Erythropoietin production in renal cell carcinoma and renal cysts in autosomal dominant polycystic kidney disease in a chronic dialysis patient with polycythemia: A case report

Abstract

In patients undergoing chronic hemodialysis (HD), erythropoietin (EPO) production from the kidney generally decreases and renal anemia develops. Patients without anemia, but with high serum EPO (sEPO) levels are rare among HD patients. The current study presents the case of a 67-year-old female HD patient with autosomal dominant polycystic kidney disease (ADPKD) and renal cell carcinoma (RCC), manifesting polycythemia with elevated sEPO levels. A radical nephrectomy was performed, which diminished the polycythemia, but the sEPO levels remained high. To determine the origin of the EPO production, immunohistochemistry was performed to detect EPO in the RCC and the renal cysts of the surgically resected kidney. In addition, the sEPO and EPO levels in a renal cyst were determined by enzyme immunoassay. EPO expression was demonstrated in RCC and cyst epithelial cells using immunohistochemistry, revealing extremely high EPO levels in the cyst fluid. Due to the remission of polycythemia following the nephrectomy, EPO production from the resected kidney appeared to have been the cause of the polycythemia. Positive EPO staining of the renal cysts in the resected polycystic kidney and sustained sEPO elevation following nephrectomy led to the hypothesis of EPO production in the renal cysts of the contralateral polycystic kidney. Although the postoperative EPO level was higher than the normal range, the hematocrit (Hct) level gradually decreased and recombinant human EPO was required again three months following the nephrectomy. Eight months after the nephrectomy, the Hct level was 30.2% with the use of rHuEPO. In conclusion, EPO production from RCC and renal cysts in ADPKD appeared to cause polycythemia in the HD patient.

Keywords: autosomal dominant polycystic kidney disease; erythropoietin; immunohistochemistry; polycythemia; renal cell carcinoma.

Figure 1

Magnetic resonance imaging (coronal view) revealing a highly enhanced tumor (white arrows) in the lower part of the left polycystic kidney.

Figure 2

(A) Microscopic findings of the renal tumor with hematoxylin-eosin staining revealing a diagnosis of clear cell renal cell carcinoma (histological grades 1 and 2; pT1a). (B–D) Immunohistochemical analysis using anti-EPO antibody. (B) Positive staining was observed in the cytoplasm of the cancer cells. (C) Cells lining the cyst wall were positively stained with anti-EPO antibody (arrows), as well as those in the cytoplasm. (D) Positively-stained particles (arrows) were detected in the cytoplasm of the cyst-lining cells. EPO, erythropoietin.