PathPointers highlight important everyday teaching points when reviewing kidney histology. These brief and easy-to-read blog posts include real clinical images to demonstrate various biopsy findings.

Deposition of immune complexes in kidney disease commonly involves the glomerulus. The dynamic process of filtration, regulated by the specialized microanatomy of the glomerulus, is susceptible to pathologic deposition of circulating immune complexes in several glomerular compartments. 

Although less attention is paid to them compared to their glomerular counterparts, immune complexes may also deposit in tubular basement membranes. These TBM deposits may sometimes receive less attention, but an increasing variety of diseases shares the propensity for TBM immune complex deposition. These disease processes can be distinguished by the ultrastructural appearance, location, and composition of the deposits. Some diseases with tubular basement membrane deposits are lupus nephritis, monoclonal immunoglobulin deposition disease, IgG4 nephritis, fibrillary glomerulonephritis, and BK nephropathy.

Another example is presented in the following case. A 64-year-old male with fever of unknown origin and acute kidney injury requiring dialysis underwent kidney biopsy. On light microscopy, the biopsy demonstrates a diffuse infiltrate of predominantly lymphocytes in the interstitium. There is frequent tubulitis, and interstitial fibrosis is severe. Glomeruli are unremarkable aside from focal global sclerosis. 

Biopsy demonstrating diffuse infiltrate of predominantly lymphocytes in the interstitium, with frequent tubulitis, and severe interstitial fibrosis.

Immunofluorescence showing positive IgG staining of tubular basement membranes and at the luminal epithelial surface, indicating the presence of immune complexes.

IgG is also positive at Bowman’s capsule and focal segmental glomerular tuft. Electron microscopy confirms immune complex-type deposits in the tubular basement membranes, and there are occasional glomerular subepithelial deposits.

Bowman’s capsule and focal segmental glomerular tuft showing immune complex-type deposits in the tubular basement membranes, with occasional glomerular subepithelial deposits.

The unusual pattern of staining of both tubular basement membrane and luminal epithelial surface prompted consideration for anti-brush border antibody (ABBA) syndrome. The antigen targeted in the ABBA syndrome was recently identified as LDL receptor-related protein 2 (LRP2), also known as megalin, a protein expressed at the brush border of tubular epithelium. Immunostaining for this antigen showed its presence in deposits located in the tubular basement membrane  as well as brush border, confirming this case as anti-LRP2 tubulointerstitial nephritis.

The pathophysiology underlying this relatively newly described entity is still being worked out, but Heymann nephritis may serve as one model. Heymann nephritis is a longstanding rat model for membranous nephropathy, induced by immunizing rats with renal cortex homogenates. The target antigen turns out to be megalin (LRP2), which in rats is expressed in both tubular and glomerular epithelium. By contrast, human megalin is predominantly expressed in tubular epithelium, thus giving rise to the tubulointerstitial nephritis when megalin is targeted by autoantibody in patients with anti-LRP2 disease. The reason for the characteristic segmental subepithelial deposits in the glomeruli in this disease is unclear.

When presented with tubular basement membrane deposits, particularly if they coincide with glomerular and Bowman’s capsular deposits, consider this interesting and recently elucidated disease among the differential diagnostic possibilities.

– Post prepared by Matt Palmer, AJKD Pathology Editor.