Current guidelines illogically recommend that a different approach is taken to the correction for creatinine generation rate when estimating glomerular filtration rate (GFR) and when interpreting urine albumin:creatinine ratio (ACR). Age, gender and race are routinely used to adjust for predicted muscle mass in GFR estimation, even though estimated GFR is expressed per unit body surface area. Conversely, ACR is at most adjusted with the use of gender-specific classification thresholds. This difference is surprising since the proportional effect of muscle mass on serum and urine creatinine is identical. Failure to adjust for creatinine generation rate compromises ACR, potentially adversely affecting management decisions and mislabelling individuals as having/not having CKD. A greater ACR is also a marker of low muscle mass, which has confounding prognostic effects. Determination of the optimal method to adjust ACR for estimated muscle mass should improve its performance. Routine reporting of the resulting ‘estimated albumin excretion rate’, as for routine eGFR reporting, would remove the need for gender-specific thresholds.

Keywords:
Albuminuria, Proteinuria, Glomerular filtration rate
1.
Hallan SI, Orth SR: The K/DOQI 2002 classification of chronic kidney disease: For whom the bell tolls. Nephrol Dial Transplant 2010;25:2832–2836.
2.
Early identification and management of chronic kidney disease in adults in primary and secondary care (http://wwwnice.org.uk/cg73).
3.
K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39:S1–S266.
4.
Cockcroft DW, Gault MH: Prediction of creatinine clearance from serum creatinine. Nephron 1976;16:31–41.
5.
Ginsberg JM, Chang BS, Matarese RA, Garella S: Use of single voided urine samples to estimate quantitative proteinuria. N Engl J Med 1983;309:1543–1546.
6.
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.
7.
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.
8.
Sardinha LB, Carnero EA, Martins S, Branco T, Teixeira PJ: Body surface area estimation and its impact on predicting appendicular skeletal muscle mass with a mechanistic model based on the reference man. Acta Diabetol 2003;40(suppl 1):S29–S31.
9.
Rose BD PT: Measurement of urinary protein excretion (www.uptodate.com). 2010.
10.
Delanaye P, Mariat C, Cavalier E, Krzesinski JM: Errors induced by indexing glomerular filtration rate for body surface area: reductio ad absurdum. Nephrol Dial Transplant 2009;24:3593–3596.
11.
Schwab SJ, Christensen RL, Dougherty K, Klahr S: Quantitation of proteinuria by the use of protein-to-creatinine ratios in single urine samples. Arch Intern Med 1987;147:943–944.
12.
Methven S, MacGregor MS, Traynor JP, O’Reilly DS, Deighan CJ: Assessing proteinuria in chronic kidney disease: protein-creatinine ratio versus albumin-creatinine ratio. Nephrol Dial Transplant 2010;25:2991–2996.
13.
Younes N, Cleary PA, Steffes MW, de Boer IH, Molitch ME, Rutledge BN, Lachin JM, Dahms W: Comparison of urinary albumin:creatinine ratio and albumin excretion rate in the diabetes control and complications trial/epidemiology of diabetes interventions and complications study. Clin J Am Soc Nephrol 2010;5:1235–1242.
14.
Jafar TH, Chaturvedi N, Hatcher J, Levey AS: Use of albumin creatinine ratio and urine albumin concentration as a screening test for albuminuria in an Indo-Asian population. Nephrol Dial Transplant 2007;22:2194–2200.
15.
Cirillo M, Laurenzi M, Mancini M, Zanchetti A, De Santo NG: Low muscular mass and overestimation of microalbuminuria by urinary albumin/creatinine ratio. Hypertension 2006;47:56–61.
16.
Jafar TH, Schmid CH, Levey AS: Serum creatinine as marker of kidney function in South Asians: a study of reduced GFR in adults in Pakistan. J Am Soc Nephrol 2005;16:1413–1419.
17.
Jacobs DR Jr, Murtaugh MA, Steffes M, Yu X, Roseman J, Goetz FC: Gender- and race-specific determination of albumin excretion rate using albumin-to-creatinine ratio in single, untimed urine specimens: the coronary artery risk development in young adults study. Am J Epidemiol 2002;155:1114–1119.
18.
James GD, Sealey JE, Alderman M, Ljungman S, Mueller FB, Pecker MS, Laragh JH: A longitudinal study of urinary creatinine and creatinine clearance in normal subjects. Race, sex, and age differences. Am J Hypertens 1988;1:124–131.
19.
Warram JH, Gearin G, Laffel L, Krolewski AS: Effect of duration of type 1 diabetes on the prevalence of stages of diabetic nephropathy defined by urinary albumin/creatinine ratio. J Am Soc Nephrol 1996;7:930–937.
20.
Cirillo M, Senigalliesi L, Laurenzi M, Alfieri R, Stamler J, Stamler R, Panarelli W, De Santo NG: Microalbuminuria in nondiabetic adults: relation of blood pressure, body mass index, plasma cholesterol levels, and smoking: The Gubbio Population Study. Arch Intern Med 1998;158:1933–1939.
21.
Standards of medical care in diabetes, 2010. Diabetes Care 2010;33(suppl 1):S11–S61.
22.
Garg AX, Kiberd BA, Clark WF, Haynes RB, Clase CM: Albuminuria and renal insufficiency prevalence guides population screening: results from the NHANES III. Kidney Int 2002;61:2165–2175.
23.
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.
24.
Jacobsen FK, Christensen CK, Mogensen CE, Andreasen F, Heilskov NS: Postprandial serum creatinine increase in normal subjects after eating cooked meat. Proc Eur Dial Transplant Assoc 1979;16:506–512.
25.
Witte EC, Lambers Heerspink HJ, de Zeeuw D, Bakker SJ, de Jong PE, Gansevoort R: First morning voids are more reliable than spot urine samples to assess microalbuminuria. J Am Soc Nephrol 2009;20:436–443.
26.
Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, de Jong PE, Coresh J, Gansevoort RT: Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet 2010;375:2073–2081.
27.
Hemmelgarn BR, Manns BJ, Lloyd A, James MT, Klarenbach S, Quinn RR, Wiebe N, Tonelli M: Relation between kidney function, proteinuria, and adverse outcomes. JAMA 2010;303:423–429.
28.
Ruggenenti P, Gaspari F, Perna A, Remuzzi G: Cross-sectional longitudinal study of spot morning urine protein:creatinine ratio, 24-hour urine protein excretion rate, glomerular filtration rate, and end-stage renal failure in chronic renal disease in patients without diabetes. BMJ 1998;316:504–509.
29.
Lambers Heerspink HJ, Gansevoort RT, Brenner BM, Cooper ME, Parving HH, Shahinfar S, de Zeeuw D: Comparison of different measures of urinary protein excretion for prediction of renal events. J Am Soc Nephrol 2010;21:1355–1360.
30.
Hallan SI, Ritz E, Lydersen S, Romundstad S, Kvenild K, Orth SR: Combining GFR and albuminuria to classify CKD improves prediction of ESRD. J Am Soc Nephrol 2009;20:1069–1077.
31.
Gerstein HC, Mann JF, Yi Q, Zinman B, Dinneen SF, Hoogwerf B, Halle JP, Young J, Rashkow A, Joyce C, Nawaz S, Yusuf S: Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA 2001;286:421–426.
32.
Hillege HL, Fidler V, Diercks GF, van Gilst WH, de Zeeuw D, van Veldhuisen DJ, Gans RO, Janssen WM, Grobbee DE, de Jong PE: Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population. Circulation 2002;106:1777–1782.
33.
Gansevoort RT, Lambers H, Witte EC: Methodology of screening for albuminuria. Nephrol Dial Transplant 2007;22:2109–2111.
34.
Ix JH, de Boer IH, Wassel CL, Criqui MH, Shlipak MG, Whooley MA: Urinary creatinine excretion rate and mortality in persons with coronary artery disease: the Heart and Soul Study. Circulation 2010;121:1295–1303.
35.
Oterdoom LH, Gansevoort RT, Schouten JP, de Jong PE, Gans RO, Bakker SJ: Urinary creatinine excretion, an indirect measure of muscle mass, is an independent predictor of cardiovascular disease and mortality in the general population. Atherosclerosis 2009;207:534–540.
36.
Oterdoom LH, van Ree RM, de Vries AP, Gansevoort RT, Schouten JP, van Son WJ, Homan van der Heide JJ, Navis G, de Jong PE, Gans RO, Bakker SJ: Urinary creatinine excretion reflecting muscle mass is a predictor of mortality and graft loss in renal transplant recipients. Transplantation 2008;86:391–398.
37.
Ellam T, El-Nahas AM: Proteinuria thresholds are irrational: a call for proteinuria indexing. Nephron Clin Pract 2011 (in press).
© 2011 S. Karger AG, Basel
2011
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.