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Saudi Journal of Kidney Diseases and Transplantation
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RENAL DATA FROM THE ASIA - AFRICA  
Year : 2013  |  Volume : 24  |  Issue : 1  |  Page : 172-177
Prevalence of renal disease in Nigerian children infected with the human immunodeficiency virus and on highly active anti-retroviral therapy


Department of Child Health, University of Benin/University of Benin Teaching Hospital, Benin City, Nigeria

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Date of Web Publication22-Jan-2013
 

   Abstract 

Access to highly active anti-retroviral therapy (HAART) has improved the prognosis of Nigerian children infected with the human immunodeficiency virus (HIV); thus, more children are surviving. Long-term exposure to HAART is potentially nephrotoxic. We therefore aimed at assessing the prevalence of renal disease in Nigerian children infected with HIV, who are on HAART. In this cross-sectional study, we studied children, aged ten months to 17 years, infected with HIV, attending the pediatric HIV clinics of the University of Benin Teaching Hospital. Demographic and clinical data were obtained by parental interview as well as from the medical records. Each child's urine was tested for albumin and microalbuminuria using multi test strips and mitral test strips, respectively. The serum creatinine level of each child was also estimated and used in calculating the glomerular filtration rate (GFR). Renal disease was defined as the presence of significant proteinuria of 1+ and above on dipstick or the presence of microalbuminuria of ≥20 mg and/or GFR <60 mL/min/1.73 m 2 . Of the 99 children recruited, 60 were males and 39 were females. The mean age of the children was 6.6 ± 3.5 years. All the children were on HAART and 85% had acquired the HIV infection by vertical transmission. The overall prevalence of renal disease was 16.2%. Microalbuminuria was seen in 11 children with renal disease (11.1%); 3 of them had significant proteinuria. GFR of less than 60 mL/min/1.73 m 2 was seen in five children (5.1%) with renal disease, but none had end-stage renal disease (GFR less than 15 mL/min/1.73 m 2 ). Renal disease was found to be significantly associated with advanced stage of HIV infection (P < 0.049). Our study showed that t he prevalence of renal disease in HAART-treated Nigerian children is high and majority of them are asymptomatic of renal disease, but in the advanced stages of HIV infection.

How to cite this article:
Iduoriyekemwen NJ, Sadoh WE, Sadoh AE. Prevalence of renal disease in Nigerian children infected with the human immunodeficiency virus and on highly active anti-retroviral therapy. Saudi J Kidney Dis Transpl 2013;24:172-7

How to cite this URL:
Iduoriyekemwen NJ, Sadoh WE, Sadoh AE. Prevalence of renal disease in Nigerian children infected with the human immunodeficiency virus and on highly active anti-retroviral therapy. Saudi J Kidney Dis Transpl [serial online] 2013 [cited 2019 Oct 23];24:172-7. Available from: http://www.sjkdt.org/text.asp?2013/24/1/172/106364

   Introduction Top


The human immunodeficiency virus (HIV) affects virtually every organ system in the body, including the kidneys. [1],[2] Most of the HIV-related renal diseases reported in children manifest as chronic kidney disease (CKD). [3],[4],[5] Isolated cases of nephrotoxicity have also been reported with almost all highly active anti-retroviral therapy (HAART) agents. [6]

There is paucity of information on the prevalence of renal involvement in HIV-infected Nigerian children. In the only study on Nigerian children, [7] a prevalence of 13.3% was reported.

The use of HAART is known to reduce morbidity and mortality in HIV-infected children. [8],[9] With the recent improved access to HAART and expected longer survival among HIV-infected Nigerian children, it is possible that the long-term complications of renal toxicity would increase. This prompted us to study the prevalence of renal disease among HIV-infected Nigerian children who are on HAART.


   Subjects and Methods Top


Study setting and subjects

This descriptive cross-sectional study was carried out in the pediatric HIV/AIDS clinics of University of Benin Teaching Hospital (UBTH), Benin City, from October to December 2009. The pediatric HIV/AIDS clinics is one of the President's Emergency Plan For AIDS Relief (PEPFAR) sites where general and pediatric care of HIV/AIDS patients, including anti-retroviral therapy (ART) are provided free.

The study subjects were consecutive children aged ten months to 17 years, attending the pediatric HIV/AIDS clinics. Confirmation of HIV was done by DNA polymerase chain reaction (PCR) in children younger than 18 months, and by serology for children older than 18 months and who had been on HAART for at least one month. Children who were febrile, those with complaints suggestive of symptomatic urinary tract infection (UTI), such as dysuria, loin pain, supra-pubic pain, frequency, and urgency, those with pre-existing renal disease not related to HIV infection, and those who were positive for hepatitis B surface antigen (HBsAg) and antibody to hepatitis C virus (HCV) were excluded.

Data collection

Ethical clearance was obtained from university ethics committee. Verbal parental consent as well as assent from children older than ten years was obtained for all subjects. Data on age, gender, socioeconomic class of the family (derived using the method described by Olusanya et al), [10] possible route of acquisition of the HIV infection, the presence of tuberculosis coinfection and duration, as well as type of HAART combination were obtained. Physical examination of each child was carried out and was aimed at eliciting features suggestive of chronic kidney disease. Parameters evaluated included anthropometric measurements, blood pressure, and presence of edema and anemia. The most recent CD4 count and the World Health Organization (WHO) clinical stage [11] of the subjects at enrollment into the treatment program were obtained from their medical records.

Laboratory workup

Each child was instructed to pass urine into a sterile universal bottle and urinalysis was carried out for each specimen using Combi 10 multi test strips. In the same urine sample, the presence of microalbuminuria was determined using mitral test strips. Five milliliters of blood was obtained from each child for the estimation of packed cell volume (PCV) and serum creatinine levels. The obtained serum creatinine was used to determine the glomerular filtration rate (GFR) by the Schwartz formula. [12]

Renal disease was defined as the presence of significant proteinuria of 1+ and above on dipstick or presence of microalbuminuria of ≥20 mg and/or GFR <60 mL/min/1.73 m 2 .


   Statistical Analysis Top


Data were analyzed using Statistical Package for Social Sciences (SPSS) version 16. Chi-square test was used to assess the association between variables and student's t-test was used to compare means. Level of significance was set at P values less than 0.05.


   Results Top


Characteristics of the study group

One hundred HIV-positive children met the criteria for the study, but only 99 of the recruited children were analyzed, as data were incomplete for one child. Among these children, there were 60 males (60.6%) and 39 females (39.4%), giving a male to female ratio of 1.5:1. The mean age of the children was 6.6 ± 3.5 years (range ten months-17 years). Children younger than six years constituted 47.4% of the study population, while children aged six-12 years and those older than 12 years constituted 40.4% and 12.1%, respectively. Socioeconomic class was computed for only 67 children who had complete data. Of these, 28.4% were from the upper social class, 16.4% from middle social class, and 55.2% were from lower social class. Majority of the children acquired the HIV infection by vertical transmission [Table 1]. All the children were receiving HAART. Eighty-eight (88.9%) study subjects had received the ART for less than five years, while 11 (11.1%) had been on the therapy for longer than five years.
Table 1. Clinical characteristics of the children with or without renal disease.

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Subjects with renal disease

There were 16 children (16.2%) (eight males and eight females) with evidence of renal disease. Microalbuminuria was present in 11 (11.1%) of these children. Three of the children also had significant proteinuria. GFR was less than 60 mL/min/1.73 m 2 in five children (5.1%), but none were in end-stage renal disease (ESRD; GFR less than 15 mL/min/1.73 m 2 ). None of the children with low GFR had micro-albuminuria or significant proteinuria.

The age of the study children ranged from 1.5 to 17 years with a mean of 7.5 ± 3.9 and a median age of 6.6 years. Renal disease was more prevalent in children aged six -12 years [9 (56.2%)], followed by the age-group younger than six years [5 (31.5%)] and was least in those older than 12 years [2 (12.5%)]. Only ten of the children with renal disease had complete data for determining socioeconomic class; two (12.5%) were from the upper social class, one (6.2%) was from the middle social class, while the remaining seven (43.8%) were from the lower social class.

Most of the children with renal disease acquired the HIV infection by vertical transmission [Table 1]. All the studied children were on HAART which consisted of three anti-retroviral drugs. Majority of the children with renal disease [15 (93.8%)] were on first-line HAART regimen which consisted of Nevirapine, Stavudine or Zidovudine, and Lamivudine, or Lamivudine, Zidovudine, and Efavirenz. Only one child was on second-line regimen of Lamivudine, Zidovudine, and Lopinavir/Ritonavir. Fourteen (87.5%) of the children with renal disease had been on HAART for a duration less than five years, while two (12.5%) had been on the therapy for longer than five years.

Clinically, none of the children with renal disease had symptoms suggestive of renal disease. Their blood pressure measurements were normal; systolic blood pressure (SBP) ranged between 60 and 110 mmHg (mean ± SD 87.9 ± 14.1 mmHg), while diastolic blood pressure (DBP) ranged from 30 to 80 mmHg (mean ± SD 57.0 ± 15.3 mmHg). These readings were not significantly different from the blood pressure of patients without renal disease (P = 0.447 and 0.594, respectively, for SBP and DBP). The body mass index (BMI) of the children ranged from 14 to 19 kg/m 2 (mean ± SD 15.6 ± 1.4 kg/m 2 ); this was not significantly different from the BMI of patients without renal disease (P = 0.326). Using the WHO clinical staging of the HIV disease at enrollment into the treatment program, majority of the children with renal disease [11 (68.8%)] were in the advanced stages of the HIV disease (stages 3 and 4), 3 (18.8%) were in stage 2 while two (12.5%) were in stage 1 of the disease. Renal disease was found to be significantly (P <0.049) associated with advanced stage of HIV infection. However, 14 (87.7%) of the children with renal disease had CD4 count greater than 350 cells/mL. Only two children had marked reduction in CD4 count of ≤200 cells/mL, which suggests severe immunodeficiency, in association with advanced HIV disease. The mean and standard deviation of PCV was 34 ± 3.6%, with a range of 29-40%. Only three children had a PCV below 30%, which is indicative of anemia.

The clinical and laboratory characteristics of children with renal disease were similar to those without renal disease [Table 1].


   Discussion Top


The prevalence of renal disease (16.2%) in this study is higher than in studies carried out on children infected with HIV in the United States in the pre-HAART era, which documented a prevalence of 7-9%. [3],[13] It is also higher than the finding of Esezobor et al in their study conducted in Lagos, Nigeria, among HIV-infected children not on HAART. [7] It is, however, similar to that of Chenuy and co-workers in China, who reported a prevalence of renal disease of 16.8% in HIV- infected adults who were on HAART. [14] Differences in the criteria for defining renal disease in the various studies may have accounted for the differences in prevalence. In this study as well as the Chinese study, [14] renal disease was defined as the combination of presence of proteinuria, i.e. (macro or microalbuminuria), and reduced GFR below 60 mL/min/1.73 m 2 , as recommended by the National Kidney Foundation. [15] In contrast, the Lagos study [7] used only the GFR derived from the Cystatin C-based formula, which has been argued to be more accurate than the GFR derived from the widely used creatinine-based formula because it is less affected by non-glomerular factors such as lean mass, diet, and tubular secretion. However, using reduced GFR alone as a criterion for renal disease does not give the true prevalence of renal disease because proteinuria, which is a marker of glomerular disease, can be present with normal GFR. Also, reduced GFR (an indicator of nephron loss) can occur in the absence of proteinuria. In the work of Chenuy et al, [14] among 322 adults, 14 (4.3%) had a GFR <60 mL/min/1.73 m 2 , 40 (12.4%) had proteinuria, while only eight (2.5%) had a combination of both. Similar findings were also reported by Szczech et al [16] and also in this study.

The male:female ratio of the children with renal disease in this study was equal, This is in contrast to majority of other studies, [13],[14],[15],[16],[17],[18] where there is usually a male preponderance. However, equal male:female ratio also has been reported previously. [7],[19]

The median age of 6.6 years among the children infected with HIV with renal disease in this study is comparable to the Lagos study [7] with a median age of 5.5 years and a Jamaican study [17] (five years). The finding that renal disease was more prevalent in the younger age-group children who were on HAART is surprising, as renal disease in HIV is generally viewed as a late complication, which is therefore expected at a much older age. This finding may be because most of the study children acquired the infection by vertical transmission. It is possible that acquisition of HIV at a time when the kidneys are still developing may predispose to renal disease earlier than that observed in adults.

Clinically, none of the children had symptoms indicative of renal disease, with normal blood pressure and PCV, thus suggesting that the children were in the asymptomatic stage of renal disease. This correlates well with the finding that majority of the children with renal diseases had microalbuminuria, which is an early marker of glomerular dysfunction. This underscores the need for routine screening of all children infected with HIV for latent renal damage.

In this study, renal disease was significantly associated with advanced stage of the HIV disease adjudged by the WHO HIV clinical staging. This is consistent with the findings in the literature. [14],[16],[19],[20],[21] However, majority of the studies used the immunological criteria rather than clinical. In the reports of Chenuy et al, [14] Winston et al, [20] and Szczech et al, [22] renal disease was significantly associated with severe immunodeficiency (CD4 count <200 cells/mL). This was, however, not observed in our study. The reason for this difference may be effective adherence to ART, which we believed was suppressing the viral load, and hence, the higher CD4 count. Viral load estimation was not done and constitutes a limitation in our study.

This study reveals that the prevalence of renal disease in HAART-treated Nigerian children is high and majority of those with the disease, although asymptomatic, were in the advanced stages of HIV infection. It is therefore important that early detection of renal damage, in the asymptomatic stage, is made in order to institute measures early, which may reverse or slow down the progression of kidney disease to ESRD. This may be the most significant preventive strategy, especially as facilities for renal replacement care are limited and expensive in resource-poor countries.

 
   References Top

1.Bruggeman LA, Ross MD, Tanji N, et al. Renal epithelium is a previously unrecognized site of HIV-1 infection. J Am Soc Nephrol 2000;11:2079-87.  Back to cited text no. 1
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2.Ray PE, Liu XH, Henry D, et al. Infection of human primary renal epithelial cells with HIV-1 from children with HIV-associated nephropathy. Kidney Int 1998;53:1217-29.  Back to cited text no. 2
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3.Connor E, Gupta S, Joshi V, et al. Acquired immunodeficiency syndrome associated renal disease in children. J Pediatr 1988;113:39-44.  Back to cited text no. 3
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4.Strauss J, Abitbol C, Zilleruelo G, et al. Renal disease in children with the acquired immuno-deficiency syndrome. N Engl J Med 1989;7: 625-30.  Back to cited text no. 4
    
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6.Winston J, Deray G, Hawkins T, Szczech L, Christina W, Benjamin Y. Kidney disease in patients with HIV infection and AIDs. Clin Infect Dis 2008;47:129-37.  Back to cited text no. 6
    
7.Esezobor CI, Iroha E, Oladipo O, et al. Kidney function of HIV-infected children in Lagos, Nigeria: using Filler's serum cystatin C- based forumular. J Int AIDS Soc 2010;13:17.  Back to cited text no. 7
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8.McConnell MS, Byers RH, Frederick T, et al. Trends in Antiretroviral Therapy Use and Survival Rates for a Large Cohort of HIV-Infected Children and Adolescents in the United States, 1989-2001. J Acquir Immune Defic Syndr 2005;38:488-94.  Back to cited text no. 8
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9.ánchez GJ, Ramos AJ, Sira Fernández D, et al. Impact of highly active antiretroviral therapy on the morbidity and mortality in Spanish human immunodeficiency virus-infected children. Pediatr Infect Dis J 2003;22: 863-68.  Back to cited text no. 9
    
10. Olusanya O, Okpere E, Ezimokai M. The importance of social class in voluntary fertility control in a developing country. West Afr J Med 1985;4:205-12.  Back to cited text no. 10
    
11.WHO. HIV/AIDS Programme. WHO case definition of HIV for surveillance and revised clinical staging and immunological classification of HIV-related disease in adults and children. Available from: http://www.who.int/hiv/pub/guidelines/HIVstaging150307.pdf [Last assessed on 2011 May 18].  Back to cited text no. 11
    
12.Schwartz GJ, Haycock GB, Edelmann CM, Spitzer A. A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 1976; 58:259-63.  Back to cited text no. 12
    
13.Ingulli E, Tejani A, Fikrig S, Nicastri A, Chen CK, Pomrantz A. Nephrotic syndrome associated with acquired immunodeficiency syndrome in children. J Pediatr 1991;119:710-6.  Back to cited text no. 13
    
14.Cheung CY, Wong KM, Lee MP, Liu YL, Heidi K, Chung R. Prevalence of chronic kidney disease in Chinese HIV-infected patients. Nephrol Dial Transplant 2007;22:3186-90.  Back to cited text no. 14
    
15.Levey AS, Coresh J, Balk E, et al. National Kidney Foundation practice guidelines for chronic kidney disease: Evaluation, classification, stratification. Ann Intern Med 2003; 139:137-47.  Back to cited text no. 15
    
16.Szczech LA, Menezes P, Byrd Quinlivan E, van der Horst C, Bartlett JA, Syetkey LP. Microalbuminuria predicts over proteinuria among patients with HIV infection. HIV Med 2010;11:419-26.  Back to cited text no. 16
    
17.Steel-Duncan J, Miller M, Pierre RB, et al. Renal manifestations in HIV-infected children. West Indian Med J 2008;57:246-51.  Back to cited text no. 17
    
18.Agaba EI, Agaba PA, Sirisena ND, Anteyi EA, Idoko JA. Renal disease in the acquired immunodeficiency syndrome in north central Nigeria. Niger J Med 2003;12:3.   Back to cited text no. 18
    
19.Emem CP, Arogundade F, Sanusi A, Adelusola K, Wokoma F, Akinsola A. Renal disease in HIV-seropositive patients in Nigeria: An assessment of prevalence, clinical features and risk factors. Nephrol Dial Transplant 2008;23: 741-6.  Back to cited text no. 19
    
20.Winston JA, Klotman ME, Klotman PE. HIV-associated nephropathy is a late, not early, manifestation of HIV-1 infection. Kidney Int 1999;55:1036-40.   Back to cited text no. 20
    
21.Mocroft A, Kirk O, Gatell J, et al. Chronic renal failure among HIV-infected patients. AIDS 2007;21:1119-27.  Back to cited text no. 21
    
22.Szczech LA, Gange SJ, van der Horst C, et al. Predictors of proteinuria and renal failure among women with HIV infection. Kidney Int 2002;61:195-202.  Back to cited text no. 22
    

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Correspondence Address:
Nosakhare J Iduoriyekemwen
Department of Child Health, University of Benin/University of Benin Teaching Hospital, P.M.B. 1111, Benin City
Nigeria
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DOI: 10.4103/1319-2442.106364

PMID: 23354220

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    Abstract
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