Abstract
The 2019 coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has posed a considerable challenge to global healthcare. Acute interstitial nephritis (AIN) post SARS-CoV-2 infection and vaccination has been reported, but its clinical features and pathogenesis remained unclear. We reviewed so far the largest 22 cases of AIN post SARS-CoV-2 infection and 36 cases of AIN following COVID-19 vaccination. The onset of AIN was mainly related to messenger RNA vaccines (52.8%). Apart from fever, proteinuria (45.5%) was the main manifestation of AIN post SARS-CoV-2 infection, left acute kidney injury (AKI, 63.9%) in patients post COVID-19 vaccination. The potential mechanism of vaccination induced AIN was conjugating vaccines with proteins to form a hapten, which activated dendritic cells and promoted a cascade immunological reaction leading to AIN.
Similar content being viewed by others
Avoid common mistakes on your manuscript.
1 Introduction
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was one of the deadliest viral epidemics in human history, posing a serious threat to human health and economic development [1]. Due to the wide distribution of angiotensin-converting enzyme 2 (ACE2) receptors, the gastrointestinal tract, kidney, and liver were often involved, with more severe clinical symptoms and higher mortality [2, 3]. COVID-19 vaccination was one of the key strategies for controlling the disease. After vaccination, the innate and adaptive immune systems would be initiated by the vaccine itself or by vaccine adjuvants, producing protective antibodies [4, 5], and based on previous evidence, most adverse events following vaccination were nonserious, such as fatigue, headache, and myalgia [6]. However, with widespread vaccination, acute interstitial nephritis (AIN) has been reported.
AIN was characterized by the presence of inflammatory infiltrates and edema within the interstitium, usually associated with an acute deterioration in renal function. AIN was one of the common causes of acute kidney injury (AKI) from biopsy samples [7]. Although the hapten formation was thought to be the key process that triggered the immune response, the exact mechanisms of AIN post SARS-CoV-2 infection and COVID-19 vaccination were unclear [8].
In the present analysis, we summarized the clinical evidence of AIN following the SARS-CoV-2 infection and COVID-19 vaccination published by September 9, 2023, with the largest sample size, and analyzed the clinical characteristics of the included cases.
2 Methods
In this review, we searched relevant literature on AIN post SARS-CoV-2 infection or vaccination through electronic databases, including PubMed, EMBASE, and Web of Science, using keywords (“Interstitial Nephritis” OR “Interstitial Nephritides” OR “Tubulointerstitial Nephritides” OR “Tubulointerstitial Nephritis”) AND (“COVID-19” OR “Novel Corona Virus” OR “Coronavirus” OR “2019-nCoV” OR “SARS-CoV-2”) or (“Interstitial Nephritis” OR “Interstitial Nephritides” OR “Nephritides, Tubulointerstitial” OR “Tubulointerstitial Nephritides” OR “Tubulointerstitial Nephritis”) AND (“COVID-19” OR “Novel Corona Virus” OR “Coronavirus” OR “2019-nCoV” OR “SARS-CoV-2”) AND (“Vaccines” OR “Vaccination”).
We reported medians and ranges for continuous data and numbers and percentages for categorical data. We used descriptive statistics in this report and performed statistical analysis. The Mann–Whitney Test was used for continuous data, and the Chi-Square Test was used for categorical data to determine whether the two groups were statistically different. Since our sample size was less than 40, the Fisher's Exact Test was used for both simple four-table and R × C table data. All statistical analyses were performed using SPSS 25.0 software, and P value < 0.05 was considered to be statistically significant.
3 Results
3.1 Baseline Demographic and Clinical Characteristics of Patients with AIN Post-SARS-CoV-2 Infection
There were 22 patients appeared with AIN after SARS-CoV-2 infection [9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24] (Table 1), including 10 (45.5%) tubulointerstitial nephritis and uveitis (TINU) [16, 20, 23, 24]. The median age was 15 (10–78) years old, and 68.2% (15 of 22) of the patients were male. The majority of patients were European (68.2%), followed by Asian (18.2%). The median time from SARS-CoV-2 infection to AIN was 14.5 (1–37) days.
Of the 22 patients, 4 received renal replacement therapy and immunotherapy, 17 received immunosuppressive therapy, and only 1 received conservative therapy. Of the available follow-up data, 21 patients responded well to treatment. Case 6 [14] progressed to chronic kidney disease despite some recovery of renal function (Table 2).
3.2 Baseline Demographic and Clinical Characteristics of Patients with AIN Post-COVID-19 Vaccination
A total of 36 patients were diagnosed with AIN following COVID-19 vaccination [25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46] (Table 3), 35 of which were confirmed by renal biopsy, and all patients were first diagnosed. The majority of patients were European (47.2%), followed by Americans (25%) and Asians (22.2%). In addition, 52.8% of the patients received the BNT162b2 (Pfizer) vaccine, 22.2% received the mRNA-1273 (Moderna) vaccine, 19.4% received the AstraZeneca vaccine, and another 5.6% received the inactivated (Sinovac) vaccine. Common clinical presentations were AKI, proteinuria, hematuria, and leukocyturia. The median serum creatinine value was 355 (86—1679) μmol/L. Follow-up data were obtained for 35 patients, with 32 responding well to treatment (Table 4).
There were 12 patients with clinical symptoms after the first dose of vaccines, of which 2 patients with a history of cancer were treated with an immune checkpoint inhibitor [35]. Case 4 [28] had a history of Sjogren's syndrome and rheumatoid arthritis. Case 6 [30] had a history of on-demand lansoprazole administration. Case 11[35] had a history of taking non-steroid anti-inflammation drugs (NSAIDs) for muscle pain. In addition to leukocyturia and proteinuria, case 8 [32] had a symptom of vascular purpura, with multiple necrotic lesions involving the hands, arms, thighs, and feet and a skin biopsy suggesting leukocytoclastic vasculitis. Follow-up data were obtained for all patients, and 9 of them responded well to treatment. Case 12 [35] was admitted to the hospital with pneumonia-infected shock at month 5 of follow-up and died of multiorgan failure. Case 5 [29] developed AKI and nephrotic proteinuria after the first dose of the Moderna vaccine and went on to receive the second dose of the vaccine. Kidney biopsy was diagnosed as AIN with IgA nephropathy, and he was treated with steroid pulse therapy, but the disease progressed without responding. Case 4 [28] relapsed after one month of steroid discontinuation, but symptoms were quickly controlled with the reintroduction of steroids.
Twenty-one patients developed clinical symptoms after the second dose of the vaccines, with a median onset time of 7 (1–82) days. Of the 21 patients, three had a history of neoplastic disease, including hepatocellular carcinoma, prostate cancer, and diffuse large B-cell lymphoma [34, 36, 42]. Three cases had a history of autoimmune disease, including inflammatory bowel disease, rheumatoid arthritis, and systemic lupus erythematosus [36, 42]. Follow-up data were obtained for all patients, and they responded well to treatments.
In contrast, only 3 patients developed clinical symptoms after the third dose of the vaccines, with a median onset time of 21 (21–30) days. Case 35 [35] had a history of invasive bladder neoplasm and responded well to conservative treatment after discontinuation of Pembrolizumab. The other two patients were treated with immunotherapy and responded well.
4 Discussion
4.1 AIN and COVID-19 Vaccination
It was well known that drugs were the most common cause of AIN, especially NSAIDs [47], and currently, the most widely accepted mechanism of drug-induced AIN was the cell-mediated type IV hypersensitivity theory. However, the exact pathophysiological mechanism remained to be elucidated [48].
The manufacturing process of inactivated SARS-CoV-2 vaccine is traditionally used for various vaccines such as influenza vaccine, hepatitis A, and hepatitis B, which suggested some similarities in potential side effects. Of the 35 cases we collected, case 8 presented with leukocytoclastic vasculitis after inactivated COVID-19 vaccination, and leukocytoclastic vasculitis with or without renal symptoms have been described as a side effect of several vaccines, such as influenza virus, hepatitis B virus (HBV), Bacillus Calmette-Guerin (BCG), and human papillomavirus (HPV) [49,50,51,52], which strongly supported a causal relationship between vaccines and symptomatology, although these observations were poorly documented and the causal relationship remained to be verified. In the reported patients, almost all started days or weeks after vaccination and showed infiltration of monocytes, neutrophils, and eosinophils on renal biopsy and negative immune fluorescence staining for immune deposits, suggesting that they had a predominantly cell-mediated immune response. 54.3% received the BNT162b2 (Pfizer) vaccine, and a meta-analysis demonstrated that anaphylaxis with the Pfizer-BioNTech vaccine was approximately 10 times higher than that associated with all other vaccines [53]. Components in the SARS-CoV-2 vaccines, such as polyethylene glycol, are also known to be immunogenic and can trigger hypersensitivity-like reactions [54]. Eight patients [25, 27, 31, 32, 35, 37, 38, 45] developed leukocyturia after vaccination, and two patients [27, 28] had peripheral eosinophilia. Therefore, we suspected AIN was an allergic reaction triggered by the vaccines. Case 24 [38] was evaluated 2 months after hospital discharge in the Department of Allergy and Clinical Immunology. The lymphocyte transformation test (LTT) was positive, which supported the involvement of T cells and pointed to a type IV hypersensitivity reaction according to the classification of Gell and Coombs [55, 56].
The COVID-19 vaccine caused AIN in the form of hapten via a type IV hypersensitivity reaction (Fig. 1). We speculated that vaccines could bind to proteins like drugs to produce immunogenic hapten filtered and endocytosed by peritubular mesangial or tubular epithelial cells [57,58,59,60]. These cells acted as antigen presenters, presenting antigenic stimuli to dendritic cells in direct contact with the basal surface of the renal tubular epithelium [61,62,63]. Once exposed to the antigen or injury signal, normally quiescent dendritic cells were activated and expressed the antigenic compound MHC II molecules in the form of peptides. After that, dendritic cells migrate through the renal lymphatics to regional lymph nodes, where they present antigens to naive T cells, which are activated and migrate to the source of antigenic injury [64,65,66,67]. The renal interstitium also contains dormant macrophages and fibroblasts, which are activated and contribute to this initial inflammatory response. This inflammatory response was further amplified by the recruitment of neutrophils, including eosinophils, and was further amplified by bidirectional crosstalk between dendritic cells and T cells or neutrophils [68].
The assumed mechanisms of AIN post COVID-19 vaccination. Hypothesis of AIN caused by COVID-19 vaccination. Haptens: The vaccine may bind to proteins to form protein complexes called "hapten", which are recognized and presented by DCs, causing a subsequent T-cell-mediated toxic response, as well as activation of intrinsic immune cells in the renal stroma, and further amplification of the inflammatory response by crosstalk between different immune cells. P-i concept: some specific structures of the vaccine may stimulate T cells, thus allowing binding to the major histocompatibility peptide complexes and causing inflammatory factor production. Direct injury: vaccines and their products may cause direct renal tubular injury. Molecular mimicry: some structures of vaccines or adjuvants may be homologous to human proteins, and exposure to vaccines triggers antigenic epitopes of cross-reactive antibodies and thus disrupts immune tolerance. The figure refers to the pathogenesis of AIN by Sanchez-Alamo B et al. [48]
4.2 AIN and SARS-CoV-2 Infection
Infections were known to be a common cause of AIN. Many cases of AIN were caused by infections of the distal kidney, such as hepatitis C virus (HCV) [69], Epstein-Barr virus (EBV) [70], and cytomegalovirus (CMV) [71], which supported a possible causal relationship between SARS-CoV-2 infection and AIN. SARS-CoV-2 has been detected in a kidney allograft associated with a monocyte cell infiltration [17], which suggested that the virus could enter the renal parenchyma and may cause AIN. These findings were supported by recent postmortem histopathological analysis showing positive SARS-CoV nucleoprotein antibody immunostaining in the tubules [72]. In addition, medications were the most common cause of AIN [73, 74]. However, although severely ill COVID-19 patients in intensive care units may be treated with multiple medications, drug-induced AIN was still uncommon in these cases.
Viral infections can disrupt immune tolerance by exposing antigenic epitopes and triggering cross-reactive antibodies [75]. There were numerous reports of antigenic mimicry between viral and human proteins. For example, lupus patients could have immune responses to EBV [76]. Some epitopes of SARS-CoV-2 have been found to exhibit cross-reactivity with autoantigens. Such as respiratory failure [77] and Green-Barre syndrome [78] associated with COVID-19 may be associated with molecular mimicry mechanisms. Similarly, the emergence of Guillain–Barre syndrome (GBS) after influenza vaccination and demyelinating neuropathy after HBV vaccination have been reported [79,80,81]. Despite the lack of specific evidence for any significant homology between the molecular components of influenza viruses and those in human myelin, molecular mimicry was considered the most likely mechanism. Therefore, we hypothesized that COVID-19 vaccination could induce AIN by the same mechanism.
SARS-CoV-2 infection may also trigger hypersensitivity reactions just as it does after vaccination. Viral and bacterial antigens may trigger cell-mediated injury where they were filtered, concentrated, and secreted in the kidney, accompanied by high blood flow, increasing their exposure and making them targets of immune responses [82, 83]. For example, respiratory viruses can trigger Kawasaki disease [84], while bacterial superantigens of Staphylococcus aureus or Streptococcus pyogenes may lead to toxic shock syndrome [85].
Most patients in the data we collected responded well to steroid therapy, and clinicians should be aware of this renal side effect of SARS-CoV-2 infection. AIN in this condition may be caused not only by the pathogen directly invading the kidney but through different immune mechanisms [86]. Timely diagnosis, including biopsy evaluation, was essential for correct treatment, a good prognosis, and preservation of renal function.
5 Conclusion
AIN post SARS-CoV-2 infection and COVID-19 vaccination was rare but with potentially serious complications and satisfactory response to steroid therapy. The pathogenesis, treatment, and long-term prognosis of AIN following SARS-CoV-2 infection and COVID-19 vaccination still need to be further explored.
6 Limitations
This review has some limitations. First, the association between AIN and COVID-19 vaccination can only be based on timing and excluding other predisposing factors, such as a history of NSAIDs use in some patients and a history of connective tissue disease (CTD) in others. Second, some reports did not describe a complete etiological study of other causes of AIN. Third, there may be many unreported cases of vaccine-associated AIN, and epidemiological investigations were lacking to determine the true incidence of AIN after vaccination. Fourth, the mechanisms we elucidated need further confirmation. And fifth, due to the small sample size, there may be errors in our statistical analysis.
Availability of Data and Material
Not applicable.
References
Maeda K, Higashi-Kuwata N, Kinoshita N, et al. Neutralization of SARS-CoV-2 with IgG from COVID-19-convalescent plasma. Sci Rep. 2021;11(1):5563. https://doi.org/10.1038/s41598-021-84733-5.
Zhong P, Xu J, Yang D, et al. COVID-19-associated gastrointestinal and liver injury: clinical features and potential mechanisms. Signal Transduct Target Ther. 2020;5(1):256. https://doi.org/10.1038/s41392-020-00373-7.
Walsh EE, Frenck RW Jr, Falsey AR, et al. Safety and immunogenicity of Two RNA-based Covid-19 vaccine candidates. N Engl J Med. 2020;383(25):2439–50. https://doi.org/10.1056/NEJMoa2027906.
Pardi N, Hogan MJ, Naradikian MS, et al. Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses. J Exp Med. 2018;215(6):1571–88. https://doi.org/10.1084/jem.20171450.
Jackson LA, Anderson EJ, Rouphael NG, et al. An mRNA Vaccine against SARS-CoV-2—preliminary report. N Engl J Med. 2020;383(20):1920–31. https://doi.org/10.1056/NEJMoa2022483.
Rosenblum HG, Gee J, Liu R, et al. Safety of mRNA vaccines administered during the initial 6 months of the US COVID-19 vaccination programme: an observational study of reports to the Vaccine Adverse Event Reporting System and v-safe. Lancet Infect Dis. 2022;22(6):802–12. https://doi.org/10.1016/S1473-3099(22)00054-8.
Raghavan R, Eknoyan G. Acute interstitial nephritis—a reappraisal and update. Clin Nephrol. 2014;82(3):149–62. https://doi.org/10.5414/cn108386.
Praga M, González E. Acute interstitial nephritis. Kidney Int. 2010;77(11):956–61. https://doi.org/10.1038/ki.2010.89.
Tuma J, Neugebauer F, Rohacek M, Serra A. Nierensonomorphologie bei COVID-19 mit akuter Niereninsuffizienz [Renal Monomorphology in COVID-19 with Acute Renal Insufficiency]. Praxis. 2020;109(9):731–5. https://doi.org/10.1024/1661-8157/a003526.
Azukaitis K, Besusparis J, Laurinavicius A, Jankauskiene A. Case Report: SARS-CoV-2 Associated Acute Interstitial Nephritis in an Adolescent. Front Pediatr. 2022;10:861539. https://doi.org/10.3389/fped.2022.861539.
Buyansky D, Fallaha C, Gougeon F, Pépin MN, Cailhier JF, Beaubien-Souligny W. Acute tubulointerstitial nephritis in a patient on anti-programmed death-ligand 1 triggered by COVID-19: a case report. Can J Kidney Health Dis. 2021;8:20543581211014744. https://doi.org/10.1177/20543581211014745.
León-Román J, Agraz I, Vergara A, et al. COVID-19 infection and renal injury: where is the place for acute interstitial nephritis disease? Clin Kidney J. 2022;15(9):1698–704. https://doi.org/10.1093/ckj/sfac079.
Alotaibi M, Ellis C, Wadhwani S, Peleg Y. A rare case of granulomatous interstitial nephritis in a patient with COVID-19. J Investig Med High Impact Case Rep. 2022;10:23247096221114516. https://doi.org/10.1177/23247096221114517.
Szajek K, Kajdi ME, Luyckx VA, et al. Granulomatous interstitial nephritis in a patient with SARS-CoV-2 infection. BMC Nephrol. 2021;22(1):19. https://doi.org/10.1186/s12882-020-02213-w.
Serafinelli J, Mastrangelo A, Morello W, et al. Kidney involvement and histological findings in two pediatric COVID-19 patients. Pediatr Nephrol. 2021;36(11):3789–93. https://doi.org/10.1007/s00467-021-05212-7.
Eser-Ozturk H, Izci Duran T, Aydog O, Sullu Y. Sarcoid-like Uveitis with or without Tubulointerstitial Nephritis during COVID-19. Ocul Immunol Inflamm. 2023;31(3):483–90. https://doi.org/10.1080/09273948.2022.2032195.
Westhoff TH, Seibert FS, Bauer F, et al. Allograft infiltration and meningoencephalitis by SARS-CoV-2 in a pancreas-kidney transplant recipient. Am J Transplant. 2020;20(11):3216–20. https://doi.org/10.1111/ajt.16223.
Sobieszczańska-Droździel A, Strzoda A, Sowiński W. Acute tubulointerstitial nephritis in 10-year-old boy following severe acute respiratory syndrome coronavirus 2 infection. Pediatr Pol. 2021;96(4):281–4. https://doi.org/10.5114/POLP.2021.110553.
Nikolova M, Angelova I, Kotseva V, et al. Acute Kidney Injury and Acute Renal Failure in Coronaviral Infection. Acta Medica Bulgarica. 2022;07:38–42. https://doi.org/10.2478/amb-2022-0028.
Bilak VM, Ilko AV, Ignatko YY, Ignatko LV. rare complication of COVID-19 disease TINU syndrome in a 11-year-old boy, features and managment. Wiad Lek. 2022;75(10):2541–3. https://doi.org/10.36740/WLek202210142.
Nowak PJ, Forycka J, Cegielska N, et al. Glucocorticoids Induce Partial Remission of Focal Segmental Glomerulosclerosis but Not Interstitial Nephritis in COVID-19 Acute Kidney Injury in an APOL1 Low-Risk Genotype White Patient. Am J Case Rep. 2021;22:e933462. https://doi.org/10.12659/AJCR.933462.
Lebedeva MV, Chebotareva NV, Beketov VD. Ter Arkh. 2022;94(6):769–71. https://doi.org/10.2642/00403660.2022.06.201566.
Sakhinia F, Brice V, Ollerenshaw R, Gajendran S, Ashworth J, Shenoy M. Tubulointerstitial nephritis and uveitis in children during the COVID-19 pandemic: report of four cases. J Nephrol. 2023;36(5):1451–5. https://doi.org/10.1007/s40620-022-01564-x.
Maggio MC, Collura F, D’Alessandro MM, Gramaglia B, Corsello G. Tubulointerstitial nephritis and uveitis syndrome post-COVID-19. Pediatr Investig. 2023;7(1):57–9. https://doi.org/10.1002/ped4.12362.
Dheir H, Sipahi S, Cakar GC, Yaylaci S, Hacibekiroglu T, Karabay O. Acute tubulointerstitial nephritis after COVID-19 m-RNA BNT162b2 vaccine. Eur Rev Med Pharmacol Sci. 2021;25(20):6171–3. https://doi.org/10.26355/eurrev_202110_26985.
Fenoglio R, Lalloni S, Marchisio M, et al. New onset biopsy-proven nephropathies after COVID vaccination. Am J Nephrol. 2022;53(4):325–30. https://doi.org/10.1159/000523962.
de la Flor Merino JC, Linares Gravalos T, Alonso-Riaño M, et al. A case of acute interstitial nephritis following the Pfizer-BioNTech COVID-19 vaccine. Nefrologia (Engl Ed). 2022;42(5):617–20. https://doi.org/10.1016/j.nefroe.2021.05.007.
Wu HHL, Li JWC, Bow A, Woywodt A, Ponnusamy A. Acute interstitial nephritis following SARS-CoV-2 vaccination. Clin Kidney J. 2021;15(3):576–81. https://doi.org/10.1093/ckj/sfab253.
Klomjit N, Alexander MP, Fervenza FC, et al. COVID-19 vaccination and glomerulonephritis. Kidney Int Rep. 2021;6(12):2969–78. https://doi.org/10.1016/j.ekir.2021.09.008.
Tan FS, Kabir ME, Bhandari S. Acute interstitial nephritis after COVID-19 vaccination. BMJ Case Rep. 2022;15(5):246841. https://doi.org/10.1136/bcr-2021-246841.
Rieckmann S, Seibert FS, Hogeweg M, et al. Acute interstitial nephritis after vaccination with BNT162b2. J Nephrol. 2022;35(3):779–82. https://doi.org/10.1007/s40620-022-01275-3.
Missoum S, Lahmar M, Khellaf G. Vascularite leucocytoclasique et néphrite interstitielle aiguë après vaccin à SARS-CoV-2 inactivé [Leukocytoclastic vasculitis and acute renal failure following inactivated SARS-CoV-2 vaccine]. Nephrol Ther. 2022;18(4):287–90. https://doi.org/10.1016/j.nephro.2021.10.006.
Jongvilaikasem P, Rianthavorn P. Minimal change disease and acute interstitial nephritis following SARS-CoV-2 BNT162b2 vaccination. Pediatr Nephrol. 2022;37(6):1419–21. https://doi.org/10.1007/s00467-022-05470-z.
Lim JH, Kim MS, Kim YJ, et al. New-onset kidney diseases after COVID-19 vaccination: a case series. Vaccines (Basel). 2022;10(2):302. https://doi.org/10.3390/vaccines10020302.
Baker R, Gosalia K, Jhaveri KD, Gudsoorkar, P. Acute kidney injury (AKI) post-mRNA SARS-CoV-2 vaccine in patients with cancer, treated with immune check point inhibitor (ICPi): An immune double whammy! Journal Onco-Nephrology. https://doi.org/10.1177/23993693221135222
Czerlau C, Bocchi F, Saganas C, Vogt B. Acute interstitial nephritis after messenger RNA-based vaccination. Clin Kidney J. 2021;15(1):174–6. https://doi.org/10.1093/ckj/sfab180.
Unver S, Haholu A, Yildirim S. Nephrotic syndrome and acute kidney injury following CoronaVac anti-SARS-CoV-2 vaccine. Clin Kidney J. 2021;14(12):2608–11. https://doi.org/10.1093/ckj/sfab155.
Mira FS, Costa Carvalho J, de Almeida PA, et al. A Case of acute interstitial nephritis after two doses of the BNT162b2 SARS-CoV-2 vaccine. Int J Nephrol Renovasc Dis. 2021;14:421–6. https://doi.org/10.2147/IJNRD.S345898.
Choi JH, Kang KS, Han KH. Two adolescent cases of acute tubulointerstitial nephritis after second dose of COVID-19 mRNA vaccine. Hum Vaccin Immunother. 2022;18(5):2059308. https://doi.org/10.1080/21645515.2022.2059308.
Caza TN, Cassol CA, Messias N, et al. Glomerular disease in temporal association with SARS-COV-2 vaccination: a series of 29 cases. Kidney 360. 2021;2(11):1770–80. https://doi.org/10.3467/KID.0005372021.
Liew SK, Nair B, So B, Ponnusamy A, Bow A, Woywodt A. Acute interstitial nephritis following SARS-CoV-2 virus vaccination. Clin Nephrol. 2022;97(4):242–5. https://doi.org/10.5414/CN110753.
Schaubschlager T, Rajora N, Diep S, et al. De novo or recurrent glomerulonephritis and acute tubulointerstitial nephritis after COVID-19 vaccination: a report of six cases from a single center. Clin Nephrol. 2022;97(5):289–97. https://doi.org/10.5414/CN110794.
Baskaran K, Cohen AWS, Weerasinghe N, Vilayur E. Report of two cases of minimal change disease following vaccination for COVID -19. Nephrology (Carlton). 2022;27(1):111–2. https://doi.org/10.1111/nep.13995.
Nakamura H, Ueda M, Anayama M, Makino M, Makino Y. Hilar lymphadenopathy, development of tubulointerstitial nephritis, and dense deposit disease following Pfizer-BioNTech COVID-19 vaccination. CEN Case Rep. 2023;12(3):287–91. https://doi.org/10.1007/s13730-022-00762-7.
Williams SBM, Holwill SDJ, Clissold RL, Bingham C. A case of acute tubulointerstitial nephritis following administration of the Oxford-AstraZeneca COVID-19 vaccine: a case report. BMC Nephrol. 2023;24(1):52. https://doi.org/10.1186/s12882-023-03089-2.
Ghanekar K, Ghanekar H, Saxena R. Late onset granulomatous interstitial nephritis after booster dose of COVID-19 vaccination: case report and review of literature. Clin Nephrol. 2023;99(6):299–306. https://doi.org/10.5414/CN110965.
Moledina DG, Perazella MA. Drug-induced acute interstitial nephritis. Clin J Am Soc Nephrol. 2017;12(12):2046–9. https://doi.org/10.2215/CJN.07630717.
Agus D, Mann R, Cohn D, et al. Inhibitory role of dietary protein restriction on the development and expression of immune-mediated antitubular basement membrane-induced tubulointerstitial nephritis in rats. J Clin Invest. 1985;76(3):930–6. https://doi.org/10.1172/JCI112092.
Bonetto C, Trotta F, Felicetti P, et al. Vasculitis as an adverse event following immunization—systematic literature review. Vaccine. 2016;34(51):6641–51. https://doi.org/10.1016/j.vaccine.2015.09.026.
Ulm S, Hummel M, Emig M, et al. Leukocytoclastic vasculitis and acute renal failure after influenza vaccination in an elderly patient with myelodysplastic syndrome. Onkologie. 2006;29(10):470–2. https://doi.org/10.1159/000095412.
Tavadia S, Drummond A, Evans CD, Wainwright NJ. Leucocytoclastic vasculitis and influenza vaccination. Clin Exp Dermatol. 2003;28(2):154–6. https://doi.org/10.1046/j.1365-2230.2003.01188.x.
Schattner A. Consequence or coincidence? The occurrence, pathogenesis and significance of autoimmune manifestations after viral vaccines. Vaccine. 2005;23(30):3876–86. https://doi.org/10.1016/j.vaccine.2005.03.005.
Sharif N, Alzahrani KJ, Ahmed SN, Dey SK. Efficacy, immunogenicity and safety of covid-19 vaccines: a systematic review and meta-analysis. Front Immunol. 2021;12:714170. https://doi.org/10.3389/fimmu.2021.714170.
Carvalho JC, Cunha F, Coutinho IA, Loureiro C, Faria E, Bom AT. Hypersensitivity reactions to vaccines: current evidence and standards for sars-cov-2 vaccines. Acta Med Port. 2021;34(7–8):541–7. https://doi.org/10.20344/amp.16096.
Watad A, De Marco G, Mahajna H, et al. Immune-Mediated Disease Flares or New-Onset Disease in 27 Subjects Following mRNA/DNA SARS-CoV-2 Vaccination. Vaccines (Basel). 2021;9(5):435. https://doi.org/10.3390/vaccines9050435.
Rajan TV. The Gell-Coombs classification of hypersensitivity reactions: a re-interpretation. Trends Immunol. 2003;24(7):376–9. https://doi.org/10.1016/s1471-4906(03)00142-x.
Sanchez-Alamo B, Cases-Corona C, Fernandez-Juarez G. Facing the challenge of drug-induced acute interstitial nephritis. Nephron. 2023;147(2):78–90. https://doi.org/10.1159/000525561.
Pichler WJ. Pharmacological interaction of drugs with antigen-specific immune receptors: the p-i concept. Curr Opin Allergy Clin Immunol. 2002;2(4):301–5. https://doi.org/10.1097/00130832-200208000-00003.
Krishnan N, Perazella MA. Drug-induced acute interstitial nephritis: pathology, pathogenesis, and treatment. Iran J Kidney Dis. 2015;9(1):3–13.
Spanou Z, Keller M, Britschgi M, et al. Involvement of drug-specific T cells in acute drug-induced interstitial nephritis. J Am Soc Nephrol. 2006;17(10):2919–27. https://doi.org/10.1681/ASN.2006050418.
Ferenbach D, Hughes J. Macrophages and dendritic cells: what is the difference? Kidney Int. 2008;74(1):5–7. https://doi.org/10.1038/ki.2008.189.
Soos TJ, Sims TN, Barisoni L, et al. CX3CR1+ interstitial dendritic cells form a contiguous network throughout the entire kidney. Kidney Int. 2006;70(3):591–6. https://doi.org/10.1038/sj.ki.5001567.
John R, Nelson PJ. Dendritic cells in the kidney. J Am Soc Nephrol. 2007;18(10):2628–35. https://doi.org/10.1681/ASN.2007030273.
Dong X, Swaminathan S, Bachman LA, Croatt AJ, Nath KA, Griffin MD. Antigen presentation by dendritic cells in renal lymph nodes is linked to systemic and local injury to the kidney. Kidney Int. 2005;68(3):1096–108. https://doi.org/10.1111/j.1523-1755.2005.00502.x.
Macconi D, Chiabrando C, Schiarea S, et al. Proteasomal processing of albumin by renal dendritic cells generates antigenic peptides. J Am Soc Nephrol. 2009;20(1):123–30. https://doi.org/10.1681/ASN.2007111233.
Rees A. Cross dendritic cells anger T cells after kidney injury. J Am Soc Nephrol. 2009;20(1):3–5. https://doi.org/10.1681/ASN.2008111200.
Pindjakova J, Griffin MD. The renal lymph node and immune tolerance to filtered antigens. J Am Soc Nephrol. 2013;24(4):519–21. https://doi.org/10.1681/ASN.2013020164.
Raghavan R, Shawar S. Mechanisms of drug-induced interstitial nephritis. Adv Chronic Kidney Dis. 2017;24(2):64–71. https://doi.org/10.1053/j.ackd.2016.11.004.
Ozkok A, Yildiz A. Hepatitis C virus associated glomerulopathies. World J Gastroenterol. 2014;20(24):7544–54. https://doi.org/10.3748/wjg.v20.i24.7544.
Moretti M, Lava SAG, Zgraggen L, et al. Acute kidney injury in symptomatic primary Epstein-Barr virus infectious mononucleosis: systematic review. J Clin Virol. 2017;91:12–7. https://doi.org/10.1016/j.jcv.2017.03.016.
Bae SH, Chung BH, Park YK, et al. Cytomegalovirus induced interstitial nephritis and ureteral stenosis in renal transplant recipient. Korean J Intern Med. 2012;27(4):470–3. https://doi.org/10.3904/kjim.2012.27.4.470.
Su H, Yang M, Wan C, et al. Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China. Kidney Int. 2020;98(1):219–27. https://doi.org/10.1016/j.kint.2020.04.003.
Sales GTM, Foresto RD. Drug-induced nephrotoxicity. Rev Assoc Med Bras (1992). 2020;66Suppl 1 (Suppl 1):s82–s90. https://doi.org/10.1590/1806-9282.66.S1.82
Naughton CA. Drug-induced nephrotoxicity. Am Fam Physician. 2008;78(6):743–50.
Reyes-Castillo Z, Valdés-Miramontes E, Llamas-Covarrubias M, Muñoz-Valle JF. Troublesome friends within us: the role of gut microbiota on rheumatoid arthritis etiopathogenesis and its clinical and therapeutic relevance. Clin Exp Med. 2021;21(1):1–13. https://doi.org/10.1007/s10238-020-00647-y.
Harley JB, James JA. Everyone comes from somewhere: systemic lupus erythematosus and Epstein-Barr virus induction of host interferon and humoral anti-Epstein-Barr nuclear antigen 1 immunity. Arthritis Rheum. 2010;62(6):1571–5. https://doi.org/10.1002/art.27421.
Lucchese G, Flöel A. Molecular mimicry between SARS-CoV-2 and respiratory pacemaker neurons. Autoimmun Rev. 2020;19(7): 102556. https://doi.org/10.1016/j.autrev.2020.102556.
Lucchese G, Flöel A. SARS-CoV-2 and Guillain-Barré syndrome: molecular mimicry with human heat shock proteins as potential pathogenic mechanism. Cell Stress Chaperones. 2020;25(5):731–5. https://doi.org/10.1007/s12192-020-01145-6.
Grotto I, Mandel Y, Ephros M, Ashkenazi I, Shemer J. Major adverse reactions to yeast-derived hepatitis B vaccines–a review. Vaccine. 1998;16(4):329–34. https://doi.org/10.1016/s0264-410x(97)00214-4.
Kaplanski G, Retornaz F, Durand J, Soubeyrand J. Central nervous system demyelination after vaccination against hepatitis B and HLA haplotype. J Neurol Neurosurg Psychiatry. 1995;58(6):758–9. https://doi.org/10.1136/jnnp.58.6.758-a.
Vital C, Vital A, Gbikpi-Benissan G, et al. Postvaccinal inflammatory neuropathy: peripheral nerve biopsy in 3 cases. J Peripher Nerv Syst. 2002;7(3):163–7. https://doi.org/10.1046/j.1529-8027.2002.02010.x.
Roy S, Awogbemi T, Holt RCL. Acute tubulointerstitial nephritis in children- a retrospective case series in a UK tertiary paediatric centre. BMC Nephrol. 2020;21(1):17. https://doi.org/10.1186/s12882-020-1681-7.
Joyce E, Glasner P, Ranganathan S, Swiatecka-Urban A. Tubulointerstitial nephritis: diagnosis, treatment, and monitoring. Pediatr Nephrol. 2017;32(4):577–87. https://doi.org/10.1007/s00467-016-3394-5.
Turnier JL, Anderson MS, Heizer HR, Jone PN, Glodé MP, Dominguez SR. Concurrent respiratory viruses and kawasaki disease. Pediatrics. 2015;136(3):e609–14. https://doi.org/10.1542/peds.2015-0950.
McCormick JK, Yarwood JM, Schlievert PM. Toxic shock syndrome and bacterial superantigens: an update. Annu Rev Microbiol. 2001;55:77–104. https://doi.org/10.1146/annurev.micro.55.1.77.
Ng JH, Zaidan M, Jhaveri KD, Izzedine H. Acute tubulointerstitial nephritis and COVID-19. Clin Kidney J. 2021;14(10):2151–7. https://doi.org/10.1093/ckj/sfab107.
Funding
This study was supported by the National Natural Science Foundation of China (No. 81970583 and No. 82060138), the Key Projects of Jiangxi Natural Science Foundation (No. 20224ACB206008), the Kidney Disease Engineering Technology Research Centre Foundation of Jiangxi Province (No. 20164BCD40095), the Key Projects in the Second Affiliated Hospital of Nanchang University (No. 2022efyB01), and the Thousand Talents Plan project of introducing and training high-level talents of innovation and entrepreneurship in Jiangxi Province (No. JXSQ2023201030).
Author information
Authors and Affiliations
Contributions
YW and LY performed data collection and wrote the manuscript. GX was responsible for the idea, funds, and paper revision. The authors have all read and approved the final version of the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no competing interests.
Ethics Approval and Consent to Participate
Not applicable.
Consent for Publication
Not applicable.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Wang, Y., Yang, L. & Xu, G. New-Onset Acute Interstitial Nephritis Post-SARS-CoV-2 Infection and COVID-19 Vaccination: A Panoramic Review. J Epidemiol Glob Health 13, 615–636 (2023). https://doi.org/10.1007/s44197-023-00159-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s44197-023-00159-4