Lignt chain-associated acute tubulointerstitial nephritis

Clinical presentation  of kidney involvement in plasma cell dyscrasia (PCD) are variable. Patients may present with nephrotic syndrome due to AL amyloidosis or acute kidney injury due to light chain cast nephropathy (LCN). Similarly, histopathology may show severe kidney injury as in LCN or subtle change as in light chain proximal tubulopathy. Cheung et al. reported a poorly recognized kidney involvement in PCD called light chain-associated acute tubulointerstitial nephritis (LC-ATIN). The entity is characterized by tubulointerstitial inflammatory cell infiltrate by LM, linear tubular basement membrane and granular cytoplasmic proximal tubular staining by kappa or lambda light chain by IF and atypical lysosomes in proximal tubular cells with focal granular punctate depostis in TBM by EM.

LM finding is indisguishable from acute tubulointerstitial nephritis due to drug hypersensivity. The detection of monoclonal light chain staining in linear pattern along TBM and granular cytoplasmic in proximal tubules is crucial for diagnosis. The deposition of punctate electron dense deposits along TBM seems to be at least focally, as immunogold EM labeling demonstrated the presence of monoclonal light chain in TBM without deposits. The TBM linear light chain staining and punctate deposits also characterize light chain deposition disease, but LCDD lacks significant tubulointerstitial infiltrate and usually presents with glomerular and/or vascular involvement. It is arguable that LC-ATIN may be an early stage of LCDD.

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A increased and atypical lysosomes in proximal tubular cells, B punctate deposits along TBM similar to LCDD, C-D immunogold labeling demonstrates monoclonal light chain in lysosomes and TBM (Image from Cheung et al.)

Cheng M, Gu X, Turbat-Herrera EA, Herrera GA. Tubular Injury and Dendritic Cell Activation Are Integral Components of Light Chain-Associated Acute Tubulointerstitial Nephritis. Arch Pathol Lab Med. 2019;143(10):1212-1224. doi:10.5858/arpa.2018-0032-OA