Sharp rise in proteinuria after mRNA vaccination: minimal change disease superimposed on membranous nephropathy
Background: Sudden worsening of proteinuria in a patient with stable membranous nephropathy
A 72-year-old Japanese man with a 32-year history of type 2 diabetes and membranous nephropathy (MN) that had remained stable for 11 years developed nephrotic syndrome after his third dose of the BNT162b2 mRNA vaccine. Proteinuria, which had been about 0.5 g/gCr for several years, rose sharply to 14.3 g/gCr. Based on multiple test findings and the clinical course, the investigators diagnosed minimal change disease (MCD) superimposed on pre-existing MN.
Key findings: Multiple findings supported a diagnosis of superimposed minimal change disease
Kidney biopsy showed diffuse thickening of the glomerular basement membrane, subepithelial spike formation, and phospholipase A2 receptor (PLA2R)-positive deposits located within the membrane. The investigators interpreted these findings as consistent with chronic, inactive MN. Serum anti-PLA2R antibodies, however, were not detected. Tissue deposits and circulating antibodies are distinct test findings; the investigators assessed the non-detection of serum antibodies alongside the other clinical findings.
The clinical course was also atypical for an MN relapse. The protein selectivity index was low, indicating highly selective proteinuria, and proteinuria temporarily decreased spontaneously during hospitalization. Early gastric cancer was also found and curatively resected by endoscopic submucosal dissection, but nephrotic syndrome recurred shortly afterward. The abstract described this course but did not establish a causal relationship between the gastric cancer and nephrotic syndrome.
After steroid pulse therapy, proteinuria rapidly fell to its previous baseline level. This is a characteristic treatment response in MCD. Considering the tissue and serum tests, the characteristics of the proteinuria, its spontaneous decrease, and the treatment response together, the investigators diagnosed vaccine-associated MCD superimposed on stable MN. The treatment response was one of several clues supporting the diagnosis; the reported outcome was a decrease in proteinuria to its previous baseline level.
Implications and outlook: Clues to distinguishing relapse of an existing disease from a superimposed condition
This case suggests that when a patient with a pre-existing glomerular disease experiences unusually rapid worsening after vaccination, clinicians may consider a newly superimposed podocytopathy as well as relapse of the original disease. The investigators explained that distinguishing the two conditions matters because MCD and MN are managed differently.
However, this is a case report of one patient’s course after vaccination and cannot establish that the vaccine caused MCD or determine the risk of developing it. The abstract provided does not give the exact interval from vaccination to onset, the steroid dose, or long-term follow-up results for kidney function. The decrease in proteinuria should not be interpreted as complete recovery of kidney function or prevention of permanent damage.
Source: Nephrology case report abstract.
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.
A sudden increase in proteinuria in a patient with pre-existing membranous nephropathy warrants assessment of whether relapse of the original disease alone explains it. In this case, the diagnosis of superimposed minimal change disease was based on a combined assessment of tissue PLA2R-positive deposits, undetectable serum antibodies, highly selective proteinuria, a temporary spontaneous decrease, and a response to steroids. The case illustrates an approach that combines multiple tests with the clinical course over time when evaluating the cause of rapid worsening. Because MCD and MN are managed differently, this distinction can inform treatment decisions. A single case, however, does not establish the general effectiveness of any particular test or treatment, and long-term preservation of kidney function was not confirmed.