Diabetic nephropathy

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Diabetic nephropathy is one of the main determinants of morbidity and mortality in diabetes mellitus. Indeed end-stage renal disease (ESRD) in Europe and the USA is mainly caused by type 2 diabetes mellitus. This epidemiology is changing world wide as historically ESRD was relatively uncommon while most patients died of cardiovascular events or other, mostly infectious, complications. The main interventions to minimize diabetic nephropathy are control of the diabetes (glycemic control controversy noted as best control for microvascular complications is not the same as best control to optimise mortality), treat associated hypertension[1] and manipulation of the renin-angiotensin system to slow down the progression of renal disease and therefore provide a renal-protective effect[2]. This is with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. There is evidence in type 1 diabetes mellitus that tight glucose control reduces its incidence and progression.

Contents

Albuminuria

Albuminuria has been known since the 19th century to be associated with diabetes mellitus. More recently it has been shown that it may not only be the consequence of diabetes but may also predict future diabetes[3][4]. Albuminuria is strongly associated with the risks of cardiovascular events[5],loss of renal function and mortality[6]. In early type 2 diabetes albuminuria is related to both HbA1c and systolic blood pressure[3]

Associations

Presentations

  • Kimmestiel-Wilson's disease (classic diabetic nephropathy)
  • Ischaemic nephropathy
    • Shrunken kidneys
    • Little or no proteinuria
  • Primary nephropathy with diabetes as aggravating factor

Prognosis

Defined by UKPDS[10] annual rates of progression

  • From normo-to-microalbuminuria - 2%
  • From micro-to-macroalbuminuria - 3%
  • From macroalbuminuria to elevation of serum creatinine - 2%.
  • Diabetic annual death rate was:
    • Normoalbuminuria - 0.7%
    • Microalbuminuria (<30 mg/day) - 2.0%
    • Macroalbuminuria - 3.5%
    • Eevated serum creatinine - 12.1%

References

  1. de Galan BE, Perkovic V, Ninomiya T, Pillai A, Patel A, Cass A, Neal B, Poulter N, Harrap S, Mogensen CE, Cooper M, Marre M, Williams B, Hamet P, Mancia G, Woodward M, Glasziou P, Grobbee DE, MacMahon S, Chalmers J. Lowering blood pressure reduces renal events in type 2 diabetes. Journal of the American Society of Nephrology : JASN. 2009 Apr; 20(4):883-92.(Link to article – subscription may be required.)
  2. Mehdi UF, Adams-Huet B, Raskin P, Vega GL, Toto RD. Addition of angiotensin receptor blockade or mineralocorticoid antagonism to maximal angiotensin-converting enzyme inhibition in diabetic nephropathy. Journal of the American Society of Nephrology : JASN. 2009 Dec; 20(12):2641-50.(Link to article – subscription may be required.)
  3. a b Tapp RJ, Shaw JE, Zimmet PZ, Balkau B, Chadban SJ, Tonkin AM, Welborn TA, Atkins RC. Albuminuria is evident in the early stages of diabetes onset: results from the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab). American journal of kidney diseases : the official journal of the National Kidney Foundation. 2004 Nov; 44(5):792-8.
  4. Halimi JM, Bonnet F, Lange C, Balkau B, Tichet J, Marre M. Urinary albumin excretion is a risk factor for diabetes mellitus in men, independently of initial metabolic profile and development of insulin resistance. The DESIR Study. Journal of hypertension. 2008 Nov; 26(11):2198-206.(Link to article – subscription may be required.)
  5. Solomon SD, Lin J, Solomon CG, Jablonski KA, Rice MM, Steffes M, Domanski M, Hsia J, Gersh BJ, Arnold JM, Rouleau J, Braunwald E, Pfeffer MA. Influence of albuminuria on cardiovascular risk in patients with stable coronary artery disease. Circulation. 2007 Dec 4; 116(23):2687-93.(Link to article – subscription may be required.)
  6. Ninomiya T, Perkovic V, de Galan BE, Zoungas S, Pillai A, Jardine M, Patel A, Cass A, Neal B, Poulter N, Mogensen CE, Cooper M, Marre M, Williams B, Hamet P, Mancia G, Woodward M, Macmahon S, Chalmers J. Albuminuria and kidney function independently predict cardiovascular and renal outcomes in diabetes. Journal of the American Society of Nephrology : JASN. 2009 Aug; 20(8):1813-21.(Link to article – subscription may be required.)
  7. Ritz E, Zeng X. Diabetic nephropathy - Epidemiology in Asia and the current state of treatment. Indian journal of nephrology. 2011 Apr; 21(2):75-84.(Link to article – subscription may be required.)
  8. Vieira SM, Monteiro MB, Marques T, Luna AM, Fortes MA, Nery M, Queiroz M, Dib SA, Vendramini MF, Azevedo MJ, Canani LH, Parisi MC, Pavin EJ, Giannella-Neto D, Corrêa-Giannella ML. Association of genetic variants in the promoter region of genes encoding p22phox (CYBA) and glutamate cysteine ligase catalytic subunit (GCLC) and renal disease in patients with type 1 diabetes mellitus. BMC medical genetics. 2011; 12:129.(Epub) (Link to article – subscription may be required.)
  9. Wessman M, Forsblom C, Kaunisto MA, Söderlund J, Ilonen J, Sallinen R, Hiekkalinna T, Parkkonen M, Maxwell AP, Tarnow L, Parving HH, Hadjadj S, Marre M, Peltonen L, Groop PH. Novel susceptibility locus at 22q11 for diabetic nephropathy in type 1 diabetes. PloS one. 2011; 6(9):e24053.(Link to article – subscription may be required.)
  10. Adler AI, Stevens RJ, Manley SE, Bilous RW, Cull CA, Holman RR. Development and progression of nephropathy in type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney international. 2003 Jan; 63(1):225-32.(Link to article – subscription may be required.)

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