Recurrent proteinuria with graft dysfunction: a diagnostic and clinical conundrum

Area of Science:

• Nephrology
• Immunology
• Transplantation

Background:

• Kidney transplantation is a vital treatment for end-stage renal disease.
• Monitoring for and managing post-transplant complications like antibody-mediated rejection (AMR) is crucial for long-term graft survival.
• Early diagnosis and intervention can significantly impact patient outcomes.

Observation:

• A kidney transplant recipient developed significant proteinuria and rising creatinine levels two years post-transplant.
• Initial biopsies showed glomerular changes, but lacked definitive markers for common causes like PLA2R nephropathy.
• A subsequent biopsy revealed thickened glomerular basement membranes, C4d deposition, and importantly, positive donor-specific antibodies (HLA DR).

Findings:

• The patient's condition was diagnosed as antibody-mediated rejection (AMR) driven by donor-specific antibodies (DSA), despite negative serum PLA2R antibodies.
• Treatment with a combination of pulse methylprednisolone, plasma exchange, intravenous immunoglobulin, and rituximab was initiated.
• This intensive immunosuppressive therapy led to a significant reduction in DSA levels and improvement in renal function, with decreased proteinuria and stabilized serum creatinine.

Implications:

• This case underscores the importance of comprehensive DSA screening in transplant recipients presenting with graft dysfunction, even with atypical biopsy findings.
• It demonstrates the efficacy of multi-agent immunosuppressive therapy in managing DSA-mediated AMR, even in later stages post-transplant.
• The findings contribute to understanding the complex mechanisms of AMR and optimizing treatment strategies in kidney transplant recipients.