Prevalence of persistent microalbuminuria and associated factors among HIV infected children attending a Tertiary Hospital in Northern Tanzania: a cross sectional, analytical study

Introduction Human Immunodeficiency Virus (HIV) infection is a significant cause of paediatric morbidity and mortality especially in Sub-Saharan Africa. It affects the kidney by injuring the glomerular and tubular epithelial cells causing leakage of albumin in urine. Microalbuminuria is known to be an early indicator of kidney injury including HIVAN. The purpose of this study was to identify the prevalence and factors associated with microalbuminuria among HIV infected children receiving care and treatment at Kilimanjaro Christian Medical Centre (KCMC). Methods We conducted a cross sectional hospital based analytical study at KCMC from December 2012 to April 2013. It involved children who are HIV infected attending child centred family care clinics (CCFCC). Patients’ demographic and clinical characteristics were extracted from the file; physical examination performed. Urine samples were analysed for by HemoCue Albumin 201 system analyzer. Statistical package for social sciences (SPSS) version 16.0 was be used to process and analyze the data. Results Three hundred thirty HIV-infected children under 18 years were recruited during the study period. Mean age was 119.4 (5-218) months. Prevalence of microalbuminuria by using HemoCue Albumin 201 analyzer was 28.8% (n = 95). Presence of microalbuminuria was significantly associated with severity of HIV disease progression according to WHO disease stage (p = 0.0015) and CD4 count less than 350 cells/µL (p = 0.044). Conclusion The study has shown that microalbuminuria is common in HIV infected children. Early screening and treatment of microalbuminuria is important to minimize the risk of developing end stage kidney disease. Children with advanced HIV disease and those with CD4 count less than 350cells/µL should be given priority for urinary albumin screening in a setting without routine screening for microalbuminuria.


Introduction
Human Immunodeficiency Virus (HIV) infection is a significant cause of paediatric morbidity and mortality [1]. Almost 90% of all children living with HIV are in Sub-Saharan Africa [1]. In 2011, there were 1.9 million new infections, of which 390,000 were children under 15 years, while there were 2.1 million deaths, of which 250,000 were children, which was 20% fewer than in 2005 [1]. Tanzania has been hit by the AIDS pandemic although the current estimates are beginning to show a decline in prevalence from 5. Studies have shown an association between HIV infection and development of renal diseases, both in adults and children [5][6][7].
This warrants a close follow up and monitoring of these children before they develop End Stage Renal Disease (ESRD) since renal diseases are indolent and need time for progression [8]. Chronic kidney diseases are not so common in children and the true prevalence is currently unknown, therefore their management is not getting enough attention [9]. Childhood human immunodeficiency virus-associated nephropathy (HIVAN) is defined by the presence of proteinuria associated with mesangial hyperplasia or global-focal segmental glomerulosclerosis and microcytic transformation of renal tubules [7]. Genetic susceptibility has being implicated in enhancing the risk of HIVAN development and it has been shown that black race is the most affected group, commonly presenting with focal segmental glomerulosclerosis [10,11]. Linkage studies have found genetic susceptibility loci for developing microalbuminuria and HIVAN on chromosomes 3q, 10q and 18q [12]. A polymorphism in the gene for angiotensin II type 1 (AT1) receptor located at chromosome 3q21-25 has been found to be associated with both diabetic and non-diabetic associated nephropathy [13]. Studies have linked the presence of glomerulosclerosis and genetic variants in the MYH9 gene located in the long arm of chromosome 22 [10,14,15].
According to a report from the US Renal Data System, HIVAN had the strongest association with black race in all causes of renal failure among patients who were on maintenance dialysis [13][14][15].
If all HIV infected children are screened for HIVAN and appropriate management instituted, there is a possibility of preventing ESRD in these children [8]. Microalbuminuria defined as urinary albumin excretion between 30 to 300mg/day [16,17], is known to be an early marker of HIVAN but it is often undetected because it remains asymptomatic [18,19]. The prevalence of microalbuminuria varies from region to region and within regions, e.g. in the USA it ranges from 11% [20] to 34% [21] and Africa from 12% [22] to 72% [23].
In Tanzania The clinical examination findings were recorded in a pretested case report form including WHO clinical stage, weight, height, blood pressure and ART status. Blood was sent to the laboratory for CD4 percentage for the children less than 5 years and CD4 count for those aged 5 years and above whose most recent CD4 count was done more than 6 months ago with flow cytometry and expressed in Advanced HIV disease was defined as WHO clinical stage 3 and 4, while stage 1 and 2 was defined as nonadvanced.
Immunosuppression was defined as CD4 count less than 350 cells/µL in children aged 5 years and above, and for those below age 5 years a CD4 percentage less than 25.
Results were analyzed using statistical package for social sciences (SPSS) version 16

Results
Three hundred and forty HIV-infected children aged up to 17 years were recruited during the study period. Ten children were excluded: four started anti-tuberculosis treatment and six were not available to provide the second urine specimen. Three hundred and thirty HIV   [29]. Advanced HIV disease was found in this study to be significantly associated with microalbuminuria in children. Similar findings have been shown by other authors [24][25][26]. This can be explained by the fact that as the disease advances there is profound immunity suppression favouring unchecked viral replication and hence kidney involvement.
Using HAART was not influencing the occurrence of microalbuminuria. This was also observed by other researchers [30][31][32][33][34]. Apparently kidneys may act as reservoir for HIV and even at suppressed viral load, HIV can still induce kidney damage. It can also be explained by the presence of other intrinsic factors like genetic predisposition shown to be associated with the occurrence of kidney diseases but not assessed in this study [10][11][12][13][14]. We screened the presence of urine albumin in more than one urine sample taken at least one month apart to define microalbuminuria.
This helped to exclude the possibility of transient microalbuminuria which is common in young age.
There were some limitations. We did not limit physical exercise 24 hour before urine collection and this could have had an effect on microalbuminuria especially in lean adolescents. Viral load was not tested in all children and therefore it was not possible to establish the association between viral load and the presence of microalbuminuria. Renal biopsy was not preformed and therefore in

Competing interests
The authors declare no competing interests.  Table 1: clinical characteristics of the study population (n=330)