Thrombotic microangiopathy associated with calcineurin inhibitor induction doses in patients with a kidney transplant.

We present a case of a 23-year-old male who developed thrombotic microangiopathy associated with the induction dose of tacrolimus. Get an early diagnosis and give timely treatment of thrombotic microangiopathy is essential to improve the prognosis of the kidney transplant.

Phenotypes of Mineral Bone Disorder in Chronic Kidney Disease in a Dialysis Population.

BACKGROUND: Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is associated with clinical outcomes. It is necessary to identify the phenotype to make clinical decisions that optimize resources and follow-up. OBJECTIVE: To determine the frequency of the CKD-MBD phenotype in dialysis patients and the associated factors. METHODS: Cross-sectional study in 440 patients, evaluated for CKD-MBD. Phenotypes show frequency of high, low or on target levels of PTH, vitamin D and phosphorus. The most common phenotype was used for comparisons. RESULTS: Age was 37.5 ± 15.8 years, 53% male, 28% were diabetic, 60% on peritoneal dialysis (PD), dialysis vintage was 12.0 months (IQR 3.0-34.3). High PTH was 58%, low vitamin D 82%, high phosphorus 39%, low calcium 50%, and vascular calcification 55%. The combination of high PTH and low vitamin D and high on-target phosphorus was 39%. Those with high PTH and low vitamin D were more likely to use PD (71 vs 51%; p <0.0001), had higher lipids: total cholesterol (159 vs. 152; p = 0.002) and triglycerides (137 vs. 123; p = 0.02), higher potassium (4.7 ± 0.7 vs. 4.9 ± 0.9 mg/dL; p = 0.04), and higher serum creatinine (11.9 ± 4.4 vs. 10.6 ± 3.7 mg/dL; p = 0.01). Predictors of the most common phenotypes were PD use, total cholesterol, and serum creatinine. CONCLUSIONS: More than one third (38%) of our sample of patients had high PTH and low vitamin D with either high or normal phosphorus. Patients with these phenotypes more frequently used PD, had higher lipids and low potassium. PD use, total cholesterol and serum creatinine were significantly associated with these phenotypes.

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.

Procalcitonina sérica como marcador de la función del injerto en el postrasplante renal inmediato

Contexto la procalcitonina (PCT) podría ser útil en la evaluación de la función del injerto renal (IR) en el postrasplante inmediato, ya que sus niveles se incrementan posterior a la elevación de citocinas inflamatorias (IL-6, TNF-ß) durante eventos de disfunción renal. Objetivo determinar la asociación de la PCT sérica con la función del injerto renal en el periodo postrasplante inmediato. Metodología cohorte retrospectiva de septiembre del 2018 a abril del 2019 en la División de Nefrología y Trasplantes, del Centro Médico Nacional de Occidente (CMNO), del Instituto Mexicano del Seguro Social (IMSS). Se incluyeron 62 receptores de trasplante renal de donante vivo (DV) y fallecido (DF) con determinación de PCT antes del séptimo día del TR y el registro de eventos de disfunción temprana del injerto (DTI), comparados con pacientes sin DTI (sDTI). Resultados los receptores con DTI presentaron niveles más altos de PCT (13,90, 3,90, 1,22 ng/mL) comparado con el grupo sin DTI (0,32, 0,31 y 0,22 ng/ml) en los días 1, 3 y 5 respectivamente; p < 0,05. Conclusiones la PCT es un marcador biológico asociado a DTI en el postrasplante renal inmediato.

Background Procalcitonin (PCT) could be useful for evaluation of the renal allograft (RG) in the immediate post-transplant since its levels increase after elevation of the inflammatory cytokines (IL-6, TNF-ß) during events of renal failure. Purpose Our objective was to determine the association of serum PCT with the function of the RG in the immediate post-transplant. Methodology A retrospective cohort from September 2018- April 2019 in the National Western Medical Center of the Mexican Social Security Institute (IMSS), was performed. Sixty-two recipients of living donor (LD) and deceased donor (DD) renal transplant (RT) with PCT evaluation before the seventh days of RT were included; and, events of early renal allograft failure (EAF) were recorded and compared to patients no EAF (nEAF). Results The recipients with EAF presented with higher PCT levels (13.90, 3.90, 1.22 ng/mL) compared to the nEAF group (0.32, 0.31, and 0.22 ng/ml) on days 1, 3, and 5, respectively (p < 0.05). Conclusions The PCT is a biological marker associated with EAF in the immediate post-transplant.

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.

Occult hepatitis B in kidney transplants recipients and donors from Western Mexico.

BACKGROUND: Occult hepatitis B virus infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in serum and/or liver from HBsAg-negative subjects. Our aim was to determine OBI frequency in serum and genomic DNA in patients undergoing renal transplant and their cognate donors in a selected population from Western Mexico. METHODS: Blood samples were obtained from 94 donors and their cognate recipients (188 participants) before kidney transplantation. Identification of HBV DNA was carried-out by nested (S-region) and semi-nested (Pol-region) PCR in both genomic and serum DNA samples from 188 participants at pre-surgical stage and from a subset of 73 recipients at three-month follow-up. RESULTS: HBV-DNA was not detected in either genomic or serum DNA samples from recipients or donors prior to transplantation. After three-months of follow-up, 2 out of 73 (2.7%, 95% CI: 0.9-11.9%) recipients were positive to HBV-DNA (Pol-region) in genomic DNA samples using a high sensitivity Taq DNA polymerase. CONCLUSIONS: OBI incidence in recipients of kidney transplant may be higher than previously recognized. Detection of HBV-DNA was higher in genomic DNA than in serum samples using a high sensitivity Taq DNA polymerase. To the best of our knowledge, this is the first report regarding this specific topic in Mexicans.

Toxoplasma infection in kidney donors and transplant recipients from Western Mexico: A one-year follow-up.

PURPOSE: Solid organ transplant recipients are highly susceptible to Toxoplasma gondii infection. We aimed to describe the 12-month follow-up risk of seroconversion in renal transplant recipients. METHODOLOGY: Anti-T gondii antibodies were investigated in donors and recipients of renal transplants. In donors, anti-T gondii were evaluated before transplantation. In recipients, anti-T gondii were monitored over a 12-month period to evaluate potential seroconversion or reactivation. IgG and IgM anti-T gondii antibodies were investigated through enzyme immunoassay and Western blot. Molecular diagnosis was performed on peripheral blood leukocytes using PCR to amplify fragments corresponding to the T gondii B1 gene and the repetitive 529-bp element. RESULTS: The basal frequency of seropositive IgG anti-T gondii antibodies was higher in donors than in recipients (38.4% vs 25.2%; P = .03). During the 12-month follow-up, the accumulated seroconversion to IgG and IgM antibodies was 3/99 (3.0%), and the accumulated reactivation was 11/99 (11.0%). None of the samples exhibited positivity to T gondii DNA. CONCLUSIONS: This study showed that there is an increased risk of seroconversion or reactivation in renal transplant recipients over a 12-month follow-up. Our data suggest that prophylaxis with trimethoprim and sulfamethoxazole effectively prevented toxoplasmosis, since neither T gondii DNA nor clinical toxoplasmosis was detected.

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.