NLRP3 Inflammasome Activation and Atherogenic Lipid Profile in Hemodialysis Patients

End-stage renal disease (ESRD) patients who undergo hemodialysis treatment experience accelerated atherosclerosis development, which results from two main causes: atherogenic dyslipidemia and chronic inflammation. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, which serves as an essential innate immunity regulator, has links to cardiovascular disease development; yet researchers have not effectively studied its connection to atherogenic lipid profiles among dialysis patients. This study examined the association between NLRP3 inflammasome levels and the atherogenic index of plasma (AIP) in hemodialysis patients.

This study at Mansoura University Hospital focused on adults with ESRD or chronic kidney disease (CKD) stage 5 undergoing hemodialysis. Participants over 18 years attended three sessions weekly, with exclusions for pregnant individuals, previous kidney transplant patients, those on different dialysis methods, active infection sufferers, and recent medication users. The research measured serum NLRP3 inflammasome levels, hematological parameters, and lipid profiles, calculating the AIP. Sequential multivariable linear regression sensitivity models with bootstrapping examined the association between NLRP3 levels and the atherogenic index, while ensuring accuracy by checking for multicollinearity using variance inflation factors (VIFs).

Of 44 hemodialysis patients (median age 49 years, 57% female, 75% hypertensive), NLRP3 inflammasome levels showed wide variation (median 168.7 ng/L, IQR: 76.6-404.6), alongside atherogenic dyslipidemia marked by elevated indices: AIP 0.04 (-0.14 to 0.34), Castelli I 3.42 (3.01-4.61), remnant cholesterol 0.54 mmol/L (0.39-0.84), and atherogenic coefficient 2.42 (2.01-3.61), with lipids including TG 1.18 mmol/L (0.85-1.82), HDL-C 1.08 (0.92-1.21), LDL-C 2.14 (1.62-2.89). Sequential multivariable linear regression sensitivity models with bootstrapping revealed NLRP3 levels significantly associated with AIP (unadjusted B = 0.001, p < 0.001; age and gender-adjusted B = 0.001, p = 0.002; adjusted for smoking/uric acid/LDL-C/SBP B = 0.001, p = 0.016), robust via bootstrapping (2000 iterations, VIF < 1.5, no multicollinearity). Dialysis adequacy was good (K _t/V 1.48, urea reduction ratio [URR] 66.3%), with hypertensive nephropathy predominant (38.6%); complications like intradialytic hypotension (38.6%) were common. Metabolic syndrome affected 50%. Findings suggest NLRP3 inflammasome levels are associated with atherogenic dyslipidemia in maintenance hemodialysis patients. Further longitudinal studies are needed to determine causal relationships and whether NLRP3 inhibition could reduce cardiovascular risk in this population.

In this exploratory single-center study, circulating NLRP3 levels were associated with AIP-defined atherogenic lipid abnormalities in maintenance hemodialysis patients. These findings support further prospective and mechanistic studies to clarify temporality, pathway specificity, and clinical relevance.