ATYPICAL IGA NEPHROPATHY UNMASKED BY IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME IN A HIV PATIENT

While IRIS (Immune reconstitution inflammatory syndrome) typically refers to the unmasking of a latent infection or paradoxical worsening of a known infection after the initiation of antiretroviral therapy, it may also result in the development or worsening of autoimmune conditions like SLE and RA. However, IRIS leading to the unmasking of glomerular diseases is rarely reported.

A 42-year-old woman diagnosed with HIV presented with nausea and vomiting for 2 weeks, two months after starting highly active antiretroviral therapy (HAART) containing tenofovir disoproxil fumarate (TDF) 300 mg, lamivudine 300mg, and dolutegravir 50 mg. She had a history of intermittent hematuria over the past year. On examination, she had pallor, mild pedal edema and her blood pressure was 160/90 mm Hg. The rest of the systemic examination was normal. Her laboratory workup was notable for a serum creatinine of 12 mg/dL and hemoglobin of 7.2 g/dL (Table). Urine analysis revealed protein of 2+ and red blood cells (12-15/hpf). 24-hour urine protein excretion was 4.1 g. Her CD4+ T-cell count had increased from 80 cells/μL prior to starting HAART to 290 cells/μL at the time of presentation. Her HIV-1 RNA viral load had decreased from 18,850 IU/mL at the start of ART to less than 39.1 IU/mL at the time of presentation. A percutaneous ultrasound-guided kidney biopsy was performed after 3 sessions of hemodialysis. Light microscopy examination (Figure 1) of 16 available glomeruli showed crescents in four glomeruli (1 cellular and 3 fibrocellular). The remaining glomeruli revealed a variable mild increase in mesangial matrix/cellularity and segmental endocapillary hypercellularity. DIF studies showed mesangial IgA (3+), C3 (1+), and kappa (3+) staining and lambda (1+).

She was treated with IV methylprednisolone 500 mg for 3 doses, followed by oral prednisolone at 0.5 mg/kg body weight. HAART was modified to an abacavir-based regimen. Her renal function improved and she was discharged after 2 weeks at a stable creatinine of 3.2 mg/dL. During follow-up, her steroids were tapered and stopped over a course of two months. At the 3-month follow-up, her serum creatinine had improved to 1.27 mg/dL (Figure 2), her urinalysis was negative for protein and red blood cells, and her 24-hour urine protein excretion had declined to 240 mg.

IRIS can manifest in various forms, affecting different organ systems. The most common organ systems involved are the respiratory system and the skin. IRIS affecting kidneys is very rare, typically involving tubulointerstitial compartment. However, in our case, the patient's past history of intermittent hematuria, along with the current clinical presentation, suggests glomerular involvement. The presence of mesangial IgA deposits in the renal biopsy is suggestive of IgA nephropathy, but the atypical kappa light chain dominance suggests the possibility of an underlying, undiagnosed monoclonal gammopathy that may become apparent over time. IRIS typically occurs within the first few weeks to months after the initiation of ART, coinciding with a rise in CD4+ T-cell counts. Our patient's presentation aligns with this timeline. To conclude, this case emphasizes the need for clinicians to be aware of the diverse renal manifestations of IRIS in the setting of HIV. It also underscores the need for vigilance after initiating HAART.