Emerging drugs for chronic kidney disease

Expert Opinion on Emerging Drugs

Volumn 19, Issue 2, 2014, Pages 183-199

  Stefoni, Sergio ^a   Cianciolo, Giuseppe ^a   Baraldi, Olga ^a   Iorio, Mario ^a   Angelini, Maria Laura ^a  

^a UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

Albuminuria; Bardoxolone; Chronic kidney disease; End stage renal disease; Endothelin receptor antagonist; Paricalcitol; Renin angiotensin aldosterone system

Indexed keywords

ANGIOTENSIN RECEPTOR ANTAGONIST; ANTIFIBROTIC AGENT; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ATRASENTAN; AVOSENTAN; GLYCOSAMINOGLYCAN; PYRIDINE DERIVATIVE; PYRIDOXAMINE; PYRIMIDINE DERIVATIVE; PYRROLIDINE DERIVATIVE; SULODEXIDE;

AGING; ANTIHYPERTENSIVE ACTIVITY; ANTIINFLAMMATORY ACTIVITY; CHRONIC KIDNEY DISEASE; DIABETES MELLITUS; END STAGE RENAL DISEASE; HUMAN; HYPERTENSION; INCIDENCE; KIDNEY FUNCTION; MEDLINE; NONHUMAN; REVIEW; SCIENTIFIC LITERATURE; ANALOGS AND DERIVATIVES; ANIMAL; RENAL INSUFFICIENCY, CHRONIC;

ANGIOTENSIN RECEPTOR ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; ANIMALS; GLYCOSAMINOGLYCANS; HUMANS; PYRIDINES; PYRIDOXAMINE; PYRIMIDINES; PYRROLIDINES; RENAL INSUFFICIENCY, CHRONIC;

EID: 84901258175     PISSN: 14728214     EISSN: 17447623     Source Type: Journal    
DOI: 10.1517/14728214.2014.900044     Document Type: Review

References (129)

1. KDOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Available from: http://www.kidney.org/professionals/KDOQI/guidelines-ckd/p4-class-g1.htm
2. Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 2013;3:19-62
3. Couser WG, Remuzzi G, Mendis S, Tonelli M. The contribution of chronic kidney disease to the global burden of major noncommunicable diseases. Kidney Int 2011;80:1258-70
4. Zoccali C, Kramer A, Jager KJ. Epidemiology of CKD in Europe: An uncertain scenario. Nephrol Dial transplant 2010;25:1731-3
5. Stenvinkel P. Chronic kidney disease: A public health priority and harbinger of premature cardiovascular disease. J Intern Med 2010;268:456-67
6. Jha V, Garcia-Garcia G, Iseki K, et al. Chronic kidney disease: Global dimension and perspectives. Lancet 2013;382:260-72
7. UNITED STATES RENAL DATA SYSTEM. Atlas of CKD & ESRD. 2013. Available from: http://www.usrds.org/atlas.aspx
8. Centers for Disease Control and Prevention (CDC). Prevalence of chronic kidney disease and associated risk factors-United States, 1999-2004. MMWR Morb Mortal Wkly Rep 2007;56:161-5
9. Zhang QL, Rothenbacher D. Prevalence of chronic kidney disease in populationbased studies: Systematic review. BMC Public Health 2008;8:117
10. Vassalotti JA, Li S, Chen SC, Collins AJ. Screening populations at increased risk of CKD: The Kidney Early Evaluation Program (KEEP) and the public health problem. Am J Kidney Dis 2009;53(3 Suppl 3):S107-14
11. Rajapurkar MM, John GT, Kirpalani AL, et al. What do we know about chronic kidney disease in India: First report of the Indian CKD registry. BMC Nephrol 2012;13:10
12. Arogundade FA, Barsoum RS. CKD prevention in sub-Saharan Africa: A call for governmental, nongovernmental, and community support. Am J Kidney Dis 2008;51:515-23 (Pubitemid 351284498
13. Engelgau MM, El-Saharty S, Kudesia P, et al. Capitalizing on the demographic transition: Tackling non communicable diseases in South Asia. World Bank, Washington, DC; 2011. p. 15-40
14. Stenvinkel P, Ikizler TA, Mallamaci F, Zoccali C. Obesity and nephrology: Results of a knowledge and practice pattern survey. Nephrol Dial Transplant 2013;28(Suppl 4):iv99-104
15. Dinsa GD, Goryakin Y, Fumagalli E, Suhrcke M. Obesity and socioeconomic status in developing countries: A systematic review. Obes Rev 2012;13:1067-79
16. Collins AJ, Vassalotti JA, Wang C, et al. Who should be targeted for CKD screening?. Impact of diabetes, hypertension, and cardiovascular disease. Am J Kidney Dis 2009;53(3 Suppl 3):S71-7
17. Jha V, Wang AY, Wang H. The impact of CKD identification in large countries: The burden of illness. Nephrol Dial Transplant 2012;27(Suppl 3):iii32-8
18. Ozyilmaz A, de Jong PE, Gansevoort RT. Screening for chronic kidney disease can be of help to prevent atherosclerotic end-organ damage. Nephrol Dial Transplant 2012;27:4046-52
19. Vassalotti JA, Li S, McCullough PA, et al. Kidney early evaluation program: A community-based screening approach to address disparities in chronic kidney disease. Semin Nephrol 2010;30:66-73
20. Minutolo R, De Nicola L, Mazzaglia G, et al. Detection and awareness of moderate to advanced CKD by primary care practitioners: A cross-sectional study from Italy. Am J Kidney Dis 2008;52:444-53
21. Plantinga LC, Boulware LE, Coresh J, et al. Patient awareness of chronic kidney disease: Trends and predictors. Arch Intern Med 2008;168:2268-75
22. Ravera M, Noberasco G, Weiss U, et al. CKD awareness and blood pressure control in the primary care hypertensive population. Am J Kidney Dis 2011;57:71-7
23. Turner JM, Bauer C, Abramowitz MK, et al. Treatment of chronic kidney disease. Kidney Int 2012;81:351-62
24. Hsu CY, Ordoñez JD, Chertow GM, et al. The risk of acute renal failure in patients with chronic kidney disease. Kidney Int 2008;74:101-7 (Pubitemid 351841887
25. Chertow GM, Burdick E, Honour M, et al. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol 2005;16:3365-70 (Pubitemid 46179340
26. Campbell GA, Bolton WK. Referral and comanagement of the patient with CKD. Adv Chronic Kidney Dis 2011;18:420-7
27. Levey AS, Schoolwerth AC, Burrows NR, et al. Comprehensive public health strategies for preventing the development, progression, and complications of CKD: Report of an expert panel convened by the Centers for Disease Control and Prevention. Am J Kidney Dis 2009;53:522-35
28. Briet M, Burns KD. Chronic kidney disease and vascular remodelling: Molecular mechanisms and clinical implications. Clin Sci (Lond) 2012;123:399-416
29. Wilmer WA, Rovin BH, Hebert CJ, et al. Management of glomerular proteinuria: A commentary. J Am Soc Nephrol 2003;14:3217-32 (Pubitemid 37509297
30. Hebert LA, Wilmer WA, Falkenhain ME, et al. Renoprotection: One or many therapies?. Kidney Int 2001;59:1211-26
31. Lea J, Greene T, Hebert L, et al. The relationship between magnitude of proteinuria reduction and risk of endstage renal disease: Results of the African American study of kidney disease and hypertension. Arch Intern Med 2005;165:947-53 (Pubitemid 40563243
32. Doulton TW, He FJ, MacGregor GA. Systematic review of combined angiotensin-converting enzyme inhibition and angiotensin receptor blockade in hypertension. Hypertension 2005;45(5):880-6 (Pubitemid 40628932
33. Scaglione R, Argano C, Di Chiara T, et al. Effect of dual blockade of reninangiotensin system on TGFbeta1 and left ventricular structure and function in hypertensive patients. J Hum Hypertens 2007;21(4):307-15 (Pubitemid 46443592
34. Gaddam KK, Pimenta E, Husain S, Calhoun DA. Aldosterone and cardiovascular disease. Curr Probl Cardiol 2009;34(2):51-84
35. Cortinovis M, Perico N, Cattaneo D, Remuzzi G. Aldosterone and progression of kidney disease. Ther Adv Cardiovasc Dis 2009;3(2):133-43
36. Toto R, Palmer BF. Rationale for combination angiotensin receptor blocker and angiotensin-converting enzyme inhibitor treatment and end-organ protection in patients with chronic kidney disease. Am J Nephrol 2008;28:372-80 (Pubitemid 351501602
37. Rüster C, Wolf G. Renin-Angiotensin-Aldosterone system and progression of renal disease. J Am Soc Nephrol 2006;17:2985-91 (Pubitemid 44707758
38. Pitt B, Stier CT Jr, Rajagopalan S. Mineralocorticoid receptor blockade: New insights into the mechanism of action in patients with cardiovascular disease. J Renin Angiotensin Aldosterone Syst 2003;4(3):164-8 (Pubitemid 37407163
39. Haller H, Ito S, Izzo JL Jr, et al. Olmesartan for the delay or prevention of microalbuminuria in type 2 diabetes. N Engl J Med 2011;364(10):907-17
40. Schrier RW, Abdallah JG, Weinberger HH, Abraham WT. Therapy of heart failure. Kidney Int 2000;57(4):1418-25 (Pubitemid 30207901
41. Siragy HM, Carey RM. Role of the intrarenal renin-Angiotensin-Aldosterone system in chronic kidney disease. Am J Nephrol 2010;31(6):541-50
42. Bakris GL, Ruilope L, Locatelli F, et al. Treatment of microalbuminuria in hypertensive subjects with elevated cardiovascular risk: Results of the IMPROVE trial. Kidney Int 2007;72(7):879-85 (Pubitemid 47462081
43. Kunz R, Friedrich C, Wolbers M, Mann JF. Meta-Analysis: Effect of monotherapy and combination therapy with inhibitors of the renin angiotensin system on proteinuria in renal disease. Ann Intern Med 2008;148(1):30-48 (Pubitemid 351688350
44. Mann JF, Schmieder RE, McQueen M, et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): A multicentre, randomised, double-blind, controlled trial. Lancet 2008;372:547-53
45. Yusuf S, Teo KK, Pogue J, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008;358(15):1547-59 (Pubitemid 351522739
46. Sleight P, Redon J, Verdecchia P, et al. Prognostic value of blood pressure in patients with high vascular risk in the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial study. J Hypertens 2009;27(7):1360-9
47. Ruggenenti P, Perna A, Gherardi G, et al. Renoprotective properties of ACEinhibition in non-diabetic nephropathies with non-nephrotic proteinuria. Lancet 1999;354(9176):359-64 (Pubitemid 29355751
48. Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001;345(12):861-9
49. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med 1993;329(20):1456-62 (Pubitemid 23335891
50. Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001;345(12):851-60
51. Fried LF, Emanuele N, Zhang JH, et al. Combined angiotensin inhibition for the treatment of diabetic nephropathy. N Engl J Med 2013;369(20):1892-903
52. Parving HH, Brenner BM, McMurray JJ, et al. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med 2012;367(23):2204-13
53. Pfeffer MA, McMurray JJ, Velazquez EJ, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003;349(20):1893-906 (Pubitemid 37409706
54. Maggioni AP, Greene SJ, Fonarow GC, et al. Effect of aliskiren on post-discharge outcomes among diabetic and nondiabetic patients hospitalized for heart failure: Insights from the ASTRONAUT trial. Eur Heart J 2013;34(40):3117-27
55. Snyder JJ, Foley RN, Collins AJ. Prevalence of CKD in the United States: A sensitivity analysis using the National Health and Nutrition Examination Survey (NHANES) 1999-2004. Am J Kidney Dis 2009;53:218-28
56. Levey AS, Atkins R, Coresh J, et al. Chronic kidney disease as a global public health problem: Approaches and initiatives-A position statement from Kidney Disease Improving Global Outcomes. Kidney Int 2007;72:247-59 (Pubitemid 47172384
57. Collins AJ, Foley RN, Herzog C, et al. United States Renal Data System 2008 annual data report. Am J Kidney Dis 2009;53:S1-374
58. Smith DH, Gullion CM, Nichols G, et al. Cost of medical care for chronic kidney disease and comorbidity among enrolees in a large HMO population. J Am Soc Nephrol 2004;15:1300-6 (Pubitemid 38526011
59. Barsoum RS. Chronic kidney disease in the developing world. N Engl J Med 2006;354:997-9 (Pubitemid 43357803
60. Vilayur E, Harris DC. Emerging therapies for chronic kidney disease: What is their role?. Nat Rev Nephrol 2009;5:375-83
61. Onuigbo MA. Reno-prevention vs. renoprotection: A critical re-Appraisal of the evidence-base from the large RAAS blockade trials after ONTARGET-A call for more circumspection. QJM 2009;102:155-67
62. Onuigbo MA. Is renoprotection with RAAS blockade a failed paradigm?. Have we learnt any lessons so far?. Int J Clin Pract 2010;64:1341-6
63. Cravedi P, Ruggenenti P, Remuzzi G. Which antihypertensive drugs are the most nephroprotective and why?. Expert Opin Pharmacother 2010;11:2651-63
64. Hsu CY, Vittinghoff E, Lin F, Shlipak MG. The incidence of end-stage renal disease is increasing faster than the prevalence of chronic renal insufficiency. Ann Intern Med 2004;141:95-101
65. Szczech LA, Lazar IL. Projecting the United States ESRD population: Issues regarding treatment of patients with ESRD. Kidney Int Suppl 2004;90:S3-7
66. Jones CA, Krolewski AS, Rogus J, et al. Epidemic of end-stage renal disease in people with diabetes in the United States population: Do we know the cause?. Kidney Int 2005;67:1684-91
67. Kensler TW, Wakabayashi N, Biswal S. Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol 2007;47:89-116
68. Motohashi H, Yamamoto M. Nrf2-Keap1 defines a physiologically important stress response mechanism. Trends Mol Med 2004;10:549-57 (Pubitemid 39433824
69. Sporn MB, Liby KT, Yore MM, et al. New synthetic triterpenoids: Potent agents for prevention and treatment of tissue injury caused by inflammatory and oxidative stress. J Nat Prod 2011;74:537-45
70. Zoja C, Benigni A, Remuzzi G. The Nrf2 pathway in the progression of renal disease. Nephrol Dial Transplant 2014;29(Suppl 1):i19-24
71. Kelly KJ, Dominguez JH. Rapid progression of diabetic nephropathy is linked to inflammation and episodes of acute renal failure. Am J Nephrol 2010;32:469-75
72. Miyamoto T, Carrero JJ, Stenvinkel P. Inflammation as a risk factor and target for therapy in chronic kidney disease. Curr Opin Nephrol Hypertens 2011;20:662-8
73. Onuigbo M. Renoprotection and the bardoxolone methyl story-is this the right way forward?. A novel view of renoprotection in CKD trials: A new classification scheme for renoprotective agents. Nephron Extra 2013;3:36-49
74. Pergola PE, Raskin P, Toto RD, et al. Bardoxolone methyl and kidney function in CKD with type 2 diabetes. N Engl J Med 2011;365:327-36
75. Chin M, Lee CY, Chuang JC, et al. Bardoxolone methyl analogs RTA 405 and dh404 are well tolerated and exhibit efficacy in rodent models of type 2 diabetes and obesity. Am J Physiol Renal Physiol 2013;304:F1438-46
76. McMahon GM, Forman JP. Bardoxolone methyl, chronic kidney disease, and type 2 diabetes. N Engl J Med 2011;365:1745; author reply 1745-1747
77. Rogacev KS, Bittenbring JT, Fliser D. Bardoxolone methyl, chronic kidney disease, and type 2 diabetes. N Engl J Med 2011;365:1745-6; author reply 1746-1747
78. Upadhyay A, Sarnak MJ, Levey AS. Bardoxolone methyl, chronic kidney disease, and type 2 diabetes. N Engl J Med 2011;365:1746; author reply 1746-1747
79. Ruggenenti P, Porrini EL, Gaspari F, et al. Glomerular hyperfiltration and renal disease progression in type 2 diabetes. Diabetes Care 2012;35:2061-8
80. Reisman SA, Chertow GM, Hebbar S, et al. Bardoxolone methyl decreases megalin and activates nrf2 in the kidney. J Am Soc Nephrol 2012;23:1663-73
81. Ding Y, Stidham RD, Bumeister R, et al. The synthetic triterpenoid, RTA 405, increases the glomerular filtration rate and reduces angiotensin II-induced contraction of glomerular mesangial cells. Kidney Int 2013;83:845-54
82. de Zeeuw D, Akizawa T, Agarwal R, et al. Rationale and trial design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes: The Occurrence of Renal Events (BEACON). Am J Nephrol 2013;37:212-22
83. de Zeeuw D, Akizawa T, Audhya P, et al. Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease. N Engl J Med 2013;369(26):2492-503
84. Cheng S, Coyne D. Oral paricalcitol for the treatment of secondary hyperparathyroidism in chronic kidney disease. Ther Clin Risk Manag 2006;2:297-301 (Pubitemid 44349504
85. Dusso AS, Brown AJ, Slatopolsky E. Vitamin D. Am J Physiol Renal Physiol 2005;289:F8-28
86. Nagpal S, Na S, Rathnachalam R. Noncalcemic actions of vitamin D receptor ligands. Endocr Rev 2005;26:662-87 (Pubitemid 41127276
87. Agarwal R, Acharya M, Tian J, et al. Antiproteinuric effect of oral paricalcitol in chronic kidney disease. Kidney Int 2005;68:2823-8 (Pubitemid 43251029
88. Mizobuchi M, Morrissey J, Finch JL, et al. Combination therapy with an angiotensin-converting enzyme inhibitor and a vitamin D analog suppresses the progression of renal insufficiency in uremic rats. J Am Soc Nephrol 2007;18:1796-806 (Pubitemid 46870316
89. de Zeeuw D, Agarwal R, Amdahl M, et al. Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diabetes (VITAL study): A randomised controlled trial. Lancet 2010;376:1543-51
90. Zhang Z, Zhang Y, Ning G, et al. Combination therapy with AT1 blocker and vitamin D analog markedly ameliorates diabetic nephropathy: Blockade of compensatory renin increase. Proc Natl Acad Sci USA 2008;105:15896-901
91. Freundlich M, Quiroz Y, Zhang Z, et al. Suppression of renin-Angiotensin gene expression in the kidney by paricalcitol. Kidney Int 2008;74:1394-402
92. Li YC, Kong J, Wei M, et al. 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the reninangiotensin system. J Clin Invest 2002;110:229-38
93. Duplancic D, Cesarik M, Poljak NK, et al. The influence of selective vitamin D receptor activator paricalcitol on cardiovascular system and cardiorenal protection. Clin Interv Aging 2013;8:149-56
94. Freundlich M, Quiroz Y, Zhang Z, et al. Suppression of reninangiotensin gene expression in the kidney by paricalcitol. Kidney Int 2008;74:1394-402
95. Mizobuchi M, Morrissey J, Finch JL, et al. Combination therapy with an angiotensin-converting enzyme inhibitor and a vitamin D analog suppresses the progression of renal insufficiency in uremic rats. J Am Soc Nephrol 2007;18:1796-806 (Pubitemid 46870316
96. Tan X, Li Y, Liu Y. Paricalcitol attenuates renal interstitial fibrosis in obstructive nephropathy. J Am Soc Nephrol 2006;17:3382-93 (Pubitemid 44865281
97. Schwarz U, Amann K, Orth SR, et al. Effect of 1,25 (OH)2 vitamin D3 on glomerulosclerosis in subtotally nephrectomized rats. Kidney Int 1998;53:1696-705
98. Li M, Batuman V. Vitamin D: A new hope for chronic kidney disease?. Kidney Int 2009;76:1219-21
99. Tan X, Wen X, Liu Y. Paricalcitol inhibits renal inflammation by promoting vitamin D receptor-mediated sequestration of NF-kappaB signaling. J Am Soc Nephrol 2008;19:1741-52
100. Eleftheriadis T, Antoniadi G, Liakopoulos V, et al. Vitamin D receptor activators and response to injury in kidney diseases. J Nephrol 2010;23:514-24
101. Packer M, McMurray J, Massie BM, et al. Clinical effects of endothelin receptor antagonism with bosentan in patients with severe chronic heart failure: Results of a pilot study. J Card Fail 2005;11:12-20 (Pubitemid 40215308
102. Anand I, McMurray J, Cohn JN, et al. Long-Term effects of darusentan on leftventricular remodelling and clinical outcomes in the EndothelinA Receptor Antagonist Trial in Heart Failure (EARTH): Randomised, double-blind, placebo-controlled trial. Lancet 2004;364:347-54
103. Schildroth J, Rettig-Zimmermann J, Kalk P, et al. Endothelin type A and B receptors in the control of afferent and efferent arterioles in mice. Nephrol Dial Transplant 2011;26:779-89
104. Dhaun N, Goddard J, Webb DJ. The endothelin system and its antagonism in chronic kidney disease. J Am Soc Nephrol 2006;17:943-55
105. Neuhofer W, Pittrow D. Endothelin receptor selectivity in chronic kidney disease: Rationale and review of recent evidence. Eur J Clin Invest 2009;39(Suppl 2):50-67
106. Weber MA, Black H, Bakris G, et al. A selective endothelin-receptor antagonist to reduce blood pressure in patients with treatment-resistant hypertension: A randomised, double-blind, placebocontrolled trial. Lancet 2009;374:1423-31
107. Wenzel RR, Littke T, Kuranoff S, et al. Avosentan reduces albumin excretion in diabetics with macroalbuminuria. J Am Soc Nephrol 2009;20:655-64
108. Mann JF, Green D, Jamerson K, et al. Avosentan for overt diabetic nephropathy. J Am Soc Nephrol 2010;21:527-35
109. Kohan DE, Pritchett Y, Molitch M, et al. Addition of atrasentan to reninangiotensin system blockade reduces albuminuria in diabetic nephropathy. J Am Soc Nephrol 2011;22:763-72
110. Study of Diabetic Nephropathy With Atrasentan (SONAR). Available from: Http://clinicaltrials.gov/ct2/show/NCT01858532
111. Williams ME, Bolton WK, Khalifah RG, et al. Effects of pyridoxamine in combined phase 2 studies of patients with type 1 and type 2 diabetes and overt nephropathy. Am J Nephrol 2007;27:605-14 (Pubitemid 350014947
112. Lewis EJ, Greene T, Spitalewiz S, et al. Pyridorin in type 2 diabetic nephropathy. J Am Soc Nephrol 2012;23:131-6
113. Lauver DA, Lucchesi BR. Sulodexide: A renewed interest in this glycosaminoglycan. Cardiovasc Drug Rev 2006;24:214-26 (Pubitemid 46435004
114. Harenberg J. Review of pharmacodynamics, pharmacokinetics, and therapeutic properties of sulodexide. Med Res Rev 1998;18:1-20 (Pubitemid 28037477
115. Solini A, Carraro A, Barzon I, Crepaldi G. Therapy with glycosaminoglycans lowers albumin excretion rate in non-insulin dependent diabetic patients with microalbuminuria. Diabetes Nutr Metab 1994;7:304-7
116. Solini A, Vergnani L, Ricci F, Crepaldi G. Glycosaminoglycans delay the progression of nephropathy in NIDDM. Diabetes Care 1997;20:813-17
117. Cernigoi M, Velussi AM, Dapas F, De Monte A. Glycosaminoglycans oral therapy reduces microalbuminuria, blood fibrinogen levels and limb arteriopathy clinical signs in patients with non-insulin dependent diabetes mellitus. Diabetes Nutr Metab 1996;9:53-8 (Pubitemid 26177692
118. Poplawska A, Szelachowska M, Topolska J, et al. Effect of glycosaminoglycans on urinary albumin excretion in insulin dependent diabetic patients with micro-or macroalbuminuria. Diabetes Res Clin Pract 1997;38:109-14 (Pubitemid 28103652
119. Szelanowska M, Poplawska A, Jopdska J, et al. A pilot study of the effect of the glycosaminoglycan sulodexide on microalbuminuria in type 1 diabetic patients. Curr Med Res Opin 1997;13:539-45 (Pubitemid 27199156
120. Lewis EJ, Lewis JB, Greene T, et al. Sulodexide for kidney protection in type 2 diabetes patients with microalbuminuria: A randomized controlled trial. Am J Kidney Dis 2011;58:729-36
121. Packham DK, Wolfe R, Reutens AT, et al. Sulodexide fails to demonstrate renoprotection in overt type 2 diabetic nephropathy. J Am Soc Nephrol 2012;23:123-30
122. Iyer SN, Gurujeyalakshmi G, Giri SN. Effects of pirfenidone on transforming growth factor-beta gene expression at the transcriptional level in bleomycin hamster model of lung fibrosis. J Pharmacol Exp Ther 1999;291:367-73 (Pubitemid 29451612
123. RamachandraRao SP, Zhu Y, Ravasi T, et al. Pirfenidone is renoprotective in diabetic kidney disease. J Am Soc Nephrol 2009;20:1765-75
124. Shimizu T, Fukagawa M, Kuroda T, et al. Pirfenidone prevents collagen accumulation in the remnant kidney in rats with partial nephrectomy. Kidney Int Suppl 1997;63:S239-43
125. Sharma K, Ix JH, Mathew AV, et al. Pirfenidone for diabetic nephropathy. J Am Soc Nephrol 2011;22:1144-51
126. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med 1993;329:1456-62 (Pubitemid 23335891
127. Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001;345:851-60
128. Stefoni S, Mosconi G, La Manna G, et al. Low-dosage ibopamine treatment in progressive renal failure: A long-Term multicentre trial. Am J Nephrol 1996;16:489-99 (Pubitemid 26387934
129. Feenstra H, Grobbee RE, in'tVeld BA, et al. Confounding by contraindication in a nationwide cohort study of risk for death in patients taking ibopamine. Ann Intern Med 2001;134:569-72