Acquired cytoresistance in the setting of hematopoietic cell transplantation

造血干细胞移植后获得的细胞耐药性

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Abstract

BACKGROUND AND OBJECTIVES: Pre-existent renal insufficiency is a widely accepted risk factor for superimposed renal damage (e.g., due to ischemia or nephrotoxic drug administration). However, both experimental renal injury and surgical ablation of renal mass in rodents confer protection against superimposed renal insults (the so-called "acquired cytoresistance" state). This study addressed whether baseline renal function is associated with either increased or decreased susceptibility to renal injury in patients undergoing hematopoietic cell transplantation (HCT), a procedure that is widely recognized to induce acute or subacute renal damage. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Estimated GFRs (eGFRs; Modification of Diet in Renal Disease formula) were assessed at baseline and approximately 1 year after HCT in 1216 patients who were transplanted at the Fred Hutchinson Cancer Center between 1991 and 2002. The frequency of a renal functional decline (arbitrarily defined, a priori, as ≥25% loss of baseline eGFR) and absolute reductions in eGFR (in ml/min) were calculated. RESULTS: Both the frequency and degree of post-HCT eGFR reductions directly and linearly correlated with baseline eGFRs (range, 25 to 135 ml/min). Thus, the higher the baseline eGFR, the greater the risk and severity of subsequent loss of renal function (P < 0.0001). CONCLUSIONS: These data indicate that reduced baseline renal function is not necessarily a risk factor for post-HCT renal functional declines. Rather, these observations support the concept that "acquired cytoresistance," as seen in experimental animals, may, under selected circumstances, be expressed in the clinical arena.

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