ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: SA-PO1092

Paraneoplastic Cast Nephropathy Associated with Secretary Pancreatic Carcinoma

Session Information

Category: Pathology and Lab Medicine

  • 1502 Pathology and Lab Medicine: Clinical

Authors

  • Wehbe, Edgard I., Wichita Nephrology Group, Wichita, Kansas, United States
  • Said, Samar M., Mayo Clinic, Rochester, Minnesota, United States
  • Nasr, Samih H., Mayo Clinic, Rochester, Minnesota, United States
Introduction

We report the case of a patient with pancreatic mixed acinar-neuroendocrine carcinoma who presented with irreversible acute kidney injury ( AKI ) due to myeloma-like cast nephropathy. We performed proteomic and immunohistochemical studies which revealed that the AKI was triggered by tubular obstruction by acinar cell carcinoma-secreted proteins. A novel pathomechanism for carcinoma-associated nephropathy is being described.

Case Description

A 64-year old male was found with a large abdominal mass after workup for unintentional 35 pound weight loss over 6 month period. Biopsy of the mass showed pancreatic mixed acinar-neuroendocrine carcinoma. He developped AKI after the diagnosis. Urinalysis showed 1 + protein but no hematuria. Serologies were negative. Serum protein electrophoresis with immunofixation did not show monoclonal protein and serum free kappa/lambda ratio was normal. Kidney biopsy showed myeloma-like cast nephropathy. He was initiated on hemodialysis and received rescue plasmapheresis without success in renal recovery. He received gemcitabine and Abraxane with no improvement in his condition. He remained on dialysis, had a decline in his clinical condition, developed severe refractory septic shock and died 4 months after cancer diagnosis.

Discussion

Kidney biopsy showed acute cast nephropathy with many distal tubular PAS-negative and trichrome-polychromatic casts, associated with mononuclear and giant cell reaction, acute tubular injury, and mild interstitial inflammation and fibrosis . Ultrastructurally, the casts were electron dense and some were admixed with fibrillar uromodulin casts. The casts did not stain for kappa or lambda on immunofluorescence. Analysis by laser microdissection/mass spectrometry and by immunohistochemistry detected large amounts of two acinar-cell specific proteins, , REG 1α and CPA1, in the renal casts and the patient’s pancreatic carcinoma cells. Thus, the acute kidney injury in this patient is likely due to distal tubular obstruction by aggregates of filtered carcinoma-secreted proteins and uromodulin, with subsequent tubular injury, interstitial inflammation and fibrosis, as has been proposed in myeloma cast nephropathy. This case describe a new mechanism for paraneoplastic cast nephropathy in the absence of multiple myeloma.