A TRIGLYCERIDE-RICH LIPOPROTEIN ENVIRONMENT EXACERBATES RENAL INJURY IN THE ACCELERATED NEPHROTOXIC NEPHRITIS MODEL

Summary

Hyperlipidemia accompanies chronic renal disease either as a consequence of the renal dysfunction or as part of generalised metabolic derangements. Under both situations, the lipid profile is characterised by accumulation of triglyceride-rich lipoproteins (TGRLs). This lipid profile is increasingly recognised as a risk factor for cardiovascular complications. Whether it may pose a risk for renal injury as well remains unclear. A hyper-TGRL state was generated in C57BL/6 mice using the poloxamer-407 (P-407) and immune complex-mediated renal injury was triggered using the accelerated nephrotoxic nephritis (ANTN) model. The hyper-TGRL animals were hypersensitive to ANTN demonstrated by greater haematuria and glomerular cellularity. These changes were accompanied by increased glomerular accumulation of CD68⁺ macrophages. The hypersensitive response to ANTN was not seen in low density lipoprotein receptor knock-out mice fed with high fat diet, where triglyceride levels were lower but cholesterol levels comparable to those obtained using P-407. These data indicate that a hyper-TGRL state might be more detrimental to the kidneys than low density lipoprotein driven hypercholesterolemia during immune complex-mediated nephritis. We speculate that the hyper-TGRL environment primes the kidney to exacerbated renal damage following an inflammatory insult with increased accumulation of macrophages that may play a key role in mediating the injurious effects. This article is protected by copyright. All rights reserved.