Abstract
Advanced multiomics analysis has revealed novel pathophysiological mechanisms in kidney disease. In particular, proteomic and metabolomic analysis shed light on mitochondrial dysfunction (mitochondrial stress) by glycation in diabetic or age-related kidney disease. Further, metabolic damage often results from organelle stress, such as mitochondrial stress and endoplasmic reticulum (ER) stress, as well as interorganelle communication, or “organelle crosstalk”, in various kidney cells. These contribute to progression of the disease phenotype. Aberrant tubular mitochondrial lipid metabolism leads to tubular inflammation and fibrosis. This review article summarizes updated evidence regarding organelle stress, organelle crosstalk, and metabolic derangement in kidney disease.
Highlights
Significant population growth and aging have contributed to a global increase in chronic kidney disease (CKD)
Based on findings that (1) the cyclic GMP-AMP synthase stimulator of interferon genes (STING) pathway detects cytosolic DNA and induces innate immunity and (2) STING is an endoplasmic reticulum (ER) membrane resident molecule, we investigated the role of the cGAS-STING pathway on mitochondrial damage of Acute Kidney Injury (AKI)
I summarize how multiomics analysis helps us understand the novel mechanisms of development and progression of disease phenotypes
Summary
Significant population growth and aging have contributed to a global increase in chronic kidney disease (CKD). 850 million people are estimated to have some form of kidney disease, making it the 11th leading cause of global mortality. 2.6 million people with end-stage kidney disease receive dialysis or transplantation, and the annual costs of dialysis and transplantation range from 35,000 USD to 100,000 USD per patient. The high costs of these treatment modalities lead to a more serious problem, namely huge gaps between the actual number of patients undergoing kidney replacement therapy, and the estimated number of patients with end-stage kidney disease in low-middle income countries and low-income countries [1]. Analysis of the Global Burden of Disease study data from 1990 to 2016 has revealed increases in the incidence of CKD of 89%, prevalence of CKD of 87%, death due to CKD of 98%, and disability-adjusted-life-years (DALYs) of 62% [2]. It is critical to understand the pathophysiology of kidney disease and develop novel therapeutic approaches
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