Albumin to creatinine ratio in a random urine sample: Correlation with severity of preeclampsia

Peer review under responsibility of Alexandria University Faculty of Medicine.

Available online 31 January 2014

Abstract

Background

Albumin to creatinine ratio (ACR) in random urine samples correlates well with 24-h protein excretion in potential glomerulopathy as in diabetic renal microangiopathy. Using this ratio as an appropriate screening test for proteinuria or for the disease severity in hypertensive disorders with pregnancy needs still to be verified.

Objective

To investigate the role of albumin to creatinine ratio in a random urine sample for assessment of severity of preeclampsia.

Patients & methods

Two separate groups, fifty women each, were enrolled. All were pregnant at their third trimester with confirmed preeclampsia. Based on their blood pressure levels, Group A, included patients with mild form of preeclampsia, whereas group B included cases with severe form. Albumin to creatinine ratio in random urine samples and the 24-h protein content in urine were assessed.

Results

ACR and the 24-h urine protein excretion were significantly correlated, (r = 0.583, p < 0.001). Cut-off value for ACR for this group of patients was calculated to be 14.65 mg/mmol, above which severity of the disease is highly probable. The sensitivity and specificity were 100% and 58.0%, respectively. The positive predictive value was 70.4% and negative predictive value was 100%.

Conclusions

Random urine ACR may be a reliable method for prediction and assessment of severity of preeclampsia. Using the estimated cut-off may add to the predictive value of such a simple quick test.

KEYWORDS:

• Albumin
• Creatinine
• Ratio
• Albumin to creatinine ratio
• Preeclampsia

1 Introduction

Hypertensive disorders complicating pregnancy are common and form one of the deadly triad, along with hemorrhage and infection that contribute greatly to maternal morbidity and mortality.^1,2 Preeclampsia is defined as a pregnancy-specific syndrome of reduced organ perfusion secondary to vasospasm and endothelial activation.^3–6 Proteinuria is an important sign of preeclampsia, without which, the diagnosis is questionable.^7,8 Significant proteinuria is defined by 24-h urinary protein exceeding 300 mg or persistent 30 mg/dl in random urine samples. The degree of proteinuria may fluctuate widely over any 24-h period, even in severe cases. Therefore a single random sample may fail to demonstrate significant proteinuria.^9,10

Severe preeclampsia may be diagnosed clinically by persistent diastolic hypertension at or above 110 mm Hg, marked headache, visual symptoms, oliguria or right upper quadrant pain. Persistent proteinuria and abnormal liver or renal function tests are all signs of disease severity as well.¹¹

The measurement of protein excretion in a 24-h urine collection is used as the gold standard for the diagnosis and follow-up of pathologic urinary excretion.¹² However, 24-h urine collection is time consuming, inconvenient and often inaccurate especially during pregnancy with less patient’s compliance.

It is of utmost importance to highlight new diagnostic or predictive reliable tests, and hence introduce and apply them in a population with still fairly high maternal mortality rate, such as the Egyptian population. Many suggestions of predictors of severity of preeclampsia in the Egyptian population have been published, such as blood lead level,¹³ genetic mutation in Endothelial nitric oxide synthase (eNOS) (Glu298Asp) or urotensin II (UTS2 S89N) gene polymorphisms,¹⁴ and maternal serum leptin.¹⁵

In this study we studied a random urine albumin to creatinine ratio as a simple quick test to predict the presence of significant proteinuria and to assess severity of preeclampsia in Egyptian patients.

2 Patients and methods

One hundred pregnant women attending the Antenatal clinic of our University hospital were enrolled. All women were primigravidae, at or above 28 weeks of gestation and with confirmed diagnosis of preeclampsia. Based on their blood pressure levels, and after a full informed consent was signed, women were recruited into two separate equal groups (50 women each); group A, consisted of patients with mild form of preeclampsia (diastolic blood pressure less than 110 mm Hg3⁴) and Group B consisted of patients with severe form (diastolic blood pressure at or above 110 mm Hg3⁴). Patients with chronic hypertension, diabetes mellitus, preexisting renal or vascular disease or urinary tract infection were excluded. The study was formally approved by the Ethical Committee of the Faculty of Medicine, Alexandria University with the following ID:[IRB No. 00006555, FWA No. 00011712,May 2008]. Microalbumin in urine was tested by NycoCard Microalbumin Single Test (Axis-Shield^® plc, Oslo, Norway) based upon an immunometric flow-through principle. Quantitative determination of both creatinine and albumin in urine sample was done by Roche/Hitachi 902 analyzer (Roche Diagnostics^®, Basel, Switzerland).^16,17

The statistical analysis of the data obtained in the present study was carried out using the Statistical Packages for the Social Sciences (SPSS version 15.0, Chicago, IL). Normally distributed data were presented as mean, standard deviation, whereas skewed data were expressed as median and range. Pearson coefficient of correlation was used to find the correlation between two parameters in the same group. ROC curve was plotted to find the diagnostic performance of the variables.

3 Results

The mean values of albumin (mg/L), creatinine (mmol/L), ACR in a random urine sample, and 24-h protein in urine (mg/24-h) in both groups are shown in Table 1. Significant statistical differences were found between both studied groups regarding albumin in random urine sample, ACR, and 24-h protein in urine, however, it was not significantly different when it came to creatinine in a random urine sample (Table 1).

Table 1 Albumin, creatinine, ACR and protein in urine.

	Group A (Mild) n = 50	Group B (Severe) n = 50	Z (p)
Albumin (mg/L)
Range	1.19–6500.00	34.40–29500.00	6.613^* (<0.001)
Mean ± SD	717.99 ± 1273.03	3976.97 ± 5580.22
Median	20.80	2650.00
Creatinine (mmol/L)
Range	0.32–18.64	0.60–39.91	1.896 (0.058)
Mean ± SD	5.53 ± 4.76	8.24 ± 7.86
Median	3.97	5.54
ACR (mg/mmol)
Range	0.31–980.39	14.85–2673.48	6.225^* (<0.001)
Mean ± SD	140.36 ± 232.59	631.62 ± 530.60
Median	4.59	533.67
Protein (mg/24-h)
Range	390.00–4410.00	14.85–11850.00	6.894^* (<0.001)
Mean ± SD	1285.60 ± 945.14	7066.08 ± 2795.22
Median	887.50	7565.00

Z: Z for Mann Whitney test.

* Statistically significant at p ⩽ 0.05.

There was a strong positive correlation between ACR and the severity of preeclampsia when Spearman coefficient was applied (r = 0.518, p < 0.001), similarly, the correlation between ACR and the 24-h protein in urine was also found to be significantly positive (r = 0.583, p < 0.001) (Fig. 1).

Figure 1 The correlation between ACR and the 24-h protein in urine.

Using the ROC curve, the cut-off value of ACR for the study subjects was calculated to be 14.65. ACR above this value could be used as a good predictor for the disease severity, with a sensitivity of 100% and a specificity of 58.0%. The positive predictive value was 70.4% and negative predictive value was 100%. The area under the curve (AUC) represented the diagnostic performance of both 24-h urine protein, and ACR. It confirmed a better role for the latter (AUC 0.93) (Fig. 2).

Figure 2 Receiver operating characteristic (ROC) curve comparing the diagnostic performance of ACR (dashed line) and protein in 24-h urine (continuous line) (AUC) for ACR was 0.93 (AUC) for protein in 24-h urine was 0.89.

4 Discussion

Preeclampsia is associated with the highest risk of adverse maternal and perinatal complications that affect 2–5% of pregnancies.¹⁶ Assessing the presence or absence of significant proteinuria (⩾0.3 g/day) represents a key component in the evaluation of pregnant women with hypertension. Urine collection over 24 h is considered the traditional way for quantification of proteinuria in pregnancy, however, timed collections delay clinical diagnosis and may result in prolonged hospital stay, thereby increasing patient anxiety and healthcare costs. Moreover, it requires more patients’ compliance than could be usually found in pregnancy. Alternatives include: urinary dipsticks, urine collections over a shorter period, the urinary spot protein: creatinine ratio, and the urinary spot albumin: creatinine ratio (ACR). The dipstick is inexpensive, easy to use, and provides a rapid result but has low sensitivity and specificity.^18,17 Shorter timed urine collections (2, 4, 8, or 12 h) were also suggested to diagnose proteinuria in pregnancy but still, they have their own limitations.^18–20 The spot protein: creatinine ratio and spot ACR have been well studied and used. The National Kidney Foundation now recommends these tests (instead of 24-h urine collection) to diagnose proteinuria in most situations, without specific mention of pregnancy.¹⁷ The Australasian Society for the Study of Hypertension in Pregnancy and the International Society for the Study of Hypertension in Pregnancy have proposed the use of the urinary spot protein: creatinine ratio as an alternative to 24 h urine collection.^21–25 Up to our knowledge, the spot protein: creatinine ratio is not widely used for the diagnosis of proteinuria in pregnant women with hypertension. In our study, it was shown that ACR is significantly higher in patients with severe preeclampsia than those with a mild form of the disease. Moreover, the correlation between ACR and the 24-h protein in urine was also found to be positive, independent of gestational age, maternal age, blood chemistry or time of disease onset. It was also possible, in the light of this work, to calculate the cut-off value for ACR for the enrolled patients, above which, a severe form of the disease might be predicted. This is to our knowledge the first report in Egypt, to recommend such a test and a cut-off for diagnosis/follow up of albuminuria in pregnancy, which can, thus, be used as a marker of severity of preeclampsia. Finally, a better diagnostic potential for ACR than a 24-h urine protein, was suggested based on our result analysis. In conclusion, ACR measurement is a simple, quick, and reasonably-reliable method for assessment of severity of preeclampsia.

Conflicts of interest

None.

Notes

Peer review under responsibility of Alexandria University Faculty of Medicine.

Available online 31 January 2014