ABSTRACT
Objective: A new generation of vaccine technology platform has been developed to combat the COVID- 19 pandemic, the mRNA vaccine. The EMA granted the Pfizer- BioNTech COVID-19 vaccine an emergency use authorization in December 2020 with limited clinical experience, especially in the pediatric population. Method(s): Here, we present a case-report of a 17-yearold girl, who was vaccinated with the mRNA-COVID vaccine in October 2021, and developed a gross hematuria and proteinuria the day after the vaccination. Result(s): The patient presented at our outpatient clinic three days after the vaccination with new-onset hematuria and proteinuria. Up to this date, she had no former known medical conditions and the family history was negative regarding kidney diseases. We excluded nephrolithiasis, autoimmune glomerulonephritis and urinary tract infection as causes. The laboratory chemistry of the kidney was within normal range. The proteinuria dissolved spontaneously, and a microhematuria persisted. One day after the second dose of Cominarty in November 2021, the gross hematuria with proteinuria relapsed. A treatment with an ACE-inhibitor did not have any effect on the proteinuria. At this point, only a few casereports of patients with a comparable clinical course, especially from Japan, were published. In suspicion of a vaccine-triggered nephritis we started a prednisolon therapy which dissolved the proteinuria and induced a regression of the haematuria to a minimal stage. Conclusion(s): Within the last year, the medical community has gained more insights concerning mRNA vaccines. There is growing evidence, that mRNA vaccines can trigger de novo or relapse IgA nephropathy. But more systematic research and long-term evaluation is desirable to elucidate the underling pathophysiology as well as the influence on kidney survival of affected patients in the future. Furthermore, patient education should incorporate the risk of hematuria and proteinuria in children when applying mRNA vaccines.
ABSTRACT
Introduction: The incidence of glomerular diseases varies across different countries and criteria for kidney biopsy has changed over time. In Uruguay, glomerular diseases (GD) are a frequent cause of end stage kidney disease (ESKD) and renal replacement therapy with an annual incidence of 25.0 patients per million population according to data from the Uruguayan Dialysis Registry (UDR, year 2020). Since 1970, the Uruguayan Registry of Glomerulopathies has been recording the incidence, epidemiology and evolution of patients with GP in our country. In 2018, the Glomerulopathies Biobank (GB) began to operate including all patients with a native kidney biopsy performed at the Nephrology Department of the teaching hospital Hospital de Clinicas in Montevideo, Uruguay. The purpose of the BG is to record the phenotype (clinical and paraclinical) of patients with GD diagnosed by renal biopsy and at the same time store blood, urine, renal tissue and DNA samples. The aim of this report is to communicate the first 110 patients enrolled in the BG, which started in February 2018. Method(s): The BG protocol includes the collection of patronymic data, personal history, and clinical and paraclinical features of renal pathology. Plasma, urine and cell samples are stored for subsequent DNA extraction at the time of the kidney biopsy. In our country, all renal biopsies are performed by nephrologists. The Glomerular Biobank project is funded by the Nephrology Research Fund (School of Medicine, University of the Repubic) and was approved by the Ethics Committee of the Hospital de Clinicas and the Regulatory Verification Unit of the National Institute of Donation and Transplantation. The results are presented as mean and standard deviation (SD) for the continuous variables;and qualitative variables are described with percentages. Result(s): Patient recruitment began in February 2018 and we have recruited 110 patients. The mean age at the time of biopsy was 38.3+/-16.1 (min:16;max:78) years. Regarding sex distribution, the female sex slightly predominated (55.3%). Plasma creatinine was 2.1+/-1.45 mg/dL, proteinuria was 3.1+/-3.7 gr/dL and albuminaemia was 3.2+/-1.0 mg/dL. Microhaematuria was present in 61% of patients in the sediment study. Figure 1 shows the negative impact of the COVID 19 pandemic on the incidence of patients undergoing kidney biopsy. IgA nephropathy (13,8%)was the most frequent primary glomerular disease, followed by d focal and segmental glomerulosclerosis and membranous nephropathy. Consernig the glomerulopathies secondary to a systemic disease, the most frequent diagnosis was lupus nephritis (34,5%) followed by vasculitis, amyloidosis and diabetes. Conclusion(s): Having a prospective cohort of patients with glomerular disease, including reliable data and biological samples, will allow us to perform clinical and epidemiological analyses quickly and reliably in the future. The data and aliquots of biological material are available to any local nephrologist who proposes a hypothesis and has the approval of the corresponding ethics committee. The medium-term objective is to incorporate other national reference institutions in the care of patients with glomerular diseases. The data collected by the Glomerular Biobank will be a valuable input to the process of continuous improvement, and will serve as a basis for future nephrological research of excellence. No conflict of interestCopyright © 2023
ABSTRACT
Introduction: There have been some reports on flare-ups of kidney diseases following COVID-19 vaccines such as IgA nephropathy and minimal change disease. However, there have been few reports on those of IgA vasculitis following the vaccines yet. We report a case of IgA vasculitis with a flare-up of gross hematuria and lower-limb purpura following Moderna COVID-19 vaccines. Method(s): The patient is a 16-year-old female with no previous history of abnormal results of urinalyses before April in 2021. She had developed microscopic hematuria, proteinuria and purpura on both of her lower limbs that emerged and then disappeared repeatedly since then. She received Moderna COVID-19 vaccines in August and September in 2021, both of which were followed by gross hematuria lasting for around 10 days. The lower-limb purpura reemerged at the same time as the hematuria. Microscopic hematuria of around 30-49 RBC/HPF, glomerular hematuria of moderate degree and urine protein-to-creatinine ratio (UPCR) of around 0.8 g/gCr had continuously been detected. Skin and kidney biopsies were performed in December in 2021 and in February in 2022 respectively. Result(s): The skin tissue showed formation of leukocytoclastic vasculitis, and the kidney tissue showed that of cellular and fibrocellular crescents and endocapillary hypercellularity. Immunofluorescence staining of both tissues showed deposition of galactose-deficient IgA1(Gd-IgA1) and C3, and she was diagnosed as IgA vasculitis. She received steroid pulse therapy followed by tonsillectomy. The lower-limb purpura has disappeared after she received three courses of the steroid pulse therapy, but microscopic hematuria and UPCR of around 0.8 g/gCr have still continued. Conclusion(s): IgA vasculitis is leukocytoclastic vasculitis characterized by deposition of Gd-IgA1 on microvessel walls in skin and on glomerular capillaries in kidneys. The detailed mechanism of IgA vasculitis has not been fully elucidated yet. Gross hematuria following an upper respiratory infection is considered as a characteristic clinical symptom of IgA vasculitis as well as IgA nephropathy. Post-vaccination gross hematuria of patients with IgA nephropathy has been reported, and it is believed that innate immunity is related to its mechanism. Moderna COVID-19 vaccines, which the patient received, are mRNA vaccines. We estimate that exposure to the mRNA vaccine triggered excess glomerular deposition of Gd-IgA1-containing immune complexes and subsequent gross hematuria by overactivation of innate immunity such as Toll-like receptors that detect RNA. This case suggests that such immune activation by a mRNA vaccine might be related not only to the mechanism of IgA nephropathy but also to that of IgA vasculitis. No conflict of interestCopyright © 2023
ABSTRACT
Immunoglobulin A (IgA) nephropathy is the most common type of glomerulonephritis worldwide characterized by excessive serum levels of glycosylated which triggers the generation of glycan-specific IgG and IgA autoantibodies. This pathological condition results in the formation of circulatory IgA immune complexes, which are essential for the development of glomerular inflammation, especially IgA nephropathy. The serum galactosylated IgA1, IgG, and IgA autoantibodies are suggested as the biomarkers of IgA nephropathy since IgA antibodies are early markers for disease activity too. Serum IgA antibodies emerged as the early COVID-19-specific antibody response about two days after initial symptoms of COVID-19 in comparison with IgG and IgM antibody concentrations, which appeared after five days. IgA nephropathy is frequently presented as microscopic or macroscopic hematuria and proteinuria with a male predominance. COVID-19 infection can include several organs aside from the lungs, such as kidneys through different mechanisms. It is demonstrated in most cases that short-lasting symptoms such as gross hematuria resolve either spontaneously or following a short course of steroids. This review summarized the reported cases of relapses or denovo reported cases of relapses or de-novo IgA nephropathy and IgA vasculitis following COVID-19 vaccination.Copyright © 2023 The Author(s);Published by Society of Diabetic Nephropathy Prevention. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Introduction: The effective control of coronavirus disease 2019 (COVID-19) can be achieved by implementing a global vaccination strategy. After millions of mRNA vaccines targeting severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have been administered worldwide, several reports have shown the cases with gross hematuria (GH) following the mRNA vaccine against SARS-CoV2 in patients with glomerulonephritis, especially immunoglobulin A nephropathy (IgAN). A total of 22 articles including 36 cases of GH after COVID-19 vaccination as on July 31, 2022, were found in PubMed and Google Scholar databases. The most cases which had performed kidney biopsy were IgAN or IgA vasculitis. So, it suggested that GH after COVID-19 vaccination is rerated IgAN. Although there are many reported cases of IgAN after COVID-19 vaccination, the detailed clinical characteristics and outcome have not determined in these patients. Moreover, it remains unclear whether COVID-19 vaccination causes the new onset of nephritis or exacerbates pre-existing nephritis. To address this, herein, we conducted a prospective cohort study over a six-month period. Method(s): We analyzed 82 patients who presented with GH after COVID-19 vaccination and conducted a 6-month observational study. Patients, 18 years or older, who presented to the hospital with GH after COVID-19 vaccination were recruited. All the patients visited either Juntendo University Hospital or Juntendo University Urayasu Hospital between May 11, 2021, and July 31, 2022. Result(s): During the study period, a total of 82 individuals who presented with GH after COVID-19 vaccination were enrolled. The median age of the patients was 38 years;58 cases (70.7%) were females. All the patients received an mRNA COVID-19 vaccine. Most patients showed GH within three days after the second or third dose. Among the 82 patients, 22 had been already diagnosed with IgAN or IgA vasculitis (IgAV) before vaccination, and 45 of the 60 undiagnosed patients had a history of abnormal urinary findings. We performed kidney biopsies on 42 of the 60 undiagnosed patients, who were then diagnosed with IgAN (N=41) or IgAV (N=1). Pathological findings demonstrated that chronic inflammation of glomeruli, such as the expansion of mesangial matrix and glomerular sclerosis, is similarly observed in these newly diagnosed patients compared to patients with IgAN unrelated to vaccination. Finally, we evaluated the levels of biomarkers known to be elevated in IgAN at diagnosis during the course of the study and found that they did not increase. Notably, only few cases showed a slight increase in the level of serum creatinine, and no patients progressed to severe renal dysfunction. Conclusion(s): Present prospective study with 82 cases with GH after COVID-19 vaccination have identified their clinical characteristics and outcome. Furthermore, the acute manifestation of vaccine-induced GH may have highlighted the high prevalence of undiagnosed or preclinical IgAN in Japan. No conflict of interestCopyright © 2023
ABSTRACT
Introduction: There have been scattered reports of IgA nephropathy (IgAN) patients with gross hematuria and acute deterioration of urinary findings and kidney function following SARS-CoV-2 mRNA vaccination ("vaccination"). Recent case series studies have indicated a possible link between remission of urinary findings at the time of vaccination and subsequent appearance of gross hematuria. In this study, we aimed to determine whether the remission status of pre-vaccination urinary findings is associated with gross hematuria following vaccination in patients with already diagnosed IgAN. Method(s): Outpatients with IgAN who had been followed for at least 6 months after biopsy diagnosis were included. We analyzed the association between remission of microscopic hematuria (urine sediment <5/HPF) or proteinuria (<0.3 g/gCr) before vaccination and gross hematuria following vaccination. Remission of urinary findings was evaluated based on the criteria proposed by the Japanese Society of Nephrology in patients who had undergone at least three urine tests in the 6 months before the first vaccination. Result(s): A total of 372 patients with IgAN (mean age 53 years, 53 % female, eGFR 56 mL/min/1.73 m2) were included. The frequency of gross hematuria following vaccination was higher in 21/140 patients (15%) without remission of microscopic hematuria than in 4/232 patients (2%) with remission of microscopic hematuria prior to vaccination (p < 0.001). There was no association between remission of proteinuria before vaccination and gross hematuria following vaccination. After adjustment for potential confounders such as gender (female), age (<50 years), eGFR (>=60 mL/min/1.73m2), histories of tonsillectomy and corticosteroid therapy, non-remission of microscopic hematuria was still associated with gross hematuria following vaccination (OR 6.97, p < 0.001). Conclusion(s): Patients with IgAN who have not achieved remission of microscopic hematuria prior to vaccination are at higher relative risk of gross hematuria following vaccination regardless of treatment history for IgAN. No conflict of interestCopyright © 2023
ABSTRACT
Introduction: Since the beginning of the coronavirus infection 2019 (COVID-19) pandemic, the population of dialysis patients has been recognized as a population at high risk of infection due to immune background and comorbidities. This study aims to describe the epidemiological characteristics, mortality and risk factors for COVID-19 infection in this population. Study design: Retrospective cohort study Methods: Patients on peritoneal dialysis in a university hospital center tested positive for coronavirus-19 by PCR method by nasopharyngeal swab from January 2020 to June 2022. Epidemiological and medical data collected from computerized medical records and from the Registry of French language peritoneal dialysis. Analytical approach: Logistic regression analyzes conducted to identify epidemiological and clinical characteristics associated with COVID-19 and risk factors associated with COVID-19 infection Results: 21 (31.8%) patients on peritoneal dialysis developed COVID-19. The male sex was slightly predominant with 11 men (52.4%). The average age of the patients was 67.48 years +/- 16.48, the average body mass index of the patients affected was 24.26, the average length of seniority in dialysis of the patients was 2.54 years +/- 1.3 years. The predominant initial nephropathy was diabetic nephropathy, glomerulosclerosis, IgA nephropathy and interstitial nephropathy with rates of 38.1%, 19%, 9.5% and 9.5% respectively. The risk factors for covid infection found were: an antecedent of ischemic cardiopathy, the diabetic nephropathy Conclusion(s): While it is true that Sars-cov 2 infection and its complications have increased the mortality rate in most dialysis centres, it should be noted that other factors have contributed to the increase in mortality such as socioeconomic circumstances related to financial financial difficulties, missed consultation appointments secondary to the apprehension of contracting the disease while traveling to the centers as well as the difficult due to confinement. No conflict of interestCopyright © 2023
ABSTRACT
A 27-year-old man underwent a deceased kidney transplant. Three days after transplantation, COVID-19 was diagnosed for our patient. Immunosuppressants were reduced and a renal biopsy was conducted, which showed acute T cell-mediated rejection. We intened to share a case to help clinicians to understand the risks that kidney transplant recipients face.Copyright © 2023 The Author(s);Published by Society of Diabetic Nephropathy Prevention.
ABSTRACT
COVID-19 is a global pandemic with the chronically immunosuppressed transplant recipients being the most vulnerable both to infection as well as complications of COVID-19. Here, we report a case of live-related renal allograft recipient who presented with complaints of loose stools and new-onset graft dysfunction 2 years posttransplant. He tested positive for COVID-19 infection. On allograft biopsy, there were significant immunoglobulin A (IgA) deposits with no evidence of rejection or ATN or crescents or significant chronicity. The initial pretransplant biopsy of the recipient had revealed chronic glomerulonephritis with nil deposits. The donor had no evidence of hematuria or hypertension and had a preserved GFR. We, therefore, considered the possibility of the unmasking of IgA deposits posttransplantation diagnosed in a recipient with COVID-19 infection. Copyright © 2022 Indian Journal of Transplantation.
ABSTRACT
Background: Recently, the role of IL-6 in IgAN pathogenesis is becoming increasingly important. A possible hypothesis emerges from our recent work on genomewide DNA methylation screening in patients with IgAN, which identified, among other findings, a hypermethylated region comprising Vault 2-1 RNA (VTRNA2-1), a non-RNA coding also known as a precursor of miR-886 (pre-mi-RNA). Consistently, VTRNA2-1 expression was found downregulated in IgAN patients. Method(s): Total RNA were isolated from PBMCs of IgAN patients, transplanted IgAN patients (TP-IgAN), non-IgAN transplanted patients (TP) and healthy subjects (HS). VTRNA2-1, CREB, PKR and IL-6 were evaluated by RT-PCR and by ELISA. Poly (I:C) and Pfizer-BioNTech COVID-19 COMIRNATY vaccine were used to transfect patient PBMCs. PKR inhibitor imoxin (C16) 1 muM was used to stimulate patient PBMCs. Result(s): Here we confirm that VTRNA2-1 is low expressed in IgAN subjects compared to HS and we found that also in TP-IgAN, compared to TP, the VTRNA2-1 transcript was expressed at level very low. We found that in IgAN patients with downregulated VTRNA2-1, PKR is overactivated, coherently with the role of the VTRNA2-1 that binds to PKR and inhibits its phosphorylation. The loss of the VTRNA2-1 natural restrain caused the activation of CREB by PKR, a classical cAMPinducible CRE-binding factor interacting with a region of the IL-6 promoter and leading to IL-6 production. We found higher CREB phosphorylation levels and IL-6 levels both in IgAN and in TP-IgAN patients. Since PKR is normally activated by bacterial and viral RNA, we hypothesized that these microorganisms can further activate the PKR/CREB/ IL-6 pathway leading to an excess of IL-6 production, explaining both the high levels of IL-6, both infection involvement in the disease, both cases of IgAN associated with COVID-19 infection and with COVID-19 RNA-vaccination. Both the RNA poly(I:C) and the COVID-19 RNA-vaccine stimulation significantly increase the IL-6 levels in IgAN patient PBMCs. Conclusion(s): In conclusion, the discovery of the upregulated VTRNA2-1/PKR/ CREB/IL-6 pathway in IgAN patients may provide a new pathogenic mechanism in IgAN and may be useful for the development of novel therapeutic approaches, likely by modulating the VTRNA2-1 methylation level in IgAN patients.
ABSTRACT
Background: IgA nephropathy (IgAN) flairs with gross hematuria after COVID-19 vaccination have been recently reported as adverse events of immunization, but no study to date has examined the incidence and clinical course of IgAN patients with gross hematuria following vaccination. Method(s): A single-center retrospective observational study included 301 patients with biopsy-proven IgAN and followed-up for more than 6 months with therapeutic intervention and received at least one dose of COVID-19 vaccination. We examined from medical records the incidence of gross hematuria following vaccination and also evaluated the clinical course of eGFR, spot urine protein/Cr ratio (UPCR), urinary erythrocyte count (URBC) /hpf among IgAN patients with gross hematuria following COVID-19 vaccination. Result(s): We identified 7 (3.0 %) patients with gross hematuria following COVID-19 vaccination. 6 patients were female. The median age was 42 (range, 33 to 48). Median time to develop gross hematuria after vaccination was 1 (range, 0 to 4) day and gross hematuria resolved within 3 (range, 1 to 7) days. 6 patients presented gross hematuria after the second dose. Mean baseline eGFR and UPCR before vaccination were 73.7 (IQR, 61.3 to 86.0) ml/min/1.73m2 and 0.23 (range, 0.01 to 0.70) g/g Cr, respectively, and median grade of hematuria was URBC 10-19/hpf. With mean follow up of 238.7 (range, 184 to 282) days after the onset of gross hematuria, 4 patients were introduced steroid therapy. Within one month after the onset of gross hematuria, mean eGFR decreased -13 (range, -29.2 to -5.2) % and UPCR increased +0.70 (range, +0.02 to + 2.59) g/gCr from baseline, and median grade of hematuria increased to URBC 50- 99/hpf as compared to baseline. At 6 months, mean eGFR and UPCR improved to 73.9 (IQR, 60.2 to 88.0) ml/min/1.73m2 and 0.30 (range, 0.06 to 0.74) g/g Cr, respectively, and median grade of hematuria decreased to URBC 5-9/hpf. Conclusion(s): Our study revealed the incidence of gross hematuria following vaccination in IgAN patients and also suggested that eGFR, proteinuria and hematuria may transiently worsen but improve almost to baseline with appropriate therapeutic intervention or careful follow-up.
ABSTRACT
Background: After infection with SARS-Cov-2 or vaccination against COVID-19, some patients develop kidney diseases, including minimal change nephrotic syndrome and IgA Nephropathy (IgAN). Here we characterized renal injury and inflammatory response in biopsies from patients with new onset IgAN diagnosed promptly after COVID-19 disease or vaccination. Method(s): Eleven kidney biopsies from patients who developed IgAN after SARSCov-2 infection and 6 from patients with new onset IgAN after vaccination against COVID-19 were diagnosed at Dep. of Nephropathology, FAU Erlangen-Nuremberg. Biopsies from patients with IgAN who had no prior COVID-19 disease (n=10) and zero-time biopsies from transplants (ZB;n=6) served as controls. Serum creatinine was assessed and kidney injury by analysis of podocyte loss, detection of Pax-8 positive parietal epithelial cells on the glomerular tuft and IF/TA. Macrophages and granulocytes were detected by triple staining of CD68, CD163 and myeloperoxidase. Result(s): Significant podocyte loss, as assessed by nephrin staining, was observed in all three IgAN groups compared to ZB, as well as Pax8-positve parietal epithelial cells on glomerular tuft. The serum creatinine, as a marker of kidney function, was on average 1.8-3.5-fold higher in the IgAN groups compared to ZB, but did not reach significance level due to small sample numbers. IF/TA was below 20% in most investigated biopsies. No significant differences in renal function or injury were observed between different IgAN groups. While CD68+CD163+MPO+, CD68+CD163-MPO+ and CD68+CD163+MPO-(M2c-like macrophages) inflammatory cells were significantly increased in both COVID-19 IgAN groups, significant increase of CD68-CD163+MPO-cells compared to ZB control was restricted to IgAN w/o COVID-19 group (11.7+/-8.1 vs 0.8+/-0.9 cells / mm2). CD68+CD163-MPO-M1-like macrophages and CD68-CD163-MPO+ neutrophils tended to be higher in all IgAN groups but failed to reach the level of significance. Conclusion(s): Changes in kidney function and renal damage was comparable in all three investigated IgAN groups independent on experience of COVID-19 or vaccination. Renal macrophage and neutrophil invasion tended to by higher in COVID-19 IgAN groups. However, no significant differences in inflammatory were observed in direct comparisons of IgAN groups.
ABSTRACT
Background: Presenting features for glomerular disease can be varied, including but not exclusively, acute kidney injury, nephrotic syndrome or haemo-proteinuria. At our regional tertiary centre we conducted a retrospective study to see whether clinical presentations of glomerular diseases had changed during the COVID-19 pandemic. Method(s): In this study, new and repeat native renal biopsies were included from January 2018 to October 2021. Glomerular pathologies of interest included minimal change disease, membranous nephropathy, IgA nephropathy, lupus nephritis and pauciimmune glomerulonephritis. We looked at three periods of time: prior to the start COVID-19 pandemic in 2018/19;during the COVID-19 pandemic in 2020;and after the introduction of COVID-19 vaccines in 2021. Result(s): 263 biopsies were identified over the 4-year period. IgA nephropathy - n = 13. Lupus nephritis - n = 43. The different classes of lupus nephritis are shown in (see figure 1) Minimal change disease - n = 57. All presented with the nephrotic syndrome. Between 6-25% over the study period presented with AKI (mean 19%) Pauci-immune glomerulonephritis - n = 85. Between 81%-91% over the study period presented with AKI, or AKI on CKD (mean 84%) Membranous glomerulopathy - n = 66. 50%, presented with the nephrotic syndrome. 20% presented with AKI in addition to proteinuria. Conclusion(s): Our analysis has not shown a significant change in clinical presentations of glomerular disease. There has not been an increased propensity in presenting with AKI in minimal change disease or membranous nephropathy. We saw the highest proportion of class IV lupus nephritis in 2021.
ABSTRACT
Background: Glomerular disease carries a significant burden of morbidity and mortality. There is emerging evidence of the impact of the COVID-19 pandemic and COVID-19 vaccination on glomerular disease. The aim of the study was to retrospectively analyse our experience of the incidence of glomerular disease between 2018 and 2021. Method(s): Native renal biopsy results were reviewed to compare the incidence of glomerular disease prior to the COVID-19 pandemic (2018/19);prior to development of COVID-19 vaccination (2020);and after the introduction of COVID-19 vaccines (2021). Biopsy data from January 2018 to October 2021 were collated from pathology records for all glomerular disease patients in our unit. We focused on the incidence of IgA nephropathy, lupus nephritis, minimal change disease, membranous nephropathy and pauci-immune glomerulonephritis. Result(s): 263 native biopsies were performed;45 biopsies in 2018, 75 in 2019, 65 in 2020 and 78 in the first ten months of 2021. The proportional incidence of each disease is shown in figure 1. The incidence of membranous nephropathy was noted to be higher in 2021, coinciding with the introduction of the COVID-19 vaccine programme in the UK, from an average of 23% of cases between 2018-2020, to 31% in the first ten months of 2021. The overall incidence of glomerular disease, excluding vasculitis, seemed to have fallen during 2020. Conclusion(s): The emergence of COVID-19 does not appear to have caused a significant increase in the overall incidence of glomerular disease in our population. We noted an increase in the incidence of membranous nephropathy following the introduction of the COVID-19 vaccination programme in 2021. The relatively lower incidence in 2020 could be related to limited access to primary health care practitioners and consequent reduction in referrals to secondary care at the time.
ABSTRACT
Newly-diagnosed or relapses of immunoglobulin A nephropathy (IgAN) have been associated with COVID-19 vaccination in the literature. Most reported cases were mild clinical diseases characterized by microscopic haematuria and do not require dialysis treatment. This current case report describes a 55-year-old male patient that presented to the emergency department with acute kidney injury after receiving the first dose of the mRNA-1273 COVID-19 vaccine. After admission, his renal function deteriorated rapidly, and then he developed uraemic encephalopathy. He underwent emergency haemodialysis with a rapid improvement in his mental status. Renal biopsy showed newly-diagnosed IgA nephropathy along with markedly elevated plasma level of galactose-deficient-IgA1 (Gd-IgA1) antibody. The patient did not receive immunosuppressive treatment and is now dialysis-free. Immune activation is considered an essential factor in developing or exacerbating IgAN following COVID-19 vaccination. This current case report demonstrates that elevated Gd-IgA1 antibody may be the potential mechanistic link between COVID-19 vaccination and IgAN.
Subject(s)
COVID-19 Vaccines , COVID-19 , Glomerulonephritis, IGA , Humans , Male , Middle Aged , 2019-nCoV Vaccine mRNA-1273 , COVID-19 Vaccines/adverse effects , Galactose , Immunoglobulin A , RNA, Messenger , Vaccination/adverse effectsABSTRACT
Purpose: Adverse events of a novel mRNA vaccine are not well described in Kidney Transplant Recipients(KTR), especially the risk of immune activation or recurrent glomerulonephritis(GN), which has been described in native GN after COVID-19 vaccines. Method(s): In this single-center prospective study, 147 KTR were enrolled after informed consent and administered 2 doses of Pfizer/BioNTech vaccine 21 days apart. Follow-up was 3 weeks after Dose2. Result(s): Mean age of KTR was 51 years;55.1% male;65.3% Chinese, 19% Malay, 11.6% Indian;69.5% Living donor, 29.9% Deceased donor, 0.7% Pancreas-kidney transplants;71.5% had biopsy-proven or presumptive chronic GN(CGN), 12.9% diabetic nephropathy, 15.6% other causes. 11(7.5%) KTR had delayed Dose2 administered at median 29 days(range 24-93) after Dose1. 7(4.8%)were delayed due to renal events: rise in creatinine(n=3), or proteinuria(n=2), or both creatinine and proteinuria with allograft biopsy showing acute T-cell and antibody-mediated rejection(n=1), new BK viraemia(n=1). Other reasons were possible anaphylaxis(n=1), intercurrent infection(n=2), and inability to attend due to quarantine(n=1). 27 KTR had new microhaematuria(MH) after Dose1;9 persisted after Dose2. Additional 18 had new MH after Dose2. Of 45 KTR with new MH, 7 had underlying IgAN, 5 had other biopsy-proven-CGN and 22 had presumed CGN, suggesting 34/45 with possible immune activation. 12 KTR had new onset proteinuria (rise in urine protein:creatinine ratio (UPCR) <=30 to >30mg/mmol);5/7 who developed a rise after Dose1 remained elevated;additional 5 had a rise after Dose2. 7 KTR had rise in proteinuria from UPCR <=100 to >100mg/mmol. Conclusion(s): Subclinical changes in allograft monitoring parameters are frequent after COVID-19 mRNA vaccines with up to 40.1% of KTRs showing rises in creatinine, proteinuria or new MH. Although overt recurrent GN and acute rejection are infrequent, high vigilance and monitoring for these occurrences should be undertaken in KTRs receiving mRNA vaccines.
ABSTRACT
Purpose: Kidney transplantation has become the optimal treatment for end stage renal disease (ESRD), allowing dialysis free survival. Despite widespread availability of transplant programs;rural patients have limited access to transplantation due to several barriers including increased travel time and financial burden. We report outcomes after establishment of a kidney transplant program serving rural West Virginia. Method(s): A retrospective review of the first 15 kidney transplants performed at a newly established Appalachian transplant program was conducted. Primary outcomes measured were graft survival and function. Other outcomes included graft rejection, patient survival and complications. Data related to patient demographics, etiology of ESRD, type of renal replacement therapy, time on transplant waitlist and average travel to transplant center were also collected. Result(s): The first 15 kidneys transplanted had an overall death censored graft survival rate of 100%. Median patient age was 53 (Range 31- 73 years) and a median follow-up of 6 months (Range 1-13 months). The average time on dialysis for this cohort was 4 years (n=13, Range 1-6 years) and average time on waitlist was 4.06 months (Range 0.4-13.2 months). The most common type of dialysis was hemodialysis (77%) followed by peritoneal dialysis (15%). Two patients were predialysis. Diabetes with hypertension (20%), IgA nephropathy (13%) and diabetes without hypertension (13%) were the most common causes of ESRD. Median graft creatinine was 1.51 mg/dL (Range 1.26 - 1.83 mg/dL) with a glomerular filtration rate (GFR) at 51.38 (Range 41.86-70) at one year. One patient developed acute antibody mediated rejection and one developed borderline T cell mediated rejection (13.3%), which were successfully treated with steroids, plasmapheresis and immune globulin therapy. Two patients died (13.3 %);one from acute respiratory failure following coronavirus (COVID-19) infection and one from cardiac arrest secondary to myocarditis (possible COVID-19). Patients experienced COVID-19 infection at a rate of 13.3 %. The average distance patients had to travel was 94 miles (Range 12 - 164 miles) with a travel time of 1 hour and 52 minutes on average (Range 20 minutes - 2.5 hours) to reach the transplant center. Conclusion(s): We report comparable outcomes from our new rural transplant program despite several barriers to delivery of quality care to our population.
ABSTRACT
Introduction: Vaccination is a known trigger for the development of de-novo or flare of glomerular diseases. Here we present a case series of fourteen patients with COVID vaccine- associated glomerular diseases (CVAGD). Methods: Patients with new onset proteinuria, hematuria or renal failure after SARS- CoV2 vaccine were included in the study. Demographic and clinical details were collected and laboratory investigations including serum creatinine, albumin, urine microscopy and urine spot protein creatinine ratio were done. Renal biopsy specimens were subjected to light microscopy and immunofluorescence examination. Results: We cared for 14 patients with CVAGD. Of them, eight patients were males. The mean age was 25.7 years. Three patients had relapse of their previous disease while eleven patients had no previously detected renal diseases. Eleven patients had received COVISHIELD and three had received COVAXIN. All patients presented after the first vaccine dose. At presentation, seven patients had nephrotic syndrome, two patients had rapidly progressive renal failure and five patients had nephritic syndrome. The mean duration of symptom onset after vaccination was 18 days. Renal biopsy revealed IgA nephropathy in 3 patients, endocapillary proliferative glomerulonephritis in 2 patients, minimal change disease in 5 patients, pauci- immune glomerulonephritis (ANCA associated vasculitis) in one patient, lupus nephritis ISN/RPS class 3 in one and focal segmental glomerulosclerosis in two patients. There was no history of COVID infection in any of our patients. Three patients had renal failure at presentation but none required renal replacement therapy. The patients with MCD and FSGS were treated with steroids, patients with ANCA vasculitis and lupus nephritis were managed with the appropriate Cyclophosphamide and steroid regimens while the others were managed conservatively with anti-proteinuric medications. On follow up, five patients (One IgAN, three MCD, one endocapillary proliferative GN) achieved complete remission of proteinuria and resolution of renal failure, while the remaining eight patients achieved partial remission. One patient with MCD had a relapse of proteinuria 3 weeks after achieving partial remission, he responded well to steroid therapy. All 14 patients remain on close follow up. Conclusions: Although causality cannot be definitively established, there is a definite temporal association between the presentation of glomerular diseases and COVID vaccination, in the absence of other inciting factors. Hence, new-onset or relapse of glomerular diseases presenting post vaccination, although rare, should be observed as a possible adverse event. Intriguing questions such as how to proceed with the vaccination schedule in patients with CVAGD and would changing the vaccine type reduce the risk of relapse remain unanswered. No conflict of interest
ABSTRACT
In response to the COVID-19 pandemic, worldwide efforts contributed to the largest vaccination campaign in history. Thus far, 17 cases of IgA nephropathy (IgAN) following COVID-19 vaccine were reported in adults, all after mRNA vaccines. Most patients had gross hematuria (GH) and sub-nephrotic range proteinuria (SNRP) within 2 days after the second dose. A 23-year-old White female with recent mild COVID-19 infection developed asymptomatic GH with SNRP 2 days after receiving the first and the second dose of Pfizer-BioNTech vaccine. Laboratory studies showed normal kidney function and serum albumin. Negative rheumatologic workup. Urinalysis revealed proteinuria, dysmorphic red blood cells, and rare granular casts. Urine protein-creatinine ratio (UPr/Cr) was 1,4g/g. Within 1 week the GH self-resolved, however, she continued to have persistent microscopic hematuria and subnephrotic proteinuria. Kidney biopsy showed IgAN. The Oxford MEST-C score was M1E0S1T0C0. She was started on Lisinopril. Upr was 976mg/24h. Subsequently, 2 days after the booster vaccine she developed GH, Upr increased to 2063mg/24h and was started on Dapagliflozin. This is the first reported case of de novo IgAN following each dose of COVID-19 vaccine and booster presenting with recurrent GH and SNRP. This case illustrates the need for pharmacovigilance and whether we should use non-mRNA or a different vaccine schedule in this vulnerable population. The new-onset and recurrence of GH shortly after the COVID-19 vaccines suggests a potential association with the development of IgAN and relapses. Further studies are needed to understand the pathophysiology of the vaccine-associated glomerular diseases, optimize vaccine strategies and guide optimal therapeutic management. (Figure Presented)
ABSTRACT
Since the spread of the novel coronavirus infection, most researchers have noted a low proportion of sick children in general pediatric cohort compared to adults, who had a mild disease course and rare complications. The most frequent clinical manifestations of the disease are respiratory and, some less frequently diarrheal syndromes. The disease has predominantly mild or asymptomatic course. The risk of adverse outcomes in children, similar to adults, clearly correlate with the presence of background chronic pathology. The need for respiratory support prevails in children with a severe premorbid burden. Here, a clinical case of ongoing novel coronavirus infection in adolescent patient comorbid with chronic kidney pathology is described. In adolescence, the patient was diagnosed with mesangioproliferative glomerulonephritis (IgA-nephropathy), and further registered at the dispensary receiving a combination therapy with angiotensin converting enzyme inhibitors and disaggregation drugs. The epidemiological history contained no established contacts with infectious patients. The clinical manifestations of COVID-19 in the patient are represented by catarrhal and diarrheal syndromes, transient renal dysfunction in the acute period of the disease. The onset of coronavirus infection was clinically characterized by symptoms of damaged gastrointestinal tract and was considered as acute gastroenteritis of infectious etiology. Empirically prescribed antibacterial therapy in combination with antiplatelet agents and symptomatic drugs had no effect. The diagnosis of the novel coronavirus infection was verified only on day 4 of hospitalization, clinical and laboratory signs of lung damage emerged. The inflammatory process developed in the patient lungs was secondary to the main pathology. The severity of the patient’s condition was determined by the presence of respiratory and renal insufficiency. Lung damage with minimal severity complaints and clinical data had a bimodal pattern and required respiratory support. A comprehensive approach to treatment, including respiratory, antiviral, enterosorption, anticoagulation, anti-inflammatory, antihypertensive, hepatoprotective, symptomatic therapy with change in antibacterial drugs allowed to achieve positive dynamics. On day 12 of the illness, the patient required no respiratory support. The presence of symptoms of gastrointestinal tract damage in COVID-19 necessitates the mandatory inclusion of PCR assay for SARS-CoV-2 into diagnostic protocol in patients with diarrheal syndrome to perform etiological disease interpretation.