Acute renal insufficiency after high-dose melphalan in patients with primary systemic amyloidosis during stem cell transplantation.
BACKGROUND
Patients with primary systemic amyloidosis (AL) have a poor prognosis. Median survival time from standard treatments is only 17 months. High-dose intravenous melphalan followed by peripheral blood stem cell transplant (PBSCT) appears to be the most promising therapy, but treatment mortality can be high. The authors have noted the development of acute renal insufficiency immediately after melphalan conditioning. This study was undertaken to further examine its risk factors and impact on posttransplant mortality.


METHODS
Consecutive AL patients who underwent PBSCT were studied retrospectively. Acute renal insufficiency (ARI) after high-dose melphalan was defined by a minimum increase of 0.5 mg/dL (44 micromol/L) in the serum creatinine level that is greater than 50% of baseline immediately after conditioning. Urine sediment score was the sum of the individual types of sediment identified on urine microscopy.


RESULTS
Of the 80 patients studied, ARI developed in 18.8% of the patients after high-dose melphalan. Univariate analysis identified age, hypoalbuminemia, heavy proteinuria, diuretic use, and urine sediment score (>3) as risk factors. Age and urine sediment score remained independently significant risk factors in the multivariate analysis. Patients who had ARI after high-dose melphalan underwent dialysis more often (P = 0.007), and had a worse 1-year survival (P = 0.03).


CONCLUSIONS
The timing of renal injury strongly suggests melphalan as the causative agent. Ongoing tubular injury may be a prerequisite for renal injury by melphalan as evidenced by the active urinary sediment. Development of ARI adversely affected the outcome after PBSCT. Effective preventive measures may help decrease the treatment mortality of PBSCT in AL patients.
Leung
Nelson
N
Department of Medicine, Division of Nephrology, Mayo Clinic, Rochester, MN 55905, USA. leung.nelson@mayo.edu
Slezak
Jeff M
JM
Bergstralh
Erik J
EJ
Dispenzieri
Angela
A
Lacy
Martha Q
MQ
Wolf
Robert C
RC
Gertz
Morie A
MA
D058186:Acute Kidney Injury / Q000139:chemically induced*; D000328:Adult; D000368:Aged; D000686:Amyloidosis / Q000150:complications* / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D012189:Retrospective Studies; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D015996:Survival Rate
D008558:Melphalan