(dyslipidemia) (CKD) (CVD) (CKD) (nephrotic syndrome) (dyslipidemia) (proteinuria) (hypercholesterolemia) (hypertriglyceridemia) B (apolipoprotein(apo)b) (VLDL) (IDL)(LDL) (HDL) ( VLDL) (HDL-C) LDL-C HDL-C LDL-C (GFR)3 5 ( VLDL IDL) 76 96 19 2
(atherogenic) B (apolipoprotein (apo)b) (lipase) (hyperlipidemia) (glomerulosclerosis)(mesangial proliferation) [1] [2,3,4]5/6 HDL [5] (endothelial) (mesangial) ( ) [2] mesangial LDL-C LDL-C[6] mesangial LDL-C LDL-C (mesangial proliferation) (epidemiologic) Physicians Health Study 13 4483 132 µmol/l (renal insufficiency, 132 µmol/l) (creatinine) HDL [7] (atherosclerosis risk in communities study) dyslipidemia (Modification of Diet in Renal Disease Study)HDL [8] (Hyperlipidemia) ( )(phospholipids) (tubulointerstitial) [2,9] (glomerular mesangium) (matrix) (glomerulosclerosis) [3,10,11] LDL (mesangial)(matrix proteins) (proinflammatory cytokines) [2,12,13,14] H D L (Reverse cholesterol transport) HDL [7,15] (LCAT) HDL 96 19 2 77
HDL [16] (Nephrotic syndrome) (LCAT)HDL [17,18]Acyl-CoA: cholesterol acyltransferase (ACAT) [5,19] (CKD) (CKD) statin [20,21] (meta-analysis) 13 statins (GFR) (ESRD) [22] (Heart Protection Study) statin creatinine[23] 3 statin [24] (post hoc analysis) Cholesterol and Recurrent Event Study [25] (CKD) (GFR) statin GFR 40 ml/min statin (GFR)[25] statinsgfr 12CKD (metaanalysis)statins GFR (0.16 ml/min/month; 95% CI, 0.03 to 0.29) [26] 690( GFR 60 ml/min/1.73 m 2 ) statins [27] Bianchi 56 atorvastatin 10 40 [28] (P 0.01) (CKD) (Veterans Affairs facilities) gemfibrozil 5 [29] gemfibrozil Fibrates creatinine [30] GFRcreatinine creatinine [31,32,33]niceritrol (nicotinic acid ) 12 (CKD) [34] (Hyperlipidemia) 78 96 19 2
statins statins proteinuria statins statins statins 1. Kasiske BL, O Donnell MP, Schmitz PG, Kim Y, Keane WF: Renal injury of diet-induced hypercholesterolemia in rats. Kidney Int 1990; 37: 880-91. 2. Magil AB: Interstitial foam cells and oxidized lipoprotein in human glomerular disease. Mod Pathol 1999; 12: 33-40. 3. Moorhead JF, Wheeler DC, Varghese Z: Glomerular structures and lipids in progressive renal disease. Am J Med 1989; 87: 12-20. 4. Vazquez-Perez S, Aragoncillo P, de Las Heras N, et al: Atorvastatin prevents glomerulosclerosis and renal endothelial dysfunction in hypercholesterolaemic rabbits. Nephrol Dial Transplant 2001; 16 40-4. 5. Vaziri ND, Liang K: ACAT inhibition reverses LCAT deficiency and improves plasma HDL in chronic renal failure. Am J Physiol Renal Physiol 2004; 287: 1038-43. 6. Epstein M, Campese VM: Pleiotropic effects of 3-hydroxy- 3-methylglutaryl coenzyme A reductase inhibitors on renal function. Am J Kidney Dis 2005; 45: 2-14. 7. Schaeffner ES, Kurth T, Curhan GC, et al: Cholesterol and the risk of renal dysfunction in apparently healthy men. J Am Soc Nephrol 2003; 14: 2084-91. 8. Muntner P, Coresh J, Smith JC, Eckfeldt J, Klag MJ: Plasma lipids and risk of developing renal dysfunction: the atherosclerosis risk in communities study. Kidney Int 2000; 58: 293-301. 9. Brunskill NJ: Albumin signals the coming of age of proteinuric nephropathy. J Am Soc Nephrol 2004; 15: 504-5. 10. Lee HS, Lee JS, Koh HI, Ko KW: Intraglomerular lipid deposition in routine biopsies. Clin Nephrol 1991; 36: 67-75. 11. Wheeler DC, Chana RS: Interactions between lipoproteins, glomerular cells and matrix. Miner Electrolyte Metab 1993; 19: 149-64. 12. Coritsidis G, Rifici V, Gupta S, Rie J, Shan ZH, Neugarten J, Schlondorff D: Preferential binding of oxidized LDL to rat glomeruli in vivo and cultured mesangial cells in vitro. Kidney Int 1991; 39: 858-66. 13. Gupta S, Rifici V, Crowley S, Brownlee M, Shan Z, Schlondorff D: Interactions of LDL and modified LDL with mesangial cells and matrix. Kidney Int 1992; 41: 1161-9. 14. Rovin BH, Tan LC: LDL stimulates mesangial fibronectin production and chemoattractant expression. Kidney Int 1993; 43: 218-25. 15. Hunsicker LG, Adler S, Caggiula A, et al: Predictors of the progression of renal disease in the Modification of Diet in Renal Disease Study. Kidney Int 1997; 51: 1908-19. 16. Kuivenhoven JA, Pritchard H, Hill J, Frohlich J, Assmann G, Kastelein J: The molecular pathology of lecithin: cholesterol acyltransferase (LCAT) deficiency syndrome. J Lipid Res 1997; 38: 191-205. 17. Vaziri ND, Liang K, Park JS: Acquired lecithin-cholesterol acyltransferase deficiency in nephrotic syndrome. Am J Physiol Renal Physiol 2001; 280: F823-8. 18. Vaziri ND, Liang K, Parks JS: Downregulation of lecithin: cholesterol acyltransferase (LCAT) in chronic renal failure. Kidney Int 2001; 59: 2192-6. 19. Vaziri N, Liang K: ACAT inhibition ameliorates proteinuria, hyperlipidemia, LCAT, SRB-1 and LDL receptor deficiencies in nephrotic syndrome. Circulation 2004; 110: 419-25. 20. Bianchi S, Bigazzi R, Caiazza A, Campese VM: A controlled, prospective study of the effects of atorvastatin on proteinuria and progression of kidney disease. Am J Kidney Dis 2003; 41: 565-70. 21. Tonolo G, Melis MG, Formato M, et al: Additive effects of simvastatin beyond its effects on LDL cholesterol in hypertensive type 2 diabetic patients. Eur J Clin Invest 2000; 30: 980-7. 22. Fielding CJ, Fielding PE: Cellular cholesterol efflux. Biochim Biophys Acta 2001; 1533: 175-89. 23. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomized placebo-controlled trial. Lancet 2002; 360: 7-22. 24. Athyros VG, Elisaf M, Papageorgiou AA, et al: Effect of statins versus untreated dyslipidemia on serum uric acid levels in patients with coronary heart disease: a subgroup analysis of the Greek Atorvastatin and Coronary-Heart- Disease Evaluation (GREACE) study. Am J Kidney Dis 2004; 43: 589-99. 25. Tonelli M, Moye L, Sacks FM, Cole T, Curhan GC: Effect of pravastatin on loss of renal function in people with moderate chronic renal insufficiency and cardiovascular disease. J Am Soc Nephrol 2003; 14: 1605-13. 26. Fried LF, Orchard TJ, Kasiske BL: Effect of lipid reduction on the progression of renal disease: a meta-analysis. Kidney Int. 2001; 59: 260-9. 27. Tonelli M, Moye L, Sacks FM, Cole T, Curhan GC: Effect of pravastatin on loss of renal function in people with moderate chronic renal insufficiency and cardiovascular disease. J Am Soc Nephrol. 2003; 14: 1605-13. 28. Bianchi S, Bigazzi R, Caiazza A, Campese VM: A controlled, 96 19 2 79
prospective study of the effects of atorvastatin on proteinuria and progression of kidney disease. Am J Kidney Dis 2003; 41: 565-70. 29. Owada A, Suda S, Hata T: Antiproteinuric effect of niceritrol, a nicotinic acid derivative, in chronic renal disease with hyperlipidemia: a randomized trial. Am J Med 2003; 114: 347-53. 30. Broeders N, Knoop C, Antoine M, Tielemans C, Abramowicz D: Fibrate-induced increase in blood urea and creatinine: is gemfibrozil the only innocuous agent? Nephrol Dial Transplant 2000; 15: 1993-9. 31. Dierkes J, Westphal S, Luley C: Serum homocysteine increases after therapy with fenofibrate or bezafibrate. Lancet 1999; 354: 219-20. 32. Hottelart C, El Esper N, Rose F, Achard JM, Fournier A: Fenofibrate increases creatininemia by increasing metabolic production of creatinine. Nephron 2002; 92: 536-41. 33. Westphal S, Dierkes J, Luley C: Effects of fenofibrate and gemfibrozil on plasma homocysteine. Lancet 2001; 358: 39-40. 34. Tonelli M, Collins D, Robins S, Bloomfield H, Curhan GC: Effect of gemfibrozil on change in renal function in men with moderate chronic renal insufficiency and coronary disease. Am J Kidney Dis 2004; 44: 832-9. 80 96 19 2