A broad range of glomerular diseases is associated with different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations [1]. In this context, atypical haemolytic uraemic syndrome (aHUS) due to glomerular thrombotic microangiopathy (TMA) has not been reported in the literature so far following SARS-CoV-2 vaccination with Comirnaty (BioNTech, Mainz, Germany).
We herein describe a 60-year-old woman who was admitted to a rural hospital because of general discomfort. She was then transferred to our institution for suspicion of aHUS. On admission, she presented with a serum creatinine of 2.1 mg/dL, a platelet count of 42 g/L, a haemoglobin of 7.1 g/dL and lactate dehydrogenase of 1700 U/L and schistocytes were detectable on a peripheral blood smear (21 ppt). Haptoglobin was not detectable and the activity of a disintegrin and metalloprotease with thrombospondin type 1 motif 13 was 53%, ruling out the presence of thrombotic thrombocytopaenic purpura. Her medical history and laboratory workup were unremarkable with regard to potential causes of secondary TMAs such as active cancer, hypertensive emergency, drugs, infections or autoimmune diseases [2, 3]. Of note, after suffering from mild coronavirus disease 2019 (COVID-19) some 6 months ago, she received her first SARS-CoV-2 vaccination (Comirnaty) about 2 weeks before the onset of symptoms of her current illness. She did not carry pathogenic variants in CFH, CFI or CD46. However, she showed the CFH-H3 haplotype (heterozygous), which results in slightly reduced plasma levels of factor H and is strongly associated with a risk for aHUS. A kidney biopsy showed a glomerular TMA (Figure 1). She responded well to plasma exchange and currently has preserved renal function.
FIGURE 1:
Kidney biopsy showing glomerular thrombotic microangiopathy (arrow). Staining: acid fuchsin orange G, bar = 50 µm, original magnification × 80.
In summary, we propose a clinical diagnosis of aHUS, triggered by the messenger RNA (mRNA) SARS-CoV-2 vaccination. Causality, in this case, is based on a temporal association and we cannot demonstrate a direct link with vaccination. However, our observation finds support with reports describing renal TMA lesions in kidney biopsies in two cases with minimal change disease not presenting with aHUS following vaccination with Comirnaty [4, 5]. Furthermore, vaccination with the vector-based ChAdOx1 nCoV-19 vaccine led to aHUS in another case described by Ferrer et al. [6]. Finally, thrombotic thrombocytopaenic purpura may also be associated with SARS-CoV-2 vaccination [7]. Thus mRNA- and vector-based COVID-19 vaccines seem to represent important trigger factors for the rare development of different TMA entities. In our case, the competent authority made an exception to full immunization with a second and subsequent booster vaccinations given the potential risk for recurrence of aHUS.
PATIENT CONSENT
The patient gave informed consent to publish this case.
CONFLICT OF INTEREST STATEMENT
None declared.
Contributor Information
Sophie H Schmidt, Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria; Sigmund Freud University, Medical School, Vienna, Austria.
Alice Schmidt, Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria.
Christof Aigner, Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria.
Renate Kain, Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria.
Gere Sunder-Plassmann, Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria.
REFERENCES
- 1. Kronbichler A, Jung SY, Kim MSet al. Distinct glomerular disease association after vaccination with BNT162b2 and mRNA-1273: a VigiBase analysis. Kidney Int 2022; 101: 415–416 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Aigner C, Schmidt A, Gaggl Met al. An updated classification of thrombotic microangiopathies and treatment of complement gene variant-mediated thrombotic microangiopathy. Clin Kidney J 2019; 12: 333–337 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Fakhouri F, Fremeaux-Bacchi V. Thrombotic microangiopathy in aHUS and beyond: clinical clues from complement genetics. Nat Rev Nephrol 2021; 17: 543–553 [DOI] [PubMed] [Google Scholar]
- 4. De Fabritiis M, Angelini ML, Fabbrizio Bet al. Renal thrombotic microangiopathy in concurrent COVID-19 vaccination and infection. Pathogens 2021; 10: 1045. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Tanaka F, Katayama K, Joh Ket al. Minimal change disease with thrombotic microangiopathy following the Pfizer-BioNTech COVID-19 vaccine. Clin Kidney J 2021; 15: 567–568 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Ferrer F, Roldão M, Figueiredo Cet al. Atypical hemolytic uremic syndrome after ChAdOx1 nCoV-19 vaccination in a patient with homozygous CFHR3/CFHR1 gene deletion. Nephron 2022; 146: 185–189 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. Kirpalani A, Garabon J, Amos K.et al. Thrombotic thrombocytopenic purpura temporally associated with BNT162b2 vaccination in an adolescent successfully treated with caplacizumab. Br J Haematol 2022; 196: e11–e14 [DOI] [PMC free article] [PubMed] [Google Scholar]