How would you manage a patient with HIV-associated nephropathy, significant renal impairment, edema, and elevated Blood Urea Nitrogen (BUN), with a CD4 count of 506 and normal Complete Blood Count (CBC), and should hemodialysis and antiretroviral therapy be initiated?

Management of HIV-Associated Nephropathy with Severe Renal Impairment

Start antiretroviral therapy (HAART) immediately at diagnosis of HIVAN, regardless of the severity of renal dysfunction, and initiate hemodialysis urgently given the creatinine of 601 µmol/L (approximately 6.8 mg/dL), edema, and elevated BUN. 1

Immediate Initiation of Both Therapies

Start HAART Without Delay

• Patients with HIVAN should be treated with HAART at diagnosis (B-II recommendation), and HAART should not be withheld from patients simply because of the severity of their renal dysfunction. 1
• The CD4 count of 506 cells/mm³ is actually favorable and does not contraindicate HAART initiation—historically, concerns existed primarily for CD4 counts <200 cells/mm³. 1
• Case reports demonstrate marked improvement and even resolution of renal function following HAART initiation in patients with HIVAN, including those requiring dialysis. 2
• HAART may reduce HIV replication in renal tissue, which appears central to HIVAN pathogenesis, potentially slowing or reversing disease progression. 1

Initiate Hemodialysis Urgently

• Renal replacement therapy should begin prior to the development of life-threatening complications (grade E recommendation), and given this patient's severe uremia (creatinine 601 µmol/L), edema, and elevated BUN, dialysis is indicated immediately. 1
• Dialysis improves short-term survival in severe acute renal failure (level III evidence), and conventional criteria apply: diuretic-unresponsive pulmonary edema, hyperkalemia, and uremic complications. 1
• Dialysis and placement of arteriovenous fistulae should not be withheld for patients solely because of HIV infection (A-II recommendation). 1
• The consequences of uremic complications are likely more severe in critically ill patients, supporting earlier rather than later intervention. 1

Antiretroviral Selection and Dosing

Avoid Nephrotoxic Agents

• Tenofovir disoproxil fumarate should be avoided in this patient with creatinine clearance well below 50 mL/min, as it requires dosing interval adjustment and carries risk of further renal toxicity. 1, 3
• Tenofovir is principally eliminated by the kidney, and renal impairment including acute renal failure and Fanconi syndrome has been reported with its use. 3
• No safety or efficacy data are available for tenofovir in patients with severe renal impairment using adjusted dosing guidelines. 3

Recommended HAART Regimen Components

• Select a combination regimen with two nucleoside reverse transcriptase inhibitors (NRTIs) plus either a protease inhibitor or integrase inhibitor, avoiding tenofovir. 1, 2
• Appropriate dose reductions for antiretrovirals that are primarily renally eliminated are warranted (C-III recommendation), with additional doses given after hemodialysis for drugs readily removed by dialysis. 1
• Consult current antiretroviral dosing guidelines or a clinical pharmacist for specific dose adjustments based on the estimated GFR <15 mL/min. 1

Adjunctive Medical Therapy

ACE Inhibitors or ARBs

• Addition of ACE inhibitors or angiotensin receptor blockers should be considered if HAART alone does not result in improvement of renal function (B-II recommendation). 1
• ACE inhibition has shown protective effects in HIVAN animal models and improved outcomes in small human observational studies, potentially through improved renal hemodynamics, reduced proteinuria, or cytokine modulation. 1
• Start with a low dose (e.g., enalapril 2.5 mg daily or lisinopril 5 mg daily) and monitor closely for hyperkalemia and further decline in renal function. 1

Corticosteroids for Refractory Disease

• Prednisone should be considered in treating adult patients with refractory HIVAN (B-II recommendation), particularly if kidney function deteriorates despite HAART. 1
• Before initiating steroids, actively rule out underlying infection, which would be a contraindication for immunosuppressive therapy (B-III recommendation). 1
• If appropriate, use prednisone 1 mg/kg/day (maximum 80 mg/day) for 2 months, followed by a 2-4 month taper. 1
• The CD4 count of 506 cells/mm³ provides some reassurance regarding infection risk, though vigilance is still required. 1

Blood Pressure Management

• Control blood pressure with preferential use of ACE inhibitors or ARBs for patients with proteinuria (B-II recommendation). 1
• Calcium channel blockers should be avoided if protease inhibitors are used in the HAART regimen due to drug interactions (D-II recommendation). 1

Monitoring During Treatment

Renal Function and Dialysis Parameters

• Monitor serum creatinine, electrolytes (particularly potassium and phosphorus), and BUN at least twice weekly initially, then weekly once stable on dialysis. 1
• Assess dialysis adequacy using Kt/V or urea reduction ratio, with predialysis BUN drawn before dialysis starts and postdialysis BUN drawn 3-5 minutes after dialysis ends to account for urea rebound. 1
• Continue renal replacement therapy as long as criteria defining severe renal failure are present (grade E recommendation). 1

HIV-Specific Monitoring

• Check HIV viral load and CD4 count at 4 weeks after HAART initiation, then every 3 months to assess virologic response. 1
• Monitor for immune reconstitution syndrome, which may occur as the immune system responds to HAART, potentially unmasking indolent infections. 1

Proteinuria Assessment

• Quantify proteinuria using spot urine protein-to-creatinine ratio monthly to assess response to therapy. 1
• A decrease in proteinuria of 50% or more suggests therapeutic benefit from HAART and/or ACE inhibitor therapy. 1

Hepatitis B Vaccination

• HIV-infected patients requiring hemodialysis should have anti-HBs titers checked after receiving a standard primary series of 3 hepatitis B vaccinations and should receive a fourth injection if titers are <10 IU/L (B-II recommendation). 1
• This is critical given the high risk of hepatitis B transmission in the dialysis setting. 1

Common Pitfalls to Avoid

• Do not delay HAART initiation while waiting for renal biopsy confirmation—the clinical presentation (nephrotic-range proteinuria, rapid progression, young patient, HIV infection) is highly suggestive of HIVAN, and treatment should begin immediately. 1, 4
• Do not withhold dialysis due to concerns about poor prognosis—survival in HIV-infected dialysis patients has improved dramatically in the HAART era, with first-year survival now 74% and annual death rates approaching those of HIV-uninfected dialysis patients. 1
• Do not use standard doses of renally-eliminated antiretrovirals without adjustment—this increases toxicity risk significantly in patients with GFR <15 mL/min. 1, 3
• Do not assume the absence of edema rules out severe nephrotic syndrome in HIV patients—elevated serum globulins in HIV infection contribute to oncotic pressure, potentially delaying clinical edema despite severe hypoalbuminemia and proteinuria. 5
• Do not use nephrotoxic agents concurrently (e.g., high-dose or multiple NSAIDs, aminoglycosides)—alternatives should be considered in patients at risk for renal dysfunction. 3

Prognosis and Expectations

• Before HAART, HIVAN had a fulminant course with progression to end-stage renal disease within weeks and poor survival despite dialysis. 6, 7
• With HAART, some patients experience stabilization or even improvement in renal function, though many still progress to ESRD through uncertain mechanisms. 1
• The relatively preserved CD4 count (506 cells/mm³) in this patient is favorable and associated with better outcomes compared to those with advanced immunosuppression. 1