Sharief M; Khudier AW

Special Article - Pre-Eclampsia

Austin J Reprod Med Infertil. 2019; 6(1): 1051.

Protein/Creatinine Ratio in Random Urine Sample for Quantitation of Proteinuria Compared with 24 Hour Urine Collection in Patients with Pre-Eclampsia

Sharief M* and Khudier AW

Department of Gynecology and Obstetrics, University of Basrah, Iraq

*Corresponding author: Maysoon Sharief, Department of Gynecology and Obstetrics, College of Medicine, University of Basrah, Basrah, Iraq

Received: December 06, 2018; Accepted: January 30, 2019; Published: February 06, 2019

Abstract

Objective: To evaluate the diagnostic value of protein/creatinine (p/c) ratio in a single voided urine sample for quantitation compared to those of 24h urine sample in patient with pre-eclampsia.

Patients and Methods: A prospective study was conducted in Basrah maternity and child hospital during the period from October 2013 to October 2014. The study involved 60 pregnant women with hypertension attending the antenatal clinic and admitted to obstetrics ward regardless the severity of the disease. The main measurement was estimation the urinary protein to urinary creatinine ratio by random direct measurement and a 24-hour urinary protein excretion. The data obtained was statically analyzed.

Results: Out of 60 patients with gestational hypertension, 49 patients had significant proteinuria (>300 mg/day) and 11 patients had proteinuria less than (300 mg/day). Also, 17 out of 60 patients had p/c ratio <3 mg/dl and 43 patients had p/c ratio >3.5 mg/dl. The p/c ratio was able to correctly identify 42 out of 49 patients with significant proteinuria. It has been estimated that protein/creatinine ratio with sensitivity of 81.6%, specifity of 27.7% positive predictive value 93%, negative predictive value 70%, false positive rate 27.2%, false negative rate 18.3%.

Conclusion: The study suggest that the p/c ratio in single voiding urine is highly accurate test (P<0.01) for discriminating between in significant proteinuria. This could be a reasonable alteration to the 24-hour collection for detection of significant proteinuria in hospitalized pregnant women with suspected preeclampsia.

Keywords: Pre-eclampsia; Protein/creatinine ratio; Proteinuria; Urinary system

Introduction

Precamplsia is idiopathic disorder of pregnancy characterized by hypertension and proteinuria [1]. About 10% of women will develop Pre-eclampsia in the first pregnancy. It usually occurs after 20 weeks of gestation most often near term [1]. In severe disease there may be thrombocytopenia, hemolysis, impair liver and renal function, swelling, dyspnea or visual disturbance [2].

Maternal death worldwide is 12% and is due to hypertension disorder of pregnancy and it has been shown that patients with significant proteinuria have significant reduction in mean birth weight for gestational age due to intra-uterine growth retarded compared to the patients with hypertension alone. While, the mean birth weight for gestational age among women with hypertension alone same as normotensive [3].

So, early detection and proper management of patients with proteinuria is therefore, beneficial for mother and fetus [3]. Preeclampsia can be perceived as an Pre-eclampsia impairment of maternal immune system which prevent it from recognizing the fetoplacental unit. Excessive production of immune cells causes secretion of tumor necrosis factors alpha and induce apoptosis of extra villous cytotrophlpast. The Human Leukocyte Antigen (HLA) system also appears to play a role in defective invasion of the spiral arteries [1].

The use of the term albuminuria to describe proteinuria is incorrect because there is an increase permeability to large molecular weight protein with any glomerulopathy. Thus, albumin excretion is accompanied by other protein such as globulines, haemoglobuline and transferring [4]. Normally, those of a large protein molecules are not filtered by the glomeruli and thus their appearance in urine signifies glomerulopathic process [5].

Proteinuria of Pre-eclampsia involves predominantly high molecular weight proteins such as albumin and large amount of IgM, IgG, fibronectin and B2 microglobulin are found in urine. It is caused by reversible structural alteration of glomerular filter resulting from injury of endothelial cells in glomerular capillaries [6]. Both proteinuria and alteration of glomerular histology develop late in the course of pre-eclampsia [7].

Therefore, the aim of the study is to evaluate the diagnostic value of protein/creatinine (p/c) ratio in a single voided urine sample for quantitation compared to those of 24h urine sample in patient with pre-eclampsia.

Patients and Methods

This prospective study was conduct in AL-Basrah Maternity and Child Hospital during the period from October 2013 to October 2014. Sixty inpatient pregnant women more than 20 weeks with gestational hypertension (defined as blood pressure more than 140/90 mmHg in 2 different measurements obtained at interval more than 6 hours). Their ages ranged between 16-39 years and parity (0-6) .

Patients with chronic renal disease, chronic hypertension, diabetes mellitus, bacteruria, urinary tract infection or catheter not insert after rupture of membrane were excluded from the study.

On admission all patient were interviewed and examined carefully, gestational age was determined by the Last Menstrual Period (LMP) and any previous Ultra Sound (U/S). Then each patient was asked for:-

24h urine collection on clean bottle was started before midday. First morning sample was discarded and the time was noted .

A single voided urine specimen for spot protein/creatinine ratio was obtained as soon as possible after the 24h collection.

Morning sample was excluded for estimation of urine P/C ratio.

The data obtained was statistically analyzed.

Results

Study population

A total of 60 pregnant women were admitted for the evaluation and the age group 30-39 contributed the highest percentage (45%) followed by age = 20-29 (34%) Table 1.

Table 1: Distribution of the studied subjects (n=60) according to age.




  
    Age (in years)
    Number (n)
    Percentage (%)
  
  
    <20
    13
    21
  
  
    20-29
    20
    34
  
  
    30-39
    27
    45
  
  
    Total
    60
    100



Table 1: Distribution of the studied subjects (n=60) according to age.

Table 2 shows the distribution of the patients according to the parity. Majority of the studied group were multiparty patient = 3 (39%) followed by para 2 (25%) and prim gravida (20%).

Table 2: Distribution of the studied subjects (n=60) according to parity.




  
    Parity (p)
    Number (n)
    Percentage (%)
  
  
    0
    12
    20
  
  
    1
    10
    16
  
  
    2
    15
    25
  
  
    =    3
    23
    39
  
  
    Total 
    60 
    100



Table 2: Distribution of the studied subjects (n=60) according to parity.

Table 3 shows the distribution of the studied subjects according to 24 urine protein. Out of 60 patients 26 (34%) had significant protein urea of the range more than 300 gm/day.

Table 3: Distribution of the studied subjects (n=60) according to 24 hour urine protein.




  
    24 hour urine protein (mg/day)
    Number (n)
    Percentage (%)
  
  
    <300
    11
    18
  
  
    300-400
    23
    39
  
  
    >400
    26
    43
  
  
    Total 
    60 
    100



Table 3: Distribution of the studied subjects (n=60) according to 24 hour urine
protein.

Table 4 shows the distribution of patients according to p/c ratio in spot urine sample. Among 60 patients, 17 (28%) had p/c ratio less than 3.5 mg/dL and 26 (44%) greater than 4.5 mg/dL.

Table 4: Distribution of the studied subjects (n=60) according to protein/ creatinine ratio.




  
    Protein creatinine ratio mg/dL
    Number (n)
    Percentage (%)
  
  
    <3.5
    17
    28
  
  
    3.5-4.5
    17
    28
  
  
    >4.5
    26
    44
  
  
    Total
    60 
    100



Table 4: Distribution of the studied subjects (n=60) according to protein/
creatinine ratio.

Table 5 shows the comparison of p/c ratio in single voided urine sample to 24h urine protein in the studied group. Out of the total 60 patients with gestational hypertension 49 patients had 24h urine protein excretion more than 300 mg and out of 49 positive protein urea there was 40 positive p/c ratio and 9 patient were false negative (protein/creatinine ratio <0.3 mg/dL) on the other hand 11 patients with gestational hypertension had negative 24h protein urine (<300 mg ) out of them 3 patients were false positive for p/c ratio >3.5 mg/ dL and 8 patients with true negative (<3.5 mg/dL).

Table 5: Comparison of protein/creatinine ratio in single voided urine sample to 24 hour urine protein in the studied subjects (n=60).




  
    Protein/ creatinine ratio in single voided urine sample
    24 hour urine protein
    Total

      (n)
  
  
    Positive

      300 mg
    Negative

      <300 mg
  
  
    Positive 3.5 mg/dL
    40    TP
    3    FP
    43
  
  
    Negative <3.5 mg/dL
    9    FN
    8    TN
    17
  
  
    Total
    49
    11
    60



Table 5: Comparison of protein/creatinine ratio in single voided urine sample to
24 hour urine protein in the studied subjects (n=60).

Table 6 shows test of validity for p/c ratio in patients with preeclampsia. P/c ratio had 81.6% sensitivity, 72.7% specificity and positive predictive value of 93%, negative predictive value of 70%, false negative rate 27.2%, false negative rate 18.3%, Odds ratio 11.85%, P <0.01.

Table 6: Diagnostic value of protein/creatinine ratio patients with suspected preeclampsia (n=60) compared to 24 hour urine protein.




  
    Test of validity
    Protein/ Creatinine ratio
  
  
    Sensitivity
    81.60%
  
  
    Specificity
    72.70%
  
  
    Positive Predictive value
    93%
  
  
    Negative Predictive value
    70%
  
  
    False Positive rate 
    27.20%
  
  
    False Negative rate
    18.30%



Table 6: Diagnostic value of protein/creatinine ratio patients with suspected
preeclampsia (n=60) compared to 24 hour urine protein.

Discussion

Pre-eclampsia with various severity (mild, moderate, severe), proteinuria is estimated =+1 on dipstick test or urine protein =300mg/24h is mandatory for diagnosis and evaluation of the severity of pre-eclampsia beside maternal and perinatal morbidity and mortality increased with amount of proteinuria [8]. Several methods are available for measuring proteinuria but 24h urine protein excretion has long been regarded as the gold standard. This test has some disadvantages such as inconvenience for patients, inaccuracy due to incomplete collection, cost and delay of diagnosis and management, which make it difficult for wide use for clinician [9].

One of most commonly used is the urinary dipstick test because it is simple and cheap but this method has high false positive and false negative rate beside associated with fluctuation throughout the day due to water intake, exercises, diet, posture, and properly trained laboratory staff [9,10]. Thus, the determination of the protein/ creatinine ratio in single urine sample in pregnancy seems a sufficient valid method to assess the amount of protein excretion.

The socio demographic variable shows that the peak age more than 30 years (45%) and multiparty ( =3 ) 39% which in contrast to what is usually reported and shows that prim gravida and age peak of 20-29 years to be at high risk of developing pre-eclampsia [11]. Various studies have shown that women aged more than 40 years twice risk of pre-eclampsia regardless of parity [12].

In this study, sensitivity of 81.6% allows the clinician to correctly identify greater than 8 out of 10 cases a significant protein urea. Specificity of a diagnostic test is the probability that patient without proteinuria will have a negative result. In the present study, the specificity was (72.7%) which higher than urine dipstick test had a (47%) specificity. The false positive rate of (27%) in contrast with studies have demonstrated that false positive reaction was (14%) false positive lead to error in diagnosis and early interference increase maternal and fetal complications. Positive predictive value (93%) and negative predictive value (70%) which is higher than that for the dipstick test (48%) which demonstrated the unreliability of the dipstick test.

The effectiveness or validity of a test is important to aid clinical decision making the above method is faster in comprising to 24h protein collections as well as the difficult in ensuring complete collection make it unfit for routine use in clinical practice.

Conclusion

P/c ratio had a sensitivity of 81.6%, which will allow the clinician to correctly identify greater than 8 0ut of 10 cases of significant proteinuria. Therefore, routine use of either p/c ratio quantitation of proteinuria in patient with pre-eclampsia could be adapted which is reliable, relatively faster and correlating well with 24h urinary protein excretion in clinical practice.

References

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Citation: Sharief M and Khudier AW. Protein/Creatinine Ratio in Random Urine Sample for Quantitation of Proteinuria Compared with 24 Hour Urine Collection in Patients with Pre-Eclampsia. Austin J Reprod Med Infertil. 2019; 6(1): 1051.

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Parity (p)	Number (n)	Percentage (%)
0	12	20
1	10	16
2	15	25
= 3	23	39
Total	60	100