Gemcitabine nephrotoxicity and hemolytic uremic syndrome: report of 29 cases from a single institution.
BACKGROUND
Gemcitabine is used in a variety of advanced malignancies. Hemolytic uremic syndrome has been reported as a side effect.


METHODS
we reviewed medical records of 29 patients with gemcitabine nephrotoxicity.


RESULTS
The median cumulative dose of gemcitabine was 22 g/m2 (4 - 81) given over 7.5 months (2 - 34). Prior chemotherapy with mitomycin had been given to 9 patients, and in 4 the hemolytic uremic syndrome was particularly severe and appeared shortly after gemcitabine initiation. All patients had renal insufficiency. Microhematuria and proteinuria were present in 27 patients and red blood cell casts were seen in 8. Renal biopsies in 4 patients showed thrombotic microangiopathy. Worsening or new-onset hypertension was seen in 26 patients. Edema, shortness of breath and congestive heart failure were present in 21, 15 and 7 patients, respectively. All had anemia, thrombocytopenia and elevated serum lactate dehydrogenase. Haptoglobin was low in 23 of the 26 patients who had it measured. Schistocytes were present in 21 of the 24 patients who had blood smear reviewed. Gemcitabine was discontinued once hemolytic uremic syndrome was recognized. Full or partial recovery of renal function occurred in 19 patients. 7 patients progressed to end-stage renal disease and 3 patients developed chronic renal failure.


CONCLUSIONS
Gemcitabine nephrotoxicity presents as new-onset renal disease with associated hypertension, thrombocytopenia and microangiopathic hemolytic anemia. Prior chemotherapy with mitomycin, especially when given in close proximity, may be synergistic. A high index of suspicion is essential to make an early diagnosis. Stopping gemcitabine improves the outcome.
Glezerman
I
I
Renal Service, Memorial Sloan Kettering Cancer Center, Weill Medical College of Cornell University, New York, NY, USA.
Kris
M G
MG
Miller
V
V
Seshan
S
S
Flombaum
C D
CD
D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D002423:Cause of Death; D003404:Creatinine / Q000378:metabolism; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives*; D018450:Disease Progression; D005260:Female; D006463:Hemolytic-Uremic Syndrome / Q000139:chemically induced*; D006801:Humans; D006977:Hypertension, Renal / Q000139:chemically induced; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013921:Thrombocytopenia / Q000139:chemically induced; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D003404:Creatinine; D007770:L-Lactate Dehydrogenase; D000093542:Gemcitabine