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Identification of a shared gene expression pattern between T cell-mediated rejection (TCMR) and antibody-mediated rejection (AMR) in human kidney allografts may help prioritize targets for the treatment of both types of acute rejection.

We performed RNA sequencing and bioinformatics of genome-wide transcriptome profiles of urinary cells to identify novel mRNAs shared between TCMR and AMR and of mechanistic relevance. Customized RT-QPCR assays were then used to validate their abundance in urinary cells. Urinary cell transcriptome profiles and mRNA abundance were assessed in 22 urine samples matched to 22 TCMR biopsies, 7 samples matched to 7 AMR biopsies, and 24 samples matched to 24 No Rejection (NR) biopsies and correlated with biopsy diagnosis.

RNA sequencing data and bioinformatics identified 127 genes in urine to be shared between TCMR and AMR. We selected 3 novel mRNAs-ITM2A, SLAMF6, and IKZF3-for absolute quantification and validation by customized RT-QPCR assays. The abundance of all 3 mRNAs was significantly higher in urine matched to TCMR or AMR than in urine matched to NR biopsies. Receiver-operating-characteristic curve analysis showed that all 3 mRNAs distinguished TCMR or AMR from NR. Their abundance was similar in patients with TCMR and those with AMR.

State-of-the-art antirejection therapies are mostly effective to treat TCMR but not AMR. Our identification of mRNAs shared between TCMR and AMR and contributing to T cell-B cell interactions may help prioritize therapeutic targets for the simultaneous treatment of TCMR and AMR.

State-of-the-art antirejection therapies are mostly effective to treat TCMR but not AMR. Our identification of mRNAs shared between TCMR and AMR and contributing to T cell-B cell interactions may help prioritize therapeutic targets for the simultaneous treatment of TCMR and AMR.Normothermic ex vivo kidney perfusion (NEVKP) is an emerging technique for renal graft preservation. We investigated whether NEVKP could improve early function of severely injured grafts and reduce the incidence of significant renal dysfunction (SRD) similar to delayed graft function in a model of donation after circulatory death.

Kidneys from 30-kg Yorkshire pigs were removed following 120 minutes of warm ischemia (WI). These grafts were then preserved in static cold storage (SCS, n = 6) or subjected to NEVKP (n = 5) for 8 hours before heterotopic autotransplantation. SRD was defined as postoperative day (POD) 4 oliguria <500 mL/24 h with serum K +> 6.0 mmol/L.

All 4 surviving animals with 120 minutes WI grafts stored with SCS developed SRD, compared with 1/5 in the NEVKP group (

= 0.02). The NEVKP group, when compared with SCS, also demonstrated significantly decreased serum creatinine peak values (1118.51 ± 206.90 µmol/L versus 1675.56 ± 98.15 µmol/L;

= 0.002) and higher creatinine clearance (POD4 9.05 ± 6.97 mL/min versus 0.89 ± 0.56 mL/min;

= 0.05). By POD7, serum creatinine was not significantly different than baseline in the NEVKP (431.49 ± 492.50 µmol/L versus 90.19 ± 14.15 µmol/L, respectively;

= 0.20) but remained elevated following SCS (1189.25 ± 309.47 µmol/L versus 97.26 ± 29.18 µmol/L, respectively;

< 0.01). Histology demonstrated significantly decreased tubular injury scores compared with SCS grafts (

= 0.03).

Kidney grafts subjected to 120 minutes WI before retrieval showed significant improvement in function, prevention of SRD, and decreased injury following 8 hours of NEVKP.

Kidney grafts subjected to 120 minutes WI before retrieval showed significant improvement in function, prevention of SRD, and decreased injury following 8 hours of NEVKP.

Patients face obstacles in finding a transplant program that meets their healthcare needs. Acceptance criteria and waiting times vary by region and program. The Scientific Registry of Transplant Recipients provides program-specific information, but it is unclear what patients and referring physicians need to know.

We examined variability in program-specific characteristics that could influence access to transplantation. Temozolomide ic50 We also conducted 20 interviews and 16 focus groups with transplant candidates, recipients, and their family members. Participants were shown prototypes of a patient-specific search tool and evaluated its capacity to identify programs tailored to the needs of individual patients.

The distribution of recipient and donor characteristics that may impact access to transplantation, such as recipients on Medicaid, varied across programs (all with

< 0.01). Several themes emerged related to impressions of access to transplantation and the usability of patient-specific search functions. Perceptions of the prototypes and results varied, but were positive overall and support providing an individualized search of program level data. Participants revealed significant barriers to identifying and evaluating transplant programs and suggest that patient-specific search results reduce the anxiety associated with selecting a program.

Providing patient-specific tools is valued by patients and important to maximizing access to transplant.

Providing patient-specific tools is valued by patients and important to maximizing access to transplant.

Cholestasis is a sign of hepatic ischemia-reperfusion injury (IRI), which is caused by the dysfunction of hepatocyte membrane transporters (HMTs). As transcriptional regulation of HMTs during oxidative stress is mediated by nuclear factor erythroid 2-related factor 2, we hypothesized that bardoxolone methyl (BARD), a nuclear factor erythroid 2-related factor 2 activator, can mitigate cholestasis associated with hepatic IRI.

BARD (2 mg/kg) or the vehicle was intravenously administered into rats immediately before sham surgery, 60 min of ischemia (IR60), or 90 min of ischemia (IR90); tissue and blood samples were collected after 24 h to determine the effect on key surrogate markers of bile metabolism and expression of HMT genes (Mrp (multidrug resistance-associated protein) 2, bile salt export pump,

, sodium-taurocholate cotransporter, and organic anion-transporting polypeptide 1).

Significantly decreased serum bile acids were detected upon BARD administration in the IR60 group but not in the IR90 group.