Treatment of dyslipidemia in patients with metabolic syndrome and chronic kidney disease
Authors:
V. Monhart 1,2
Authors‘ workplace:
Interní klinika 1. lékařské fakulty UK a ÚVN Praha, přednosta prof. MUDr. Miroslav Zavoral, Ph. D.
1; KlinLab s. r. o. Praha
2
Published in:
Vnitř Lék 2009; 55(7-8): 671-678
Category:
134th Internal Medicine Day - 23rd Vanysek's Day Brno 2009 - Vanysek's Lecture
Overview
Dyslipidemia, often present in patients with metabolic syndrome and chronic kidney disease, contributes to increased cardiovascular risk and progression of renal impairment. In these patients, the probability of death from cardiovascular complications is higher than death consequent to terminal renal failure. Positive neuroprotective effects of statins and fibrates are being attributed to hypolipidemic as well as other, lipid-unrelated, properties. Statins are able to slow down the decline in glomerular filtration rate and may decrease proteinuria. Nevertheless, conclusive evidence that statins decrease the incidence of cardiovascular complications in patients with advanced chronic kidney disease is still lacking. Through their effect on albuminuria, fibrates contribute to slowing down of the progression of diabetic nephropathy. Controlled trials and clinical practice have shown that monotherapy with statins as well as fibrates is safe. Management of combined dyslipidemia requires, apart from the selection of a suitable statin-fibrate combination, careful monitoring of potential adverse effects and treatment tolerability and compliance. The results of the Czecho-Slovakian pivot study KOLCHRI have demonstrated the efficacy and safety of fenofibrate combined with low dose statin in patients with metabolic syndrome and stage 2–4 chronic kidney disease.
Key words:
dyslipidemia – metabolic syndrome – chronic kidney disease – statins – fibrates – KOLCHRI study
Sources
1. De Zeeuw D, Hillege HL, de Jong PE. The kidney, a cardiovascular risk marker and a new target for therapy. Kidney Int 2005; 98 (Suppl): S25–S29.
2. Coresh J, Astor BC, Greene T et al. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis 2003; 41: 1–12.
3. Jabor A, Hornová L, Fantová L et al. Vyšetření funkce ledvin: možnosti biochemické laboratoře. Postgrad Med 2006; 9: 18–23.
4. Ninomiya T, Kiyohara Y. Albuminuria and chronic kidney disease in association with the metabolic syndrome. J Cardiometab Syndr 2007; 2: 104–107.
5. Bonnet F, Marre M, Halimi JM et al. DESIR Study Group. Waist circumference and the metabolic syndrome predict the development of elevated albuminuria in non‑diabetic subjects: the DESIR Study. J Hypertens 2006; 24: 1157–1163.
6. Chandie Shaw PK, Berger SP, Mallat M et al. Central obesity is an independent risk factor for albuminuria in nondiabetic South Asian subjects. Diabetes Care 2007; 30: 1840–1844.
7. Lambert G, Sakai N, Vaisman BL et al. Analysis of glomerulosclerosis and atherosclerosis in lecithin cholesterol acyltransferase-deficient mice. J Biol Chem 2001; 276: 15090–15098.
8. Samuelsson O, Mulec H, Knight-Gibson C.Lipoprotein abnormalities are associated with increased rate of progression of human chronic renal insufficiency. Nephrol Dial Transplant 1997; 12: 1908–19015.
9. Agarwal R. Statin induced proteinuria: renal injury or renoprotection? J Am Soc Nephrol 2004; 15: 2502–2503.
10. Verhulst A, D’Haese PC, De Broe ME. Inhibitors of HMG-CoA reductase reduce receptor-mediated endocytosis in human kidney proximal tubular cells. J Am Soc Nephrol 2004; 15: 2249–2257.
11. Douglas K, O’Malley PG, Jackson JL. Meta‑analysis: the effect of statins on albuminuria. Ann Intern Med 2006; 145: 117–124.
12. Atthobari J, Brantsma AH, Gansevoort RT et al. The effect of statins on urinary albumin excretion and glomerular filtration rate: results from both a randomized clinical trial and an observational cohort study. Nephrol Dial Transplant 2006; 21: 3106–3114.
13. Tonelli M, Moyé L, Sacks FM et al. Effect of pravastatin on loss of renal function in people with moderate chronic renal insufficiency and cardiovascular disease. J Am Soc Nephrol 2003; 14: 1605–1613.
14. Collins R, Armitage J, Parish S et al. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet 2003; 361: 2005–2016.
15. Shepherd J, Kastelein JJ, Bittner V et al. Effect of intensive lipid lowering with atorvastatin on renal function in patients with coronary heart disease: the Treating to New Targets (TNT) study. Clin J Am Soc Nephrol 2007; 2: 1131–1139.
16. Tonelli M, Isles C, Craven T et al. Effect of pravastatin on rate of kidney function loss in people with or at risk for coronary disease. Circulation 2005; 112: 171–178.
17. Sandhu S, Wiebe N, Fried LF et al. Statins for improving renal outcomes: a meta‑analysis. J Am Soc Nephrol 2006; 17: 2006–2016.
18. Kaysen GA. New insights into lipid metabolism in chronic kidney disease: What are the practical implications? Blood Purif 2009; 27: 86–91.
19. Wanner C, Krane V, März W et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med 2005; 353: 238–248.
20. Fellström BC, Jardine AG, Schmieder RE et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med 2009; 360: 1395–1407.
21. Graham DJ, Staffa JA, Shatin D. Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. JAMA 2004; 292: 2585–2590.
22. Ballantyne CM, Corsini A, Davidson MH. Risk for myopathy with statin therapy in high‑risk patients. Arch Intern Med 2003; 163: 553–564.
23. Monhart V. Statiny: renoprotektivní nebo nefrotoxické? Pokroky v oboru nefrologie 2008; 2: 80–89.
24. Holdaas H, Fellström B, Jardine AG et al. Assesment of LEscol in Renal transplantation (ALERT) Study Investigators. Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial. Lancet 2003; 361: 2024–2031.
25. Fruchart JC, Sacks FM, Hermans MP et al. The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in dyslipidaemic patient. Diab Vasc Dis Res 2008; 5: 319–335.
26. Caramori ML, Fioretto P, Mauer M. The need for early predictor of diabetic nephropathy risk: is albumin excretion rate sufficient? Diabetes 2000; 49: 1399–1408.
27. Retnakaran R, Cull CA, Thorne KI et al. UKPDS Study Group. Risk factors for renal dysfunction in type 2 diabetes: UK Prospective Diabetes Study 74. Diabetes 2006; 55: 1832–1839.
28. Chaturvedi N, Fuller JH, Taskinen MR. EURODIAB PCS Group. Differing associations of lipid and lipoprotein disturbances with the macrovascular and microvascular complications of type 1 diabetes. Diabetes Care 2001; 24: 2071–2077.
29. Jenkins AJ, Lyons TJ, Zheng D et al. DCCT/EDIC Research Group. Lipoproteins in the DCCT/EDIC Research Group: associations with diabetic nephropathy. Kidney Int 2003; 64: 817–828.
30. Molitch ME, Rupp D, Carnethon M. Higher levels of HDL cholesterol are associated with a decreased likelihood of albuminuria in patients with long‑standing type 1 diabetes. Diabetes Care 2006; 29: 78–82.
31. Bláha V. Kombinovaná hypolipidemická léčba u pacientů s vysokým kardiovaskulárním (KV) rizikem. Interní Med 2009; 11: 7–12.
32. Guan Y. Peroxisome Proliferator-Activated Receptor Family and Its Relationship to Renal Complications of the Metabolic Syndrome. J Am Soc Nephrol 2004; 15: 2801–2815.
33. Vakkilainen J, Steiner G, Ansquer JC et al. Relationships between low-density lipoprotein particle size, plasma lipoproteins, and progression of coronary artery disease: the Diabetes Atherosclerosis Intervention Study (DAIS). Circulation 2003; 107: 1733–1737.
34. Birjmohun RS, Hutten BA, Kastelein JJ et al. Efficacy and safety of high‑density lipoprotein cholesterol-increasing compounds: a meta‑analysis of randomized controlled trials. J Am Coll Cardiol 2005; 45: 185–197.
35. Heinonen OP, Huttunen JK, Manninen V et al. The Helsinki Heart Study: coronary heart disease incidence during an extended follow‑up. J Intern Med 1994; 235: 41–49.
36. Huttunen JK, Heinnonen OP, Manninen V et al. The Helsinki Heart Study: an 8.5-year safety and mortality follow‑up. J Intern Med 1994; 235: 31–39.
37. Rubins HB, Robins SJ, Collins D et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high‑density lipoprotein cholesterol. Veterans Affairs High‑Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 1999; 341: 410–418.
38. The BIB study group: Secondary prevention by raising HDL‑C and reducing triglycerides in patients with coronary artery disease: the Bezafibrate Infarction Prevention (BIP) study. Circulation 2000; 102: 21–27.
39. Keech A, Simes RJ, Barter P et al. FIELD Study Investigators. Effects of long‑term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 2005; 366: 1849–1861.
40. Keech AC, Grieve SM, Patel A et al. Urinary albumin levels in the normal range determine arterial wall thickness in adults with Type 2 diabetes: a FIELD substudy. Diabet Med 2005; 22: 1558–1565.
41. Diabetes atherosclerosis intervention study investigators: Effect of fenofibrate on progression of coronary-artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study, a randomised study. Lancet 2001; 357: 905–910.
42. Ansquer JC, Foucher C, Rattier S et al. DAIS Investigators. Fenofibrate reduces progression to microalbuminuria over 3 years in a placebo-controlled study in type 2 diabetes: results from the Diabetes Atherosclerosis Intervention Study (DAIS). Am J Kidney Dis 2005; 45: 485–493.
43. Tonelli M, Collins D, Robins S et al. Effect of gemfibrozil on change in renal function in men with moderate chronic renal insufficiency and coronary disease. Am J Kidney Dis 2004; 44: 832–839.
44. Bláha V, Dusilová Sulková S, Mistrík S. Fibráty, diabetes mellitus a ledviny. In: Dusilová Sulková S, Šmahelová A (eds). Multidisciplinární přístup k diabetikovi s onemocněním ledvin. Praha: TIGIS 2007: 24–31.
45. Grundy SM, Vega GL, Yuan Z et al. Effectiveness and tolerability of simvastatin plus fenofibrate for combined hyperlipidemia (the SAFARI trial). Am J Cardiol 2005; 95: 462–468.
46. Grieve SM, Ansquer J-C, Keech AC. Micronized fenofibrate: a useful choice for the correction of dyslipidemia in metabolic syndrome and Type 2 diabetes. Future Cardiol 2006; 2: 635–646.
47. Kim KY, Mancano MA. Fenofibrate potentiates warfarin effects. Ann Pharmacother 2003; 37: 212–215.
48. Boissonnat P, Salen P, Guidollet J et al. The long‑term effects of the lipid-lowering agent fenofibrate in hyperlipidemic heart transplant recipients. Transplantation 1994; 58: 245–247.
49. Jones PH, Davidson MH. Reporting rate of rhabdomyolysis with fenofibrate + statin versus gemfibrozil + any statin. Am J Cardiol 2005; 95: 120–122.
50. Prueksaritanont T, Tang C, Qiu Y et al. Effects of fibrates on metabolism of statins in human hepatocytes. Drug Metab Dispos 2002; 30: 1280–1287.
51. Ballantyne CM, Davidson MH. Possible differences between fibrates in pharmacokinetic interactions with statins. Arch Intern Med 2003; 163: 2394–2395.
52. Ellen RL, McPherson R. Long‑term efficacy and safety of fenofibrate and a statin in the treatment of combined hyperlipidemia. Am J Cardiol 1998; 81: 60B–65B.
53. Derosa G, Cicero AE, Bertone G et al. Comparison of fluvastatin + fenofibrate combination therapy and fluvastatin monotherapy in the treatment of combined hyperlipidemia, type 2 diabetes mellitus, and coronary heart disease: a 12–month, randomized, double-blind, controlled trial. Clin Ther 2004; 26: 1599–1607.
54. Keating GM, Croom KF. Fenofibrate: a review of its use in primary dyslipidaemia, the metabolic syndrome and type 2 diabetes mellitus. Drugs 2007; 67: 121–153.
55. Rosenson RS. Current overview of statin‑induced myopathy. Am J Med 2004; 116: 408–416.
56. Molitch ME. Management of Dyslipidemias in Patients with Diabetes and Chronic Kidney Disease. Clin J Am Soc Nephrol 2006; 1: 1090–1099.
57. Davidson MH, Armani A, McKenney JM et al. Safety considerations with fibrate therapy. Am J Cardiol 2007; 99: 3C–18C.
58. Harper CR, Jacobson TA. Managing dyslipidemia in chronic kidney disease. J Am Coll Cardiol 2008; 51: 2375–2384.
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Diabetology Endocrinology Internal medicineArticle was published in
Internal Medicine
2009 Issue 7-8
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