P3D316: Importance of Renal Biopsy in an Atypical Case of Pediatric Glomerulonephritis

Introduction: Systemic lupus erythematosus (SLE) is a multiorgan system chronic inflammatory disease which commonly presents in adolescent females. Lupus nephritis presents with a constellation of findings including edema, hypertension, proteinuria, and hematuria in addition to positive serologic markers. Here we introduce an atypical presentation of lupus nephritis ultimately diagnosed by renal biopsy.

Case Description: Patient is a 13yo female with spinocerebellar ataxia type 29 (ITPR1 pathogenic variant) who initially presented for well check and she was noted to have an elevated blood pressure (132/90). Urinalysis was remarkable for proteinuria (3+), microscopic hematuria (RBC 26-50/hpf) and pyuria (WBCs 6-10/hpf) with hyaline casts. Her creatinine was elevated (eGFR of 35 ml/min/1.73 m2). Patient also had normocytic anemia and mildly elevated ANA (1:80). Anti-dsDNA was negative. Serum C3 and C4 were normal. Further work-up showed markedly elevated anti-MPO titer that was above the level of detection for the reference lab.

Due to concern for ANCA-associated vasculitis, renal biopsy was performed and revealed diffuse immune complex deposition with full house staining (+IgA, IgM, C3, IgG- C1q was not performed) and both membranoproliferative and membranous features, consistent with Class IV and V lupus nephritis. Biopsy was also notable for significant chronicity with ~30% interstitial fibrosis present.

Six months after treatment with mycophenolate mofetil and prednisone, patient’s eGFR has increased to >80 ml/min/1.73m2, although she continues to have heavy proteinuria and is currently receiving belimumab infusions for treatment of refractory lupus nephritis.

Discussion: Lupus nephritis is confirmed by histologic findings, which are then used to define the nature of kidney involvement, determine the histopathologic subtype of LN (Class I-V), and assess disease activity and chronicity. Renal biopsy is invaluable in cases of autoimmune glomerulonephritis as sole reliance of serology studies could otherwise elicit misdiagnoses. Positive p-ANCA and anti-MPO antibodies have been previously described in patients with lupus nephritis, including up to 30% of patients in one single center study. However, the combination of normal serum complements and only mildly elevated ANA titer seen in our patient is unusual given the severity of nephritis observed in this patient relative to the degree of MPO titer elevation. There are no reports in the literature to suggest any link between this patient’s underlying genetic syndrome and risk of glomerulonephritis.

Conclusion: Renal biopsy remains the gold standard for diagnosis of autoimmune glomerulonephritis in children. Lupus nephritis should be highly suspected in pediatric glomerulonephritis, particularly when the serologic picture is conflicting. ANCA titers may be positive in the setting of other autoimmune disease and must be interpreted with caution.