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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2008  |  Volume : 19  |  Issue : 4  |  Page : 603-607
Correlation of CD4 Counts with Renal Disease in HIV Positive Patients

1 Department of Medicine, Sri Ramachandra Medical College and Research Institute, Chennai, India
2 Department of Pathology, Sri Ramachandra Medical College and Research Institute, Chennai, India
3 Y.R.G. Care in Chennai, Chennai, India
4 Weill Medical College of Cornell University, New York, USA
5 Madras Medical Mission, Chennai, India

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To correlate CD 4 counts with albuminuria and glomerular lesions in patients infected with human immunodeficiency virus (HIV), we studied 104 HIV positive patients (68 males, 36 females) of whom 100 patients were infected by heterosexual contact, 3 by transfusion, and 1 by IV drug abuse. We screened over nine months for albuminuria by urine dip stick method, and performed renal biopsy on patients with albuminuria 2+ or more. Histological examination was accomplished by light microscopy in all and by electron microscopy when it was feasible. Albuminuria was observed in 29 (27%) patients, and it revealed a significant negative correlation with CD4 count (p < 0.01). Patients with CD4 cells < 350 cells/mm [3] disclosed a 3.5 fold increased risk of albuminuria as compared with patients with CD4 > 350 cells/mm [3] . There was no significant correlation between proteinuria and the duration of infection from the time of diagnosis. Albuminuria also demonstrated a significant negative correlation with the levels of hemoglobin (p< 0.05). In addition, low numbers of CD4 cells were associated with lower levels of hemoglobin (p< 0.001). Only 10 patients received renal biopsies, and the results revealed HIV-associated nephro­pathy (HIVAN) in 7 (70%) patients, chronic tubulointerstitial nephritis in 1, membranous glome­rulopathy in 1, and diffuse proliferative glomerulonephritis in 1. Acute renal failure was present in 5 patients, of whom four had a pre renal component and one had multiorgan dysfunction syndrome. We conclude that our study demonstrates that both proteinuria and HIVAN are common in HIV infected patients. Proteinuria has a negative correlation with the CD4 counts and hemoglobin levels.

Keywords: HIV, CD4, Renal, Albuminuria, Proteinuria, Biopsy, Glomerulonephritis, Glomerulopathy

How to cite this article:
Janakiraman H, Abraham G, Matthew M, Kuruvilla S, Panikar V, Solomon S, Kumaraswamy, Seshan SV, Lesley N. Correlation of CD4 Counts with Renal Disease in HIV Positive Patients. Saudi J Kidney Dis Transpl 2008;19:603-7

How to cite this URL:
Janakiraman H, Abraham G, Matthew M, Kuruvilla S, Panikar V, Solomon S, Kumaraswamy, Seshan SV, Lesley N. Correlation of CD4 Counts with Renal Disease in HIV Positive Patients. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2022 Dec 9];19:603-7. Available from: https://www.sjkdt.org/text.asp?2008/19/4/603/41321

   Introduction Top

The world wide scourge of human immu­nodeficiency virus (HIV) infection and AIDS has impacted profoundly on the practice of medicine with about 5.2 million people in­fected in India alone. [1] Due to its prolonged latency period from the initial infection to the full manifestations and chronic seque­lae, the HIV associated diseases will con­tinue to prevail indefinitely, even if current efforts to develop effective preventive stra­tegies are successful.

A broad spectrum of renal diseases is reported in patients with HIV/AIDS, and ranges from acid base disturbances to acute renal failure (ARF) and glomerular diseases such as IgA nephropathy, membranous nephropathy, membranoproliferative, mesan­gial proliferative, diffuse proliferative, or crescentic glomerulonephritis, [2],[3] In addition, there is a distinctive form of sclerosing glomerulopathy HIV-associated nephropa­thy (HIVAN), which develops in 5 to 10 % of patients.

HIVAN develops as a result of HIV gene expression in renal tissue that results in cytopathic effects via the viral transcrip­tional factors or cytokines. Clinical presen­tation typically includes proteinuria without significant hematuria on urinalysis, rapidly progressive renal insufficiency, and large echogenic kidneys. Histological characte­ristics of HIVAN include glomerular, tubu­lointerstitial, and ultrastructural lesions that have been demonstrated in greater fre­quency and severity in the African/black population. Other HIV infected patients re­gardless of age, sex, race and mode of HIV acquisition may develop varied, albeit mil­der, forms of renal lesions. However, some lesions may progress with a fulminant course to end-stage renal disease (ESRD).

Since HIVAN was first described 25 years ago, much has been published regarding the epidemiology, pathogenesis, and treatment of this disease. Despite these advances, however, HIVAN continues to be an impor­tant cause of renal failure.

Mild ARF has been reported to occur in up to 20% of hospitalized HIV-infected pa­tients. [4] This percentage is higher than the 4­5% incidence of ARF in non-HIV-infected patients. [5] Hence, there is appropriate em­phasis on distinguishing reversible from irreversible renal lesions in patients with HIV infection and renal failure.

Absolute CD4 counts are accepted as the best indicator of immunologic competence of patients with HIV infection and they are an indirect reflection of HIV viral load and activity. [6]

We conducted cross sectional this study to establish the prevalence of albuminuria and the glomerular lesion in HIV positive pa­tients and correlate this to the CD4 cell counts.

   Methods and Patients Top

This is a cross sectional study performed in our center over a period of nine months during which 104 patients, who were HIV positive confirmed by western blot analysis, were screened for albuminuria semiquanti­tatively by urine dip stick method. Patients who had diabetes mellitus, urinary tract infections, fever were excluded from the study.

Patients who had urine albumin of 2+ or more were offered renal biopsies. After appropriate consent and evaluation for blee­ding abnormalities, uncontrolled hyperten­sion, and urinary tract infection, the patients were biopsied with ultrasound guidance. Histological examination was performed with light and electron microscopy.

Statistical analysis

Demographic and laboratory variables were compared using Chi-square test. Correlation between variables was analyzed by using Pearson's correlation coefficient. P value of < 0.05 was considered as significant.

   Results Top

A total of 104 (68 males, 36 females) HIV positive patients were screened for albu­minuria, of whom 100 patients were in­fected by heterosexual contact, 3 by blood transfusion, and 1 patient by intravenous drug abuse. The mean age of the patients in the study was 34.4 ± 7.9 The mean duration of illness was 24.6 ± 24.1 months. The mean CD4 counts was 310 ± 297, and the mean hemoglobin was 12.2 ± 1.9 g/dl, [Table 1].

There were 29 (27%) patients with albu­minuria, of whom 19 revealed albuminuria 1+, 9 albuminuria 2+, and 1 albuminuria 3+. There were 71 (68.2%) patients with CD4 count < 350 and 33 (31.8%) with CD4 > 350 cells/mm 3 . There is no statistically sig­nificant correlation between albuminuria and duration from diagnosis of the disease.

Albuminuria correlated inversely with the CD4 count (p< 0.01), and hemoglobin (p< 0.05). However, CD 4 counts correlated proportionally with hemoglobin levels (p< 0.001) [Table 2].

Acute renal failure was observed in 5 pa­tients; 4 patients had pre-renal cause of ARF, and 1 patient had multi organ dys­function syndrome.

Renal biopsies were performed in 10 pa­tients (6 males, 4 females). The renal biopsies results revealed HIV-associated nephropathy (HIVAN) in 7 (70%) patients, chronic tubu­lointerstitial nephritis in 1, membranous glo­merulopathy in 1, and diffuse proliferative glomerulonephritis in 1. Electron microscopy was performed in two patients; one patient with lupus erythematosus had features of both lupus nephritis and HIVAN, and one patient with hepatitis C virus (HCV), who revealed diffuse proliferative glomerulo­nephritis.

   Discussion Top

The incidence of albuminuria in our study was comparable to that reported in other studies. [7] However, the incidence of pro­teinuria is lower when compared to studies done in patients with acquired immuno-deficiency syndrome (AIDS). [8],[9] This diffe­rence can be explained by the fact that most of our patients were asymptomatic.

In our study, albuminuria correlated in­versely with the CD 4 cell counts, which is an indirect reflection of HIV viral load and activity. [6] HIV viral replication and retro­viral antigens are present in the renal tissue, resulting in injury of glomerular and tubular epithelial cells have been postulated as a mechanism for the development of HIVAN. Moreover, persistently low CD4 counts form a surrogate for the viral load, which we did not quantify in our study, and an important predictor of onset of renal disease, regard­less of the duration of HIV infection.

There was no significant correlation bet­ween albuminuria and the duration of the disease in our study which is similar to the observations made by varma et al. [7]

The albuminuria correlated inversely with hemoglobin levels. The possible mechanisms are hemodynamic alterations, lymphokine in­duction, or direct viral invasion of renal tissue in patients with HIVAN. Further­more, renal hyperfiltration may result in increased urinary loss of erythropoietin along with protein and decreased production/de­gradation ratio of erythropoietin. [10] Low levels of CD4 also correlated significantly with low levels of hemoglobin.

The true prevalence of HIVAN is not known, and its distribution is not uniform; it is high in patients of African descent, males, IV drug uses. The most consistent findings include collapsing focal segmental glomerular sclerosis. [11],[12] The available stu­dies have shown that HIVAN is more common in USA and in U.K [3],[13] and mesan­ gioproliferative glomerulonephritis, membra­nous nephropathy and membranoprolife­rative glomerulonephritis are more common in Italy, Thailand and in northern India. [2],[8],[14],[15] While the exact cause for this discrepancy is not entirely clear, racial pre­disposition, viral genotype and other immu­nomodulatory host susceptibility factors may play a role.

The patients with HIVAN are usually trea­ted with highly active anti-retroviral thera­py (HAART) and enalapril. [16],[17],[18] None of the patients received steroids. When patients with HIVAN progress to end-stage renal disease, renal replacement therapy is mandatory, the choice is either hemodialysis or peritoneal dialysis. Renal transplantation can be per­formed in patients with undetectable viral burden on a stable HAART regimen, who have no evidence of neoplasms or oppor­tunistic infections, and CD4 counts should be > 200 cells/mm 3[19]

The incidence of ARF in our study was lower than 20% reported by other studies. [4] This disparity could be explained by the fact that majority of the patients in our study group were asymptomatic. The two most common causes of ARF included pre­renal failure due to dehydration and acute tubular necrosis (ATN) due to sepsis, hypo­tension, and drugs such as aminoglycosides, pentamidine, acyclovir, foscarnet, amphote­ricin, adefovir, and cidofovir. Other causes of ARF include hemolytic uremic syndrome, acute interstitial nephritis, and various glo­merulonephritides. However, when under­lying cause of ARF is reversible, it will usually reverse with dialysis and conven­tional supportive care.

We conclude that our study demonstrates that both proteinuria and HIVAN are com­mon in HIV infected patients. Proteinuria has a negative correlation with the CD4 counts and hemoglobin levels.

   References Top

1.National AIDS control organization of India, www.Naco.nic.in .  Back to cited text no. 1    
2.Praditpornsilpa K, Napathorn S, Yenrudi S, Wankrairot P, Tungsaga K, Sitprija V. Renal pathology and HIV infection in Thailand. Am J Kidney Dis 1999;33(2):282-6.  Back to cited text no. 2    
3.Williams BA, Wei A, Burns GC. Saint Vincents's medical center, A single center clinicopathological study of 100 consecutive renal biopsy of HIV infected patients (1990-2002). New York. International conference of Neprology. 2002.  Back to cited text no. 3    
4.Winston JA, Klotman PE. Are we missing an epidemic of HIV-associated nephropathy? J Am Soc Nephrol 1996;7(1):1-7.  Back to cited text no. 4    
5.Valeri A, Neusy AJ. Acute and chronic renal disease in hospitalized AIDS patients. Clin Nephrol 1991;35(3):110-8.  Back to cited text no. 5    
6.Fauci AS, Lane CH. Harrison's principles of internal medicine, 16th ed, Vol 1, chapter 173, 1103.  Back to cited text no. 6    
7.Varma PP, Prasher PK, Spectrum of renal Lesions in HIV patients. JAPI 2000;48(12): 1151.  Back to cited text no. 7    
8.Pardo V, Aldana M, Colton RM, et al. Glo­merular lesions in the acquired immuno­deficiency syndrome. Ann Intern Med 1984;101:429-34.  Back to cited text no. 8  [PUBMED]  
9.Soni A, Agarwal A, Chander P, et al Evidence for HIV related nephropathy: a clinico­pathological study. Clin Nephrol 1990;31 (1):12-7.  Back to cited text no. 9    
10.Nowicki M, Kokot F, Kokot M, Bar A. Renal clearance of endogenous erythro­poietin in patients with proteinuria. Int Urol Nephrol 1994;26(6):691-9.  Back to cited text no. 10    
11.Pardo V, Meneses R, Ossa L, et al. AIDS­related glomerulopathy: occurrence in spe­cific risk groups. Kidney Int 1987;31(5): 1167-73.  Back to cited text no. 11    
12.Cohen AH, Nast CC. HIV-associated nephro­pathy. A unique combined glomerular, tubular and interstitial lesion. Mod Pathol 1988;1(2):87-97.  Back to cited text no. 12    
13.Connolly JO, Weston CE, Hendry BM. HIV­associated renal disease in London hospitals. Q J Med 1995;88(9):627-34.  Back to cited text no. 13    
14.Casanova S, Mazzucco G, Barbiano di Belgiojoso G, et al. Pattern of glomerular involvement in human immunodeficiency virus-infected patients: an Italian study. Am J Kidney Dis 1995;26(3):446-53.  Back to cited text no. 14    
15.Nochy D, Glotz D, Dosquet P, et al. Renal disease associated with HIV infection: a multicentric study of 60 patients from Paris hospitals. Nephrol Dial Transplant 1993;8 (1):11-9.  Back to cited text no. 15    
16.Ifudu O, Rao TK, Tan CC, Fleischman H, Chirgwin K, Friedman EA. Zidovudine is beneficial in human immunodeficiency virus associated nephropathy. Am J Nephrol 1995;15:217-21.  Back to cited text no. 16  [PUBMED]  
17.Wali RK, Drachenberg CI, Papadimitriou JC, Keay S, Ramos E. HIV I - associated neohropathy and response to highly active anti retroviral therapy. Lancet 1998;352: 783-4.  Back to cited text no. 17  [PUBMED]  [FULLTEXT]
18.Burns GC, Paul SK, Toth IR, Sivak SL. Effect of angiotensin converting enzyme inhibition in HIV associated nephropathy. J Am Soc Nephrol 1997;8:1140-6.  Back to cited text no. 18  [PUBMED]  [FULLTEXT]
19.Roland ME, Adey D, Carlson LL, Terrault NA. Kidney and Liver transplantation in HIV infected patients: case presentation and review. AIDS Patient Care STDs 2003;17 (10):501-7.  Back to cited text no. 19    

Correspondence Address:
Hari Janakiraman
Department of Medicine, Sri Ramachandra Medical College and Research Institute, Chennai
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Source of Support: None, Conflict of Interest: None

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  [Table 1], [Table 2]

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