Neuroendocrine Nephrotoxicity: A Case of Chromogranin A Tubulopathy

Introduction: Neuroendocrine neoplasms (NENs) are capable of secreting functional peptides such as chromogranin A (CgA), an acidic glycoprotein that serves as a NEN biomarker. Although CgA is normally present at basal levels and is easily filtered, reabsorbed, and metabolized within the nephron, when filtered into the urinary space in large amounts, increased resorption can engorge proximal tubular epithelial cells beyond capacity causing cellular damage. We present a case of progressive renal insufficiency in the setting of metastatic NEN consistent with CgA tubulopathy. Case Description: A 78-year-old female with known metastatic NEN maintained on somatostatin analog therapy was referred for progressive renal dysfunction. Urine microscopy was negative for hematuria or pyuria, and ultrasonography revealed structurally normal kidneys. Total proteinuria was elevated out of proportion to microalbuminuria in the setting of normal serum and urine protein electrophoresis but a rising serum CgA. Due to persistent renal function decline, kidney biopsy was performed, which demonstrated acute tubular injury with proximal tubular epithelial cell resorption granules identified as CgA by immunohistochemistry; these granules demonstrated neither light chain restriction on frozen or paraffin-based immunofluorescence nor evidence of Congo red staining (Figure 1). Discussion: CgA tubulopathy has been described histologically as acute tubular injury resulting from intracellular CgA resorption granules or intratubular cast formation, both of which lead to direct epithelial cytotoxicity. Management centers on early detection and targeted NEN therapy; plasma exchange has been attempted without demonstrated effectiveness. Although rare, a keen awareness of the clinicopathologic consequences of CgA tubulopathy must be shared by oncologists and nephrologists to facilitate early and optimal diagnosis and management.