Glomerular hyperfiltration in morbid obesity: Role of the inflammasome signalling

Aim 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-beta/Caspase-1, insulin sensitivity and hyperfiltration in subjects with severe obesity, before and after weight loss. Methods Forty-six patients with BMI > 35 kg/m(2), without type-2-diabetes or hypertension, were evaluated at baseline and 6 months 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-1 beta/Caspase-1 were measured with the ELISA-kit. HF was defined as eGFR >= 140 ml/min (non-indexed for BSA). Results Sixteen subjects at baseline had hyperfiltration, with a higher insulin resistance, BMI, lean mass and plasma levels of IL-1 beta/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-1 beta/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-1 beta before surgery (p = .01 and p = .03, respectively), were the only predictors of hyperfiltration. Conclusion 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-1 beta/Caspase-1, suggesting a pathogenetic role of the inflammasome signalling in the early stages of nephropathy.

Automated summary

Obesity is associated with glomerular hyperfiltration, and inflammasome signaling may play a role in this process. This study found that weight loss can reduce hyperfiltration in most obese patients, but not all. Patients who did not show a decrease in IL-1 beta/Caspase-1 levels had persistent hyperfiltration. Early intervention targeting inflammasome signaling may be important in preventing the development of obesity-related kidney disease.