Albumin to creatinine catio: A screening test with limitations

doi:10.1053/ajkd.2002.33388

American Journal of Kidney Diseases

Volume 39, Issue 6, June 2002, Pages 1183-1189

https://doi.org/10.1053/ajkd.2002.33388 Get rights and content

Abstract

The aim of this study is to assess the effects of age on (1) the ability of a spot albumin-creatinine ratio (ACR) to accurately predict 24-hour albumin excretion rate (AER), and (2) the performance of spot ACR as a screening test for microalbuminuria. Three hundred fourteen patients with diabetes aged 18 to 84 years attending a tertiary outpatient clinic underwent one 24-hour urine collection and, immediately after completion, provided one fasting spot morning urine sample. Twenty-four-hour AER and spot ACR were determined. Performance of spot ACR was assessed according to age and sex. Fifty-three percent of men and 32% of women had an AER of 20 μg/min or greater. Multiple regression analysis showed age was an independent predictor of spot ACR. For an AER of 20 μg/min for patients in the age range of 40 to 80 years, there was an increase in corresponding values for spot ACR from 18.2 mg/g (95% confidence interval [CI], 15.6 to 21.3) to 32.5 mg/g (95% CI, 27.5 to 38.4) in men and from 22.1 mg/g (95% CI, 18.0 to 27.1) to 56.4 mg/g (95% CI, 47.2 to 67.4) in women. Using ACR cutoff values of 22.1 mg/g or greater and 30.9 mg/g or greater in conventional units (equivalent to ≥2.5 and ≥3.5 mg/mmol in SI units) in men and women, the spot ACR provided high sensitivities (men, 95.7%; women, 93.35%) and had excellent receiver operator characteristic curves, respectively. However, the spot ACR false-positive rate increased with age from 15.9% (age, 40 to 65 years) to 31.8% (>65 years) in men and from 10.5% (age, 45 to 65 years) to 28.3% (>65 years) in women. Spot ACR is a good screening test for microalbuminuria, but a poor predictor of quantitative AER, and should not be used as a diagnostic test. The increase in spot ACR relative to 24-hour AER with age supports the use of sex- and age-adjusted ACR cutoff values. © 2002 by the National Kidney Foundation, Inc.

Section snippets

Patients

In this prospective study, 385 consecutive samples were collected over a 6-month period from patients with type 1 (30%) and type 2 (70%) diabetes undergoing routine assessment for diabetic kidney disease at the Austin and Repatriation Medical Center (Heidelberg, Victoria, Australia). Of subjects with type 2 diabetes, 51% were women and 49% were men. Subjects undertaking assessment of AER were asked to avoid strenuous exercise the day of the urine collection. Each patient provided one timed

Effect of age on albumin and creatinine excretion

Patient characteristics are listed in Table 1.

. Clinical and Biochemical Characteristics of Patients

Empty Cell	Men	Women	P^*
No. of patients	173	141
Age (y)	59 ± 1	62 ± 1	0.05
Age by group (y)			0.46
<40	19 (11)	13 (9)	—
40-65	79 (46)	57 (40)	—
>65	75 (43)	71 (50)	—
24-Hour AER (μg/min)	31 ×/÷ 1.1	18 ×/÷ 1.1	<0.001
AER by group			<0.001
Normoalbuminuria	81 (47)	96 (68)	—
Microalbuminuria	72 (42)	37 (26)	—
Macroalbuminuria	20 (12)	8 (6)	—
24-Hour UCreat (mg/d)	1,413 ± 30	975 ± 23	<0.001
Spot ACR (mg/g)	38 ×/÷ 1.1	34 ×/÷ 1.1	0.54
^*Unpaired t-tests, except

Discussion

This study shows an important association between age and the relationship between AER and ACR in both sexes. Age has not been widely recognized as an important predictor of ACR, and current guidelines only take sex into account.⁵ In one previous study examining the interindividual variability of UCreat excretion and its influence on ACR in subjects with diabetes, only sex and body mass index, but not age, were found to be significant determinants.¹ However, on that study, subjects were studied

Acknowledgements

The authors thank Mary Tsamitros, hospital scientist, for technical assistance with the measurement of UCreat.

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An increased urinary albumin excretion rate is an important early risk factor for chronic kidney disease and other major outcomes and is usually measured using the urinary albumin-creatinine ratio (ACR). Obesity is highly prevalent in the general and chronic kidney disease populations and is an independent risk factor for moderately increased albuminuria (henceforth, moderate albuminuria). In this review, we describe how the ACR was developed and used to define moderate albuminuria. We then investigate how biases related to urinary creatinine excretion are introduced into the ACR measurement and how the use of the 30-mg/g threshold decreases the performance of the test in populations with higher muscle mass, with a primary focus on why and how this occurs in the obese population. The discussion then raises several strategies that can be used to mitigate such bias. This review provides a comprehensive overview of the medical literature on the uses and limitations of ACR in individuals with obesity and critically assesses related issues. It also raises into question the widely accepted 30-mg/g threshold as universally adequate for the diagnosis of moderate albuminuria. The implications of our review are relevant for clinicians, epidemiologists, and clinical trialists.
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A protein biomarker discovery workflow was applied to plasma samples from patients at different stages of diabetic kidney disease. The proteomics platform produced a panel of significant plasma biomarkers that were statistically scrutinised against the current gold standard tests on an analysis of 572 patients. Five proteins were significantly associated with diabetic kidney disease defined by albuminuria, renal impairment (eGFR) and chronic kidney disease staging (CKD Stage ≥1, ROC curve of 0.77). The results prove the suitability and efficacy of the process used, and introduce a biomarker panel with the potential to improve diagnosis of diabetic kidney disease.
Establish Albumin-creatinine Ratio Reference Value of Adults in the Rural Area of Hebei Province
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To establish albumin-creatinine ratio (ACR) reference value of the rural population in Hebei province.
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Similar race-specific differences were also found among non-Hispanic whites (7.2%) compared with non-Hispanic blacks (10.2%). Houlihan et al. [27] evaluated the characteristics of the ACR using gender-specific cutoff values (22.1 mg/g in men and 30.9 mg/g in women) as a screening tool and found that spot ACR testing provided high sensitivities (95.7% for men and 93.35% for women) [27]. These studies indicate that gender- and race-specific ACR reference values should be determined for children as well.
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A total of 1986 healthy children (1078 males, 908 females) aged 6–19 y were enrolled. The 95th percentile of ACR was used as the normal upper limit. The associations between ACR and gender, age, body mass index (BMI), systolic blood pressure (SBP), preterm birth, intake of fruits, smoking, and geographical area were examined.
The normal upper limit of ACR was 14.7 mg/g for male children and 19.8 mg/g for female children. The ACR value for girls was significantly higher than that for boys (P < 0.001). ACR was inversely correlated with age (P < 0.001) and positively correlated with BMI, SBP, and smoking (all P < 0.01).
The ACR reference value for healthy children in southwest China is approximately the same as the value for adults, but lower than that for the Western population. Age, SBP, BMI, and smoking in children influence ACR.

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: Address reprint requests to George Jerums, MD, Endocrine Unit, Austin and Repatriation Medical Centre, Studley Rd, Heidelberg 3084, Victoria, Australia. E-mail: [email protected]

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Original Investigations: Pathogenesis and Treatment of Kidney Disease and HypertensionAlbumin to creatinine catio: A screening test with limitations

Abstract

Section snippets

Patients

Effect of age on albumin and creatinine excretion

Discussion

Acknowledgements

Lancet

Gender and the clinical usefulness of the albumin:creatinine ratio

Diabet Med

Screening and management of microalbuminuria in patients with diabetes mellitus: Recommendations to the Scientific Advisory Board of the National Kidney Foundation from an ad hoc committee of the Council on Diabetes Mellitus of the National Kidney Foundation

Am J Kidney Dis

Microalbuminuria in diabetes

Med J Aust

St Vincent Declaration, Guidelines for the prevention of diabetic renal failure

Use of the albumin/creatinine ratio in patient care and clinical studies

Prediction of albumin excretion rate from albumin-to-creatinine ratio

Diabetes Care

Detection of microalbuminuria. Receiver operating characteristic curve analysis favors albumin-to-creatinine ratio over albumin concentration

Diabetes Care

Albumin excretion rate, albumin concentration, and albumin/creatinine ratio compared for screening diabetics for slight albuminuria

Clin Chem

Screening for diabetic microalbuminuria in routine clinical care: Which method?

Arch Dis Child

Original Investigations: Pathogenesis and Treatment of Kidney Disease and Hypertension
Albumin to creatinine catio: A screening test with limitations