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- Verissimo, T., et al.
(författare)
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Decreased Renal Gluconeogenesis Is a Hallmark of Chronic Kidney Disease
- 2022
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Ingår i: Journal of the American Society of Nephrology. - : Ovid Technologies (Wolters Kluwer Health). - 1046-6673 .- 1533-3450. ; 33:4, s. 810-827
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Tidskriftsartikel (refereegranskat)abstract
- Introduction CKD is associated with alterations of tubular function. Renal gluconeogenesis is responsible for 40% of systemic gluconeogenesis during fasting, but how and why CKD affects this process and the repercussions of such regulation are unknown.Methods We used data on the renal gluconeogenic pathway from more than 200 renal biopsies performed on CKD patients and from 43 kidney allograft patients, and studied three mouse models, of proteinuric CKD (POD-ATTAC), of ischemic CKD, and of unilateral urinary tract obstruction. We analyzed a cohort of patients who benefitted from renal catheterization and a retrospective cohort of patients hospitalized in the intensive care unit.Results Renal biopsies of CKD and kidney allograft patients revealed a stage-dependent decrease in the renal gluconeogenic pathway. Two animal models of CKD and one model of kidney fibrosis confirm gluconeogenic downregulation in injured proximal tubule cells. This shift resulted in an alteration of renal glucose production and lactate clearance during an exogenous lactate load. The isolated perfused kidney technique in animal models and renal venous catheterization in CKD patients confirmed decreased renal glucose production and lactate clearance. In CKD patients hospitalized in the intensive care unit, systemic alterations of glucose and lactate levels were more prevalent and associated with increased mortality and a worse renal prognosis at follow-up. Decreased expression of the gluconeogenesis pathway and its regulators predicted faster histologic progression of kidney disease in kidney allograft biopsies.Conclusion Renal gluconeogenic function is impaired in CKD. Altered renal gluconeogenesis leads to systemic metabolic changes with a decrease in glucose and increase in lactate level, and is associated with a worse renal prognosis.
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- Apostolopoulou, E., et al.
(författare)
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Radical social innovations and the spatialities of grassroots activism: navigating pathways for tackling inequality and reinventing the commons
- 2022
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Ingår i: Journal of Political Ecology. - 1073-0451. ; 29, s. 143-188
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Tidskriftsartikel (refereegranskat)abstract
- In this article, by drawing on empirical evidence from twelve case studies from nine countries from across the Global South and North, we ask how radical grassroots social innovations that are part of social movements and struggles can offer pathways for tackling socio-spatial and socio-environmental inequality and for reinventing the commons. We define radical grassroots social innovations as a set of practices initiated by formal or informal community-led initiatives or/and social movements which aim to generate novel, democratic, socially, spatially and environmentally just solutions to address social needs that are otherwise ignored or marginalised To address our research questions, we draw on the work of Cindi Katz to explore how grassroots innovations relate to practices of resilience, reworking and resistance. We identify possibilities and limitations as well as patterns of spatial practices and pathways of re-scaling and radical praxis, uncovering broadly-shared resemblances across different places. Through this analysis we aim to make a twofold contribution to political ecology and human geography scholarship on grassroots radical activism, social innovation and the spatialities of resistance. First, to reveal the connections between social-environmental struggles, emerging grassroots innovations and broader structural factors that cause, enable or limit them. Second, to explore how grassroots radical innovations stemming from place-based community struggles can relate to resistance practices that would not only successfully oppose inequality and the withering of the commons in the short-term, but would also open long-term pathways to alternative modes of social organization, and a new commons, based on social needs and social rights that are currently unaddressed.
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- Legouis, D., et al.
(författare)
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Altered proximal tubular cell glucose metabolism during acute kidney injury is associated with mortality
- 2020
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Ingår i: Nature Metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:8
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Tidskriftsartikel (refereegranskat)abstract
- Acute kidney injury (AKI) is strongly associated with mortality, independently of its cause. The kidney contributes to up to 40% of systemic glucose production by gluconeogenesis during fasting and under stress conditions. Whether kidney gluconeogenesis is impaired during AKI and how this might influence systemic metabolism remain unknown. Here we show that glucose production and lactate clearance are impaired during human and experimental AKI by using renal arteriovenous catheterization in patients, lactate tolerance testing in mice and glucose isotope labelling in rats. Single-cell transcriptomics reveal that gluconeogenesis is impaired in proximal tubule cells during AKI. In a retrospective cohort of critically ill patients, we demonstrate that altered glucose metabolism during AKI is a major determinant of systemic glucose and lactate levels and is strongly associated with mortality. Thiamine supplementation increases lactate clearance without modifying renal function in mice with AKI, enhances glucose production by renal tubular cells ex vivo and is associated with reduced mortality and improvement of the metabolic pattern in a retrospective cohort of critically ill patients with AKI. This study highlights an unappreciated systemic role of renal glucose and lactate metabolism under stress conditions, delineates general mechanisms of AKI-associated mortality and introduces a potential intervention targeting metabolism for a highly prevalent clinical condition with limited therapeutic options.
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