The sodium-dependent dicarboxylate cotransporter (NaDC1) has a proposed function of reabsorbing various Krebs cycle intermediates in the kidney and the small intestine. Since Krebs cycle intermediates have been suggested to be important for renal cell survival and recovery after hypoxia and reoxygenation, the transporter may play a role in the recovery of the kidney. Additionally, mutations in the transporter homolog in Drosophila led to fly longevity which was thought to be similar to that induced by caloric restriction (CR). To clarify the role of the sodium dicarboxylate cotransporter in vivo we generated cotransporter-deficient mice. These knockout mice excreted significantly higher amounts of various Krebs cycle intermediates in their urine; thus confirming the proposed function to reabsorb these metabolic intermediates in the kidney. No other phenotypic change was identified in these mice, however. Transporter deficiency did not affect renal function under normal physiological conditions, nor did it have an effect on renal damage and recovery from ischemic injury. Additionally, the absence of the transporter did not lead to metabolic or physiological changes associated with CR. Our results suggest that although the sodium dicarboxylate cotransporter is involved in regulating levels of various Krebs cycle intermediates in the kidney, impaired uptake of these intermediates does not significantly affect renal function under normal or ischemic stress.
Background: Although there are international guidelines on management of antithrombotics (anti-platelet agents and anticoagulants) in patients undergoing colonoscopic polypectomy, both clinicians' adherence to guidelines and patients' compliance to clinicians' instructions are largely unknown. We previously reported in a retrospective study that less than 15% of clinicians documented their periendoscopy instructions on anti-thrombotic use. Aim: We aim to investigate prospectively clinician's adherence to international guideline and patients' compliance to clinicians' instructions on peri-endoscopic management of antithrombotics. Methods: The Colonoscopy Registry was established in November 2017. It collects prospective data from patients on antithrombotics use undergoing elective colonoscopies in a tertiary referral center in Hong Kong. Demographic data, types and indications of antithrombotics, peri-endoscopic management, colonoscopic findings, 7-day and 6-month follow-up for resumption of antithrombotics, post-polypectomy bleeding and serious cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or death from a vascular cause) were collected. Peri-endoscopic management of antithrombotics is defined as thoroughly adherent to the guidelines developed by Asian Pacific Association of Gastroenterology and Asian Pacific Society for Digestive Endoscopy when all conditions are fulfilled: correct decision of withholding/resuming drug, appropriate drug discontinuation, INR <2.0 before colonoscopic polypectomy and appropriate use of bridging therapy in patients on warfarin. Patient's compliance to clinicians' instructions is defined whether the use of antithrombotics during the peri-endoscopy period is consistent with clinicians' advice. Doctors' adherence was captured from casenotes while patient's compliance to clinicians' instructions were collected at face-to-face interview. Results: From November 2017 to September 2019, 610 patients receiving antithrombotics with colonoscopic polypectomy were recruited. One hundred percent, 41.2%, 71.4% of clinicians adhered to the guidelines for aspirin alone, clopidogrel alone, and dual antiplatelet therapy (DAPT), respectively. As for warfarin and direct oral anti-coagulant (DOAC), 10.2% and 41.1% of clinicians respectively has full adherence. Regarding patients' compliance, 75.3%, 41.2% ,85.7%, 38.8% and 36.8% were compliant in aspirin-alone, clopidogrel alone, DAPT, warfarin, and DOAC, respectively. Twenty patients (3.3%) developed immediate polypectomy bleeding,17 patients (2.8%) had delayed polypectomy bleeding, and 7 had serious cardiovascular events within 6-months of colonoscopy. Conclusion: Both clinicians' adherence to guidelines and patient's compliance to instructions on clopidogrel and anticoagulant use were sub-optimal. More emphasis should be put to it.
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