Global Kidney Exchange: opportunity or exploitation? An ELPAT/ESOT appraisal

This paper addresses ethical, legal, and psychosocial aspects of Global Kidney Exchange (GKE). Concerns have been raised that GKE violates the nonpayment principle, exploits donors in low- and middle-income countries, and detracts from the aim of self-sufficiency. We review the arguments for and against GKE. We argue that while some concerns about GKE are justified based on the available evidence, others are speculative and do not apply exclusively to GKE but to living donation more generally. We posit that concerns can be mitigated by implementing safeguards, by developing minimum quality criteria and by establishing an international committee that independently monitors and evaluates GKE’s procedures and outcomes. Several questions remain however that warrant further clarificati

Preoperative dietary intake of low-dose sulforaphane induces no clinically significant effect in living donor kidney transplantation

Introduction: Sulforaphane (SFN) has anti-inflammatory properties, and is found in broccoli sprouts. Studies suggest that it protects against disease due to its anti-inflammatory activity. The impact of SFN on healthy people undergoing a surgical procedure has not been investigated. Objective: To explore the effect of SFN in living kidney donors on the postoperative inflammatory response and recovery. Methods: We performed a double-blind randomised controlled trial where donors followed a SFN-enriched (8 mg) preoperative diet. Results:A total of 42 donors were included, there were no significant differences at baseline. Postoperative inflammatory response was consistent among both arms and subjective recovery showed no significant difference. Findings regarding postoperative kidney function suggest no consistently significant impact. Discussion: A well-defined SFN-enriched diet did not have anti-inflammatory or a clinically relevant effect on the outcome. Due to the complexity of dietary modification of the inflammatory response, additional research is needed.</p

Preoperative dietary intake of low-dose sulforaphane induces no clinically significant effect in living donor kidney transplantation

Introduction: Sulforaphane (SFN) has anti-inflammatory properties, and is found in broccoli sprouts. Studies suggest that it protects against disease due to its anti-inflammatory activity. The impact of SFN on healthy people undergoing a surgical procedure has not been investigated. Objective: To explore the effect of SFN in living kidney donors on the postoperative inflammatory response and recovery. Methods: We performed a double-blind randomised controlled trial where donors followed a SFN-enriched (8 mg) preoperative diet. Results:A total of 42 donors were included, there were no significant differences at baseline. Postoperative inflammatory response was consistent among both arms and subjective recovery showed no significant difference. Findings regarding postoperative kidney function suggest no consistently significant impact. Discussion: A well-defined SFN-enriched diet did not have anti-inflammatory or a clinically relevant effect on the outcome. Due to the complexity of dietary modification of the inflammatory response, additional research is needed.</p

Caloric restriction is associated with preservation of muscle strength in experimental cancer cachexia

Caloric restriction increases lifespan and healthspan, and limits age-associated muscle wasting. In this study, we investigate the impact of 30% caloric restriction (CR) in a murine cancer cachexia model. Forty CD2F1 mice were allocated as C26 tumor-bearing (TB) + ad libitum food intake (dietary reference intake [DRI]), TB CR, non-TB (NTB) CR, or NTB matched intake (MI). TB groups were inoculated subcutaneously with 0.5x106 C26 cells 14 days after initiating CR. Bodyweight, food intake, and grip-strength were recorded periodically. Gastrocnemius (GCM) and tibialis anterior (TA) muscles were resected and weighed 3 weeks after tumor inoculation. mRNA expression of MuRF1, Atrogin-1, myogenin, and MyoD was determined. At tumor inoculation, the mean body weight of TB CR was 88.6% of initial body weight and remained stable until sacrifice. TB DRI showed wasting befor

Quercetin supplementation attenuates muscle wasting in cancer-associated cachexia in mice

BACKGROUND: Quercetin is a flavonoid with reported antioxidant, anti-inflammatory and anti-aging effects, and may limit muscle wasting in cancer cachexia. OBJECTIVE: To investigate the effect of quercetin on muscle wasting in the murine C26 cancer-cachexia model and assess the feasibility of non-invasive micro-CT analysis of skeletal muscle. MATERIALS AND METHODS: Custom CRM(P) diets supplemented with 250 mg/kg quercetin (Q) were obtained. Thirty CD2F1 mice were equally randomized to non-tumor-bearing (NTB), C26 tumor-bearing (TB), TB + Q. All groups started their allocated diet and underwent hindlimb micro-CT. Bodyweight, food intake, and grip-strength were recorded periodically. After 21 days, repeat micro-CT was performed. Gastrocnemius (GCM) and tibialis anterior (TA) muscles were resected. mRNA expression of MuRF1, Atrogin-1, myogenin, and MyoD was determined

A signature of renal stress resistance induced by short-Term dietary restriction, fasting, and protein restriction

During kidney transplantation, ischemia-reperfusion injury (IRI) induces oxidative stress. Short-Term preoperative 30% dietary restriction (DR) and 3-day fasting protect against renal IRI. We investigated the contribution of macronutrients to this protection on both phenotypical and transcriptional levels. Male C57BL/6 mice were fed control food ad libitum, underwent two weeks of 30%DR, 3-day fasting, or received a protein-, carbohydrate-or fat-free diet for various periods of time. After completion of each diet, renal gene expression was investigated using microarrays. After induction of renal IRI by clamping the renal pedicles, animals were monitored seven days postoperatively for signs of IRI. In addition to 3-day fasting and two weeks 30%DR, three days of a protein-free diet protected against renal IRI as well, whereas the other diets did not. Gene expression patterns significantly overlapped between all diets except the fat-free diet. Detailed meta-Analysis showed involvement of nuclear receptor signaling via transcription factors, including FOXO3, HNF4A and HMGA1. In conclusion, three days of a protein-free diet is sufficient to induce protection against renal IRI similar to 3-day fasting and two weeks of 30%DR. The elucidated network of common protective pathways and transcription factors further improves our mechanistic insight into the increased stress resistance induced by short-Term DR

Lack of efficacy of Doxil® in TNF-α-based isolated limb perfusion in sarcoma-bearing rats

textabstractHere we show that Doxil® has minimal antitumour activity in the isolated limb perfusion (ILP) setting and its activity was not enhanced by the addition of tumour necrosis factor (TNF). Doxil® accumulation in tumour tissue was low and also not augmented by TNF. In contrast, activity of free conventional doxorubicin was enhanced by TNF. We conclude that application of Doxil® in a TNF-based ILP is not a useful alternative to free conventional doxorubicin or melphalan

Degree of tumour vascularity correlates with drug accumulation and tumour response upon TNF-α-based isolated hepatic perfusion

Isolated hepatic perfusion (IHP) with melphalan with or without tumour necrosis factor alpha (TNF-α) is currently performed in clinical trials in patients with hepatic metastases. Previous studies led to the hypothesis that the use of TNF-α in isolated limb perfusion causes specific destruction of tumour endothelial cells and thereby induces an increased permeability of tumour vasculature. However, whether TNF-α contributes to the therapeutic efficacy in IHP still remains unclear. In an in vivo rat liver metastas

Impaired neutralising antibody formation and high transduction efficacy after isolated hepatic perfusion with adenoviral vectors

Local adenoviral gene transfer can be performed by means of isolated hepatic perfusion (IHP). This methodology is a very effective and safe way to deliver adenoviral vectors. We studied the immune response after IHP, A decreased neutralising antibody formation was observed, offering possibilities for further research in the field of gene therapy in isolated perfusion settings