Seminars in Nephrology
Volume 27, Issue 2 , Pages 172-181 , March 2007

Albuminuria: A Target for Treatment of Type 2 Diabetic Nephropathy

  • Dick de Zeeuw, MD, PhD

      Affiliations

    • Corresponding Author InformationAddress reprint requests to Dick de Zeeuw, MD, PhD, Department of Clinical Pharmacology, University Medical Center Groningen, Ant Deusinglaan 1, 9713 AV Groningen, The Netherlands.

References 

  1. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339:229–234
  2. Keane WF, Brenner BM, de Zeeuw D, Grunfeld JP, Lash J, Lyle PA, et al. RENAAL Study Investigators A risk score for predicting end-stage renal disease in patients with type 2 diabetes and nephropathy: the RENAAL study. Clin J Am Soc Nephrol. 2006;1:761–767
  3. Levey AS, Eckardt KU, Tsukamoto Y, Levin A, Coresh J, Rossert J, et al. Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2005;67:2089–2100
  4. Hillege HL, Fidler V, Diercks GF, van Gilst WH, de Zeeuw D, van Veldhuisen DJ, et al. Prevention of Renal and Vascular End Stage Disease (PREVEND) Study Group Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population. Circulation. 2002;106:1777–1782
  5. Klausen K, Borch-Johnsen K, Feldt-Rasmussen B, Jensen G, Clausen P, Scharling H, et al. Very low levels of microalbuminuria are associated with increased risk of coronary heart disease and death independently of renal function, hypertension, and diabetes. Circulation. 2004;110:32–35
  6. Verhave JC, Gansevoort RT, Hillege HL, Bakker SJ, De Zeeuw D, de Jong PE PREVEND Study Group. An elevated urinary albumin excretion predicts de novo development of renal function impairment in the general population. Kidney Int Suppl. 2004;92:S18–S21
  7. Ruggenenti P, Remuzzi G. Time to abandon microalbuminuria?. Kidney Int. 2006;70:1214–1222
  8. Zandi-Nejad K, Eddy AA, Glassock RJ, Brenner BM. Why is proteinuria an ominous biomarker of progressive kidney disease?. Kidney Int Suppl. 2004;92:S76–S89
  9. Brinkman JW, Bakker SJ, Gansevoort RT, Hillege HL, Kema IP, Gans RO, et al. Which method for quantifying urinary albumin excretion gives what outcome? (A comparison of immunonephelometry with HPLC). Kidney Int Suppl. 2004;92:S69–S75
  10. Polkinghorne KR, Su Q, Chadban SJ, Shaw JE, Zimmet PZ, Atkins RC. Population prevalence of albuminuria in the Australian Diabetes, Obesity, and Lifestyle (AusDiab) study: immunonephelometry compared with high-performance liquid chromatography. Am J Kidney Dis. 2006;47:604–613
  11. Florvall G, Basu S, Helmersson J, Larsson A. Hemocue urine albumin point-of-care test shows strong agreement with the results obtained with a large nephelometer. Diabetes Care. 2006;29:422–423
  12. Mogensen CE. Microalbuminuria as a predictor of clinical diabetic nephropathy. Kidney Int. 1987;31:673–689
  13. Berrut G, Bouhanick B, Fabbri P, Guilloteau G, Bled F, Le Jeune JJ, et al. Microalbuminuria as a predictor of a drop in glomerular filtration rate in subjects with non-insulin-dependent diabetes mellitus and hypertension. Clin Nephrol. 1997;48:92–97
  14. Nosadini R, Tonolo G. Blood glucose and lipid control as risk factors in the progression of renal damage in type 2 diabetes. J Nephrol. 2003;16(Suppl 7):S42–S47
  15. Mogensen CE. Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med. 1984;310:356–360
  16. Nelson RG, Knowler WC, Pettitt DJ, Saad MF, Charles MA, Bennett PH. Assessment of risk of overt nephropathy in diabetic patients from albumin excretion in untimed urine specimens. Arch Intern Med. 1991;151:1761–1765
  17. Ruggenenti P, Fassi A, Ilieva AP, Bruno S, Iliev IP, Brusegan V, et al. Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) Investigators Preventing microalbuminuria in type 2 diabetes. N Engl J Med. 2004;351:1941–1951
  18. Remuzzi G, Bertani T. Is glomerulosclerosis a consequence of altered glomerular permeability to macromolecules?. Kidney Int. 1990;38:384–394
  19. Abbate M, Zoja C, Remuzzi G. How does proteinuria cause progressive renal damage?. J Am Soc Nephrol. 2006;17:2974–2984
  20. Ruggenenti P, Perna A, Mosconi L, Pisoni R, Remuzzi G “Gruppo Italiano di Studi Epidemiologici in Nefrologia” (GISEN). Urinary protein excretion rate is the best independent predictor of ESRF in non-diabetic proteinuric chronic nephropathies. Kidney Int. 1998;53:1209–1216
  21. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, et al. RENAAL Study Investigators Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345:861–869
  22. Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, et al. Collaborative Study Group Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345:851–860
  23. Keane WF, Brenner BM, de Zeeuw D, Grunfeld JP, McGill J, Mitch WE, et al. RENAAL Study Investigators The risk of developing end-stage renal disease in patients with type 2 diabetes and nephropathy: the RENAAL study. Kidney Int. 2003;63:1499–1507
  24. Atkins RC, Briganti EM, Lewis JB, Hunsicker LG, Braden G, Champion de Crespigny PJ, et al. Proteinuria reduction and progression to renal failure in patients with type 2 diabetes mellitus and overt nephropathy. Am J Kidney Dis. 2005;45:281–287
  25. Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000;342:145–153
  26. Mogensen CE. Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med. 1984;310:356–360
  27. Marshall SM. Blood pressure control, microalbuminuria and cardiovascular risk in type 2 diabetes mellitus. Diabet Med. 1999;16:358–372
  28. Yuyun MF, Dinneen SF, Edwards OM, Wood E, Wareham NJ. Absolute level and rate of change of albuminuria over 1 year independently predict mortality and cardiovascular events in patients with diabetic nephropathy. Diabet Med. 2003;20:277–282
  29. Sukhija R, Aronow WS, Kakar P, Garza L, Sachdeva R, Sinha A, et al. Relation of microalbuminuria and coronary artery disease in patients with and without diabetes mellitus. Am J Cardiol. 2006;98:279–281
  30. Mykkanen L, Zaccaro DJ, O’Leary DH, Howard G, Robbins DC, Haffner SM. Microalbuminuria and carotid artery intima-media thickness in nondiabetic and NIDDM subjects (The Insulin Resistance Atherosclerosis Study (IRAS)). Stroke. 1997;28:1710–1716
  31. Keech AC, Grieve SM, Patel A, Griffiths K, Skilton M, Watts GF, et al. Urinary albumin levels in the normal range determine arterial wall thickness in adults with type 2 diabetes: a FIELD substudy. Diabet Med. 2005;22:1558–1565
  32. Dinneen 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;157:1413–1418
  33. Kannel WB, Stampfer MJ, Castelli WP, Verter J. The prognostic significance of proteinuria: the Framingham study. Am Heart J. 1984;108:1347–1352
  34. de Zeeuw D, Remuzzi G, Parving HH, Keane WF, Zhang Z, Shahinfar S, et al. Albuminuria, a therapeutic target for cardiovascular protection in type 2 diabetic patients with nephropathy. Circulation. 2004;110:921–927
  35. Anavekar NS, Gans DJ, Berl T, Rohde RD, Cooper W, Bhaumik A, et al. Predictors of cardiovascular events in patients with type 2 diabetic nephropathy and hypertension: a case for albuminuria. Kidney Int Suppl. 2004;92:S50–S55
  36. Vogt L, Navis G, de Zeeuw D. Renoprotection: a matter of blood pressure reduction or agent-characteristics?. J Am Soc Nephrol. 2002;13(Suppl 3):S202–S207
  37. Rossing P, Hommel E, Smidt UM, Parving HH. Reduction in albuminuria predicts a beneficial effect on diminishing the progression of human diabetic nephropathy during antihypertensive treatment. Diabetologia. 1994;37:511–516
  38. Apperloo AJ, de Zeeuw D, de Jong PE. Short-term antiproteinuric response to antihypertensive treatment predicts long-term GFR decline in patients with non-diabetic renal disease. Kidney Int Suppl. 1994;45:S174–S178
  39. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD The Collaborative Study Group. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med. 1993;329:1456–1462
  40. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet. 1997;349:1857–1863
  41. de Zeeuw D, Remuzzi G, Parving HH, Keane WF, Zhang Z, Shahinfar S, et al. Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: lessons from RENAAL. Kidney Int. 2004;65:2309–2320
  42. Parving HH, Lehnert H, Brochner-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;345:870–878
  43. Andersen S, Brochner-Mortensen J, Parving HH. Irbesartan in Patients With Type 2 Diabetes and Microalbuminuria Study Group (Kidney function during and after withdrawal of long-term irbesartan treatment in patients with type 2 diabetes and microalbuminuria). Diabetes Care. 2003;26:3296–3302
  44. Eijkelkamp WBA, Zhang Z, Remuzzi G, Parving H-H, Cooper ME, Keane WF, et al. Albuminuria is a target for renoprotective therapy independent from blood pressure in patients with type 2 diabetic nephropathy: post-hoc analysis from the RENAAL trial. JASN. In press.
  45. Lindholm LH, Ibsen H, Dahlof B, Devereux RB, Beevers G, de Faire U, et al. LIFE Study Group Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002;359:1004–1010
  46. Ibsen H, Olsen MH, Wachtell K, Borch-Johnsen K, Lindholm LH, Mogensen CE, et al. Reduction in albuminuria translates to reduction in cardiovascular events in hypertensive patients: losartan intervention for endpoint reduction in hypertension study. Hypertension. 2005;45:198–202
  47. Asselbergs FW, Diercks GF, Hillege HL, van Boven AJ, Janssen WM, Voors AA, et al. Prevention of Renal and Vascular Endstage Disease Intervention Trial (PREVEND IT) Investigators Effects of fosinopril and pravastatin on cardiovascular events in subjects with microalbuminuria. Circulation. 2004;110:2809–2816
  48. Buter H, Hemmelder MH, Navis G, de Jong PE, de Zeeuw D. The blunting of the antiproteinuric efficacy of ACE inhibition by high sodium intake can be restored by hydrochlorothiazide. Nephrol Dial Transplant. 1998;13:1682–1685
  49. Schmieder RE, Klingbeil AU, Fleischmann EH, Veelken R, Delles C. Additional antiproteinuric effect of ultrahigh dose candesartan: a double-blind, randomized, prospective study. J Am Soc Nephrol. 2005;16:3038–3045
  50. Rossing K, Schjoedt KJ, Jensen BR, Boomsma F, Parving HH. Enhanced renoprotective effects of ultrahigh doses of irbesartan in patients with type 2 diabetes and microalbuminuria. Kidney Int. 2005;68:1190–1198
  51. Gambaro G, Kinalska I, Oksa A, Pont’uch P, Hertlova M, Olsovsky J, 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;13:1615–1625
  52. Agarwal R, Acharya M, Tian J, Hippensteel RL, Melnick JZ, Qiu P, et al. Antiproteinuric effect of oral paricalcitol in chronic kidney disease. Kidney Int. 2005;68:2823–2828
  53. Palmer AJ, Annemans L, Roze S, Lamotte M, Lapuerta P, Chen R, et al. Cost-effectiveness of early irbesartan treatment versus control (standard antihypertensive medications excluding ACE inhibitors, other angiotensin-2 receptor antagonists, and dihydropyridine calcium channel blockers) or late irbesartan treatment in patients with type 2 diabetes, hypertension, and renal disease. Diabetes Care. 2004;27:1897–1903

PII: S0270-9295(07)00003-4

doi: 10.1016/j.semnephrol.2007.01.002

Seminars in Nephrology
Volume 27, Issue 2 , Pages 172-181 , March 2007

Article Tools

* Image Usage & Resolution