J Korean Med Sci.  2009 Jan;24(Suppl 1):S75-S81. 10.3346/jkms.2009.24.S1.S75.

The Clinical Characteristics of Normoalbuminuric Renal Insufficiency in Korean Type 2 Diabetic Patients: A Possible Early Stage Renal Complication

• An JH
• Cho YM
• Yu HG
• Jang HC
• Park KS
• Kim SY
• Lee HK

• KMID: 1778144
• DOI: http://doi.org/10.3346/jkms.2009.24.S1.S75

Abstract

It has been recently reported that a considerable portion of diabetic patients with renal insufficiency show normoalbuminuria. As little is known about normoalbuminuric renal insufficiency in the Asian population, we examined its prevalence and clinical characteristics in Korean type 2 diabetic patients. We studied 562 patients with type 2 diabetes from Seoul National University Hospital. The estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease formula and the degree of albuminuria was evaluated by spot urine albumin-creatinine ratio. Of 562 patients, 151 (26.9%) patients had renal insufficiency (eGFR <60 mL/min/ 1.73m(2)). Among them, 44 (29.1%) patients had normoalbuminuria. After excluding the patients using renin-angiotensin system (RAS) inhibitors, the prevalence of normoalbuminuric renal insufficiency was 35.3% (18 of 51 patients). Compared with microand macroalbuminuric renal insufficiency, normoalbuminuric renal insufficiency was associated with the female predominance, shorter duration of diabetes, lower prevalence of diabetic retinopathy, and lower prevalence of using antihypertensive drugs except RAS inhibitors. The prevalence decreased progressively with an increase in the duration of diabetes and an increase in the severity of retinopathy. Normoalbuminuric renal insufficiency was prevalent in Korean type 2 diabetic patients. The association with a shorter duration of the diabetes and a lower prevalence of retinopathy suggests that it might be an early stage renal complication.

Keyword

Normoalbuminuria; Renal Insufficiency; Diabetes Mellitus; Type 2

MeSH Terms

Aged
Albuminuria/diagnosis
Body Mass Index
Diabetes Complications/*diagnosis
Diabetes Mellitus, Type 2/ethnology/*pathology
Female
Glomerular Filtration Rate
Humans
Kidney Diseases/complications/*etiology
Korea
Male
Middle Aged
Renal Insufficiency/complications/*etiology
Renin-Angiotensin System
Time Factors

Figure

• 

  Fig. 1 Inverse linear relationship between albumin-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR).

• 

  Fig. 2 The relationship between the degree of urinary albumin excretion and the duration of diabetes in type 2 diabetic patients with renal insufficiency. p for trend <0.001 by Mantel-Haenszel χ2 test.

Reference

1. Collins AJ, Kasiske B, Herzog C, Chavers B, Foley R, Gilbertson D, Grimm R, Liu J, Louis T, Manning W, Matas A, McBean M, Murray A, St Peter W, Xue J, Fan Q, Guo H, Li S, Roberts T, Snyder J, Solid C, Wang C, Weinhandl E, Arko C, Chen SC, Dalleska F, Daniels F, Dunning S, Ebben J, Frazier E, Johnson R, Sheets D, Forrest B, Berrini D, Constantini E, Everson S, Frederick P, Eggers P, Agodoa L. Excerpts from the United States Renal Data System 2004 annual data report: atlas of end-stage renal disease in the United States. Am J Kidney Dis. 2005. 45:1 Suppl 1. A5–A7. S1–S280.

2. Ritz E, Rychlik I, Locatelli F, Halimi S. End-stage renal failure in type 2 diabetes: A medical catastrophe of worldwide dimensions. Am J Kidney Dis. 1999. 34:795–808.

3. Retnakaran R, Cull CA, Thorne KI, Adler AI, Holman RR. Risk factors for renal dysfunction in type 2 diabetes: U.K. Prospective Diabetes Study 74. Diabetes. 2006. 55:1832–1839.

4. Mogensen CE. Microalbuminuria, blood pressure and diabetic renal disease: origin and development of ideas. Diabetologia. 1999. 42:263–285.

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

6. Parving HH, Oxenboll B, Svendsen PA, Christiansen JS, Andersen AR. Early detection of patients at risk of developing diabetic nephropathy. A longitudinal study of urinary albumin excretion. Acta Endocrinol (Copenh). 1982. 100:550–555.

7. Hovind P, Tarnow L, Rossing P, Jensen BR, Graae M, Torp I, Binder C, Parving HH. Predictors for the development of microalbuminuria and macroalbuminuria in patients with type 1 diabetes: inception cohort study. BMJ. 2004. 328:1105.

8. Forsblom CM, Groop PH, Ekstrand A, Groop LC. Predictive value of microalbuminuria in patients with insulin-dependent diabetes of long duration. BMJ. 1992. 305:1051–1053.

9. Rossing P, Hougaard P, Parving HH. Progression of microalbuminuria in type 1 diabetes: ten-year prospective observational study. Kidney Int. 2005. 68:1446–1450.

10. Giorgino F, Laviola L, Cavallo Perin P, Solnica B, Fuller J, Chaturvedi N. Factors associated with progression to macroalbuminuria in microalbuminuric Type 1 diabetic patients: the EURODIAB Prospective Complications Study. Diabetologia. 2004. 47:1020–1028.

11. Rychlik I, Jancova E, Tesar V, Kolsky A, Lacha J, Stejskal J, Stejskalova A, Dusek J, Herout V. The Czech registry of renal biopsies. Occurrence of renal diseases in the years 1994-2000. Nephrol Dial Transplant. 2004. 19:3040–3049.

12. Kramer HJ, Nguyen QD, Curhan G, Hsu CY. Renal insufficiency in the absence of albuminuria and retinopathy among adults with type 2 diabetes mellitus. JAMA. 2003. 289:3273–3277.

13. Lane PH, Steffes MW, Mauer SM. Glomerular structure in IDDM women with low glomerular filtration rate and normal urinary albumin excretion. Diabetes. 1992. 41:581–586.

14. Tsalamandris C, Allen TJ, Gilbert RE, Sinha A, Panagiotopoulos S, Cooper ME, Jerums G. Progressive decline in renal function in diabetic patients with and without albuminuria. Diabetes. 1994. 43:649–655.

15. MacIsaac RJ, Tsalamandris C, Panagiotopoulos S, Smith TJ, McNeil KJ, Jerums G. Nonalbuminuric renal insufficiency in type 2 diabetes. Diabetes Care. 2004. 27:195–200.

16. MacIsaac RJ, Panagiotopoulos S, McNeil KJ, Smith TJ, Tsalamandris C, Hao H, Matthews PG, Thomas MC, Power DA, Jerums G. Is nonalbuminuric renal insufficiency in type 2 diabetes related to an increase in intrarenal vascular disease? Diabetes Care. 2006. 29:1560–1566.

17. Rigalleau V, Lasseur C, Raffaitin C, Beauvieux MC, Barthe N, Chauveau P, Combe C, Gin H. Normoalbuminuric renal-insufficient diabetic patients: a lower-risk group. Diabetes Care. 2007. 30:2034–2039.

18. Kramer CK, Leitao CB, Pinto LC, Silveiro SP, Gross JL, Canani LH. Clinical and laboratory profile of patients with type 2 diabetes with low glomerular filtration rate and normoalbuminuria. Diabetes Care. 2007. 30:1998–2000.

19. Knobler H, Zornitzki T, Vered S, Oettinger M, Levy R, Caspi A, Faraggi D, Livschitz S. Reduced glomerular filtration rate in asymptomatic diabetic patients: predictor of increased risk for cardiac events independent of albuminuria. J Am Coll Cardiol. 2004. 44:2142–2148.

20. Nag S, Bilous R, Kelly W, Jones S, Roper N, Connolly V. All-cause and cardiovascular mortality in diabetic subjects increases significantly with reduced estimated glomerular filtration rate (eGFR): 10 years' data from the South Tees Diabetes Mortality study. Diabet Med. 2007. 24:10–17.

21. Morrish NJ, Wang SL, Stevens LK, Fuller JH, Keen H. Mortality and causes of death in the WHO Multinational Study of Vascular Disease in Diabetes. Diabetologia. 2001. 44:Suppl 2. S14–S21.

22. Karter AJ, Ferrara A, Liu JY, Moffet HH, Ackerson LM, Selby JV. Ethnic disparities in diabetic complications in an insured population. JAMA. 2002. 287:2519–2527.

23. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999. 130:461–470.

24. 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–S154.

25. Mattix HJ, Hsu CY, Shaykevich S, Curhan G. Use of the albumin/creatinine ratio to detect microalbuminuria: implications of sex and race. J Am Soc Nephrol. 2002. 13:1034–1039.

26. Warram JH, Gearin G, Laffel L, Krolewski AS. Effect of duration of type I diabetes on the prevalence of stages of diabetic nephropathy defined by urinary albumin/creatinine ratio. J Am Soc Nephrol. 1996. 7:930–937.

27. Diabetic retinopathy study. Report Number 6. Design, methods, and baseline results. Report Number 7. A modification of the Airlie House classification of diabetic retinopathy. Prepared by the Diabetic Retinopathy. Invest Ophthalmol Vis Sci. 1981. 21:1–226.

28. Araki S, Haneda M, Sugimoto T, Isono M, Isshiki K, Kashiwagi A, Koya D. Polymorphisms of the protein kinase C-beta gene (PRKCB1) accelerate kidney disease in type 2 diabetes without overt proteinuria. Diabetes Care. 2006. 29:864–868.

29. Poggio ED, Wang X, Greene T, Van Lente F, Hall PM. Performance of the modification of diet in renal disease and Cockcroft-Gault equations in the estimation of GFR in health and in chronic kidney disease. J Am Soc Nephrol. 2005. 16:459–466.