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Indian Journal of Nephrology

Indian J Nephrol 2001;11: 6-11

ARTICLE

Prevalence of microalbuminuria in essential

hypertension: A study of patients with mild to
moderate hypertension.
S Jalal *, FA Sofi ** , MS Alai **, MA Sidiqqi***, MA Bhat #, KA Khan #, VM Jan #, NA Lone**, HA Rather**,
* Prof. & Head, Deptt. of Cardiology, ** Senior Resident, *** Professor, Deptt. of Immunology, # Lecturer,
Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir.

Abstract
To determine the frequency of increased urinary albumin excretion (UAE) in essential
hypertension and to establish whether this abnormality is associated with deranged renal
function, we measured UAE in a group of 288 patients with essential hypertension and
240 normal subjects. Mean arterial pressure (MAP) in patients with essential hypertension
and control subjects was 121.61 5.82 and 92.78 5.66 mmHg respectively (P<0.001).
Mean UAE was 5.35 0.84 mg/24 hr. in normal subjects and 31.64 4.91mg/24 hr. in
patients with essential hypertension (P<0.001). One hundred and eight (37.5%) patients
with essential hypertension manifested microalbuminuria (UAE> 30mg/24hr.) and had an
average UAE of 76.37 29.49 mg/24hr. versus 12.04 6.53mg/24 hr. in normo-albuminuric
patients (P< 0.001). MAP and creatinine clearance in patients with micro-albuminuria and
normoalbuminuria were comparable (122.3 6.20 versus 121.19 5.66 mmHg; 93.57
6.75 versus 93.02 8.74ml/min; P>0.1 and >0.5 respectively). We noted a UAE of 5.35,26.61
and 36.67 mg/24 hr. in normal subjects, patients with mild and moderate essential
hypertension respectively (P <0.001); signifying an increasing trend in UAE with the
presence and severity of essential hypertension. Long term prospective studies are needed
to establish whether an increase in UAE may predict future nephrosclerosis in essential
hypertension.
Key words : microalbuminuria, essential hypertension, prevalence, severity

Introduction
Hypertension is a major public health problem all over
the world. The incidence of hypertension in India is 5
15% in the adult population against 1012% in the West.1
Essential hypertension produces clinical proteinuria and
a significant reduction in renal function in 5 15% of
patients.2 The advent of more sensitive methods to
quantitate the urinary albumin excretion (UAE) has
revealed higher frequency (25100%) of
microalbuminuria in patients with hypertension than in
normotensive population 3,4,5. This wide variability in the
incidence of micro-albuminuria in these studies may be
related to the severity of hypertension, selection criteria,
racial difference and, in some cases, to smaller number
of patients studied.
Address for Correspondence:
Prof. S. Jalal
Head. Deptt. of Cardiology &
Dean Medical faculty.
Sher-i-Kashmir Institute of Medical Sciences,Soura,
GPO Post Bag No. 27
Srinagar.- 190011
Copyright 2001 by The Indian Society of Nephrology

Several epidemiological studies have shown that

proteinuria as well as micro-albuminuria are independent
predictors of cardiovascular morbidity 6,7 and mortality
in patients with essential hypertension. Morever, 25%
of patients with end stage renal disease have
hypertension as the primary diagnosis 2. It becomes of
paramount importance to study UAE and progression
of nephropathy in hypertensive patients. The purpose
of this study was to evaluate the frequency of
microalbuminuria in a large population with mild to
moderate hypertension and its relation with severity of
hypertension and renal function.

Material and Methods

This study was conducted at outpatient clinic of
Cardiology and General Medicine department of SK.
Institute of Medical Sciences, Srinagar, Kashmir. Three
hundred patients with mild to moderate hypertension in
the age range of 44-64 years with diastolic blood
pressure (DBP) consistently ranging between 95 and
115 mmHg during the three subsequent visits to the
outpatient clinic and creatinine clearance greater than

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Indian J Nephrol 2001;11: 6-11

Microalbuminuria in essential hypertension

80 ml/min/1.73m2 were included in the study.

Antihypertensive drug therapy was withheld at least for
four weeks prior to the entry into the study in patients
already on treatment. The diagnosis of secondary
hypertension was adequately excluded in an appropriate
manner with the regular laboratory analyses. Renal
cause for hypertension was excluded by finding of normal
urinalysis, serum electrolytes, serum creatinine,
creatinine clearance and renal ultrsonography, and when
clinically indicated, by magnetic resonance angiography.
Patients with clinical or laboratory evidence of hepatic,
renal, thyroid or any other major disease like diabetes
mellitus, females on birth control pills and patients with
doubtful history of essential hypertension were excluded
from the study.
A control group consisting of 240 healthy volunteers
(normotensive), age and sex matched were also entered
into the study. They were thoroughly screened for any
disease especially hypertension, renal disease and
diabetes mellitus.
All patients and control subjects were encouraged to
continue their regular diet and to refrain from stressful
physical activity on the day of urine collection. During
the third outpatient clinic visit, each patient and control
subject brought his/her previous 24 hours urine collection

for UAE and creatinine clearance estimation. Blood and

urine creatinine were measured by autoanalyser. Urine
for estimation of microalbuminuria was stored at - 200C
till processing of samples. UAE was estimated by an
immunoturbidometry method which permits the
quantitative determination of albumin by
immunoprecipitin analysis using an automated
Biochemistry Analyser (Hitachi 704). Microalbuminuria
was defined as UAE between 30 300 mg/24 hours 8.
Arterial blood pressure was measured by mercury
sphygmomanometer after 5 minutes of rest; the values
reported represented the average of three consecutive
measurements taken over a 15 min period. Mean arterial
pressure was calculated as diastolic blood pressure plus
one third of pulse pressure.
Statistical analysis was performed by standard methods
for rates and proportions; chi square test, paired t-test,
un-paired t test, one- way analysis of variance. A two
tail p-value was used for calculating statistical
significance. A pvalue of < 0.05 was taken statistically
significant.

Observations
Among the hypertensive group, 12 patients were
excluded from the study because of their poor

Table 1 : Clinical characteristics of study subjects.

S.No.

Parameter

Hypertensive group
n = 288

Control group
n = 240

P- value

1.

Age (years)
Mean + S.D
Sex
M:F
BMI (kg/m2)
Mean + S. D
Smokers No.(%)
Males No. (%)
Females No.(%)
Blood pressure
(mmHg)
SBP; Mean + SD

51.85 + 5.56
(44 - 64)

51.05 + 5.10
(45-64)

> 0.05

156 : 132
25.38 + 3.34
(18.36 - 32.37)
114 (39.58)
78 (68.42)
36 (31.58)

128 : 112
24.88 + 2.66
(18.42 - 30.58)
84 (35)
60 (71.43)
24 (28.57)

> 0.75
> 0.1

160.33 + 11.34
(140 - 178)
102.29 + 4.72
(96 - 119)
121.61 + 5.82
(113.3 - 134.6)

123.7 + 9.63
(110 - 140)
77 + 4.37
(70 - 82)
92.78 + 5.66
(83.3 - 101.3)

< 0.001

2.
3.
4.

5.

DBP; Mean + SD
MAP; Mean + SD

> 0.25

< 0.001
< 0.001

BMI : Body mass index

SBP : Systolic blood pressure
DBP : Diastolic blood pressure
MAP : Mean arterial pressure.
Figures in parenthesis indicate range, unless specified.
Copyright 2001 by The Indian Society of Nephrology

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Indian Journal of Nephrology

Indian J Nephrol 2001;11: 6-11

compliance; thus only 288 patients completed their follow

up. Among the hypertensive patients, 258 (89.58%)
patients had never received antihypertensive drugs prior
to the study and the remaining 30 (10.42%) patients
had stopped the drugs at least four weeks prior to the
study. Mean age of these patients was 51.85 5.56
years. One hundred and fiftysix (54.17%) of these
patients were males. The hypertensive patients and
control subjects were of comparable age, sex and BMI.
Mean arterial pressure in hypertensive patients was
121.61 5.82 mmHg against 92.78 5.66 mmHg in
control group (P < 0.001) [Table 1].
Serum creatinine, urea, uric acid (although in normal
range) were significantly higher in hypertensive group
than in controls (P < 0.001). Mean creatinine clearance,
although in normal range, was significantly lower (P <
0.001) in hypertensive patients than in normotensive
subjects. The hypertensive patients manifested a mean
urinary alumin excretion (UAE) of 31.94 4.91 mg/24
hour, which is significantly higher (P < 0.001) than that

of control group (Table 2). One hundred and eight

(37.5%) patients in hypertensive group had
microalbuminuria while none among normotensive group
had it. Comparison of various parameters between
microalbuminuric and normoalbuminuric hypertensive
patients did not reveal any significant difference except
in their UAE rate and chest X-ray. Out of 108
microalbuminuric patients, 45 (41.66%) had
hypertensive retinopathy (grade I in 14 and grade II in
31 patients; Keith Wagener Barker classification)
while in normoalbuminuric group, 50 (27.78%) patients
had hypertensive retinopathy (grade I in 36 and grade II
in 14 patients) [P> 0.05]. Fortytwo (38.89%) patients in
microalbuminuric group had abnormal chest x-ray in the
form of cardiomegaly compared to 48 (26.67%) patients
in normoalbuminuric group (P < 0.05) [Table 3].
Out of 288 hypertensive patients, 78 (27.08%) had mild
and 210 (72.92%) patients moderate hypertension.
Microalbuminuria was present in 24 (30.77%) and 84
(40%) patients with mild and moderate hypertension

Table 2 : Laboratory characteristics of study subjects.

S.No.

Parameter

1.

Haemoglobin (gm/dl)

2.

Blood Glucose (mg/dl)

3.

Serum cholesterol (mg/dl)

4.

Serum uric acid (mg/dl)

5.

Serum proteins (gm/dl)

6.

Serum albumin (gm/dl)

7.

Serum urea (mg/dl)

8.

Serum creatinine (mg/dl)

9.

Serum soduim (mEq/L)

10.

Serum potassuim (mEq/L)

11.

Creatinine clearance
(ml/min)
Urinary albumin
excretion (mg/24 hr.)
Patients with Micro albuminuria No. (%)

12.
13.

Hypertensive group
n = 288
11.94 + 1.61
(7.4 - 15.8)
95.56 + 2.27
(66 - 100)
175.81+38.51
(90 - 260)
4.99 + 0.96
(3.0 - 7.0)
7.11 + 0.87
(4.9 - 8.5)
3.98 + 0.72
(2.4 - 5.2)
37.10 + 9.66
(18 - 40)
0.95 + 0.17
(0.58 - 1.42)
137.65 + 7.81
(122 - 158)
3.89 + 0.53
(3.0 - 5.0)
93.23 + 7.98
(80.8 - 106.2)
31.94 + 4.91*
(1.92 - 128.0)

Control group
n = 240
11.89 + 1.14
(9.9 - 13.6)
95.85 + 5.93
(76 - 101)
142.80 + 39.67
(90 - 208)
4.32 + 0.83
(3.0 - 6.0)
6.99 + 1.01
(4.9 - 8.4)
4.12 + 0.87
(2.8 - 5.8)
30.11 + 5.42
(22 - 40)
0.86 + 0.14
(0.62 - 1.09)
136.9 + 6.93
(128 - 150)
3.83 + 0.58
(3.0 - 5.1)
98.25 + 9.45
(82.8 - 114.6)
5.35 + 0.84*
(0.70 - 20.40)

108 (37.50)

Nil

P- value
> 0.5
> 0.25
< 0.001
< 0.001
> 0.1
> 0.1
< 0.001
< 0.001
> 0.25
< 0.001
< 0.001
< 0.001

Values are expressed mean SD, unless specified; Figures in parenthesis indicate range *Standard error of mean (SEM)
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Indian J Nephrol 2001;11: 6-11

Microalbuminuria in essential hypertension

Table 3 - Characteristics of microalbuminuric and normoalbuminuric hypertensive patients.

S.No

Parameter

1.
2.

MAP (mmHg)
Serum creatinine
(mg/dl)
Serum cholesterol
(mg/dl)
Serum albumin
(gm/dl)
Cr. Cl (ml/min)
UAE (mg/24hr.)
Abnormal CXR.
No. (%)
Abnormal EKG
No. (%)

3.
4.
5.
6.
7.
8.

Microalbuminuric gr.
n = 108
122.3 + 6.20
0.96 + 0.17

Normoalbuminuric gr.
n = 180
121.19 + 5.66
0.98 + 0.16

P-value
>0.1
>0.3

175 + 30.77

182.3 + 41.08

>0.05

4.12 + 0.57

3.99 + 0.80

>0.1

93.57 + 6.75
76.37+29.49
42 (38.89)

93.02 + 8.74
12.04 + 6.53
48 (26.67)

>0.5
<0.001
<0.05

30 (27.78)

36 (20)

>0.1

MAP : Mean arterial pressure;

Cr. Cl : Creatinine clearance.
UAE : Urinary albumin excretion.
Values expressed as Mean + S.D, unless specified
CXR : Xray chest
respectively (P > 0.1). Mean UAE was 5.35 0.84 mg,
26.61 6.82, 36.67 6.22mg/24hr. in normotensive
subjects, patient with mild hypertension and moderate
hypertension respectively. A positive correlation was
found between severity of hypertension and UAE (P<
0.001) [Fig.1].

Discussion
The conventional method of detecting renal damage in
hypertensive patients which include the measurement
of blood urea nitrogen creatinine and proteinuria, are
relatively insensitive and only show abnormalities when

the disease process is advanced. There has recently

been considerable interest in the quantitative
measurement of albuminuria to detect subtle effects of
hypertension on the kidney. The term micro-albuminuria
was first used by Viberti et al to describe the subclinical
elevation of urinary albumin (30-300 mg/24 hours) in
patients with diabetic nephropathy8,9. In the present
study, we documented microalbuminuria in 37.5% of
patients with hypertension, possibly pointing toward the
subclinical and subtle changes occurring in the glomeruli
of these patients. The prevalence of microalbuminuria
is not well established and it may vary from 15

Fig. 1 - Showing increasing trend of UAE with the

presence and severity of hypertension (p< 0.001).
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Indian Journal of Nephrology

Indian J Nephrol 2001;11: 6-11

100%2,5,10. This variation is probably due to difference in

the age, race, severity of hypertension and coexistent
renal disease in these study populations.
We studied 288 patients with hypertension and 240
healthy, normotensive control subjects drawn from the
same general population with similar demographic and
clinical characteristics and found that urinary albumin
excretion rates were significantly greater in hypertensive
patients than in control subjects (P < 0.001). which is
consistent with previous studies 2,11.
In addition to this, hypertensive patients had significantly
higher levels of urea, creatinine, uric acid and lesser
levels of creatinine clearance compared to control
subjects (P < 0.001); although, all these values fell well
in the normal laboratory range. These differences are
again, probably the result of subclinical ultrastructural
changes going on in the glomeruli of these hypertensive
patients due to ill effects of persistently elevated blood
pressure over some period.
We did not find any difference in the prevalence of
microalbuminuria between mild and moderate
hypertensive patients (P> 0.1). However, an increasing
urinary albumin excretion rate was noted with presence
and severity of hypertension which goes with the
previous studies 4,10,12. We failed to document any
significant difference in creatinine clearance between
microalbuminuric and normo-albuminuric hypertensive
patients; however, we excluded patients with significant
decrease in renal function. It is conceivable that patients
with essential hypertension and more advanced
nephrosclerosis and renal insufficiency might display

greater amounts of UAE.

Several studies have indicated that the presence of
proteinuria or microalbuminuria is an independent
predictor of cardiovascular morbidity and mortality in
patients with essential hypertension13-18. We could
demonstrate cardiomegaly (roentegenographically) in
significant number of patients with microalbuminuria
compared to hypertensive patients with
normoalbuminuria.
Proteinuria has been shown to represent a significant
predictor of progressive renal failure in virtually all forms
of glomerulonephritis 19,20. Viberti 9, Mogensen21 and
Parving12 have shown that the presence of
microalbuminuria in early phases of the disease is an
important independent predictor of progressive renal
failure in patients with insulin and non-insulin dependent
diabetes mellitus. No long-term studies have been
performed to ascertain whether microalbuminuria can
be used as a predictor of progressive deterioration in
renal function in patients with essential hypertension. It
is of interest, however, that elevated UAE has been found
to be associated with more severe hypertension in many
studies including our own study4,10,12. Obviously further
prospective studies are needed to assess the predictive
value of microalbuminuria in essential hypertension.
In summary, our data suggest that microalbuminuria is
prevalent in 37.5% of patients with essential
hypertension and has a positive correlation with the
severity of hypertension and thus may be an early marker
for end-organ damage susceptibility.

Reference
1.

2.

3.

4.

5.

6.

Datey KK, Kumar M, Goyal BK. Recent advances in the

management of hypertension. Indian Heart Journal 1982;
vol. 34, No. 6 : 349 355.
Bigazzi R, Bianchi S, Campese VM, Baldari G.
Prevalence of microalbuminuria in a large population of
patients with mild to moderate hypertention. Nephron
1992; 61 : 94 97.
Parving HH, Jensen HE, Mogensen CE, Evrin PE.
Increased urinary albumin excretion in benign essential
hypertension. Lancet 1974 ; 1 : 231 237.
Losito A, Fortunati F, Zampi I, Del Favero A. Impaired
functional reserve and albuminuria in essential
hypertension. Br Med J 1988 ; 1 : 1562 64.
Giaconi S, Levanti C, Fommei E, Innocenti F, et al. Microalbuminuria and casual and ambulatory blood pressure
monitoring in normotensives and in patients with
borderline and mild hypertension. Am J Hypertens 1989;
2 : 259 61.
Bianchi S, Bigazzi R, Baldari G, Campese VM.
Microalbuminuria in patients with essential hypertension.
Effect of several anti hypertensive drugs. Am J Med
1992; 93 : 52528.

Copyright 2001 by The Indian Society of Nephrology

7.

Yudkin JS, Forrest RD, Jackson CA. Microalbuminuria

as a predictor of vascular disease in non-diabetic
subjects. Lancet 1988; 2 : 530 33.
8. Ljungman S. Microalbuminuria in essential hypertension.
Am J Hyperten 1990 ; 3 : 956 60.
9. Viberti GC, Hill RD, Jarrat RD, Argyropoulos A, Mahumud
U, Keen H. Microalbuminuria as a predictor of clinical
nephropathy in insulin-dependent diabetes mellitus.
Lancet 1982 ; 1 : 1430-32.
10. Pedersen EP, Mogensen CE. Effect of antihypertensive
treatment on urinary albumin excretion, glomerular
filtration rate and renal plasma flow in patients with
essential hypertension. Scand J clin lab Invest 1976; 36:
100 : 550 555.
11. Gerber LM, Shmukler C, Alderman MH. Differences in
urinary albumin excretion rate between normotensive and
hypertensive, white and non-white subjects. Arch Intern
Med 1992;152 : 373-77.
12. Parving HH, Oxenboll B, Svendsen PA, Christiansen JS,
Andersen AR. Early detection of patients at risk of
developing diabetic nephropathy: A longitudinal study
of urinary albumin excretion. Acta Endocrinol 1982 ; 100:
550 -55.

[Downloaded free from http://www.indianjnephrol.org on Tuesday, August 11, 2015, IP: 59.90.136.61]
Indian J Nephrol 2001;11: 6-11

13. Lewin A, Blaufox D, Castle H, Entwisle G, Langford H.

Apparent prevalence of curable hypertension in the
hypertension detection and follow up programme. Arch
Intern Med 1985; 145 : 424 27.
14. Samuelsson O, Wilhelmsen L, Elmfeldt D, Pennert K,
Wedel H, Wikstrand J, Berglund G. Predictors of
cardiovascular morbidity in treated hypertension: Results
from the primary preventive trial in Goteborg, Sweden. J
Hyperten 1985 ; 3 : 167 76.
15. Wolf FW, Lindeman RD. Effects of treatment on
hypertension: Results of a controlled study J Chronic
Dis 1966 ; 19 : 227 40.
16. Bulpitt CJ, Beevers DG, Butler A. et al. The servival of
treated hypertensive patients and their cause of death:
A report from the DHSS hypertensive care computing
project (DHCCP). J Hypertens 1986 ; 4 : 93 99.

Microalbuminuria in essential hypertension

11

17. Kannel WB, Stamfer MJ, Castelli WP, Verter J. The

prognostic significance of proteinuria: The Framingham
Study. Am Heart J 1984 ; 108 : 1347 52.
18. Pedrinelli R, Giampietro O, Carmassi F, Mellillo E. et al.
Micro- albuminuria and endothelial dysfunction in
essential hypertension. Lancet 1994 ; 344 : 14 - 18.
19. Neelakantappa K, Gallo GR, Baldwin DS. Proteinuria in
IgA nephropathy. Kidney Int 1988 ; 33 : 716 21.
20. Maschio G, Oldrizzi L, Rugin C, Valvo E, Lupo A,
Loschiavo C, Tessitore N, Fabris A, Gammoro L.Factors
affecting progression of renal failure in patients on longterm dietary protein restriction. Kidney Int 1983 ; 32
(suppl.22) : 49 52.
21. Mogensen CE. Microalbuminuria predicts clinical
proteinuria and early mortality in maturity onset diabetes.
N Eng J Med 1986 ; 310 : 356 60.

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