What are the implications and treatment options for a patient with IgG (Immunoglobulin G) deposition on a kidney biopsy?

IgG Deposition on Kidney Biopsy: Diagnostic Approach and Clinical Implications

When IgG is detected on kidney biopsy, you must immediately perform IgG subclass staining to determine if the deposits are monoclonal or polyclonal, as this fundamentally changes diagnosis, prognosis, and treatment. 1

Mandatory Next Steps After Detecting IgG

IgG Subclass Staining is Essential

• IgG subclass staining (IgG1, IgG2, IgG3, IgG4) is recommended for all patients with IgG deposits to confirm whether deposits are monotypic (monoclonal) or polytypic (polyclonal). 1
• This staining serves two critical purposes: it confirms monotypic deposits and provides important clinical implications based on the specific subclass found. 1

Critical Distinction by IgG Subclass

• IgG3 deposits (most common monoclonal subtype): Less likely to have a detectable serum monoclonal protein or identifiable lymphoproliferative disorder. 1
• IgG1 deposits (second most common monoclonal subtype): Generally associated with a detectable serum monoclonal immunoglobulin and an underlying lymphoproliferative disorder requiring hematologic workup. 1
• Polyclonal IgG with IgG1 dominance/codominance plus IgG3 and IgG2 but weak/absent IgG4: Favors underlying autoimmune disease. 2

Correlation with Serum and Urine Studies

Mandatory Laboratory Workup

• All IgG deposits detected by kidney biopsy must be correlated with serum and urine tests for monoclonal immunoglobulin. 1
• Order serum protein electrophoresis with immunofixation, serum free light chains (kappa/lambda ratio), and 24-hour urine protein electrophoresis with immunofixation. 1

Additional Staining Requirements

• Congo red staining is strongly advised in all patients with serum/urine monoclonal immunoglobulin to exclude amyloidosis. 1
• Light chain restriction (kappa or lambda) must be assessed alongside IgG to determine if deposits are truly monoclonal. 1, 2

Common Diagnostic Scenarios

Monoclonal IgG Deposition Diseases

When IgG subclass staining reveals monoclonal deposits, consider:

• Monoclonal immunoglobulin deposition disease (MIDD): Organized deposits along basement membranes. 1
• Proliferative glomerulonephritis with monoclonal IgG deposits: Requires IgG subclass staining for diagnosis. 2
• AL amyloidosis: Must be excluded with Congo red staining. 1
• Immunotactoid glomerulonephritis: Microtubular structures on electron microscopy. 1

Polyclonal IgG Deposition Diseases

When IgG subclass staining reveals polyclonal deposits, consider:

• Lupus nephritis: Typically shows "full house" pattern with multiple immunoglobulins and complement. 1
• Membranous nephropathy: IgG4 dominance suggests primary disease; IgG1/IgG2 suggests secondary causes. 2
• IgA nephropathy: May have IgG autoantibodies specific for galactose-deficient IgA1 even when routine immunofluorescence is IgG-negative. 3
• Infection-related glomerulonephritis: Polyclonal IgG with complement deposition. 4

Critical Pitfalls to Avoid

Don't Rely on Light Chain Staining Alone

• Monoclonality of IgG deposits cannot always be reliably determined based on kappa and lambda light chain staining alone, particularly if concomitant (frequently nonspecific) IgM staining is present. 2
• IgG subclass staining is necessary to definitively establish monoclonality. 2

Consider Masked Deposits

• Paraffin immunofluorescence on protease-digested tissue is suggested when routine immunofluorescence is negative or equivocal but electron microscopy shows deposits. 1
• This technique can detect masked monoclonal immunoglobulin deposits, particularly in complement 3 glomerulopathy. 1

Don't Miss IgG in "IgG-Negative" Cases

• Even kidney biopsies without IgG by routine immunofluorescence microscopy may contain IgG-specific autoantibodies (as demonstrated in IgA nephropathy with anti-Gd-IgA1 antibodies). 3
• Consider more sensitive techniques if clinical suspicion remains high. 3

Treatment Implications

Monoclonal Gammopathy of Renal Significance (MGRS)

• If monoclonal IgG deposits are confirmed, evaluate for MGRS and underlying hematologic disorders including multiple myeloma, Waldenström macroglobulinemia, or monoclonal gammopathy of undetermined significance. 1
• Treatment targets the clone-producing monoclonal immunoglobulin with chemotherapy or immunotherapy regimens. 1

Autoimmune Disease

• If polyclonal IgG with autoimmune pattern is identified, initiate immunosuppression targeting the underlying autoimmune process (corticosteroids, mycophenolate, cyclophosphamide, or rituximab depending on specific diagnosis). 1

Prognostic Significance

• Urinary IgG excretion predicts clinical course better than total proteinuria in membranous nephropathy, with IgG excretion ≥110 mg/g creatinine associated with only 20% remission versus 100% remission when <110 mg/g. 5
• IgG excretion correlates significantly with tubulointerstitial damage extent and progression to chronic renal failure. 5