Randomized, double-blinded, controlled clinical trial of the effect of captopril, telmisartan and their combination on systemic inflammation of patients on hemodialysis.

To evaluate individual and combined effect of captopril and telmisartan on systemic inflammation markers of hemodialysis (HD) patients. Randomized, double-blinded, controlled clinical trial. Patients on HD at least 2 months, with arteriovenous fistula, were randomly allocated to groups: (1) captopril/placebo (N 13); (2) telmisartan/placebo (N 13); (3) captopril + telmisartan (N 12); or (4) placebo/placebo (N 12). During 3 months, patients received oral drugs as follows: captopril 50 mg/day, telmisartan 80 mg/day or placebo. Patients excluded if they had conditions or were on drugs potentially influencing on inflammation. Clinical and biochemical evaluations were performed monthly. Serum tumor necrosis factor alpha (TNFα), interleukin 6 (IL-6), and C-reactive protein (CRP) were measured at 0, 1 and 3 months. Baseline, demographic, clinical and biochemical variables were comparable between groups. Baseline versus final inflammatory markers were: captopril/placebo TNFα, 2.47 (0.1-4.5) versus 1.73 (0.3-3.8) pg/ml; IL-6, 17.03 (7.2-23) versus 7.90 (0.7-19) pg/ml; CRP, 4.21 (1.6-18) versus 5.9 (3.0-28) mg/l; telmisartan/placebo TNFα, 3.03 (2.3-4.6) versus 1.70 (1.2-2.0) pg/ml; IL-6, 14.10 (5.5-23) versus 9.85 (6.2-13) pg/ml; CRP, 5.74 (2.1-13) versus 10.60 (1.5-27) mg/l; captopril + telmisartan TNFα, 1.43 (0.7-5.4) versus 0.40 (0.1-2.1) pg/ml; IL-6, 10.05 (4.9-23) versus 4.00 (0.7-7.7) pg/ml (p < 0.05); CRP, 3.26 (0.7-12) versus 2.83 (0.6-6.5) mg/l; placebo/placebo TNFα, 3.13 (1.6-5.6) versus 1.64 (1.6-2.3) pg/ml; IL-6, 8.12 (5.4-16) versus 7.60 (2.4-15) pg/ml; CRP, 5.23 (1.9-16) versus 3.13 (1.5-18) mg/l. Monotherapy with captopril or telmisartan display a trend, but their combined treatment significantly decreased serum levels of IL-6. No remarkable changes on TNFα and CRP were observed.

Can the implementation of clinical practice guidelines improve clinical competence of physicians and kidney function of patients with type 2 diabetes mellitus?

Background: There are many clinical practice guidelines (CPGs) in Nephrology; however, there is no evidence that their availability has improved the clinical competence of physicians or the outcome of patients with chronic kidney disease (CKD). This study was aimed to evaluate the effect of implementation of CPGs for early CKD on family physicians (FP) clinical competence and subsequently on kidney function preservation of type 2 diabetes mellitus (DM2) patients at a primary healthcare setting. Methods: A prospective educative intervention (40-h) based on CPGs for Prevention, Diagnosis and Treatment of Early CKD was applied to FP; a questionnaire to evaluate clinical competence was applied at the beginning and end of the educative intervention (0 and 2 months), and 12 months afterwards. DM2 patients with CKD were evaluated during 1-year of follow-up with estimated glomerular filtration rate (eGFR) and albuminuria. Results: After educative intervention, there was a significant increase in FP clinical competence compared to baseline; although it was reduced after 1 year, it remained higher compared to baseline. One-hundred thirteen patients with early nephropathy (58 stage 1, 55 stage 2) and 28 with overt nephropathy (23 stage 3, 5 stage 4) were studied. At final evaluation, both groups maintained eGFR [(mean change) early 0.20 ± 19 pNS; overt 0.51 ± 13 mL/min pNS], whereas albuminuria/creatinuria (early -67 ± 155 p < 0.0001; overt -301 ± 596 mg/g p < 0.0001), systolic blood pressure (early -10 ± 18 p < 0.05; overt -8 ± 20 mmHg p < 0.05), and total cholesterol (early -11 ± 31 p < 0.05; overt -17 ± 38 mg/dL p < 0.05) decreased. Diastolic blood pressure, waist circumference and LDL-cholesterol were also controlled in early nephropathy patients. Conclusions: CPGs for Prevention, Diagnosis and Treatment of CKD, by means of an educative intervention increases FP clinical competence and improves renal function in DM2 patients with CKD.

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.

Cytomegalovirus in renal transplant recipients from living donors with and without valganciclovir prophylaxis and with immunosuppression based on anti-thymocyte globulin or basiliximab.

BACKGROUND: In our population, anti-thymocyte globulin (ATG) of 1 mg/Kg/day for 4 days is used; which permits not using valgancyclovir (VGC) prophylaxis in some renal transplant recipients (RTR) with moderate risk (R+), to reduce costs. This study aimed to determine the incidence and risk of developing cytomegalovirus (CMV), with or without prophylaxis, when exposed to low doses of ATG or basiliximab (BSL). PATIENTS AND METHODS: A retrospective cohort included 265 RTR with follow-up of 12 months. Prophylaxis was used in R-/D+ and some R+. Tacrolimus (TAC), mycophenolate mofetil, and prednisone were used in all patients. Logistic regression analysis was performed to estimate the risk of CMV in RTR with or without VGC. RESULTS: Cytomegalovirus was documented in 46 (17.3%) patients: 20 (43.5%) with CMV infection, and 26 (56.5%) with CMV disease. Anti-thymocyte globulin was used in 39 patients (85%): 32 R+, six D+/R-, and one D-/R-. ATG was used in 90% (27 of 30) of patients with CMV and without prophylaxis. The multivariate analysis showed an association of risk for CMV with the absence of prophylaxis (RR 2.29; 95% CI 1.08-4.86), ATG use (RR 3.7; 95% CI 1.50-9.13), TAC toxicity (RR 3.77; 95% CI 1.41-10.13), and lymphocytes at the sixth post-transplant month (RR 1.77; 95% CI 1.0-3.16). CONCLUSIONS: Low doses of ATG favored the development of CMV and a lower survival free of CMV compared with BSL. In scenarios where resources for employing VGC are limited, BSL could be an acceptable strategy.

Vascular calcification in Mexican hemodialysis patients.

BACKGROUND AND AIMS: Vascular calcification (VC) is a predictor of poor survival and cardiovascular outcome in end-stage renal disease (ESRD) patients; however, there is scarce information of VC in Latin America, and virtually no data in our setting. We undertook this study to evaluate the prevalence and characteristics of VC in a hemodialysis (HD) population from western Mexico and to determine possible associated factors. METHODS: This was a cross-sectional study performed in 52 patients. VC was evaluated using plain X-ray films (Adragao's score) of hands and pelvis; clinical and biochemical variables were also collected. Statistical analysis was carried out with Student t and χ(2) tests performed as appropriate and logistic regression to determine predictors of VC. RESULTS: Mean age was 43 years, 48% were female, 23% had diabetes mellitus (DM), and median time on dialysis was 46 months. Percentage prevalence was 52% with a mean calcification score of 2.0 ± 2.6; 23% of patients had severe calcification. VC was present in about 23-37% among the different vascular territories evaluated (radial, digital, femoral and iliac). Patients with calcification were significantly older, had a higher frequency of DM, higher alkaline phosphatase and lower HDL lipoproteins than those without VC. In the multivariate analysis, VC in these patients was significantly predicted only by an older age (OR [95% CI]: 1.15 [1.01-1.31], p = 0.04); lower HDL-cholesterol and higher alkaline phosphatase were marginal predictors. CONCLUSIONS: Half of our HD patients had VC. Territories of radial, iliac, femoral and digital arteries were roughly equally affected, and 25% of patients had a calcification considered as severe. Older age was the only significant predicting variable for VC, with low HDL-cholesterol and high alkaline phosphatase as marginal predictors.