AB1380 INTRINSIC RENAL IgG4-RELATED DISEASE IN A MULTI-ETHNIC SINGAPORE COHORT

Background: Renal involvement in IgG4-related disease (IgG4-RD) comprises intrinsic renal parenchymal disease and retroperitoneal fibrosis with resultant obstructive uropathy. The former is less often reported and mainly found in the Mikulicz/systemic sub-type. Widely accepted criteria for intrinsic renal IgG4-RD are typical histological features (i.e. storiform fibrosis, obliterative phlebitis, increased IgG4 plasma cells), IgG4- tubulointerstitial nephritis (IgG4-TIN) and radiographic features (renal pelvis thickening, renal cortex low-density areas) in the appropriate clinical settings as recommended by the 2019 ACR/EULAR classification criteria and Raissian et al. Renal biopsy findings of membranous nephropathy (MN) and focal segmental glomerulosclerosis (FSGS) in IgG4-RD patients have been reported but not included in any diagnostic/classification criteria. Objectives: To describe the characteristics and management of intrinsic renal IgG4-RD patients in a Southeast Asian population. Methods: Chart review was performed for all IgG4-RD patients seen between 1 January 2015 and 30 September 2021 at our hospital. Clinical, imaging, histopathologic data, treatment and outcomes were collected from medical records. All patients fulfilled the 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD for at least possible IgG4-RD and were scored against the 2019 ACR/EULAR IgG4-RD classification criteria. Renal involvement was evaluated in patients with laboratory evidence of kidney injury (raised creatinine, proteinuria, or hematuria), radiographic kidney abnormalities (renal parenchymal, renal pelvic and perinephric lesions), and obstructive uropathy due to retroperitoneal fibrosis. Results: Of 58 IgG4-RD patients, 9 (15.5%) had findings suggestive of renal involvement – 7 intrinsic renal disease, 2 obstructive uropathy. 6/7 (85.7%) intrinsic renal IgG4-RD patients were male and median age at diagnosis was 61; 5 were smokers, 2 had cancers, and 5 had underlying metabolic comorbidities. 4 patients had probable and 3 possible IgG4-RD based on the RCD. 3/7 fulfilled the 2019 ACR/EULAR classification criteria. Of these 7 patients, 3 had serum IgG4 ≥135mg/dL, 5 raised serum creatinine, 5 significant proteinuria ≥1g/day, 3 microscopic hematuria, and 2 low C3/C4. Compared with patients without intrinsic renal IgG4-RD, these 7 patients had significantly higher median maximum ESR 88mm/hr (IQR 78-125) (p = 0.050), median maximum serum total IgG 3140mg/dL (IQR 2550 - 5310) (p = 0.003), IgG1 1600mg/dL (1350 – 2040) (p = 0.003) and IgG2 919mg/dL (743 – 2320) (p = 0.027). 5/7 patients received renal biopsy – 1 storiform fibrosis, 1 IgG4-TIN, 1 dense sclerosis with lymphoplasmacytic aggregates, 1 FSGS, and 1 primary MN. Remaining 2 patients had radiological findings suspicious for renal IgG4-RD. For treatment, prednisolone was most commonly prescribed (6/7) followed by azathioprine (3/7). Other immunosuppressants given were ciclosporine, methotrexate and rituximab. 1 patient required short-term dialysis for acute kidney injury. 2 patients had demised – 1 from adenocarcinoma of stomach and 1 from infection. All survivors achieved renal remission after initial presentation, of which 2/5 patients were in drug-free remission. Table 1 shows details of the intrinsic renal IgG4-RD patients and Table 2 compares between patients with and without intrinsic renal disease. Conclusion: Intrinsic renal involvement in IgG4-RD patients is not uncommon and is associated with a high incidence of proteinuria in our cohort. The histopathological findings on renal biopsy varied widely with only 2/5 patients with suspected intrinsic renal IgG4-RD exhibiting findings included in the recommended IgG4-RD classification/diagnostic criteria. Further epidemiological and histo-pathological studies are required to determine the types of pathology associated with renal IgG4-RD, and potentially an expansion of renal IgG4-RD criteria. Overall prognosis for IgG4-RD patients with renal involvement is good with none progressing to end-stage-renal-failure in our cohort. REFERENCES: NIL. Acknowledgements: TTSH IgG4-RD Review Group. Disclosure of Interests: None declared.