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 Table of Contents  
ORIGINAL ARTICLE
Year : 2014  |  Volume : 1  |  Issue : 2  |  Page : 86-90

Microalbuminuria in Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Patients on Antiretroviral Therapy in Zaria, Nigeria


1 Department of Chemical Pathology, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria
2 Department of Haematology, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria

Date of Submission23-Feb-2014
Date of Acceptance22-May-2014
Date of Web Publication16-Jul-2014

Correspondence Address:
Rasheed Yusuf
Department of Chemical Pathology, Ahmadu Bello University Teaching Hospital, Zaria
Nigeria
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DOI: 10.4103/2384-5147.136818

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  Abstract 

Introduction: Microalbuminuria (MA) an early marker of glomerular dysfunction is also associated with increased risk of cardiovascular disease (CVD) in the general population, and is frequently seen among patients with human immunodeficiency virus (HIV) infection. Measurement of MA is not routinely done in many HIV/acquired immunodeficiency syndrome (AIDS) patients in our environment, especially those on antiretroviral therapy (ART). This study was to determine the prevalence of MA among HIV/AIDS patients in Zaria. Subjects and Methods: Screening for MA was carried out in this cross-sectional study involving 101 HIV/AIDS patients on ART. Patients with hypertension, diabetes, renal disease, pregnancy, and with features suggestive of malignancy were excluded from the study. Urinary albumin and creatinine, serum creatinine, glucose, cholesterol, and CD4 count were assayed. The data obtained were analyzed using the statistical software package for the social sciences version 16.0 (SPSS 16.0). Result: The mean values for urine albumin, urine creatinine, and albumin creatinine ratio (ACR) were 9.35 mg/L ± 1.32 mg/L, 6.50 mmol/L ± 0.35 mmol/L and 1.77 mg/mmol ± 0.34 mg/mmol, respectively. Twenty-one (20.8%) patients were found to have MA (ACR 3-30 mg/mmol) with remaining 80 (79.2%) having normoalbuminuria (ACR <3 mg/mmol). Among patients with MA, 6 (5.9%) had estimated creatinine clearance of <60 ml/min. There was a statistically significant association (P < 0.001) between ACR and age in microalbuminuric patients. Conclusion: Prevalence of MA is high among HIV/AIDS patients on ART in Zaria. Routine measurement of microalbumin in urine is suggested for early identification of renal disease and CVD and possibly reduces morbidity and mortality among patients with HIV/AIDS infection.

Keywords: Acquired immunodeficiency syndrome, albumin creatinine ratio, antiretroviral therapy, human immunodeficiency virus, microalbuminuria


How to cite this article:
Yusuf R, Aliyu IS, Muktar HM, Hassan A. Microalbuminuria in Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Patients on Antiretroviral Therapy in Zaria, Nigeria. Sub-Saharan Afr J Med 2014;1:86-90

How to cite this URL:
Yusuf R, Aliyu IS, Muktar HM, Hassan A. Microalbuminuria in Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Patients on Antiretroviral Therapy in Zaria, Nigeria. Sub-Saharan Afr J Med [serial online] 2014 [cited 2019 Oct 17];1:86-90. Available from: http://www.ssajm.org/text.asp?2014/1/2/86/136818


  Introduction Top


Human immunodeficiency virus (HIV) infection is a worldwide health problem that affects millions of men and women. [1] Since the emergence of acquired immunodeficiency syndrome (AIDS) more than 25 years ago, renal disease has been recognized as a common complication associated HIV infection. [2]

The association between HIV/AIDS infection and renal disease was the first reported as far back as 1984 by researchers in New York and Miami. They reported series of HIV-1 infected patients with renal syndrome characterized by proteinuria and progressive renal failure. [3],[4],[5] Renal disease may also result from the medications used in HIV/AID treatment. [2]

Human immunodeficiency virus/AIDS patients are at greater risk for the development of a variety of acute and chronic renal diseases. [6] HIV-1 associated nephropathy is now the third leading cause of end-stage renal disease (ESRD) in blacks 20-64 years of age. [7],[8],[9] These patients typically have proteinuria followed by a reduction in the glomerular filtration rate that progresses to ESRD in few weeks or months. Moreover, HIV-associated renal disease with overt proteinuria has been associated with increased mortality. [10],[11]

The term microalbuminuria (MA) is used to describe albumin concentrations in the urine that are greater than normal, but not detectable with conventional urine dipstick analysis. The normal albumin excretion rate is <20 μg/min or <30 mg/day, thus urinary albumin excretion rate between 20 and 200 μg/min or albumin creatinine ratio (ACR) of 3-30 mg/mmol is termed MA. [12]

Microalbuminuria, an indicator of glomerular injury, is associated with an increased risk of progressive renal deterioration, cardiovascular disease (CVD), and mortality. [13] However, the prevalence of MA has barely been investigated in HIV-infected individuals, [13] especially in Nigeria. The reported studies on this aspect were carried out elsewhere in the world. In view of its clinical importance, there is therefore the need to carry out a study on the prevalence of MA and association between MA and age, estimated creatinine clearance (eCrCl), CD4 count and duration on antiretroviral therapy (ART) in HIV-infected patients attending antiretroviral (ARV) clinic in Ahmadu Bello University Teaching Hospital (ABUTH), Zaria. This could help in the diagnostic, therapeutic and prognostic purposes, and therefore reduces the morbidity and mortality associated with renal diseases among this group of patients in Nigeria.


  Subjects and methods Top


This cross-sectional study was conducted between January and March, 2011 among HIV/AIDS patients attending ARV clinic in ABUTH, Zaria in Northern Nigeria. The study was approved by the Health Research Ethics Committee of the hospital. Informed written consent was obtained from all participants.

One hundred and one HIV/AIDS patients on ART (zidovudine, lamivudine, and nevirapine combination therapy) aged between 15 and 50 years were randomly selected from among patients attending ARV clinic in ABUTH, Zaria. The patients with features suggestive of diabetes mellitus, hypertension, congestive cardiac failure, renal disease, those with macroalbuminuria and leukocyturia using urine dipstick, and those that are pregnant were excluded from the study to rule out other factor(s) that could cause albuminuria.

Weight (kg) and height (m) of the studied subjects were recorded using a stadiometer with patients wearing light clothing and without shoes. Body mass index (BMI) was calculated as weight (kg)/height 2 (m 2 ). Blood pressures of the patients were also measured in mmHg while sitting down. Ten milliliters of fasting venous blood sample was collected from each patient. From the sample collected 6 ml was dispensed into plain bottles and serum obtained from the clotted blood samples after centrifuging at 3000 rpm for 15 min. The sample was stored at 4°C until assayed within 4 days after collection.

Serum creatinine, glucose, and cholesterol were assayed based on Jaffe's reaction, hexokinase, and cholesterol esterase methods, respectively using SELECTRA XL automated chemistry analyzer (ELITech group, vital scientific, Chicago, IL (USA)) with analysis in batches. Each assay was validated using commercial quality control samples, standards as well as previous assayed human sera. The eCrCl was calculated using Cockcroft and Gault formula. [14] The remaining 4 ml of blood was collected into EDTA containing bottles for CD4 count analysis using Cyflow meter (Partek).

About 10-15 ml of spot urine was collected into urine sample bottle by the study patients for analysis. Immunoturbidimetric and Jaffe's reaction methods were used for measurement of urinary albumin and creatinine, respectively. Urinary ACR was calculated (urinary albumin (mg)/urinary creatinine (mmol)) and MA defined as ACR of 3-30 mg/mmol.

The data obtained were analyzed using the statistical software package for the social sciences (SPSS Inc., Chicago, USA) version 16.0 (SPSS 16.0). The analysis of variance and Student's t-test were used to compare mean values of variables. Also Pearson's linear correlation analysis to test significance of association was carried out. A P ≤ 0.05 was considered to be statistically significant.


  Results Top


The studied patients were made up of 45 (44.55%) males with a mean age of 42 years, and 56 (55.45%) females with a mean age of 36 years. The mean duration on ARV drugs was 37.75 ± 2.88 months. However, the duration on ARV drugs were significantly lower (P < 0.05) in microalbuminuric patients.

Twenty-one patients (20.8%) were found to have MA using urinary ACR while 11 (10.9%) of them are microalbuminuric using only urinary albumin. Among the patients with MA, 6 (5.9%) had eCrCl of <60 ml/min.

[Table 1] shows mean values of clinical parameters in micro- and normo-albuminuric HIV-infected patients on ART. There were no statistically significant differences in BMI, systolic blood pressure (SBP) and diastolic blood pressure (DBP) between the micro- and normo-albuminuric patients (P > 0.05). Deranged BMI ranging from overweight to obesity is present in 57.1% of microalbuminuric patients as against 48.75% of the normoalbuminuric patients (P > 0.05).
Table 1: BMI and blood pressure (mean ± SEM) in micro-and normo-albuminuric HIV/AIDS patients on ART

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The mean values of fasting serum glucose, cholesterol, creatinine and CD4 count in micro- and normo-albuminuric patients are shown in [Table 2]. There were no statistically significant differences (P > 0.05) in the mean concentrations of these parameters between the two groups.
Table 2: Fasting serum glucose, cholesterol, creatinine and CD4 count (mean ± SEM) in micro-and normo-albuminuric HIV/ AIDS patients on ART

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The mean values of urinary albumin and ACR were significantly higher (P < 0.001) in microalbuminuric than normoalbuminuric patients. There were no statistically significant differences (P > 0.05) in the mean values of urinary creatinine and eCrCl in the micro- and normo-albuminuric patients [Table 3].
Table 3: Urinary albumin, creatinine, ACR and eCrCl (mean ± SEM) in micro-and normoalbuminuric HIV/AIDS patients on ART

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There was a statistically significant association (P < 0.001) between ACR and age as shown in [Figure 1], but no statistically significant correlation between ACR and eCrCl, and CD4 count in microalbuminuric patients.
Figure 1: Relationship between albumin creatinine ratio and age in microalbuminuric human immunodeficiency virus/acquired immunodefi ciency syndrome patients on antiretroviral therapy

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There were statistically significant positive correlations between ACR and urinary albumin in both microalbuminuric (r = 0.684, P = 0.001) and normoalbuminuric patients (r = 0.854), P = 0.000) as shown in [Figure 2] and [Figure 3], respectively.
Figure 2: Relationship between albumin creatinine ratio and urinary albumin in microalbuminuric human immunodeficiency virus/acquired immunodefi ciency syndrome patients on antiretroviral therapy

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Figure 3: Relationship between albumin creatinine ratio and urinary albumin in normoalbuminuric human immunodefi ciency virus/acquired immunodefi ciency syndrome patients on antiretroviral therapy

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  Discussion Top


Presence of proteinuria among HIV/AIDS patients has been linked to increased risk of chronic kidney disease, ESRD, new AIDS defining illness and mortality.

In this study, with apparently normal renal function and no hypertension or diabetes mellitus and with MA defined as ACR 3-30 mg/mmol, the prevalence of MA was found to be 20.8% among the HIV/AIDS patients on ART.

The finding in this study is comparable to findings of 19.4% by Luka et al. in New Jeysey, [15] 29.8% by Kimmel et al. in Washington, [16] 24.0% by Han et al. in South Africa [17] and 20.2% by Szczech et al. among the HIV-infected veterans in USA. [18]

The prevalence of MA in this study is higher than 14.0% reported by Crowley et al. in New Heaven, [19] 8.0% by Szczech et al. in USA, [20] 11.0% also in USA by Szczech et al.[21] and 8.7% by Baekken et al. in Oslo Norway [13] but lower than 70.8% reported by Aderibigbe et al. in Nigeria among highly active ART (HAART)-naοve HIV patients. [22] Differences in methods for assessment of MA may have contributed to the differences found in these studies. Most of the studies mentioned above used Micral test strip for urinary albumin assessment. The Micral test strip is less sensitive than the immunoturbidimetric method [23] employed in this study.

The significant positive correlation between age and ACR in microalbuminuric HIV/AIDS patients observed in this study is in agreement with findings of strong association between older age and MA in previous studies. [13],[21] This may probably be due to more leakage of albumin disproportionately as a result of significant damage to the glomeruli integrity with advancing age.

An apparently higher SBP and DBP was seen in microalbuminuric patients, but was not statistically significant. This finding agrees with that of Szczech et al.[21] and Baekken et al.[13] among HIV/AIDS patients.

It has been reported that HIV/AIDS patients with MA had a trend toward more insulin resistance, though not statistically significant. [21] Furthermore, diabetes mellitus has been reported as possible complication of use of HAART. [24] The mean concentration of fasting serum glucose was found to be apparently higher in microalbuminuric patients than normoalbuminuric patients though not statistically significant, this is in agreement with finding of Szczech et al. [21]

In agreement with previous study by Baekken et al., [13] the present study shows no significant difference in CD4 count between microalbuminuric and normoalbuminuric patients, but apparently higher in the normoalbuminuric patients. There was no association found between CD4 count and ACR in both microalbuminuric and normoalbuminuric patients in this study. This is in agreement with finding by Baekken et al.[13] but in contrast to that of other studies in which they could not obtain information on the use of antihypertensive such as angiotensin converting enzyme inhibitors and ARV drugs shown to affect urine protein excretion from their patients. [15],[18],[22] Similarly, in this study majority of patients had evidence of moderate immunosuppression with some preservation of immune function. This is in contrast to the finding of Szczech et al.[21] where microalbuminuric patients had mean CD4 count <200 cells/μl. It is noteworthy that, though insignificant, the association between CD4 count and ACR in microalbuminuric patients was negative, that is with decreasing CD4 count which is a sign of severity or chronicity, ACR increases. This agrees with findings by Szczech et al.[21] and Luka et al. [15]

In this study, it was observed that duration on ART was apparently lower among the microalbuminuric patients. This agrees with earlier report by Schwartz et al.[25] that HAART therapy seem to be protective against HIV-related kidney disease.

From this study, it has been shown that prevalence of MA among HIV/AIDS patients is high and as such detection of MA as early as possible in the course of the disease and prompt initiation of therapy is very important in the management of HIV-nephropathy in our resource poor environment. Although some commonly used ARV drugs can be nephrotoxic, several reports suggest that the overall effect of ART is beneficial to the kidneys compared with the potential harm associated with uncontrolled viral replication. [26] Therefore, early initiation of ART to preserve kidney function may be protective against progression to ESRD, premature CVD and death.

 
  References Top

1.Dubin J. HIV infection and AIDS. e-Medicine 2002. [Last updated on 5 Feb 2007; last accessed on 2009 Jun 15].  Back to cited text no. 1
    
2.Cohen SD, Kimmel PL. HIV-associated renal diseases in Africa a desperate need for additional study. Nephrol Dial Transplant 2007;22:2116-9.  Back to cited text no. 2
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3.Gardenswartz MH, Lerner CW, Seligson GR, Zabetakis PM, Rotterdam H, Tapper ML, et al. Renal disease in patients with AIDS: A clinicopathologic study. Clin Nephrol 1984;21:197-204.  Back to cited text no. 3
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4.Pardo V, Aldana M, Colton RM, Fischl MA, Jaffe D, Moskowitz L, et al. Glomerular lesions in the acquired immunodeficiency syndrome. Ann Intern Med 1984;101:429-34.  Back to cited text no. 4
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5.Ross MJ, Klotman PE. Recent progress in HIV-associated nephropathy. J Am Soc Nephrol 2002;13:2997-3004.  Back to cited text no. 5
    
6.Ross MJ, Klotman PE, Winston JA. HIV-associated nephropathy: Case study and review of the literature. AIDS Patient Care STDS 2000;14:637-45.  Back to cited text no. 6
    
7.Winston JA, Bruggeman LA, Ross MD, Jacobson J, Ross L, D'Agati VD, et al. Nephropathy and establishment of a renal reservoir of HIV type 1 during primary infection. N Engl J Med 2001;344:1979-84.  Back to cited text no. 7
    
8.Szczech LA, Gupta SK, Habash R, Guasch A, Kalayjian R, Appel R, et al. The clinical epidemiology and course of the spectrum of renal diseases associated with HIV infection. Kidney Int 2004;66:1145-52.  Back to cited text no. 8
    
9.Eggers PW, Kimmel PL. Is there an epidemic of HIV Infection in the US ESRD program? J Am Soc Nephrol 2004;15:2477-85.  Back to cited text no. 9
    
10.Gardner LI, Holmberg SD, Williamson JM, Szczech LA, Carpenter CC, Rompalo AM, et al. Development of proteinuria or elevated serum creatinine and mortality in HIV-infected women. J Acquir Immune Defic Syndr 2003;32:203-9.  Back to cited text no. 10
    
11.Szczech LA, Hoover DR, Feldman JG, Cohen MH, Gange SJ, Goozé L, et al. Association between renal disease and outcomes among HIV-infected women receiving or not receiving antiretroviral therapy. Clin Infect Dis 2004;39:1199-206.  Back to cited text no. 11
    
12.Lindsey BJ. Amino acids and proteins. In: Micheal LB, Edward PF, Larry ES, editors. Clinical Chemistry - Principles, Procedures, Correlations. 5 th ed. USA: Lippincott Williams and Wilkins; 2005. p. 212-3.  Back to cited text no. 12
    
13.Baekken M, Os I, Sandvik L, Oektedalen O. Microalbuminuria associated with indicators of inflammatory activity in an HIV-positive population. Nephrol Dial Transplant 2008;23:3130-7.  Back to cited text no. 13
    
14.Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16:31-41.  Back to cited text no. 14
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15.Luke DR, Sarnoski TP, Dennis S. Incidence of microalbuminuria in ambulatory patients with acquired immunodeficiency syndrome. Clin Nephrol 1992;38:69-74.  Back to cited text no. 15
    
16.Kimmel PL, Umana WO, Bosch JP. Abnormal urinary protein excretion in HIV-infected patients. Clin Nephrol 1993;39:17-21.  Back to cited text no. 16
    
17.Han TM, Naicker S, Ramdial PK, Assounga AG. A cross-sectional study of HIV-seropositive patients with varying degrees of proteinuria in South Africa. Kidney Int 2006;69:2243-50.  Back to cited text no. 17
    
18.Szczech LA, Menezes P, Byrd Quinlivan E, van der Horst C, Bartlett JA, Svetkey LP. Microalbuminuria predicts overt proteinuria among patients with HIV infection. HIV Med 2010;11:419-26.  Back to cited text no. 18
    
19.Crowley ST, Cantwell B, Abu-Alfa A, Rigsby MO. Prevalence of persistent asymptomatic proteinuria in HIV-infected outpatients and lack of correlation with viral load. Clin Nephrol 2001;55:1-6.  Back to cited text no. 19
    
20.Szczech L, Grunfeld C, Canchola J, Sydney S, Shlipak M. HIV is associated with increased prevalence of microalbuminuria. 12 th Conference on Retroviruses and Opportunistic Infections (CROI), 2005, 12: Abstract No 821.  Back to cited text no. 20
    
21.Szczech LA, Grunfeld C, Scherzer R, Canchola JA, van der Horst C, Sidney S, et al. Microalbuminuria in HIV infection. AIDS 2007;21:1003-9.  Back to cited text no. 21
    
22.Aderibigbe A, Olanrewaju TO, Chijioke A, Salami AK, Dada SA, Adewale AA. Microalbuminuria in HAART-naïve HIV patients in Nigeria. Niger Postgrad Med J 2010;17:27-8.  Back to cited text no. 22
    
23.Lutale JJ, Thordarson H, Abbas ZG, Vetvik K. Microalbuminuria among Type 1 and Type 2 diabetic patients of African origin in Dar Es Salaam, Tanzania. BMC Nephrol 2007;8:2.  Back to cited text no. 23
    
24.Wyatt CM, Klotman PE. Antiretroviral therapy and the kidney: Balancing benefit and risk in patients with HIV infection. Expert Opin Drug Saf 2006;5:275-87.  Back to cited text no. 24
    
25.Schwartz EJ, Szczech LA, Ross MJ, Klotman ME, Winston JA, Klotman PE. Highly active antiretroviral therapy and the epidemic of HIV+ end-stage renal disease. J Am Soc Nephrol 2005;16:2412-20.  Back to cited text no. 25
    
26.Choi AI, Li Y, Deeks SG, Grunfeld C, Volberding PA, Shlipak MG. Association between kidney function and albuminuria with cardiovascular events in HIV-infected persons. Circulation 2010;121:651-8.  Back to cited text no. 26
    


    Figures

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    Tables

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