Journal Information
Vol. 43. Issue. 5.September - October 2023
Pages 517-662
Vol. 43. Issue. 5.September - October 2023
Pages 517-662
Letter to the Editor
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Hematuria in patients with IgA nephropathy after vaccine for SARS-CoV-2
Hematuria macroscópica en pacientes con nefropatía IgA tras vacuna para SARS-CoV-2
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Leonardo Calle Garciaa,
Corresponding author
sailorleo20@hotmail.com

Corresponding author.
, Carmen Martin Varasa, Giomar Urzola Rodrigueza, Maria Marcos Hidalgoa, Astrid Rodriguez Gomeza, Alvaro Molina Ordasa, Veronica Fidalgo Gonzaleza, Pablo Sanchez Garrotea, Paulo Garcia Gutierreza, Marta Garcia de Burgosb, Maria Jose Fernandez-Reyes Luisa
a Servicio de Nefrología, CA Segovia, Spain
b Servicio de Análisis Clínicos, CA Segovia, Spain
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Table 1. Clinical data of the patients, before and after vaccination.
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Dear Editor,

The devastating COVID-19 pandemic has led to rapid mass vaccination of the population in record time. Vaccine types different from classical inactivated virus or conjugate vaccines are being used for this purpose, based on the administration of a purified nucleoside of the virus messenger RNA (Moderna®, Pfizer®) or virus DNA viral vector (AstraZeneca®).1

Recently, several cases2–6 of patients with IgA nephropathy who developed macroscopic hematuria after administration of SARS-CoV-2 vaccines have been reported. We present three cases of patients with IgA nephropathy, vaccinated with different types of SARS-CoV-2 vaccine and being followed in our hospital, who developed macroscopic hematuria.Case 1

A 52-year-old male under follow-up and being treated since 1995 for IgA nephropathy. His renal function was normal and he tested negative for proteinuria. He had not had COVID-19. He attended emergency department 48h after administration of the second dose of the Moderna® vaccine due to onset of macroscopic hematuria. He was totally asymptomatic. After 24h of observation, the clinical signs and symptoms resolved spontaneously. Macroscopic hematuria was confirmed by urgent assessment by the Laboratory Testing Department (Table 1).

Table 1.

Clinical data of the patients, before and after vaccination.

Patient  Age, years  Gender  IgA nephropathy diagnosis with biopsy  Vaccine  PCr mg/dl pre-vaccine  PCr mg/dl post-vaccine  US pre-vaccine  US post-vaccine  Associated symptoms 
52  Yes  Moderna®  0.8  0.7  1–3dysmorphic red blood cells/field  +100 dysmorphic red blood cells/field  No 
63  Yes  Moderna®  3.5  3.9  10–30 dysmorphic red blood cells/field  +100 dysmorphic red blood cells/field  No 
45  No  AstraZeneca®  1.5  1.3  20–40 dysmorphic red blood cells/field  15–20 dysmorphic red blood cells/field  No 

PCr: plasma creatinine; US: urine sediment; M: male.

Case 2

A 63-year-old male, diagnosed in December 2019 with IgA nephropathy with rapidly progressive component and extracapillary proliferation. He started peritoneal dialysis in October 2020. He was infected with COVID-19 in December 2020, with a good clinical course. He currently experiences bouts of asymptomatic macroscopic hematuria, which are self-limiting and disappear after resolution of the clinical signs and symptoms. Vaccination with the Moderna® vaccine started between February and March 2021. Onset of macroscopic hematuria occurred 48h after the first dose, which disappeared 48h later. There were no complications in his peritoneal dialysis treatment. The episode recurred after administration of the second dose of the vaccine (Table 1).

Case 3

A 45-year-old male, under follow-up for probable Henoch-Schonlein purpura and IgA nephropathy (episodes of dark urines coinciding with upper respiratory tract symptoms, purpuric dermatosis, etc.). He had not had COVID-19. The first AstraZeneca® vaccination dose was administered according to the schedule. After 24h, macroscopic hematuria developed and continued for 36h until it disappeared completely. He was asymptomatic at all times. This same clinical picture reocurred after administration of the second vaccine dose. There was no purpuric dermatosis or other clinical manifestations (Table 1).

The development of glomerular diseases, especially vasculitis, secondary to the administration of vaccines for viruses or bacteria, is widely reported in the literature.2,3 With particular regard to SARS-CoV-2 vaccines, there have been reported small case series of patients with IgA nephropathy who developed macroscopic hematuria following administration of the first or second dose, or both.2–5

It has been postulated that these vaccines trigger CD4 and CD8 T-lymphocyte activation, leading to a systemic cytokine cascade.1 This cascade would be mediated by an increase in IgA1 production, which would lead to the development of a bout of macroscopic hematuria in these patients.2–5

Recent cases have been described in patients who have received messenger RNA vaccines.2–4 In our series, two patients received a messenger RNA vaccine, while the other was administered a viral vector vaccine. In some cases, there were associated symptoms such as arthralgia, abdominal pain or urticaria.4 Our patients were asymptomatic throughout (Table 1). Occasionally, a transient increase in proteinuria has been described,2–5 coinciding with macroscopic hematuria, which is self-limiting over time. In our series, it was not possible to quantify the proteinuria, but there was no worsening of renal function. No treatment was required to correct the hematuria as the episodes were self-limiting within 24–72h, consistent with the cases reported in the literature.2–5

In our three patients, the onset of macroscopic hematuria occurred mainly with the administration of the second dose. This may lead to hesitancy in completing the vaccination regimen because of the risk of progression of glomerular disease. This recent debate, with the cases reported in the literature,6,7 could make this decision difficult. However, if we compare the possibility of developing a treatable flare-up after vaccination against the high mortality risk of COVID-19 in renal patients, we consider that completing vaccination in these particularly vulnerable patients is sufficiently justified.7

In conclusion, the use of this type of vaccine in patients with IgA nephropathy may cause macroscopic hematuria. In our patients, the onset of the clinical picture was asymptomatic and resolved spontaneously. This side effect should alert us to monitor renal function and proteinuria in such patients. We believe it is important to complete SARS-CoV-2 vaccination and to achieve immunisation. More conclusive assessments are required to fully understand the effect of these vaccines on the renal population with IgA nephropathy.

Funding

The authors declare that they received no funding.

Conflict of interest

The authors declare that they have no conflicts of interest.

References
[1]
Martín De Francisco AL. Vacunas SARS-COV2 Mar. 2021. Catedratico medicina Universidad de Cantabria. Servicio de Nefrologia HU Marqués de Valdecilla. [Accessed 22 July 2021]. Available from: www.nefrologiaaldia.org/es.
[2]
L. Negrea, B.H. Rovin.
Gross Hematuria following vaccination for severe acute respiratory síndrome coronavirus 2 in 2 patients with IgA nephropathy.
Kidney Int, 99 (2021), pp. 1487-1501
[3]
S.E. Gul Rahim, J.T. Lin, J.C. Wang.
A case of gross hematuria and IgA nephropathy flare-up following SARS-CoV2 vaccination.
Kidney Int, 100 (2021), pp. 238
[4]
P. Perrin, X. Bassand, I. Benotmane, N. Bouvier.
Gross hematuria following SARS-CoV-2 vaccination in patients with IgA nephropathy.
Kidney Int, 100 (2021), pp. 466-468
[5]
S. Kudose, P. Friedmann, O. Albajrami, V.D. D’Agati.
Histologic correlates of gross hematuria following Moderna COVID-19 vaccine in patients with IgA nephropathy.
Kidney Int, 100 (2021), pp. 468-469
[6]
A.S. Bomback, S. Kudose, V.D. D’Agati.
De novo and relapsing glomerular diseases after COVID-19 vaccination: What do we know so far?.
Am J Kidney Dis, 78 (2021), pp. 477-480
[7]
C.C. Lim, J. Choo, C.S. Tan.
COVID-19 Vaccination in Immunoglobulin A Nephropathy.
Am J Kidney Dis, 78 (2021), pp. 317
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