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J Natl Med Assoc. Nov 2004; 96(11): 1445–1454.
PMCID: PMC2568593

Diabetic nephropathy--a review of the natural history, burden, risk factors and treatment.

Abstract

The earliest clinical evidence of diabetic nephropathy is microalbuminuria. Progression from microalbuminuria to overt nephropathy occurs in 20-40% within a 10-year period with approximately 20% of these patients progressing to end-stage renal disease. End-stage renal disease develops in 50% of type-1 diabetes patients with overt nephropathy within 10 years and in more than 75% by 20 years in the absence of treatment. In type-2 diabetes, a greater proportion of patients have microalbuminuria and overt nephropathy at or shortly after diagnosis of diabetes. The incidence of diabetes is increasing worldwide, with subsequent increase in the incidence of diabetic nephropathy. The risk factors identified in the development of DN from longitudinal and cross-sectional studies include race, genetic susceptibility, hypertension, hyperglycemia, hyperfiltration, smoking, advanced age, male sex, and high-protein diet. Treatment interventions in diabetic nephropathy include glycemic control, treatment of hypertension, hyperlipidemia, cessation of smoking, protein restriction, and renal replacement therapy. Multifactorial approach includes combined therapy targeting hyperglycemia, hypertension, microalbuminuria, and dyslipidemia.

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  • Reeves WB, Andreoli TE. Transforming growth factor beta contributes to progressive diabetic nephropathy. Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7667–7669. [PMC free article] [PubMed]
  • Hostetter TH, Troy JL, Brenner BM. Glomerular hemodynamics in experimental diabetes mellitus. Kidney Int. 1981 Mar;19(3):410–415. [PubMed]
  • Hostetter TH, Rennke HG, Brenner BM. The case for intrarenal hypertension in the initiation and progression of diabetic and other glomerulopathies. Am J Med. 1982 Mar;72(3):375–380. [PubMed]
  • Reddi AS, Camerini-Davalos RA. Diabetic nephropathy. An update. Arch Intern Med. 1990 Jan;150(1):31–43. [PubMed]
  • Remuzzi Giuseppe, Schieppati Arrigo, Ruggenenti Piero. Clinical practice. Nephropathy in patients with type 2 diabetes. N Engl J Med. 2002 Apr 11;346(15):1145–1151. [PubMed]
  • Ritz E, Orth SR. Nephropathy in patients with type 2 diabetes mellitus. N Engl J Med. 1999 Oct 7;341(15):1127–1133. [PubMed]
  • Kurokawa Kiyoshi, Nangaku Masaomi, Saito Akira, Inagi Reiko, Miyata Toshio. Current issues and future perspectives of chronic renal failure. J Am Soc Nephrol. 2002 Jan;13 (Suppl 1):S3–S6. [PubMed]
  • King H, Aubert RE, Herman WH. Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998 Sep;21(9):1414–1431. [PubMed]
  • Ritz E, Stefanski A. Diabetic nephropathy in type II diabetes. Am J Kidney Dis. 1996 Feb;27(2):167–194. [PubMed]
  • Akinsola W, Odesanmi WO, Ogunniyi JO, Ladipo GO. Diseases causing chronic renal failure in Nigerians--a prospective study of 100 cases. Afr J Med Med Sci. 1989 Jun;18(2):131–137. [PubMed]
  • Salako BL, Ayodele OE, Kadiri S, Arije A. Prevalence of hepatitis B and C viruses in pre-dialysis patients with chronic renal failure. Afr J Med Med Sci. 2002 Dec;31(4):311–314. [PubMed]
  • Abboud OL, Osman EM, Musa AR. The aetiology of chronic renal failure in adult Sudanese patients. Ann Trop Med Parasitol. 1989 Aug;83(4):411–414. [PubMed]
  • Muntner Paul, He Jiang, Hamm Lee, Loria Catherine, Whelton Paul K. Renal insufficiency and subsequent death resulting from cardiovascular disease in the United States. J Am Soc Nephrol. 2002 Mar;13(3):745–753. [PubMed]
  • Krolewski AS. Genetics of diabetic nephropathy: evidence for major and minor gene effects. Kidney Int. 1999 Apr;55(4):1582–1596. [PubMed]
  • Pettitt DJ, Saad MF, Bennett PH, Nelson RG, Knowler WC. Familial predisposition to renal disease in two generations of Pima Indians with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia. 1990 Jul;33(7):438–443. [PubMed]
  • Gall MA, Hougaard P, Borch-Johnsen K, Parving HH. Risk factors for development of incipient and overt diabetic nephropathy in patients with non-insulin dependent diabetes mellitus: prospective, observational study. BMJ. 1997 Mar 15;314(7083):783–788. [PMC free article] [PubMed]
  • Ravid M, Neumann L, Lishner M. Plasma lipids and the progression of nephropathy in diabetes mellitus type II: effect of ACE inhibitors. Kidney Int. 1995 Mar;47(3):907–910. [PubMed]
  • Hovind P, Rossing P, Tarnow L, Smidt UM, Parving HH. Progression of diabetic nephropathy. Kidney Int. 2001 Feb;59(2):702–709. [PubMed]
  • Cooper ME. Pathogenesis, prevention, and treatment of diabetic nephropathy. Lancet. 1998 Jul 18;352(9123):213–219. [PubMed]
  • Pugh JA, Stern MP, Haffner SM, Eifler CW, Zapata M. Excess incidence of treatment of end-stage renal disease in Mexican Americans. Am J Epidemiol. 1988 Jan;127(1):135–144. [PubMed]
  • Brancati FL, Whittle JC, Whelton PK, Seidler AJ, Klag MJ. The excess incidence of diabetic end-stage renal disease among blacks. A population-based study of potential explanatory factors. JAMA. 1992 Dec 2;268(21):3079–3084. [PubMed]
  • Seaquist ER, Goetz FC, Rich S, Barbosa J. Familial clustering of diabetic kidney disease. Evidence for genetic susceptibility to diabetic nephropathy. N Engl J Med. 1989 May 4;320(18):1161–1165. [PubMed]
  • Jeffers BW, Estacio RO, Raynolds MV, Schrier RW. Angiotensin-converting enzyme gene polymorphism in non-insulin dependent diabetes mellitus and its relationship with diabetic nephropathy. Kidney Int. 1997 Aug;52(2):473–477. [PubMed]
  • Kuramoto N, Iizuka T, Ito H, Yagui K, Omura M, Nozaki O, Nishikawa T, Tsuchida H, Makino H, Saito Y, et al. Effect of ACE gene on diabetic nephropathy in NIDDM patients with insulin resistance. Am J Kidney Dis. 1999 Feb;33(2):276–281. [PubMed]
  • Kunz R, Bork JP, Fritsche L, Ringel J, Sharma AM. Association between the angiotensin-converting enzyme-insertion/deletion polymorphism and diabetic nephropathy: a methodologic appraisal and systematic review. J Am Soc Nephrol. 1998 Sep;9(9):1653–1663. [PubMed]
  • Shah VO, Scavini M, Nikolic J, Sun Y, Vai S, Griffith JK, Dorin RI, Stidley C, Yacoub M, Vander Jagt DL, et al. Z-2 microsatellite allele is linked to increased expression of the aldose reductase gene in diabetic nephropathy. J Clin Endocrinol Metab. 1998 Aug;83(8):2886–2891. [PubMed]
  • Blüthner M, Schmidt S, Siffert W, Knigge H, Nawroth P, Ritz E. Increased frequency of G-protein beta 3-subunit 825 T allele in dialyzed patients with type 2 diabetes. Kidney Int. 1999 Apr;55(4):1247–1250. [PubMed]
  • Arauz-Pacheco Carlos, Parrott Marian A, Raskin Philip. The treatment of hypertension in adult patients with diabetes. Diabetes Care. 2002 Jan;25(1):134–147. [PubMed]
  • Arauz-Pacheco Carlos, Parrott Marian A, Raskin Philip. Treatment of hypertension in adults with diabetes. Diabetes Care. 2003 Jan;26 (Suppl 1):S80–S82. [PubMed]
  • Earle K, Viberti GC. Familial, hemodynamic and metabolic factors in the predisposition to diabetic kidney disease. Kidney Int. 1994 Feb;45(2):434–437. [PubMed]
  • Ismail N, Becker B, Strzelczyk P, Ritz E. Renal disease and hypertension in non-insulin-dependent diabetes mellitus. Kidney Int. 1999 Jan;55(1):1–28. [PubMed]
  • Nakano S, Fukuda M, Hotta F, Ito T, Ishii T, Kitazawa M, Nishizawa M, Kigoshi T, Uchida K. Reversed circadian blood pressure rhythm is associated with occurrences of both fatal and nonfatal vascular events in NIDDM subjects. Diabetes. 1998 Sep;47(9):1501–1506. [PubMed]
  • Mogensen CE. Microalbuminuria, blood pressure and diabetic renal disease: origin and development of ideas. Diabetologia. 1999 Mar;42(3):263–285. [PubMed]
  • Mulec H, Blohmé G, Grände B, Björck S. The effect of metabolic control on rate of decline in renal function in insulin-dependent diabetes mellitus with overt diabetic nephropathy. Nephrol Dial Transplant. 1998 Mar;13(3):651–655. [PubMed]
  • Orth SR, Ritz E, Schrier RW. The renal risks of smoking. Kidney Int. 1997 Jun;51(6):1669–1677. [PubMed]
  • Stegmayr BG. A study of patients with diabetes mellitus (type 1) and end-stage renal failure: tobacco usage may increase risk of nephropathy and death. J Intern Med. 1990 Aug;228(2):121–124. [PubMed]
  • Klein R, Klein BE, Moss SE, Cruickshanks KJ, Brazy PC. The 10-year incidence of renal insufficiency in people with type 1 diabetes. Diabetes Care. 1999 May;22(5):743–751. [PubMed]
  • Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. JAMA. 2002 May 15;287(19):2563–2569. [PMC free article] [PubMed]
  • Ohkubo Y, Kishikawa H, Araki E, Miyata T, Isami S, Motoyoshi S, Kojima Y, Furuyoshi N, Shichiri M. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract. 1995 May;28(2):103–117. [PubMed]
  • Bakris G, Viberti G, Weston WM, Heise M, Porter LE, Freed MI. Rosiglitazone reduces urinary albumin excretion in type II diabetes. J Hum Hypertens. 2003 Jan;17(1):7–12. [PubMed]
  • Bakris GL, Williams M, Dworkin L, Elliott WJ, Epstein M, Toto R, Tuttle K, Douglas J, Hsueh W, Sowers J. Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Am J Kidney Dis. 2000 Sep;36(3):646–661. [PubMed]
  • Peterson JC, Adler S, Burkart JM, Greene T, Hebert LA, Hunsicker LG, King AJ, Klahr S, Massry SG, Seifter JL. Blood pressure control, proteinuria, and the progression of renal disease. The Modification of Diet in Renal Disease Study. Ann Intern Med. 1995 Nov 15;123(10):754–762. [PubMed]
  • Parving HH, Andersen AR, Smidt UM, Svendsen PA. Early aggressive antihypertensive treatment reduces rate of decline in kidney function in diabetic nephropathy. Lancet. 1983 May 28;1(8335):1175–1179. [PubMed]
  • Sowers JR, Epstein M, Frohlich ED. Diabetes, hypertension, and cardiovascular disease: an update. Hypertension. 2001 Apr;37(4):1053–1059. [PubMed]
  • Chobanian Aram V, Bakris George L, Black Henry R, Cushman William C, Green Lee A, Izzo Joseph L, Jr, Jones Daniel W, Materson Barry J, Oparil Suzanne, Wright Jackson T, Jr, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003 May 21;289(19):2560–2572. [PubMed]
  • Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, Ritz E, Atkins RC, Rohde R, Raz I, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001 Sep 20;345(12):851–860. [PubMed]
  • Viberti Giancarlo, Wheeldon Nigel M. Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus: a blood pressure-independent effect. Circulation. 2002 Aug 6;106(6):672–678. [PubMed]
  • Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001 Sep 20;345(12):861–869. [PubMed]
  • Goldstein S. Beta-blockers in hypertensive and coronary heart disease. Arch Intern Med. 1996 Jun 24;156(12):1267–1276. [PubMed]
  • Sawicki PT, Siebenhofer A. Betablocker treatment in diabetes mellitus. J Intern Med. 2001 Jul;250(1):11–17. [PubMed]
  • Bakris GL, Mangrum A, Copley JB, Vicknair N, Sadler R. Effect of calcium channel or beta-blockade on the progression of diabetic nephropathy in African Americans. Hypertension. 1997 Mar;29(3):744–750. [PubMed]
  • Bakris GL. Effects of diltiazem or lisinopril on massive proteinuria associated with diabetes mellitus. Ann Intern Med. 1990 May 1;112(9):707–708. [PubMed]
  • Bakris GL, Copley JB, Vicknair N, Sadler R, Leurgans S. Calcium channel blockers versus other antihypertensive therapies on progression of NIDDM associated nephropathy. Kidney Int. 1996 Nov;50(5):1641–1650. [PubMed]
  • Velussi M, Brocco E, Frigato F, Zolli M, Muollo B, Maioli M, Carraro A, Tonolo G, Fresu P, Cernigoi AM, et al. Effects of cilazapril and amlodipine on kidney function in hypertensive NIDDM patients. Diabetes. 1996 Feb;45(2):216–222. [PubMed]
  • Salako BL, Finomo FO, Kadiri S, Arije A, Olatosin AO. Comparative effect of lisinopril and lacidipine on urinary albumin excretion in patients with type 11 diabetic nephropathy. Afr J Med Med Sci. 2002 Mar;31(1):53–57. [PubMed]
  • Rossing P, Tarnow L, Boelskifte S, Jensen BR, Nielsen FS, Parving HH. Differences between nisoldipine and lisinopril on glomerular filtration rates and albuminuria in hypertensive IDDM patients with diabetic nephropathy during the first year of treatment. Diabetes. 1997 Mar;46(3):481–487. [PubMed]
  • Curb JD, Pressel SL, Cutler JA, Savage PJ, Applegate WB, Black H, Camel G, Davis BR, Frost PH, Gonzalez N, et al. Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension. Systolic Hypertension in the Elderly Program Cooperative Research Group. JAMA. 1996 Dec 18;276(23):1886–1892. [PubMed]
  • Mogensen CE, Neldam S, Tikkanen I, Oren S, Viskoper R, Watts RW, Cooper ME. Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study. BMJ. 2000 Dec 9;321(7274):1440–1444. [PMC free article] [PubMed]
  • Jacobsen Peter, Andersen Steen, Jensen Berit R, Parving Hans-Henrik. Additive effect of ACE inhibition and angiotensin II receptor blockade in type I diabetic patients with diabetic nephropathy. J Am Soc Nephrol. 2003 Apr;14(4):992–999. [PubMed]
  • Rossing Kasper, Christensen Per K, Jensen Berit R, Parving Hans-Henrik. Dual blockade of the renin-angiotensin system in diabetic nephropathy: a randomized double-blind crossover study. Diabetes Care. 2002 Jan;25(1):95–100. [PubMed]
  • Rosner Mitchell H, Okusa Mark D. Combination therapy with angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists in the treatment of patients with type 2 diabetes mellitus. Arch Intern Med. 2003 May 12;163(9):1025–1029. [PubMed]
  • Ritz E, Ogata H, Orth SR. Smoking: a factor promoting onset and progression of diabetic nephropathy. Diabetes Metab. 2000 Jul;26 (Suppl 4):54–63. [PubMed]
  • Levey AS, Adler S, Caggiula AW, England BK, Greene T, Hunsicker LG, Kusek JW, Rogers NL, Teschan PE. Effects of dietary protein restriction on the progression of advanced renal disease in the Modification of Diet in Renal Disease Study. Am J Kidney Dis. 1996 May;27(5):652–663. [PubMed]
  • Klahr S. Is there still a role for a diet very low in protein, with or without supplements, in the management of patients with end-stage renal failure? Curr Opin Nephrol Hypertens. 1996 Jul;5(4):384–387. [PubMed]
  • Zeller K, Whittaker E, Sullivan L, Raskin P, Jacobson HR. Effect of restricting dietary protein on the progression of renal failure in patients with insulin-dependent diabetes mellitus. N Engl J Med. 1991 Jan 10;324(2):78–84. [PubMed]
  • Lam KS, Cheng IK, Janus ED, Pang RW. Cholesterol-lowering therapy may retard the progression of diabetic nephropathy. Diabetologia. 1995 May;38(5):604–609. [PubMed]
  • Fried LF, Orchard TJ, Kasiske BL. Effect of lipid reduction on the progression of renal disease: a meta-analysis. Kidney Int. 2001 Jan;59(1):260–269. [PubMed]
  • Zoja Carla, Corna Daniela, Camozzi Davide, Cattaneo Dario, Rottoli Daniela, Batani Cristian, Zanchi Cristina, Abbate Mauro, Remuzzi Giuseppe. How to fully protect the kidney in a severe model of progressive nephropathy: a multidrug approach. J Am Soc Nephrol. 2002 Dec;13(12):2898–2908. [PubMed]
  • 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 Aug;42(2):285–291. [PubMed]
  • Gambaro Giovanni, Kinalska Ida, Oksa Adrian, Pont'uch Peter, Hertlová Miluse, Olsovsky Jindrich, Manitius Jacek, Fedele Domenico, Czekalski Stanislaw, Perusicová Jindriska, et al. 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 Jun;13(6):1615–1625. [PubMed]
  • Gokal R, Mallick NP. Peritoneal dialysis. Lancet. 1999 Mar 6;353(9155):823–828. [PubMed]
  • Gudex CM. Health-related quality of life in endstage renal failure. Qual Life Res. 1995 Aug;4(4):359–366. [PubMed]
  • Mallick NP, Gokal R. Haemodialysis. Lancet. 1999 Feb 27;353(9154):737–742. [PubMed]
  • Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Agodoa LY, Held PJ, Port FK. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med. 1999 Dec 2;341(23):1725–1730. [PubMed]
  • Humar A, Johnson EM, Gillingham KJ, Sutherland DE, Payne WD, Dunn DL, Wrenshall LE, Najarian JS, Gruessner RW, Matas AJ. Venous thromboembolic complications after kidney and kidney-pancreas transplantation: a multivariate analysis. Transplantation. 1998 Jan 27;65(2):229–234. [PubMed]
  • Tuomilehto J, Lindström J, Eriksson JG, Valle TT, Hämäläinen H, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001 May 3;344(18):1343–1350. [PubMed]
  • Pan XR, Li GW, Hu YH, Wang JX, Yang WY, An ZX, Hu ZX, Lin J, Xiao JZ, Cao HB, et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care. 1997 Apr;20(4):537–544. [PubMed]
  • Knowler William C, Barrett-Connor Elizabeth, Fowler Sarah E, Hamman Richard F, Lachin John M, Walker Elizabeth A, Nathan David M. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002 Feb 7;346(6):393–403. [PMC free article] [PubMed]
  • Stewart Kerry J. Exercise training and the cardiovascular consequences of type 2 diabetes and hypertension: plausible mechanisms for improving cardiovascular health. JAMA. 2002 Oct 2;288(13):1622–1631. [PubMed]

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