Are PPAR alpha agonists a rational therapeutic strategy for preventing abnormalities of the diabetic kidney?

Pharmacological Research

Volumn 65, Issue 4, 2012, Pages 430-436

  Balakumar, Pitchai ^a   Kadian, Supriya ^a   Mahadevan, Nanjaian ^a  

^a Rajendra Institute of Technology and Sciences   (India)

Author keywords

Abnormal lipoprotein metabolism; Diabetic nephropathy; Dyslipidemia; PPAR agonists; Renal dysfunction

Indexed keywords

FENOFIBRATE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA AGONIST; PLACEBO;

CHRONIC KIDNEY DISEASE; DIABETIC NEPHROPATHY; DISEASE ASSOCIATION; DISEASE COURSE; DOSE RESPONSE; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG MECHANISM; DRUG RESPONSE; DRUG WITHDRAWAL; DYSLIPIDEMIA; HUMAN; HYPERTRIGLYCERIDEMIA; KIDNEY FIBROSIS; LIPOTOXICITY; MICROALBUMINURIA; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; RENAL PROTECTION; REVIEW; SIDE EFFECT; TREATMENT OUTCOME; UREA NITROGEN BLOOD LEVEL;

ANIMALS; DIABETES MELLITUS; DIABETIC NEPHROPATHIES; DYSLIPIDEMIAS; FENOFIBRATE; HUMANS; HYPOLIPIDEMIC AGENTS; PPAR ALPHA;

EID: 84858339432     PISSN: 10436618     EISSN: 10961186     Source Type: Journal    
DOI: 10.1016/j.phrs.2012.01.004     Document Type: Review

References (83)

1. C. Maric, and J.E. Hall Obesity, metabolic syndrome and diabetic nephropathy Contrib Nephrol 170 2011 28 35
2. P. Rossing, and D. de Zeeuw Need for better diabetes treatment for improved renal outcome Kidney Int Suppl 120 2011 S28 S32
3. P. Balakumar, M.K. Arora, S.S. Ganti, J. Reddy, and M. Singh Recent advances in pharmacotherapy for diabetic nephropathy: current perspectives and future directions Pharmacol Res 60 2009 24 32
4. P. Balakumar, J. Reddy, and M. Singh Do resident renal mast cells play a role in the pathogenesis of diabetic nephropathy? Mol Cell Biochem 330 2009 187 192
5. A.M. Sharma, and M.R. Weir The role of angiotension receptor blockers in diabetic nephropathy Postgrad Med 123 2011 109 121
6. S.M. Udani, and G.L. Bakris Do fibrates truly preserve kidney function? Nat Rev Endocrinol 7 2011 130 131
7. R. Retnakaran, C.A. Cull, K.I. Thorne, A.I. Alder, R.R. Holman UKPDS Study Group Risk factors for renal dysfunction in type 2 diabetes: U.K. Prospective Diabetes Study 74 Diabetes 55 2006 1832 1839 (Pubitemid 44324140)
8. J.C. Rutledge, K.F. Ng, H.H. Aung, and D.W. Wilson Role of triglyceride-rich lipoproteins in diabetic nephropathy Nat Rev Nephrol 6 2010 361 370
9. Y.S. Kanwar, J. Wada, L. Sun, P. Xie, E.I. Wallner, and S. Chen Diabetic nephropathy: mechanisms of renal disease progression Exp Biol Med (Maywood) 233 2008 4 11
10. P. Balakumar, M.K. Arora, J. Reddy, and M.B. Anand-Srivastava Pathogenesis of diabetic nephropathy: involvement of multifaceted signalling mechanism J Cardiovasc Pharmacol 54 2009 129 138
11. V.P. Bilan, E.M. Salah, S. Bastacky, H.B. Jones, R.M. Mayers, and B. Zinker Diabetic nephropathy and long-term treatment effects of rosiglitazone and enalapril in obese ZSF1 rats J Endocrinol 210 2011 293 308
12. D. de Zeeuw, G. Remuzzi, H.H. Parving, W.F. Keane, Z. Zhang, and S. Shahinfar Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: lessons from RENAAL Kidney Int 65 2004 2309 2320 (Pubitemid 38670018)
13. V. Wiwanitkit Glucosuria and albuminuria in diabetic nephropathy: a consideration at nanolevel J Diabetes Complications 21 2007 164 165 (Pubitemid 46687065)
14. P. Balakumar, V.A. Chakkarwar, V. Kumar, A. Jain, J. Reddy, and M. Singh Experimental models for nephropathy J Renin Angiotensin Aldosterone Syst 9 2008 189 195
15. M.K. Arora, K. Reddy, and P. Balakumar The low dose combination of fenofibrate and rosiglitazone halts the progression of diabetes-induced experimental nephropathy Eur J Pharmacol 636 2010 137 144
16. R.S. Rosenson, P. Fioretto, and P.M. Dodson Does microvascular disease predict macrovascular events in type 2 diabetes? Atherosclerosis 218 2011 13 18
17. Z. Wang, T. Jiang, J. Li, G. Proctor, J.L. McManaman, and S. Lucia Regulation of renal lipid metabolism, lipid accumulation, and glomerulosclerosis in FVB db/db mice with type 2 diabetes Diabetes 54 2005 2328 2335 (Pubitemid 41134259)
18. P. Balakumar, M.K. Arora, and M. Singh Emerging role of PPAR ligands in the management of diabetic nephropathy Pharmacol Res 60 2009 170 173
19. P. Balakumar, V.A. Chakkarwar, and M. Singh Ameliorative effect of combination of benfotiamine and fenofibrate in diabetes-induced vascular endothelial dysfunction and nephropathy in the rat Mol Cell Biochem 320 2009 149 162
20. D. Taneja, J. Thompson, P. Wilson, K. Brandewie, L. Schaefer, and B. Mitchell Reversibility of renal injury with cholesterol lowering in hyperlipidemic diabetic mice J Lipid Res 51 2010 1464 1470
21. A.Y. Kang, S.K. Park, S.Y. Park, H.J. Lee, Y. Han, and S.R. Lee Therapeutic target achievement in type 2 diabetic patients after hyperglycemia, hypertension, dyslipidemia management Diabetes Metab J 35 2011 264 272
22. Y.F. Guan, and M.D. Breyer Peroxisome proliferator-activated receptors (PPARs): novel therapeutic targets in renal disease Kidney Int 60 2001 14 30 (Pubitemid 32587535)
23. J. Plutzky Preventing type 2 diabetes and cardiovascular disease in metabolic syndrome: the role of PPAR alpha Diab Vasc Dis Res 4 2007 S12 S14 (Pubitemid 350013472)
24. J.C. Ansquer, C. Foucher, P. Aubonnet, and K. Le Malicot Fibrates and microvascular complications in diabetes - insight from the FIELD study Curr Pharm Des 15 2009 537 552
25. M. Olukman, E.D. Sezer, S. Ulker, E.Y. Sözmen, and G.M. Cinar Fenofibrate treatment enhances antioxidant status and attenuates endothelial dysfunction in streptozotocin-induced diabetic rats Exp Diabetes Res 2010 2010 828531
26. D. Portilla, G. Dai, J.M. Peters, F.J. Gonzalez, M.D. Crew, and A.D. Proia Etomoxir-induced PPARalpha-modulated enzymes protect during acute renal failure Am J Physiol Renal Physiol 278 2000 F667 F675 (Pubitemid 30215246)
27. S. Li, K.K. Nagothu, V. Desai, T. Lee, W. Branham, and C. Moland Transgenic expression of proximal tubule peroxisome proliferator-activated receptor-alpha in mice confers protection during acute kidney injury Kidney Int 76 2009 1049 1062
28. J.A. Farmer Diabetic dyslipidemia and atherosclerosis: evidence from clinical trials Curr Atheroscler Rep 9 2007 162 168 (Pubitemid 47376987)
29. X. Hou, Y.H. Shen, C. Li, F. Wang, C. Zhang, and P. Bu PPARalpha agonist fenofibrate protects the kidney from hypertensive injury in spontaneously hypertensive rats via inhibition of oxidative stress and MAPK activity Biochem Biophys Res Commun 394 2010 653 659
30. C. Wanner, and V. Krane Recent advances in the treatment of atherogenic dyslipidemia in type 2 diabetes mellitus Kidney Blood Press Res 34 2011 209 217
31. C.W. Park, Y. Zhang, X. Zhang, J. Wu, L. Chen, and D.R. Cha PPARalpha agonist fenofibrate improves diabetic nephropathy in db/db mice Kidney Int 69 2006 1511 1517
32. J.C. Ansquer, C. Foucher, S. Rattier, M.R. Taskinen, G. Steiner 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 45 2005 485 493 (Pubitemid 40341327)
33. T.M. Davis, R. Ting, J.D. Best, M.W. Donoghoe, P.L. Drury, and D.R. Sullivan Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study Diabetologia 54 2011 280 290
34. K. Vijayaraghavan Treatment of dyslipidemia in patients with type 2 diabetes Lipids Health Dis 9 2010 144
35. M.P. Solano, and R.B. Goldberg Management of dyslipidemia in diabetes Cardiol Rev 14 2006 125 135 (Pubitemid 44350383)
36. M. Adiels, S.O. Olofsson, M.R. Taskinen, and J. Borén Diabetic dyslipidemia Curr Opin Lipidol 17 2006 238 246
37. M. Adiels, S.O. Olofsson, M.R. Taskinen, and J. Borén Overproduction of very low-density lipoproteins is the hallmark of the dyslipidemia in the metabolic syndrome Arterioscler Thromb Vasc Biol 28 2008 1225 1236
38. A.J. Krentz Lipoprotein abnormalities and their consequences for patients with type 2 diabetes Diabetes Obes Metab 5 2003 S19 S27 (Pubitemid 37483614)
39. D. Muačević-Katanec, and Z. Reiner Diabetic dyslipidemia or 'diabetes lipidus'? Expert Rev Cardiovasc Ther 9 2011 341 348
40. R. de Vries, S.E. Borggreve, and R.P. Dullaart Role of lipases, lecithin: cholesterol acyltransferase and cholesteryl ester transfer protein in abnormal high density lipoprotein metabolism in insulin resistance and type 2 diabetes mellitus Clin Lab 49 2003 601 613 (Pubitemid 37493458)
41. S.E. Borggreve, R. De Vries, and R.P. Dullaart Alterations in high-density lipoprotein metabolism and reverse cholesterol transport in insulin resistance and type 2 diabetes mellitus: role of lipolytic enzymes, lecithin:cholesterol acyltransferase and lipid transfer proteins Eur J Clin Invest 33 2003 1051 1069 (Pubitemid 38019139)
42. N.A. van Herpen, and V.B. Schrauwen-Hinderling Lipid accumulation in non-adipose tissue and lipotoxicity Physiol Behav 94 2008 231 241 (Pubitemid 351615422)
43. J. Thompson, P. Wilson, K. Brandewie, D. Taneja, L. Schaefer, and B. Mitchell Renal accumulation of biglycan and lipid retention accelerates diabetic nephropathy Am J Pathol 179 2011 1179 1187
44. A.L. Rops, J. van der Vlag, J.F. Lensen, T.J. Wijnhoven, L.P. van den Heuvel, and T.H. van Kuppevelt Heparan sulfate proteoglycans in glomerular inflammation Kidney Int 65 2004 768 785 (Pubitemid 38251053)
45. L.C. Wilsie, S. Chanchani, D. Navaratna, and R.A. Orlando Cell surface heparan sulfate proteoglycans contribute to intracellular lipid accumulation in adipocytes Lipids Health Dis 4 2005 2
46. H. Makino, S. Ikeda, T. Haramoto, and Z. Ota Heparan sulfate proteoglycans are lost in patients with diabetic nephropathy Nephron 61 1992 415 421
47. J. van den Born, B. Pisa, M.A. Bakker, J.W. Celie, C. Straatman, and S. Thomas No change in glomerular heparan sulfate structure in early human and experimental diabetic nephropathy J Biol Chem 281 2006 29606 29613 (Pubitemid 44536968)
48. S.J. Shin, J.H. Lim, S. Chung, D.Y. Youn, H.W. Chung, and H.W. Kim Peroxisome proliferator-activated receptor-alpha activator fenofibrate prevents high-fat diet-induced renal lipotoxicity in spontaneously hypertensive rats Hypertens Res 32 2009 835 845
49. C.W. Park, H.W. Kim, S.H. Ko, H.W. Chung, S.W. Lim, and C.W. Yang Accelerated diabetic nephropathy in mice lacking the peroxisome proliferator-activated receptor alpha Diabetes 55 2006 885 893
50. J. DiRenzo, M. Söderstrom, R. Kurokawa, M.H. Ogliastro, M. Ricote, and S. Ingrey Peroxisome proliferator-activated receptors and retinoic acid receptors differentially control the interactions of retinoid X receptor heterodimers with ligands, coactivators, and corepressors Mol Cell Biol 17 1997 2166 2176 (Pubitemid 27133303)
51. N. Latruffe, M. Cherkaoui Malki, V. Nicolas-Frances, B. Jannin, M.C. Clemencet, and F. Hansmannel Peroxisome-proliferator-activated receptors as physiological sensors of fatty acid metabolism: molecular regulation in peroxisomes Biochem Soc Trans 29 2001 305 309 (Pubitemid 32587522)
52. M. Rakhshandehroo, B. Knoch, M. Müller, and S. Kersten Peroxisome proliferator-activated receptor alpha target genes PPAR Res 201 2010 0 pii:612089
53. A. Keech, P. Drury, T.M. Davis, M. Donoghoe, M. Laakso, and M. Whiting Protection against nephropathy with fenofibrate in type 2 diabetes mellitus: the FIELD study Circulation 120 2009 S419 S420
54. C.F. Cheng, H.H. Chen, and H. Lin Role of PPARα and its agonist in renal diseases PPAR Res 2010 2010 345098
55. W.F. Keane Lipids and progressive renal failure Wien Klin Wochenschr 108 1996 420 424 (Pubitemid 26253643)
56. W.F. Keane The role of lipids in renal disease: future challenges Kidney Int Suppl 75 2000 S27 S31 (Pubitemid 30205436)
57. C. Guijarro, and W.F. Keane Effects of lipids on the pathogenesis of progressive renal failure: role of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in the prevention of glomerulosclerosis Miner Electrolyte Metab 22 1996 147 152 (Pubitemid 126448826)
58. P. Balakumar, V.A. Chakkarwar, P. Krishan, and M. Singh Vascular endothelial dysfunction: a tug of war in diabetic nephropathy? Biomed Pharmacother 63 2009 171 179
59. N. Watanabe, K. Shikata, Y. Shikata, K. Sarai, K. Omori, and R. Kodera Involvement of MAPKs in ICAM-1 expression in glomerular endothelial cells in diabetic nephropathy Acta Med Okayama 65 2011 247 257
60. J. Jankun, A. Al-Senaidy, and E. Skzypczak-Jankun Can inactivators of plasminogen activator inhibitor alleviate the burden of obesity and diabetes? Int J Mol Med 29 2012 3 11
61. L. Chen, J. Zhang, Y. Zhang, Y. Wang, and B. Wang Improvement of inflammatory responses associated with NF-kappa B pathway in kidneys from diabetic rats Inflamm Res 57 2008 199 204
62. L.L. Chen, J.Y. Zhang, and B.P. Wang Renoprotective effects of fenofibrate in diabetic rats are achieved by suppressing kidney plasminogen activator inhibitor-1 Vascul Pharmacol 44 2006 309 315
63. H.Y. Lan, and A.C. Chung Transforming growth factor-β and Smads Contrib Nephrol 170 2011 75 82
64. X. Zhong, A.C. Chung, H.Y. Chen, X.M. Meng, and H.Y. Lan Smad3-mediated upregulation of miR-21 promotes renal fibrosis J Am Soc Nephrol 22 2011 1668 1681
65. L. Li, N. Emmett, D. Mann, and X. Zhao Fenofibrate attenuates tubulointerstitial fibrosis and inflammation through suppression of nuclear factor-κB and transforming growth factor-β1/Smad3 in diabetic nephropathy Exp Biol Med (Maywood) 235 2010 383 391
66. H.W. Chung, J.H. Lim, M.Y. Kim, S.J. Shin, S. Chung, and B.S. Choi High-fat diet-induced renal cell apoptosis and oxidative stress in spontaneously hypertensive rat are ameliorated by fenofibrate through the PPARα-FoxO3a-PGC-1α pathway Nephrol Dial Transplant 2011 10.1093/ndt/gfr613
67. Y. Tanaka, S. Kume, S. Araki, K. Isshiki, M. Chin-Kanasaki, and M. Sakaguchi Fenofibrate, a PPARα agonist, has renoprotective effects in mice by enhancing renal lipolysis Kidney Int 79 2011 871 882
68. H.J. Zhao, S. Wang, H. Cheng, M.Z. Zhang, T. Takahashi, and A.B. Fogo Endothelial nitric oxide synthase deficiency produces accelerated nephropathy in diabetic mice J Am Soc Nephrol 17 2006 2664 2669 (Pubitemid 44484656)
69. T. Nakagawa, W. Sato, O. Glushakova, M. Heinig, T. Clarke, and M. Campbell-Thompson Diabetic endothelial nitric oxide synthase knockout mice develop advanced diabetic nephropathy J Am Soc Nephrol 18 2007 539 550 (Pubitemid 46193319)
70. S. Prabhakar, J. Starnes, S. Shi, B. Lonis, and R. Tran Diabetic nephropathy is associated with oxidative stress and decreased renal nitric oxide production J Am Soc Nephrol 18 2007 2945 2952 (Pubitemid 350058402)
71. A. Tomizawa, Y. Hattori, T. Inoue, S. Hattori, and K. Kasai Fenofibrate suppresses microvascular inflammation and apoptosis through adenosine monophosphate-activated protein kinase activation Metabolism 60 2011 513 522
72. R. Cetinkaya, A. Uyanik, R. Yildirim, Y. Bilen, and M. Keles Fenofibrate monotherapy-induced rhabdomyolysis in a patient with type-2 diabetes Indian J Med Sci 62 2008 458 459
73. J. Wu, Y. Song, H. Li, and J. Chen Rhabdomyolysis associated with fibrate therapy: review of 76 published cases and a new case report Eur J Clin Pharmacol 65 2009 1169 1174
74. P. Balakumar, M. Rose, S.S. Ganti, P. Krishan, and M. Singh PPAR dual agonists: are they opening Pandora's Box? Pharmacol Res 56 2007 91 98 (Pubitemid 47304493)
75. A. Zambon, and K. Cusi The role of fenofibrate in clinical practice Diab Vasc Dis Res 4 2007 S15 S20 (Pubitemid 350013473)
76. C. Hottelart, N. El Esper, F. Rose, J.M. Achard, and A. Fournier Fenofibrate increases creatininemia by increasing metabolic production of creatinine Nephron 92 2002 536 541
77. Y.M. Smulders, A.E. van Eeden, C.D. Stehouwer, R.N. Weijers, E.H. Slaats, and J. Silberbusch Can reduction in hypertriglyceridemia slow progression of microalbuminuria in patients with non-insulin-dependent diabetes mellitus? Eur J Clin Invest 27 1997 997 1002 (Pubitemid 28012621)
78. T. Nagai, T. Tomizawa, K. Nakajima, and M. Mori Effect of bezafibrate or pravastatin on serum lipid levels and albuminuria in NIDDM patients J Atheroscler Thromb 7 2000 91 96
79. P. Balakumar, and N. Mahadevan Interplay between statins and PPARs in improving cardiovascular outcomes: a double-edged sword? Br J Pharmacol 165 2012 373 379
80. P. Balakumar, S. Kathuria, G. Taneja, S. Kalra, and N. Mahadevan Is targeting eNOS a key mechanistic insight of cardiovascular defensive potentials of statins? J Mol Cell Cardiol 52 2012 83 92
81. C.R. McQuade, J. Griego, J. Anderson, and A.B. Pai Elevated serum creatinine levels associated with fenofibrate therapy Am J Health Syst Pharm 65 2008 138 141
82. S. Paul, and V. Mohan Fenofibrate can increase serum creatinine levels in renal insufficiency J Assoc Physicians India 54 2006 337 (Pubitemid 43528618)
83. C. Hottelart, N. el Esper, J.M. Achard, A. Pruna, and A. Fournier Fenofibrate increases blood creatinine, but does not change the glomerular filtration rate in patients with mild renal insufficiency Nephrologie 20 1999 41 44 (Pubitemid 29091030)