Background/Aims: Microalbuminuria is associated with diabetes and is an independent risk factor for developing diabetic nephropathy. We have previously reported the overall prevalence of normoalbuminuria, microalbuminuria, and macroalbuminuria to be 51, 39, and 9.8%, respectively, in an unselected population of patients with type 2 diabetes. Renal dysfunction was present in a large proportion of these patients without proteinuria, assessed by a single random albumin-to-creatinine ratio (ACR) . We therefore undertook to characterize the nature of this association of non-proteinuric renal dysfunction in type 2 diabetes. Methods: In the DEMAND (Developing Education on Microalbuminuria for Awareness of Renal and Cardiovascular Risk in Diabetes) study, a global, cross-sectional study which described the prevalence and risk factors for albuminuria in a clinic-based cohort, kidney function was assessed in 11,573 patients; ACR was measured using the Bayer reagent strip Multistix® 10SG. Normoalbuminuria was defined as ACR <30 mg/g, microalbuminuria as 30–299 mg/g, and macroalbuminuria as >300 mg/g. Results: Among the patients with estimated kidney function determined, chronic kidney disease was noted in 17% of those with normoalbuminuria (stage 3–5), and significant kidney dysfunction was found in 27% of those with microalbuminuria and 31% of those with overt proteinuria. CrCl was <60 ml/min in 20.5% of normoalbuminurics, 30.7% of microalbuminurics, and 35.0% of macroalbuminurics (p < 0.0001). Conclusion: A large proportion of diabetic patients with completely normal urinary albumin excretion or microalbuminuria presented with significant kidney dysfunction. Therefore, further investigation is warranted.

1.
Keen H, Chlouverakis C, Fuller J, Jarrett RJ: The concomitants of raised blood sugar: studies in newly-detected hyperglycaemics. II. Urinary albumin excretion, blood pressure and their relation to blood sugar levels. Guys Hosp Rep 1969;118:247–254.
2.
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.
3.
Viberti GC, Hill RD, Jarrett RJ, Argyropoulos A, Mahmud U, Keen H: Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus. Lancet 1982;1:1430–1432.
4.
Mogensen CE: Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med 1984;310:356–360.
5.
Parving HH, Lewis JB, Ravid M, Remuzzi G, Hunsicker LG: Prevalence and risk factors for microalbuminuria in a referred cohort of type II diabetic patients: a global perspective. Kidney Int 2006;69:2057–2063.
6.
Levey A, Greene T, Kusek J, Beck G: A simplified equation to predict glomerular filtration rate from serum creatinine. J Am Soc Nephrol 2000;11:155A.
7.
Cockcroft DW, Gault MH: Prediction of creatinine clearance from serum creatinine. Nephron 1976;16:31–41.
8.
Foundation NK: K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39:S1–S266.
9.
Rule AD, Larson TS, Bergstralh EJ, Slezak JM, Jacobsen SJ, Cosio FG: Using serum creatinine to estimate glomerular filtration rate: accuracy in good health and in chronic kidney disease. Ann Intern Med 2004;141:929–937.
10.
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J: A new equation to estimate glomerular filtration rate. Ann Intern Med 2009;150:604–612.
11.
Cirillo M, Laurenzi M, Mancini M, Zanchetti A, Lombardi C, De Santo NG: Low glomerular filtration in the population: prevalence, associated disorders, and awareness. Kidney Int 2006;70:800–806.
12.
Leitao CB, Canani LH, Kramer CK, Boza JC, Pinotti AF, Gross JL: Masked hypertension, urinary albumin excretion rate, and echocardiographic parameters in putatively normotensive type 2 diabetic patients. Diabetes Care 2007;30:1255–1260.
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.
Caramori ML, Fioretto P, Mauer M: Low glomerular filtration rate in normoalbuminuric type 1 diabetic patients: an indicator of more advanced glomerular lesions. Diabetes 2003;52:1036–1040.
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.
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.
17.
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.
18.
So WY, Kong AP, Ma RC, Ozaki R, Szeto CC, Chan NN, Ng V, Ho CS, Lam CW, Chow CC, Cockram CS, Chan JC, Tong PC: Glomerular filtration rate, cardiorenal end points, and all-cause mortality in type 2 diabetic patients. Diabetes Care 2006;29:2046–2052.
19.
Keith DS, Nichols GA, Gullion CM, Brown JB, Smith DH: Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization. Arch Intern Med 2004;164:659–663.
20.
Berl T, Hunsicker LG, Lewis JB, Pfeffer MA, Porush JG, Rouleau JL, Drury PL, Esmatjes E, Hricik D, Pohl M, Raz I, Vanhille P, Wiegmann TB, Wolfe BM, Locatelli F, Goldhaber SZ, Lewis EJ: Impact of achieved blood pressure on cardiovascular outcomes in the irbesartan diabetic nephropathy trial. J Am Soc Nephrol 2005;16:2170–2179.
21.
Messerli FH, Mancia G, Conti CR, Hewkin AC, Kupfer S, Champion A, Kolloch R, Benetos A, Pepine CJ: Dogma disputed: can aggressively lowering blood pressure in hypertensive patients with coronary artery disease be dangerous? Ann Intern Med 2006;144:884–893.
22.
Olsen S, Mogensen CE: How often is NIDDM complicated with non-diabetic renal disease? An analysis of renal biopsies and the literature. Diabetologia 1996;39:1638–1645.
23.
Schwartz MM, Lewis EJ, Leonard-Martin T, Lewis JB, Batlle D: Renal pathology patterns in type II diabetes mellitus: relationship with retinopathy. The Collaborative Study Group. Nephrol Dial Transplant 1998;13:2547–2552.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.