C1q-POSITIVE DE NOVO IgA NEPHROPATHY FOLLOWING COVID-19 INFECTION, CONFIRMED BY Gd-IgA1 STAINING AFTER KIDNEY TRANSPLANTATION

De novo IgA nephropathy (IgAN) in kidney transplant recipients is increasingly recognized, yet its clinical characteristics remain poorly defined, and distinguishing it from non-specific IgA deposition remains challenging. Viral infections, including COVID-19, have been implicated as triggers of IgA deposition. Here, we report a case of a kidney transplant recipient with de novo IgAN accompanied by C1q deposition following COVID-19 Infection, confirmed by galactose-deficient IgA1 (Gd-IgA1) staining.

Case Presentation:

A 29-year-old woman with prior living-donor kidney transplantation presented with proteinuria. Five years earlier, she was diagnosed with ANCA-associated vasculitis and received standard treatment. Her kidney function deteriorated, requiring ABO-incompatible kidney transplantation from her father two years ago. She was maintained on steroids, tacrolimus, azathioprine and everolimus, and serum creatinine remained stable at 1.0-1.2 mg/dL. She contracted COVID-19 and was treated with molnupiravir three months before this visit. At this visit, laboratory test showed undetectable MPO-ANCA, with urine analysis showing occult blood 5-9/HPF and proteinuria of 3.0 g/gCre. A kidney biopsy revealed mild interstitial infiltrate and fibrosis, mesangial proliferation and fibrocellular crescents on light microscopy. Immunofluorescent analysis showed IgA deposits in the mesangium with C1q deposits. Electron-dense deposits were detected in the para-mesangial and subendothelial regions. Further immunofluorescent staining of Gd-IgA1 demonstrated colocalization with IgA deposits, confirming de novo IgAN post-transplantation. Standard therapy with Pozzi protocol and tonsillectomy was performed; however, kidney function declined and proteinuria persisted. A follow-up biopsy six months post-treatment showed residual fibrocellular crescents. Consequently, treatment with enalapril and dapagliflozin was initiated, and steroid dosage was tapered.

Discussion:

The patient exhibited no risk factors for secondary IgAN, and the diagnosis of IgAN was confirmed through Gd-IgA1 staining. In this instance, it was hypothesized that de novo IgAN was precipitated by a COVID-19 infection. The association between IgAN and COVID-19 infection has been documented since the onset of the pandemic. The mucosal immune response to SARS-CoV-2 may result in the overactivation of the complement system, thereby increasing Gd-IgA1 deposition in the glomeruli. Moreover, IgAN that develops post-COVID-19 infection frequently demonstrates C4d positivity, and in this case, new C4d deposits were identified. These observations suggest that the presence of Gd-IgA1 and C4d deposits may assist in distinguishing COVID-19–related de novo IgAN from other forms of nephritis.

The relative resistance to steroid therapy observed in this case is consistent with the characteristics of de novo IgA. Furthermore, the presence of C1q deposits, which are uncommon and considered indicators of poor renal prognosis in primary IgAN, was noted in this patient. Based on the clinical progression, C1q deposits in de novo IgAN may similarly be associated with adverse renal outcomes.

This work was first presented at ASN Kidney Week 2025, and re-submission is permitted by ASN.