Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits with Severe Acute Kidney Injury Successfully Managed by Clone-Directed Therapy: A Case Report.

<p>Introduction: Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a form of monoclonal gammopathy of renal significance, characterized by kidney injury caused by monoclonal immunoglobulin deposition in the glomeruli. While detectable clones are only found in 20-30% of PGNMID, plasma cell- or B-cell-targeting therapies are suggested to be effective. Recent case reports suggested immune dysregulation, such as viral infections or vaccinations, could potentially trigger the onset or relapse of PGNMID. Here, we report a case of PGNMID without detectable clones, which relapsed after viral enteritis, presenting with severe acute kidney injury (AKI) and nephrotic syndrome. Case Presentation: A 60-year-old man, originally diagnosed with IgG3 lambda type PGNMID with nephrotic syndrome (urine protein/creatinine ratio (UPCR) of 5.3 g/gCr), was treated with non-clone-directed therapeutic regimens, including glucocorticoids. The patient initially achieved a partial response with a UPCR of 1-3 g/gCr and negative microhematuria. Approximately 2 years later, the patient presented with severe AKI (Cr 11.0 mg/dL) requiring dialysis, and nephrotic syndrome (UPCR 5.5 g/gCr, and serum albumin 2.4 g/dL) after having had viral enteritis. Second kidney biopsy confirmed a similar pattern of injury consistent with PGNMID with IgG3 lambda deposition, severe endocapillary inflammation, mesangial expansion, and remarkable narrowing of the glomerular capillary lumina. As it was refractory to glucocorticoid pulse therapy, clone-directed therapies with daratumumab and bortezomib were initiated. This intervention resulted in the cessation of dialysis and an improvement in urinary parameters. Conclusion: Clinicians should recognize that severe AKI may develop during the course of PGNMID, potentially triggered by infections. Furthermore, this case highlights the efficacy of clone-directed therapy with daratumumab and bortezomib in treating recurrent PGNMID without detectable clones. </p>.