Abstract: TH-PO192

Complement Factor C4d Staining in Gemcitabine-Induced Thrombotic Microangiopathy: A Case Series

Session Information

Category: Nephrology Education

  • 1302 Fellows and Residents Case Reports


  • Muro, Koji, Kyoto University Hospital, Kyoto, Japan
  • Yokoi, Hideki, Kyoto University Hospital, Kyoto, Japan
  • Sakai, Kaoru, Kyoto University Hospital, Kyoto, Japan
  • Endo, Shuichiro, Kyoto University Hospital, Kyoto, Japan
  • Matsubara, Takeshi, Kyoto University Hospital, Kyoto, Japan
  • Yanagita, Motoko, Kyoto University Hospital, Kyoto, Japan

Complement factor C4d staining is a common finding in thrombotic microangiopathy (TMA), regardless of the underlying clinical condition. However, there are few reports in the literature investigating C4d staining of drug-toxicity-induced TMA, especially of gemcitabine (GEM)-induced TMA (GCI-TMA). We aim to examine the pattern of C4d staining in renal biopsy specimens from three patients with GCI-TMA.


Case 1 A 52-year-old man was diagnosed with hilar cholangiocarcinoma at the age of 46. Following surgery, he had been treated with GEM therapy (cumulative dose of 64,400 mg). His serum creatinine (Cr) level started increasing to 3.5 mg/dL from a baseline of 0.8 mg/dL within 22 months. Proteinuria appeared and his urinary protein-to-Cr ratio reached 2.5 g/g Cr. Case 2 A 64-year-old woman was diagnosed with pancreatic cancer. She was treated with concurrent chemoradiotherapy and GEM was administered. Four months later, cumulative dose of GEM was 23,800 mg and her serum Cr level started increasing to 1.69 mg/dL from a baseline of 0.7 mg/dL within 5 months. Her urine dipstick revealed 2+ proteinuria, and her urinary protein-to-Cr ratio was 1.5 g/g Cr. Case 3 A 70-year-old woman with recurrent angioimmunoblastic T-cell lymphoma was referred to our hospital. She had started to receive GEM since the age of 69. After cumulative dose of 15,250 mg, her serum Cr level was elevated to 1.4 mg/dL from a baseline of 0.6 mg/dL within 17 months, and proteinuria appeared reaching to 3.4 g/day. Result Light microscopy showed mesangiolysis and double contours in glomeruli. Immunofluorescence study demonstrated segmental deposits of C4d along glomerular capillaries (GBM-C4d) in all cases. Electron microscopy showed glomerular basement membraine (GBM) duplication and no dense deposit. In all three cases, GEM was discontinued. Renal function of these patients partially improved but did not fully recover.


A recent study showed that isolated strong GBM-C4d can highlight architectural glomerular remodeling. In our cases, segmental GBM-C4d and GBM duplication were observed, and their renal function did not fully recover. GBM-C4d staining in GCI-TMA might imply relatively poor renal prognosis.