Monotypic IgA nephropathy: A large health system experience

AIMS: IgA nephropathy (IgAN) is traditionally considered a polytypic disorder, although λ light chain predominance on immunofluorescence (IF) is common. In some cases, monotypic IgA (mIgA) staining is identified. Whether mIgA represents a variant of IgAN or should be classified as proliferative glomerulonephritis with monoclonal immune deposits (PGNMID) remains controversial, particularly in cases with isolated κ deposits or membranoproliferative (MP) or membranous patterns. We performed this study to characterize all mIgA cases in our institutional biopsy database, with emphasis on hematologic evaluation and clinical outcomes. MATERIALS AND METHODS: The Northwell Health kidney biopsy database was reviewed, identifying 8 mIgA cases (1.3% of IgA biopsies). Electronic medical records were reviewed for clinical, laboratory, histological, and follow-up data. RESULTS: Five cases demonstrated κ restriction, and 3 showed λ. Median age was 42 years, and 75% were male. No patient had a known hematologic disorder at presentation. Median serum creatinine was 1.75 mg/dL. Histological patterns included mesangioproliferative +/- sclerosing (62.5%), sclerosing alone (25%), and MP (12.5%). Only 1 patient had a monoclonal gammopathy, but it was non-IgA. Bone marrow biopsies and flow cytometry revealed no hematologic neoplasms. One patient underwent blood mass spectrometry, which was negative. Treatments varied, and most patients achieved stable or improved renal function. One patient with a prior transplant and diabetic nephropathy developed thrombotic microangiopathy and entered hospice. Among 6 patients with follow-up (mean 39.5 months), none developed hematologic malignancy. CONCLUSION: These findings support the non-monoclonal nature of most mIgA cases, with no detectable clones at baseline or follow-up. Larger studies using advanced detection techniques are needed to clarify clonal risk and guide optimal therapy.