Saudi Journal of Kidney Diseases and Transplantation

RENAL DATA FROM ASIA - AFRICA
Year
: 2013  |  Volume : 24  |  Issue : 6  |  Page : 1291--1297

Renal function, urinalysis abnormalities and correlates among HIV-infected cameroonians naive to antiretroviral therapy


Francois FolefackKaze1, Andre-Pascal Kengne2, Eric Walter PefuraYone3, Nelly Sandra NdamFemben4, Gloria Ashuntantang1,  
1 Department of Internal Medicine and Specialties, Faculty of Medicine and Biomedical Sciences, University of Yaoundé 1, Department of Internal Medicine, Yaoundé General Hospital, Yaoundé, Cameroon
2 South African Medical Research Council and University of Cape Town, Cape Town, South Africa
3 Department of Internal Medicine and Specialties, Faculty of Medicine and Biomedical Sciences; Chest Unit of Yaoundé Jamot Hospital, University of Yaoundé 1, Yaoundé, Cameroon
4 Faculty of Medicine and Biomedical Sciences, University of Yaoundé 1, Yaoundé, Cameroon

Correspondence Address:
Francois FolefackKaze
Department of Internal Medicine, Yaoundé General Hospital, P.O. Box 33127 Yaoundé
Cameroon

Abstract

As per guidelines and recommendations, screening for renal diseases should be performed at the time of diagnosis of human immuno-deficiency virus (HIV) infection; however, this remains largely unimplemented in many settings across Sub-Saharan Africa. We evaluated the renal function, urinalysis abnormalities and their correlates in HIV-infected individuals who were naïve to highly active antiretroviral therapy (HAART). This was a cross-sectional study of 2 months«SQ» duration involving 104 HIV-infected outpatients naive to HAART (71 women, 68%) attending the HIV clinic of the Yaoundé General Hospital in Cameroon. Renal and urinalysis parameters were measured and the Student t-test and Fischer exact test were used to compare the groups of participants. The mean age and CD4 count were, respectively, 35 ± 10.7 years and 305 ± 202/mL. Fifty-six (54%) patients presented with stages 3 and 4 of HIV infection. Forty-three (41%) patients had urinalysis abnormalities, including proteinuria (36%), leukocyturia (13%) and hematuria (12%). Proteinuria was associated with increased age, advanced stage of HIV infection, decreased CD4 count, hematuria and renal failure (P <0.04). Hematuria and leukocyturia were associated with decreased CD4 count and advanced stage of HIV infection, respectively (P = 0.04). The mean estimated glomerular filtration (eGFR) rate was100.2 ± 32.7 mL/min; three (3%) patients had renal failure (eGFR <60 mL/min) and 45 (43%) patients had reduced kidney function 60 ≤eGFR ≤90 mL/min. There was a high prevalence of decreased kidney function and proteinuria among Cameroonian HIV-infected patients naïve to HAART. Indicators of the severity of HIV infection, including advanced stage and low CD4 count, were associated with urinalysis abnormalities.



How to cite this article:
FolefackKaze F, Kengne AP, PefuraYone EW, NdamFemben NS, Ashuntantang G. Renal function, urinalysis abnormalities and correlates among HIV-infected cameroonians naive to antiretroviral therapy.Saudi J Kidney Dis Transpl 2013;24:1291-1297


How to cite this URL:
FolefackKaze F, Kengne AP, PefuraYone EW, NdamFemben NS, Ashuntantang G. Renal function, urinalysis abnormalities and correlates among HIV-infected cameroonians naive to antiretroviral therapy. Saudi J Kidney Dis Transpl [serial online] 2013 [cited 2019 Aug 17 ];24:1291-1297
Available from: http://www.sjkdt.org/text.asp?2013/24/6/1291/121280


Full Text

 Introduction



During the course of human immuno-deficiency virus (HIV) infection, several organs are involved both as the result of a natural history of HIV infection and opportunistic affections as well as from the treatments given. The spectrum of kidney diseases associated with HIV infection is broad, affecting all parts of the kidney, resulting from the direct effects of HIV and/or other reasons. It presents as acute kidney injury or chronic kidney disease, with an estimated prevalence in Sub-Saharan Africa (SSA) ranging from 6% to 48.5%. [1] These include HIV-associated nephropathy (HIVAN), HIV-immune complex-mediated glomerulonephritis (post-infectious glomerulonephritis, membranous nephropathy, IgA nephropathy, fibrillary glomerulonephritis, immunotactoidglomerulopathy and membranoproliferative glomerulonephritis), HIV-associated thrombotic microangiopathy, infectious and non-infectious interstitial nephritis and electrolyte and acid-base disturbances. [1] The prevalence of dipstick urinary abnormalities ranged from 30% to 44% in HIV-infected patients naive to highly active antiretroviral therapy (HAART), while 3.5-4.7% present with renal failure. [2],[3],[4] The prevalence of HIVAN, the leading kidney complication of HIV infection, has been estimated to range from 3.5-12% in the USA. [5] The importance of kidney involvements during HIV infection was recognized by the World Health Organization (WHO), who in 2006 adopted HIVAN as a criterion for its clinical staging of HIV infection. [6] Based on the WHO 2006 classification, HIV-infected patients with HIVAN are graded at stage 4 and are therefore eligible for HAART initiation, regardless of CD4 count. [6]

Despite the guidelines and recommendations of screening individuals for kidney diseases via urinalysis and estimation of renal function at the time of their diagnosis with HIV infection, renal investigations are not systematically performed in many SSA countries with a high prevalence of HIV infection. [7],[8],[9] Therefore, the opportunity of early detection of kidney involvement and implementation of disease prevention or modifying therapies to reduce the long-term impact is being missed in many settings. Quantitative data on the magnitude of renal diseases in HIV-infected patients naïve to HAART may aid to project the potential impact or early renal screening in this population, but such evidence remains very scanty in some regions in Africa. [2],[10],[11]

We assessed the kidney function, the prevalence of urinalysis abnormalities and their correlates among Cameroonian adult HIV-infected patients naïve to HAART.

 Materials and Methods



This was a cross-sectional study of 2 months' duration from December 2009 to January 2010, conducted at the HIV clinic of the Yaoundé General Hospital (YGH). The YGH has been described in detail previously. [12],[13] The HIV clinic of this hospital was established in 2001. In 2009, the clinic provided care to about 4500 patients and, in the same year, about 40 new cases of HIV infection were diagnosed per month. The staff of the clinic includes a multidisciplinary team of specialists of internal medicine, several general practitioners and qualified nurses who regularly follow HIV-infected patients of all ages and sex, giving a good representation of the national HIV-infected population. This study received administrative authorization from the national ethics committee and participants provided their informed consent.

Data collection

We included all newly diagnosed HIV-infected patients naive to HAART aged 15 years and above who attended the HIV clinic during the study period. All patients with the following signs suggestive of urinary tract infection were excluded from the study: (1) the presence of nitrites and leukocytes associated or not associated with the presence of bacteria or epithelial cells on urinalysis and clinical symptoms of cystitis or (2) the presence of clinical symptoms of cystitis associated with leukocytes and epithelial cells with or without the presence of nitrites and bacteria on urinalysis. Patients with signs of any active infection and those with conditions that could interfere with the interpretation urinalysis or renal function tests (such as viral hepatitis B or C, diabetes mellitus, joint inflammatory diseases, systemic lupus erythematosis, sickle cell disease or urinary stone) were also excluded from the study. Clinical and laboratory data for each patient were recorded using a pre-designed questionnaire. General individual information included age and gender. Clinical data including the past medical history, stage of HIV infection (2006 WHO classification [6] ), ongoing treatment and history of tobacco and drug or alcohol abuse were recorded. Urinary and blood biological parameters, including urinary dipstick and sediment, serum creatinine and CD4 count, were also recorded. Urinary dipstick tests were performed with CombiScreen 7SL PLUS 7 test strips (Analyticon Biotechnologies AG, D-35104 Lichentenfeis, Germany). Urinary pH, specific gravity and glucose were not taken into consideration for the purpose of the study. Urinalysis followed the guidelines. [14] Serum creatinine was analyzed with a kinetic modification of the Jaffé reaction using a Beckman creatinine analyzer (Beckman CX Systems Instruments, Anaheim, CA, USA). All specimens were analyzed in the YGH laboratory in respect of routine practice.

Definitions and calculations

Stages 3 and 4 of HIV infection, based on the 2006 WHO classification, [6] were considered advanced stages of HIV infection. The national guidelines in force at the time of the study [8] were used to rank participants into three groups according to their CD4 count: Less than 200/ mm 3 (indication of HAART), more than 350/ mm 3 (no indication of HAART) and between the two values (indication of HAART depending on the clinical condition or comorbidities). The estimated glomerular filtration rate (eGFR; mL/min) was the average of the predicted values from the modification of diet in renal disease (MDRD) study equation (four-variable equation) and the Cockcroft - Gault formula. [15],[16] The diagnosis of proteinuria was based on a urinary dipstick of at least 1+; meanwhile, hematuria and leukocyturia were diagnosed using urinary dipstick and sediment. The type of microscopic hematuria was not specified.

 Statistical Analysis



Statistical analysis used the SPSS ® 17 software for Windows (SPPS Inc., Chicago, IL, USA). We have reported the results as mean (standard deviation, SD) and count (percentages).

Group comparisons used the Student t-test and equivalents for quantitative variables and the Fischer exact test or the Freeman-Halton extension of the Fisher exact test for qualitative variables, as appropriate. [17] The level of significance was set at P <0.05.

 Results



Study population

A total of 104 patients were recruited in the study, including 71 (68%) women. Their age ranged from 16 to 61 years, with a mean of 35 (SD = 10.7) years, and women were younger than men (34 years vs. 43 years, P <0.001). The sex-specific profile of the participants is summarized in [Table 1]. Fifty-six (54%) patients presented with an advanced stage of HIV infection. The CD4 count ranged from 4 to 730/mL, with a mean of 305/mL (SD = 202). The CD4 count was less than 200/mL in 22 (21%) patients. The levels of the other clinical and biological characteristics were similar in men and women.{Table 1}

Urinalysis profile, kidney function and associated factors

Forty-three (41%) patients presented with urinalysis abnormalities [Table 1], including proteinuria (36%), leukocyturia (13%) and hematuria (12%). As presented in [Table 2], proteinuria was significantly associated with increasing age (P = 0.002), advanced stage of HIV infection (P = 0.003), decreased CD4 count (P = 0.02), hematuria (P <0.0001) and renal failure (P = 0.04). Hematuria and leukocyturia were significantly associated with decreased CD4 count (P = 0.002) and advanced stage of HIV infection (P = 0.04), respectively. The eGFR from the mean value of the two formulas ranged from 37 to 135 mL/ min, with a mean of 100.2 mL/min (SD = 32.7), [Table 1]. Three (3%) patients had renal failure (eGFR <60 mL/min) and 45 (43%) patients had reduced kidney function (60 ≤eGFR ≤90 mL/min). Proteinuria was the only factor that was associated with renal failure (P = 0.04).{Table 2}

 Discussion



Our study revealed a high prevalence of decreased kidney function and urinalysis abnormalities among HIV-infected patients naïve to HAART in our study population. These urina-lysis abnormalities observed were associated with advanced stage of HIV infection, decreased CD4 count and renal failure, mostly in line with the reports from other settings. [1],[2],[3],[4],[10],[11],[18],[19],[20],[21]

In HIV-infected individuals, none of the available formulas to estimate renal function has yet been validated or calibrated, and they tend to be inaccurate and less reliable. [4],[7],[10],[22] To empirically circumvent these limitations, renal function was assessed in the current study using the average values of the Cockcroft-Gault and MDRD estimations of kidney function. As reported in the literature, we observed that nearly one in two patients presented with decreased renal function, of whom 3% had renal failure. [3],[10],[20],[23] Renal failure was associated with proteinuria; meanwhile, decreased CD4 count and advanced stage of HIV infection were not determinants of renal failure in this study as reported elsewhere. [10],[11],[20],[22] These differences were likely explained by the limited statistical power because of the small size of our sample.

Proteinuria was the leading urinary abnormality, and was associated with advanced age and stage of HIV infection, decreased CD4 count, hematuria and renal failure. A similar prevalence and associated factors have been reported elsewhere. [7],[10],[11],[18],[19] The diagnosis of proteinuria at microalbuminuria stage, the hallmark of HIVAN, may aid the early detection of kidney involvement and implementation of disease-modifying therapies such as initiation of HAART that have shown some benefits on proteinuria and kidney function. [6],[21],[22]

Hematuria and leukocyturia were the other common urinalysis abnormalities, and were associated with decreased CD4 count and advanced stage of HIV infection. A higher prevalence of such abnormalities reported elsewhere could be due to the presence of confounding factors. [2],[19],[24] Urologic evaluation of asymptomatic hematuria in HIV-infected patients with normal renal function and free of any history of urologic condition has revealed a congestive mucosa that can be linked to viral replication in the urothelial cells and absence of tumor, and less than 1% of the patients needed an appropriate treatment. [24] This has prompted recommendations against urologic examination of HIV patients with microscopic hematuria and normal kidney function. [24]

The present study has some limitations. The small sample size precluded reliable investigation of some of the studied questions as well as performing multiple regressions analysis to test the robustness of some of our findings to make adjustments for possible confounders. It is also possible that the absence of an association of some predictors with the study outcomes in the univariables analysis was just a reflection of the limited statistical power. We did not screen patients with normoalbuminuria on dipstick for microalbuminuria, which is the early manifestation of HIVAN. [21] However, the higher prevalence of decreased renal function and urinalysis abnormalities revealed by this study highlights the need for a strict implementation of the guidelines and recommendations to screen for renal disease at the time of diagnosis of HIV infection in our settings.

In conclusion, this study revealed the high prevalence of kidney function alterations and urinalysis abnormalities as well as other potential determinants in people with HIV infection naive to antiretroviral therapies in a set up like ours. Our findings, largely in line with the reports from other parts of Africa and elsewhere, emphasize the need to improve the implementation of guidelines and recommendations pertaining to renal screening in people with HIV infection. A proactive approach may help in the early detection of renal diseases and implementation of nephro-protection strategies to promote healthy survival, free of advanced stage kidney disease in our HIV-infected population.

 Acknowledgments



The authors would like to thank the medical and nursing staff of the HIV clinic at the YGH in Cameroon.

Conflict of Interest: None.

References

1Fabian J, Naicker S. HIV and kidney disease in sub-Saharan Africa. Nat Rev Nephrol 2009;5: 591-8.
2Fabian J, Naicker S, Venter WD, et al. Urinary screening abnormalities in antiretroviral-naïve HIV-infected outpatients and implications for management. A single-center study in South Africa. Ethn Dis. 2009;19(Suppl 1):S180-5.
3Mocroft A, Kirk O, Gatell J, et al. Chronic renal failure among HIV-1-infected patients. AIDS 2007;21:1119-27.
4Winston JA. Estimating glomerular filtration rate in patients with HIV infection. Semin Nephrol 2008;28:576-80.
5Ross MJ, Klotman PE. Recent progress in HIV-associated nephropathy. J Am Soc Nephrol 2002;13:2997-3004.
6World Health Organization (WHO). Programme VIH/SIDA 2006. Available from: http://www.who.int/hiv/pub/guidelines/artadult guidelines_fr.pdf. (Last accessed on 2011 Oct 25).
7Gupta SK, Eustace JA, Winston JA, et al. Guidelines for the management of chronic kidney disease in HIV infected patients: Recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis 2005;40:1559-85.
8World Health Organization (WHO). National support guide for people living with the HIV/AIDS-Cameroon. Available from: http:// www.who.int/medicines/areas/coordination/ca meroon. [Last accessed on 2011 Oct 25].
9Kengne AP, Kaze FF, Dzudie A, Awah KP, Ngu KB. HIV/AIDS occurrence in the main university teaching hospital in Cameroon: Audit of the 2001 activities of the service of internal medicine. J Int Assoc Physicians AIDS Care (Chic) 2007;6:61-5.
10Wools-Kaloustian K, Gupta SK, Muloma E, et al. Renal disease in an antiretroviral-naïve HIV-infected outpatient population in western Kenya. Nephrol Dial Transplant 2007;22: 2208-12.
11Emen 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.
12Kaze FF, Ashuntantang G, Kengne AP, Hassan A, Halle MP, Muna W. Acute hemodialysis complications in end-stage renal disease patients: The burden and implications for the under-resourced Sub-Saharan Africa health systems. Hemodial Int 2012;16:526-31.
13Halle MP, KengneAP, Ashuntantang G. Referral of patients with kidney impairment for specialist care in a developing country of Sub-Saharan Africa. Ren Fail 2009;31:341-8.
14Fogazzi GB, Verdesca S, Garigali, G. Urinalysis: Core Curriculum 2008. Am J Kidney Dis 2008;51:1052-67.
15Levey AS, Coresh J, Greene T, et al. Using standardized serum creatinine values in the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate. Ann Intern Med 2006;145:247-54.
16Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16:31-41.
17Freeman GH, Halton JH. Note on exact treatment of contingency, goodness of fit and other problems of significance. Biometrika 1951;38:141-9.
18Janakiraman H, Abraham G, Matthew M, et al. Correlation of CD4 counts with renal disease in HIV positive patients. Saudi J Kidney Dis Transpl 2008;19:603-7.
19Mortier E, Toure S, Seyler C, Bloch M, Anglaret X. Urinary pH in HIV-infected adults in Ivory Coast and in France. AIDS 2003;17:2003-5.
20Jab³onowska E, Ma³olepsza E, Wójcik K. The assessment of renal function in HIV-positive patients before the introduction of anti-retroviral therapy. HIV and AIDS review 2010 ;9:45-7.
21Han 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.
22Peters PJ, Moore DM, Mermin J, et al. Anti-retroviral therapy improves renal function among HIV-infected Ugandans. Kidney Int 2008;74:925-9.
23Mulenga LB, Kruse G, Lakhi S, et al. Baseline renal insufficiency and risk of death among HIV-infected adults on antiretroviral therapy in Lusaka, Zambia. AIDS 2008;22:1821-7.
24Cespedes RD, Peretsman SJ, Blatt SP. The significance of hematuria in patients infected with the human immunodeficiency virus. J Urol 1995;154:1455-6.