Recurrent glomerular disease after kidney transplantation diagnostic and management dilemmas

Recurrent glomerular disease after kidney transplant remains an important cause of allograft failure. Many of the different entities post-transplant still suffer from incomplete knowledge on pathophysiology, and therefore lack targeted and effective therapies. In this review, we focus on specific clinical dilemmas encountered by physicians in managing recurrent glomerular disease by highlighting new insights into the understanding and treatment of post-transplant focal segmental glomerulosclerosis, membranous nephropathy, atypical hemolytic uremic syndrome, C3 glomerulopathy, amyloid light-chain (AL) amyloidosis, and IgA nephropathy

March1-dependent modulation of donor MHC II on CD103+ dendritic cells mitigates alloimmunity.

In transplantation, donor dendritic cells (do-DCs) initiate the alloimmune response either by direct interaction with host T cells or by transferring intact donor MHC to host DCs. However, how do-DCs can be targeted for improving allograft survival is still unclear. Here we show CD103+ DCs are the major do-DC subset involved in the acute rejection of murine skin transplants. In the absence of CD103+ do-DCs, less donor MHC-II is carried to host lymph nodes, fewer allogenic T cells are primed and allograft survival is prolonged. Incubation of skin grafts with the anti-inflammatory mycobacterial protein DnaK reduces donor MHC-II on CD103+DCs and prolongs graft survival. This effect is mediated through IL-10-induced March1, which ubiquitinates and decreases MHC-II levels. Importantly, in vitro pre-treatment of human DCs with DnaK reduces their ability to prime alloreactive T cells. Our findings demonstrate a novel therapeutic approach to dampen alloimmunity by targeting donor MHC-II on CD103+DCs

Pediatric kidney transplants with multiple renal arteries show no increased risk of complications compared to single renal artery grafts

BackgroundKidney allografts with multiple renal arteries (MRA) are not infrequent and have been historically associated with a higher risk of developing vascular and urologic complications. Reports of kidney transplantation using MRA allografts in the pediatric population remain scarce. The aim of this study was to evaluate if transplantation of allografts with MRA with a surgical intent of creating a single arterial inflow using vascular reconstruction techniques when required, and without the routine use of surgical drains or ureteral stents, is associated with an increased risk of complications when compared to single renal artery (SRA) grafts.MethodsWe retrospectively analyzed all pediatric renal transplant recipients performed by a single surgeon at our center between January 2015 and June 2022. Donor and recipient demographics, intraoperative data, and recipient outcomes were included. Recipients were divided into two groups based on SRA vs. MRA. Baseline variables were described using frequency distributions for categorical variables and means and standard errors for continuous variables. Comparisons of those distributions between the two groups were performed using standard chi-squared and t-tests. Time-to-event distributions were compared using the log-rank test.ResultsForty-nine pediatric transplant recipients were analyzed. Of these, 9 had donors with MRA (Group 1) and 40 had donors with SRA (Group 2). Native kidney and liver mobilization was performed in 44.4% (4/9) of Group 1 vs. 60.0% (24/40) of Group 2 cases (p = 0.39). There were no cases of delayed graft function or graft primary nonfunction. No surgical drainage or ureteral stents were used in any of the cases. One patient in Group 2 developed a distal ureter stricture. The geometric mean serum creatinine at 6- and 12-months posttransplant was 0.7 */ 1.2 and 0.9 */ 1.2 mg/dl in Group 1 and 0.7 */ 1.1 and 0.7 */ 1.1 mg/dl in Group 2. Two death-censored graft failures were observed in Group 2, with no significant difference observed between the two groups (p = 0.48).ConclusionsOur study demonstrates that pediatric renal transplantation with MRA grafts, using a surgical approach to achieve a single renal artery ostium, can be safely performed while achieving similar outcomes as SRA grafts and with a low complication rate

Immunophenotyping and Efficacy of Low Dose ATG in Non-Sensitized Kidney Recipients Undergoing Early Steroid Withdrawal: A Randomized Pilot Study

Rabbit antithymocyte globulin (ATG) is commonly used as an induction therapy in renal transplant recipients, but the ideal dosage in tacrolimus-based early steroid withdrawal protocols has not been established. The purpose of this pilot study was to determine the immunophenotyping and efficacy of lower dose ATG in low immunological-risk kidney transplant recipients. In this prospective study, 45 patients were randomized (1∶1) to our standard dose ATG (total dose 3.75 mg/kg)(sATG) vs. lower dose 2.25 mg/kg (lowATG). All patients underwent early steroid withdrawal within 7 days. The primary end point was biopsy-proven acute rejection at 12 months. Prospective immunophenotyping of freshly isolated PBMCs was performed at baseline, 3, 6, 12 months post-transplant. The rate of acute rejection was 17% and 10% in the sATG and lowATG, respectively. Effector memory T cells, Tregs and recent thymic emigrants T cells had similar kinetics post-transplant in both groups. No statistically significant differences were found in graft survival, patient survival or infections between the two groups, though there was a non-significant increase in leukopenia (43%v s. 30%), CMV (8% vs. 0) and BK (4% vs. 0) infections in sATG group vs. lowATG. In sum, in low immunological risk kidney recipients undergoing steroid withdrawal, low dose ATG seems to be efficacious in preventing acute rejection and depleting T cells with potentially lower infectious complications. A larger study is warranted to confirm these findings. Trial Registration ClinicalTrials.gov NCT0054840

Adsorption and incorporation of the zinc oxide nanoparticles in seeds of corn: germination performance and antimicrobial protection

The treatments of the seeds are important procedures applied by the agronomical area to improve the culture yield. From these procedures the micronutrients are available for the seeds before and during the germination stages. One high challenge is make efficient these treatment processes and to ensure the adsorption and the incorporation of these micronutrients in the seeds and to improve its performance in the germination phase. In this work studies explored the optimization of the incorporation process and the characteristics of the zinc oxide clusters adsorbed on the surface of the seed. The results were associated with the agronomic responses during the germinations stages of the seeds of corn. The seeds were treated in suspensions containing different concentrations of nanoparticles of zinc oxide and during different treatment times. The adsorptions in the corn surface and the absorption of the nanoparticles for the inner of the seeds were studied together with its antibacterial characteristics and correlated with the germinations indicators. The results showed that is possible to incorporate nanoparticles of zinc oxide in inner of the seeds of corn and improve the germinations indicators. Antibacterial protection was aggregated on the seeds of corn. It´s possible to incorporate 0.280 mg of zinc oxide nanoparticle per seed mass in inner of seeds with the optimal treatment conditions with nanoparticle concentration of 50 mg/L in the suspension and with treatment time of 180 minutes. With the optimal treatment concentration the normal plant percentage increase of 2.70% in relationship to the seeds not treated

mTORC1 Inhibition Protects Human Regulatory T Cells From Granzyme-B-Induced Apoptosis

Regulatory T cells (T-regs) have shown great promise as a means of cellular therapy in a multitude of allo- and auto-immune diseases-due in part to their immunosuppressive potency. Nevertheless, the clinical efficacy of human T-regs in patients has been limited by their poor in vivo homeostasis. To avert apoptosis, T-regs require stable antigenic (CD3 zeta/T-cell-receptor-mediated), co-stimulatory (CD28-driven), and cytokine (IL-2-dependent) signaling. Notably, this sequence of signals supports an activated T-reg phenotype that includes a high expression of granzymes, particularly granzyme B (GrB). Previously, we have shown that aside from the functional effects of GrB in lysing target cells to modulate allo-immunity, GrB can leak out of the intracellular lysosomal granules of host T-regs, initiating pro-apoptotic pathways. Here, we assessed the role of inhibiting mechanistic target of rapamycin complex 1 (mTORC1), a recently favored drug target in the transplant field, in regulating human T-reg apoptosis via GrB. Using ex vivo models of human T-reg culture and a humanized mouse model of human skin allotransplantation, we found that by inhibiting mTORC1 using rapamycin, intracytoplasmic expression and functionality of GrB diminished in host T-regs; lowering human T-reg apoptosis by in part decreasing the phosphorylation of S6K and c-Jun. These findings support the already clinically validated effects of mTORC1 inhibition in patients, most notably their stabilization of T-reg bioactivity and in vivo homeostasis

Produção de biomassa, composição química e atributos químicos do solo do consórcio milho-leguminosas forrageiras na comunidade Boqueirão, Sobral-CE.

Objetivou-se avaliar a produção de biomassa, composição química e os atributos químicos do solo do consórcio milho-leguminosas forrageiras numa comunidade do município de Sobral, CE. Foram avaliados os consórcios milho-cunhã e milho-crotalária num delineamento de blocos completos casualizados, com quatro repetições. As parcelas experimentais foram constituídas de seis fileiras, com 5 m de comprimento, espaçadas entre si de um metro entre milho. O plantio do milho foi realizado no dia 01 de março de 2019, enquanto que o plantio das leguminosas foi realizado no dia 14 de março de 2019. Foram observadas diferenças de teores de matéria seca entre os consórcios cunhã-milho e crotalária-milho. Observou-se que a produção do consórcio crotalária-milho foi superior em relação ao consórcio cunhã-milho, com média de 2806 kg ha-1 MS e produção superior em 45,8% em relação ao consórcio cunhã-milho. Não foram observadas diferenças de tores de proteína bruta (PB) entre os consórcios testados, com média de 12,7% de PB. Não foram observadas diferenças de tores de fibra em detergente neutro (FDN) e de ligninas (LIG) entre os consórcios testados, com médias de 43,7 e 6,7%, respectivamente. Para a fertilidade do solo, houve diferença para o emprego dos consórcios com as diferentes leguminosas para os atributos K, Cu e B. Observaram-se maiores concentrações de Cu e B no consórcio cunhã-milho, justificadas pela maior concentração desses micronutrientes na matéria seca da cunhã. O consórcio crotalária-milho apresenta maior produção e melhor qualidade do material em caso de uso para produção de volumoso no semiárido, enquanto que, para o uso como cobertura morta superficial no solo, ambos os consórcios podem ser utilizados como estratégias para ciclagem de nutrientes no solo. [Biomass production, chemical composition and soil chemical attributes of maize-legumes intercropping in boqueirão community, Sobral, CE]. Abstract: The objective of this study was to evaluate the biomass production, chemical composition and soil chemical attributes of the forage maize-legume consortium in a community of Sobral, CE. The corn-cunha and corn-crotalaria intercropping were evaluated in a randomized complete block design with four replications. The experimental plots consisted of 6 rows, 5 m long, spaced 1.0 meter apart between maize. The maize was planted on March 1, 2019, while leguminous plants were planted on March 14, 2019, in the rows of maize crop through furrows. Differences in dry matter contents were observed between the maize-cunha and maize-crotalaria intercropping. It was observed that the production of the maize-crotalaria intercropping was higher than the maizecunha, with an average of 2806 kg ha-1 DM and 45.8% higher production compared to the maize-cunha. No differences in crude protein (CP) contents were observed between the treatments, with an average of 12.7% of CP. There were no differences in neutral detergent fiber (NDF) and lignins (LIG) contents between the treatments, with means of 43.7 and 6.7%, respectively. For soil fertility there was difference for the use of intercropping with different legumes for attributes K, Cu and B. Higher concentrations of Cu and B were observed in the maize-cunha intercopping, justified by the higher concentration of these micronutrients in the dry matter of cunha. Maize-crotalaria intercropping presents higher yield and better quality of material in case of use for roughage production in the semiarid, while for use as soil mulch, both intercropping can be used as strategies for nutrient cycling in the soil.bitstream/item/208407/1/CNPC-2019-BPD-12.pd