Outcomes of kidney transplant recipients exposed to Chagas disease under Benznidazole prophylaxis. A single center 10-year experience.

BACKGROUND: Chagas disease (ChD) is endemic in many parts of the world and can be transmitted through organ transplantation or reactivated by immunosuppression. Organs from infected donors are occasionally used for transplantation, and the best way of managing the recipients remains a subject of debate. METHODS: We present a single-center cohort study describing a 10-year experience of kidney transplantation in patients at risk of donor-derived ChD and or reactivation. Patients received prophylactic treatment with Benznidazole and were monitored for transmission or reactivation. Monitoring included assessing direct parasitemia, serology, and polymerase chain reaction (PCR). RESULTS: Fifty-seven kidney transplant recipients (KTRs) were enrolled in the study. Forty-four patients (77.2%) were at risk of primary ChD infection, nine patients (15.8%) were at risk of disease reactivation, and four patients (7.0%) were at risk of both. All patients received Benznidazole prophylaxis, starting on the first day after transplantation. Parasitemia was assessed in 51 patients (89.5%), serology also in 51 patients (89.5%), and PCR in 40 patients (70.2%). None of the patients exhibited clinically or laboratory-detectable signs of disease. A single patient experienced a significant side effect, a cutaneous rash with intense pruritus. At 1-year post-transplantation, the patient and graft survival rates were 96.5% and 93%, respectively. CONCLUSION: In this study, no donor-derived or reactivation of Trypanosoma cruzi infection occurred in KTRs receiving Benznidazole prophylaxis.

Recurrence of membranous nephropathy after kidney transplantation: A multicenter retrospective cohort study.

Membranous nephropathy (MN) is a leading cause of kidney failure worldwide and frequently recurs after transplant. Available data originated from small retrospective cohort studies or registry analyses; therefore, uncertainties remain on risk factors for MN recurrence and response to therapy. Within the Post-Transplant Glomerular Disease Consortium, we conducted a retrospective multicenter cohort study examining the MN recurrence rate, risk factors, and response to treatment. This study screened 22,921 patients across 3 continents and included 194 patients who underwent a kidney transplant due to biopsy-proven MN. The cumulative incidence of MN recurrence was 31% at 10 years posttransplant. Patients with a faster progression toward end-stage kidney disease were at higher risk of developing recurrent MN (hazard ratio [HR], 0.55 per decade; 95% confidence interval [CI], 0.35-0.88). Moreover, elevated pretransplant levels of anti-phospholipase A2 receptor (PLA2R) antibodies were strongly associated with recurrence (HR, 18.58; 95% CI, 5.37-64.27). Patients receiving rituximab for MN recurrence had a higher likelihood of achieving remission than patients receiving renin-angiotensin-aldosterone system inhibition alone. In sum, MN recurs in one-third of patients posttransplant, and measurement of serum anti-PLA2R antibody levels shortly before transplant could aid in risk-stratifying patients for MN recurrence. Moreover, patients receiving rituximab had a higher rate of treatment response.

Single-dose antithymocyte globulin in standard immunological risk kidney transplant recipients: efficacy and kinetics of peripheral blood CD3+ T lymphocyte modulation.

BACKGROUND: Polyclonal anti-T cell antibodies (ATG or thymoglobulin®) are used as induction therapy in kidney transplant recipients. This study evaluates the safety, efficacy, and CD3+ T lymphocyte modulation of two ATG regimens. METHODS: The trial included two cohorts of kidney transplant recipients that were followed for one year. The study group, including standard immunological risk recipients, received one 3 mg/kg dose of ATG. The comparator group, including standard and high immunological risk kidney transplant recipients, received a fractionated dose regimen (up to four 1.5 mg/kg doses). Patient and graft outcomes and the kinetics of CD3+ T lymphocyte modulation in the peripheral blood were evaluated. RESULTS: One hundred kidney transplant recipients were included in each group. The one-year incidence of treated acute rejection, and patient and graft survival did not differ between groups. Bacterial infections were significantly more frequent in fractionated-dose group patients (66% versus 5%; P = 0.0001). At one-year follow-up, there was no difference in the incidence of cytomegalovirus infection (P = 0.152) or malignancies (P = 0.312). CD3+ T lymphocyte immunomodulation in the single-dose group was more effective in the first two days after transplantation. After the third post-transplant day, CD3+ T lymphocyte modulation was more efficient in the fractionated dose group. CONCLUSION: Both regimens resulted in low rejection rates and equivalent survival. The single and reduced dose regimen protects from the occurrence of bacterial infections. CD3+ T lymphocyte modulation occurred with different kinetics, although it did not result in distinct outcomes.

Case reports of hypercalcemia and chronic renal disease due to cosmetic injections of polymethylmethacrylate (PMMA) / Relatos de casos de hipercalcemia e doença renal crônica devidas a injeções de polimetilmetacrilato (PMMA) por razões estéticas

Abstract Cosmetic injections of fillers are common plastic surgery procedures worldwide. Polymethylmethacrylate (PMMA) is a filler approved only for minimally invasive procedures in facial tissue and is among the most frequently used injectable substances for cosmetic purposes. Injection of a large volume of PMMA may lead to the development of severe hypercalcemia and chronic kidney damage in a probably underestimated frequency. In such cases, hypercalcemia develops due to a granulomatous foreign body reaction with extrarenal production of calcitriol. In the present report, we describe the cases of two patients who received injections of large volumes of PMMA and developed severe hypercalcemia and advanced chronic kidney disease. These reports highlight the importance of adhering to regulations regarding the use of PMMA and properly informing patients of the possibility of complications before undertaking such procedures.

Resumo Injeções de preenchimento de caráter estético são procedimentos comuns em cirurgia plástica em todo o mundo. O polimetilmetacrilato (PMMA) é um material de preenchimento aprovado apenas para procedimentos minimamente invasivos no tecido facial, e está entre as substâncias injetáveis mais frequentemente usadas para fins estéticos. A injeção de um grande volume de PMMA pode levar ao desenvolvimento de hipercalcemia grave e lesão renal crônica em uma frequência provavelmente subestimada. Nesses casos, a hipercalcemia se desenvolve devido a uma reação granulomatosa de corpo estranho, secundária à produção extrarenal de calcitriol. No presente artigo, descrevemos os casos de dois pacientes que receberam injeções de grandes volumes de PMMA e desenvolveram hipercalcemia grave e doença renal crônica avançada. Esses relatos destacam a importância de seguir as regulamentações sobre o uso do PMMA e informar adequadamente os pacientes sobre a possibilidade de complicações antes de realizar tais procedimentos.

Case reports of hypercalcemia and chronic renal disease due to cosmetic injections of polymethylmethacrylate (PMMA).

Cosmetic injections of fillers are common plastic surgery procedures worldwide. Polymethylmethacrylate (PMMA) is a filler approved only for minimally invasive procedures in facial tissue and is among the most frequently used injectable substances for cosmetic purposes. Injection of a large volume of PMMA may lead to the development of severe hypercalcemia and chronic kidney damage in a probably underestimated frequency. In such cases, hypercalcemia develops due to a granulomatous foreign body reaction with extrarenal production of calcitriol. In the present report, we describe the cases of two patients who received injections of large volumes of PMMA and developed severe hypercalcemia and advanced chronic kidney disease. These reports highlight the importance of adhering to regulations regarding the use of PMMA and properly informing patients of the possibility of complications before undertaking such procedures.

Immunosuppression in Kidney Transplantation: State of the Art and Current Protocols.

Currently, kidney transplantation is the best treatment option for kidney failure for a majority of eligible patients. It is associated with a better quality of life and reduced mortality as compared to staying on dialysis. Many of the improvements in kidney transplant outcomes, observed in recent decades, are due to more efficient immunosuppression strategies. Therefore, developing expertise in the management of immunosuppressive drugs is key to the success of kidney transplantation. In this review, the historical aspects of organ transplant immunosuppression are briefly addressed and the basis of the allograft immune response to contextualize the main topic is provided, which is a deeper view of the immunosuppressive agents, including their known mechanisms of action, pharmacokinetics, interactions, toxicities, and clinical use. The most commonly used immunosuppressive protocols employed based on patients' and donors' characteristics are also presented here.

Recurrence of FSGS after Kidney Transplantation in Adults.

BACKGROUND AND OBJECTIVES: FSGS recurrence after kidney transplantation is a major risk factor for graft loss. However, the natural history, clinical predictors, and response to treatment remain unclear because of small sample sizes and poor generalizability of single-center studies, and disease misclassification in registry-based studies. We therefore aimed to determine the incidence, predictors, and treatment response of recurrent FSGS in a large cohort of kidney transplant recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Post-Transplant Glomerular Disease (TANGO) project is an observational, multicenter, international cohort study that aims to investigate glomerular disease recurrence post-transplantation. Transplant recipients were screened for the diagnosis of idiopathic FSGS between 2005 and 2015 and details were recorded about the transplant, clinical outcomes, treatments, and other risk factors. RESULTS: Among 11,742 kidney transplant recipients screened for FSGS, 176 had a diagnosis of idiopathic FSGS and were included. FSGS recurred in 57 patients (32%; 95% confidence interval [95% CI], 25% to 39%) and 39% of them lost their graft over a median of 5 (interquartile range, 3.0-8.1) years. Multivariable Cox regression revealed a higher risk for recurrence with older age at native kidney disease onset (hazard ratio [HR], 1.37 per decade; 95% CI, 1.09 to 1.56). Other predictors were white race (HR, 2.14; 95% CI, 1.08 to 4.22), body mass index at transplant (HR, 0.89 per kg/m2; 95% CI, 0.83 to 0.95), and native kidney nephrectomies (HR, 2.76; 95% CI, 1.16 to 6.57). Plasmapheresis and rituximab were the most frequent treatments (81%). Partial or complete remission occurred in 57% of patients and was associated with better graft survival. CONCLUSIONS: Idiopathic FSGS recurs post-transplant in one third of cases and is associated with a five-fold higher risk of graft loss. Response to treatment is associated with significantly better outcomes but is achieved in only half of the cases.

K121Q polymorphism in the Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 gene is associated with acute kidney rejection.

The identification of risk factors for acute rejection (AR) may lead to strategies to improve success of kidney transplantation. Ectonucleotidases are ectoenzymes that hydrolyze extracellular nucleotides into nucleosides, modulating the purinergic signaling. Some members of the Ectonucleotidase family have been linked to transplant rejection processes. However, the association of Ectonucleotide Pyrophosphatase / Phosphodiesterase 1 (ENPP1) with AR has not yet been evaluated. The aim of this study was to evaluate the association between the K121Q polymorphism of ENPP1 gene and AR in kidney transplant patients. We analyzed 449 subjects without AR and 98 with AR from a retrospective cohort of kidney transplant patients from Southern Brazil. K121Q polymorphism was genotyped using allelic discrimination-real-time PCR. Cox regression analysis was used to evaluate freedom of AR in kidney transplant patients according to genotypes. Q allele frequency was 17.6% in recipients without AR and 21.9% in those with AR (P = 0.209). Genotype frequencies of the K121Q polymorphism were in Hardy-Weinberg equilibrium in non-AR patients (P = 0.70). The Q/Q genotype (recessive model) was associated with AR (HR = 2.83, 95% CI 1.08-7.45; P = 0.034) after adjusting for confounders factors. Our findings suggest a novel association between the ENPP1 121Q/Q genotype and AR in kidney transplant recipients.

Different Dietary Patterns and New-Onset Diabetes Mellitus After Kidney Transplantation: A Cross-Sectional Study.

OBJECTIVE: To verify the association of dietary patterns and dietary components with new-onset diabetes mellitus after transplantation (NODAT). DESIGN: Cross-sectional study. SUBJECTS: Adult kidney transplant recipients, without history of diabetes before transplantation, who received a kidney transplant and were followed up for at least 1 year. One hundred and sixteen subjects recruited between January 2013 and August 2014. Diagnosis of NODAT was established according to the American Diabetes Association criteria for type 2 diabetes. METHODS: Demographic, clinical, and anthropometric data were collected. Dietary intake was assessed by food frequency questionnaire, administered by a registered dietitian. Dietary patterns were identified by cluster analysis. Chi-square test was used to verify the association between dietary patterns and NODAT. Total energy, fiber, and cholesterol intake were calculated. Consumption of macronutrients, carbohydrates, proteins, and fats (total fats and saturated, monounsaturated, polyunsaturated and trans fatty acids), were expressed in percentage of total energy intake. RESULTS: Twenty-eight patients developed NODAT in the follow-up period. They presented higher body mass index and body fat percentage, as well as higher levels of triglycerides and urinary protein/creatinine ratio than the non-NODAT group. Two dietary patterns, I and II, were identified. Pattern II was characterized by higher intake of total, saturated, monounsaturated, and trans fats than pattern I. No association between the dietary patterns and NODAT was identified (P = .905), and there was no difference in the distribution of macronutrients, dietary fiber, and dietary cholesterol between the groups with and without NODAT. CONCLUSION: Posttransplant dietary patterns were not different between patients with and without NODAT. Further larger and prospective studies are needed to evaluate a possible relationship between dietary components and NODAT incidence in kidney transplant recipients.

Safety and Efficacy Outcomes 3 Years After Switching to Belatacept From a Calcineurin Inhibitor in Kidney Transplant Recipients: Results From a Phase 2 Randomized Trial.

BACKGROUND: In a phase 2 study, kidney transplant recipients of low immunologic risk who switched from a calcineurin inhibitor (CNI) to belatacept had improved kidney function at 12 months postconversion versus those continuing CNI therapy, with a low rate of acute rejection and no transplant loss. STUDY DESIGN: 36-month follow-up of the intention-to-treat population. SETTING & PARTICIPANTS: CNI-treated adult kidney transplant recipients with stable transplant function (estimated glomerular filtration rate [eGFR], 35-75mL/min/1.73m2). INTERVENTIONS: At 6 to 36 months posttransplantation, patients were randomly assigned to switch to belatacept-based immunosuppression (n=84) or continue CNI-based therapy (n=89). OUTCOMES: Safety was the primary outcome. eGFR, acute rejection, transplant loss, and death were also assessed. MEASUREMENTS: Treatment exposure-adjusted incidence rates for safety, repeated-measures modeling for eGFR, Kaplan-Meier analyses for efficacy. RESULTS: Serious adverse events occurred in 33 (39%) belatacept-treated patients and 36 (40%) patients in the CNI group. Treatment exposure-adjusted incidence rates for serious infections (belatacept vs CNI, 10.21 vs 9.31 per 100 person-years) and malignancies (3.01 vs 3.41 per 100 person-years) were similar. More patients in the belatacept versus CNI group had any-grade viral infections (14.60 vs 11.00 per 100 person-years). No posttransplantation lymphoproliferative disorder was reported. Belatacept-treated patients had a significantly greater estimated gain in mean eGFR (1.90 vs 0.07mL/min/1.73m2 per year; P for time-by-treatment interaction effect = 0.01). The probability of acute rejection was not significantly different for belatacept (8.38% vs 3.60%; HR, 2.50 [95% CI, 0.65-9.65; P=0.2). HR for the comparison of belatacept to the CNI group for time to death or transplant loss was 1.00 (95% CI, 0.14-7.07; P=0.9). LIMITATIONS: Exploratory post hoc analysis with a small sample size. CONCLUSIONS: Switching patients from a CNI to belatacept may represent a safe approach to immunosuppression and is being further explored in an ongoing phase 3b trial.

Effects of metabolic syndrome on kidney transplantation outcomes: a systematic review and meta-analysis.

Metabolic syndrome (MS) has been associated with proteinuria and reduced glomerular filtration rate. Immunosuppressive agents increase the incidence of traditional risk factors for cardiovascular disease (CVD) and have known effects on MS components after kidney transplantation. The purpose of this meta-analysis was to evaluate the impact of MS on relevant outcomes after kidney transplantation. MEDLINE, EMBASE, and Cochrane Library were searched up to November 7, 2015. Papers that compared patients with and without MS and assessed one of the following outcomes, graft loss, death by cardiovascular disease, and all-cause mortality, were included. Of 585 studies identified, five studies including 1269 patients were evaluated. MS was identified as a risk factor for graft loss [relative risk, 3.06; 95% confidence interval (CI), 2.17, 4.32; I² = 0%; P heterogeneity = 0.72] and death by CVD (relative risk, 3.53; 95% CI, 1.27, 9.85; I² = 0%; P heterogeneity = 0.40). Results on the association between MS and all-cause mortality were inconclusive (relative risk, 2.61; 95% CI, 0.70, 9.81; I² = 58%; P heterogeneity = 0.09). Graft loss and death by CVD were associated with the presence of MS after transplantation. Randomized clinical trials should be conducted to define whether interventions on each MS component would result in better outcomes after transplantation.