The human immunodeficiency virus is a highly variable pathogen associated with renal disease since the early days of the epidemic. Traditionally, HIV-related kidney complications have been attributed to collapsing focal segmental glomerulosclerosis, although they also happen in the form of HIV-immune-complex kidney disease and thrombotic microangiopathy. Since the advent of combination antiretroviral therapy, patients are living longer and manifesting fewer classic symptoms of HIV-related kidney disease. However, nephrotoxicity from some HIV medications is becoming more common, along with an increase in non-infectious comorbidities like diabetes and hypertension that are also contributing to kidney problems in people living with HIV. Renal disease remains one of the important causes of mortality in HIV-infected patients, such that patients who have acute kidney injury or chronic kidney disease have a six-fold increased risk of death. Equally, since HIV can infect and replicate within the renal epithelial cells, a complete virologic cure may demand the eradication of the virus from the kidney, which seems to act independently from the bloodstream. 

The highest number of HIV-related kidney diseases occurred in the 1990s when it affected USA between 3.5% to 10% people in HIV+ among them with Africana being presented as more likely to contract them. In spite of this, widespread use of antiretroviral drugs has seen this percentage number declining steadily. 

HIV-1 infection seems to be a prerequisite for the pathogenesis of HIV-associated nephropathy (HIVAN); however, the exact mechanism of viral infection on renal epithelial cells is not clear. Viruses or portions of them have been found in renal tissues by numerous studies, though classical receptors for viral entry have not been expressed on renal epithelial cells, immune effector cells (macrophages and T cells), or, in particular, classical targets for viral infection. What is known is, for example, that macrophages and lymphocytes can facilitate transfer of the virus to renal epithelial cells. Key players in this regard are the CD209 antigen, also known as dendritic-cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), that mediates HIV infection of dendritic cells, and the lymphocyte antigen 75 (DEC-205). That may directly facilitate infection of the renal tubular epithelial cells.

Genetic variations in APOL1 that increase risk of HIV infection have been identified but how the gene affects risk remains undefined. The most probable HIV acquisition by renal cells would involve the transfer of virus from infected leukocytes to the renal tubular and endothelial cells; another likely mechanism of entry of HIV into the renal cells is phagocytosis of dying CD4+ T cells. Circulating HIV proteins, for example, Vpr and Tat, could gain access to the podocytes, and their local interaction with the proteoglycans or lipid rafts would mediate cellular uptake. 

Renal pathologies in PLWHIV range from lesions directly caused by intrarenal HIV gene expression to injuries related to comorbidities, drug-induced nephrotoxicity, and immune dysregulation. Glomerular diseases predominate in HIV-related renal disease and can be classified into two main groups: podocytopathies and immune complex-mediated diseases. 

Podocytopathies include, HIVAN (HIV-associated nephropathy), focal segmental glomerulosclerosis not otherwise specified, and less common forms such as minimal change disease and diffuse mesangial hypercellularity. These are characterized by significant podocyte foot process effacement and proteinuria, resulting from direct infection of renal epithelial cells with HIV, dysregulation of host genes and intrarenal viral gene expression. The immune complex-mediated conditions in PLWHIV include the following: post- lupus-like nephritis, membranous nephropathy, membranoproliferative glomerulonephritis, infectious glomerulonephritis, and IgA nephropathy. A causal relationship with HIV cannot be established in these conditions. Hence, ruling out of secondary causes has to be done. 

Before the introduction of combined antiretroviral therapy, HIV-associated nephropathy was a severe condition that led to faster progression to final stage kidney disease in a period of two to four months. Today the prognosis has improved significantly. Nonetheless, patients suffering from HIVAN still fare worse compared to those with other types of renal disease. 

HIVAN typically presents with severe proteinuria and a rapid reduction in glomerular filtration rate. Other signs of nephropathy like hypertension and peripheral edema of lower extremities are less common in these patients. Given the likelihood of coexisting infections and conditions, it is crucial to rule out other potential causes of nephropathy in this population. 

The physical examination of a patient with HIVAN focuses on identifying sign sof renal impairment and related complications. 

General appearance: Chronic renal disease can cause patients to appear fatigued, while peripheral edema, a less common condition may be present in the lower extremities. 

Vital signs: This condition can cause hypertension which may not present always and pulse that can lead to tachycardia especially in advanced stage of renal disease or fluid imbalances. 

Cardiovascular examination:  Signs for heart failure or other cardiac issues should be observed which may arise due to hypertension or fluid overload. 

Respiratory examination: Observe for signs of pulmonary edema or fluid overload which might be present with crackles or rales in breathing sounds. 

Abdominal examination: Tenderness in renal area is less common in HIVAN while renal enlargement is uncommon but may be observed in other kidney related conditions. 

Skin examination: HIV patients might be present with skin conditions or rashes related to HIV or opportunistic infections, but these are not specific to HIVAN. 

Extremities: Peripheral edema may be observed particularly if renal function is significantly impaired. 

1. CKD (chronic kidney disease) 
2. ESRD (End-stage renal disease) 
3. Edema of lower extremities 
4. Hypertension 

The treatment of HIVAN involves a combination of antiretroviral therapy to control HIV infection and supportive measures to manage kidney function and related complications. 

ART (Antiretroviral therapy): The goal is to achieve and maintain viral suppression to slow the progression of HIVAN and improve renal function. Common regimens include using a combination of antiretroviral drugs from different classes such as INSTIs (integrase strand transfer inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), PIs (protease inhibitors), and NRTIs (nucleoside reverse transcriptase inhibitors). Adjustment is made based in the renal function of the patient, avoiding nephrotoxic drugs when possible. Common classes include Tenofovir disoproxil fumarate, Emtricitabine, Rilpivirine, Efavirenz, BIC, Darinavir, and Dolutegravir. 

Management of proteinuria: ACE inhibitors reduce proteinuria and slow the progression of kidney disease while ARBs (angiotensin-II receptor blockers) are used as alternatives if ACE inhibitors are not tolerated or contraindicated. 

Supportive care: Blood pressure should be maintained within the target ranges usually less than 130/80mm Hg to lower renal damage. To manage edema and fluid overload diuretics can be used.  

Nephrology

Dietary modifications: A diet low in proteins and restricted salt should be encouraged to maintain proteinuria and fluid balance.  

Management of electrolyte imbalances: Abnormalities such as hypocalcaemia or hypokalaemia must be monitored and treated accordingly. 

Management or comorbidities: Blood sugar levels should be controlled in case of diabetes where cholesterol levels must be maintained with respect to hyperlipidaemia. 

Nephrology

Tenofovir disoproxil fumarate: This is a nucleoside reverse transcriptase inhibitor which can be used to treat kidney toxicity. Adjustment of dose is indicated in case of creatinine clearance of <50mL/min. 

Protease inhibitors: These are also implicated for use in case of kidney toxicity. 

Enfuviritide: This belongs to the new class of drugs called as fusion inhibitors which targets gp4 protein present on the surface of the HIV and prevents the entry of virus into the cells. 

Raltegravir: It belongs to the class of INSTIs (integrase strand transferase inhibitors). 

Nephrology

Captopril improved renal survival with a median of 37-156 days in patients with advanced kidney insufficiency. A median of 479.5 days was seen in patients treated with fosinopril with only one developing ESRD. ACE inhibitors in HIVAN may have a hemodynamic effect, reduced transglomerular protein passage, and antiproliferative effect. 

Nephrology

Corticosteroids have been associated with short-term benefits in HIVAN as demonstrated in kidney biopsy results of improved kidney function and reduced lymphocyte and macrophage infiltration. In a study, treatment by prednisone resulted in 8 patients requiring dialysis, 11 died and 7 lived with ESRD. 

Treatment of HIV-associated nephropathy is done in several phases. Phase one is that of diagnosis and initial evaluation that includes clinical assessment, laboratory tests, HIV viral load and CD4 count, and kidney biopsy. Treatment involves ART, renal protective medications, management of hypertension, and periodic management that includes recurrent monitoring, laboratory tests, and adjustments of medication. Complication management involves the management of comorbidities, consideration of the institution of dialysis if renal function worsens, and assessment of suitability for renal transplantation. Patient education and support are provided, along with support services. Long-term follow-up is required for checking the health of kidneys, control of HIV, and new complication development. Treatment plans will be regularly reviewed and evolved in response to the assessment of health and medical research. Up-to-date information about treatment and research into HIVAN remains crucial for its integration with the management of new evidence-based practices.