HDCN Article Review/Hyperlink

Birmingham DJ, Shen XP, Hartman JA, Dillon JJ, Hebert LA

ACTH lowers serum lipids in steroid-treated hyperlipemic patients with kidney disease

Kidney Int (Aug) 50:538-542 1996

Hyperlipidemias are common in patients with nephrotic syndrome, progressive forms of chronic renal failure, dialysis and renal transplantation. Moreover, hyperlipidemia may play an important role in the pathogenesis of atherosclerosis and development of life-threatening cardiovascular diseases in these patient populations. The mechanisms of hyperlipidemia in these situations are complex and incompletely understood. In addition, corticosteroids (and other immunosuppressives) can cause hyperlipidemia. How steroids induce hyperlipidemia is the subject of intense investigation and debate. Moreover, it appears that multiple factors are probably involved. Increased hepatic VLDL production owing to increased insulin levels, increased dietary intake of calories and fat as a result of appetite stimulation and impaired clearance of apoB containing lipoproteins have all been suggested as explanatory factors. This study tested a new hypothesis, namely that ACTH deficiency in steroid-treated renal transplant patients and patients with chronic glomerulonephritides causes dyslipidemia. Plasma ACTH levels were at the lower limit of normal in patients prior to ACTH administration. After ACTH (1 mg subcutaneously on 8 days) over a 17 day period, the authors found that plasma concentrations of total cholesterol, LDL cholesterol, total triglycerides and total apoB decreased by 30-40% in both groups of patients. In addition, HDL cholesterol and lipoprotein lipase activity, but not hepatic lipase activity were significantly increased. Although plasma ACTH concentrations did not change both plasma and urinary cortisol levels increased markedly in response to ACTH. The fact that ACTH administration increased lipoprotein lipase activity may in part explain the lowering of plasma triglyceride. Yet other mechanisms may also be operative. In vitro evidence suggests that ACTH can directly stimulate uptake of apoB containing lipoproteins in Hep G2 cells. Whatever the mechanism, this study may have important therapeutic implications in the future.

Comment: If long-term treatment with ACTH or analogs is safe and effective for lowering elevated LDL-cholesterol and triglycerides in patients with renal disease, it could be important in affecting patient outcome. (Robert D. Toto, M.D., University of Texas Southwestern Medical Center)