What Is HIV-Associated Nephropathy?
Human immunodeficiency virus (HIV)-associated nephropathy is a militant condition that needs timely diagnosis to avoid permanent damage to renal function. While the onset of combined antiretroviral therapy and fast diagnosis of HIV has made this condition rare, it is important to realize the repercussions it could have, especially for those with inadequate access to health care. The human immunodeficiency virus (HIV) is a quickly growing virus that is related to renal disease since the early days of the HIV wave. HIV-associated nephropathy is directly related to collapsing focal segmental glomerulosclerosis and also manifests as HIV-immune-complex kidney disease and thrombotic microangiopathy.
In the last few years, with the origin of combination antiretroviral therapy and beneficial dispersion of these medications, patients are living longer lives without particular appearances of the disease. Nowadays, disorders associated with nephrotoxicity of certain HIV therapies seem to be more common, as well as a rise in non-infectious comorbidities, such as diabetes or hypertension, as a cause of nephropathy in people living with HIV. Renal disease continues to be one of the main causes of mortality in patients infected with HIV, with a six-fold rise in mortality for those suffering from acute kidney injury (AKI) and chronic kidney disease (CKD). HIV can infect and replicate inside the renal epithelial cells, a complete virologic treatment can only be feasible with the complete removal of the viral reservoir in the kidney as this compartment acts separately from the blood.
What Causes HIV-Associated Nephropathy?
The causes of HIV-associated nephropathy include:
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There is a distinct range of renal pathologies such as lesions arising directly from injuries secondary to comorbidities, drug-induced nephrotoxicity, intrarenal HIV gene expression, and immune dysregulation, among others.
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Renal disease related to HIV infection is mostly a glomerular dominant disease and is classified into two main categories: immune complex-mediated disease and podocytopathies.
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The main subtypes of podocytopathy are classic HIV-associated nephropathy, focal segmental glomerulosclerosis, minimal change disease, and diffuse mesangial hypercellularity.
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These are distinguished by extensive podocyte foot process effacement and proteinuria moderated by direct HIV infection of renal epithelial cells, dysregulation of host genes, and intrarenal viral gene expression.
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Several forms of the immune complex-mediated disease in cases of lupus-like nephritis, IgA nephropathy, post-infectious glomerulonephritis membranous nephropathy, and membranoproliferative glomerulonephritis can be seen.
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The manner of HIV-1 genes in the kidney epithelial cells is required for the growth of HIV-associated nephropathy.
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The means by which HIV infects renal epithelial cells stay unclear. The classical receptors required for access of the virus into T cells and macrophages are missing from renal cells.
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According to various studies lymphocytes and macrophages appears to be vectors essential for renal epithelial cell transmission of HIV. Among these are CD209 antigen (DC-SIGN), which moderates HIV infection of dendritic cells, and lymphocyte antigen 75, which may rapidly contribute to infection of renal tubular epithelial cells.
What Are HIV-Related Renal Disorders?
The HIV-related renal disorders are:
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HIV-Associated Immune Complex Kidney Disease - Several glomerular lesions associated with HIV-associated immune complex kidney disease are caused by co-infection with hepatitis B and C. Studies performed before the origin of combined antiretroviral therapy revealed anti-HIV antibodies which may form immune complexes that can result in glomerulonephritis, but the means and relevancy in the post-antiretroviral are unknown.
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HIV-Associated Thrombotic Microangiopathy - Thrombotic microangiopathy is a recognized complication of late-stage HIV/AIDS (acquired immunodeficiency syndrome). But its incidence has reduced since the arrival of combined antiretroviral treatment. The basis of endothelial injury is the vulnerability to circulating viral proteins combined with other factors such as medications, pro-inflammatory molecules, and antiphospholipid antibodies.
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Acute Renal Failure in HIV-Associated Patients - Acute renal failure in HIV-infected persons can be a result of the similar mechanisms that cause it in HIV-uninfected patients. Drugs used for the treatment of HIV infection that is related to nephrotoxicity include Amphotericin, Aminoglycosides, Foscarnet, Trimethoprim-sulfamethoxazole, Tenofovir, Indinavir, and Acyclovir. Moreover, acute renal failure can be associated with thrombotic thrombocytopenic purpur, hemolytic uremic syndrome, or pharmacotherapy. Acute renal failure is a common outcome in HIV-infected patients and is related to advanced stages of HIV infection, hepatitis C virus coinfection, and a history of antiretroviral treatment.
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Chronic Renal Failure in HIV-Associated Patients -Chronic kidney disease in the several stages of HIV infection is difficult to assess. Proteinuria and elevated creatinine levels in HIV-seropositive patients are associated with an increased rate of death. Proteinuria however stays a nonspecific result in HIV-infected patients. HAART (highly active antiretroviral therapy) was found to reduce the progression from AIDS (acquired immunodeficiency syndrome) to end-stage renal disease. The reason for chronic renal disease in HIV-infected patients can be difficult to examine on a clinical basis alone and can most frequently only be determined by renal biopsy.
How Are HIV-Associated Nephropathy and Other HIV-Related Renal Disorders Diagnosed?
The diagnosis includes:
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Lab Tests - Screening for HIV nephropathy in HIV-positive patients must include serum creatinine and estimated glomerular filtration rate (GFR) along with a urinalysis. A measure of proteinuria is required at the beginning and during antiretroviral therapy (ART).
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Imaging Tests - Imaging techniques, such as ultrasonography of the kidneys, can be done as it is a non-invasive method. Renal pathogenicity with high scores is a strong predictor for HIV-associated nephropathy, while low scores could effectively rule it out.
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Kidney Biopsy - A kidney biopsy is generally the only way of achieving a definitive diagnosis. Indications for biopsy stay the same as for the general population. The decision to undergo a kidney biopsy should be taken by considering the clinical presentation, alternate diagnosis, therapeutic options, and the risks associated with the procedure.
How Are HIV-Associated Nephropathy and Other HIV-Related Renal Disorders Treated?
HIV-associated nephropathy is involved with a high risk for progression to end-stage renal disease (ESRD) and increased mortality, therefore, the treatment should not be delayed.
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Combined antiretroviral therapy remains the mainstay of treatment for HIV-associated nephropathy, as it has been shown to reduce the probability of progression into end-stage kidney disease. In patients with refractory renal injury after ART (antiretroviral therapy) and RAAS (renin angiotensin aldosterone system) blockade treatment, steroids can be added as an adjunct but they cannot be used as a primary treatment as the side effect profile is broad.
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It is essential to adjust ART (antiretroviral therapy) therapy to renal function as it can directly affect renal function, such as Tenofovir, Atazanavir, and Indinavir.
Conclusion
Human immunodeficiency virus infection associated with nephropathy involves progressive renal failure. It is accompanied by proteinuria and ultrasonic findings of echogenic and enlarged kidneys. Diagnosis requires blood and urine profiles, imaging tests, and kidney biopsy. The treatment involves the use of antiretroviral therapy and in severe cases renal replacement. renal replacement and renal transplantation remain the mainstay of management and are effective in patients with controlled HIV.
