#2154 Imlifidase a new treatment for severe minimal change disease?

Abstract Background and Aims Minimal change disease (MCD) is an immune-mediated podocytopathy recently characterized by the presence of circulating and kidney-bound anti-nephrin antibodies in a significant subset of patients. Imlifidase (Hansa Biopharma, Lund, Sweden) is an IgG-degrading enzyme that cleaves all human IgG subclasses, producing [F(ab′)2] and Fc fragments. It shows promise in treating autoimmune diseases like anti-GBM disease. Herein we report a case of MCD treated with imlifidase. Method An 82-year old patient with no significant prior medical history was admitted in our renal intensive care unit for a nephrotic syndrome complicated with acute kidney injury. On admission his blood pressure was measure at 190/120 mmHg with evidence of volume overload. Biologically, severe KDIGO stage 3 AKI was noted, with a creatinine level of 319 µmol/L (eGFR 16 ml/min/1.73 m²), along with a nephrotic syndrome defined by low levels of plasma albumin at 18 g/L and proteinuria at 20.8 g/L, of which 16 g/L was albuminuria (77%). Urinary biochemistry was consistent with prerenal azotemia with restricted natriuresis (NaU < 20 mmol/L) and elevated urinary creatinine (20 mmol/L). The patient was started on hemodialysis 12 hours following admission for life-threatening hyperkalemia. A kidney biopsy performed on day 5 revealed no glomerular lesions upon optical microscopy. Immunofluorescence showed fine granular podocytic staining, consistent with anti-IgG antibodies consistent with anti-nephrin deposits. A diagnosis of minimal change disease was posed. The patient was immediately started on prednisone 1 mg/kg. Two weeks after starting corticosteroid therapy, the patient remained severely oliguric (100–200 mL per day), requiring repeated hemodialysis, with while heavy proteinuria. (Fig. 1). Serum sampling was performed for anti-nephrin antibody testing at various time points but the results are expected soon. Results Imlifidase was administered intravenously at a dose of 22 mg (equivalent to 0.30 mg/kg) on the 14 days after initiation of cortisteroid therapy. Following the injection, a rapid and significant increase in urine output was observed without any changes to the diuretic treatment, allowing for the discontinuation of renal replacement therapy. By the fourth day post-injection, urine output exceeded 1.5 liters per day. Kidney function plateaued 48 hours after the administration of imlifidase and improved rapidly from the fourth day onward. By 10 days after the imlifidase injection, kidney function had returned to baseline level with a serum creatinine at 88 µmol/L (ie., an eGFR at 76 ml/min/1.73m²), and antihypertensive medications including diuretics were discontinued. A 50% reduction in proteinuria levels was observed 48 hours after the injection (4 g/L vs. 8 g/L), plummeting to less than 1 g/L by the fourth day. By day 7 post-imlifidase, total proteinuria was below 0.5 g/L. Imlifidase injection was well tolerated. Rituximab was administered 5 days after imlifidase. Thirty days after imlifidase injection, the patient remained in remission from MCD with a kidney function at baseline level plasma creatinine at 99 µmol/L (eGFR: 66 mL/min/1.73 m2) normal plasma albumin (39 g/L) and albuminuria within physiological range (19.1 mg/L). Corticosteroid therapy was gradually tapered down to 5 mg two months after its initiation. Conclusion Imlifidase may offer a potential add-on therapeutic option for minimal change disease (MCD) patients when used in combination with other anti-B cell targeted therapies. Methodologically rigorous studies are needed to confirm these findings.

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