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Hypothermic oxygenated machine perfusion (HOPE) was recently tested in preclinical trials in kidney transplantation (KT). Here we investigate the effects of HOPE on extended-criteria-donation (ECD) kidney allografts (KA). Fifteen ECD-KA were submitted to 152 ± 92 min of end-ischemic HOPE and were compared to a matched group undergoing conventional-cold-storage (CCS) KT (n = 30). Primary (delayed graft function-DGF) and secondary (e.g. postoperative complications, perfusion parameters) endpoints were analyzed within 6-months follow-up. There was no difference in the development of DGF between the HOPE and CCS groups (53% vs. 33%, respectively; p = 0.197). Serum urea was lower following HOPE compared to CCS (p = 0.003), whereas the CCS group displayed lower serum creatinine and higher eGFR rates on postoperative days (POD) 7 and 14. The relative decrease of renal vascular resistance (RR) following HOPE showed a significant inverse association with serum creatinine on POD1 (r = − 0.682; p = 0.006) as well as with serum urea and eGFR. Besides, the relative RR decrease was more prominent in KA with primary function when compared to KA with DGF (p = 0.013). Here we provide clinical evidence on HOPE in ECD-KT after brain death donation. Relative RR may be a useful predictive marker for KA function. Further validation in randomized controlled trials is warranted. Trial registration: clinicaltrials.gov (NCT03378817, Date of first registration: 20/12/2017).

Increased hydration is recommended as healthy habit with several merits. However, supportive data are sparse. To assess the efficacy of increased daily water intake, we tested the effect of water supplementation on biomarkers in blood, urine, and saliva. Twenty-four healthy Japanese men and 31 healthy Japanese women with fasting blood glucose levels ranging from 90–125 mg/dL were included. An open-label, two-arm, randomized controlled trial was conducted for 12 weeks. Two additional 550 mL bottles of water on top of habitual fluid intake were consumed in the intervention group. The subjects drank one bottle of water (550 mL) within 2 h of waking, and one bottle (550 mL) 2 h before bedtime. Subjects increased mean fluid intake from 1.3 L/day to 2.0 L/day, without changes in total energy intake. Total body water rate increased with associated water supplementation. There were no significant changes in fasting blood glucose and arginine vasopressin levels, but systolic blood pressure was significantly decreased in the intervention group. Furthermore, water supplementation increased body temperature, reduced blood urea nitrogen concentration, and suppressed estimated glomerular filtration rate reduction. Additionally, existence of an intestinal microbiome correlated with decreased systolic blood pressure and increased body temperature. Habitual water supplementation after waking up and before bedtime in healthy subjects with slightly elevated fasting blood glucose levels is not effective in lowering these levels. However, it represents a safe and promising intervention with the potential for lowering blood pressure, increasing body temperature, diluting blood waste materials, and protecting kidney function. Thus, increasing daily water intake could provide several health benefits.

ObjectivesThis study is aimed to establish a fusion model of radiomics-based nomogram to predict the renal function of autosomal dominant polycystic kidney disease (ADPKD).MethodsOne hundred patients with ADPKD were randomly divided into training group (n = 69) and test group (n = 31). The radiomics features were extracted from T1-weighted fat suppression images (FS-T1WI) and T2-weighted fat suppression images (FS-T2WI). Decision tree algorithm was employed to build radiomics model to get radiomics signature. Then multivariate logistic regression analysis was used to establish the radiomics nomogram based on independent clinical factors, conventional MR imaging variables and radiomics signature. The receiver operating characteristic (ROC) analysis and Delong test were used to compare the performance of radiomics model and radiomics nomogram model, and the decision curve to evaluate the clinical application value of radiomics nomogram model in the evaluation of renal function in patients with ADPKD.ResultsFourteen radiomics features were selected to establish radiomics model. Based on FS-T1WI and FS-T2WI sequences, the radiomics model showed good discrimination ability in training group and test group [training group: (AUC) = 0.7542, test group (AUC) = 0.7417]. The performance of radiomics nomogram model was significantly better than that of radiomics model in all data sets [radiomics model (AUC) = 0.7505, radiomics nomogram model (AUC) = 0.8435, p value = 0.005]. The analysis of calibration curve and decision curve showed that radiomics nomogram model had more clinical application value.Conclusionradiomics analysis of MRI can be used for the preliminary evaluation and prediction of renal function in patients with ADPKD. The radiomics nomogram model shows better prediction effect in renal function evaluation, and can be used as a non-invasive renal function prediction tool to assist clinical decision-making.Trial Registration ChiCTR, ChiCTR2100046739. Registered 27 May 2021—retrospectively registered, http://www.ChiCTR.org.cn/showproj.aspx?proj=125955.

Background and Objective Zibotentan, a selective endothelin A receptor antagonist, is in development for chronic liver and kidney disease. The pharmacokinetics (PK) of zibotentan were previously investigated in patients with either renal impairment or hepatic impairment, but the impact of both pathologies on PK was not evaluated. This study evaluated the PK and tolerability of a single oral dose of zibotentan in participants with concurrent moderate renal impairment and moderate hepatic impairment versus control participants. Methods Twelve participants with moderate renal and hepatic impairment and 11 healthy matched control participants with no clinically significant liver or kidney disease were enrolled in an open-label, parallel-group study design. After administration of a single oral dose of zibotentan 5 mg, blood and urine sampling was performed. Pharmacokinetic parameters were determined for each of the two cohorts and compared. Comparisons between the cohorts were based on the geometric least squares mean ratio for the primary endpoints, which were area under the plasma concentration-time curve (AUC) from time zero to infinity (AUC ∞ ) and from time zero to the time of the last measurable concentration (AUC last ), and maximum plasma drug concentration ( C max ) on Day 1 through 120 h post-dose. Secondary endpoints included apparent total body clearance (CL/F) on Day 1 through 120 h post-dose. Safety endpoints were assessed up to discharge. Results In total, 11 participants with concurrent moderate renal and hepatic impairment, and 11 controls, completed the study. Zibotentan was generally well tolerated, and no new clinically significant safety findings were observed. Total exposure (AUC ∞ and AUC last ) was approximately 2.10-fold higher in participants with concurrent moderate renal and hepatic impairment versus controls, while C max and total nonrenal body clearance were similar among all groups. A regression-based post hoc analysis, comparing exposure and CL/ F in patients with concurrent impairment to patients with either renal or hepatic impairment alone, showed that CL/ F with concurrent impairment was approximately half of that in controls and was positively correlated with reduction of renal function. Inclusion of the data on concurrent moderate renal and hepatic impairment in the regression analysis led to a narrower confidence interval for the predicted mean CL/ F in participants with moderate hepatic impairment. Conclusion The presented findings advance the understanding of the PK of zibotentan in both renal impairment and hepatic impairment, with and without overlapping pathologies, and will thus increase the confidence of dose selection in future studies, particularly in vulnerable patient populations with concurrent renal and hepatic impairment. Trial Registration ClinicalTrials.gov identifier: NCT05112419.