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The human soluble epoxide hydrolase (sEH) is a bifunctional enzyme that modulates the levels of regulatory epoxy lipids. The hydrolase activity is carried out by a catalytic triad located at the center of a wide L-shaped binding site, which contains two hydrophobic subpockets at both sides. On the basis of these structural features, it can be assumed that desolvation is a major factor in determining the maximal achievable affinity that can be attained for this pocket. Accordingly, hydrophobic descriptors may be better suited to the search of novel hits targeting this enzyme. This study examines the suitability of quantum mechanically derived hydrophobic descriptors in the discovery of novel sEH inhibitors. To this end, three-dimensional quantitative structure-activity relationship (3D-QSAR) pharmacophores were generated by combining electrostatic and steric or alternatively hydrophobic and hydrogen-bond parameters in conjunction with a tailored list of 76 known sEH inhibitors. The pharmacophore models were then validated by using two external sets chosen (i) to rank the potency of four distinct series of compounds and (ii) to discriminate actives from decoys, using in both cases datasets taken from the literature. Finally, a prospective study was performed including a virtual screening of two chemical libraries to identify new potential hits, which were subsequently experimentally tested for their inhibitory activity on human, rat, and mouse sEH. The use of hydrophobic-based descriptors led to the identification of six compounds as inhibitors of the human enzyme with IC50 < 20 nM, including two with IC50 values of 0.4 and 0.7 nM. The results support the use of hydrophobic descriptors as a valuable tool in the search of novel scaffolds that encode a proper hydrophilic/hydrophobic distribution complementary to the target's binding site.

Manuel Torres-Gutiérrez,1 Nicolás Lozano-Suárez,2 Viviana A Burgos-Camacho,1 Jessica Caamaño-Jaraba,1 Julia Andrea Gómez-Montero,2 Andrea García-López,2 Fernando Girón-Luque2,3 1Department of Mental Health, Colombiana de Trasplantes, Bogotá, Colombia; 2Department of Transplant Research, Colombiana de Trasplantes, Bogotá, Colombia; 3Department of Transplant Surgery, Colombiana de Trasplantes, Bogotá, ColombiaCorrespondence: Andrea García-López, Transplant Research, Colombiana de Trasplantes, Av Carrera, 30 No. 47 A-74, Bogota, 111311, Colombia, Email aegarcia@colombianadetrasplantes.comIntroduction: Non-adherence in kidney transplants is diversely defined. Immunosuppression non-adherence (INA) is the most used definition and has been associated with graft loss and acute rejection. But INA assesses only one fraction of adherence. Therefore, we analyzed the association of a holistic non-adherence definition with transplant outcomes and compared its prediction performance with other definitions.Methods: We retrospectively included 739 kidney recipients between 2019 and 2021. We evaluated holistic non-adherence (HNA), suboptimal-immunosuppressor levels (SIL), appointment non-adherence (ANA), procedure non-adherence (PNA) and INA. The main outcomes were graft loss, graft rejection, and mortality. A backward logistic regression was performed estimating adjusted and un-adjusted odds ratio (OR) for each outcome. Finally, we compared the non-adherence definitions’ prediction for the main outcomes using the area under the curve.Results: HNA was present in 28.7% of patients. Non-adherent patients had an adjusted OR of 2.66 (1.37– 5.15) for mortality, 6.44 for graft loss (2.71– 16.6), and 2.28 (1.15– 4.47) for graft rejection. INA and PNA presented a moderate discrimination for graft loss and HNA and ANA mild-to-moderate discrimination for graft loss and death.Conclusion: Holistic non-adherence was associated with worst outcomes in kidney recipients and had a significant prediction performance for graft loss and mortality.Keywords: kidney transplantation, patient adherence, mortality, graft survival, patient outcome assessment

Manuel Torres-Gutiérrez,1 Viviana Burgos-Camacho,1 Jessica Paola Caamaño-Jaraba,1 Nicolás Lozano-Suárez,2 Andrea García-López,2 Fernando Girón-Luque2,3 1Department of Mental Health, Colombiana de Trasplantes, Bogotá, Colombia; 2Department of Transplant Research, Colombiana de Trasplantes, Bogotá, Colombia; 3Department of Transplant Surgery, Colombiana de Trasplantes, Bogotá, ColombiaCorrespondence: Andrea García-López, Transplant Research, Colombiana de Trasplantes, Av Carrera, 30 No. 47 A-74, Bogota, 111311, Colombia, Email aegarcia@colombianadetrasplantes.comIntroduction: In renal transplant recipients, compliance with medical therapy is vital. Non-adherence is considered a risk factor for worst outcomes in kidney recipients, with attributed outcomes of 64% for graft loss and 80% for late acute rejection. Most literature defines adherence as self-based immunosuppression compliance but does not consider other relevant factors such as consult and procedure compliance. Therefore, this study aims to describe adherence prevalence in kidney transplant recipients and the factors related to non-adherence.Methods: This cross-sectional study included 1030 renal transplant patients followed by Colombiana de Trasplantes between January 2019 and July 2021. Sociodemographic and clinical variables were obtained based on clinical records. The mental-health group diagnosed holistic adherence in a semi-structured interview. The diagnosis considered medication intake failure, frequency and number of failures to medical controls or other procedures, suspicious non-adherence behaviors, and serum levels of immunosuppressants. A bivariate followed a descriptive analysis, and a forward logistic regression was performed for non-adherence.Results: Patients had a median of 47 years, and 58.1% were male. Non-adherence was presented in 30.7% of patients. The non-adherence patients were younger, with a higher prevalence of males, single, divided transplant care, had a longer time after transplantation, psychopathological diagnosis, and more reinforcement education by only nursing. Older age and multidisciplinary reinforcement education were protective factors. On the other hand, poor social support, psychopathology diagnosis, and longer time after transplant presented as non-adherence risk factors.Conclusion: Holistic non-adherence was diagnosed in approximately one-third of renal transplant recipients. Its definition included more than just medication non-compliance and could identify more non-adherent patients. Notably, there is a need to consider the related factors in the health follow-up and encourage future research in modifiable factor interventions aiming to increase adherence and achieve better outcomes for renal transplant patients.Keywords: treatment adherence and compliance, kidney transplantation, patient compliance, social support, patient education, mental health, psychopathology

Laura Nino-Torres,1 Andrea Garcia-Lopez,2 Nasly Patino-Jaramillo,2 Fernando Giron-Luque,1 Alejandro Nino-Murcia1 1Department of Transplantation Surgery, Colombiana de Trasplantes, Bogotá, Colombia; 2Department of Transplantation Research, Colombiana de Trasplantes, Bogotá, ColombiaCorrespondence: Alejandro Nino-Murcia, Transplant Surgeon, Colombiana de Trasplantes, Av Carrera, 30 No. 47 A-74, Bogota, 111311, Colombia, Tel +57 3112499999, Email anino@colombianadetrasplantes.comBackground and Purpose: Kidney transplantation (KT) is the best therapy for chronic kidney disease (CKD). Major urologic complications (MUCs) are the second etiology associated to morbidity and graft loss following KT, after rejection episodes. The objective of this study was to estimate the incidence, risk factors and impact on graft survival associated to urological complications in KT patients.Patients and Methods: A retrospective cohort based on electronic patient files of kidney transplant recipients from Colombiana de Trasplantes was created for the period August 2008 to September 2019. Initiation of follow-up was defined as the date of transplantation up to 3 years post-transplantation. Incidence of ureteral stenosis, ureteral obstruction, and ureteral leak was measured. A logistic regression multivariate model was adjusted to determine the associated factors to MUCs (yes/no). Patient and graft survival time were analyzed using a Kaplan-Meier method.Results: A total of 1584 KT patients were included in the cohort. MUCs were present in 195 (12.6%) KT patients. We found that dialysis duration (OR: 1.004; p = 0.02) remained significant for the incidence of MUCs in KT patients of deceased donors. Probability of graft and patient survival at 3 years of follow-up was 90.5% and 85.5%, respectively. No significant difference was found on graft and patient survival in KT patients with or without MUCs.Conclusion: MUCs are frequent complications for KT. We did not observe significant differences in graft or patient survival according to the presence of MUCs. The identification of MUCs and risk factors may guide transplant teams for future surgical and clinical decisions.Keywords: major urologic complications, kidney transplantation, graft survival, patient survival

Fernando Giron-Luque,1 Yenny Baez-Suarez,1 Andrea Garcia-Lopez,2 Nasly Patino-Jaramillo2 1Surgery Department, Colombiana de Trasplantes, Bogotá, Colombia; 2Research Department, Colombiana de Trasplantes, Bogotá, ColombiaCorrespondence: Andrea Garcia-LopezResearch Department, Colombiana de Trasplantes, Av Carrera 30, No. 47A-74, Bogotá, ColombiaTel +57 300 502 4618Email aegarcia@colombianadetrasplantes.comBackground and Purpose: Vascular multiplicity is the most frequent anatomic variation in kidney donors. Despite concerns about risks, these allografts are increasingly used to overcome the shortage of kidney donors. The safety and clinical outcomes in living kidney donors were evaluated with vascular multiplicity after hand-assisted laparoscopic living donor nephrectomy (HALDN).Patients and Methods: Data from all living kidney donors who underwent HALDN from 2008 to 2021 was retrospectively reviewed. Patients were divided into two groups as single (SRV) and multiple renal vessels (MRV), and a comparative analysis was done. The primary outcomes include operating room time (ORT), days of hospital stay, estimated blood loss, complications, conversion, and re-operations.Results: MRV were present in 166 out of 612 donors (27.1%). Among those, 10 (1.6%) donors had simultaneous multiple arteries and veins. Additionally, the prevalence of artery and vein multiplicity was 21.8% (n = 134) and 3.5% (n = 22), respectively. Warm ischemia time was significantly different among the two groups but not clinically important. The number of conversions to open technique, the mean ORT, the median blood loss, and days of hospital stay were similar between the SRV and MRV groups, without significant differences. According to the modified Clavien-classification system, no differences were found in the complication rates between the two groups (p = 0.29). Complication rates were 3.3% and 3.6% for the SRV and MRV groups, respectively.Conclusion: HALDN is a procedure with safe intraoperative results, even with vascular multiplicity. The presence of multiple renal arteries or veins has no negative impact on the outcome of the donor after living donor nephrectomy.Keywords: kidney transplant, vascular multiplicity, living kidney donors, laparoscopic nephrectomy, anatomic variation