|Year : 2016 | Volume
| Issue : 3 | Page : 74-78
Impact of Human Immunodeficiency Virus/AIDS on the Kidneys: Radiologist Perspective
Regina Chinwe Onwuchekwa
Department of Radiology, Faculty of Clinical Sciences, College of Health Sciences, University of Port Harcourt, Port Harcourt, Nigeria
|Date of Web Publication||4-Aug-2016|
Regina Chinwe Onwuchekwa
Department of Radiology, Faculty of Clinical Sciences, College of Health Sciences, University of Port Harcourt, Port Harcourt
Source of Support: None, Conflict of Interest: None
Human immunodeficiency virus (HIV)/AIDS is unique for its devastating impact on social, economic, and demographic developments. Recent studies have thrown more light on the reasons for the mortality and morbidity associated with HIV/AIDS in general and on its renal complications in particular. The classic involvement of the kidney by HIV infection in HIV-associated nephropathy (HIVAN) was reported in New York in 1984. HIVAN clinically presents with proteinuria and renal dysfunction and pathologically with focal segmental glomerulosclerosis. The imaging modality most commonly used in the assessment of renal dysfunction is ultrasonography, followed by computerized tomography. These renal lesions manifest in a protean number of ways in sonography. Renal survival has improved with the introduction of highly active antiretroviral therapy.
Keywords: Glomerulosclerosis, human immunodeficiency virus, nephropathy, renal diseases
|How to cite this article:|
Onwuchekwa RC. Impact of Human Immunodeficiency Virus/AIDS on the Kidneys: Radiologist Perspective. J Integr Nephrol Androl 2016;3:74-8
| Introduction|| |
Human immunodeficiency virus (HIV) infection is a worldwide public health challenge, especially in the Sub-Saharan Africa. The majority of the 35.3 million people living with HIV worldwide reside in Sub-Saharan Africa, an estimated 24.7 million people.  In 2004, Nigeria ranked 3 rd among countries with people living with HIV in Africa, 3.6 million Nigerians were HIV positive.  Rivers state, a metropolitan state in south-south geopolitical zone of Nigeria, had a prevalence of 7.3% in 2008 and 6.0% in 2010. 
HIV/AIDS is unique for its devastating impact on social, economic, and demographic developments. Recent studies have thrown more light on the reasons for the mortality and morbidity associated with HIV/AIDS in general and on its renal complications in particular. ,
HIV-associated nephropathy (HIVAN) is characterized by high-grade proteinuria and rapid progression to end-stage renal disease (ESRD) which incur high cost  and has been associated with very high mortality before the introduction of highly active antiretroviral therapy (HAART) which has enhanced kidney preservation. 
| History of Human Immunodeficiency Virus-associated Nephropathy|| |
The association of HIV infection and renal disease first emerged in the mid-1980s with the initial description of HIVAN.  After a brief debate on whether this syndrome was related to heroin nephropathy, clinical experience subsequently revealed that HIVAN was indeed a distinct clinicopathologic entity.  The classic involvement of the kidney by HIV infection in HIVAN was reported in New York in 1984.  The HIV-infected population with HIVAN in the USA were predominantly individuals of African ancestry. 
| Prevalence|| |
Renal involvement in HIV/AIDS was prevalent, and in 2003, HIV-related kidney disease was the third most common cause of ESRD in Africans between the ages of 20 and 64 years.  Okafor et al.,  in Benin, Nigeria, reported a prevalence of renal affectation in HIV infection as 53.3%, similar to 52% prevalence rate reported in North Central Nigeria.  Emem et al.  in a related study in South-Southern Nigeria noted a lower prevalence (36.6%) in their study participants. In the United States of America, 11-32.6% of HIV patients had renal involvement.  A study by Valeri and Neusy  conducted before the introduction of antiretroviral therapy showed that while 20% of hospitalized HIV patients had acute renal failure, only 5% of HIV-negative control group had acute renal failure. In Europe, a cross-sectional study by Mocroft  with 4474 HIV-positive participants reported a prevalence of 3.5%, whereas 6.2% and 16.8% were reported for South Africa and China, respectively. 
HIVAN is the most common lesion encountered in renal HIV infection, and it is seen in up to 60% of all renal biopsies performed for HIV patients with chronic kidney disease.  According to the United States renal data system, AIDS-related renal disease accounted for 0.5% of all cases of ESRD between 1989 and 1992. 
The true prevalence of HIVAN in West Africa is unknown largely due to lack of surveillance and reporting of kidney disease in HIV-positive patients. Ross and Klotman  gave an estimate of 1.0-3.4 million prevalent cases of HIVAN for Sub-Saharan Africa with suggestion of higher prevalence rate with improving life expectancy following the introduction of HAART.
| Spectrum of Renal Diseases In Human Immunodeficiency Virus/AIDS|| |
Acute renal infection and chronic renal disease are the renal effects of HIV/AIDS. The spectrum of acute kidney infection comprises prerenal azotemia, acute tubular nephritis, acute interstitial nephritis, drug-related nephrotoxicity, postinfectious immune complex glomerulonephritis, hemolytic uremic syndrome (HUS), and thrombotic thrombocytopenic purpura.  Others are postrenal causes of renal failure due to urinary tract outflow obstruction including bladder and urethral obstruction; extrinsic compression from tumor, lymph nodes, or retroperitoneal fibrosis; and intrinsic obstruction from blood clots, fungus balls, or crystalluria. 
On the other hand, chronic kidney disease seen comprise HIVAN, HIV-related immune complex-mediated kidney disease, immunoglobulin-A nephropathy, lupus-like glomerulonephritis, postinfectious glomerulonephritis, and hepatitis C-related membranoproliferative glomerulonephritis. In addition, interstitial nephritis, thrombotic microangiopathy, and more traditional chronic kidney disease causes, such as diabetic or hypertensive nephropathy, may occur in HIV infection. 
| Risk factors and pathogenesis|| |
Risk factors for developing chronic kidney disease among HIV-infected individuals include African ancestry, HIV disease stage, hepatitis C coinfection, cocaine use, hypertension, diabetes, dyslipidemia, and perhaps acute kidney infection.  Others are positive family history of renal disease, HIV load (>400 copies/mL), low CD4 + cell count (<200 cells/mm 3 ), and baseline presence of proteinuria with or without concomitant elevation in serum creatinine level. 
Although male sex has also been reported as a risk factor,  the incidence of HIVAN in women is increasing proportionately to the escalating rate of HIV infection in this group.  The low socioeconomic class has also been identified as a risk factor. Most HIV-infected patients develop renal impairment at some point during their illness.  Although risk is greater with low CD4 + cell counts (counts <200), renal impairment has also been observed in patients with normal CD4 + cell counts.  Nephropathy may be the first manifestation of HIV infection and often occurs before opportunistic infections develop. 
Complex immunologic, environmental, and genetic factors have been implicated in the pathophysiology of renal affectation in HIV.  The kidney is thought to be a reservoir of HIV as HIV replication in glomerular epithelial cells has been observed despite undetectable serum viral loads. From extrapolation in mouse models, renal and tubular cells in HIV-positive patients have increased expression of mesenchymal markers such as α-smooth muscle actin and fibroblast-specific protein-1. This suggests that epithelial-mesenchymal transition may contribute to HIVAN,  which is the most common renal lesion in HIV-infected adults. Activation of the mammalian target of rapamycin also contributes to the development of HIVAN.  The Duffy antigen receptor for chemokines (DARC) has also been proposed as a candidate gene involved in HIVAN pathogenesis. The DARC promoter has a high prevalence of polymorphisms in patients; increased DARC expression has been demonstrated in renal specimens from children with HIVAN and HUS.  The genetic susceptibility to HIVAN has been linked to polymorphisms on chromosome 22 in individuals of African descent. 
| Radiologic features|| |
It is worthy of note that renal biopsy is the only means of establishing the diagnosis of HIVAN; imaging findings are only suggestive as a combination of some features visualized on images may prove high index of suspicion for the disease.
The imaging modality most commonly used in the assessment of renal dysfunction is ultrasonography, followed by computerized tomography (CT). Magnetic resonance imaging (MRI) is used if ultrasonic and computerized tomographic findings are inconclusive or in patients with allergies to iodine-based contrast media used in CT. 
These renal lesions manifest in a protean number of ways in sonography. In a study carried out in Los Angeles involving 76 participants, of the 152 kidneys imaged, sonography showed that 20% were enlarged, 89% were abnormal echogenicity, 53% were globular, and 38% had decreased corticomedullary differentiation. Nine percent had decreased renal sinus fat [Figure 1]a, and 43% had heterogeneous parenchyma [Figure 1]b].  Other reported findings are pelvicalyceal thickening and cortical calcification.  Fungal infection of the kidney may manifest as focal microabscesses and hydronephrosis on ultrasound [Figure 2]. In renal tuberculosis, thick-walled hypoechoic lesions are seen, whereas in long-standing cases, small, shrunken, scarred, and calcified kidneys may be seen. Renal lymphoma in HIV patients is typically hypoechoic and homogeneous with a displacement of normal renal vessels. 
|Figure 1: Ultrasound image of a female patient with human immunodeficiency virus-associated nephropathy showing (a) right kidney with marked reduction in sinus fat and (b) increased renal size with heterogeneous parenchymal echogenicity|
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|Figure 2: Ultrasound image of hydronephotic kidneys in human immunodeficiency virus-associated nephropathy patient|
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|Figure 3: Echogenic left kidney (a) and right kidney (b) in human immunodeficiency virus-associated nephropathy patient|
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Increase in renal echogenicity is the most common sonographic finding in HIV-infected patients [Figure 3]. There are four categories: category 0 indicates that the renal cortex is less echogenic than the liver; category 1, the renal cortex and liver are equal in echogenicity; category 2, the renal cortex is more echogenic than the liver; and category 3, the renal cortex and renal sinus are equal in echogenicity.  This increase in renal echogenicity is thought to reflect underlying parenchymal disease.  Although no correlation has been found between the severity of glomerular disease and the degree of increased cortical echogenicity, Atta et al.  noted that the highest and lowest levels of sonographic echogenicity have diagnostic value in establishing or excluding HIVAN.
In a study by Igbinedion et al.  in Benin, Nigeria, renomegaly was observed in 19% of patients without significant correlation with their CD4 + cell counts. In these patients, bilateral, right-sided, and left-sided renal enlargement was observed in 39.3%, 19.6%, and 41.1%, respectively. Kidney enlargement is predominantly in the axial direction with the kidney losing its ellipsoid shape and becoming more rounded on ultrasonography.  Again in Benin, Nigeria, Adeyekun et al.  observed that 85%, 7%, and 8% of his participants had normal, small, and large renal size, whereas 41.7% had increased renal cortical echoes.
A study by Ulu et al.  in Plateau State, North Central Nigeria, involving 302 participants between the ages of 4 and 80 years, observed that there was a significant negative correlation between renal length and measured CD4 + cell count and also between the renal length and age of the participant. No significant correlation between renal echogenicity and CD4 + cell count was noted. In South West Nigeria, Obajimi et al.  observed that there was no significant statistical difference in both HIV-positive and HIV-negative control group in renal cortical and medullary echotexture.
CT findings in HIVAN are less described.  However, enlarged kidneys, hyperdense medulla on noncontrast scans, and striated nephrograms have been observed in HIVAN [Figure 4]. The striated nephrographic appearance is a result of dilated protein-filled tubules. Low attenuating collections occupying the renal parenchyma and hydronephrosis have also been described in fungi microabscesses. In lymphoma, soft-tissue mass infiltrating the retroperitoneum with encasement of the renal vessels and poorly-enhancing soft-tissue masses have also been described. 
|Figure 4: Postcontrast computerized tomography showing enlarged kidney with striated nephrogram in a patient with human immunodeficiency virus nephropathy|
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MRI shows renal enlargement and loss of corticomedullary differentiation. Hydronephrosis and hypointense nonenhancing masses have been visualized.
| Treatment outcome and prognosis|| |
There is no specific treatment for HIVAN. Some groups have found a benefit using zidovudine, and angiotensin converting enzyme inhibitors in slowing the progression of renal failure. , Use of steroid was associated with significant reduction in the risk of renal death, especially in combination with antiretroviral therapy. In a study of 31 patients with HIVAN, who were followed for at least 12 months, significant longer renal survival before ESRD was noted in patients who received both prednisone and antiretroviral therapy compared to antiretroviral therapy alone or those who received neither prednisone nor antiretroviral therapy. 
In a study of 51 participants by Ortiz et al.  to determine the outcome of renal involvement in HIV-positive patients, it was noted that regardless of when they contracted the infection, AIDS patients who required maintenance hemodialysis had a poor prognosis. All 17 patients who developed AIDS died after a mean of 93 ± 32 days on hemodialysis, whereas 12 asymptomatic HIV carriers were alive after a mean follow-up on hemodialysis of 488 ± 75 days. Increased parenchymal echogenicity together with decreased visibility of renal sinus fat, poor corticomedullary differentiation, and low CD4 + cell count (<50) is associated with poor prognosis. 
| Conclusion|| |
HIV-infected patients are predisposed to various complications. Kidney complications are increasingly common due to the increase in life expectancy following the introduction of HAART. Ultrasonography is the imaging modality of choice in assessing the renal diseases associated with HIV/AIDS. The imaging features are diverse; hence, it is paramount that the radiologist and managing physicians acquaint themselves with the diverse characteristics of theses renal diseases. As early detection and administration of appropriate therapy are beneficial to renal survival.
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