Skip to main content
SpringerLink
Log in

Diabetic Nephropathy Clinical Trials: A Critical Appraisal

  • Chapter
Informing Clinical Practice in Nephrology

  • 900 Accesses

Abstract

Over the last quarter of a century, diabetic nephropathy has steadily increased in incidence and prevalence to become one of the most common causes of ESRD. Worldwide, obesity and the associated type 2 diabetes mellitus (T2DM) have reached epidemic proportions leading to a significant rise in those suffering from diabetic kidney disease (DKD) [1]. This has coincided with considerable preclinical research aimed at a better understanding of the pathophysiology of diabetic nephropathy (DN) and its progression [2].

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 54.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Hossain P, Kawar B, El Nahas M. Obesity and diabetes in the developing world – a growing challenge. N Engl J Med. 2007;356(3):213–5.

    Article  CAS  PubMed  Google Scholar 

  2. Harjutsalo V, Groop PH. Epidemiology and risk factors for diabetic kidney disease. Adv Chronic Kidney Dis. 2014;21(3):260–6.

    Article  PubMed  Google Scholar 

  3. Giorgino F, Leonardini A, Laviola L. Cardiovascular disease and glycemic control in type 2 diabetes: now that the dust is settling from large clinical trials. Ann N Y Acad Sci. 2013;1281:36–50.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Yamout H, Lazich I, Bakris GL. Blood pressure, hypertension, RAAS blockade, and drug therapy in diabetic kidney disease. Adv Chronic Kidney Dis. 2014;21(3):281–6.

    Article  PubMed  Google Scholar 

  5. Anderson S, Brenner BM. Influence of antihypertensive therapy on development and progression of diabetic glomerulopathy. Diabetes Care. 1988;11(10):846–9.

    Article  CAS  PubMed  Google Scholar 

  6. 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.

    Article  CAS  PubMed  Google Scholar 

  7. Stanton RC. Clinical challenges in diagnosis and management of diabetic kidney disease. Am J Kidney Dis. 2014;63(2 Suppl 2):S3–21.

    Article  PubMed  Google Scholar 

  8. Khwaja A, El Kossi M, Floege J, El Nahas M. The management of CKD: a look into the future. Kidney Int. 2007;72(11):1316–23.

    Article  CAS  PubMed  Google Scholar 

  9. Fernandez-Fernandez B, Ortiz A, Gomez-Guerrero C, Egido J. Therapeutic approaches to diabetic nephropathy-beyond the RAS. Nat Rev Nephrol. 2014;10:325–46. doi:10.1038/nrneph.2014.74.

    Article  CAS  PubMed  Google Scholar 

  10. Giorgino F, Leonardini A, Laviola L. Cardiovascular disease and glycemic control in type 2 diabetes: now that the dust is settling from large clinical trials. Ann N Y Acad Sci. 2013;1281:36–50.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Macisaac RJ, Ekinci EI, Jerums G. Progressive diabetic nephropathy. How useful is microalbuminuria?: contra. Kidney Int. 2014;86:50–7. doi:10.1038/ki.2014.98.

    Article  PubMed  Google Scholar 

  12. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329(14):977–86.

    Article  Google Scholar 

  13. Bakris GL, Molitch M. Microalbuminuria as a risk predictor in diabetes: the continuing saga. Diabetes Care. 2014;37(3):867–75.

    Article  PubMed  Google Scholar 

  14. Mauer M, Zinman B, Gardiner R, Suissa S, Sinaiko A, Strand T, Drummond K, Donnelly S, Goodyer P, Gubler MC, Klein R. Renal and retinal effects of enalapril and losartan in type 1 diabetes. N Engl J Med. 2009;361(1):40–51.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. DCCT/EDIC Research Group, de Boer IH, Sun W, Cleary PA, Lachin JM, Molitch ME, Steffes MW, Zinman B. Intensive diabetes therapy and glomerular filtration rate in type 1 diabetes. N Engl J Med. 2011;365(25):2366–76.

    Article  Google Scholar 

  16. Giorgino F, Leonardini A, Laviola L. Cardiovascular disease and glycemic control in type 2 diabetes: now that the dust is settling from large clinical trials. Ann N Y Acad Sci. 2013;1281:36–50.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Rosansky SJ, Glassock RJ. Is a decline in estimated GFR an appropriate surrogate end point for renoprotection drug trials? Kidney Int. 2014;85(4):723–7.

    Article  PubMed  Google Scholar 

  18. Thomas MC, Jerums G, Tsalamandris C, Macisaac R, Panagiotopoulos S, Cooper ME, MDNSG Study Group. Increased tubular organic ion clearance following chronic ACE inhibition in patients with type 1 diabetes. Kidney Int. 2005;67(6):2494–9.

    Article  PubMed  Google Scholar 

  19. Mancia G, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013;34(28):2159–219.

    Article  PubMed  Google Scholar 

  20. Niiranen TJ, Mäki J, Puukka P, Karanko H, Jula AM. Office, home, and ambulatory blood pressures as predictors of cardiovascular risk. Hypertension. 2014. pii: HYPERTENSIONAHA.114.03292. [Epub ahead of print].

    Google Scholar 

  21. Brenner BM, Cooper ME, de Zeeuw D, et al. The Losartan Renal Protection Study: rationale, study design and baseline characteristics of RENAAL (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan). J Renin Angiotensin Aldosterone Syst. 2000;1(4):328–35.

    Article  CAS  PubMed  Google Scholar 

  22. Heart Outcomes Prevention Evaluation Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet. 2000;355(9200):253–9.

    Article  Google Scholar 

  23. Thomas MC, Tikellis C, Burns WC, Thallas V, Forbes JM, Cao Z, Osicka TM, Russo LM, Jerums G, Ghabrial H, Cooper ME, Kantharidis P. Reduced tubular cation transport in diabetes: prevented by ACE inhibition. Kidney Int. 2003;63(6):2152–61.

    Article  CAS  PubMed  Google Scholar 

  24. Thomas MC, Jerums G, Tsalamandris C, Macisaac R, Panagiotopoulos S, Cooper ME, MDNSG Study Group. Increased tubular organic ion clearance following chronic ACE inhibition in patients with type 1 diabetes. Kidney Int. 2005;67(6):2494–9.

    Article  PubMed  Google Scholar 

  25. Montori VM, Permanyer-Miralda G, Ferreira-González I, Busse JW, Pacheco-Huergo V, Bryant D, Alonso J, Akl EA, Domingo-Salvany A, Mills E, Wu P, Schünemann HJ, Jaeschke R, Guyatt GH. Validity of composite end points in clinical trials. BMJ. 2005;330:594.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Niiranen TJ, Mäki J, Puukka P, Karanko H, Jula AM. Office, home, and ambulatory blood pressures as predictors of cardiovascular risk. Hypertension. 2014. pii: HYPERTENSIONAHA.114.03292. [Epub ahead of print].

    Google Scholar 

  27. Svensson P, de Faire U, Sleight P, Yusuf S, Ostergren J. Comparative effects of ramipril on ambulatory and office blood pressures: a HOPE Substudy. Hypertension. 2001;38(6):E28–32.

    Article  CAS  PubMed  Google Scholar 

  28. Rodby RA, Rohde RD, Clarke WR, et al. The Irbesartan type II diabetic nephropathy trial: study design and baseline patient characteristics. Nephrol Dial Transplant. 2000;15:487–97.

    Article  CAS  PubMed  Google Scholar 

  29. Thomas MC, Tikellis C, Burns WC, Thallas V, Forbes JM, Cao Z, Osicka TM, Russo LM, Jerums G, Ghabrial H, Cooper ME, Kantharidis P. Reduced tubular cation transport in diabetes: prevented by ACE inhibition. Kidney Int. 2003;63(6):2152–61.

    Article  CAS  PubMed  Google Scholar 

  30. Thomas MC, Jerums G, Tsalamandris C, Macisaac R, Panagiotopoulos S, Cooper ME, MDNSG Study Group. Increased tubular organic ion clearance following chronic ACE inhibition in patients with type 1 diabetes. Kidney Int. 2005;67(6):2494–9.

    Article  PubMed  Google Scholar 

  31. Montori VM, Permanyer-Miralda G, Ferreira-González I, Busse JW, Pacheco-Huergo V, Bryant D, Alonso J, Akl EA, Domingo-Salvany A, Mills E, Wu P, Schünemann HJ, Jaeschke R, Guyatt GH. Validity of composite end points in clinical trials. BMJ. 2005;330:594.

    Article  PubMed Central  PubMed  Google Scholar 

  32. Packham DK, Ivory SE, Reutens AT, Wolfe R, Rohde R, Lambers Heerspink H, Dwyer JP, Atkins RC, Lewis J, Collaborative Study Group. Proteinuria in type 2 diabetic patients with renal impairment: the changing face of diabetic nephropathy. Nephron Clin Pract. 2011;118(4):c331–8.

    Article  CAS  PubMed  Google Scholar 

  33. Tuomi T, Santoro N, Caprio S, Cai M, Weng J, Groop L. The many faces of diabetes: a disease with increasing heterogeneity. Lancet. 2014;383(9922):1084–94.

    Article  PubMed  Google Scholar 

  34. ONTARGET Investigators, Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H, Dagenais G, Sleight P, Anderson C. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358(15):1547–59.

    Article  Google Scholar 

  35. Parving HH, Brenner BM, McMurray JJ, de Zeeuw D, Haffner SM, Solomon SD, Chaturvedi N, Persson F, Desai AS, Nicolaides M, Richard A, Xiang Z, Brunel P, Pfeffer MA, ALTITUDE Investigators. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med. 2012;367(23):2204–13.

    Article  CAS  PubMed  Google Scholar 

  36. Bakris GL, Sarafidis PA, Weir MR, Dahlöf B, Pitt B, Jamerson K, Velazquez EJ, Staikos-Byrne L, Kelly RY, Shi V, Chiang YT, Weber MA, ACCOMPLISH Trial Investigators. Renal outcomes with different fixed-dose combination therapies in patients with hypertension at high risk for cardiovascular events (ACCOMPLISH): a prespecified secondary analysis of a randomised controlled trial. Lancet. 2010;375(9721):1173–81.

    Article  CAS  PubMed  Google Scholar 

  37. ONTARGET Investigators, Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H, Dagenais G, Sleight P, Anderson C. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358(15):1547–59.

    Article  Google Scholar 

  38. Parving HH, Brenner BM, McMurray JJ, de Zeeuw D, Haffner SM, Solomon SD, Chaturvedi N, Persson F, Desai AS, Nicolaides M, Richard A, Xiang Z, Brunel P, Pfeffer MA, ALTITUDE Investigators. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med. 2012;367(23):2204–13.

    Article  CAS  PubMed  Google Scholar 

  39. ONTARGET Investigators, Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H, Dagenais G, Sleight P, Anderson C. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358(15):1547–59.

    Article  Google Scholar 

  40. Ruggenenti P, Fassi A, Ilieva AP, Bruno S, Iliev IP, Brusegan V, Rubis N, Gherardi G, Arnoldi F, Ganeva M, Ene-Iordache B, Gaspari F, Perna A, Bossi A, Trevisan R, Dodesini AR, Remuzzi G, Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) Investigators. Preventing microalbuminuria in type 2 diabetes. N Engl J Med. 2004;351(19):1941–51.

    Article  CAS  PubMed  Google Scholar 

  41. Haller H, Ito S, Izzo Jr JL, Januszewicz A, Katayama S, Menne J, Mimran A, Rabelink TJ, Ritz E, Ruilope LM, Rump LC, Viberti G, ROADMAP Trial Investigators. Olmesartan for the delay or prevention of microalbuminuria in type 2 diabetes. N Engl J Med. 2011;364(10):907–17.

    Article  CAS  PubMed  Google Scholar 

  42. Estacio RO, Savage S, Nagel NJ, Schrier RW. Baseline characteristics of participants in the Appropriate Blood Pressure Control in Diabetes trial. Control Clin Trials. 1996;17:242–57.

    Article  CAS  PubMed  Google Scholar 

  43. Abstract; Savage et al. American Society of Nephrology Meeting. 1993.

    Google Scholar 

  44. Kohan DE, Pritchett Y, Molitch M, Wen S, Garimella T, Audhya P, Andress DL. Addition of atrasentan to renin-angiotensin system blockade reduces albuminuria in diabetic nephropathy. J Am Soc Nephrol. 2011;22(4):763–72.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. Stanton RC. Clinical challenges in diagnosis and management of diabetic kidney disease. Am J Kidney Dis. 2014;63(2 Suppl 2):S3–21.

    Article  PubMed  Google Scholar 

  46. Miyata T, Suzuki N, van Ypersele de Strihou C. Diabetic nephropathy: are there new and potentially promising therapies targeting oxygen biology? Kidney Int. 2013;84(4):693–702.

    Article  CAS  PubMed  Google Scholar 

  47. Arora MK, Singh UK. Oxidative stress: meeting multiple targets in pathogenesis of diabetic nephropathy. Curr Drug Targets. 2014;15(5):531–8.

    Article  CAS  PubMed  Google Scholar 

  48. Rojas-Rivera J, Ortiz A, Egido J. Antioxidants in kidney diseases: the impact of bardoxolone methyl. Int J Nephrol. 2012;2012:321714.

    PubMed Central  PubMed  Google Scholar 

  49. Pergola PE, Raskin P, Toto RD, Meyer CJ, Huff JW, Grossman EB, Krauth M, Ruiz S, Audhya P, Christ-Schmidt H, Wittes J, Warnock DG, BEAM Study Investigators. Bardoxolone methyl and kidney function in CKD with type 2 diabetes. N Engl J Med. 2011;365(4):327–36.

    Article  CAS  PubMed  Google Scholar 

  50. Tayek JA, Kalantar-Zadeh K. The extinguished BEACON of bardoxolone: not a Monday morning quarterback story. Am J Nephrol. 2013;37(3):208–11.

    Article  PubMed Central  PubMed  Google Scholar 

  51. Sharma K, Ix JH, Mathew AV, Cho M, Pflueger A, Dunn SR, Francos B, Sharma S, Falkner B, McGowan TA, Donohue M, Ramachandrarao S, Xu R, Fervenza FC, Kopp JB. Pirfenidone for diabetic nephropathy. J Am Soc Nephrol. 2011;22(6):1144–51.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Tayek JA, Kalantar-Zadeh K. The extinguished BEACON of bardoxolone: not a Monday morning quarterback story. Am J Nephrol. 2013;37(3):208–11.

    Article  PubMed Central  PubMed  Google Scholar 

  53. Pirfenidone. First, do no harm. Prescrire Int. 2013;22(138):117–9.

    Google Scholar 

  54. Stanton RC. Clinical challenges in diagnosis and management of diabetic kidney disease. Am J Kidney Dis. 2014;63(2 Suppl 2):S3–21.

    Article  PubMed  Google Scholar 

  55. D’Agati V, Yan SF, Ramasamy R, Schmidt AM. RAGE, glomerulosclerosis and proteinuria: roles in podocytes and endothelial cells. Trends Endocrinol Metab. 2010;21(1):50–6.

    Article  PubMed  Google Scholar 

  56. Degenhardt TP, Alderson NL, Arrington DD, Beattie RJ, Basgen JM, Steffes MW, Thorpe SR, Baynes JW. Pyridoxamine inhibits early renal disease and dyslipidemia in the streptozotocin-diabetic rat. Kidney Int. 2002;61:939–50.

    Article  CAS  PubMed  Google Scholar 

  57. Williams ME, Bolton WK, Khalifah RG, Degenhardt TP, Schotzinger RJ, McGill JB. 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.

    Article  CAS  PubMed  Google Scholar 

  58. Lauver DA, Lucchesi B. Sulodexide: a renewed interest in this glycos-aminoglycan. Cardiovasc Drug Rev. 2006;24:214–26.

    Article  CAS  PubMed  Google Scholar 

  59. Gambaro G, Cavazzana AO, Luzi P, Piccoli A, Borsatti A, Crepaldi G, Marchi E, Venturini AP, Baggio B. Glycosaminoglycans prevent morphological renal alterations and albuminuria in diabetic rats. Kidney Int. 1992;42:285–91.

    Article  CAS  PubMed  Google Scholar 

  60. Gambaro G, Kinalska I, Oksa A, Pont’uch P, Hertlová M, Olsovsky J, Manitius J, Fedele D, Czekalski S, Perusicová J, Skrha J, Taton J, Grzeszczak W, Crepaldi G. Oral sulodexide reduces albuminuria in microalbuminuric and macroalbuminuric type 1 and type 2 diabetic patients: the Di.N.A.S. randomized trial. J Am Soc Nephrol. 2002;13:1615–25.

    Article  CAS  PubMed  Google Scholar 

  61. Achour A, Kacem M, Dibej K, Skhiri H, Bouraoui S, El May M. One year course of oral sulodexide in the management of diabetic nephropathy. J Nephrol. 2005;18:568–74.

    CAS  PubMed  Google Scholar 

  62. Pérez-Gómez MV, Ortiz-Arduán A, Lorenzo-Sellares V. Vitamin D and proteinuria: a critical review of molecular bases and clinical experience. Nefrologia. 2013;33(5):716–26.

    PubMed  Google Scholar 

  63. Wang Y, Deb Dk, Zhang Z, et al. Vitamin D receptor signalling in podocytes protects against diabetic nephropathy. J Am Soc Nephrol, 2012;23:1977–86.

    Google Scholar 

  64. Weir MR. Short term effects of vitamin D receptor activation on serum creatinine, creatinine generation and glomerular filtration. Kidney Int, 2011;80:1016–7.

    Google Scholar 

  65. ONTARGET Investigators, Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H, Dagenais G, Sleight P, Anderson C. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358(15):1547–59.

    Article  Google Scholar 

  66. Fried LF, Emanuele N, Zhang JH, Brophy M, Conner TA, Duckworth W, Leehey DJ, McCullough PA, O’Connor T, Palevsky PM, Reilly RF, Seliger SL, Warren SR, Watnick S, Peduzzi P, Guarino P, VA NEPHRON-D Investigators. Combined angiotensin inhibition for the treatment of diabetic nephropathy. N Engl J Med. 2013;369(20):1892–903.

    Article  CAS  PubMed  Google Scholar 

  67. Mann JF, Green D, Jamerson K, Ruilope LM, Kuranoff SJ, Littke T, Viberti G, ASCEND Study Group. Avosentan for overt diabetic nephropathy. J Am Soc Nephrol. 2010;21(3):527–35.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  68. Giorgino F, Leonardini A, Laviola L. Cardiovascular disease and glycemic control in type 2 diabetes: now that the dust is settling from large clinical trials. Ann N Y Acad Sci. 2013;1281:36–50.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  69. Arguedas JA, Leiva V, Wright JM. Blood pressure targets for hypertension in people with diabetes mellitus. Cochrane Database Syst Rev. 2013;10:CD008277. doi:10.1002/14651858.CD008277.pub2.

  70. Reboldi G, Gentile G, Manfreda VM, Angeli F, Verdecchia P. Tight blood pressure control in diabetes: evidence-based review of treatment targets in patients with diabetes. Curr Cardiol Rep. 2012;14(1):89–96.

    Article  PubMed  Google Scholar 

  71. Casas JP, Chua W, Loukogeorgakis S, Vallance P, Smeeth L, Hingorani AD, MacAllister RJ. Effect of inhibitors of the renin-angiotensin system and other antihypertensive drugs on renal outcomes: systematic review and meta-analysis. Lancet. 2005;366(9502):2026–33.

    Article  CAS  PubMed  Google Scholar 

  72. Wu HY, Huang JW, Lin HJ, Liao WC, Peng YS, Hung KY, Wu KD, Tu YK, Chien KL. Comparative effectiveness of renin-angiotensin system blockers and other antihypertensive drugs in patients with diabetes: systematic review and bayesian network meta-analysis. BMJ. 2013;347:f6008. doi:10.1136/bmj.f6008.

    Article  PubMed Central  PubMed  Google Scholar 

  73. Blood Pressure Lowering Treatment Trialists’ Collaboration, Ninomiya T, Perkovic V, Turnbull F, Neal B, Barzi F, Cass A, Baigent C, Chalmers J, Li N, Woodward M, MacMahon S. Blood pressure lowering and major cardiovascular events in people with and without chronic kidney disease: meta-analysis of randomised controlled trials. BMJ. 2013;347:f5680. doi:10.1136/bmj.f5680.

    Article  PubMed Central  Google Scholar 

  74. Savarese G, Costanzo P, Cleland JG, Vassallo E, Ruggiero D, Rosano G, Perrone-Filardi P. A meta-analysis reporting effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients without heart failure. J Am Coll Cardiol. 2013;61(2):131–42.

    Article  CAS  PubMed  Google Scholar 

  75. Thomas MC, Tikellis C, Burns WC, Thallas V, Forbes JM, Cao Z, Osicka TM, Russo LM, Jerums G, Ghabrial H, Cooper ME, Kantharidis P. Reduced tubular cation transport in diabetes: prevented by ACE inhibition. Kidney Int. 2003;63(6):2152–61.

    Article  CAS  PubMed  Google Scholar 

  76. Thomas MC, Jerums G, Tsalamandris C, Macisaac R, Panagiotopoulos S, Cooper ME, MDNSG Study Group. Increased tubular organic ion clearance following chronic ACE inhibition in patients with type 1 diabetes. Kidney Int. 2005;67(6):2494–9.

    Article  PubMed  Google Scholar 

  77. Bakris GL, Sarafidis PA, Weir MR, Dahlöf B, Pitt B, Jamerson K, Velazquez EJ, Staikos-Byrne L, Kelly RY, Shi V, Chiang YT, Weber MA, ACCOMPLISH Trial investigators. Renal outcomes with different fixed-dose combination therapies in patients with hypertension at high risk for cardiovascular events (ACCOMPLISH): a prespecified secondary analysis of a randomised controlled trial. Lancet. 2010;375(9721):1173–81.

    Article  CAS  PubMed  Google Scholar 

  78. Fernandez-Fernandez B, Ortiz A, Gomez-Guerrero C, Egido J. Therapeutic approaches to diabetic nephropathy-beyond the RAS. Nat Rev Nephrol. 2014. doi:10.1038/nrneph.2014.74.

    PubMed  Google Scholar 

  79. Khwaja A, El Kossi M, Floege J, El Nahas M. The management of CKD: a look into the future. Kidney Int. 2007;72(11):1316–23.

    Article  CAS  PubMed  Google Scholar 

  80. Macisaac RJ, Ekinci EI, Jerums G. Progressive diabetic nephropathy. How useful is microalbuminuria?: contra. Kidney Int. 2014;86:50–7. doi:10.1038/ki.2014.98.

    Article  PubMed  Google Scholar 

  81. Tuomi T, Santoro N, Caprio S, Cai M, Weng J, Groop L. The many faces of diabetes: a disease with increasing heterogeneity. Lancet. 2014;383(9922):1084–94.

    Article  PubMed  Google Scholar 

  82. Packham DK, Ivory SE, Reutens AT, Wolfe R, Rohde R, Lambers Heerspink H, Dwyer JP, Atkins RC, Lewis J, Collaborative Study Group. Proteinuria in type 2 diabetic patients with renal impairment: the changing face of diabetic nephropathy. Nephron Clin Pract. 2011;118(4):c331–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Sheffield Kidney Institute, Global Kidney Academy, Sheffield, UK

    Meguid El Nahas MD, PhD, FRCP

  2. Department of Nephrology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, Copenhagen, 2100, Denmark

    Bo Feldt-Rasmussen MD, DMSc

Authors
  1. Meguid El Nahas MD, PhD, FRCP
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bo Feldt-Rasmussen MD, DMSc
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Meguid El Nahas MD, PhD, FRCP .

Editor information

Editors and Affiliations

  1. Doncaster Royal Infirmary, Doncaster, United Kingdom

    Mohsen El Kossi

  2. Sheffield Kidney Institute Northern General Hospital, Sheffield, United Kingdom

    Arif Khwaja

  3. Sheffield Kidney Institute Northern General Hospital, Sheffield, United Kingdom

    Meguid El Nahas

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

El Nahas, M., Feldt-Rasmussen, B. (2015). Diabetic Nephropathy Clinical Trials: A Critical Appraisal. In: El Kossi, M., Khwaja, A., El Nahas, M. (eds) Informing Clinical Practice in Nephrology. Springer, Cham. https://doi.org/10.1007/978-3-319-10292-4_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-10292-4_9

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-10291-7

  • Online ISBN: 978-3-319-10292-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation