Obesity-related glomerulopathy: clinical and pathologic characteristics and pathogenesis.
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.
Department of Pathology, Columbia University Medical Center, 630 W. 168 Street, Room VC14-224, New York, New York 10032, USA.
Vivette D
VD
D'Agati
Department of Nephrology and Hypertension, Rabin Medical Center, 39 Jabotinsky Street, 4941492, Petah Tikva, Israel and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Avry
A
Chagnac
Department of Medicine, Division of Nephrology, Leiden University Medical Center and Leiden University, Room C7-036, PO Box 9600, 2300 RC, Leiden, Netherlands.
Aiko P J
AP
de Vries
Department of Medicine, Physiology, and Biophysics and Bioengineering, Division of Renal Diseases and Hypertension, University of Colorado, Denver, CO and University of Colorado Hospital, 12605 E 16 Ave, Aurora, Colorado 80045, USA.
Moshe
M
Levi
Center for Biomedical Research of the Canary Islands CIBICAN, University of La Laguna; Nephrology Service, Hospital Universitario de Canarias, c/OFRA s/n, 38320, La Laguna, Tenerife, Spain.
Esteban
E
Porrini
Felsenstein Medical Research Center and Department of Nephrology, Rabin Medical Center, 39 Jabotinsky Street, 4941492, Petah Tikva, Israel and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Michal
M
Herman-Edelstein
Department of Medicine, Complutense University, Instituto de Investigación, Hospital 12 de Octubre, Madrid, Spain and Department of Nephrology, Hospital 12 de Octubre. Avda de Córdoba s/n. 28041 Madrid, Spain.
Manuel
M
Praga
D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology / Q000473:pathology; D006801:Humans; D007674:Kidney Diseases / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology* / Q000628:therapy; D007678:Kidney Glomerulus / Q000473:pathology*; D009765:Obesity / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy