Acute renal insufficiency after high-dose melphalan in patients with primary systemic amyloidosis during stem cell transplantation

Nelson Leung, Jeff M. Slezak, Erik J. Bergstralh, Angela Dispenzieri, Martha Lacy, Robert C. Wolf, Morie Gertz

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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 μmol/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). Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)102-111
Number of pages10
JournalAmerican Journal of Kidney Diseases
Volume45
Issue number1
DOIs
StatePublished - Jan 2005

Fingerprint

Melphalan
Stem Cell Transplantation
Acute Kidney Injury
Urine
Transplants
Amyloidosis
Mortality
Wounds and Injuries
Kidney
Hypoalbuminemia
Survival
Therapeutics
Primary amyloidosis
Proteinuria
Diuretics
Dialysis
Microscopy
Creatinine
Multivariate Analysis
Peripheral Blood Stem Cells

Keywords

  • melphalan
  • nephrotic syndrome
  • peripheral blood stem cell transplant (PBSCT)
  • Primary amyloidosis
  • renal insufficiency
  • urine sediment

ASJC Scopus subject areas

  • Nephrology

Cite this

Acute renal insufficiency after high-dose melphalan in patients with primary systemic amyloidosis during stem cell transplantation. / Leung, Nelson; Slezak, Jeff M.; Bergstralh, Erik J.; Dispenzieri, Angela; Lacy, Martha; Wolf, Robert C.; Gertz, Morie.

In: American Journal of Kidney Diseases, Vol. 45, No. 1, 01.2005, p. 102-111.

Research output: Contribution to journalArticle

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abstract = "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 μmol/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). Conclusion: 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.",
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