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\title{Correlates of Impaired Renal Function in Highly Active Antiretroviral Therapy (HAART) Naive HIV Infected Patients in Maiduguri, Nigeria}
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             \author[1]{Dr. Ballah Akawu  Denue}

             \author[2]{Mr. Dawurung Joshua  Shehu}

             \affil[1]{  Universit of Maiduguri Teaching Hospital, Maiduguri Borno state.}

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\date{\small \em Received: 10 August 2012 Accepted: 4 September 2012 Published: 16 September 2012}

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\begin{abstract}
        


Background : Although renal function may be abnormal in as many as 30% of HIV -1 patients even in the era of highly active antiretroviral therapy, it may not be apparent at the initial stage and laboratory tests are needed to detect it. We determined the factors associated with impaired renal function in HIV infected patient initiating highly active antiretroviral therapy in North-eastern Nigeria.Materials and Methods : This was a retrospective study among HIV-1 infected patients that presented at infectious diseases clinic at the university of Maiduguri Teaching Hospital(UMTH) for care between July 2008-March 2009. Data were analysed for age, gender, weight, height, WHO clinical stage, HIV-1 RNA viral load, HBsAg and anti-HCV antibody status. Estimated glomerular filtration rate eGFR was calculated using the Cockcroft -Gault equation.

\end{abstract}


\keywords{Highly active antiretroviral therapy, human immunodeficiency virus, correlates, serum creatinine.}

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\let\tabcellsep& 	 	 		 
\section[{Introduction}]{Introduction}\par
espite the widespread use of highly active antiretroviral therapy (HAART), HIV disease remains associated with increased kidney an often unrecognised problem as kidney function may be abnormal in up to 30\% in HIV population \hyperref[b14]{(Gupta et al.,2005;} {\ref Szczechet al.,2002)}. HIV-infected patients may HIV-associated nephropathy (HIVAN) is traditionally the most common renal lesion affecting HIVinfected patients; it is the commonest cause of end stage renal disease (ESRD), often requiring renal replacement therapy. Although HIVAN has been documented in indigenous African patients, little is known about the prevalence or risk factors for renal disease in this population \hyperref[b32]{(Winston et al., 1999;} {\ref Cosgrove et al., 2002;} {\ref Szczechet al.,2004)}.\par
The aim of this study was to determine the factors associated with impaired renal function among the patients initiating highly active antiretroviral therapy. 
\section[{II.}]{II.}\par
Patients and Method disease risk  {\ref (Phair and Palella,2011)} Kidney function can be measured by determining the glomerular filtration rate (GFR), the decrease in GFR has been shown to correlates with the severity of kidney disease. The Cockcroft-Gault equation, which estimates GFR using serum creatinine and anthropometric variables has been shown to predict renal function  {\ref (Cockcroft and Gault,1976)}. The use of this equation in assessing GFR has been validated among black HIV positive patients  {\ref (Chukwuonye,2007)}. such as Cameroon, Niger and Chad Republics. Maiduguri the capital of Borno State is situated in the north eastern Nigeria and the largest settlement near the Lake Chad.\par
Study procedure : Cross-sectional data of 415 HIV positive patients were abstracted for the purpose of this study.\par
Variable abstracted included age, gender, weight and WHO clinical stage of HIV disease. Blood samples were collected for CD4 count using standardized flow cytometricCyflow machine (manufactured by Cytec, Partec, Germany 2005). While plasma HIV RNA levels was measured using freshly frozen specimen separated within 6 hours of phlebotomy utilizing the Amplicor HIV-1 Monitor Test, version 1.5 Manufactured by Roche® Germany, with a minimum cut off value of 200 copies per ml. Enzyme linked immunosorbentassay kits was used to detect the presence of HBsAg and HCV antibodies (DIA, PRO, DiagosticBioprobes Sri, via columella no 20128 milano-Italy).\par
The estimated Glomerular Filtration Rates (eGFRs) were calculated from serum creatinine measurements using the Cockcroft Gault equation Statistical analysis : Data were analyzed using SPSS ® , version 16.0 for Windows (SPSS Inc., Chicago, IL, USA). Categorical variables were compared using Chi-square test, group means were compared the students t-test. Mann Whitney test was used to compare variables that did not follow normal distribution.\par
Factors associated with reduced eGFR (defined as <60mL/min) were tested for inclusion in a multivariate logistic regression model. A P-value of < 0.05 was considered statistically significant. 
\section[{III. Results}]{III. Results} 
\section[{a) Stratification of participants based on gender}]{a) Stratification of participants based on gender}\par
A total of 415 HIV positive, highly active antiretroviral therapy (HAART) naive patients with mean age of 43.65±9.70 (95\% CI; 42.77 -44.52), were considered for this study. Out of this 182 (43.6\%) participants were males, with a mean age of 47.43±9.00, they were older than their female counterpart that had a mean age of 40.54±9.08 (p<0.05). Female gender was associated with significantly low haemoglobin, viral load, and proportion significantly high proportion of participants infected with hepatitis B virus, while the body mass index and AIDS status between the males and females were not comparable as shown in Table On multivariate analysis, with younger age(<50 years), Hb?10g/dl,WBC?3X10 9 /l, platelets?150x10 9 /l, HIV-1RNA?100000copies/ml, no AIDS status, Normal BMI(18.5-25.0kg/m2) as a referent, it shows that older age (?50 years), anaemia (Hb<10g/dl), abnormal BMI (<18.5kg/m 2 or >25.0 kg/m 2 ) had significant associations with reducedeGFR (eGFR<60ml/min) as shown in Table  {\ref 3}.  
\section[{IV. Discussion}]{IV. Discussion}\par
Our study examined the pattern of renal impairment and its associated factors among highly active anti retroviral naive HIV infected individuals. The prevalence of renal impairment as defined by an eGFR<60 ml/min/1.73m2 among HIV patients in our cohort was 14.7\% similar to previous studies that reported a prevalence rate of 10 to 30\% \hyperref[b30]{(Weiner et al., 2002;} {\ref Szczechet al., 2004;} {\ref Winston et al., 1979)} characteristicsincluding demographic characteristics, stage of HIV infection, and access to health care services. Of note, our population was relatively young (mean age 44 years), presented at late stage of the disease.Although somehow expected, this finding of prevalence of 14.7\% in our cohort was worrisome for us. We used Cockcroft-Gaultequations to estimate glomerular filtration rate (eGFR), and since these equations can underestimate the actual GFR or creatinine clearance in patients with malnourishment or reduced muscle mass related to advance HIV, it is possible that the true prevalence of CKD in our cohorts is underestimated.\par
Table  {\ref 3} : Multivariate analysis of correlates of reduced eGFR (< 60ml/min) among HIV-infected patients. 
\section[{2004), 3\% reported in California (Crum-Cianfloneet}]{2004), 3\% reported in California (Crum-Cianfloneet}\par
This study demonstrates older age, abnormal weight (under weight or over weight/obesity) and anaemia at presentation to be independent predictors of renal impairment in our cohort. Renal function is known to decline with age. Older age is an established risk factor for a decline in creatinine clearance in the general population (Davies and Shock, 1950). Similarly, older agehas been independently associated with renal function decline among HIV-infected subjects.\par
(Mocroftet al.,2007; Cheung et al., 2007).The preponderance of renal impairment in our male cohort may be related to significantly older male than female population.\par
The mean CD4 count of 222 cells/ul in patients with normal renal function was significantly higher than 182 cells/ul in our cohort with renal impairment. This is consistent with earlier studies that reported an association between impaired renal function in HIV infected patients with significantimmuno suppression, having CD4 cell count less than 200ul/L. Immunological AIDS (CD4 count <200ul/L) is known to be associated with development of opportunistic infections, malignancies and other organ diseases that affects kidney functions. (Winston et al.,1999; Szczech et al.,  2004; Winston et al.,2001; Krawczyket al.,2004). CD4 cell had a protective role in the development of renal Reports from sub-Saharan Africa, indicated that the prevalence of decreased eGFR is high and varied substantially depending on the estimating method used  {\ref (Chukwuonye,2007;}\hyperref[b28]{Van Deventer et al.,2008;}\hyperref[b11]{Eastwood et al.,2010)}. However the use of Cockcroft-Gault equations have been validated for use as it has been shown to predicts renal function in black HIV population \hyperref[b5]{(Chukwuonye, 2007)}  
\section[{V. Limitations}]{V. Limitations}\par
This study is limited in its retrospective design, with the greater proportion of HIV-infected with AIDS with advanced clinical disease, it implies that prevalence estimates derived from this study may not be generalizable to patients with early stage of HIV infection. In addition, we were limited by the use of a single serum creatinine, hence spurious results were not excluded. Finally, there was no assessment for protenuria; however, this was the standard of care in the centre at the time of this study.  
\section[{Global Journal of}]{Global Journal of} 
\section[{Medical}]{Medical}\begin{figure}[htbp]
\noindent\textbf{}\includegraphics[]{image-2.png}
\caption{\label{fig_0}(}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{} \par 
\begin{longtable}{P{0.85\textwidth}}
undergo renal damage related to the HIV infection itself,\\
to the presence of co-infection, arterial hypertension,\\
diabetes or to the exposure to nephrotoxic drugs.\\
Consequences of kidney disease in HIV-infected\\
persons include increased risk of atherosclerosis and\\
mortality, in addition immunosuppression that is known\\
to be associated with development of opportunistic\\
infections, malignancies and other organ diseases that\\
affects kidney functions. (Choi A et al.,2010; Choi AI et\\
al.,2010).\\
highly\\
active antiretroviral therapy for effective and proper\\
management.\end{longtable} \par
  {\small\itshape [Note: Results : A total of 415 participants with mean age of 43.65±9.70 (95\% CI; 42.77 -44.52), were considered for this study. Out of this 182 (43.6\%) were males, with a mean age of 47.43±9.00, they were older than females with mean age of 40.54±9.08 (p<0.05). A total of 61(14.7\%) had an eGFR<60mL/min, with disproportionately more males (17.0\%vs 12.5\%) having eGFR<60mL/min than females (p<0.05). On multivariate analysis, older age ( ?50 years), anaemia (Hb<10g/dl), abnormal BMI (<18.5 kg/m 2 or >25.0 kg/m 2 ) had significant associations with reduced GFR. Conclusion : Older age, anaemia and abnormal weight are independently associated with risk of having impaired renal function in our cohort. We therefore recommend renal function tests to HIV infected patients at commencement of]} 
\caption{\label{tab_0}}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{1} \par 
\begin{longtable}{P{0.3\textwidth}P{0.375\textwidth}P{0.175\textwidth}}
Males(n=182)\tabcellsep Females (n=233)\tabcellsep P-value\end{longtable} \par
 
\caption{\label{tab_2}Table 1 :}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{2} \par 
\begin{longtable}{P{0.30780730897009967\textwidth}P{0.0070598006644518275\textwidth}P{0.005647840531561462\textwidth}P{0.0070598006644518275\textwidth}P{0.21038205980066446\textwidth}P{0.20473421926910298\textwidth}P{0.10730897009966776\textwidth}}
\tabcellsep \tabcellsep \tabcellsep \tabcellsep (eGFR?60mL/min)\tabcellsep (eGFR<60ml/min)\tabcellsep P-value\\
\tabcellsep \tabcellsep \tabcellsep \tabcellsep N=356\tabcellsep N=61\tabcellsep \\
\multicolumn{2}{l}{Age (years)}\tabcellsep \tabcellsep \tabcellsep 42.46±8.90\tabcellsep 49.87±11.07\tabcellsep 0.000*\\
Gender\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \\
\multicolumn{2}{l}{Male, no (\%)}\tabcellsep \tabcellsep \tabcellsep 161(83.0\%)\tabcellsep 31(17.0\%)\tabcellsep 0.000*\\
\multicolumn{2}{l}{Female, no (\%)}\tabcellsep \tabcellsep \tabcellsep 104(87.5\%)\tabcellsep 29(12.5\%)\tabcellsep 0.000*\\
\multicolumn{2}{l}{Mean Hb (g/dl)}\tabcellsep \tabcellsep \tabcellsep 11.60±2.05\tabcellsep 10.19±2.31\tabcellsep 0.000*\\
\multicolumn{2}{l}{Mean WBC}\tabcellsep \tabcellsep \tabcellsep 5.05±1.93\tabcellsep 5.68±2.90\tabcellsep 0.115\\
\multicolumn{2}{l}{Mean platelets}\tabcellsep \tabcellsep \tabcellsep 262.12±103.00\tabcellsep 251.32±113.34\tabcellsep 0.471\\
\multicolumn{3}{l}{Mean CD4 count(cells/µl)}\tabcellsep \tabcellsep 222.04±152.03\tabcellsep 182.21±105.46\tabcellsep 0.013*\\
Mean\tabcellsep viral\tabcellsep load\tabcellsep log10\tabcellsep 4.96±5.44\tabcellsep 4.97±5.27\tabcellsep 0.958\\
\multicolumn{2}{l}{(copies/ml)}\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \\
\multicolumn{2}{l}{Hepatitis C}\tabcellsep \tabcellsep \tabcellsep 3\tabcellsep 0\tabcellsep \\
\multicolumn{2}{l}{Hepatitic B}\tabcellsep \tabcellsep \tabcellsep 48(13.5\%)\tabcellsep 10(16.4\%)\tabcellsep 0.000*\\
BMI\tabcellsep \tabcellsep \tabcellsep \tabcellsep 22.77±4.48\tabcellsep 20.70±3.90\tabcellsep 0.013*\\
\multicolumn{3}{l}{AIDS status, no=231}\tabcellsep \tabcellsep \tabcellsep \tabcellsep \\
yes\tabcellsep \tabcellsep \tabcellsep \tabcellsep 193(83.5\%)\tabcellsep 38(16.5\%)\tabcellsep 0.000*\\
no\tabcellsep \tabcellsep \tabcellsep \tabcellsep 162(88.0\%)\tabcellsep 22(12.0\%)\tabcellsep 0.000*\\
\multicolumn{3}{l}{BMI (body mass index).}\tabcellsep \tabcellsep \tabcellsep \tabcellsep \\
\multicolumn{3}{l}{*Statistically significant.}\tabcellsep \tabcellsep \tabcellsep \tabcellsep \end{longtable} \par
 
\caption{\label{tab_3}Table 2 :}\end{figure}
 \begin{figure}[htbp]
\noindent\textbf{} \par 
\begin{longtable}{P{0.85\textwidth}}
ear 2012\\
Y\end{longtable} \par
 
\caption{\label{tab_6}}\end{figure}
 			\footnote{© 2012 Global Journals Inc. (US)} 			\footnote{Correlates of Impaired Renal Function in Highly Active Antiretroviral Therapy (HAART) Naive HIV Infected Patients in Maiduguri, Nigeria} 			\footnote{© 2012 Global Journals Inc. (US) © 2012 Global Journals Inc. (US) Correlates of Impaired Renal Function in Highly Active Antiretroviral Therapy (HAART) Naive HIV Infected Patients in Maiduguri, Nigeria} 		 		\backmatter  			  				\begin{bibitemlist}{1}
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\end{document}
