ORIGINAL  
Niger J Paed 2013; 40 (1):65 - 69  
Urinary findings in HIV positive  
children by dipstick screening test in  
Enugu  
Ezeonwu BU  
Oguonu T  
Ikefuna AN  
Okafor HU  
DOI:http://dx.doi.org/10.4314/njp.v40i1.12  
Accepted: 7th July 2012  
Abstract Background: Human im-  
munodeficiency virus (HIV) affects  
the kidney. Urine screening for ab-  
normalities can detect early renal  
parenchymal diseases.  
Objectives: To determine the preva-  
lence of abnormal urinary findings  
in HIV positive children in Univer-  
sity of Nigeria Teaching Hospital,  
(UNTH), Enugu.  
Method: Urinary screening was car-  
ried out in 159 HIV positive chil-  
dren in UNTH over a period of4-  
months, to detect presence of abnor-  
malities such as glycosuria, protein-  
uria, haematuria, as well as the pres-  
ence of nitrite and leucocyte es-  
terase, abnormal urine pH and spe-  
cific gravity (SG).  
leucocyte esterase. Subjects with  
proteinuria were older (5-14 years),  
had longer duration of HIV diagno-  
sis, longer duration of treatment  
with HAART, and a lower CD4 cell  
count (p=0.01). Sixty percent of  
those with proteinuria had severe  
immunosuppression, with 4 out of  
the 5 of them with urine SG more  
than 1.015. The children with urine  
SG more than 1.015 were among  
the older age group (5-14 years), on  
HAART, had non-advanced HIV  
disease as well as low CD4 cell  
count (p= <0.0001).  
Conclusion: Urinary abnormalities  
occur among HIV infected children.  
Longer duration of HIV diagnosis,  
older age and low CD4 cell count,  
are probable factors associated with  
proteinuria.We recommend routine  
urinary examination for HIV posi-  
tive children.  
(
)
Ezeonwu BU  
Department of Paediatrics, Federal  
Medical Center Asaba , Nigeria.  
Email: uzovin@yahoo.com.  
Tel: +2348033257313  
Oguonu T, Ikefuna AN, Okafor HU  
Department of Paediatrics,  
University of Nigeria Teaching  
Hospital, Ituku Ozalla Enugu,  
Nigeria.  
Results: Eighty males and 79 fe-  
males were screened. Five (5), 4,  
and a child had proteinuria, SG of >  
1
.015 and alkaline urine, giving a  
prevalence rate of 3.1%, 2.5% and  
.6% respectively. Neither of the  
0
Key words: Urinary abnormalities,  
proteinuria, advanced HIV disease,  
immunosuppression  
subjects had glycosuria, haematuria  
nor tested positive to nitrite and  
3
, 4  
Introduction  
population. The prevalence of haematuria in HIV in-  
fected adults was 3.3%, inability to concentrate urine  
3
Human immunodeficiency virus (HIV) pandemic is a  
major global health emergency. It affects multiple or-  
gans and the kidney is a common target. A variety of  
acute and chronic renal syndromes may occur during the  
course of HIV infection such as acute tubular dysfunc-  
tion caused by infections and nephrotoxic drugs, HIV  
glomerulopathies related to immunological abnormali-  
ties, HIV associated thrombotic microangiopathies and  
HIV associated nephropathy (HIVAN) caused by direct  
was found in 16% of the subjects. Afhami and col-  
leagues found no glycosuria among their subjects. The  
1
4
2
prevalence rates of the various urinary abnormalities in  
HIV inf5e,6cted children have been document5ed by several  
studies.  
Steel-Duncan and colleagues found 3%  
prevalence for proteinuria while Esezobor and cowork-  
ers documented 20.5%. Steel-Duncan and colleagues  
6
5
documented haematuria in 3 of the 7 children who were  
commenced on Indinavir and found the prevalence of  
UTI to be 16.8%. However, the prevalence of other uri-  
nary abnormalities (glycosuria, urine concentration ab-  
normality) has not been documented in children.  
2
HIV infection of renal epithelial cells. These renal syn-  
dromes can present with varied abnormal urinary find-  
ings including haematuria, proteinuria, glycosuria, poor  
urine concentration ability and urinary tract infection  
(
UTI).  
With increasing prevalence of HIV/AIDs in the country  
and among the paediatric age group, the determination  
of the renal consequence of the disease in this popula-  
tion cannot be further ignored. This study is timely as  
Some studies have shown varied prevalence rates of  
various urinary abnormalities in HIV infected adult  
6
6
there has been no published study on other urinary ab-  
normalities in HIV positive children in Nigeria, other  
than proteinuria.  
dipstick reading from trace (100mg/dL) to 4+ (2000mg/  
4 14  
dL). High specific gravity (SG) was value >1.015  
while normal specific gravity (SG) was between 1.005  
1
4
and 1.015. Urinary tract infection was suspected by the  
positive leucocyte esterase (LE) and nitrite in urinary  
1
5
dipstick. Urine sa1m4 ple with pH value above 7 was re-  
garded as alkaline.  
Subjects and methods  
Demographic and laboratory data were analyzed using  
the Software Package for Social Science (SPSS) version  
15.0 for Windows®. Continuous variables such as age,  
duration of HIV diagnosis and CD4 cell count, were  
analyzed and expressed as mean and standard devia-  
tions. For tests of significance: Chi squared test was  
used and ANOVA for comparison of means of continu-  
ous variables while for categorical variables, Chi  
squared test was used. Significant levels were set with p-  
value of < 0.05 and 95% confidence interval.  
This study was carried out at the University of Nigeria  
Teaching Hospital, (UNTH), Enugu, in the Paediatric  
Infectious Disease Clinic of the hospital. The clinic was  
established in the year 2005 with a total of 236 patients  
registered at the time of the study. Ethical approval was  
obtained from the UNTH Health Research and Ethics  
Committee before subject recruitment. The minimum  
sample size of 146 was determined using the sampling  
method for estimation of proportions of study popula-  
7
tion less than 10, 000. This was a cross sectional de-  
scriptive study in which consecutive HIV infected chil-  
dren who were aged 18 months to 14 years, were en-  
rolled from October 2009 to January 2010. The study  
participants were recruited from the patients attending  
the clinic. On presentation to the clinic, a written con-  
sent was obtained, while data on gender, age, HAART  
use and duration, duration of HIV diagnosis, CD4 cell  
count and percent were collected from the clinic records.  
The physical examination was done on all subjects to  
elicit vital clinical features for categorizing them accord-  
ing to WHO clinical staging system for infants and chil-  
Results  
One hundred and fifty nine subjects were enrolled and  
comprised of 80 (50.3%) males and 79 (49.7%) females.  
The means (in months) for the respective ages, duration  
of HIV diagnosis and HAART use of the study popula-  
tion were;79.4±39.7 (95% CI, 73.1 to 85.6, p=<0.0001),  
21.1±15.8 (95% CI, 18.6 to 3.6, p=<0.0001) and  
16.4±16.0 (95% CI, 13.9 to 18.9, p=<0.0001) respec-  
tively. The mean CD4 cell count was 696.0±446.5 cell/  
8
dren. Each child was given a universal bottle for urine  
collection to fill up to about two thirds of the bottle  
3
(
about 15mls). The urine testing was done with  
mm (95% CI, 626.0 to 765.9, p=<0.0001) while that of  
Multistix (Combi 11 strip series, urine reagent strip,  
Korea, LOT 90219) according to manufacturer’s specifi-  
cation. The urine dipstick was used for the study due to  
CD4% was 23.1±12.6% (95% CI, 21.1 to 5.1,  
p=<0.0001). The proportion of the subjects who were on  
HAART was 77.4%, 92.5% had vertical transmission,  
those with advanced HIV disease was 4.4%, those who  
had severe immunosuppression was 23.3% (Table 1).  
9
proven sensitivity and specificity in detecting urinary  
‘contents’.  
For standard assessment of the subjects the HIV- posi-  
tive children, were stratified into three different age  
groups; 18 months - 35 months, 36 month - 59 months  
and five years - 14 years according to the WHO age  
stratification for age –related CD4 values. Using the  
WHO classification of HIV disease the children were  
categorized on the basis of their clinical attributes.  
Table 1: General characteristics of the HIV positive  
children  
Parameter  
Frequency  
%
1
0
Medication  
On HAART  
123  
36  
77.4  
Not on HAART  
Mode of transmission  
22.6  
Advanced HIV disease was defined with WHO clinical  
stage three and four while stages one and two defined  
1
1
Vertical  
Blood transfusion  
Disease severity  
147  
12  
92.5  
7.5  
non-advanced disease. Severe immunosuppression was  
3
defined as CD4 cell count of less than 200cells/mm in  
those subjects equal to or more than five years old,  
CD4% of less than 15% for those between 36 and 59  
months, CD4%10 of less than 20% for those between 18  
and 35months.  
Advanced HIV disease  
7
4.4  
Non advanced HIV disease  
152  
95.6  
Immunosuppression  
For the assessment of the outcome different parameters  
were defined accordingly. Haematuria was indicated by  
urinary dipstick reading of greater than 50 RBC/µL of  
Severe immunosuppression  
37  
23.3  
76.7  
Non severe immunosuppression  
122  
6
urine (50x10 cells/L) which corresponds to urinary ex-  
cretion of greater than five red blood cells (RBC)/high  
power field (hpf).  
protein 1+ on urinary dipstick. Glycosuria was urinary  
The most important urinary abnormalities observed were  
proteinuria and high SG, with the prevalence rate of  
3.1%, and 2.5% respectively (Table 2). None of the sub-  
1
2,13  
Proteinuria was defined as urine  
6
7
jects had haematuria, glycosuria or findings suggestive  
of UTI. There was no significant gender difference in  
the distribution of the urinary abnormalities, for protein-  
uria and high SG (Table 3).  
Table 5: The clinical characteristics of HIV disease and occur-  
rence of proteinuria  
Parameter  
Frequency  
Proteinuria  
Fisher’s  
exact (p  
value)  
No proteinuria  
On HAART  
4
1
5
0
119  
35  
Table 2: Prevalence of urinary abnormalities among  
HIV positive children by age  
0.70 (0.02)  
1.00 (0.42)  
Not on HAART  
Vertical transmission  
Blood transfusion  
142  
12  
Age range  
Proteinuria  
Specific gravity  
Alkaline urine  
Positive  
Negative  
1.015  
>1.015  
Positive  
Negative  
Advanced HIV disease  
Non advanced HIV disease  
Severe immunosuppression  
1
4
3
6
148  
34  
1
8-35  
months  
6-59  
months  
-14 years  
0
1
22  
44  
22  
0
1
0
0
22  
45  
0.20 (2.98)  
0.08 (3.90)  
3
44  
Non severe immunosuppres-  
sion  
2
120  
5
4
88  
89  
3
4
1
91  
Total  
5
154  
155  
2.5  
1
158  
Prevalence  
3.1  
0.6  
Table 6: Specific gravity and general characteristics of the  
(
χ (p value)  
%)  
study population  
2
1.28 (0.50)  
0.79 (0.70)  
0.73 (0.70)  
Mean of parameters  
Normal SG  
High SG  
t
p value  
Age in months±SD  
Duration of HIV diagnosis  
in months±SD  
79.2±39.7  
21.0±15.8  
86.2±49.2  
24.7±15.0  
0.90  
0.32  
0.70  
0.60  
Table 3: Urinary abnormalities among HIV positive children  
by gender  
Gender  
Proteinuria  
Positive  
Specific gravity  
Alkaline urine  
Duration of HAART use in  
months ±SD  
16.2±16.0  
23.0±17.2  
0.61  
0.20  
0.40  
0.03  
Negative  
1.015  
>1.015  
Positive  
Negative  
CD4 cell count in cells/  
708.1±444.1  
226.7±268.  
9
3
Male  
Female  
Total  
Fisher’s  
exact (p  
value)  
3
2
5
0.19 (0.50)  
77  
77  
154  
78  
77  
155  
2
2
4
0
80  
mm ±SD  
1
78  
1
158  
Table 7: HIV disease characteristics and specific gravity  
0.00 (1.00)  
1.02 (0.50)  
Parameter  
Frequency  
Normal SG  
Fisher’s  
exact (p  
value)  
High SG  
On HAART  
120  
35  
3
1
The subjects with proteinuria had longer duration of  
HIV diagnosis, longer duration of HAART use and low  
CD4 cell counts, as shown in Table 4. Among the group  
with proteinuria, 3 subjects (60%) were immunosup-  
pressed while 4 (80%) were on HAART, (Table 5) .All  
the subjects with proteinuria had vertical transmission,  
and the time of duration from diagnosis of HIV infection  
to the commencement of HAART treatment was shorter  
0.01 (1.00)  
4.14 (0.20)  
Not on HAART  
Advanced HIV disease  
Non advanced HIV disease  
Severe immunosuppression 35  
6
149  
1
3
2
1
.64 (0.20)  
Non severe immunosup-  
pression  
120  
2
(
(
1.6±2.1 months) compared to those without proteinuria  
5.1±9.8 months), p= 0.40.  
Discussion  
The four children whose urine SG was more than 1.015  
were predominantly among the older age group  
The important urinary abnormalities found in this study  
among HIV infected children were proteinuria and high  
specific gravity. The prevalence of proteinuria in the  
index study was 3.1%, which is comparably low as Ese-  
(
Table 2). All the 4 children had proteinuria (Fisher’s  
exact = 126.38, p value = <0.0001) while their CD4 cell  
counts were comparatively lower than those with normal  
SG (Table 6). In addition, three out of these four were  
on HAART while 1 had advanced HIV disease (Table  
6
zobor and c6oworkers found 20.5% while Chaparro and  
1
colleagues noted 33%. We found low risk factors for  
the development of proteinuria in our study population:  
they were younger, had non-advanced disease, on  
7
).  
Table 4: Proteinuria and general characteristics of HIV  
positive children  
HAART treatment and had high 2,C6,1D7 4 cell count.  
2
Younger age, non-advanced disease,  
ment  
HAART treat-  
3
,6,16,18  
2,5,16,18  
are docu-  
and high CD4 cell count  
Mean of parameters  
Positive pro-  
teinuria  
Negative  
proteinuria  
t
p value  
mented low risk factors for proteinuria in HIV infected  
children.  
Age in months±SD  
95% CI)  
102.6±56.1  
(32.9 to 172.3)  
78.6±39.1  
(72.9 to 84.8)  
0.10  
0.14  
0.20  
0.50  
(
18  
Duration of HIV  
diagnosis in  
25.8±13.2  
(9.4 to 42.2)  
21.0±15.9  
(18.4 to 23.5)  
Leroy and co-workers found no proteinuria among  
HIV infected children with mean age of 44 months and  
prevalence rate for proteinuria was zero percent. Steel-  
months±SD (95%  
CI)  
Duration of HAART  
use in months±SD  
95% CI)  
24.2±15.2  
(5.4 to 43.0)  
16.1±16.0  
(13.6 to 18.7)  
0.33  
0.08  
0.30  
0.01  
5
Duncan and colleagues found a prevalence of 3% in  
(
HIV infected children w16ith mean age of 60 months,  
Chaparro and coworkers documented 33% and mean  
age of their subjects was 132 months. Though our study  
had a relatively lower prevalence of proteinuria, it  
seemed to show proteinuria to occur more in the older  
CD4 cell count in  
219.4±233.4  
(-70.4 to  
509.2)  
711.4±443.6  
(640.8 to 782.1)  
3
cells/mm ±SD (95%  
CI)  
6
8
children. The reason for this predilection could be be-  
cause older children have supposedly longer duration of  
exposure to HIV. The natural course of HIV infection is  
such that with increasing duration of exposure, there is  
disease progression which is characterized by increase  
viral load and depletion of CD4 cells which are pr1o9ven  
high risk factors for the development of proteinuria.  
results from pres1e3nce of molecules in urine such as pro-  
tein and glucose.  
The presence of alkaline urine in one subject may be an  
aberrant finding, for there was no explicable factor that  
could be responsible for it. The subject lacked any of the  
features such as UTI, use of amphotericin B and sodium  
bicarbonate which could account for the presence of  
1
7
The use of HAART suppresses viral load and the direct  
effect of the HIV on the renal cells, re16stores normal re-  
nal function and reduces proteinuria. Leroy and oth-  
alkaline urine. None of the subjects had haematuria or  
glycosuria which is similar to the findings by Afhami  
4
and colleagues. The absence of glycosuria could be at-  
1
8
ers found zero percent as all the children were3,6o,1n6  
HAART, whereas the subjects in the other studies,  
with varying prevalence rates of proteinuria were  
HAART naïve. Although the increased proportion of  
those on HAART treatment in our study may explain the  
low prevalence of proteinuria in this population of chil-  
dren, majority of those with proteinuria were already on  
HAART treatment and for a longer duration too. Ordi-  
narily the assumption that the use of HAART may sup-  
press the virus that affects the renal cells may be rational  
but this finding seems to counter the argument but rein-  
forces the possibility of multi-factorial influence to19its  
occurrence such as the viral load and CD4 cell count.  
tributed partly to the preservation of renal tubular func-  
tion which is commonly deranged in HIV positive sub-  
jects on protease inhibitors, notably tenofovir and Indi-  
5
navir. Subjects in the study by Afhami and in the index  
study were not on protease inhibitor. The absence of  
Indinavir use in the subjects could also explain the ab-  
sence of evidence of UTI and absence of haematuria.  
The risk of UTI and haematuria in HIV positive subjects  
is increased by use of Indinavir because of the nephro-  
5
lithiasis associated with its use.  
Conclusion  
Subjects with high CD4 cell count are less likely to de-  
velop HIVAN and hence proteinuria, because of the low  
Urinary abnormalities occur in HIV positive children.  
Older age and low CD4 cell count are risk factors asso-  
ciated with proteinuria. Dipstick urine testing for urinary  
abnormalities is good screening tool in HIV positive  
children and should be done routinely in the clinic.  
1
9
viral load associated with high CD4 cell count. On the  
other hand, low CD4 cell count is a risk factor for the  
2
, 6,  
development of proteinuria in HIV positive children.  
16  
We found that subjects with proteinuria had compara-  
bly lower CD4 cell count and CD4% and majority were  
severely immunosuppressed.  
Author’s contribution: Ezeonwu BU conceived the  
study,  
All authors reviewed the study and analysed the data  
Conflict of interest: None.  
The normal SG in the study subjects indicates optimal  
renal concentrating ability. Contrary to this finding,  
Estremadoyro and colleagues, found several evidence  
3
of renal tubular dysfunction among their subjects, in-  
cluding poor urine concentrating ability and renal tubu-  
lar acidosis. This finding could be attributed to the use  
Funding : None  
3
of amphotericin B for the treatment of fungal infection  
among their subjects, as this drug causes renal tubular  
damage. The high specific gravity noted in some sub-  
jects in the index study could be attributed to the pres-  
ence of protein in their urine. High specific gravity  
Acknowledgement  
1
3
We are grateful to all the children who participated, with  
their parents/caregivers.  
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