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1.
D. Chhabra A. Alvarado P. Dalal J. Leventhal C. Wang N. Sustento‐Reodica N. Najafian A. Skaro J. Levitsky V. Mas L. Gallon 《American journal of transplantation》2013,13(11):2902-2911
Traditionally, chronic calcineurin inhibitor (CNI) nephrotoxicity has been considered to be one of the main nonimmune mechanisms causing chronic renal allograft dysfunction. CNI minimization and withdrawal strategies have yielded inconsistent results. Few studies address the feasibility of CNI elimination in a prednisone‐free regimen. We report a prospective, randomized trial in 200 patients evaluating the impact on renal function and incidence of acute rejection after conversion from tacrolimus (Tac) to sirolimus (SRL). Patients with recent (<3 months) acute rejection episodes or with >0.5 g/day of proteinuria were excluded. All were induced with alemtuzumab, underwent rapid steroid elimination and were maintained on mycophenolate mofetil and Tac. At 12 months posttransplant, patients were randomized 2:1 to SRL (n = 123) or maintained on Tac (n = 64). Mean follow‐up was 41.1 ± 15.8 months in the SRL group and 40.7 ± 14.4 months in the Tac group. Biopsy‐proven acute rejection at 24 months postrandomization was similar between the groups. Patient survival, graft survival and estimated GFR were also not statistically different. Our study demonstrates that in a prednisone‐free immunosuppressive regimen, conversion from Tac to SRL at 12 months posttransplantation is not associated with increased rates of acute rejection and graft loss. However, despite CNI elimination, renal allograft function is equally maintained in both groups. 相似文献
2.
Carvalho C Coentrão L Bustorff M Patrício E Sampaio S Santos J Oliveira G Pestana M 《Clinical transplantation》2011,25(4):E401-E405
Carvalho C, Coentrão L, Bustorff M, Patrício E, Sampaio S, Santos J, Oliveira G, Pestana M. Conversion from sirolimus to everolimus in kidney transplant recipients receiving a calcineurin‐free regimen.Clin Transplant 2011: 25: E401–E405. © 2011 John Wiley & Sons A/S. Abstract: Background: Everolimus (EVL) and sirolimus (SRL) were introduced into immunosuppressive regimens, in an attempt to replace or reduce the dose of the nephrotoxic calcineurin inhibitors (CNI). In our institution, due to an administrative decision, conversion from SRL to EVL, was carried out, providing us the opportunity to investigate the effectiveness and safety profile of both drugs and to review the practical conversion dose between them. Methods: We retrospectively analyzed the medical records of 51 maintenance kidney transplant recipients receiving an SRL‐based CNI‐free regimen, who were switched to EVL. SRL dose was concentration controlled to a through level of 4–8 ng/mL. Patients were converted to a variable dose of EVL that was adjusted to achieve a trough concentration of 3–8 ng/mL. Results: SRL mean dose at time of conversion was 2.0 ± 0.9 mg/d. Initial EVL mean dose was 1.3 ± 0.5 mg/d. Six months after conversion, mean EVL trough level was 6.2 ± 2.8 ng/mL. EVL dose at this point was 2.0 ± 0.9 mg/d, which was not statistically different from SRL dose at the time of conversion (p = 0.575), suggesting a conversion factor of 1:1. During this six month period post conversion, no significant changes were observed in serum creatinine, hematocrit level, platelet count, proteinuria or lipid levels. No patient experienced an acute rejection episode. Conclusions: Conversion from SRL to EVL in renal transplant recipients receiving a CNI‐free immunosuppressive regimen can be performed safely with a low trough level range of EVL. We report for the first time a conversion factor between SRL and EVL. 相似文献
3.
L Gallon N Perico B D Dimitrov J Winoto G Remuzzi J Leventhal F Gaspari D Kaufman 《American journal of transplantation》2006,6(7):1617-1623
It is not known how different steroid-free immunosuppressive combinations affect renal graft survival and long-term kidney transplant function. Here we sought to compare the impact on graft survival and long-term graft function of two tacrolimus (Tac)-based, prednisone-free maintenance immunosuppressive protocols: Tac/Mycophenolate Mofetil (MMF) vs. Tac/Sirolimus (SRL). Renal transplant patients given induction therapy with IL2-RA and methylprednisolone on days 0, 1 and 2 post-transplant were prospectively randomized to two maintenance immunosuppressive regimens with Tac/MMF (n = 45) or Tac/SRL (n = 37). During the 3-year follow-up the following data were collected: patient survival, renal allograft survival, incidence of acute rejection and glomerular filtration rate (GFR) at different time-points post-transplant. Cumulative graft survival was significantly different in the two groups: one kidney loss in the Tac/MMF vs. six kidney losses in the Tac/SRL (log-rank test p = 0.04). GFR at different time-points post-transplant was consistently and statistically better in the Tac/MMF than in the Tac/SRL group. The slope of GFR decline per month was flatter in the Tac/MMF than in the Tac/SRL group. This study showed that renal graft survival and graft function were significantly lower in the combination of Tac/SRL than Tac/MMF. 相似文献
4.
Dopazo C Rodriguez R Llado L Calatayud D Castells L Ramos E Molina V García R Fabregat J Charco R 《Clinical transplantation》2012,26(1):E32-E37
Dopazo C, Rodriguez R, Llado L, Calatayud D, Castells L, Ramos E, Molina V, García R, Fabregat J, Charco R. Successful conversion from twice‐daily to once‐daily tacrolimus in liver transplantation: observational multicenter study. Clin Transplant 2012: 26: E32–E37. © 2011 John Wiley & Sons A/S. Background: Compliance with immunosuppressive therapy in liver transplant patients is critical to prevent acute organ rejection and/or late graft loss. Strategies to simplify the therapeutic regimen may improve adherence. Aim: To evaluate the safety and efficacy of conversion from a twice‐daily to once‐daily tacrolimus formulation in adult liver transplant patients. Patients and methods: This prospective observational multicenter study included 187 liver transplant patients with at least 10 months post‐transplant follow‐up, no rejection episodes in the last three months, and creatinine levels <2 mg/dL. Conversion from a twice‐daily to a once‐daily formulation was based on a 1:1 proportion. Results: Median age was 61 yr (range: 28–80 yr); 64% were men and 36% women. The main indications for liver transplant were alcoholic cirrhosis in 30%. Median conversion time was 55 months (range: 10–215 months). Serum tacrolimus levels decreased at one month after conversion (pre‐conversion levels = 5.4 ± 3.0 ng/mL vs. post‐conversion levels = 4.4 ± 2.4 ng/mL, p = 0.013); however, these values normalized at six months post‐conversion with no changes in liver function and rejection episodes were observed only in two patients. Conclusion: Conversion from a twice‐daily to a once‐daily tacrolimus formulation is a safe, effective strategy in the management of stable liver transplant patients. 相似文献
5.
Gustavo Martinez‐Mier Sandro F. Avila‐Pardo Marco T. Mendez‐Lopez Luis F. Budar‐Fernandez 《Clinical transplantation》2010,24(4):467-473
Martinez‐Mier G, Avila‐Pardo SF, Mendez‐Lopez MT, Budar‐Fernandez LF. Long‐term results after conversion from calcineurin inhibitors to sirolimus in renal transplant patients.Clin Transplant 2010: 24: 467–473.© 2009 John Wiley & Sons A/S. Abstract: Background: Calcineurin inhibitors (CNI) toxicity is one of the contributing factors for the development and progression of chronic allograft dysfunction (CAD). Conversion to sirolimus (SRL) from CNI improves renal function kidney in transplant recipients. Methods: A retrospective review from patients abruptly converted from CNI to SRL over a three yr period is reported. Results: Thirty‐nine patients were converted 55.2 ± 58 months after renal transplantation. 24 month patient and graft survival was 100% and 92%. Acute rejection incidence was 7.6%. Overall, serum creatinine (SCr) and Cockcroft–Gault creatinine clearance (CGCrCl) improved. In responders, SCr improved from 2.48 ± 0.8 to 1.94 ± 0.8 mg/dL (p < 0.05) CGCrCl improved from 37.8 ± 17.4 to 51.9 ± 23.8 mL/min at two years. An increase in proteinuria was observed from conversion to month 12 in responders (189.4 ± 512.8 to 488.3 ± 890.6 mg/day, p < 0.05) and from conversion to month six in non‐responders (1179.4 ± 2001.1 to 2357 ± 4172.9 mg/day, p < 0.05). Low proteinuria had positive predictive value for renal response after conversion. Conclusion: Conversion from CNI to SRL with CAD is associated with improved renal function with an increase in proteinuria. Low proteinuria is a possible positive predictive factor for successful conversion. 相似文献
6.
Bernhard K. Krämer Marian Klinger Zbigniew Wlodarczyk Marek Ostrowski Karsten Midvedt Sergio Stefoni Franco Citterio Frank Pietruck Jean-Paul Squifflet Giuseppe Segoloni Bernd Krüger Heide Sperschneider Bernhard Banas Lars Bäckman Markus Weber Mario Carmellini Ferenc Perner Kerstin Claesson Wojciech Marcinkowski tefan Vítko Grzegorz Senatorski Kaija Salmela Johan Nordström 《Clinical transplantation》2010,24(1):E1-E9
Krämer BK, Klinger M, Wlodarczyk Z, Ostrowski M, Midvedt K, Stefoni S, Citterio F, Pietruck F, Squifflet J‐Paul, Segoloni G, Krüger B, Sperschneider H, Banas B, Bäckman L, Weber M, Carmellini M, Perner F, Claesson K, Marcinkowski W, Vítko ?, Senatorski G, Salmela K, Nordström J. Tacrolimus combined with two different corticosteroid‐free regimens compared with a standard triple regimen in renal transplantation: one year observational results.Clin Transplant 2010: 24: E1–E9. © 2009 John Wiley & Sons A/S. Abstract: Side effects of steroid use have led to efforts to minimize their use in transplantation. Two corticosteroid‐free regimens were compared with a triple immunosuppressive therapy. Data from the original intent‐to‐treat (ITT) population (153 tacrolimus/basiliximab [Tac/Bas], 151 tacrolimus/MMF [Tac/MMF], and 147 tacrolimus/MMF/steroids [control]) were analyzed in a 12‐month follow‐up. Percentage of graft survival were 92.8%, 95.4%, and 95.9% (KM estimates 89.9%, 95.3%, 95.9%), percentage of surviving patients were 98.7%, 98.0%, and 100% (KM estimates 95.9%, 92.8%, and 100%). During months 7–12, graft loss occurred in 3 Tac/Bas, 2 Tac/MMF, and zero control patients, patient deaths in 1 Tac/Bas, 2 Tac/MMF, and zero control, and biopsy‐proven acute rejection episodes in 4 Tac/Bas, 3 Tac/MMF, and zero control. Mean serum creatinine at month 12 was 141.9 ± 69.6 μM, 144.0 ± 82.1 μM, and 134.5 ± 71.2 μM (ns). New‐onset insulin use in previously non‐diabetic patients at month 12 was 1/138, 6/127, and 4/126. Patient and graft survival as well as renal function at 12 months were not different between patient groups, despite considerably higher rates of acute rejection occurring within the first six months after transplantation in both steroid‐free patient groups. Tac/Bas therapy might offer benefits in terms of a trend for a more favorable cardiovascular risk profile. 相似文献
7.
Robinson Joannides Isabelle Etienne Michele Iacob Bruno Hurault De Ligny Stephane Barbier Jeremy Bellien Yvon Lebranchu Christian Thuillez Michel Godin 《Transplant international》2010,23(11):1135-1143
This study attempted to establish whether a calcineurin inhibitor (CNI)‐free immunosuppressant regimen based on sirolimus (SRL) is associated with a preservation of conduit arteries endothelial function in kidney recipients or not. Twenty‐nine kidney recipients were randomized to receive since transplantation SRL (n = 15) or cyclosporin A (CsA, n = 14) associated with mycophenolate mofetil (MMF) and steroids (6 months) in a parallel prospective study. Systolic, diastolic blood pressures, glomerular filtration rate (GFR) and radial artery flow‐mediated dilatation (FMD) induced by postischaemic hyperaemia were assessed in a blind manner at one (M1) and 7 months (M7) after transplantation. Endothelium‐independent dilatation was assessed by glyceryl trinitrate spray. There was no difference between the groups for all vascular parameters at M1. At M7, systolic blood pressure was lower (SRL: 119 ± 3 vs. CsA: 138 ± 4 mmHg, P < 0.05) and FMD was higher in SRL compared with CsA (SRL: 13.1 ± 0.9 vs. CsA: 9.9 ± 0.9%, P < 0.05) without any difference for hyperaemia, endothelium‐independent dilatation and GFR (SRL: 66.7 ± 1.05 vs. CsA: 67.5 ± 1.22 ml/min). Our results demonstrate that a CNI‐free regimen based on SRL and MMF prevents conduit artery endothelial dysfunction compared with CsA and MMF in kidney recipients suggesting a beneficial arterial wall effect that may also contribute to the decrease in systolic blood pressure. 相似文献
8.
H. T. Silva Jr. C. R. Felipe V. D. Garcia E. D. Neto M. A. Filho F. L. C. Contieri D. D. B. M. de Carvalho J. O. M. Pestana 《American journal of transplantation》2013,13(12):3155-3163
Planned conversion from tacrolimus to sirolimus was evaluated in de novo kidney transplant recipients. In this multicenter, randomized, open‐label study, 297 patients were initially treated with tacrolimus, mycophenolate sodium and prednisone. Of the 283 patients reaching 3 months, 97 were converted to sirolimus (SRL), 107 were maintained on tacrolimus (TAC) and 79 were patients receiving TAC without criteria to undergo intervention at month 3 (TACex). The primary objective was to show superior estimated glomerular filtration rate (eGFR) in the SRL group at month 24. Of the 258 patients who completed 24 months, 91 (94%) were in the SRL group, 101 (94%) in the TAC group and 66 (84%) in the TACex group. In the intention‐to‐treat population there were no differences in eGFR (66.2 ± 25.3 vs. 70.7 ± 25.1, p = 0.817) or in the severity of chronic sclerosing lesions scores in 24‐month protocol biopsies. Higher mean urinary protein‐to‐creatinine ratio (0.36 ± 0.69 vs. 0.15 ± 0.53, p = 0.03) and higher incidence of treated acute rejection between months 3–24 (13.4% vs. 4.7%, p = 0.047) were observed in SRL compared to TAC group. In this population planned conversion from TAC to SRL 3 months after kidney transplantation was not associated with improved renal function at 24 months. 相似文献
9.
Ulrich Frei Pierre Daloze Štefan Vítko Jürgen Klempnauer Rafael Reyes‐Acevedo Izzet Titiz Lutz Fricke Corrado Bernasconi Henrik Ekberg 《Clinical transplantation》2010,24(4):500-509
Frei U, Daloze P, Vítko ?, Klempnauer J, Reyes‐Acevedo R, Titiz I, Fricke L, Bernasconi C, Ekberg H. Acute rejection in low‐toxicity regimens: clinical impact and risk factors in the Symphony study.Clin Transplant 2010: 24: 500–509.© 2009 John Wiley & Sons A/S. Abstract: The Symphony study assessed whether mycophenolate mofetil (MMF)‐based regimens containing reduced doses of adjunct immunosuppressants could reduce toxicity while maintaining efficacy. Here, we examined the impact of acute rejection and associated risk factors. The incidence of biopsy‐proven acute rejection in the low‐dose tacrolimus group was approximately half that of the standard‐dose cyclosporine and low‐dose cyclosporine groups, and a third of that in the low‐dose sirolimus group. The low‐dose cyclosporine group had more severe rejection episodes (≥grade II) compared with other groups. Acute rejection was associated with a 10 mL/min glomerular filtration rate (GFR) reduction and a 5.3% absolute increase in graft loss at 12 months. Overall, the highest GFR was found in both rejecters and non‐rejecters receiving low‐dose tacrolimus, both in an intent‐to‐treat analysis and in patients successfully treated according to the protocol. In Cox regression models, human leukocyte antigen (HLA) mismatches and expanded criteria donors increased the acute rejection risk, while recipient age, living related donor, and MMF dose were associated with a reduced risk. Acute rejection was associated with worse outcome but did not entirely explain the differences among the treatment groups. The 2 g MMF plus low‐dose tacrolimus combination appears to be the most efficient of all regimens examined regardless of acute rejection. 相似文献
10.
Weir MR Mulgaonkar S Chan L Shidban H Waid TH Preston D Kalil RN Pearson TC 《Kidney international》2011,79(8):897-907
As part of the Spare-the-Nephron trial, we evaluated the combination mycophenolate mofetil (MMF) and sirolimus (SRL) as a calcineurin inhibitor (CNI)-free regimen for the preservation of renal function in renal allograft recipients. This 2-year, open-label, multicenter trial randomized 299 patients of which 151 were maintained on MMF and a CNI, 148 on MMF plus SRL (n=120, tacrolimus; n=31, cyclosporine). Baseline characteristics including measured (iothalamate) glomerular filtration rate (GFR) were similar between groups. After 1 year, the mean percentage change from baseline in the primary end point of measured GFR was significantly higher in the MMF/SRL group compared with the MMF/CNI group. After 2 years, the change was indistinguishable. Calculated creatinine clearance and GFR were significantly greater with MMF/SRL at 2 years within which biopsy-proven acute rejection (BPAR) occurred in 14 MMF/SRL-treated patients (3 graft losses) and in 17 receiving the MMF/CNI (6 graft losses). Significantly, no patients receiving MMF/SRL but five treated with MMF/CNI died. Thus, compared with MMF/CNI treatment, a 2-year regimen of MMF/SRL resulted in similar measures of renal function but with fewer deaths and a trend to less BPAR and graft loss. 相似文献
11.
A prospective randomized multicenter study of tacrolimus in combination with sirolimus in renal-transplant recipients 总被引:7,自引:0,他引:7
van Hooff JP Squifflet JP Wlodarczyk Z Vanrenterghem Y Paczek L 《Transplantation》2003,75(12):1934-1939
BACKGROUND: Recently, sirolimus (SRL) was introduced as an immunosuppressant in solid-organ transplantation. This study evaluated combinations of SRL and tacrolimus (Tac). METHODS: This 6-month study investigated the safety and efficacy of Tac and steroids in combination with three different doses of SRL in renal-transplant recipients. A total of 104 patients were randomized in four groups: one group received Tac and steroids (control n=28), and three groups also received the following daily SRL doses: 0.5 mg (TacSRL0.5, n=25), 1 mg (TacSRL1, n=25), or 2 mg (TacSRL2, n=26). Tac doses were adjusted to whole-blood trough levels. Steroids were tapered from 20 mg per day to 5 mg per day. The SRL groups underwent a second randomization to discontinue SRL at either month 3 or 5. RESULTS: At month 6, patient survival rates were 100%, 100%, 96.0%, and 100%, and graft survival rates were 96.4%, 84.0%, 88.0%, and 84.6%, respectively. The overall safety profile was similar in all groups. The incidences of infections during months 1 to 3 were similar in all groups (control 46.4%, TacSRL0.5 32.0%, TacSRL1 56.0%, TacSRL2 46.2%). The 3-month incidences of hypercholesteremia (cholesterol >240 mg/dL or low-density lipoprotein cholesterol >160 mg/dL) were 21.4%, 36.0%, 48.0%, and 50.0% (P=0.019). Lipid levels improved after withdrawal of SRL. The 3-month incidences of biopsy-proven acute rejection were 28.6% (control), 8.0% (TacSRL0.5), 8.0% (TacSRL1), and 3.8% (TacSRL2) (P=0.014). CONCLUSION: Tac in combination with low doses of SRL provides a very effective and safe regimen. 相似文献
12.
Complete Avoidance of Calcineurin Inhibitors in Renal Transplantation: A Randomized Trial Comparing Sirolimus and Tacrolimus 总被引:3,自引:0,他引:3
T. S. Larson P. G. Dean M. D. Stegall M. D. Griffin S. C. Textor T. R. Schwab J. M. Gloor F. G. Cosio W. J. Lund W. K. Kremers S. L. Nyberg M. B. Ishitani M. Prieto J. A. Velosa 《American journal of transplantation》2006,6(3):514-522
Calcineurin inhibitors have decreased acute rejection and improved early renal allograft survival, but their use has been implicated in the development of chronic nephrotoxicity. We performed a prospective, randomized trial in kidney transplantation comparing sirolimus-MMF-prednisone to tacrolimus-MMF-prednisone. Eighty-one patients in the sirolimus group and 84 patients in the tacrolimus group were enrolled (mean follow-up = 33 months; range 13-47 months). At 1 year, patient survival was similar in the groups (98% with sirolimus, 96% with tacrolimus; p = 0.42) as was graft survival (94% sirolimus vs. 92% tacrolimus, p = 0.95). The incidence of clinical acute rejection was 10% in the tacrolimus group and 13% in the sirolimus group (p = 0.58). There was no difference in mean GFR measured by iothalamate clearance between the tacrolimus and sirolimus groups at 1 year (61 +/- 19 mL/min vs. 63 +/- 18 mL/min, p = 0.57) or 2 years (61 +/- 17 mL/min vs. 61 +/- 19 mL/min, p = 0.84). At 1 year, chronicity using the Banff schema showed no difference in interstitial, tubular or glomerular changes, but fewer chronic vascular changes in the sirolimus group. This study shows that a CNI-free regimen using sirolimus-MMF-prednisone produces similar acute rejection rates, graft survival and renal function 1-2 years after transplantation compared to tacrolimus-MMF-prednisone. 相似文献
13.
Raja Kandaswamy J. Keith Melancon Ty Dunn Miguel Tan Vincent Casingal Abhinav Humar William D. Payne Rainer W. G. Gruessner David L. Dunn John S. Najarian David E. R. Sutherland Kristen J. Gillingham Arthur J. Matas 《American journal of transplantation》2005,5(6):1529-1536
We compared three maintenance immunosuppressive regimens in a rapid discontinuation of prednisone protocol. From March 1, 2001, through December 31, 2003, 239 first and second kidney transplant recipients (166 LD; 73 DD) were randomized. All recipients were treated with Thymoglobulin; all received steroids intraoperatively and for 5 days postoperatively. Randomization was to cyclosporine-mycophenolate mofetil (n = 85); high-level tacrolimus (TAC) (8-12 ng/mL)-low-level sirolimus (SRL) (3-7 ng/mL) (n = 72); or low-level TAC (3-7 ng/mL)-high-level SRL (8-12 ng/mL) (n = 82). We found no difference at 24 months between groups in patient, graft, death-censored graft, or acute rejection-free graft survival, or in kidney function. Wound complications were more common in SRL-treated recipients (p = 0.02); we found no other differences between groups in complication rates. Our data suggest that excellent patient and graft survival and low rejection rates can be obtained using a variety of maintenance protocols without prednisone. 相似文献
14.
Guerra G Ciancio G Gaynor JJ Zarak A Brown R Hanson L Sageshima J Roth D Chen L Kupin W Tueros L Ruiz P Livingstone AS Burke GW 《Journal of the American Society of Nephrology : JASN》2011,22(9):1758-1768
The optimal long-term regimen for immunosuppression for kidney transplant recipients is unknown. We conducted a randomized trial involving 150 kidney transplant recipients to compare tacrolimus/sirolimus, tacrolimus/mycophenolate mofetil (MMF), and cyclosporine/sirolimus. All patients received daclizumab induction and maintenance corticosteroids. Median follow-up was 8 yr post-transplant. Acute rejection (AR) occurred significantly less often among those treated with tacrolimus/MMF (12%) than among those treated with tacrolimus/sirolimus (30%) or cyclosporine/sirolimus (28%). Mean estimated GFR was consistently higher in the tacrolimus/MMF arm, especially after controlling for donor age in a multivariable model during the first 36 mo (P ≤ 0.008). The rate of dying with a functioning graft was significantly higher among those treated with tacrolimus/sirolimus (26%) than among those treated with tacrolimus/MMF (12%) or cyclosporine/sirolimus (4%). We did not observe significant differences in actuarial graft survival at 8 yr post-transplant between the groups. Patient noncompliance seemed responsible for 45% (13/29) of observed graft failures, with 11 of these occurring after 36 mo. Significantly more viral infections, protocol violations, and need for antilipid therapy occurred among patients receiving sirolimus, but we did not observe differences between the groups with regard to infections requiring hospitalization or new-onset diabetes. Taken together, these results suggest that maintenance therapy with tacrolimus/MMF is more favorable than either tacrolimus/sirolimus or cyclosporine/sirolimus. 相似文献
15.
A. S. Barbas A. S. Rege A. W. Castleberry J. Gommer M. J. Ellis T. V. Brennan B. H. Collins A. E. Martin K. V. Ravindra D. S. Vikraman D. L. Sudan 《American journal of transplantation》2013,13(3):808-810
Posterior reversible encephalopathy syndrome (PRES) is a small vessel microangiopathy of the cerebral vasculature that occurs in 0.5–5% of solid organ transplant recipients, most commonly associated with tacrolimus (Tac). Clinical manifestations include hypertension and neurologic symptoms. We report an adult multivisceral transplant recipient who experienced recurrent PRES initially associated with Tac and subsequently with sirolimus. A 49‐year‐old woman with short bowel syndrome underwent multivisceral transplantation due to total parenteral nutrition–related liver disease. She was initially maintained on Tac, mycophenalate mofetil (MMF) and prednisone. Three months after transplantation, she developed renal dysfunction, leading to a reduction in Tac and the addition of sirolimus. Eight months after transplantation, she developed PRES. Tac was discontinued and PRES resolved. Sirolimus was increased to maintain trough levels of 12–15 ng/mL. Fourteen months after transplant, she experienced recurrent PRES which resolved after discontinuing sirolimus. Currently 3 years posttransplant, she is maintained on cyclosporine, MMF and prednisone with no PRES recurrence. In addition to calcineurin inhibitors, sirolimus may also be associated with PRES after solid organ transplantation. Ours is the first report of sirolimus‐associated PRES in the setting of multivisceral transplantation. Identifying a safe alternative immunosuppression regimen was challenging but ultimately successful. 相似文献
16.
Groetzner J Kaczmarek I Schirmer J Uberfuhr P Gulbins H Daebritz S Meiser B Reichart B 《Clinical transplantation》2008,22(5):587-593
Abstract: Background: Chronic renal failure (CRF) is a common complication of calcineurin inhibitor (CNI)‐based immunosuppression following cardiac transplantation (HTx). The aim of this prospective study was to evaluate the impact of an immunosuppressive conversion from CNIs to mycophenolate mofetil (MMF) and steroids in cardiac transplant recipients with CRF on renal and cardiac graft function. Methods: Since 1999, 12 HTx recipients (10 men; 58 ± 3.6 yr of age; 8.7 ± 4.2 yr after HTx) with CNI‐based immunosuppression and a calculated creatinine clearance (CreaCl) <50 mL/min were included. Most patients (10/12) were on cyclosporine and two patients were on tacrolimus prior inclusion. MMF was started with 0.5 g/d and adjusted according to the target trough levels (2–4 ng/mL). Prednisone dosage was 0.4 mg/kg. Subsequently, CNIs were completely withdrawn. Acute rejection episodes were excluded one and three months after conversion by endomyocardial biopsy and by echocardiography every three months thereafter. Results: After a mean follow‐up of 20 ± 16 months, CreaCl improved significantly: pre‐conversion vs. post‐conversion: 32.8 ± 12.2 mg/dL vs. 42.8 ± 21.14 mg/dL, p = 0.03. However, four acute rejection episodes occurred and patients were reconverted to CNIs. Additionally, six patients had a new onset of graft vessel disease (GVD) one yr after conversion. As a result of these adverse events, the study was stopped after inclusion of only 12 of the scheduled 30 patients. Conclusions: Conversion to MMF and steroids after HTx improves renal function, but increases the risk for recurrent rejection and GVD. Therefore, MMF and steroids should only be considered in patients with a markedly low risk for rejection. 相似文献
17.
Edip Akpinar Gaetano Ciancio Jun Sageshima Linda Chen Giselle Guerra Warren Kupin David Roth Phillip Ruiz George Burke 《Clinical transplantation》2010,24(6):801-806
Akpinar E, Ciancio G, Sageshima J, Chen L, Guerra G, Kupin W, Roth D, Ruiz P, Burke G. BK virus nephropathy after simultaneous pancreas–kidney transplantation. Clin Transplant 2010: 24: 801–806. © 2010 John Wiley & Sons A/S. Abstract: Background: BK virus nephropathy (BKVN) was reported in up to 7.5% of patients after simultaneous pancreas–kidney transplantation (SPK). Its management by reduction in immunosuppression might pre‐dispose to pancreatic graft loss. Methods: A retrospective analysis of 178 SPK recipients was performed. All patients received thymoglobulin, daclizumab and a maintenance of low‐dose steroids, tacrolimus, and either sirolimus or mycophenolate. Results: Two (1.1%) patients were identified with BKVN. Time of diagnosis was 22 and 45 months after transplant. Both patients had superimposed calcineurin toxicity in their graft biopsies. Immunosuppression was reduced in both patients, and leflunomide (LEF) was used in one patient. Concurrent kidney rejection episodes were treated with steroid pulses in both patients. One kidney graft improved with a last estimated glomerular filtration rate (GFR) of 43 mL/min, and another kidney graft showed limited improvement with a last GFR of 30 mL/min. Pancreatic graft function remained excellent in both patients as assessed by serum c‐peptide, glycosylated hemoglobin, amylase‐lipase, and urine amylase levels. Conclusion: Low incidence of BKVN was observed in our SPK series. Reduction in immunosuppression and sometimes LEF can be effective. The underlying mechanism of stable pancreatic allograft function despite ongoing kidney rejection warrants further investigation. 相似文献
18.
Rapamycin in children after liver transplantation 总被引:6,自引:0,他引:6
Markiewicz M Kalicinski P Teisseyre J Ismail H Kaminski A Teisseyre M 《Transplantation proceedings》2003,35(6):2284-2286
Experience with sirolimus (SRL) in pediatric liver transplantation (LTx) is limited. The aim of the study was to present our experience with SRL in this setting. During the last 2 years we administered SRL to 9 LTx: children in 3 due to chronic rejection and 6 due to impaired renal function. SRL was started at 2 months to 2.5 years after LTx. Target trough levels for tacrolimus for patients with chronic rejection was 8 to 10 ng/mL and SRL 10 to 12 ng/mL; for patients with impaired renal function, 4 to 6 ng/mL and 8 to 10 ng/mL respectively. For patients on only SRL and steroids the target level was 12 to 20 ng/mL. Our observation on SRL varied from 3 to 21 months, including liver function, renal function, and side effects. All patients are alive. In 3 patients with chronic rejection (ChR), follow-up biopsies showed no signs of ChR; they all normalized liver biochemistry. Independent of indication all improved their renal function. Follow-up GFR in 5 patients showed significant improvement in all. All patients showed elevated serum cholesterol values. SRL was discontinued in 3 patients due to elevation of liver enzymes in 1, persistently high serum cholesterol in 1, and repeated bouts of opportunistic infection in 1. Addition of SRL with reduced doses of tacrolimus or switching to SRL alone significantly improves renal function. 相似文献
19.
Haywood S, Abecassis M, Levitsky J. The renal benefit of mycophenolate mofetil after liver transplantation.Clin Transplant 2011: 25: E88–E95. © 2010 John Wiley & Sons A/S. Abstract: Background: The risk and benefit of adding mycophenolate mofetil (MMF) to a standard immunosuppressive regimen at the time of liver transplantation (LT) is not well described. Methods: We performed a retrospective case–control analysis comparing one‐yr outcomes of all LT recipients at our institution treated with post‐operative tacrolimus (TAC), MMF, and steroids vs. TAC and steroids. Results: A total of 101 LT recipients (50:51 case:control) were analyzed. Despite more renal dysfunction at LT, the MMF + TAC group had similar serum creatinine (Cr) and glomerular filtration rate (GFR) as the TAC group one‐yr post‐LT. In this time period, Cr decreased (1.57–1.22 mg/dL, p = 0.04) and GFR increased (57.5–65.1 mL/min per 1.73 m2, p = 0.05) in the MMF + TAC group, while Cr increased (1.11–1.35, p < 0.01) and GFR declined (73.5–60.1, p < 0.001) in the TAC group. These findings occurred without a difference in absolute rejection episodes, hospitalizations, infections, deaths, or time to above events (p > 0.05). Subgroup analysis of patients stratified by pre‐transplant renal dysfunction (Cr ≥ 1.2 mg/dL) supported the previous. MMF was reasonably well tolerated with a low rate of discontinuation. Conclusions: The use of adjunctive MMF immediately after LT may protect against calcineurin inhibitor nephrotoxicity, potentially without the need for dose reduction or increased risk of adverse events. 相似文献
20.
Switching immunosuppression from cyclosporine to tacrolimus improves long-term kidney function: a 6-year study 总被引:2,自引:0,他引:2
To improve long-term kidney graft function, acute graft rejection, hyperlipidemia, hypertension, and toxic influences must be avoided because they may contribute to chronic allograft nephropathy. Many studies have demonstrated greater efficacy and tolerability of tacrolimus compared with cyclosporine with regard to these conditions. Our study investigated whether 30 patients with deteriorating renal function benefitted from conversion to tacrolimus based upon a retrospective analysis using data recorded from 3 years before to 3 years after conversion. Renal function (GFR) deteriorated progressively under cyclosporine (creatinine: baseline 1.5 mg/dL; delta(Cyc) = +1.4 mg/dL within 3 years; GFR: delta(Cyc) = -35 mL/min within 3 years). After switching to tacrolimus, kidney function stabilized and even improved (creatinine: baseline after switching 2.9 mg/dL; delta(Tac) = -0.7 mg/dL; GFR: delta(Tac) = 14 mL/min). Conversion from cyclosporine to tacrolimus is recommended for patients with a kidney transplant in which there has been a progressive decrease in renal function. It may lead to stabilization of or even improvement in transplant function. 相似文献