Clinicopathological Characteristics of Obesity-associated Focal Segmental Glomerulosclerosis

Abstract

Obesity-related glomerulopathy (ORG) is a secondary form of focal segmental glomerulosclerosis (FSGS) occurring in obese patients with a body-mass index higher than 30 kg/m(2). It is typically manifested by nephrotic-range proteinuria without full nephrotic syndrome, and progressive renal insufficiency. Characteristic morphologic features include the consistent presence of glomerulomegaly, predominance of perihilar variant of FSGS, and the relatively mild fusion of visceral epithelial cell foot processes. The concept of podocyte depletion as a driver of the glomerular scarring in obesity-associated FSGS is well documented. The underlying mechanisms are likely to be related in part to the oxidative stress and the impairment of the integrity of the slit diaphragm and cell adhesion resulting mainly from angiotensin II and transforming growth factor-β. These proapoptotic cytokines are upregulated in obesity in response to insulin resistance, compensatory hyperinsulinemia and glomerular hyperfiltration-hypertension mediated mechanical stress. This review is designed to discuss the clinicopathologic features of obesity-associated FSGS, with a focus on the podocyte injury, which is involved in the onset and progression of the glomerulosclerotic process. Ultrastructural glomerular lesions are documented.

Adiponectin Promotes Functional Recovery after Podocyte Ablation

“…With 0.1 and 0.2 mg/g dimerizer, creatinine clearance (ClCr) did not change ( Figure 2A). With 0.5 mg/g, there was a decreasing trend in ClCr from 7 to 28 days, with some recovery at 60 days, although this was not statistically significant by ANOVA (F [6,37]=2.288, P=0.06). Repeat dimerizer treatments led to a sustained decline in ClCr ( Figure 2A) and elevation of serum creatinine concentrations (Supplemental Figure 4).…”

“…Low adiponectin has been correlated with albuminuria in both mice and humans, and obesity (and, therefore, low adiponectin) may be causative in some patients with FSGS. 6,7,19,20 Adiponectin knockout (KO) mouse models demonstrate increased podocyte injury and albuminuria, with adiponectin therapies potentially restoring some renal function. 21,22 Interestingly, the relationship is inversed in human CKD: Adiponectin levels are greatly elevated in both children and adults with CKD, with serum levels directly correlated to proteinuria.…”

“…Selective injury to podocytes can result in primary diseases, such as FSGS with podocyte loss. 3,4 Podocyte loss also occurs in systemic diseases, such as early diabetic nephropathy, 5 obesity, and the metabolic syndrome, 6 resulting in a sclerosing lesion and potential progression to CKD. 7 Although the subsequent progression of these nephropathies of diverse causes may follow different paths, the loss of or injury to podocytes has become increasingly appreciated as a common starting point.…”

Obesity and kidney disease

“…28 Focal and segmental glomerulosclerosis (FSGS) is the type of glomerulonephritis most often associated with obesity. 29 FSGS associated with obesity typically presents with nephrotic syndrome and progressive renal function loss. The morphological findings include glomerulomegaly, predominance of perihilar variant and mild podocyte fusion.…”

“…The morphological findings include glomerulomegaly, predominance of perihilar variant and mild podocyte fusion. 29 Weight loss, either by dieting or through bariatric surgery, leads to proteinuria reduction. 8 The association between obesity, MS and nephrolithiasis has been observed in some studies, mainly due to increased serum uric acid levels in obese individuals.…”