Early conversion from calcineurin inhibitors to sirolimus in liver transplant patients with renal dysfunction: A systemic and splanchnic hemodynamic study.

ricardo cesar mastai, ricardo mastai, Margarita Anders, Daniel Alvarez, Federico Orozco, Florencia Antinucci, Nicolas Goldaracena, manuel cobos, lucas mccormack

Abstract


Aims: It has been demonstrated that sirolimus, a potent immnunosuppressant agent, allowing a reduction of nephrotoxic effects of CNIs.  We have evaluated whether conversion from a CNIs to sirolimus reduces nephrotoxicity in liver transplant recipients. We have also investigated whether this effect is accompanied to systemic, splanchnic and renal hemodynamic changes.

Material and methods: Twelve patients with a suboptimal renal function, defined as an estimated glomerular filtration rate (GFR) of less than 50 ml/min, were included. Hemodynamic parameters were measured by doppler. Both measurements were performed in baseline (pre conversion to sirolimus) and 30 and 90 days after sirolimus .

Results: The target range for whole blood sirolimus concentration was between 5 and 12 mg/ml. There was a significant difference in GFR at 30 (57 ± 20 ml/min) and 90 (58 ± 21 ml/min) days in patients switching to sirolimus compared to those observed during the administration of CNIs (39 ± 9 ml/min, p<0.05).  This effect on renal hemodynamic is accompanied by a significant reduction in mean arterial pressure. No significant changes were observed in the other parameters studied.

Conclusion: Our results suggest that early withdrawal of CNIs is a safe option, which allows an improvement in renal hemodynamic in liver transplant recipients.


Keywords


immunosuppression, rapamycin, tacrolimus, nephrotoxicity,mTor, doppler measurements

References


REFERENCES

- Gonwa TA, Mai ML, Melton LB Hays SR, Goldstein RM, Levy MF, Klintmalm GB. . End-stage renal disease (ESRD) after orthotopic liver transplantation (OLTX) using calcineurin-based immunotherapy: risk of development and treatment. Transplantation 2001; 1934-1939.

- Pawarode A, Fine DM, Thuluvath PJ. Independent risk factors and natural history of renal dysfunction in liver transplant recipients. Liver Transpl 2003; 741-747.

- Ojo AO, Held PJ, Port FK Wolfe RA, Leichtman AB, Young EW, Arndorfer J et al. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med 2003; 931-940.

- Campistol JM, Sacks SH. Mechanisms of nephrotoxicity. Transplantation 2000; S11-S13.

- MacDonald AS. A worldwide, phase III, randomized,controlled, safety and efficacy study of a sirolimus/cyclosporine regimen for prevention of acute rejection in recipients of primary mismatched renal allograft. Transplantation 2001; 271-280.

- Morath C, Arns W, Schwenger V, Mehrabi A, Fonouni H, Schmidt J, Zeier Met . Sirolimus in renal transplantation. Nephrol Dial Transplant. 2007; 61-65.

- Abdelmalek MF, Humar A, Stickel F, Andreone P, Pascher A, Barroso E, Neff GW et al. Sirolimus Liver Conversion Trial Study Group. Sirolimus conversion regimen versus continued calcineurin inhibitors in liver allograft recipients: a randomized trial. Am J Transplant. 2012 Mar; 694-705.

- Herlenius G, Felldin M, Nordén G Olausson M, Bäckman L, Gustafsson B, Friman S .Conversion from calcineurin inhibitor to either mycophenolate mofetil or sirolimus improves renal function in liver transplant recipients with chronic kidney disease: results of a prospective randomized trial.Transplant Proc. 2010 ;4441-4448

- Fairbanks KD, Eustace JA, Fine D, Thuluvath PJ . Renal function improves in liver transplant recipients when switched from a calcineurin inhibitor to sirolimus .Liver Transpl 2003; 1079-1085.

- Nair S, Eason J, Loss G. Sirolimus monotherapy in nephrotoxicity due to calcineurin inhibitors in liver transplant recipients. Liver Transpl. 2003 Feb; 9:126-129.

- Barkmann A, Nashan B, Schmidt HH, Böker KH, Emmanouilidis N, Rosenau J, Bahr MJ et al. . Improvement of acute and chronic renal dysfunction in liver transplant patients after substitution of calcineurin inhibitors by mycophenolate mofetil. Transplantation. 2000 May 15; 69:1886-1890.

- Simon J, Amde M, Poggio ED. Interpreting the estimated glomerular filtration rate in primary care: benefits and pitfalls. Cleve Clin J Med. 2011; 189-195.

- Alvarez D, Gerona S, Waisburg Z, Ciardullo M, de Santibañes E, Mastai R . Splanchnic hyperemia after liver transplantation in patients with end-stage liver disease. Liver Transpl Surg. 1998;300-303

- Alvarez D, de las Heras M, Abecasis R Terg R, Gerona S, Albornoz L, Galdame O et al. Daily variation in portal blood flow and the effect of propranolol administration in a randomized study of patients with cirrhosis. Hepatology. 1997; 548-550.

- Chakkera HA, Mandarino LJ. Calcineurin inhibition and new-onset diabetes mellitus after transplantation. Transplantation. 2013; 647-652.

- de Mare-Bredemeijer EL, Metselaar HJ. Optimization of the use of Calcineurin inhibitors in liver transplantation. Best Pract Res Clin Gastroenterol. 2012 ;85-95

- Bloom RD, Reese PP. Chronic kidney disease after nonrenal solid-organ transplantation. J Am Soc Nephrol. 2007 ;3031-3041

- Olyaei AJ, de Mattos AM, Bennett WM. Nephrotoxicity of immunosuppressive drugs: new insight and preventive strategies. Curr Opin Crit Care. 2001;384–389

- Flechner SM, Kobashigawa J, Klintmalm G. Calcineurin inhibitor-sparing regimens in solid organ transplantation: focus on improving renal function and nephrotoxicity. Clin Transplant. 2008; 1–15.

- Myers BD, Newton L .Cyclosporine-induced chronic nephropathy: an obliterative microvascular renal injury. J Am Soc Nephrol. 1991; S45-2.

- Pillebout E, Nochy D, Hill G Conti F, Antoine C, Calmus Y, Glotz D. Renal histopathological lesions after orthotopic liver transplantation (OLT). Am J Transplant. 2005; 1120-1129.

- Asfandiyar S, Abouljoud M, Kim D Brown K, Yoshida A, Arenas J, Sherbondy M et al. Influence of hepatitis C on renal function after liver transplantation. Transplant Proc. 2006; 3643-3645.

- Rogers CC, Johnson SR, Mandelbrot DA Pavlakis M, Horwedel T, Karp SJ, Egbuna O et al. Timing of sirolimus conversion influences recovery of renal function in liver transplant recipients. Clin Transplant. 2009; 887-896.

- Shenoy S, Hardinger KL, Crippin J Korenblat K, Lisker-Melman M, Lowell JA, Chapman W. Sirolimus conversion in liver transplant recipients with renal dysfunction: a prospective, randomized, single-center trial. Transplantation. 2007 ;1389-1392


Full Text: PDF HTML

Refbacks

  • There are currently no refbacks.


Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.