Obesity-related glomerulopathy: clinical and pathologic characteristics and pathogenesis

The incidence of obesity-related glomerulopathy (ORG) is increasing in parallel with the worldwide obesity epidemicPathologic features of ORG include glomerulomegaly and focal segmental glomerulosclerosis (FSGS), particularly the perihilar variant; the degree of foot process effacement in ORG is usually less than in primary FSGSSubnephrotic proteinuria is the most common clinical presentation of ORG; some patients have nephrotic-range proteinuria and progressive loss of renal function but full nephrotic syndrome is highly unusualMajor renal physiologic responses to obesity include increases in glomerular filtration rate, renal plasma flow, filtration fraction and tubular reabsorption of sodiumAdipokines and ectopic lipid accumulation in the kidney promote maladaptive responses of renal cells to the mechanical forces of hyperfiltration, leading to podocyte depletion, proteinuria, FSGS and interstitial fibrosisTherapeutic interventions include renin–angiotensin–aldosterone inhibition and weight loss; novel strategies involve administration of small molecules that specifically modulate deleterious pathways of fatty acid and cholesterol metabolism