The prevalence of
obesity in the United States remains high, exceeding 30% in most states. As this trend continues unhindered, we will continue see a persistent rise in
obesity-related metabolic effects—hypertension,
dyslipidemia,
diabetes mellitus, and
atherosclerosis. These diseases are also the leading causes of
chronic kidney diseases and
end-stage renal disease. The
lipid nephrotoxicity hypothesis, proposed over three decades ago, suggested that
proteinuria, decreased
albumin levels, and the resultant
hyperlipidemia may cause a glomerulosclerosis similar to
atherosclerosis. More recent studies have demonstrated the role of oxidized
high-density lipoprotein (HDL) and
low-density lipoprotein (
LDL) particles in the progression of
kidney disease. Elucidation of the role of
lipid-lowering
therapies and the concomitant improvement in tubulointerstitial and glomerular diseases is a further evidence of the role of
lipids in renal injury. Synergistic effects of
lipid-lowering drugs and blockers of the renin-angiotensin-aldosterone system (RAAS) in renal protection have also been documented.
Dyslipidemia in renal disease is usually characterized by elevated
LDL cholesterol, low
HDL cholesterol, and high
triglycerides. After an initial glomerular injury, likely to be inflammatory, a series of self-perpetuating events occur. Increased glomerular basement permeability leads to loss of
lipoprotein lipase activators, which results in
hyperlipidemia. Circulating
LDL has a charge affinity for glycoaminoglycans in the glomerular basement membrane and further increases its permeability. Substantial amounts of filtered
lipoprotein cause proliferation of mesangial cells. Proximal tubules reabsorb some of the filtered
lipoprotein, and the remainder is altered during passage through the nephron. If intraluminal pH is close to the isoelectric point of the
apoprotein,
luminal apoprotein will precipitate, causing tubulointerstitial disease. This review shows the evidence for the role of
lipids in development of
chronic renal disease, the pathophysiology of
lipid nephrotoxicity, and strategies available to clinicians to slow the progression of disease.