J Korean Diabetes.  2017 Dec;18(4):214-228. 10.4093/jkd.2017.18.4.214.

Recent Updates on Diabetic Nephropathy

Affiliations
  • 1Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. HANSH@yuhs.ac

Abstract

Diabetic nephropathy is a common complication of diabetes mellitus and is the leading cause of chronic kidney disease. Glycemic and blood pressure control constitute the main strategies of diabetic nephropathy prevention and treatment. However, despite current therapies, nephropathy progresses to renal failure and end-stage renal disease in many patients. Therefore, new therapeutic strategies targeting different pathophysiological mechanisms are needed. This review article briefly summarizes the standard therapy for diabetic nephropathy and also describes recent advances in potential renoprotective agents that could be used to prevent the development or progression of diabetic nephropathy.

Keyword

Diabetic nephropathy; Treatment

MeSH Terms

Blood Pressure
Diabetes Mellitus
Diabetic Nephropathies*
Humans
Kidney Failure, Chronic
Renal Insufficiency
Renal Insufficiency, Chronic

Cited by  1 articles

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Jieun Chu, Seon Cho, Suyoung Kim, Eunjoo Kwon, Eun-Hee Nah
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Reference

References

1. Nathan DM. DCCT/EDIC Research Group. The diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: overview. Diabetes Care. 2014; 37:9–16.
Article
2. 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; 365:2366–76.
3. Bilous R. Microvascular disease: what does the UKPDS tell us about diabetic nephropathy? Diabet Med. 2008; 25(Suppl 2):25–9.
Article
4. Action to Control Cardiovascular Risk in Diabetes Study Group. Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, Cushman WC, Genuth S, IsmailBeigi F, Grimm RH Jr, Probstfield JL, Simons-Morton DG, Friedewald WT. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008; 358:2545–59.
5. ADVANCE Collaborative Group. Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, Marre M, Cooper M, Glasziou P, Grobbee D, Hamet P, Harrap S, Heller S, Liu L, Mancia G, Mogensen CE, Pan C, Poulter N, Rodgers A, Williams B, Bompoint S, de Galan BE, Joshi R, Travert F. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008; 358:2560–72.
6. Ben Sahra I, Regazzetti C, Robert G, Laurent K, Le Marchand-Brustel Y, Auberger P, Tanti JF, Giorgetti-Peraldi S, Bost F. Metformin, independent of AMPK, induces mTOR inhibition and cell-cycle arrest through REDD1. Cancer Res. 2011; 71:4366–72.
Article
7. Jin HM, Pan Y. Renoprotection provided by losartan in combination with pioglitazone is superior to renoprotection provided by losartan alone in patients with type 2 diabetic nephropathy. Kidney Blood Press Res. 2007; 30:203–11.
Article
8. Fujita H, Morii T, Fujishima H, Sato T, Shimizu T, Hosoba M, Tsukiyama K, Narita T, Takahashi T, Drucker DJ, Seino Y, Yamada Y. The protective roles of GLP-1R signaling in diabetic nephropathy: possible mechanism and therapeutic potential. Kidney Int. 2014; 85:579–89.
Article
9. Mann JFE, Ørsted DD, Brown-Frandsen K, Marso SP, Poulter NR, Rasmussen S, Tornøe K, Zinman B, Buse JB. LEADER Steering Committee and Investigators. Liraglutide and renal outcomes in type 2 diabetes. N Engl J Med. 2017; 377:839–48.
Article
10. Hattori S. Sitagliptin reduces albuminuria in patients with type 2 diabetes. Endocr J. 2011; 58:69–73.
11. Fujita H, Taniai H, Murayama H, Ohshiro H, Hayashi H, Sato S, Kikuchi N, Komatsu T, Komatsu K, Komatsu K, Narita T, Yamada Y. DPP-4 inhibition with alogliptin on top of angiotensin II type 1 receptor blockade ameliorates albuminuria via upregulation of SDF-1α in type 2 diabetic patients with incipient nephropathy. Enocr J. 2014; 61:159–66.
12. Mori H, Okada Y, Arao T, Tanaka Y. Sitagliptin improves albuminuria in patients with type 2 diabetes mellitus. J Diabetes Investig. 2014; 5:313–9.
Article
13. Groop PH, Cooper ME, Perkovic V, Emser A, Woerle HJ, von Eynatten M. Linagliptin lowers albuminuria on top of recommended standard treatment in patients with type 2 diabetes and renal dysfunction. Diabetes Care. 2013; 36:3460–8.
Article
14. van Bommel EJ, Muskiet MH, Tonneijck L, Kramer MH, Nieuwdorp M, van Raalte DH. SGLT2 inhibition in the diabetic kidney-from mechanisms to clinical outcome. Clin J Am Soc Nephrol. 2017; 12:700–710.
Article
15. Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, Johansen OE, Woerle HJ, Broedl UC, Zinman B. EMPA-REG OUTCOME Investigators. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016; 375:323–34.
Article
16. Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR. CANVAS Program Collaborative Group. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017; 377:644–57.
Article
17. 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; 355:253–9.
18. Barnett AH, Bain SC, Bouter P, Karlberg B, Madsbad S, Jervell J, Mustonen J. Diabetics Exposed to Telmisartan and Enalapril Study Group. Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy. N Engl J Med. 2004; 351:1952–61.
Article
19. 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; 361:40–51.
Article
20. Parving HH, Lehnert H, Bröchner-Mortensen J, Gomis R, Andersen S, Arner P. Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study Group. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 2001; 345:870–8.
Article
21. Bangalore S, Fakheri R, Toklu B, Messerli FH. Diabetes mellitus as a compelling indication for use of renin angiotensin system blockers: systematic review and metaanalysis of randomized trials. BMJ. 2016; 352:i438.
Article
22. Onuigbo MA. The STOP-ACEi Trial-Apt timing for this long awaited randomised controlled trial-validation of the syndrome of late-onset renal failure from angiotensin blockade (LORFFAB)? Int J Clin Pract. 2017; 71:doi: 10.1111/ijcp.12916. [Epub ahead of print].
23. de Zeeuw D, Remuzzi G, Parving HH, Keane WF, Zhang Z, Shahinfar S, Snapinn S, Cooper ME, Mitch WE, Brenner BM. Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: lessons from RENAAL Kidney Int. 2004; 65:2309–20.
24. Hunsicker LG, Atkins RC, Lewis JB, Braden G, de Crespigny PJ, DeFerrari G, Drury P, Locatelli F, Wiegmann TB, Lewis EJ. Collaborative Study Group. Impact of irbesartan, blood pressure control, and proteinuria on renal outcomes in the Irbesartan Diabetic Nephropathy Trial. Kidney Int Suppl. 2004; 92:S99–101.
Article
25. Haller H, Ito S, Izzo JL Jr, 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; 364:907–17.
Article
26. Bilous R, Chaturvedi N, Sjølie AK, Fuller J, Klein R, Orchard T, Porta M, Parving HH. Effect of candesartan on microalbuminuria and albumin excretion rate in diabetes: three randomized trials. Ann Intern Med. 2009; 151:11–20. W3–4.
27. 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; 358:1547–59.
Article
28. Bomback AS, Kshirsagar AV, Amamoo MA, Klemmer PJ. Change in proteinuria after adding aldosterone blockers to ACE inhibitors or angiotensin receptor blockers in CKD: a systematic review. Am J Kidney Dis. 2008; 51:199–211.
Article
29. Pichler RH, de Boer IH. Dual renin-angiotensin-aldosterone system blockade for diabetic kidney disease. Curr Diab Rep. 2010; 10:297–305.
Article
30. Esteras R, Perez-Gomez MV, Rodriguez-Osorio L, Ortiz A, Fernandez-Fernandez B. Combination use of medicines from two classes of renin-angiotensin system blocking agents: risk of hyperkalemia, hypotension, and impaired renal function. Ther Adv Drug Saf. 2015; 6:166–76.
Article
31. Bakris GL, Agarwal R, Chan JC, Cooper ME, Gansevoort RT, Haller H, Remuzzi G, Rossing P, Schmieder RE, Nowack C, Kolkhof P, Joseph A, Pieper A, Kimmeskamp-Kirschbaum N, Ruilope LM. Mineralocorticoid Receptor Antagonist Tolerability Study–Diabetic Nephropathy (ARTS-DN) study Group. Effect of finerenone on albuminuria in patients with diabetic nephropathy: a randomized Clinical Trial JAMA. 2015; 314:884–94.
32. Williams B, MacDonald TM, Morant S, Webb DJ, Sever P, McInnes G, Ford I, Cruickshank JK, Caulfield MJ, Salsbury J, Mackenzie I, Padmanabhan S, Brown MJ. British Hypertension Society's PATHWAY Studies Group. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet. 2015; 386:2059–68.
Article
33. Parving HH, Persson F, Lewis JB, Lewis EJ, Hollenberg NK. AVOID Study Investigators. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Engl J Med. 2008; 358:2433–46.
Article
34. 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; 367:2204–13.
Article
35. Haynes R, Lewis D, Emberson J, Reith C, Agodoa L, Cass A, Craig JC, de Zeeuw D, Feldt-Rasmussen B, Fellström B, Levin A, Wheeler DC, Walker R, Herrington WG, Baigent C, Landray MJ. SHARP Collaborative Group; SHARP Collaborative Group. Effects of lowering LDL cholesterol on progression of kidney disease. J Am Soc Nephrol. 2014; 25:1825–33.
Article
36. Shen X, Zhang Z, Zhang X, Zhao J, Zhou X, Xu Q, Shang H, Dong J, Liao L. Efficacy of statins in patients with diabetic nephropathy: a metaanalysis of randomized controlled trials. Lipids Health Dis. 2016; 15:179.
Article
37. Sharaf El Din UA, Salem MM, Abdulazim DO. Stop chronic kidney disease progression: Time is approaching. World J Nephrol. 2016; 5:258–73.
38. Korean Diabetes Association. Medical treatment manual for diabetes-practice of dietetic therapy doctor need to know. Seoul: Korean Diabetes Association;2011. p. 27–31.
39. National Kidney Foundation. KDOQI clinical practice guideline for diabetes and CKD: 2012 update. Am J Kidney Dis. 2012; 60:850–86.
40. Gambaro G, Bax G, Fusaro M, Normanno M, Manani SM, Zanella M, Dangelo A, Fedele D, Favaro S. Cigarette smoking is a risk factor for nephropathy and its progression in type 2 diabetes mellitus. Diabetes Nutr Metab. 2001; 14:337–42.
41. Kang DH, Nakagawa T, Feng L, Watanabe S, Han L, Mazzali M, Truong L, Harris R, Johnson RJ. A role for uric acid in the progression of renal disease. J Am Soc Nephrol. 2002; 13:2888–97.
42. Siu YP, Leung KT, Tong MK, Kwan TH. Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level. Am J Kidney Dis. 2006; 47:51–9.
Article
43. Liu P, Chen Y, Wang B, Zhang F, Wang D, Wang Y. Allopurinol treatment improves renal function in patients with type 2 diabetes and asymptomatic hyperuricemia: 3-year randomized parallel-controlled study. Clin Endocrinol (Oxf). 2015; 83:475–82.
Article
44. Sircar D, Chatterjee S, Waikhom R, Golay V, Raychaudhury A, Chatterjee S, Pandey R. Efficacy of febuxostat for slowing the GFR decline in patients with CKD and asymptomatic hyperuricemia: a 6-month, double-blind, randomized, placebo-controlled trial. Am J Kidney Dis. 2015; 66:945–50.
Article
45. Jeong J, Kwon SK, Kim HY. Effect of bicarbonate supplementation on renal function and nutritional indices in predialysis advanced chronic kidney disease. Electrolyte Blood Press. 2014; 12:80–7.
Article
46. de Zeeuw D, Agarwal R, Amdahl M, Audhya P, Coyne D, Garimella T, Parving HH, Pritchett Y, Remuzzi G, Ritz E, Andress D. 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.
Article
47. Kim MJ, Frankel AH, Donaldson M, Darch SJ, Pusey CD, Hill PD, Mayr M, Tam FW. Oral cholecalciferol decreases albuminuria and urinary TGF-β1 in patients with type 2 diabetic nephropathy on established renin-angiotensin-aldosterone system inhibition. Kidney Int. 2011; 80:851–60.
Article
48. Navarro-González JF, Mora-Fernández C, Muros de Fuentes M, Chahin J, Méndez ML, Gallego E, Macía M, del Castillo N, Rivero A, Getino MA, García P, Jarque A, García J. Effect of pentoxifylline on renal function and urinary albumin excretion in patients with diabetic kidney disease: the PREDIAN trial. J Am Soc Nephrol. 2015; 26:220–9.
Article
49. 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; 22:1144–51.
Article
50. 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; 365:327–36.
Article
51. de Zeeuw D, Akizawa T, Audhya P, Bakris GL, Chin M, Christ-Schmidt H, Goldsberry A, Houser M, Krauth M, Lambers Heerspink HJ, McMurray JJ, Meyer CJ, Parving HH, Remuzzi G, Toto RD, Vaziri ND, Wanner C, Wittes J, Wrolstad D, Chertow GM. BEACON Trial Investigators. Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease. N Engl J Med. 2013; 369:2492–503.
Article
52. Tesch GH, Ma FY, Han Y, Liles JT, Breckenridge DG. Nikolic-Paterson D2. ASK1 inhibitor halts progression of diabetic nephropathy in Nos3-deficient mice. Diabetes. 2015; 64:3903–13.
Article
53. de Zeeuw D, Bekker P, Henkel E, Hasslacher C, Gouni-Berthold I, Mehling H, Potarca A, Tesar V, Heerspink HJ, Schall TJ. CCX140-B Diabetic Nephropathy Study Group. The effect of CCR2 inhibitor CCX140-B on residual albuminuria in patients with type 2 diabetes and nephropathy: a randomised trial. Lancet Diabetes Endocrinol. 2015; 3:687–96.
Article
54. Li JJ, Lee SH, Kim DK, Jin R, Jung DS, Kwak SJ, Kim SH, Han SH, Lee JE, Moon SJ, Ryu DR, Yoo TH, Han DS, Kang SW. Colchicine attenuates inflammatory cell infiltration and extracellular matrix accumulation in diabetic nephropathy. Am J Physiol Renal Physiol. 2009; 297:F200–9.
Article
55. Brosius FC, Tuttle KR, Kretzler M. JAK inhibition in the treatment of diabetic kidney disease. Diabetologia. 2016; 59:1624–7.
Article
56. Tuttle KR, McGill JB, Haney DJ, Lin TE, Anderson PW. PKC-DRS, PKC-DMES, and PKC-DRS 2 Study Groups. Kidney outcomes in longterm studies of ruboxistaurin for diabetic eye disease. Clin J Am Soc Nephrol. 2007; 2:631–6.
Article
57. Al-Onazi AS, Al-Rasheed NM, Attia HA, Al-Rasheed NM, Ahmed RM, Al-Amin MA, Poizat C. Ruboxistaurin attenuates diabetic nephropathy via modulation of TGF-β1/Smad and GRAP pathways. J Pharm Pharmacol. 2016; 68:219–32.
Article
58. Kennedy L, Solano MP, Meneghini L, Lo M, Cohen MP. Anti-glycation and anti-albuminuric effects of GLY-230 in human diabetes. Am J Nephrol. 2010; 31:110–6.
Article
59. Kohan DE, Lambers Heerspink HJ, Coll B, Andress D, Brennan JJ, Kitzman DW, Correa-Rotter R, Makino H, Perkovic V, Hou FF, Remuzzi G, Tobe SW, Toto R, Parving HH, de Zeeuw D. Predictors of atrasentan-associated fluid retention and change in albuminuria in patients with diabetic nephropathy. Clin J Am Soc Nephrol. 2015; 10:1568–74.
Article
60. Fang Y, Tian X, Bai S, Fan J, Hou W, Tong H, Li D. Autologous transplantation of adipose-derived mesenchymal stem cells ameliorates streptozotocin-induced diabetic nephropathy in rats by inhibiting oxidative stress, proinflammatory cytokines and the p38 MAPK signaling pathway. Int J Mol Med. 2012; 30:85–92.
Article
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