International Journal of Clinical Biochemistry and Research


A comparative study to determine the better predictor of renal impairment in essential hypertensive patients


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Author Details: Kruthi BN,Pushpa Sarkar,Raghunath H*

Volume : 6

Issue : 1

Online ISSN : 2394-6377

Print ISSN : 2394-6369

Article First Page : 99

Article End Page : 104


Abstract

Introduction and Objectives: Hypertension (HTN) is one of the major public health problems of adult population. HTN and renal functions are closely related and it is a predisposing factor for renal abnormalities. The objectives of the study were to estimate and compare the levels of Microalbuminuria (MAU), serum creatinine and estimated Glomerular Filtration Rate (eGFR) in essential hypertensives and to correlate their levels with duration of HTN.

Materials and Methods: The data of the cross sectional study includes physical measurements, blood pressure and biochemical investigations like serum creatinine, MAU [measured using Albumin Creatinine Ratio (ACR)] & eGFR.

Result: Out of 220 subjects, 112 (48.21% male and 51.78% female) were essential hypertensives and 112 (47.32% male and 52.68% female) were non-hypertensives. Mean value of serum creatinine was within the normal range in both the study groups. 62.5% hypertensives had MAU as compared to 4.46% non-hypertensives. The difference in eGFR was not statistically significant among the study groups. Receiver Operative Characteristic curve (ROC) for duration of HTN showed that area under the curve for MAU was more as compared to serum creatinine and eGFR.

Conclusion:  HTN is a non-communicable disease (NCD) that still remains inadequately treated. The kidney is considered as a prime target for hypertensive damage. Our study suggests that MAU is prevalent in essential hypertensive subjects and has a positive correlation with the duration of HTN. MAU can be used as a better predictor of renal impairment in essential hypertensive patients as compared to serum creatinine and eGFR. More extensive screening for MAU should be performed to facilitate better stratification of renal disease in hypertensive patients.

Keywords: HTN, Serum creatinine, MAU, ACR & eGFR.

Introduction

Hypertension (HTN) is one of the biggest health challenges in the 21st century causing about 9.4 million deaths every year and it is the leading cause of premature death. The incidence of HTN in India is 5-15%.[1] According to World Health Organization (WHO) health statistics 2012, the prevalence of HTN in India was 23.1% in men and 22.6% in women of the age of 25 years or more.[2]

HTN results from complex interactions of genes and environmental factors and hence it is difficult to understand the exact cause of it.[3] HTN doubles the risk of Cardio-Vascular Disease (CVD) and it also increases the risk of developing cerebrovascular accidents and renal diseases.[4]

Chronic uncontrolled HTN leads to renal diseases and it is symptomless in the early stage. Patients don’t realize that they have a problem until their renal function has decreased to less than 25% of the normal renal functional capacity. Hence, a better biomarker that allows detection of renal damage in the early stages is essential for the diagnosis.[5]

“Sir Robert Hutchinson's words from the beginning of 20th century are still appropriate today at the beginning of 21st century: “The ghosts of dead patients that haunt us do not ask why we did not employ the latest fad of clinical investigation. They ask us, why did you not test my urine?”

Screening for MAU is a sensitive, reliable and accessible test and it is an independent risk factor for renal disease and cardiovascular morbidity and mortality.[6]

Screening for MAU can be performed by three methods:[7]

  1. Measurement of the Albumin-Creatinine Ratio (ACR) in a random spot collection of urine
  2. Measurement of MAU in 24-hour collection of urine and
  3. Measurement of MAU in timed (e.g., 4-hours or overnight) urine sample.

The American Diabetic Association (ADA) guidelines of 2004 recommend the use of Urinary Albumin Excretion (UAE) or ACR on random samples. According to ADA, 24 hours urine collection is the gold standard method for measuring UAE. However, more convenient method to detect MAU in clinical practice is the ACR in a random urine sample and ACR correlates very well with MAU measured in 24-hour urine samples.[8][9]

Therefore in our study we have used ACR on spot urine samples to measure microalbuminuria. (Table 1)

Estimation of serum creatinine is a simple and the most commonly used biomarker of renal function. But, it may remain within the normal range even with a decrease in glomerular filtration rate (GFR) of > 50%.[10]

The first step in the prevention of renal insufficiency is early diagnosis and treatment. One of the best markers to assess the renal function is the GFR.[11] Accurate estimation of GFR requires the use of invasive techniques which is difficult to perform routinely in daily practice.[12][13]

To overcome this, endogenous biomarkers like serum creatinine and cystatin-C have been used as markers for estimation of GFR to assess the renal functional status.[14] Various formulae have been derived based on serum creatinine. One such commonly used equation is the Modification of Diet in Renal Disease (MDRD) equation.[15]

The association between essential HTN and renal disease has received little consideration because of its asymptomatic nature. Hence, the present study was undertaken to determine the correlation between the HTN, serum creatinine, MAU and eGFR and also to determine the better predictor of renal function impairment in essential hypertensive patients.

Materials and Methods

This was a cross sectional study carried out in essential hypertensive patients visiting the outpatient clinic of department of General Medicine, Mandya Institute of Medical Sciences and teaching Hospital (MIMS), Mandya. Consented individuals were included in the study, after obtaining relevant clearance from the Institutional Scientific Committee and the Institutional Ethics Committee of MIMS, Mandya.

By purposive sampling method, 224 subjects in the age group of 30–60 years who were enrolled were included in the study. According to JNC-VII and inclusion and exclusion criteriae, 112 subjects were included in hypertensive group and an equal number of age- sex matched subjects were included in non-hypertensive groups.[16]

Those who were known cases of secondary HTN, diabetes mellitus, patients with known thyroid disorders, urinary Tract Infections, pregnant and lactating women, haematuria and acute illness were excluded from the study.

Collection of [removed]iVBORw0KGgoAAAANSUhEUgAAAA0AAAASCAIAAAAPCcNlAAAAAXNSR0IArs4c6QAAAAlwSFlzAAAOxAAADsQBlSsOGwAAAFNJREFUKFNj/P//PwMRgIkINSAlZKnbns6Yvh27BWSZh8etxJrH8P//tjSs5lhNuA0MMxgAqkMAoI60bcgCCDax9lJbHSOR8Uusf4k1j9r+INY8AMSjTs6sWDWEAAAAAElFTkSuQmCC" style="height:13.5pt; width:9.75pt" /> SD

Non-hypertensives

Mean ± SD

p value

SBP (mm Hg)

146.29 ± 17.45

110.39 ± 11.29

< 0>*

DBP (mm Hg)

91.52 ± 12.27

71.20 ± 7.37

< 0>*

Serum creatinine

(mg/dl)

0.84 ± 0 .16

0.78 ± 0 .13

> 0.05

MAU#

(mg/gm)

70.65 ± 65.94

13.28 ± 8.28

< 0>*

eGFRMDRD

(ml/min/1.73m2)

92.97 ± 18.52

95.99 ± 17.81

> 0.05

# estimated using ACR and * statistically significant.

Graph 3: Distribution of MAU (estimated using ACR) with duration of HTN  

Click here to view

MAU > 30mg/gm of ACR & * statistically significant.

Graph 4 - Receiver Operating Characteristic (ROC) curve to compare serum creatinine, MAU# & eGFRMDRD with duration of HTN

Click here to view

# calculated using ACR

Limitations of the Study

A 24 hour urine sample is the gold standard to measure MAU, but, it could not be collected in the present study.

There are many limitations in the calculation of eGFRMDRD using serum creatinine, to assess renal impairment. Hence requires gold standard method for the early detection of renal impairments in hypertensive patients.

Scope for Further Studies

There is lot of confusion about reporting of results in different units. Ideally, International System of Units should be adopted to express the results for each of the parameters.

There is a need to further evaluate and re-establish the normal reference ranges of eGFR, according to each of the formulae and for different ethnic groups.

Conflict of Interest: None.

Conclusion

HTN is a major health problem in the community; a significant proportion of which still remains inadequately treated. Kidney is considered as prime target of hypertensive damage. Serum creatinine alone can be difficult to assess renal functional status at the earliest. The prevalence of MAU varies in different population groups, based on the characteristics of the population as well as techniques and protocols used for its evaluation.

The prevalence of MAU increases with the duration of HTN. Early screening of essential hypertensive patients for MAU and aggressive management of HTN might reduce the burden of diseases due to renal damage secondary to HTN in the community. The advantage of using eGFR as calculated by MDRD formula is based on its simplicity, ease of reporting and cost effectiveness. However, the MDRD equation is not without its limitations. Some studies have shown that MDRD equations may underestimate GFR in healthier populations. Thus, it may lead to misdiagnosis and misclassification of CKD in individuals with mild renal insufficiency.[24]

More extensive screening for MAU should be performed among hypertensive subjects to facilitate better stratification of renal disease in patients with essential HTN.

Our study suggests that MAU is prevalent in essential hypertensive patients and has a positive correlation with the duration of HTN and thus can be used as an early marker for end stage renal damage.

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