Clinical impact using low-dose mycophenolate mofetil with tacrolimus on infectious, noninfectious complications and acute rejection, in renal transplant: A single hospital experience in Mexico.

Evidence supporting a starting dose of 2 g/day of mycophenolate mofetil (MMF) in combination with tacrolimus (TAC) for renal transplantation (RT) is still limited, but maintaining a dose of <2 g could result in worse clinical outcomes in terms of acute rejection (AR). This study aimed to determine the association between AR and infectious and noninfectious complications after RT with a dose of 1.5 g vs 2 g of MMF. A prospective cohort study was performed with a 12-month follow-up of recipients of RT from living donors with low (1.5 g/day) or standard (2 g/day) doses of MMF. The association between adverse effects and complications and doses of MMF was examined using Cox proportional hazard models, and survival free of AR, infectious diseases, and noninfectious complications was evaluated using the Kaplan-Meier test. At the end of the follow-up, the incidence of infectious diseases was 52% versus 50% (P = .71) and AR was 5% versus 5% (P = .86), respectively. The survival rate free of gastrointestinal (GI) complications requiring medical attention was higher in the low-dose group than in the standard-dose dose (88% vs 45%, respectively; P < .001). The use of 1.5 g/day of MMF confers a reduction in GI complications without an increase in infectious diseases or the risk of AR.

The Influence of Sevelamer Hydrochloride and Calcium Carbonate on Markers of Inflammation and Oxidative Stress in Hemodialysis at Six Months of Follow-Up.

Patients with end-stage renal disease (ESRD) present alterations in mineral and bone metabolism. Hyperphosphatemia in ESRD is considered an independent risk factor for cardiovascular disease (CVD), increasing morbidity, and mortality. Sevelamer hydrochloride is a calcium-free, non-absorbable phosphate-chelating polymer. Calcium carbonate chelator is helpful in controlling serum phosphate levels. There is insufficient information on the influence of sevelamer hydrochloride and calcium carbonate on the behavior of oxidative stress (OS) markers and inflammation in patients on hemodialysis (HD). A randomized open clinical trial was carried out on patients to evaluate sevelamer hydrochloride and calcium carbonate influence at 6 months of study follow-up. Levels of oxidants (LPO, NO, and 8-isoprostanes), antioxidants (SOD and TAC), oxidative DNA damage (8-OHdG and hOGG1), pro-inflammatory cytokines (IL-6 and TNF-α), and inflammation markers (ferritin and C-reactive protein) were measured with colorimetric and ELISA methods. We found a significant increase in oxidants LPO and NO, and antioxidants SOD and TAC, and downregulation of IL-6 and TNF-α. Ferritin decrease at 6 months follow-up in the sevelamer hydrochloride group. Increase in C-reactive protein was found in the group of patients treated with calcium carbonate. In conclusion, we found an oxidative state imbalance with increase in LPO and NO oxidants. The activity of the antioxidant enzymes (SOD and TAC) was also found to increase, suggesting a compensatory effect in the face of increase in oxidants. The same phenomenon was observed with increase in the oxidative damage marker to DNA and the increase in the DNA repair enzyme, suggesting a compensatory effect. Pro-inflammatory cytokines were predominantly downregulated by TNF-α in the group that ingested sevelamer hydrochloride in the final determination at 6 months of follow-up. Serum ferritin levels decreased significantly at the end of follow-up in patients on HD in the sevelamer hydrochloride group. The management of hyperphosphatemia with sevelamer hydrochloride appears to have obvious anti-inflammatory and antioxidant benefits.

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.

Donor-specific antibodies development in renal living-donor receptors: Effect of a single cohort.

Minimization in immunosuppression could contribute to the appearance the donor-specific HLA antibodies (DSA) and graft failure. The objective was to compare the incidence of DSA in renal transplantation (RT) in recipients with immunosuppression with and without steroids. A prospective cohort from March 1st, 2013 to March 1st, 2014 and follow-up (1 year), ended in March 2015, was performed in living donor renal transplant (LDRT) recipients with immunosuppression and early steroid withdrawal (ESW) and compared with a control cohort (CC) of patients with steroid-sustained immunosuppression. All patients were negative cross-matched and for DSA pre-transplant. The regression model was used to associate the development of DSA antibodies and acute rejection (AR) in subjects with immunosuppressive regimens with and without steroids. Seventy-seven patients were included (30 ESW and 47 CC). The positivity of DSA class I (13% vs 2%; P < 0.05) and class II (17% vs 4%, P = 0.06) antibodies were higher in ESW versus CC. The ESW tended to predict DSA class II (RR 5.7; CI (0.93-34.5, P = 0.06). T-cell mediated rejection presented in 80% of patients with DSA class I (P = 0.07), and 86% with DSA II (P = 0.03), and was associated with DSA class II, (RR 7.23; CI (1.2-44), P = 0.03). ESW could favor the positivity of DSA. A most strictly monitoring the DSA is necessary for the early stages of the transplant to clarify the relationship between T-cell mediated rejection and DSA.

Insertion/deletion polymorphism of the angiotensin-converting enzyme gene in lupus nephritis among Mexicans.

UNLABELLED: The angiotensin (Ang)-converting enzyme (ACE) insertion/deletion (I/D) polymorphism determines Ang II levels, but its relationship with lupus nephritis (LN) in different populations is controversial. OBJECTIVE: To describe the allelic and genotypic distribution of the I/D polymorphism in Mexican mestizos with LN and assess an association with histological classes. METHODS: We included 24 patients with systemic lupus erythematosus (SLE) without nephropathy, 41 with LN, 144 healthy subjects, and 36 with primary glomerulonephritis (GMN). Three ACE I/D polymorphism genotypes-ID, DD, and II--were detected by PCR using peripheral blood genomic DNA. RESULTS: Frequencies for II, ID, and DD were 0.29, 0.46, and 0.25 in the SLE group; 0.17, 0.63, and 0.20 in the LN group; 0.14, 0.5, and 0.36 in the GMN group; and 0.26, 0.52, and 0.22 among healthy subjects. The I/D polymorphism distribution according to histological class was class II: 1 II, 3 ID, and 1 DD; class III: 2 II, 10 ID, and 1 DD; class IV: 2 II, 9 ID, and 2 DD; class V: 2 II, 3 ID, and 4 DD; and class VI, 1 II. The histological classes with at least three patients had ID genotype as the most frequent except for class V. CONCLUSION: No association was identified between I/D polymorphisms of ACE and SLE, LN, or GMN in a Mexican population.

Renal function preservation in type 2 diabetes mellitus patients with early nephropathy: a comparative prospective cohort study between primary health care doctors and a nephrologist.

BACKGROUND: Early referral of patients with end-stage renal disease to a nephrologist is associated with lower morbidity and mortality after initiating dialysis therapy; earlier referral may have better results. The aim of the study is to prospectively determine the impact of earlier referral to a nephrologist on renal damage progression of patients with type 2 diabetes mellitus (DM2) with early nephropathy. METHODS: Fifty-two patients (27 patients, early nephropathy [EN]; 25 patients, overt nephropathy [ON]) from a primary health care unit were referred to a nephrologist (study cohort); 65 patients (34 patients, EN; 31 patients, ON) from another health care unit remained treated by only family doctors (control cohort). Both cohorts were followed up for 1 year. RESULTS: Delta (final-baseline) in serum creatinine levels was maintained better by the nephrologist in the EN (study, 0.02 mg/dL versus control, 0.13 mg/dL [2 versus 11 micromol/L]; P = 0.02) than ON group (study, 0.15 mg/dL versus control, 0.25 mg/dL [13 versus 22 micromol/L]). In concordance, glomerular filtration rate was maintained better by the nephrologist in EN (study, 3.2 mL/min/1.73 m2 versus control, -13.3 mL/min/1.73 m2 [0.05 versus -0.22 mL/s/1.73 m2]; P = 0.01) than ON patients (study, -9.8 mL/min/1.73 m2 versus control, -10.9 mL/min/1.73 m2 [-0.16 versus -0.18 mL/s/1.73 m2]). Albuminuria increased more in patients treated by family doctors in the EN (study, 30 mg/d versus control, 116 mg/d; P < 0.05) and ON groups (study, 160 mg/d versus control, 623 mg/d). The nephrologist controlled systolic blood pressure better in both the EN (study, -3 mm Hg versus control, 2 mm Hg; P < 0.05) and ON groups (study, -19 mm Hg versus control, 5 mm Hg; P < 0.05); diastolic blood pressure had a similar pattern. The nephrologist significantly increased (P < 0.05) the use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and statins and discontinued nonsteroidal anti-inflammatory drugs more than family doctors (study, 42%, 43%, 39%, and -11% versus control, 17%, 4%, -7%, and 27%, respectively). Glycemic and lipid control and stopping smoking were not attained by either the nephrologist or family doctors. CONCLUSION: Earlier referral of patients with DM2 to a nephrologist was associated with better renal function preservation, which was significantly more evident in the EN than ON group. The nephrologist obtained better blood pressure control, more frequently used angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and statins; and discontinued nonsteroidal anti-inflammatory drugs more than family doctors. However, metabolic control and stopping smoking were not attained by either the nephrologist or family doctors.