38-Year-Old Male Presents With Lower Extremity Edema

He was discharged on trimethoprim/sulfamethoxazole and azithromycin prophylaxis and started on antiretroviral therapy (ART) once his HIV genotype was determined. Throughout the hospitalization, diuresis was continued with furosemide, and his renal function improved with his creatinine down to 1.7 before starting abacavir-dolutegravir-lamivud.

Once infected with HIV-1, the development of AIDS can be delayed up to 10 to 20 years.[3] Many individuals who seroconvert to HIV have generalized symptoms of fatigue, fever, rash, lymphadenopathy, weight loss, and myalgias.[4][5] This is an unusual presentation of HIV immune complex kidney disease (HIVICK) with newly diagnosed AIDS. This case is also atypical due to c-ANCA positivity in the presence of HIV disease.

It is important to know the limitations of laboratory data when approaching a patient with newly diagnosed renal failure. Positivity of ANCA has been found secondary to HIV infection in up to 20% to 83% of cases, with a proposed mechanism being polyclonal activation of B cells. The sensitivity of c-ANCA for GPA is 64% with indirect immunofluorescence.[6]

Renal disease in the setting of HIV manifests in several ways. HIV-associated nephropathy (HIVAN) is a form of focal segmental glomerulosclerosis with interstitial inflammation and microcysts involving direct infiltration of renal tubular and glomerular cells by HIV.[7] HIVAN is more common in advanced HIV and the black race and is associated with significant proteinuria and a rapid decline in renal function. Among the different risk factors for developing end-stage renal disease (ESRD) in HIV-infected individuals, black race is the most important factor due to the ApoL1 gene mutation. In the United States from 2002 to 2006, 88% of HIV patients with ESRD were black.[8][9]  These patients almost always have HIVAN. HIVAN is rarely associated with patients already on ART with normal CD4 counts. These individuals benefit from ART and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, but glucocorticoids have not been found to be helpful. The prognosis is poor and patients often reach ESRD with hemodialysis dependence. Despite ART, RNA viral expression can persist with the kidneys as an important reservoir for HIV-1.[10]

Another form of renal disease in the setting of HIV is called HIV immune complex kidney disease (HIVICK). It is also usually seen in advanced HIV and black race. The prognosis is also poor with 32% of patients reaching ESRD status within two years.[11] Unlike HIVAN, the beneficial role of ART has not been shown. Other forms of renal disease in the setting of HIV include IgA nephropathy, membranoproliferative glomerulonephritis, renal tubular acidosis, amyloid, acute postinfectious glomerulonephritis, membranous nephropathy, focal and segmental necrotizing glomerulonephritis, immunotactoid nephropathy, and thrombotic microangiopathy.[12]

Before starting ART in an antiretroviral naïve patient with impaired renal function, there are several considerations to keep in mind.  First, certain ART medications require renal adjustment or are contraindicated with impaired renal function.[13] Second, after ART is initiated, follow up to monitor renal function for new onset or worsening renal disease is crucial as this can modify therapy. Third, screening for the HLA-B*5701 allele must be addressed before starting ART as HLA-B*5701 positivity predisposes the patient to a hypersensitivity reaction (abacavir) that can be life-threatening.[14] This can pose a challenging dilemma for cost, compliance, and efficacy as abacavir is included in many of the current one-pill ART regimens.

Having HIV is no longer a contraindication for renal transplantation. The Infectious Diseases Society of America (IDSA) strongly recommends the evaluation of HIV patients with ESRD or imminent ESRD for kidney transplantation after considering comorbidities, history of opportunistic infections, and virologic response with ART.[13]

The initial approach to a patient with new-onset lower extremity edema can be challenging, with the initial workup, often focusing on the hepatic, cardiovascular or renal system.  Screening for a vasculitic process is often performed, particularly when it involves the renal or pulmonary systems. It is important to understand the significance and limitations of serological markers when evaluating the patient.  This case aims to highlight the potential pitfalls of positive serologic markers and the importance of keeping a broad differential in new-onset lower extremity swelling. 

This review separating vasculitic renal disease from infectious etiology highlights the importance of not empirically treating a patient with positive serological markers for vasculitis with cytotoxic agents as this could be disastrous for a patient with HIV. This case also presents an atypical presentation of HIV infection and the need to have a high index of suspicion for the disease, even when risk factors are not apparent. Treatment regimens will also differ for an HIV patient with concomitant renal impairment and special considerations must be given before starting ART.

This case presents an excellent opportunity to discuss the importance of an interprofessional team management of managing patients with renal failure and HIV. Having either HIV or renal failure can overwhelm patients due to the complexity of care required for proper management and the need for long-term treatment. Patients with renal failure who depend on hemodialysis experience extraordinarily high burdens of stress which adversely affect treatment compliance and subsequent outcomes. Thankfully, interprofessional management of dialysis patients delivers a multitude of benefits including better clinical outcomes, cost savings, and improved patient quality of life.[15] An HIV diagnosis carries significant stigma which negatively affects treatment outcomes and quality of life metrics. HIV care teams composed of physicians, pharmacists, nurses, counselors, psychologists, and social workers provide necessary holistic support to patients with demonstrable clinical improvements.[16] Complex HIV medication regimens are best managed by multidisciplinary involvement of pharmacists to help anticipate and avoid drug-drug interactions which can cause significant side effects or reduce the efficacy of treatment.[17]