Probenecid-Induced IgA Nephropathy Is Reversible

ABSTRACT

Introduction: IgA nephropathy is usually idiopathic in nature but can have a genetic predisposition & it can also be secondary to autoimmune diseases, vasculitis, infections, liver disease, or anti-VEGFdrugs like bevacizumab, & covid vaccine. We present a case of probenecid-induced IgA nephropathy. Case Description A 65-year-old male with chronic gout developed progressive chronic kidney disease over a 3-year period. He had been on probenecid 1 g twice daily for his gout for 15 yrs. His sodium iothalamate clearance deteriorated to 58 mL/min, with a serum creatinine of 1.5 mg/dL. All other serologic tests were negative. His 72-hour lead level was also normal. He did not have SLE, granulomatous disease, or systemic rheumatic disorders. Suprisingly he did not have proteinuria or hematuria. Renal biopsy revealed IgA nephropathy, with segmental mesangial hypercellularity, mild arterial sclerosis, & tubular atrophy. Cytoplasmic lipofuscin pigment was noted on PAS stain capillary loops with focal thickening of the glomerular basement membrane, engorged capillary loops, & thickened tubular basement membrane. Immunofluorescence studies showed diffuse segmental paramesangial granules of IgA [3+] & fibrinogen as well as paramesangial granules of IgG [2+], Kappa & lambda. Electron microscopy showed swollen podocytes with increased cytoplasmic organelles and vacuolization, focal foot process effacement, & electron-dense deposits in the paramesangium & mesangium. His MEST score was zero. 6 months after discontinuation of probenecid, the patient's iothalamate GFR significantly improved to 79 mL/min, followed by 82 mL/min 6 months later. He never had proteinuria, hematuria, or casts throughout his disease course. Five years later his GFR was 88 ml/min with a serum creatinine of 1.1 mg/dl. Discussion(s) Probenecid has pleiotropic effects on the human immune system. It inhibits Pannexin-1 channels which are known to modulate T-cell function. Probenecid also regulates TRPV -2 channels as an agonist. These channels are also present on human immune B and T cell lymphocytes. Probenecid inhibits VEGF in retinal endothelial cells, & bevacizumab, an anti-VEGF monoclonal antibody, has been shown to cause IgA nephropathy. We conclude that probenecid can be a cause of IgA nephropathy which is reversible upon drug discontinuation.