Obesity-related glomerulopathy: clinical and pathologic characteristics and pathogenesis - PubMed (original) (raw)

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Vivette D D'Agati et al. Nat Rev Nephrol. 2016 Aug.

Abstract

The prevalence of obesity-related glomerulopathy is increasing in parallel with the worldwide obesity epidemic. Glomerular hypertrophy and adaptive focal segmental glomerulosclerosis define the condition pathologically. The glomerulus enlarges in response to obesity-induced increases in glomerular filtration rate, renal plasma flow, filtration fraction and tubular sodium reabsorption. Normal insulin/phosphatidylinositol 3-kinase/Akt and mTOR signalling are critical for podocyte hypertrophy and adaptation. Adipokines and ectopic lipid accumulation in the kidney promote insulin resistance of podocytes and maladaptive responses to cope with the mechanical forces of renal hyperfiltration. Although most patients have stable or slowly progressive proteinuria, up to one-third develop progressive renal failure and end-stage renal disease. Renin-angiotensin-aldosterone blockade is effective in the short-term but weight loss by hypocaloric diet or bariatric surgery has induced more consistent and dramatic antiproteinuric effects and reversal of hyperfiltration. Altered fatty acid and cholesterol metabolism are increasingly recognized as key mediators of renal lipid accumulation, inflammation, oxidative stress and fibrosis. Newer therapies directed to lipid metabolism, including SREBP antagonists, PPARα agonists, FXR and TGR5 agonists, and LXR agonists, hold therapeutic promise.

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References

    1. JAMA. 2007 Nov 7;298(17):2038-47 - PubMed
    1. J Am Soc Nephrol. 2005 Oct;16(10):2953-66 - PubMed
    1. J Am Soc Nephrol. 2001 Jun;12(6):1211-7 - PubMed
    1. J Am Soc Nephrol. 2003 Sep;14(9):2255-63 - PubMed
    1. J Lipid Res. 2009 Feb;50(2):312-26 - PubMed

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