Have we missed AINything? Acute interstitial nephritis in SARS-CoV-2 infection and vaccination

Abstract

Acute interstitial nephritis (AIN), defined by the presence of interstitial inflammation accompanied by tubulitis, is an often overlooked cause of acute kidney injury (AKI). It is now well established that SARS-CoV-2 infection can cause a wide variety of kidney injuries, most commonly acute tubular injury and collapsing glomerulopathy. In comparison, AIN is rarely documented in association with SARS-CoV-2 both anecdotally and in larger series of autopsy or biopsy studies. In this issue of the Journal, León-Román describe 5 cases of AIN in patients with a history of COVID-19 and highlight AIN as a possibly under-reported or ignored facet of renal disease associated with SARS-CoV-2. They describe three scenarios in which AIN can be seen: 1) SARS-CoV-2 infection after diagnosis of AIN, 2) AIN followed by SARS-CoV-2 infection in the same admission and 3) Severe SARS-CoV-2 and AIN possibly associated with SARS-CoV-2 itself. Overall, AIN remains rare in SARS-CoV-2 and causality is difficult to ascertain. Interestingly, AIN is not only seen in association with the disease itself but also with SARS-CoV-2 vaccination. This scenario is equally rare and causality is no less difficult to prove. A history of preceding SARS-CoV-2 infection and vaccination should be actively sought when patients present with otherwise unexplained AIN.

Acute Interstitial Nephritis with Glomerular Capillary IgA Deposition Following SARS-CoV-2 mRNA Vaccination

“…We encountered a case of biopsy-proven AIN in concurrence with glomerular capillary IgA deposition and diabetic (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). Relapse of underlying IgG4-related interstitial nephritis following SARS-CoV-2 mRNA vaccination has also been described (27).…”

“…Several types of glomerulonephritis following SARS-CoV-2 vaccination, including IgA nephropathy (IgAN), antiglomerular basement membrane (GBM) glomerulonephritis, anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis, membranous nephropathy (MN), minimal change disease (MCD), focal segmental glomerulonephritis (FSGS), and lupus nephritis, have been reported to date (3)(4)(5)(6)(7)(8)(9)(10)(11). However, acute interstitial nephritis (AIN) following SARS-CoV-2 vaccination has been considered a rare clinical entity, although reports of such cases have been increasing in conjunction with the large-scale implementa-tion of COVID-19 vaccination worldwide (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26).…”

Intrinsic Kidney Pathology in Children and Adolescents Following COVID-19 Vaccination: A Systematic Review

“…There was a lack of clear-cut co-morbidities and risk factors which might have provided non-COVID-19 explanations for this pathology, but TIN is often an underdiagnosed and under-reported condition and causality is difficult to prove given a myriad of potential confounding factors [ 58 ]. The attention directed towards TIN is less compared to glomerular diseases and there are many unanswered questions regarding the temporal association between COVID-19 vaccination and TIN [ 59 , 60 ].…”

Virus-Associated Nephropathies: A Narrative Review

“…The other major cause of AKI is the development of collapsing FSGS in 25 to 40% of cases of so-called COVID-19 associated nephropathy (COVAN) [ 117 , 118 , 119 , 120 ]. The development of COVAN, similarly to HIVAN, appears to be particularly related to the APOL-1 genotype rather than disease severity, according to the “two-hits” theory [ 121 , 122 , 123 , 124 ]; see Figure 1 c. Although rare, other histological findings have been described, among which, acute interstitial nephritis [ 125 ] and thrombotic microangiopathy [ 126 , 127 ] are the main ones. Finally, allograft rejection lesions have been observed in 50% of for-cause biopsies in KTRs presenting an AKI during or after a SARS-CoV-2 infection [ 118 , 119 , 126 , 128 ].…”