LAUSR

saltinduced hypertension and its associated renal and cardiovascular complications are a major cause of chronic kidney disease (CKD), but the mechanisms are not well understood. a new study by Markus rinschen, Oleg Palygin, alexander staruschenko, Gary siuzdak and colleagues reveals the contributions of metabolic changes in renal glomeruli in a rat model of kidney hypertension and suggests that metabolic interventions might be useful in treating hypertensioninduced kidney disease. “understanding the functional processes in the whole kidney presents a tremendous experimental challenge owing to the structural and functional heterogeneity of kidney tissue, and the rapid pathophysiological changes that occur during the progression of disease states like hypertension,” explains Palygin. “in order to directly assess the metabolic aspects of hypertensioninduced glomerular sclerosis we used a multiomics strategy, integrating metabolomics, phosphoproteomics and proteomics.” the researchers performed untargeted and targeted metabolomic analyses in a wellknown model of kidney hypertension, the Dahl saltsensitive (Dss) rat. they found increases in lipid breakdown and reductions in branchedchain amino acids in Dss rats. Oxidative stress and reductions in products of central carbon metabolism were also found in glomeruli. Phosphoproteomic analysis on glomeruli of the Dss rat revealed the activation of aMPK and the inhibition of the kinasecontaining complex mtOrC1, and suggested that metabolic signalling through these kinases controls major pathophysiological pathways in glomeruli. using proteomic analysis, the researchers showed that alterations in the abundance of metabolic enzymes correlated with the metabolic changes seen during early stages of hypertensive kidney disease. the researchers say that their findings indicate that metabolic or dietary interventions might be useful in preventing the adverse effects of hypertension on the kidney.