Minimal Change Disease Superimposed on Pre‑existing Membranous Nephropathy After mRNA Vaccination, Acute Proteinuria Onset
1. Rapidly Emerging Renal Crisis: From 0.5 to 14.3
A 72‑year‑old male patient who had been living with type 2 diabetes for 32 years and had managed stable membranous nephropathy (MN) for 11 years experienced a sudden crisis. After the third dose of the BNT162b2 mRNA vaccine, his proteinuria, which had been consistently around 0.5 g/gCr, surged to 14.3 g/gCr, precipitating a nephrotic‑syndrome state. At first glance, this appeared to be a relapse or worsening of his pre‑existing membranous nephropathy.
2. Unexpected Clue from Renal Biopsy: "Something’s Not Right?"
A kidney biopsy was performed to identify the precise etiology. The findings were puzzling. Histologically, the classic features of chronic membranous nephropathy were evident, yet anti‑PLA2R antibodies were undetectable in the serum. Moreover, the protein selectivity index was markedly low, a hallmark of minimal change disease (MCD) in which predominantly albumin leaks across the glomerular barrier.
3. Steroid Therapy Confirmed the Final Diagnosis
The clinical team concluded that the presentation represented vaccine‑associated MCD superimposed on the pre‑existing disease rather than a simple exacerbation of MN, and initiated steroid pulse therapy. The response was dramatic: proteinuria returned to baseline within a short period, a rapid improvement characteristic of MCD and distinct from the slower response typically seen in membranous nephropathy.
4. Clinical Implications
This case alerts clinicians that podocytopathy can emerge de novo in patients with pre‑existing renal disease following mRNA vaccination. When a patient’s condition deteriorates unusually rapidly, the possibility of a superimposed, mechanistically distinct disease should be entertained rather than attributing the change to a simple relapse. Recognizing this distinction can prevent unnecessary drug exposure and help preserve renal function.
mRNA-based COVID-19 vaccines have been associated with rare renal complications, including podocytopathies. We report a 72-year-old Japanese man with a 32-year history of type 2 diabetes and an 11-year history of stable membranous nephropathy (MN) who developed nephrotic syndrome (NS) after receiving his third dose of the BNT162b2 mRNA vaccine. His proteinuria, which had been stable at approximately 0.5 g/gCr for years, acutely increased to 14.3 g/gCr. A kidney biopsy revealed diffuse thickening of the glomerular basement membrane with subepithelial spike formation, and phospholipid A2 receptor (PLA2R)-positive deposits embedded in the membrane (Churg stage 2-4), consistent with his chronic, inactive MN. However, several clinical features were atypical for an MN relapse: serum anti-PLA2R antibodies were undetectable, the protein selectivity index was low (indicating highly selective proteinuria), and a transient spontaneous reduction in proteinuria occurred during hospitalisation. Although early-stage gastric cancer was concurrently detected and curatively resected via endoscopic submucosal dissection, NS recurred shortly thereafter. Proteinuria rapidly decreased to baseline levels following steroid pulse therapy-a therapeutic response characteristic of minimal change disease (MCD). Based on these findings, we diagnosed the patient with vaccine-associated MCD superimposed on stable MN. This case suggests that when an existing glomerular disease follows an unusually acute course after vaccination, clinicians should consider the possibility of a superimposed podocytopathy. Accurate differentiation is essential, as the management of MCD differs significantly from that of MN.
If the episode had been misinterpreted as a flare of the existing disease and treated inappropriately, the patient’s kidneys could have suffered irreversible damage. By meticulously analyzing the atypical post‑vaccination response and identifying the true culprit, appropriate steroid therapy was administered, fully preserving the patient’s valuable renal function.