39.0 ± 1.58) (p = 0.01), while, in the final results, levels increased significantly to 30.38 ± 3.16 IU/mL (p = 0.001). Discussion. Patients with ESRD have important oxidative damage before RT. The RT significantly reduces oxidative damage and partially regulates the antioxidant enzymes (SOD and GPx).