Glomerular hyperfiltration, which is linked to obesity, may occur before overt renal damage manifests itself. However, only a few research examined the relationship between hyperfiltration and inflammasome signaling. For a study, researchers sought to assess, both before and after weight reduction in people with extreme obesity, the association between IL1-β/Caspase-1, insulin sensitivity, and hyperfiltration.
At baseline and 6 months following bariatric surgery, 46 patients with BMI > 35 kg/m2, who did not have type-2 diabetes or hypertension, were assessed using blood tests, a bioimpedance analysis, and an oral glucose tolerance test. Insulin sensitivity was determined using the Oral Glucose Insulin Sensitivity, and the eGFR was computed using the EPIcr-cys method. In addition, the ELISA-kit was used to quantify IL-1β/Caspase-1. eGFR≥ 140 ml/min was used to define HF (non-indexed for BSA).
At baseline, 16 patients showed hyperfiltration, which was accompanied by higher levels of IL-1β/Caspase-1 in their plasma and greater insulin resistance, lean mass, and BMI. All patients saw a decrease in BMI and an improvement in insulin resistance following surgery. While cytokines normalized in all other patients concurrently with the eGFR, hyperfiltration remained in 8 of 16 patients, and IL-1β/Caspase-1 levels did not decline (3.22±0.79 vs. 3.13±1.03 and 23.7±12.1 vs. 20.6±9.1, pre vs. post, pg/ml). After adjusting for the major covariates, the only predictors of hyperfiltration in a logistic regression model were lean mass and IL-1β prior to surgery (P=.01 and P=.03, respectively).
Most patients, but not all, can reduce hyperfiltration by losing weight. However, in patients who do not see a decline in IL-1β/Caspase-1, hyperfiltration does not change, pointing to a pathogenetic function for inflammasome signaling in the early stages of nephropathy.