* Unfortunately, the worldwide burden of diabetic nephropathy seems to be on the rise, with an incidence rising by 150% per one decade in USA, Europe, and Japan and a prevalence increasing from 6.4% in 2010 and estimated to reach 7.7% in 2030.<ref name="pmid19896746">{{cite journal| author=Shaw JE, Sicree RA, Zimmet PZ| title=Global estimates of the prevalence of diabetes for 2010 and 2030. | journal=Diabetes Res Clin Pract | year= 2010 | volume= 87 | issue= 1 | pages= 4-14 | pmid=19896746 | doi=10.1016/j.diabres.2009.10.007 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19896746 }} </ref><ref name="pmid7810523">{{cite journal| author=Mallick NP, Jones E, Selwood N| title=The European (European Dialysis and Transplantation Association-European Renal Association) Registry. | journal=Am J Kidney Dis | year= 1995 | volume= 25 | issue= 1 | pages= 176-87 | pmid=7810523 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7810523 }} </ref>
* Costs due to diabetic nephropathy reach as high as 30-40 billion USD annually in the USA only.<ref name="pmid22177944">{{cite journal| author=Collins AJ, Foley RN, Chavers B, Gilbertson D, Herzog C, Johansen K et al.| title='United States Renal Data System 2011 Annual Data Report: Atlas of chronic kidney disease & end-stage renal disease in the United States. | journal=Am J Kidney Dis | year= 2012 | volume= 59 | issue= 1 Suppl 1 | pages= A7, e1-420 | pmid=22177944 | doi=10.1053/j.ajkd.2011.11.015 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22177944 }} </ref><ref name="pmid11920337">{{cite journal| author=Trivedi HS, Pang MM, Campbell A, Saab P| title=Slowing the progression of chronic renal failure: economic benefits and patients' perspectives. | journal=Am J Kidney Dis | year= 2002 | volume= 39 | issue= 4 | pages= 721-9 | pmid=11920337 | doi=10.1053/ajkd.2002.31990 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11920337 }} </ref>
* The burden of diabetic nephropathy from type II diabetes is far more significant than that of type I diabetes.<ref name="pmid11742409">{{cite journal| author=Zimmet P, Alberti KG, Shaw J| title=Global and societal implications of the diabetes epidemic. | journal=Nature | year= 2001 | volume= 414 | issue= 6865 | pages= 782-7 | pmid=11742409 | doi=10.1038/414782a | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11742409 }} </ref>
* Advanced age in type 2 diabetes and early diagnosis in type 1 diabetes are associated with higher risk of DN.<ref name="pmid9080995">{{cite journal| author=Gall MA, Hougaard P, Borch-Johnsen K, Parving HH| title=Risk factors for development of incipient and overt diabetic nephropathy in patients with non-insulin dependent diabetes mellitus: prospective, observational study. | journal=BMJ | year= 1997 | volume= 314 | issue= 7083 | pages= 783-8 | pmid=9080995 | doi= | pmc=PMC2126209 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9080995 }} </ref><ref name="pmid10332675">{{cite journal| author=Klein R, Klein BE, Moss SE, Cruickshanks KJ, Brazy PC| title=The 10-year incidence of renal insufficiency in people with type 1 diabetes. | journal=Diabetes Care | year= 1999 | volume= 22 | issue= 5 | pages= 743-51 | pmid=10332675 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10332675 }} </ref>
* Gender does not seem to play a role in the risk of DN. Blacks, Hispanics, and Native Americans are at increased incidence and severity of diabetic nephropathy and are more likely to suffer ESRD, even when adjusting for other associated risk factors, such as hypertension and socioeconomic status.
* DN seems to have a familial predisposition. Diabetic siblings of patients with DN have an increased risk of DN up to 3-times as those of patients without DN.<ref name="pmid15586648">{{cite journal| author=Ayodele OE, Alebiosu CO, Salako BL| title=Diabetic nephropathy--a review of the natural history, burden, risk factors and treatment. | journal=J Natl Med Assoc | year= 2004 | volume= 96 | issue= 11 | pages= 1445-54 | pmid=15586648 | doi= | pmc=PMC2568593 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15586648 }} </ref>
* In one study evaluating familial predisposition of DN in Pima Indian families, the likelihood of developing proteinuria in patients with type 2 diabetes increased significantly when one or both parents have proteinuria.<ref name="pmid2401399">{{cite journal| author=Pettitt DJ, Saad MF, Bennett PH, Nelson RG, Knowler WC| title=Familial predisposition to renal disease in two generations of Pima Indians with type 2 (non-insulin-dependent) diabetes mellitus. | journal=Diabetologia | year= 1990 | volume= 33 | issue= 7 | pages= 438-43 | pmid=2401399 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2401399 }} </ref> Several genes have shown to have an important role in the development of DN:
*DD (homozygous deletion genotype) of the angiotensin converting enzyme (ACE) genotype<ref name="pmid9264004">{{cite journal| author=Jeffers BW, Estacio RO, Raynolds MV, Schrier RW| title=Angiotensin-converting enzyme gene polymorphism in non-insulin dependent diabetes mellitus and its relationship with diabetic nephropathy. | journal=Kidney Int | year= 1997 | volume= 52 | issue= 2 | pages= 473-7 | pmid=9264004 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9264004 }} </ref><ref name="pmid10023638">{{cite journal| author=Kuramoto N, Iizuka T, Ito H, Yagui K, Omura M, Nozaki O et al.| title=Effect of ACE gene on diabetic nephropathy in NIDDM patients with insulin resistance. | journal=Am J Kidney Dis | year= 1999 | volume= 33 | issue= 2 | pages= 276-81 | pmid=10023638 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10023638 }} </ref><ref name="pmid9727374">{{cite journal| author=Kunz R, Bork JP, Fritsche L, Ringel J, Sharma AM| title=Association between the angiotensin-converting enzyme-insertion/deletion polymorphism and diabetic nephropathy: a methodologic appraisal and systematic review. | journal=J Am Soc Nephrol | year= 1998 | volume= 9 | issue= 9 | pages= 1653-63 | pmid=9727374 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9727374 }} </ref>
*Homozygous Z-2 allelle of aldose reductase gene<ref name="pmid9709964">{{cite journal| author=Shah VO, Scavini M, Nikolic J, Sun Y, Vai S, Griffith JK et al.| title=Z-2 microsatellite allele is linked to increased expression of the aldose reductase gene in diabetic nephropathy. | journal=J Clin Endocrinol Metab | year= 1998 | volume= 83 | issue= 8 | pages= 2886-91 | pmid=9709964 | doi=10.1210/jcem.83.8.5028 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9709964 }} </ref>
*Beta subunit of G protein at position 825 allele<ref name="pmid10200987">{{cite journal| author=Blüthner M, Schmidt S, Siffert W, Knigge H, Nawroth P, Ritz E| title=Increased frequency of G-protein beta 3-subunit 825 T allele in dialyzed patients with type 2 diabetes. | journal=Kidney Int | year= 1999 | volume= 55 | issue= 4 | pages= 1247-50 | pmid=10200987 | doi=10.1046/j.1523-1755.1999.00399.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10200987 }} </ref>
The incidence and prevalence of diabetes mellitus have grown significantly throughout the world, due primarily to the increase in the incidence of type 2 diabetes.
In the United States, prevalence of Diabetes Nephropathy had increased from 7.4% to 9.6% within a 10 years period (1988 to 2008), and this trend will likely continue due to the increasing incidence of diabetes in the American populace [1]. Studies by de Boer et al showed that DN accounts for 44% of new ESRD cases with 6% attributed to type 1 DM, 38% attributed to type 2 DM, and a projected increase of 3 million cases over the course of 20 years[1]. This increased incidence and prevalence of DN is notably greater among African Americans, Asians, and Native Americans than it is among Caucasians.
Diabetic nephropathy (DN) is the most common cause of end-stage-renal-disease (ESRD) and most common cause for dialysis in the Western world, accounting for approximately 30-45% of all cases of ESRD.
Epidemiology and Demographics
Prevalence
Diabetic nephropathy is the most common etiology of nephropathy and dialysis in the Western world.[2]
Unfortunately, the worldwide burden of diabetic nephropathy seems to be on the rise, with an incidence rising by 150% per one decade in USA, Europe, and Japan and a prevalence increasing from 6.4% in 2010 and estimated to reach 7.7% in 2030.[3][4]
Costs due to diabetic nephropathy reach as high as 30-40 billion USD annually in the USA only.[5][6]
The burden of diabetic nephropathy from type II diabetes is far more significant than that of type I diabetes.[7]
Advanced age in type 2 diabetes and early diagnosis in type 1 diabetes are associated with higher risk of DN.[8][9]
Gender does not seem to play a role in the risk of DN. Blacks, Hispanics, and Native Americans are at increased incidence and severity of diabetic nephropathy and are more likely to suffer ESRD, even when adjusting for other associated risk factors, such as hypertension and socioeconomic status.
DN seems to have a familial predisposition. Diabetic siblings of patients with DN have an increased risk of DN up to 3-times as those of patients without DN.[10]
In one study evaluating familial predisposition of DN in Pima Indian families, the likelihood of developing proteinuria in patients with type 2 diabetes increased significantly when one or both parents have proteinuria.[11] Several genes have shown to have an important role in the development of DN:
DD (homozygous deletion genotype) of the angiotensin converting enzyme (ACE) genotype[12][13][14]
Homozygous Z-2 allelle of aldose reductase gene[15]
Beta subunit of G protein at position 825 allele[16]