Kidney Week

Abstract: FR-PO1008

Everolimus Has Effect on the Tacrolimus Concentration within the Renal Proximal Tubular Cells in Dose Dependent Manners

Session Information

• Transplantation: Basic and Experimental
  November 03, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Transplantation

• 1701 Transplantation: Basic and Experimental

Authors

• Lee, Haewon, Haeundae Paik Hospital, inje university, Pusan, Korea (the Republic of)

Haewon Lee,

• Kim, Yang Wook, Haeundae Paik Hospital, inje university, Pusan, Korea (the Republic of)

Yang Wook Kim,

• Park, Bongsoo, Haeundae Paik Hospital, inje university, Pusan, Korea (the Republic of)

Bongsoo Park,

• Park, Sihyung, Haeundae Paik Hospital, inje university, Pusan, Korea (the Republic of)

Sihyung Park,

• Lee, Yoo jin, Haeundae Paik Hospital, inje university, Pusan, Korea (the Republic of)

Yoo jin Lee,

• Park, Seok ju, Inje University, Busan, Korea (the Republic of)

Seok ju Park,

• Han, Sang Youb, Inje University, Busan, Korea (the Republic of)

Sang Youb Han,

Background

It was reported that everolimus in combination with varying levels of Tacrolimus is efficacious and associated with good kidney function. We aimed to investigate the effect of everolimus on the tacrolimus intracelluar concentration in the kidney cells when it is used concomitantly.

Methods

HK-2 Cells(immortalized Human Renal Proximal Tubule Cells) were treated with tacrolimus at the dose of 5 ng/ml, 10 ng/ml and 15 ng/ml. After 30 minutes, we treated with everolimus at the dose of 3 ng/ml, 9 ng/ml and 15 ng/ml, additionally, in the absence or presence of tacrolimus for 1 hour. We measured the intracelluar tacrolimus concentrations using LC/MSMS.

Results

Tacrolimus intracellular accumulation was significantly decreased by everolimus in a concentration dependent manner. At the concomitant treatment with 5 ng/ml of tacrolimus and everolimus (3 ng/ml, 9 ng/ml, 15 ng/ml), the intracellular tacrolimus concentrations was significantly decreased compared with abscence of everolimus. The intracellular tacrololimus was decreased by everolimus showing 0.348± 0.025 ng/ml/1x10⁶cells, 0.279± 0.034 ng/ml/1x10⁶cells, 0.232± 0.025 ng/ml/1x10⁶cells vs 0.643± 0.087 ng/ml/1x10⁶cells (P=0.01), respectively. At the concomitant treatment with 10 ng/ml of tacrolimus and everolimus (3 ng/ml, 9 ng/ml, 15 ng/ml), the intracellular tacrolimus concentrations was significantly decreased compared with abscence of everolimus,The intracellular tacrololimus was decreased by everolimus showing 0.544± 0.103 ng/ml/1x10⁶cells, 0.393± 0.042 ng/ml/1x10⁶cells, 0.376± 0.06 ng/ml/1x10⁶cells vs 0.71± 0.177 ng/ml/1x10⁶cells,(P=0.042), respectively. The effect of everolimus on intracelluar tacrolimus concentration decreased as the dose of tacrolimus increased. At the concomitant treatment with 15 ng/ml of tacrolimus and everolimus (3 ng/ml, 9 ng/ml, 15 ng/ml), the intracellular tacrolimus concentrations was significantly decreased compared with abscence of everolimus. The intracellular tacrololimus was decreased by everolimus showing 0.654± 0.043 ng/ml/1x10⁶cells, 0.635± 0.096 ng/ml/1x10⁶cells,0.579± 0.251 ng/ml/1x10⁶cells, vs 0.822± 0.168 ng/ml/1x10⁶cells,(P=0.038), respectively.

Conclusion

We suggest that everolimus has effect on the tacrolimus concentration within the kidney proximal tubular cells in dose dependent manners.