Collapsing Focal Segmental Glomerulosclerosis With Concurrent IgG4 Nephropathy

TL;DR

A 41-year-old man with kidney disease was found to have a rare combination of IgG4-related kidney disease and APOL1-associated collapsing glomerulopathy, which responded to steroid and immunosuppressive treatment.

Contribution

This is the first reported case of IgG4-related kidney disease co-occurring with APOL1-associated collapsing glomerulopathy.

Findings

Renal biopsy confirmed IgG4-related tubulointerstitial nephritis and membranous glomerulonephritis.

The patient had severe podocytopathy in the form of collapsing glomerulopathy and FSGS.

Treatment with prednisolone and mycophenolate mofetil stabilized kidney function and normalized IgG4 levels.

Abstract

A 41-year-old male with a history of chronic kidney disease, hypertension, and psoriasis was referred to the nephrologist for worsening kidney function associated with nephrotic range proteinuria. The patient had no symptoms, but the initial workup showed elevated erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), positive double-stranded DNA antibody(anti-DsDNA) but normal complement levels, normal antinuclear antibody (ANA) and negative beta-glycoprotein-1 IgG, IgM, and IgA. Further, the workup revealed the patient had elevated total immunoglobulin as well as elevated IgG subsets 2, 3, and 4. He was also found to have a high variant of apolipoprotein L1 (APOL1). A renal biopsy revealed diffuse active, subacute, and chronic interstitial inflammation, plasma cell-rich (25% IgG4 positive), confirming IgG4-related tubulointerstitial nephritis with concomitant IgG4 dominant, PLA2R negative membranous glomerulonephritis. There was also a severe podocytopathy in the form of diffuse segmental/global collapsing glomerulopathy with sclerosing changes as well as global glomerulosclerosis, extensive tubular atrophy with mild interstitial changes suggestive of a variant of focal segmental glomerulosclerosis (FSGS). A diagnosis of APOL-1 collapsing glomerulopathy with IgG4 nephropathy was made based on clinical and pathological findings. The patient’s kidney function stabilized, and IgG4 levels returned to normal after the patient was initiated on 60 mg daily prednisolone. The steroid was tapered off and the patient was started on mycophenolate mofetil 1000 mg twice daily. To our knowledge, this is the first reported case of IgG4-related kidney disease with concurrent severe APOL1-associated collapsing glomerulopathy.

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