Chromogranin A-Associated Tubulopathy in a Patient With Neuroendocrine Tumor

Chromogranin A (CGA) is a peptide secreted by neuroendocrine cells and filtered by the kidneys. Excessive CGA secretion is common in neuroendocrine tumors (NETs) and has been linked to organ dysfunction, though direct kidney injury remains rarely described. We present a woman in her mid-70s diagnosed with metastatic, well-differentiated pancreatic NET who developed progressive renal dysfunction. Initial CGA levels exceeded 86,000 ng/mL and later rose to >500,000 ng/mL. Despite the absence of nephrotoxic exposures, imaging abnormalities, or significant proteinuria, her serum creatinine increased from a baseline of 1.0 mg/dL to 5.6 mg/dL over several months, necessitating hemodialysis. Renal biopsy revealed acute tubular injury characterized by prominent intracytoplasmic granules in tubular epithelial cells, which were strongly positive for CGA on immunohistochemical staining, without evidence of immune complex disease. These findings suggested CGA-induced tubulopathy as the cause of her acute tubular necrosis (ATN). The patient's NET demonstrated partial radiologic response to treatment with octreotide and everolimus, but she remained dialysis-dependent until her passing six months later. This case highlights CGA tubulopathy as a rare but significant cause of acute renal failure in patients with NETs. It emphasizes the importance of early nephrology involvement and proactive renal monitoring in patients with markedly elevated CGA levels. Further research is needed to elucidate the mechanisms of CGA-induced nephrotoxicity and the potential reversibility of renal injury with NET-directed therapies.