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Mathis AS, Egloff G, Ghin HL. Calcineurin inhibitor sparing strategies in renal transplantation, part one: Late sparing strategies. World J Transplant 2014; 4:57-80. [PMID: 25032096 PMCID: PMC4094953 DOI: 10.5500/wjt.v4.i2.57] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2014] [Revised: 03/25/2014] [Accepted: 05/14/2014] [Indexed: 02/05/2023] Open
Abstract
Kidney transplantation improves quality of life and reduces the risk of mortality. A majority of the success of kidney transplantation is attributable to the calcineurin inhibitors (CNIs), cyclosporine and tacrolimus, and their ability to reduce acute rejection rates. However, long-term graft survival rates have not improved over time, and although controversial, evidence does suggest a role of chronic CNI toxicity in this failure to improve outcomes. Consequently, there is interest in reducing or removing CNIs from immunosuppressive regimens in an attempt to improve outcomes. Several strategies exist to spare calcineurin inhibitors, including use of agents such as mycophenolate mofetil (MMF), mycophenolate sodium (MPS), sirolimus, everolimus or belatacept to facilitate late calcineurin inhibitor withdrawal, beyond 6 mo post-transplant; or using these agents to plan early withdrawal within 6 mo; or to avoid the CNIs all together using CNI-free regimens. Although numerous reviews have been written on this topic, practice varies significantly between centers. This review organizes the data based on patient characteristics (i.e., the baseline immunosuppressive regimen) as a means to aid the practicing clinician in caring for their patients, by matching up their situation with the relevant literature. The current review, the first in a series of two, examines the potential of immunosuppressive agents to facilitate late CNI withdrawal beyond 6 mo post-transplant, and has demonstrated that the strongest evidence resides with MMF/MPS. MMF or MPS can be successfully introduced/maintained to facilitate late CNI withdrawal and improve renal function in the setting of graft deterioration, albeit with an increased risk of acute rejection and infection. Additional benefits may include improved blood pressure, lipid profile and serum glucose. Sirolimus has less data directly comparing CNI withdrawal to an active CNI-containing regimen, but modest improvement in short-term renal function is possible, with an increased risk of proteinuria, especially in the setting of baseline renal dysfunction and/or proteinuria. Renal outcomes may be improved when sirolimus is used in combination with MMF. Although data with everolimus is less robust, results appear similar to those observed with sirolimus.
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Wu MJ, Shu KH, Liu PH, Chiang PH, Cheng CH, Chen CH, Yu DM, Chuang YW. High risk of renal failure in stage 3B chronic kidney disease is under-recognized in standard medical screening. J Chin Med Assoc 2010; 73:515-22. [PMID: 21051028 DOI: 10.1016/s1726-4901(10)70113-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2010] [Accepted: 07/01/2010] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND The objective of this study was to determine the risk of renal failure in patients with under-recognized chronic kidney disease (CKD) in the self-pay standard medical screening program of health management centers. METHODS The abbreviated Modification of Diet in Renal Disease equation was used to calculate the estimated glomerular filtration rate (eGFR) of study subjects. Study subjects with eGFR less than 60 mL/min/1.73m(2) but with normal results of routine assessment, including serum creatinine, blood urea nitrogen, urinalysis and kidney ultrasound, were defined as having under-recognized CKD. Episodes of renal failure requiring dialysis within 2 years in subjects with stage 3 to stage 5 CKD were evaluated. RESULTS A total of 15,817 subjects were recruited and 28.4% of subjects were identified by routine assessments as having a kidney problem. The prevalences of CKD 3A, 3B, 4 and 5 were 8.3%, 1.9%, 0.3% and 0.2%, respectively. All subjects with stages 4 and 5 CKD had abnormal serum creatinine levels, but 48.7% of 1,507 subjects with stage 3 CKD (stage 3A, n = 713; stage 3B, n = 21) had normal routine assessments. Subjects with under-recognized stage 3B CKD had the highest risk (20%) of developing renal failure compared to subjects with stages 3-5 CKD and abnormal results of routine assessments. CONCLUSION Identifying subjects with CKD stage 3 by the eGFR equation, especially in stage 3B, is advantageous in detecting the risk of renal failure over the routine clinical assessment that is currently carried out by health management institutions in Taiwan.
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Affiliation(s)
- Ming-Ju Wu
- Division of Nephrology, Department of Medicine, Taichung Veterans General Hospital, 160 Section 3 Chung-Kang Road, Taichung, Taiwan, R.O.C.
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Glowacki F, Dharancy S, Noël C, Hazzan M. [Minimize kidney failure in transplantation patients with proliferation signal inhibitors]. GASTROENTEROLOGIE CLINIQUE ET BIOLOGIQUE 2009; 33 Suppl 4:S253-S256. [PMID: 20004331 DOI: 10.1016/s0399-8320(09)73162-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/28/2023]
Abstract
Chronic renal dysfunction is a multifactorial and frequent event after organ transplantation. The measurement or the estimation of glomerular filtration rate is essential to detect early progressive renal dysfunction. Proliferation signal inhibitors are nonnephrotoxic immunosuppressive drugs which may be useful to minimize calcineurin inhibitors-related side effects through a conversion strategy. Most studies in the setting of kidney transplantation showed improvement in glomerular filtration rate as high than conversion was early. Proliferation signal inhibitors may be included quickly in new immunosuppressive regimen for liver transplanted patients with chronic renal dysfunction.
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Affiliation(s)
- F Glowacki
- Pôle de Néphrologie, Hôpital Albert Calmette, CHRU de Lille, Bd du Pr Leclercq, 59037 Lille cedex, France
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Hazzan M, Glowacki F, Lionet A, Provot F, Noël C. [Immunosuppressive strategies and chronic graft dysfunction in kidney transplantation]. Nephrol Ther 2008; 4 Suppl 3:S208-13. [PMID: 19000889 DOI: 10.1016/s1769-7255(08)74237-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Chronic graft dysfunction is a major cause of return to dialysis. In the majority of cases, it is correlated with histological signs of cellular and/or humoral rejection, the nephrotoxicity of anticalcineurins, or nonspecific lesions of interstitial fibrosis and tubular atrophy. Although the incidence of acute rejection has considerably decreased, renal toxicity of the calcineurin inhibitors remains problematic. In cases of established nephrotoxicity, the use of non-nephrotoxic immunosuppressors such as mycophenolic acid or the proliferation signal inhibitors makes it possible to reduce or even stop the anticalcineurins. In prevention of anticalcineurin nephrotoxicity, many attempts to minimize or wean patients from them have shown that improvement in renal function is only obtained at the cost of an increase in the incidence of acute rejection. This makes it necessary to select patients who may benefit from anticalcineurin-sparing treatment, based on clinical, histological, and biological markers. Finally, long-term follow-up is also fundamental in order to validate the positive impact on renal function of this strategy in terms of graft survival.
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Affiliation(s)
- M Hazzan
- Pôle de Néphrologie, CHRU de Lille, boulevard du Pr Leclercq, 59037 Lille cedex, France.
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Wu M, Shu K, Lian J, Yang C, Cheng C, Chen C. Impact of Variability of Sirolimus Trough Level on Chronic Allograft Nephropathy. Transplant Proc 2008; 40:2202-5. [DOI: 10.1016/j.transproceed.2008.07.029] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Poor Tolerance of Sirolimus in a Steroid Avoidance Regimen for Renal Transplantation. Transplantation 2008; 85:636-9. [DOI: 10.1097/tp.0b013e3181613e65] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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Abstract
Sirolimus is a potent immunosuppressant drug with a novel mechanism of action. It inhibits the mammalian target of rapamycin (mTOR) and blocks the cell cycle of various cell types, including T- and B-lymphocytes. Sirolimus is widely used as a maintenance immunosuppressive agent in organ transplantation. Also, a potentially benefit of this valuable drug in some immunologic and malignant diseases is currently under scrutiny.Classical side effects: hematological (anaemia, leucopenia, thrombocytopenia), hypercholesterolemia, arthralgias, extremity oedema and impaired wound healing have been frequently associated with the use of sirolimus. Additionally with its increased use, transplant professionals are encountering a variety of previously unreported and potentially more severe side effects.Here, we review the most recent data on sirolimus unexpected side effects (with an emphasis on pulmonary and renal toxicity), its use in renal transplantation and its new potential therapeutic indications (chronic glomerulopathies, polycystic kidney disease, different types of cancer). A brief description of the current knowledge of sirolimus therapeutic drug monitoring, methods of analysis, pharmacokinetics and drug interactions with calcineurin inhibitors is also included.
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Affiliation(s)
- Irina Buhaescu
- Dialysis and Renal Transplantation Center, Parhon University Hospital, Iasi, Romania.
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Wu MJ, Wen MC, Chiu YT, Chiou YY, Shu KH, Tang MJ. Rapamycin attenuates unilateral ureteral obstruction-induced renal fibrosis. Kidney Int 2006; 69:2029-36. [PMID: 16732193 DOI: 10.1038/sj.ki.5000161] [Citation(s) in RCA: 141] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Unilateral ureteral obstruction (UUO) is a well-characterized hydronephrosis model exhibiting interstitial inflammatory-cell infiltration and tubular dilatation followed by tubulointerstitial fibrosis of the obstructed kidney. Our recent report indicates that rapamycin is effective for 50% of transplant recipients with chronic allograft nephropathy. In this study, we investigate the effect of rapamycin on UUO-induced renal fibrosis. UUO or sham-operated rats were randomly assigned to rapamycin or vehicle and were killed on days 7 and 14 after UUO or sham operation. Rapamycin decreased cross-sectional and gross-morphology changes in the obstructed kidney significantly. Rapamycin markedly blunted the increase in weight of the obstructed kidney, obstructed kidney length, and the obstructed/non-obstructed kidney weight ratio (by 74.6, 42.8, and 61.6% on day 14, respectively, all P<0.01). The scores for tubular dilatation, interstitial volume, interstitial collagen deposition, and alpha-smooth muscle actin (alpha-SMA) after UUO were significantly reduced by rapamycin. Rapamycin also decreased the number of infiltrative anti-ED1-positive cells and the gene expression of transforming growth factor (TGF)-beta1 (84.8 and 80.2% on day 7) after UUO (both P<0.01). By double immunostaining and Western analysis, rapamycin blocked the TGF-beta1-induced loss of E-cadherin expression and de novo increase of the expression of alpha-SMA in a dose-dependent manner. In conclusion, rapamycin significantly attenuated tubulointerstitial damage in a UUO-induced rat model of renal fibrosis, suggesting that rapamycin may have the potential to delay the progression of tubulointerstitial renal fibrosis.
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Affiliation(s)
- M-J Wu
- Division of Nephrology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
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Stephany BR, Augustine JJ, Krishnamurthi V, Goldfarb DA, Flechner SM, Braun WE, Hricik DE, Dennis VW, Poggio ED. Differences in proteinuria and graft function in de novo sirolimus-based vs. calcineurin inhibitor-based immunosuppression in live donor kidney transplantation. Transplantation 2006; 82:368-74. [PMID: 16906035 DOI: 10.1097/01.tp.0000228921.43200.f7] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Calcineurin inhibitor(CNI)-free protocols using sirolimus (SRL) in kidney transplantation have proven effective, although reports have linked SRL to proteinuria. We sought to investigate this link and its impact on graft function. METHODS We retrospectively analyzed 184 live donor kidney transplant recipients who exclusively received de novo CNI-based (n = 106) or SRL-based (n = 78) regimens. Estimated glomerular filtration rate (GFR) and semi-quantitative dipstick proteinuria measurements were obtained at one, six, 12, and 24 months and six and 12 months, respectively. RESULTS SRL-treated patients had higher frequencies of proteinuria (> or =1+) at 6 months (40.8% vs. 21.4%, P = 0.006) and 12 months (37.8% vs. 18.4%, P = 0.004) than those treated with CNI. Independent predictors of proteinuria at 12 months were GFR at one month (OR 0.62 per 10 ml/min/1.73 m, P<0.001), delayed graft function (OR 11.5, P = 0.02), and a SRL-based regimen (OR 4.18, P=0.002). By univariable analysis, SRL vs. CNI patients had higher GFR at each point. SRL-treated patients without proteinuria had higher GFR at 12 months compared to CNI-treated patients with and without proteinuria (66 vs. 50 or 56 ml/min/1.73 m, P < 0.05). No difference in GFR was seen between SRL-treated patients with proteinuria vs. CNI-treated patients without proteinuria (57 vs. 56 ml/min/1.73 m, P > 0.05). Absence of proteinuria and a SRL-based regimen remained independently associated FS with higher GFR at 12 months by multivariable analyses. CONCLUSIONS De novo SRL-based immunosuppression is associated with a higher frequency of semi-quantitative proteinuria, however, estimated graft function at 1 year posttransplant remains superior to that of CNI-treated patients. Nevertheless, the long-term implications of these findings need to be determined.
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Affiliation(s)
- Brian R Stephany
- Department of Nephrology and Hypertension, Cleveland Clinic Foundation, OH 44195, USA
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Meier M, Nitschke M, Weidtmann B, Jabs WJ, Wong W, Suefke S, Steinhoff J, Fricke L. Slowing the progression of chronic allograft nephropathy by conversion from cyclosporine to tacrolimus: a randomized controlled trial. Transplantation 2006; 81:1035-40. [PMID: 16612281 DOI: 10.1097/01.tp.0000220480.84449.71] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Chronic allograft nephropathy (CAN) is a multifactorial process with immunologic and nonimmunologic factors. Because tacrolimus (Tac) has been ascribed a beneficial effect on some of these factors when compared to cyclosporine A (CyA), a randomized controlled trial was conducted to investigate whether conversion from CyA to Tac can ameliorate the progression of renal dysfunction in kidney transplant recipients (KTR) with CAN. METHODS Of the 46 patients with biopsy-proven CAN enrolled, 24 were converted from CyA to Tac, whereas 22 patients were maintained on CyA. Serum creatinine (SCrea), lipid profiles and an antihypertensive score (AHS) were determined after 3, 6 and 12 months. AHS is based on the total number and dosages of antihypertensive medications used. SCrea and AHS were additionally evaluated at 36 months. RESULTS SCrea was decreased in the Tac group (Tac(baseline): 297 +/- 67 micromol/L; Tac(6): 261+/- 70 micromol/L, P < 0.001; Tac(12): 254 +/- 55 micromol/L, P < 0.001; Tac(36): 255 +/- 78 micromol/L, P = 0.235), whereas a significant increase of SCrea was detected in the CyA group (CyA(baseline): 279 +/- 77 micromol/L, CyA(12): 333 +/- 98 micromol/L, P < 0.001; CyA(36): 317 +/- 89 micromol/L, P < 0.001). Compared to CyA therapy, SCrea in the Tac group declined after 12 and 36 months (P = 0.011 and 0.048, respectively) as well as AHS (Tac(12): 59 +/- 13, CyA(12): 83 +/- 14, P < 0.001; Tac(36): 60 +/- 12, CyA(36): 84 +/- 14, P < 0.001). LDL cholesterol was lower in the Tac group after 12 months (Tac(12): 2.5 +/- 0.5 mmol/L, CyA(12): 3.5 +/- 0.6 mmol/L, P < 0.001). CONCLUSION Conversion from CyA to Tac in KTR with CAN improves allograft function, lowers blood pressure, and reduces LDL cholesterol. This superior profile may translate into improved long-term graft survival.
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Affiliation(s)
- Markus Meier
- Transplantation Center, University of Luebeck, School of Medicine, Germany.
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Falger JC, Mueller T, Arbeiter K, Boehm M, Regele H, Balzar E, Aufricht C. Conversion from calcineurin inhibitor to sirolimus in pediatric chronic allograft nephropathy. Pediatr Transplant 2006; 10:565-9. [PMID: 16856992 DOI: 10.1111/j.1399-3046.2006.00515.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
CAN is a major cause for allograft loss in renal transplantation. Sirolimus was recently introduced as a potent non-nephrotoxic alternative to CNIs. In the present study, effects of a conversion protocol were investigated in pediatric CAN with declining GFR, defined by a Schwartz formula clearance below 60 mL/1.73 m2/min, steadily increasing SCr and allograft biopsy. In eight children with a median age of 12.8 yr, sirolimus was started at median 32 months after transplantation with a loading dose of 0.24 mg/kgBW, followed by 0.2 mg/kgBW/day, aimed at trough levels of 15-20 ng/mL. CNIs were reduced to 50% at start of sirolimus and discontinued at median seven days when target levels of sirolimus were reached. Following conversion, changes of GFR significantly stabilized (-2.9 vs. +0.4 mL/min/1.73 m2/month, p = 0.025). Individual GFR increased in five of eight patients (p = 0.026), only one child exhibited unaltered progression of graft failure. In the responders, mean SCr improved by 0.3 mg/dL (p = 0.043). Effects were not dependent on GFR at conversion, nor time post-transplantation. Blood pressure, hematological parameters and proteinuria remained stable during the observation period, serum lipids transiently increased. About half of the children suffered from infectious complications. No child had to be taken off sirolimus; there was no graft loss during the observation period. In conclusion, conversion from CNIs to sirolimus is an effective protocol with tolerable side effects to stabilize renal graft function for at least one yr in the majority of children with biopsy proven CAN.
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Affiliation(s)
- Jutta C Falger
- Kinderdialyse, Department of Pediatrics, AKH Wien, Medical University of Vienna, Vienna, Austria
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Falger JC, Mueller T, Arbeiter K, Boehm M, Regele H, Balzar E, Aufricht C. Conversion from calcineurin inhibitor to sirolimus in pediatric chronic allograft nephropathy. Pediatr Transplant 2006; 10:474-8. [PMID: 16712606 DOI: 10.1111/j.1399-3046.2006.00503.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Chronic allograft nephropathy is a major cause for allograft loss in renal transplantation. Sirolimus was recently introduced as a potent non-nephrotoxic alternative to calcineurin inhibitors. In the present study, effects of a conversion protocol were investigated in pediatric chronic allograft nephropathy with declining glomerular filtration rate (GFR), defined by a Schwartz formula clearance below 60 mL/1.73 m(2)/min, steadily increasing serum creatinine and allograft biopsy. In eight children with a median age of 12.8 yr, sirolimus was started at median 32 months after transplantation with a loading dose of 0.24 mg/kg bodyweight (BW), followed by 0.2 mg/kgBW/day, aimed at trough levels of 15-20 ng/mL. Calcineurin inhibitors were reduced to 50% at the start of sirolimus and discontinued at median 7 days when target levels of sirolimus were reached. Following conversion, changes of GFR significantly stabilized (-2.9 vs. +0.4 mL/min/1.73 m(2)/month, p = 0.025). Individual GFR increased in five out of eight patients (p = 0.026), and only one child exhibited unaltered progression of graft failure. In the responders, mean serum creatinine improved by 0.3 mg/dL (p = 0.043). Effects were not dependent on GFR at conversion, or on time post-transplantation. Blood pressure, hematological parameters and proteinuria remained stable during the observation period, and serum lipids increased transiently. About half of the children suffered from infectious complications. No child had to be taken off sirolimus; there was no graft loss during the observation period. In conclusion, conversion from calcineurin inhibitors to sirolimus is an effective protocol with tolerable side effects to stabilize renal graft function for at least one yr in the majority of children with biopsy-proven chronic allograft nephropathy.
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Affiliation(s)
- Jutta C Falger
- Kinderdialyse, Department of Pediatrics, AKH Wien, Medical University of Vienna, Vienna, Austria
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Abstract
Sirolimus is a macrolide that is extensively used in transplant clinics. The most common side effects of sirolimus are hypertriglyceridemia, hypercholesterolemia, hypertension, rash, and well-tolerated diarrhea. Herein I have reported a case of intractable, disabling, chronic diarrhea secondary to sirolimus in a renal transplant recipient. The sirolimus dose had been recently increased from 2 mg to 5 mg 1 month before the patient began to complain of severe diarrhea. In addition to the case presentation, the literature is reviewed as well as possible mechanisms of sirolimus-induced diarrhea are discussed. In conclusion, clinicians should consider sirolimus as a potential etiology for severe chronic diarrhea among patients who are treated with sirolimus.
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Affiliation(s)
- A A Alkhatib
- Department of Internal Medicine, The University of Texas Medical School at Houston, Houston, Texas 77030, USA.
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Abstract
Managing the failing allograft juxtaposes immunosuppressive management and routine chronic kidney disease care. The complications of immunosuppression can be more pronounced in those with renal failure (infection, anemia, bone disease). The withdrawal of immunosuppression may be associated with acute allograft rejection, arthralgias, and the development of antidonor antibodies. Likewise depression is prevalent. Improving well-being and overall survival necessitates proper titration of immunosuppressive medications and control of blood pressure, anemia, lipids, and glucose along with attention to treatment of depression.
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Affiliation(s)
- Elizabeth A Kendrick
- Department of Medicine, Division of Nephrology, University of Washington School of Medicine, Seattle, Washington, USA
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Watson CJE, Firth J, Williams PF, Bradley JR, Pritchard N, Chaudhry A, Smith JC, Palmer CR, Bradley JA. A randomized controlled trial of late conversion from CNI-based to sirolimus-based immunosuppression following renal transplantation. Am J Transplant 2005; 5:2496-503. [PMID: 16162200 DOI: 10.1111/j.1600-6143.2005.01055.x] [Citation(s) in RCA: 115] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Maintenance immunosuppression with calcineurin inhibitors (CNIs) following renal transplantation is associated with nephrotoxicity and accelerated graft loss. We aimed to assess whether conversion to sirolimus-based immunosuppression would affect the progression of renal impairment. In this single center, randomized controlled trial, 40 renal transplant recipients between 6 months and 8 years post-transplant were randomly assigned to remain on their CNI (cyclosporin or tacrolimus) or to switch to sirolimus. The primary outcome measure was change in glomerular filtration rate (GFR) measurement at 12 months. Analysis was by intention-to-treat. Of the 40 patients randomized, 2 patients never took the study drugs and were excluded, leaving 19 patients per group. There was a significant change in GFR at 12 months following conversion to sirolimus (12.9 mL/min, 95% CI 6.1-19.7; p < 0.001). Following conversion, the principal adverse events were the development of rashes (68%), particularly acne, and mouth ulcers (32%). No patient in either group experienced an acute rejection episode. In renal transplant recipients, a change in maintenance therapy from CNIs to sirolimus is associated with significant improvement in GFR at 12 months.
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