What is the management for a patient with HIV (Human Immunodeficiency Virus) and acute kidney injury (AKI) with impaired renal function, indicated by a serum creatinine level of 4, who has a positive CMV (Cytomegalovirus) IgM result?

Management of CMV IgM Positive HIV Patient with AKI (Creatinine 4)

Initiate IV ganciclovir at renally-adjusted doses immediately for CMV treatment while simultaneously addressing the acute kidney injury through nephrotoxin removal, fluid resuscitation, and close monitoring—this patient requires urgent treatment of both conditions as CMV can worsen AKI and untreated AKI will complicate antiviral dosing. 1, 2

Immediate CMV Treatment with Renal Dose Adjustment

Ganciclovir Dosing for Severe Renal Impairment

With a serum creatinine of 4 mg/dL, the estimated creatinine clearance is likely 10-24 mL/min, requiring significant dose reduction:

• Induction therapy: 450 mg IV every other day (instead of standard 5 mg/kg twice daily) 1
• If CrCl <10 mL/min: Use IV ganciclovir rather than valganciclovir, as the oral formulation is not recommended by the manufacturer at this level of renal function 1
• Hemodialysis patients: Consider 200 mg oral powder formulation three times weekly for induction if oral route is necessary 1

The standard induction dose of 5 mg/kg IV twice daily must be avoided at this creatinine level to prevent severe toxicity 1. IV ganciclovir is preferred over valganciclovir in severe renal impairment because dosing can be more precisely controlled 1.

Simultaneous AKI Management

Identify and Remove Nephrotoxins Immediately

• Discontinue all nephrotoxic medications including NSAIDs, aminoglycosides, tenofovir (TDF), atazanavir, lopinavir/ritonavir, and any other potentially nephrotoxic antiretrovirals 1, 2
• Review all medications including over-the-counter supplements, as these can falsely elevate creatinine or cause actual nephrotoxicity 3
• The "triple whammy" combination (NSAIDs + diuretics + ACE inhibitors/ARBs) must be discontinued if present 2

Determine AKI Etiology in This Context

The most likely causes in an HIV patient with CMV infection include:

• Sepsis from CMV or concurrent infections (59% of AKI cases in HIV patients) 4
• Nephrotoxic antiretroviral therapy, particularly tenofovir-based regimens with boosted protease inhibitors 1
• Volume depletion (21.6% of cases) 4
• CMV-related glomerular disease during acute viral replication 5

Fluid Resuscitation Protocol

• Administer isotonic crystalloids (preferably lactated Ringer's over 0.9% saline) as first-line therapy 2
• Target mean arterial pressure ≥65 mmHg to ensure adequate renal perfusion 2
• Use dynamic indices (passive leg-raising test, pulse/stroke volume variation) rather than static measurements to guide fluid therapy 2
• Avoid excessive fluid administration leading to >10-15% body weight fluid overload, as this is associated with adverse outcomes 2

HIV Antiretroviral Adjustment

Modify ART Regimen for Renal Protection

• Switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) or abacavir if TDF is part of current regimen, as TDF is associated with proximal tubular dysfunction and should be avoided in patients with CrCl <60 mL/min 1
• Avoid atazanavir and lopinavir/ritonavir in the setting of CKD or rapid eGFR decline, as these have been linked to interstitial nephritis and progressive kidney disease 1
• Continue ART during AKI management, as immunovirological control reduces the incidence of AKI and HIV-related kidney diseases 1

Dose Adjustments for Other Antiretrovirals

• Lamivudine: 150 mg once daily (instead of twice daily) for CrCl 30-49 mL/min; 150 mg first dose then 100 mg once daily for CrCl 15-29 mL/min 1
• Zidovudine: 100 mg every 6-8 hours for CrCl <15 mL/min 1
• NNRTIs and most protease inhibitors do not require dose adjustment, though nevirapine should be dosed after dialysis if hemodialysis is initiated 1

Monitoring Strategy

Intensive Laboratory Surveillance

• Measure serum creatinine and electrolytes every 12-24 hours during acute management 2
• Monitor urine output, vital signs, and fluid balance closely in the first 48-72 hours 2
• Check CMV viral load to assess treatment response, as viral load eradication should occur by day 21 of therapy 6
• Monitor for CMV treatment-related toxicity including neutropenia and thrombocytopenia

Renal Function Trajectory Assessment

• Calculate creatinine clearance using the Cockcroft-Gault formula rather than relying on eGFR equations (MDRD, CKD-EPI), as these require steady-state creatinine and are inaccurate in AKI 1, 2
• Perform urinalysis to detect proteinuria or hematuria, and quantify proteinuria if present 1
• Consider nephrology referral if AKI persists despite appropriate interventions or if the cause remains unclear 1

Critical Pitfalls to Avoid

• Never use standard-dose valganciclovir or ganciclovir without renal adjustment—this will cause severe bone marrow suppression and worsening toxicity 1
• Do not use furosemide in hemodynamically unstable patients with prerenal AKI, as it worsens volume depletion and reduces renal perfusion 2
• Avoid cidofovir entirely in this patient, as it is contraindicated with serum creatinine >1.5 mg/dL or calculated creatinine clearance ≤55 mL/min 7
• Do not delay CMV treatment while waiting for renal function improvement—use appropriately dose-adjusted IV ganciclovir immediately 1
• Avoid combining multiple nephrotoxic agents, as each additional nephrotoxin increases AKI odds by 53% 2

Transition to Maintenance Therapy

Once induction is complete (typically 14-21 days) and renal function stabilizes:

• Maintenance dosing: Adjust valganciclovir to 450 mg every other day for CrCl 25-39 mL/min, or 450 mg twice weekly for CrCl 10-24 mL/min 1
• Continue maintenance therapy until immune reconstitution occurs (CD4 count >100 cells/mm³ for at least 3-6 months on ART) 1
• Monitor for CMV recurrence, which occurs in 14.3% of patients, with higher rates in those with donor-positive/recipient-negative serostatus or receiving immunosuppression 6

Prognosis and Follow-Up

• AKI in HIV patients is independently associated with 2.7-fold increased in-hospital mortality 4
• Even with complete AKI recovery, patients remain at increased risk of progressive CKD and require long-term follow-up 2
• 63.2% of patients who recover kidney function may leave hospital with persistent kidney injury 8
• Target follow-up to high-risk populations including those with baseline CKD, monitoring for development or progression of chronic kidney disease 2