SARS-CoV-2 vaccination and relapse of glomerular disease

Dear Editor,

The new SARS-CoV-2 severe acute respiratory syndrome-associated coronavirus SARS-CoV-2 (COVID-19) emerged in China in December 2019 and has spread globally, creating a major public health crisis.¹ As of January 2023, SARS-CoV-2 infections have been associated with more than 6.7 million deaths and 661 million infections. Several vaccines have been approved for SARS-CoV-2 infection, and numerous cases of both glomerulonephritis recurrence and de novo glomerulonephritis have been reported since their inception, mainly after successive doses of mRNA vaccines.^2–4 The aetiopathogenesis is not fully understood and is based on the theory of dysregulation of cellular immunity mediated by T-helper 2 cells, which increases the release of cytokines that cause podocyte injury.^4,5

We report two cases of glomerulonephritis recurrence after administration of successive doses of SARS-CoV-2 mRNA vaccine.

The first case is that of a 73-year-old male with a history of arterial hypertension and type 2 diabetes mellitus, diagnosed with primary membranous nephropathy in 2019. Anasarca secondary to nephrotic syndrome were the initial symptoms, with creatinine (Cr) of 1.25 mg/dl, glomerular filtration rate (GFR CKD-EPI) of 61 ml/min/1.73 m², hypoalbuminaemia, proteinuria of 13.44 g/24 h and hypercholesterolaemia. The complement analysis was normal and autoimmunity was negative, except for the determination of anti-PLA2R antibodies with levels of 78 UR/ml (Fig. 1). Secondary causes were ruled out and a renal biopsy was compatible with stage III membranous glomerulonephritis. After starting treatment according to Ponticelli's guidelines, the patient experienced partial clinical remission (proteinuria of 1.2 g/24 h), slight improvement in renal function, restored total protein and albumin levels with immunological remission (anti-PLA2R antibody-negative (8.84 UR/ml)). The patient remained stable with Cr 1–1.2 mg/dl, GFR(CKD-EPI) of 60-65 ml/min/1.73 m² and proteinuria 1 g/24 h until June 2021. Coinciding with the administration of the second dose of vaccine against SARS-CoV-2 (Moderna®), he experienced deterioration of renal function, with Cr 1.4 mg/dl, increase in proteinuria up to 4.68 g/24 h, total protein 5.9 g/dl, albumin 3.7 g/dl and anti-PLA2Rs-positive (32.80 UR/ml). During the following 6 months renal function worsened to Cr 2.1 mg/dl, GFR(CKD-EPI) 32 ml/min/1.73 m², fluid overload symptoms, total protein 4.5–5 g/dl, hypoalbuminaemia 2.6 g/dl, proteinuria 11 g/24 h and elevated anti-PLA2R antibodies (269.8 UR/ml). Two doses of IV rituximab 1 g were prescribed, showing partial clinical remission with proteinuria of 3.97 g/24 h, persistence of hypoproteinaemia and hypoalbuminaemia and complete immunological remission and anti-PLA2R antibody-negative (4.4 UR/ml) (Fig. 1).

Figure 1.

Change in serum creatinine, proteinuria and anti-PLA2R antibodies before and after vaccination against SARS-CoV-2 in a patient diagnosed with membranous nephropathy (left graph) and in a patient diagnosed with IgA nephropathy (right graph).

The second case is that of a 31-year-old male with a history of arterial hypertension and IgA nephropathy diagnosed in 2015 after renal biopsy (M1, E0, S0, T0 according to the Oxford Classification 2009). At the time of diagnosis, the patient had Cr 1.14 mg/dl, total protein 6.5 g/dl, albumin 4.1 g/dl, normal serum immunoglobulins (IgA 362 mg/dl), normal complement and autoimmunity studies, microhaematuria (20 red blood cells/μl) and proteinuria 5.33 g/24 h. He received supportive treatment (low-dose antiproteinuric acid) and prednisone 60 mg/day for 3 months, with a subsequent tapering regimen, showing progressive improvement in proteinuria, negative microhaematuria and normal renal function. Prednisone 2.5 mg/day was maintained, showing partial remission with proteinuria 0.8-2 g/24 h and oscillating microhaematuria (40–100 RBCs/μl) (Fig. 1). In July 2021 he had Cr 1.35 mg/dl, GFR(CKD-EPI) 70 ml/min/1.73 m², microhaematuria (71 RBCs/μl) and proteinuria 3.6 g/24 h. Following the second and third doses of vaccine (Pfizer®) against SARS-CoV-2, he had episodes of self-limiting macrohaematuria lasting 3-4 days. After the third dose Cr 1.47 mg/dl, GFR(CKD-EPI) 63 ml/min/1.73 m², persistent microhaematuria and increased proteinuria 6.96 g/day were observed. Prednisone dose was increased to 60 mg/day with good response, stable renal function and partial clinical remission (Fig. 1).

The cases reported here are two examples of patients with different stable glomerulonephritis who experienced disease reactivation coinciding with the administration of successive doses of mRNA-type COVID-19 vaccines, after ruling out other causes. Cases of recurrence of IgA nephropathy, minimal change disease, vasculitis and membranous nephropathy have been reported following vaccination against COVID-19.³ According to published literature, reactivation of glomerulonephritis after successive doses of mRNA vaccines may be justified by an aberrant immune response to the spike protein or messenger RNA of SARS-CoV-2 in predisposed individuals, whose immune response is amplified after successive doses.⁴

Although vaccines may increase the risk of causing an exacerbation of glomerular disease, the benefits of vaccination outweigh the risks, as patients with renal pathology have high morbidity and mortality following SARS-CoV-2 infection.² Given the magnitude of the COVID-19 pandemic and considering that vaccination is currently the only tool available to eradicate it, careful post-vaccination follow-up of patients with glomerular disease is advisable.

Ethical considerations

This work respects the applicable ethical considerations and has not involved animal testing.

Funding

This work is not funded in any way.

Conflict of interest

The authors declare that they have no conflicts of interest.