Chronic Renal Failure in Lung Transplant Recipients Is Predicted by Tacrolimus Toxicity Events

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• 作者：B.D. Fox¹ ; ² ; D. Rozengarten¹ ; Y. Raviv¹ ; ² ; S. Yitzhakian¹ ; M.R. Kramer¹ ; ²
• 刊名：The Journal of Heart and Lung Transplantation
• 出版年：2013
• 出版时间：April, 2013
• 年：2013
• 卷：32
• 期：4_supp_S
• 页码：S90
• 全文大小：147 K

文摘

| Figures/TablesFigures/Tables

Purpose

Chronic renal failure (CRF) is common in lung transplant (LT) recipients. Tacrolimus (Tac) exposure is an accepted risk factor for CRF but little is known about the quantitative relationship between Tac levels and LT-CRF.

Methods and Materials

Review of 173 LT recipients transplanted 2003-2010. Data were extracted on Tac levels and serum creatinine (Cr). Renal failure was defined as a doubling of Cr from baseline, further defined as chronic (sustained over ¡Ý3 months), acutely post LT (<1 month). Data were analyzed between the date of LT until the first ¡®renal endpoint¡¯ was reached - either CRF, end of laboratory follow-up, everolimus therapy or death without CRF. Tac toxicity was defined as trough >20ng/dl. The area-under-the-curve of Tac levels over time (AUC:Tac~Time) was calculated for each patient.

Results

During median 698 [IQR 133-1482] days of follow-up, 77 patients developed CRF, see . In univariate analysis, LT-CRF was associated with slightly higher median Tac levels (p=0.002), higher log (AUC:Tac~Time) (p<0.0001), more Tac-toxicity events (p<0.0001) and post-LT acute renal failure (p=0.04). Of note, age at LT, baseline creatinine, median Tac dose, pre-LT smoking status and pre-LT hypertension were not associated with development of LT-CRF. In a multivariate model, only FK toxicity events were significantly associated with development of LT-CRF (RR 2.93, 95 % CI 2.09-4.34).

Conclusions

Tac toxicity events are strongly associated with future development of CRF.

Univariate Analysis
	rong class=""boldFont"">No CRF n=96rong>	rong class=""boldFont"">CRF n=77rong>	rong class=""boldFont"">prong>
Age	51(15)	52(11)	0.69
Male Sex %	63	61	0.74
Diagnosis ( % )			0.87
Emphysema	31	30
IPF	40	45
CF	10	9
Other	19	16
PreLT HTN %	23	27	0.58
PreLT Smoking	58	62	0.78
Baseline Creat (mg/dl)	0.78 (0.3)	0.76 (0.22)	0.52
Acute RF post LT	33	19	0.04
Median FK Dose (mg)	4.5(3.8)	3.8(2.2)	0.15
Median FK level (pg/ml)	10.7(2.1)	11.5(1.5)	0.002
Log(Level~Time AUC)	10.8(2.3)	11.9(1.6)	<0.0001
FK Toxicity Events	1 [0,1]	3[2,3]	<0.0001