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Diabetes and Kidney Disease pp 107–117Cite as

Albuminuria–Proteinuria in Diabetes Mellitus

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Abstract

The presence of albuminuria–proteinuria in diabetic patients is an indication of early renal disease and signifies systemic endothelial dysfunction. Even a small amount of albuminuria (<30 mg/day) carries a risk for cardiovascular disease (CVD). Abnormalities in podocyte-specific proteins seem to be the underlying mechanisms for albuminuria–proteinuria. Whenever a diabetic patient presents with heavy albuminuria–proteinuria, the nephrologist should consider the coexistence of nondiabetic primary glomerular diseases. Renal biopsy in such a patient is clearly warranted.

The screening for albuminuria should begin from puberty and 5 years after the diagnosis of diabetes in type 1 patients. Albumin:creatinine ratio in a morning voided specimen is usually the standard way of expressing the excretion of albuminuria in the outpatient setting. Reagents strips for documenting the minute quantities of albuminuria are available in the office setting and diabetes clinics. Screening for albuminuria should begin during the first visit in type 2 diabetic patients.

Angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor-blockers (ARBs) are the drugs of choice for the treatment of albuminuria–proteinuria. Prevention of albuminuria delays the progression of kidney disease as well as CVD. Combination of an ACE-I and an ARB is not recommended; however, a combination of either one of these drugs and an aldosterone antagonist seems to have an added benefit in the prevention of renal and CV diseases. Many new drugs targeting podocytes are being evaluated in animals and humans to prevent albuminuria–proteinuria in diabetic and nondiabetic patients. It is hoped that their introduction into the clinical practice is expected to decrease the morbidity and mortality in patients with albuminuria–proteinuria.

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References

  1. Vassalotti JA, Stevens LA, Levey AS. Testing for chronic kidney disease: a position statement from the National Kidney Foundation. Am J Kidney Dis. 2007;50:169–80.

    Article  CAS  PubMed  Google Scholar 

  2. Stoycheff N, Stevens LA, Schmid CH, et al. Nephrotic syndrome in diabetic kidney disease: an evaluation and update of the definition. Am J Kidney Dis. 2009;54:840–9.

    Article  CAS  PubMed  Google Scholar 

  3. Ruggenenti P, Gambara V, Perna A, et al. The nephropathy of non-insulin-dependent diabetes: predictors of outcome relative to diverse patterns of renal injury. J Am Soc Nephrol. 1998;9:2336–43.

    CAS  PubMed  Google Scholar 

  4. Pham TT, Sim JJ, Kujubu DA, et al. Prevalence of nondiabetic renal disease in diabetic patients. Am J Nephrol. 2007;27:322–8.

    Article  PubMed  Google Scholar 

  5. KDOQI. KDOQI clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease. Am J Kidney Dis. 2007;49(2 Suppl 2):S12–54.

    Google Scholar 

  6. Mogensen CE, Christensen CK, Vittinghus E. The stages in diabetic renal disease. With emphasis on the stage of incipient diabetic nephropathy. Diabetes. 1983;32 Suppl 2:64–78.

    Article  PubMed  Google Scholar 

  7. Reddi AS. Diabetic nephropathy: theory & practice. East Hanover: College Book Publishers; 2004. Chapter 2, Natural history and clinical course of diabetic nephropathy. p. 5–26.

    Google Scholar 

  8. Reutens AT. Epidemiology of diabetic kidney disease. Med Clin North Am. 2013;97:1–18.

    Article  PubMed  Google Scholar 

  9. Dwyer JP, Lewis JB. Nonproteinuric diabetic nephropathy. Med Clin North Am. 2013;97:53–8.

    Article  PubMed  Google Scholar 

  10. Forman JP, Brenner BM. ‘Hypertension’ and ‘microalbuminuria’: the bell tolls for thee. Kidney Int. 2006;69:22–9.

    Article  CAS  PubMed  Google Scholar 

  11. Ruggenenti P, Remuzzi G. Time to abandon microalbuminuria. Kidney Int. 2006;70:1214–22.

    Article  CAS  PubMed  Google Scholar 

  12. Miller WG, Bruns DE, Hortin GL, Sandberg S, Aakre KM, McQueen MJ, et al. Current issues in measurement and reporting of urinary albumin excretion. Clin Chem. 2009;55:24–38.

    Article  CAS  PubMed  Google Scholar 

  13. Danziger J. Importance of low-grade albuminuria. Mayo Clin Proc. 2008;83:806–12.

    Article  PubMed  Google Scholar 

  14. Matshushita K, van de Velde M, Astor BC, et al. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet. 2010;375:2073–81.

    Article  Google Scholar 

  15. Viberti GC, Jarrett RJ, Mahmud U, et al. Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus. Lancet. 1982;I:1430–32.

    Article  Google Scholar 

  16. Parving H-H, Oxenboll B, Svendson PA, et al. Early detection of patients at risk of developing diabetic nephropathy. A longitudinal study of urinary albumin excretion. Acta Endocrinol. 1982;100:550–5.

    CAS  PubMed  Google Scholar 

  17. Mogensen CE, Christensen CK. Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med. 1984;311:89–93.

    Article  CAS  PubMed  Google Scholar 

  18. Mathiesen ER, Oxenboll B, Johansen K, et al. Incipient nephropathy in type 1 (insulin-dependent) diabetes. Diabetologia. 1984;26:406–10.

    Article  CAS  PubMed  Google Scholar 

  19. Almdal T, Norgaard K, Feldt-Rasmussen B, et al. The predictive value of microalbuminuria in IDDM. A five-year follow-up study. Diabetes Care. 1994;1(7):120–5.

    Article  Google Scholar 

  20. Parving H-H, Chaturvedi N, Viberti GC, et al. Does microalbuminuria predict diabetic nephropathy? Diabetes Care. 2002;25:406–7.

    Article  PubMed  Google Scholar 

  21. Mogensen CE. Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med. 1984;310:356–60.

    Article  CAS  PubMed  Google Scholar 

  22. Nelson RG, Bennett PH, Beck GJ, et al. Development and progression of renal disease in Pima Indians with non-insulin-dependent diabetes mellitus. N Engl J Med. 1996;335:1636–42.

    Article  CAS  PubMed  Google Scholar 

  23. Ravid M, Lang R, Rachmani R, et al. Long-term renoprotective effect of angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus. Arch Intern Med. 1996;156:286–9.

    Article  CAS  PubMed  Google Scholar 

  24. Ahmad J, Siddiqui MA, Ahmad H. Effect of postponement of diabetic nephropathy with enalapril in normotensive type 2 diabetic patients with microalbuminuria. Diabetes Care. 1997;20:1576–81.

    Article  CAS  PubMed  Google Scholar 

  25. Gæde P, Vedel P, Parving H-H, et al. Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno type 2 randomised study. Lancet. 1999;353:617–22.

    Article  PubMed  Google Scholar 

  26. Estacio RO, Jeffers BW, Gifford N, et al. Effect of blood pressure control on diabetic microvascular complications in patients with hypertension and type 2 diabetes. Diabetes Care. 2000;23:B54–64.

    PubMed  Google Scholar 

  27. 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.

    Article  Google Scholar 

  28. Parving H-H, Lehnert H, Bröchner-Mortensen J, et al. 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  CAS  PubMed  Google Scholar 

  29. Parving H-H. Diabetic nephropathy: prevention and treatment. Kidney Int. 2001;60:2041–55.

    Article  CAS  PubMed  Google Scholar 

  30. Berhane AM, Weil EJ, Knowler WC, et al. Albuminuria and estimated glomerular filtration rate as predictors of diabetic end-stage renal disease and death. Clin J Am Soc Nephrol. 2011;6:2444–51.

    Article  PubMed Central  PubMed  Google Scholar 

  31. Gansevoort RT, Matsushita K, van der Velde M, et al. Chronic kidney disease prognosis consortium: lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes. A collaborative meta-analysis of general and high-risk population cohorts. Kidney Int. 2011;80:93–104.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Mundel P, Shankland SJ. Podocyte biology and response to injury. J Am Soc Nephrol. 2002;13:3005–13.

    Article  PubMed  Google Scholar 

  33. Pavenstädt H, Kriz W, Kretzler M. Cell biology of the glomerular podocyte. Phys Rev. 2003;83:253–307.

    Google Scholar 

  34. Tryggvason K, Patrakka J, Wartiovaara J. Hereditary proteinuria syndromes and mechanisms. N Engl J Med. 2006;354:1387–401.

    Article  CAS  PubMed  Google Scholar 

  35. Asanuma K, Yanagida-Asanuma E, Takagi M, et al. The role of podocytes in proteinuria. Nephrology. 2007;12:S15–20.

    Article  CAS  PubMed  Google Scholar 

  36. Mundel P, Reiser J. Proteinuria: an enzymatic disease of the podocyte? Kidney Int. 2010;77:571–80.

    Article  CAS  PubMed  Google Scholar 

  37. Garg P, Rabelink T. Glomerular proteinuria: a complex interplay between unique players. Adv Chronic Kidney Dis. 2011;18:233–42.

    Article  PubMed Central  PubMed  Google Scholar 

  38. Reiser J, Sever S. Podocyte biology and pathogenesis of kidney disease. Annu Rev Med. 2013;64:357–66.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Li JJ, Kwak SJ, Jung DS, et al. Podocyte biology in diabetic nephropathy. Kidney Int. 2007;72:S36–42.

    Article  Google Scholar 

  40. Jefferson JA, Shankland SJ, Pichler RH. Proteinuria in diabetic kidney disease: a mechanistic viewpoint. Kidney Int. 2008;74:22–36.

    Article  CAS  PubMed  Google Scholar 

  41. Ziyadeh FN, Wolf G. Pathogenesis of the podocytopathy and proteinuria in diabetic glomerulopathy. Curr Diabetes Rev. 2008;4:39–45.

    Article  CAS  PubMed  Google Scholar 

  42. Weil EJ, Lemley K, Mason CC, et al. Podocyte detachment and reduced glomerular capillary endothelial fenestration promote kidney disease in type 2 diabetic nephropathy. Kidney Int. 2012;82:1010–7.

    Article  PubMed Central  PubMed  Google Scholar 

  43. Edelstein MH, Weinstein T, Grafter U. TGFβ1-dependent podocyte dysfunction. Curr Opin Nephrol Hypertens. 2013;22:93–9.

    Article  Google Scholar 

  44. Baelde HJ, Eikmans M, Lappin DWP, et al. Reduction of VEGF-A and CTGF expression in diabetic nephropathy is associated with podocyte loss. Kidney Int. 2007;71:637–45.

    Article  CAS  PubMed  Google Scholar 

  45. Reddi AS. Diabetic nephropathy: theory & practice. East Hanover: College Book Publishers; 2004. Chapter 4, Microalbuminuria in type 1 diabetes. p. 55–88.

    Google Scholar 

  46. Weir MR. Microalbuminuria and cardiovascular disease. Clin J Am Soc Nephrol. 2007;2:581–90.

    Article  PubMed  Google Scholar 

  47. Borch-Johnsen K, Kreiner S. Proteinuria: value as predictor of cardiovascular mortality in insulin-dependent diabetes mellitus. Br Med J. 1987;294:1651–4.

    Article  CAS  Google Scholar 

  48. Tarffvit O, Agardh C-D. The predictive value of albuminuria for cardiovascular and renal disease. A 5-year follow-up study of 476 patients with type 1 diabetes mellitus. J Diabetes Complications. 1993;7:49–56.

    Article  Google Scholar 

  49. Gerstein HC, Mann JFE, Yi Q, et al. Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA. 2001;286:421–6.

    Article  CAS  PubMed  Google Scholar 

  50. Dinneeen SF, Gerstein HC. The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus. A systematic overview of the literature. Arch Intern Med. 1997;157:1413–8.

    Article  Google Scholar 

  51. Wiseman M, Viberti G, Mackintosh D, et al. Glycaemia, arterial pressure and micro-albuminuria in type 1 (insulin-dependent) diabetes mellitus. Diabetologia. 1984;26:401–5.

    Article  CAS  PubMed  Google Scholar 

  52. Turgut F, Bolton WK. Potential new therapeutic agents for diabetic kidney disease. Am J Kidney Dis. 2010;55:928–40.

    Article  CAS  PubMed  Google Scholar 

  53. Mathew A, Cunard R, Sharma K. Antifibrotic treatment and other new strategies for improving renal outcomes. Contrib Nephrol. 2011;170:217–27.

    Article  CAS  PubMed  Google Scholar 

  54. Ruggennent P, Cravedi P, Remuzzi G. Mechanisms and treatment of CKD. J Am Soc Nephrol. 2012;23:1917–28.

    Article  Google Scholar 

  55. Shepler B, Nash C, Smith C, et al. Update on potential drugs for the treatment of diabetic kidney disease. Clin Ther. 2012;34:1237–46.

    Article  CAS  PubMed  Google Scholar 

  56. Kania DS, Smith CT, Nash CL, et al. Potential new treatments for diabetic kidney disease. Med Clin North Am. 2013;97:115–34.

    Article  PubMed  Google Scholar 

  57. Leeuwis JW, Nguyen TQ, Dendooven A, et al. Targeting podocyte-associated diseases. Adv Drug Deliv Rev. 2010;62:1325–36.

    Article  CAS  PubMed  Google Scholar 

  58. Reiser J, Gupta V, Kistler AD. Toward the development of podocyte-specific drugs. Kidney Int. 2010;77:662–8.

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, 525 East 68th Street, New York, NY, USA

    Surya V. Seshan M.D.

  2. Department of Medicine, Division of Nephrology & Hypertension, Rutgers New Jersey Medical School, 185 South Orange Avenue, Newark, NJ, 07103, USA

    Alluru S. Reddi M.D.

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  1. Surya V. Seshan M.D.
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Correspondence to Alluru S. Reddi M.D. .

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Editors and Affiliations

  1. University of Illinois, Chicago, Illinois, USA

    Edgar V. Lerma

  2. Nephrology Section, Tulane University Medical School, New Orleans, Louisiana, USA

    Vecihi Batuman

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Seshan, S.V., Reddi, A.S. (2014). Albuminuria–Proteinuria in Diabetes Mellitus. In: Lerma, E., Batuman, V. (eds) Diabetes and Kidney Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0793-9_9

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  • DOI: https://doi.org/10.1007/978-1-4939-0793-9_9

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