Glomerular hyperfiltration in morbid obesity: Role of the inflammasome signalling.

Abstract

Obesity is associated with glomerular hyperfiltration which may precede the development of overt renal damage. Few studies evaluated the link between inflammasome signalling and hyperfiltration. The aim is to evaluate the relationship between IL1-β/Caspase-1, insulin sensitivity and hyperfiltration in subjects with severe obesity, before and after weight loss. Forty-six patients with BMI > 35 kg/m2 , without type-2-diabetes or hypertension, were evaluated at baseline and 6months after bariatric surgery with oral glucose tollerance test, bioimpedance analysis and blood tests. The eGFR was calculated according to EPIcr-cys formula and insulin sensitivity by Oral Glucose Insulin Sensitivity. IL-1β/Caspase-1 were measured with the ELISA-kit. HF was defined as eGFR ≥ 140 ml/min (non-indexed for BSA). Sixteen subjects at baseline had hyperfiltration, with a higher insulin resistance, BMI, lean mass and plasma levels of IL-1β/Caspase-1. After surgery, there was a reduction in BMI and improvement in insulin resistance in all patients. However, in 8 of 16 patients hyperfiltration persisted and IL-1β/Caspase-1 levels did not decrease (3.22 ± 0.79 vs. 3.13 ± 1.03 and 23.7± 12.1 vs. 20.6± 9.1, pre vs. post, pg/ml), while cytokines normalized in all the other patients in parallel with the eGFR. In a logistic regression model, correcting for the main covariates, lean mass and IL-1β before surgery (p= .01 and p= .03, respectively), were the only predictors of hyperfiltration. Weight loss is effective in reducing hyperfiltration in most, but not all patients. Hyperfiltration remains unchanged in subjects who do not have a reduction in IL-1β/Caspase-1, suggesting a pathogenetic role of the inflammasome signalling in the early stages of nephropathy.