Long-term Efficacy and Safety of a Calcineurin Inhibitor-free Regimen in Live-Donor Renal Transplant Recipients

Size: px
Start display at page:

Download "Long-term Efficacy and Safety of a Calcineurin Inhibitor-free Regimen in Live-Donor Renal Transplant Recipients"

Transcription

1 JASN Express. Published on March 12, 2008 as doi: /ASN CLINICAL RESEARCH Long-term Efficacy and Safety of a Calcineurin Inhibitor-free Regimen in Live-Donor Renal Transplant Recipients Ahmed F. Hamdy, Mohamed A. Bakr, and Mohamed A. Ghoneim Urology and Nephrology Center, Mansoura University, Mansoura, Egypt ABSTRACT Calcineurin inhibitor (CNI) nephrotoxicity is a major concern after renal transplantation. To investigate the safety and efficacy of a CNI-free immunosuppressive regimen, 132 live-donor renal transplant recipients were included in a prospective, randomized controlled trial. All patients received induction therapy with basiliximab and steroids. The patients were randomized to a maintenance immunosuppression regimen that included steroids, sirolimus, and either low-dose tacrolimus or mycophenolate mofetil (MMF). Over a mean follow-up period of approximately 5 yr, patient and graft survival did not significantly differ between the two maintenance regimens. Patient survival was 93.8% and 98.5% in the tacrolimus/sirolimus and MMF/sirolimus groups, respectively, and graft survival was 83% and 88%, respectively. However, the MMF/sirolimus group had significantly better renal function, calculated by Cockcroft-Gault, from the second year post-transplant until the last follow-up. In addition, this group was less likely to require a change in their primary immunosuppression regimen than the tacrolimus/sirolimus group (20.8% versus 53.8%, P 0.001). The safety profile was similar between groups. In summary, after long-term follow-up, a CNI-free maintenance regimen consisting of sirolimus, MMF, and steroids was both safe and efficacious among low to moderate immunologic risk renal transplant recipients. J Am Soc Nephrol :, doi: /ASN Avoidance or at least minimization of the nephrotoxic effect of the calcineurin inhibitors (CNIs) is indeed a worthy goal; however, it must be approached with great care. The current CNIs in use, including cyclosporine (CsA) and tacrolimus (Tac), are, in addition to being nephrotoxic, associated with detrimental effects on cardiovascular risk factors, such as hypertension, dyslipidemia, and glucose intolerance. Besides, development of chronic allograft nephropathy (CAN) is common in recipients treated with CNI. 1 3 Recently, it was found that especially longterm treatment with CNI drugs results in fibrotic scarring of transplanted kidneys, an effect present in about 25% of the patients already during the first 6 mo post-transplant. 4 The introduction of potent immunosuppressive alternatives to CNI drugs, such as mycophenolate mofetil (MMF), mtor inhibitors (mammalian target of rapamycin, sirolimus, everolimus), and the anti-cd25 antibodies (anti-il-2 receptor antibodies daclizumab and basilixiamb) challenge investigations of less toxic immunosuppressive protocols. MMF has been shown to be a well-tolerated and effective alternative in patients with CsA-induced nephrotoxicity, not only allowing CsA dose reduction but also full CsA withdrawal in selected patients resulting in significantly improved renal function. 5 8 MMF also has a preferred profile on blood pressure, lipids, and glucose metabolism. Received September 12, Accepted December 9, Published online ahead of print. Publication date available at. Correspondence: Ahmed Farouk Hamdy, Urology and Nephrology Center, Mansoura University, Al-gomhoria Street, Mansoura, Egypt Phone: ; Fax: ; afhamdy@yahoo.com Copyright 2008 by the American Society of Nephrology J Am Soc Nephrol :, 2008 ISSN : / 00-1

2 CLINICAL RESEARCH CNI avoidance might translate into improved graft and patient survival as long as the overall immunosuppression is adequate. CNI-free regimens based on daclizumab induction followed by MMF and steroid maintenance have shown 1-yr graft survival of more than 95%; however, acute rejection rate was unacceptably high in these patients with average immunogenic risk. 9,10 The complementary properties of sirolimus (SRL) and MMF may provide the rationale for their combination in induction and maintenance regimens. SRL, an mtor inhibitor, inhibits cell proliferation driven by growth factors; and MMF, a reversible inhibitor of inosine monophosphate dehydrogenase, acts as an antiproliferative drug. Early experiences with the use of the SRL, MMF, and steroid combination yielded insufficient prophylaxis of acute rejection. 11,12 However, the introduction of induction therapy with monoclonal or polyclonal antilymphocyte antibodies to the SRL/MMF and steroid combination brings an efficient acute rejection prophylaxis while improving renal function and/or reducing chronic allograft nephropathy. 13,14 However, a recent review article of an organ-by-organ review of Organ Procurement and Transplantation Network and Scientific Registry of Transplant Recipients data showed a decline in the number of renal transplant patients who were discharged on regimens containing SRL down to 16% in Moreover, the use of the SRL/MMF combination has remained less than 1%. 15 We have previously reported on the safe and efficient use of SRL/MMF combination regimen together with steroids and basiliximab induction therapy in a short-term prospective randomized trial. 14 We hereby report on the safety and efficacy of the longer-term use of such a regimen in living donor renal transplant recipients. RESULTS Figure 1. Patient survival relative to the primary immunosuppression in groups A (Tac) and B (MMF). and 32 mo post-transplantation. Seven patients returned back to dialysis throughout the whole follow-up period. Recurrence of original kidney disease (anti-glomerular basement membrane nephritis and focal segmental glomerulosclerosis [FSGS]) was responsible for two graft failures, 4 and 7 mo post-transplantation. One patient had thrombotic microangiopathy complicated by transplant glomerulopathy and FSGS and put on dialysis 5 mo post-transplantation. Another patient had recurrent acute rejections (3 episodes) and complicated by transplant glomerulopathy resulting from minimal change disease and returned to dialysis 24 mo post-transplantation. Chronic allograft nephropathy was responsible for graft failure in the last 3 cases (28, 42, and 60 mo post-transplantation). Group B. One patient died of septicemia caused by recurrent bacterial infections secondary to multiple anal abscesses and Demography Demographic and baseline characteristics were previously outlined. 14 Both groups were homogeneous regarding recipients age, sex, body weight, original kidney disease, pretransplant hypertension, urinary bilharziasis, hepatitis C virus antibody test, donors age, and human leukocyte antigen matching. Patient and Graft Outcome Mean follow-up period was and mo for group A and B, respectively (range, 55 to 75 mo). Higher patient and graft survivals were noted among group B patients, although it does not rank to statistical significance (Figures 1 and 2; Table 1). Group A. Four patients died. The cause of death in 2 of them was miliary tuberculosis (TB), 3 and 6 mo post-transplantation. The cause of death in the others was most probably attributed to a cardiovascular cause being reported at home, 31 Figure 2. Graft survival relative to the primary immunosuppression in groups A (Tac) and B (MMF). 2 Journal of the American Society of Nephrology J Am Soc Nephrol :, 2008

3 CLINICAL RESEARCH Table 1. Patient and study outcome Group A (Tac) (N 65) Group B (MMF) (N 67) P Mean follow-up, mo (mean SD) Condition at last follow-up, no. (%) living with functioning graft 54 (83) 59 (88) living on dialysis 7 (10.8) 7 (10.5) died with functioning graft 4 (6.2) 1 (1.5) Secondary immunosuppression, no. (%) 35 (53.8) 14 (20.8) fistulae 7 mo post-transplantation. Similar to group A, 7 patients return back to dialysis during the whole follow-up period. Recurrence of original kidney disease (FSGS and membranoproliferative glomerulonephritis) was responsible for two graft failures, 8 and 43 mo post-transplantation, respectively. De novo glomerulopathy (FSGS) was responsible for one graft failure 21 mo post-transplantation. Chronic allograft nephropathy was responsible for graft failure in the last 4 cases (19, 44, 57, and 60 mo post-transplantation). Immunosuppressive Drugs After the first 3 post-transplant months, mean SRL levels were kept within the targeted therapeutic windows throughout the whole follow-up period. After the first 2 yr, there was no statistically significant difference of SRL levels between either group as the targeted window became the same (Figure 3). Subsequently, mean SRL doses were close to each other in both groups. During the fifth year, mean SRL dose was mg/d and mg/d in group A and B, respectively. Mean Tac doses and levels were kept within the targeted windows among group A patients. Fifth year mean Tac dose value was mg/d and mean level value was ng/ml. Mean MMF doses were progressively reduced over time down to g/d during last follow-up year among group B patients. Secondary Immunosuppression Statistically significant higher change rate of the primary immunosuppressive regimen was encountered among group A patients as shown in Table 2. In 21 patients of group A, Tac was replaced by MMF, in essence cross over to group B, because of biopsy-proven acute Tac toxicity despite optimum level (2 cases), chronic tubulointerstitial fibrosis of moderate degree (8 cases), recurrent severe diarrhea complicated by marked body weight reduction and frequent hospital admissions (6 cases), and uncontrolled newly discovered diabetic state (5 cases). In another 14 patients of the same group, SRL was completely withdrawn and replaced by either MMF, due to proteinuria (5 cases), surgical complications (3 cases), high liver enzymes (1 case), or replaced by azathioprine in one female who was seeking pregnancy. Two patients were maintained on steroids and Tac only because of persistent leucopenia despite therapeutic SRL blood level; and finally, 2 patients were maintained on steroids and MMF because of pulmonary TB. Among group B patients, MMF was replaced by Tac in 3 patients, in essence cross over to group A, because of persistent leucopenia with optimum SRL level. In another 11 patients, SRL was withdrawn and replaced by Tac because of proteinuria (3 patients), interstitial pneumonitis (1 case), and intolerance (1 case). In 4 females, SRL and MMF were replaced by Tac and azathioprine for the sake of getting pregnant; and finally, 2 patients with pulmonary TB were maintained on steroids and MMF only. Graft Function Based on intention-to-treat analysis, statistically significant better renal allograft function was encountered among group B patients from the second post-transplant year until the last follow-up, as measured by calculated glomerular filtration rate (GFR), in comparison with group A (Figure 4). By exclusion of those with secondary immunosuppression (35 in group A and 14 in group B), no significant difference of renal function was found, although group B patients still have higher calculated GFRs at all time periods (Figure 5). Figure 3. Sirolimus trough levels (ng/ml) in both groups. Histopathologic Findings No acute rejection episodes were encountered beyond the second year of follow-up. Meanwhile, CAN of various degrees was diagnosed among 11 and 9 patients of group A and B, respectively (Table 3). Two of those with moderate CAN and all of those with marked CAN returned back to dialysis. On studying the impact of chronic allograft damage index (CADI) obtained from protocol graft biopsies (originally 86 cases) at the end of the first post-transplant year, 14 we opted to classify whole patients of the two groups together into nearly equal two divisions: those with CADI score equal 0, 1, or 2 and those whose the score equals 4, 5, 6, or 7. Table 4 shows higher J Am Soc Nephrol :, 2008 Long-term CNI-free Regimen 3

4 CLINICAL RESEARCH Table 2. Secondary immunosuppression regimens in both groups Indications Group A (Tac) (N 65) Group B (MMF) (N 67) P Conversion to sirolimus-based regimens (crossover) acute Tac toxicity tubule-interstitial fibrosis (moderate degree) chronic diarrhea uncontrolled new DM leucopenia Conversion to non sirolimus-based regimens proteinuria surgical cause elevated liver enzymes seek pregnancy leucopenia pulmonary TB interstitial pneumonitis intolerance DM, diabetes mellitus; TB, tuberculitis. calculated GFR values among the first group, which approaches significance at the last follow-up. Among group B patients, studying the impact of each of the six elements of the CADI score (mesangial matrix increase, glomerular sclerosis, tubular atrophy, interstitial inflammation, interstitial fibrosis, and vascular intimal proliferation) on subsequent renal allograft function revealed that interstitial inflammation (which affected 30.2% of group B patients at 1 yr) was the only element found to have significant impact on GFR throughout all time points after the first year (Table 5). Adverse Events No significant difference was found regarding the incidence or the number of antihypertensive medications used in each group, nor in the hematologic complications throughout the follow-up period (Table 6). The most significant infectious complication was the development of tuberculosis among 6 and 4 patients in group A and B, respectively. No significant difference was encountered regarding the incidence of diabetes mellitus, elevated liver enzymes, osteonecrosis, proteinuria, or surgical complications. Group A shows significant higher incidence of chronic diarrhea, whereas group B shows significant higher incidence of hyperlipidemia and herpes zoster infection. No single case of malignancy was diagnosed in either group. DISCUSSION Based on data of the Organ Procurement and Transplantation Network and Scientific Registry of Transplant Recipients, which identified trends that have evolved over the past decade in the use of immunosuppression for recipients of solid organ transplants, Tac/MMF combination was found to be the most frequently used maintenance immunosuppression combination at 1 and 2 yr after kidney transplantation. At 1 yr after transplantation in 2003, 51% of patients were receiving Tac/ MMF combination, 17% were receiving CsA/MMF, 8% Tac/ SRL, and only 1% on SRL/MMF combination regimen. Moreover, a surprisingly low percentage of patients continued their Figure 4. Graft function based on intention-to-treat analysis (all cases are included) as estimated by calculated GFR (ml/min). Figure 5. Graft function based on maintenance of primary immunosuppressive regimen (all cases with secondary immunosuppression are excluded) as estimated by calculated GFR (ml/min). 4 Journal of the American Society of Nephrology J Am Soc Nephrol :, 2008

5 CLINICAL RESEARCH Table 3. 3 yr) Pathologic diagnosis of event graft biopsies (last Value Group A Group B P Chronic allograft nephropathy mild degree 4 5 moderate degree marked degree 1 1 Focal segmental glomerulosclerosis 1 0 original immunosuppressive discharge regimen through the first 3 yr following transplantation. Among patients transplanted in 2001, the change rate for Tac/MMF combination at 3 yr was 43% and that for SRL/MMF combination was up to 65%. 15 We have previously reported on the 2-yr safety and efficacy profile of SRL/steroids based regimens in combination with either low-dose Tac (group A) or MMF (group B) together with basiliximab induction therapy among live-donor renal allotransplant recipients in a prospective randomized study, and it was shown that the SRL/MMF regimen was safe regarding patient and graft survival and was associated with significant better renal function at 2 yr than the Tac/SRL regimen. 14 We hereby report on the long-term safety and efficacy profile of the same randomized patients. Throughout the follow-up period from the third to fifth year, 2 group A patients had sudden death most probably secondary to cardiovascular cause. During the same period, 3 and 4 patients in group A and B, respectively, returned back to dialysis mostly secondary to the development of CAN. Therefore, it was noted that early causes of death among our patients were infectious and late causes were cardiovascular, whereas early causes of graft failure were mostly the result of recurrent Table 4. Impact of CADI score on calculated GFR (ml/min) CADI Score 0 to 2 CADI Score 3to7 No. GFR No. GFR P 1 yr yr yr yr yr Table 5. Impact of presence or absence of interstitial inflammation of 1-yr protocol biopsies on subsequent GFR (ml/min) among group B patients Absent Present No. GFR No. GFR P 1 yr yr a 3 yr a 4 yr a 5 yr a a P Table 6. Adverse events Group A (Tac) Group B (MMF) Hypertension, no. (%) of patients 33 (61.1) 45 (76.3) No. of drugs 1 drug drugs drugs Diabetes mellitus Anemia (Hb 10 g/dl) Thrombocytopenia Infections herpes zoster a tuberculosis Elevated liver enzymes 1st and 2nd yr rd, 4th, and 5th yr Osteonecrosis Chronic diarrhea a Hyperlipidemia 1st and 2nd yr a 3rd, 4th, and 5th yr a Proteinuria 1 to 3 g/day g/day Surgical 1st and 2nd yr lymphocele 4 7 urinary fistula wound complication rd, 4th, and 5th yr renal stone 0 1 ovarian cyst 1 1 herniorrhaphy 2 3 skin ulcer a P original kidney disease and transplant glomerulopathy and late causes were the result of CAN. Slightly lower rates of patient and graft survival for the SRL/MMF arm (87.1% and 83.9%, respectively) were obtained by Flechner et al. 16 in a 5-yr prospective randomized study of either SRL/MMF or CsA/MMF with steroids and basiliximab induction in adult renal allotransplant recipients. Our group B patients show significant lower change rate of the primary immunosuppression compared with group A through the whole follow-up period, being observed in 14 patients (20.8%), 4 of which were seeking pregnancy. This comes in accordance with Flechner et al. 16 about low change rates of primary SRL/MMF regimens. Our main indications for SRL withdrawal, in addition to pregnancy, were development of proteinuria in view of several recent reports linking SRL to proteinuria 17,18 and tuberculous infection, leukopenia, and surgical causes. Group A unique indications for change of the primary regimen were mainly related to combined SRL/Tac nephrotoxicity (e.g., pathologic diagnosis of acute Tac toxicity despite optimum blood level and/or moderate tubulointersti- P J Am Soc Nephrol :, 2008 Long-term CNI-free Regimen 5

6 CLINICAL RESEARCH tial fibrosis), GIT toxicity (e.g., chronic diarrhea with marked weight reduction), and presumed islet cell toxicity 19 (e.g., newly discovered difficult controlled diabetes mellitus [DM]). Based on intention-to-treat analysis, statistically significant higher renal function obtained at 2 yr among SRL/MMF patients, 14 was maintained until the last follow-up period, a finding that comes in accordance with all short-term 12,13,20 and long-term studies 16 ; however, more recently, Larson et al., 21 in a comparison of TAC/MMF versus SRL/MMF, showed that the iothalamate clearance at 1 mo was higher in the SRL/MMF than in the TAC/MMF group (67 18 ml/min versus ml/min); however, this difference was lost at 1 yr because of the unexpected loss of GFR in the SRL/MMF group. Differences in renal function between Larson s and other studies may be explained by the different anti-calcineurinic drugs used in the control group because it seems that CsA induces more profound renal hemodynamic changes than TAC, at least at the current target levels for clinical immunosuppression. 22 By exclusion of those with secondary immunosuppression, group A patients could obtain comparable renal function with group B patients after 5 yr, however, with high exclusion rate that exceeds 50%. By classification of patients according to stages of chronic kidney diseases, 23 it was found that about one half and one third of SRL/MMF patients enjoyed quite normal renal function by 3 and 5 yr, respectively. Among our patients, who are of low to moderate immunologic risk, we reported reduced incidence of acute rejection among group B patients, in the first post-transplant year down to13.5%, 14 a finding that comes in accordance with all trials using SRL/MMF with steroids and induction therapy in which acute rejection incidence varies from 6.5%, 13 to 13%. 21 Moreover, even in patients with high immunologic risk, Lo et al. 20 reported 12-mo incidence of as low as 7%. At the end of the first post-transplant year, CADI score was not significantly different between either group. 14 On studying the impact of CADI score on the subsequent renal function among both groups to define a cut off value, it was found that CADI scores of 0,1or 2 were associated with nearly significant better renal function at 5 yr. Moreover, on studying the impact of each of the 6 elements of the score 24 on eventual renal function in both groups, interstitial inflammation among group B patients (which affected 30.2% of patients at 1 yr) was the only element found to have significant impact on GFR throughout all time points after the first year. The safety profile of both groups has markedly improved after the first 2 post-transplant years, as the immunosuppressive doses were reduced as well as the targeted therapeutic window of SRL. Therefore, low incidence of hematologic complications, apart from renal impairment induced anemia, and low surgical complications were encountered. Similarly, the incidence of infectious complications was low apart from TB, which was encountered among 10 cases (7.6%) of our patients. In a previous report on 1200 renal transplant population from the same locality, the incidence of post-transplant TB infection was 3.8%. 25 A higher incidence among our series may be explained by the use of more potent immunosuppressive medications, improper pretransplant screening, new epidemic, or combination of these factors. Early (before 1 yr) and aggressive presentation of TB (miliary form) was associated with higher mortality rates. In view of such a life-threatening disease, a policy of handling immunosuppressive drugs among recent cases could show some success, by which all group A or group B affected patients were converted to a dual regimen consisting of steroids and MMF so as to reduce net immunosuppression and avoid drug interactions of SRL and Tac with anti-tb drugs. No case of solid organ or skin cancer was diagnosed in either group, a finding that supports the hypothesis of Luan et al., 26 that SRL might prevent rather than promote tumor progression. In summary, a calcineurin-inhibitor free immunosuppressive regimen, consisting of steroids, SRL, and MMF together with monoclonal antibody induction therapy, has proven to be both safe and effective among low to moderate immunologic risk renal allotransplant patients after long-term follow-up. Avoidance of early high change rates of the regimen could be achieved by proper SRL dosages through strict follow-up of SRL blood levels. SRL administration should be delayed in certain patients at increased risk of side effects (e.g., high body mass index, delayed graft function). Administration of this regimen among high immunologic risk patients has proved success on short term, awaiting longer-term follow-up. CONCISE METHODS Patients Between May 2001 and January 2003, a total of 132 patients with end-stage renal disease, who received a live donor renal allo-transplant at the Urology and Nephrology Center, Mansoura University, Egypt, were the subjects of this study. Exclusion criteria included patients requiring second renal transplantation, patients younger than 18 yr, cases with pretransplant chemistries demonstrating a total serum cholesterol greater than 300 mg/dl, triglycerides greater than 400 mg/dl, white blood cell count less than 4000/mm 3 or platelets less than /mm 3, patients with pretransplant positive lymphocytotoxic cross-match test, and those with more than 50% DR mismatch. Immunosuppression Protocol All patients in both groups received basiliximab (Simulect, Novartis, Basel, Switzerland) 20 mg intravenously at surgery and on day 4 postoperative. Patients in both groups received intravenous methyl prednisolone 500 mg one day before and on day of surgery. Oral prednisolone was then given at a dose of 1 mg/kg per day, which is then gradually tapered down to 0.1 mg/kg by the 10th mo post-transplantation. Group A patients received SRL solution (Rapamune, Wyeth- Ayerst, Princeton, NJ) within 24 h after completion of surgery in a dose of 10 mg/d orally (single morning dose) for 3 d and then main- 6 Journal of the American Society of Nephrology J Am Soc Nephrol :, 2008

7 CLINICAL RESEARCH tained on 5 mg/d. Further doses were concentration controlled to keep 24 h whole blood trough level between 6 and 12 ng/ml. Tacrolimus (Prograf, Fujisawa Pharmaceutical, Osaka, Japan) was also administered to this group of patients on the third day postoperative, provided that creatinine clearance is more than 50 ml/min. Tacrolimus was started at a dose of 0.03 mg/kg per day in two equally divided doses targeting 12 h whole blood trough level of 3 to 7 ng/ml. Group B patients received SRL and maintained on single oral morning dose of 10 mg/d targeting 24 h whole blood trough level between 10 and 15 ng/ml. Mycophenolate Mofetil (Cellcept, Hoffman-La Roche, Nutley, NJ) 1 g twice daily was begun the morning after surgery. Patients remained on this dose unless side effects, such as gastrointestinal toxicity or leucopenia, necessitated dose reduction. No standard antimicrobial prophylaxis therapy was adopted in this study. Therapeutic Drug Monitoring Serum trough levels of SRL were evaluated by high performance liquid chromatography with mass spectroscopy detection through the first 2-yr transplant period, after which the microparticle enzyme immunoassay method was used. 27 Two years post-transplantation, SRL trough level was maintained between 5 and 10 ng/ml in both groups. Tac trough levels were evaluated using a microparticulate enzyme immunoassay method and maintained between 3 and 7 ng/ml. Clinical Assessment The patients were assessed clinically with particular emphasis on blood pressure measurement. Hypertension was defined according to the JNC v report. 28 The number of antihypertensive drugs was reported for every patient to express severity of hypertension. New-onset DM was defined as post-transplant hyperglycemia necessitating treatment with oral hypoglycemic agents or insulin injections. Clinical tolerance to the given medications was assessed, which included the safety profile and the occurrence of any adverse events. Laboratory Investigations These included complete urine analysis, serum electrolytes, liver function tests, fasting blood sugar, uric acid, calcium, phosphorus, complete lipid profile, and hematologic profile. Renal allograft function was evaluated by the estimation of serum creatinine and calculated GFR using the Cockroft-Gault formula. 29 Evaluation of Graft Biopsies Event (for cause) biopsy was carried out in case of nephrotic range proteinuria or episodes of renal dysfunction (25% increase in creatinine from baseline) for which histopathologic examination was performed according to the Banff Schema (1997). 30 Study Outcomes The study outcomes consisted of efficacy profiles, toxicity profiles, and renal allograft pathology profiles. The efficacy profiles were patient and graft survival, biopsy-confirmed acute rejection episodes, and graft function. The toxicity profiles included serious adverse events, malignancies, infections, wound complications, and metabolic complications. Renal allograft pathology was evaluated using the Banff schema (1997) for event biopsies. Statistical Analysis t test was used to compare between the two groups in continuous data. 2 was used to compare categorical variables. The survival of the patients and the grafts was computed using the Kaplan-Meier method 31 on an intention-to-treat basis. Differences in survival were calculated by the log-rank test. 32 For all of the above tests, a P value 0.05 was considered as significant. DISCLOSURES None. REFERENCES 1. Myers BD: Cyclosporine nephrotoxicity. Kidney Int 30: , Remuzzi G, Bertani T: Renal vascular and thrombotic effects of cyclosporine. Am J Kidney Dis 13: , Bennett WM, Houghton DC, Buss WC: Cyclosporine-induced renal dysfunction: Correlations between cellular events and whole kidney function. J Am Soc Nephrol 1: , Nankivell BJ, Borrows RJ, Fung CL, O Connell PJ, Allen RD, Chapman JR: The natural history of chronic allograft nephropathy. N Engl J Med 349: , Ducloux D, Fournier V, Bresson-Vautrin C, Rebibou JM, Billerey C, Saint-Hiller Y, Chalpoin JM: Mycophenolate mofetil in renal transplant recipients with cyclosporine-associated nephrotoxicity: A preliminary report. Transplantation 65: , Hueso M, Bover J, Seron D, Gil-Vernet S, Sabate I, Fulladosa X, Ramos R, Coll O, Alsina J, Grynio JM: Low-dose cyclosporine and mycophenolate mofetil in renal allograft recipients with suboptimal renal function. Transplantation 66: , Keunecke C, Rothenpieler U, Zanker B, Schneeberger H, Illner WD, Theodorakis J, Stangl M, Land W: Mycophenolate mofetil monotherapy: an example of a safe nephrotoxicity/atherogenicity-free immunosuppressive maintenance regimen in a selected group of kidneytransplanted patients. Transplant Proc 32[Suppl]: S6 S8, Schrama YC, Joles JA, van Tol A, Boer P, Koomans HA, Hene RJ: Conversion to mycophenolate mofetil in conjunction with stepwise withdrawal of cyclosporine in stable renal transplant recipients. Transplantation 69: , Vincenti F, Ramos E, Brattstrom C, Cho S, Ekberg H, Grinyo J, Johnson R, Kuypers D, Stuart F, Khanna A, Navarro M, Nashan B: Multicenter trial exploring calcineurin inhibitors avoidance in renal transplantation. Transplantation 71: , Tran HT, Acharya MK, McKay DB, Sayegh MH, Carpenter CB, Auchincloss HJR, Kirkman RL, Milford EL: Avoidance of cyclosporine in renal transplantation: Effects of daclizumab, mycophenolate mofetil, and steroids. J Am Soc Nephrol 11: , Groth CG, Backman L, Morales JM: Sirolimus (rapamycin)-based therapy in human renal transplantation: similar efficacy and different toxicity compared with cyclosporine: Sirolimus European Renal Transplant Study Group. Transplantation 67: , Kreis H, Cisterne JM, Land W: Sirolimus in association with mycophenolate mofetil induction for the prevention of acute graft rejection in renal allograft recipients. Transplantation 69: , Flechner SM, Goldfarb D, Modlin C, Feng J, Krishnamurthi V, Mastorianni B, Savas K, Cook DJ, Novick AC: Kidney transplantation without calcineurin inhibitor drugs: A prospective randomized J Am Soc Nephrol :, 2008 Long-term CNI-free Regimen 7

8 CLINICAL RESEARCH trial of sirolimus versus cyclosporine. Transplantation 74: , Hamdy AF, El-Agroudy A, Bakr MA, Mostafa A, El-baz M, El-Shahawy M, Ghoneim MA: Comparison of sirolimus with low-dose tacrolimus versus sirolimus-based calcineurin inhibitor-free regimen in live donor renal transplantation. Am J Transplant 5: , Meier-Kriesche HU, Li S, Gruessner RW, Fung JJ, Bustami RT, Barr ML, Leichtman AB: Immunosuppression: Evolution in practice and trends, Am J Transplant 6: , Flechner S, Goldfarb D, Solez K, Modlin C, Mastroianni B, Savas K, Babineau D, Kurian S, Salomon D, Novick A, Cook DJ: Kidney transplantation with sirolimus and mycophenolate mofetil-based immunosuppression: 5-year results of a randomized prospective trial compared to calcineurin inhibitor drugs. Transplantation 83: , Diekmann F, Gutierrez-Dalmau A, Lopez S, Cofan F, Esforzado N, Ricart MJ, Rossich E, Saval N, Torregrosa J, Oppenheimer F, Campistol JM: Influence of sirolimus on proteinuria in de novo kidney transplantation with expanded criteria donors: Comparison of two CNI-free protocols. Nephrol Dial Transplant 22: , Stephany B, Augustine J, Krishnamurthi V, Goldfarb D, Flechner S, Braun W, Hricik D, Dennis V, Poggio E: Differences in proteinuria and graft function in de novo sirolimus-based vs. calcineurin inhibitorbased immunosuppression in live donor kidney transplantation. Transplantation 82: , Hricik DE, Anton HA, Knauss TC, Rodriguez V, Seaman D, Siegel C, Valente J, Schulak JA: Outcomes of African American kidney transplant recipients treated with sirolimus, tacrolimus and corticosteroids. Transplantation 74: , Lo A, Egidi MF, Gaber L, Amiri H, Vera S, Nezakatgoo N, Gaber O: Comparison of sirolimus-based calcineurin inhibitor-sparing and calcineurin inhibitor-free regimens in cadaveric renal transplantation. Transplantation 77: , Larson TS, Dean PG, Stegall MD, Griffin MD, Textor SC, Schwab TR, Gloor JM, Cosio FG, Lund WJ, Kremers WK, Nyberg SL, Ishitani MB, Prieto M, Velosa JA: Complete avoidance of calcineurin inhibitors in renal transplantation: A randomized trial comparing sirolimus and tacrolimus. Am J Transplant 6: , Klein IH, Abrahams A, van Ede T, Hene RJ, Koomans HA, Ligtenberg G: Different effects of tacrolimus and cyclosporine on renal hemodynamics and blood pressure in healthy subjects. Transplantation 73: , National Kidney Foundation: K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification and stratification. Am J Kidney Dis 39[Suppl 1]: S1 S266, Isoniemi HM, Krogerus I, Von Willebrand E, Taskinen E, Ahonen J, Hayry P: Histopathological findings in well-functioning, long term renal allografts. Kidney Int 41: , El-Agroudy A, Refaie A, Moussa O, Ghoneim M: Tuberculosis in Egyptian kidney transplant recipients: Study of clinical course and outcome. J Nephrol 16: , Luan FL, Hojo M, Maluccio M, Yamaji K, Suthanthiran M: Rapamycin blocks tumour progression: Unlinking immunosuppression from antitumour efficacy. Transplantation 73: , Wilson DH, Book B, Brunet M, Engelmayer J, Gaulier JM, Luthe H, Marquet P, Moscato D, Mosso R, Oellerich M, Pescovitz M, Ramanathan L, Schmid R, Stickle D, Sarkozi L, Wallemacq P: Multicenter evaluation of an immunoassay for the measurement of sirolimus on the Abbott IMx analyzer. Transplantation 78[Suppl 1]: , Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ: The Seventh Report Joint National Committee on Prevention, Detection Evaluation and Treatment of High Blood Pressure: The JNC 7 Report. JAMA 289: , Cockroft DW, Gault MH: Prediction of creatinine clearance from serum creatinine. Nephron 16: , Racusen L, Solez K, Colvin R, Bonsib SM, Castro MC, Racusen LC, Solez K, Colvin RB, Bonsib SM, Castro MC, Cavallo T, Croker BP, Demetris AJ, Drachenberg CB, Fogo AB, Furness P, Gaber LW, Gibson IW, Glotz D, Goldberg JC, Grande J, Halloran PF, Hansen HE, Hartley B, Hayry PJ, Hill CM, Hoffman EO, Hunsicker LG, Lindblad AS, Yamaguchi Y: The Banff 97 working classification of renal allograft pathology. Kidney Int 55: , Kaplan EL, Meier P: Non parametric estimation from incomplete observation. J Am Stat Assoc 53: , Peto R, Peto J: Asymptotically efficient rank invariant test procedures. J R Stat Soc 135: , Journal of the American Society of Nephrology J Am Soc Nephrol :, 2008

SELECTED ABSTRACTS. All (n) % 3-year GS 88% 82% 86% 85% 88% 80% % 3-year DC-GS 95% 87% 94% 89% 96% 80%

SELECTED ABSTRACTS. All (n) % 3-year GS 88% 82% 86% 85% 88% 80% % 3-year DC-GS 95% 87% 94% 89% 96% 80% SELECTED ABSTRACTS The following are summaries of selected posters presented at the American Transplant Congress on May 5 9, 2007, in San Humar A, Gillingham KJ, Payne WD, et al. Review of >1000 kidney

More information

Literature Review: Transplantation July 2010-June 2011

Literature Review: Transplantation July 2010-June 2011 Literature Review: Transplantation July 2010-June 2011 James Cooper, MD Assistant Professor, Kidney and Pancreas Transplant Program, Renal Division, UC Denver Kidney Transplant Top 10 List: July Kidney

More information

Controversies in Renal Transplantation. The Controversial Questions. Patrick M. Klem, PharmD, BCPS University of Colorado Hospital

Controversies in Renal Transplantation. The Controversial Questions. Patrick M. Klem, PharmD, BCPS University of Colorado Hospital Controversies in Renal Transplantation Patrick M. Klem, PharmD, BCPS University of Colorado Hospital The Controversial Questions Are newer immunosuppressants improving patient outcomes? Are corticosteroids

More information

Intruduction PSI MODE OF ACTION AND PHARMACOKINETICS

Intruduction PSI MODE OF ACTION AND PHARMACOKINETICS Multidisciplinary Insights on Clinical Guidance for the Use of Proliferation Signal Inhibitors in Heart Transplantation Andreas Zuckermann, MD et al. Department of Cardio-Thoracic Surgery, Medical University

More information

Sirolimus versus Calcineurin Inhibitor-based Immunosuppressive Therapy in Kidney Transplantation A 4-year Follow-up

Sirolimus versus Calcineurin Inhibitor-based Immunosuppressive Therapy in Kidney Transplantation A 4-year Follow-up Transplantation Sirolimus versus Calcineurin Inhibitor-based Immunosuppressive Therapy in Kidney Transplantation A 4-year Follow-up Mohsen Nafar, 1 Behrang Alipour, 2 Pedram Ahmadpoor, 1 Fatemeh Pour-Reza-Gholi,

More information

Literature Review Transplantation

Literature Review Transplantation Literature Review 2010- Transplantation Alexander Wiseman, M.D. Associate Professor, Division of Renal Diseases and Hypertension Medical Director, Kidney and Pancreas Transplant Programs University of

More information

Proteinuria and Mammalian Target of Rapamycin Inhibitors in Renal Transplantation

Proteinuria and Mammalian Target of Rapamycin Inhibitors in Renal Transplantation Trends Fritz in Transplant. Diekmann: 2011;5:139-43 Proteinuria and Mammalian Target of Rapamycin Inhibitors in Renal Transplantation Proteinuria and Mammalian Target of Rapamycin Inhibitors in Renal Transplantation

More information

Emerging Drug List EVEROLIMUS

Emerging Drug List EVEROLIMUS Generic (Trade Name): Manufacturer: Everolimus (Certican ) Novartis Pharmaceuticals NO. 57 MAY 2004 Indication: Current Regulatory Status: Description: Current Treatment: Cost: Evidence: For use with cyclosporine

More information

James E. Cooper, M.D. Assistant Professor, University of Colorado at Denver Division of Renal Disease and Hypertension, Kidney and PancreasTransplant

James E. Cooper, M.D. Assistant Professor, University of Colorado at Denver Division of Renal Disease and Hypertension, Kidney and PancreasTransplant James E. Cooper, M.D. Assistant Professor, University of Colorado at Denver Division of Renal Disease and Hypertension, Kidney and PancreasTransplant Program Has no real or apparent conflicts of interest

More information

Immunosuppression is now manageable in the

Immunosuppression is now manageable in the EVOLVING STRATEGIES FOR IMMUNOSUPPRESSION IN RENAL TRANSPLANTATION: A REVIEW OF RECENT CLINICAL TRIALS* Stephen J. Tomlanovich, MD, Thomas C. Pearson, MD, DPhil, and Lorenzo Gallon, MD ABSTRACT When using

More information

Increased Early Rejection Rate after Conversion from Tacrolimus in Kidney and Pancreas Transplantation

Increased Early Rejection Rate after Conversion from Tacrolimus in Kidney and Pancreas Transplantation Increased Early Rejection Rate after Conversion from Tacrolimus in Kidney and Pancreas Transplantation Gary W Barone 1, Beverley L Ketel 1, Sameh R Abul-Ezz 2, Meredith L Lightfoot 1 1 Department of Surgery

More information

Impact of Subclinical Rejection on Transplantation

Impact of Subclinical Rejection on Transplantation Trends in Transplantation 2007;1:56-60 Impact of Subclinical Rejection on Transplantation David N. Rush for the Winnipeg Transplant Group Transplant Manitoba Adult Kidney Program, University of Manitoba,

More information

Steroid Minimization: Great Idea or Silly Move?

Steroid Minimization: Great Idea or Silly Move? Steroid Minimization: Great Idea or Silly Move? Disclosures I have financial relationship(s) within the last 12 months relevant to my presentation with: Astellas Grants ** Bristol Myers Squibb Grants,

More information

Kidney Allograft Fibrosis and Atrophy Early After Living Donor Transplantation

Kidney Allograft Fibrosis and Atrophy Early After Living Donor Transplantation American Journal of Transplantation 2005; 5: 1130 1136 Blackwell Munksgaard Copyright C Blackwell Munksgaard 2005 doi: 10.1111/j.1600-6143.2005.00811.x Kidney Allograft Fibrosis and Atrophy Early After

More information

BK virus infection in renal transplant recipients: single centre experience. Dr Wong Lok Yan Ivy

BK virus infection in renal transplant recipients: single centre experience. Dr Wong Lok Yan Ivy BK virus infection in renal transplant recipients: single centre experience Dr Wong Lok Yan Ivy Background BK virus nephropathy (BKVN) has emerged as an important cause of renal graft dysfunction in recent

More information

Case Report Beneficial Effect of Conversion to Belatacept in Kidney-Transplant Patients with a Low Glomerular-Filtration Rate

Case Report Beneficial Effect of Conversion to Belatacept in Kidney-Transplant Patients with a Low Glomerular-Filtration Rate Case Reports in Transplantation, Article ID 190516, 4 pages http://dx.doi.org/10.1155/2014/190516 Case Report Beneficial Effect of Conversion to Belatacept in Kidney-Transplant Patients with a Low Glomerular-Filtration

More information

Efficacy and Safety of Thymoglobulin and Basiliximab in Kidney Transplant Patients at High Risk for Acute Rejection and Delayed Graft Function

Efficacy and Safety of Thymoglobulin and Basiliximab in Kidney Transplant Patients at High Risk for Acute Rejection and Delayed Graft Function ArtIcle Efficacy and Safety of Thymoglobulin and Basiliximab in Kidney Transplant Patients at High Risk for Acute Rejection and Delayed Graft Function Guodong Chen, 1 Jingli Gu, 2 Jiang Qiu, 1 Changxi

More information

Overview of New Approaches to Immunosuppression in Renal Transplantation

Overview of New Approaches to Immunosuppression in Renal Transplantation Overview of New Approaches to Immunosuppression in Renal Transplantation Ron Shapiro, M.D. Professor of Surgery Surgical Director, Kidney/Pancreas Transplant Program Recanati/Miller Transplantation Institute

More information

Chronic Allograft Nephropathy Score Before Sirolimus Rescue Predicts Allograft Function in Renal Transplant Patients

Chronic Allograft Nephropathy Score Before Sirolimus Rescue Predicts Allograft Function in Renal Transplant Patients \, \ / 'v\ ELSEVIER Chronic Allograft Nephropathy Score Before Sirolimus Rescue Predicts Allograft Function in Renal Transplant Patients A. Basu, J.L. Falcone, H.P. Tan, D. Hassan, I. Dvorchik, K. Bahri,

More information

2017 CST-Astellas Canadian Transplant Fellows Symposium. Management of Renal Dysfunction in Extra Renal Transplants

2017 CST-Astellas Canadian Transplant Fellows Symposium. Management of Renal Dysfunction in Extra Renal Transplants 2017 CST-Astellas Canadian Transplant Fellows Symposium Management of Renal Dysfunction in Extra Renal Transplants Jeffrey Schiff, MD Dr. Jeffrey Schiff is an Assistant Professor of Medicine at the University

More information

Recognition and Treatment of Chronic Allograft Dysfunction

Recognition and Treatment of Chronic Allograft Dysfunction Recognition and Treatment of Chronic Allograft Dysfunction Alexander Wiseman, M.D. Associate Professor, Division of Renal Diseases and Hypertension Medical Director, Kidney and Pancreas Transplant Programs

More information

Long-term prognosis of BK virus-associated nephropathy in kidney transplant recipients

Long-term prognosis of BK virus-associated nephropathy in kidney transplant recipients Original Article Kidney Res Clin Pract 37:167-173, 2018(2) pissn: 2211-9132 eissn: 2211-9140 https://doi.org/10.23876/j.krcp.2018.37.2.167 KIDNEY RESEARCH AND CLINICAL PRACTICE Long-term prognosis of BK

More information

OUT OF DATE. Choice of calcineurin inhibitors in adult renal transplantation: Effects on transplant outcomes

OUT OF DATE. Choice of calcineurin inhibitors in adult renal transplantation: Effects on transplant outcomes nep_734.fm Page 88 Friday, January 26, 2007 6:47 PM Blackwell Publishing AsiaMelbourne, AustraliaNEPNephrology1320-5358 2006 The Author; Journal compilation 2006 Asian Pacific Society of Nephrology? 200712S18897MiscellaneousCalcineurin

More information

For Immediate Release Contacts: Jenny Keeney Astellas US LLC (847)

For Immediate Release Contacts: Jenny Keeney Astellas US LLC (847) For Immediate Release Contacts: Jenny Keeney Astellas US LLC (847) 317-5405 Lauren McDonnell GolinHarris (312) 729-4233 ASTELLAS RECEIVES FDA APPROVAL FOR USE OF PROGRAF (TACROLIMUS) IN CONJUNCTION WITH

More information

Considering the early proactive switch from a CNI to an mtor-inhibitor (Case: Male, age 34) Josep M. Campistol

Considering the early proactive switch from a CNI to an mtor-inhibitor (Case: Male, age 34) Josep M. Campistol Considering the early proactive switch from a CNI to an mtor-inhibitor (Case: Male, age 34) Josep M. Campistol Patient details Name DOB ESRD Other history Mr. B.I.B. 12 January 1975 (34yo) Membranous GN

More information

Date: 23 June Context and policy issues:

Date: 23 June Context and policy issues: Title: Basiliximab for Immunosuppression During a Calcineurin Inhibitor Holiday in Renal Transplant Patients with Acute Renal Dysfunction: Guidelines for Use and a Clinical and Cost-Effectiveness Review

More information

CKD in Other Organ Transplants

CKD in Other Organ Transplants CKD in Other Organ Transplants Alexander Wiseman, M.D. Associate Professor, Division of Renal Diseases and Hypertension Medical Director, Kidney and Pancreas Transplant Programs University of Colorado

More information

Kidneytransplant pathologyrelatedto immunosuppressiveagents

Kidneytransplant pathologyrelatedto immunosuppressiveagents Kidneytransplant pathologyrelatedto immunosuppressiveagents Helmut Hopfer Pathologie Women, 53 years old. 16 months after kidney transplantation for diabetic nephropathy. Metabolicsyndromeandcoronaryheartdisease.

More information

NAPRTCS Annual Transplant Report

NAPRTCS Annual Transplant Report North American Pediatric Renal Trials and Collaborative Studies NAPRTCS 2010 Annual Transplant Report This is a privileged communication not for publication. TABLE OF CONTENTS PAGE I INTRODUCTION 1 II

More information

NAPRTCS Annual Transplant Report

NAPRTCS Annual Transplant Report North American Pediatric Renal Trials and Collaborative Studies NAPRTCS 2014 Annual Transplant Report This is a privileged communication not for publication. TABLE OF CONTENTS PAGE II TRANSPLANTATION Section

More information

Early Conversion from a Calcineurin Inhibitor-Based Regimen to Everolimus-Based Immunosuppression after Kidney Transplantation

Early Conversion from a Calcineurin Inhibitor-Based Regimen to Everolimus-Based Immunosuppression after Kidney Transplantation Trends in Transplantation Transplant. 2012;6:28-33 Early Conversion from a Calcineurin Inhibitor-Based Regimen to Everolimus-Based Immunosuppression after Kidney Transplantation Hallvard Holdaas Department

More information

Conversion from calcineurin inhibitors to sirolimus in renal transplant patients

Conversion from calcineurin inhibitors to sirolimus in renal transplant patients ORIGINAL ARTICLE Port J Nephrol Hypert 2008; 22(1): 43-48 Conversion from calcineurin inhibitors to sirolimus in renal transplant patients Unidade de Transplantação Renal. Serviço de Nefrologia. Hospital

More information

Practical considerations for the use of mtor inhibitors

Practical considerations for the use of mtor inhibitors Diekmann and Campistol Transplantation Research 2015, 4(Suppl 1):5 DOI 10.1186/s13737-015-0029-5 TRANSPLANTATION RESEARCH REVIEW Practical considerations for the use of mtor inhibitors Fritz Diekmann 1,2*

More information

American Journal of Transplantation 2009; 9 (Suppl 3): S1 S157 Wiley Periodicals Inc.

American Journal of Transplantation 2009; 9 (Suppl 3): S1 S157 Wiley Periodicals Inc. American Journal of Transplantation 2009; 9 (Suppl 3): S1 S157 Wiley Periodicals Inc. 2009 The Authors Journal compilation 2009 The American Society of Transplantation and the American Society of Transplant

More information

Pharmacology notes Interleukin-2 receptor-blocking monoclonal antibodies: evaluation of 2 new agents

Pharmacology notes Interleukin-2 receptor-blocking monoclonal antibodies: evaluation of 2 new agents BUMC Proceedings 1999;12:110-112 Pharmacology notes Interleukin-2 receptor-blocking monoclonal antibodies: evaluation of 2 new agents CHERYLE GURK-TURNER, RPH Department of Pharmacy Services, BUMC wo mouse/human

More information

General Introduction. 1 general introduction 13

General Introduction. 1 general introduction 13 General Introduction In The Netherlands 13,000 patients suffer from end stage renal disease (ESRD), which left untreated inevitably results in death. Every year this number increases with approximately

More information

Chapter 6: Transplantation

Chapter 6: Transplantation Chapter 6: Transplantation Introduction During calendar year 2012, 17,305 kidney transplants, including kidney-alone and kidney plus at least one additional organ, were performed in the United States.

More information

Use of mycophenolate mofetil in steroid-dependent and -resistant nephrotic syndrome

Use of mycophenolate mofetil in steroid-dependent and -resistant nephrotic syndrome Pediatr Nephrol (2003) 18:833 837 DOI 10.1007/s00467-003-1175-4 BRIEF REPORT Gina-Marie Barletta William E. Smoyer Timothy E. Bunchman Joseph T. Flynn David B. Kershaw Use of mycophenolate mofetil in steroid-dependent

More information

Immunopathology of T cell mediated rejection

Immunopathology of T cell mediated rejection Immunopathology of T cell mediated rejection Ibrahim Batal MD Columbia University College of Physicians & Surgeons New York, NY, USA Overview Pathophysiology and grading of TCMR TCMR is still a significant

More information

Recurrent Idiopathic Membranous Glomerulonephritis After Kidney Transplantation and Successful Treatment With Rituximab

Recurrent Idiopathic Membranous Glomerulonephritis After Kidney Transplantation and Successful Treatment With Rituximab TRANSPLANTATION Recurrent Idiopathic Membranous Glomerulonephritis After Kidney Transplantation and Successful Treatment With Rituximab Khadijeh Makhdoomi, 1,2 Saeed Abkhiz, 1,2 Farahnaz Noroozinia, 1,3

More information

How do the KDIGO Clinical Practice Guidelines on the Care of Kidney Transplant Recipients apply to the UK?

How do the KDIGO Clinical Practice Guidelines on the Care of Kidney Transplant Recipients apply to the UK? How do the KDIGO Clinical Practice Guidelines on the Care of Kidney Transplant Recipients apply to the UK? Dr Richard Baker & Professor Alan Jardine, co-authors, forthcoming Renal Association module on

More information

Post Transplant Immunosuppression: Consideration for Primary Care. Sameh Abul-Ezz, M.D., Dr.P.H.

Post Transplant Immunosuppression: Consideration for Primary Care. Sameh Abul-Ezz, M.D., Dr.P.H. Post Transplant Immunosuppression: Consideration for Primary Care Sameh Abul-Ezz, M.D., Dr.P.H. Objectives Discuss the commonly used immunosuppressive medications and what you need to know to care for

More information

REACH Risk Evaluation to Achieve Cardiovascular Health

REACH Risk Evaluation to Achieve Cardiovascular Health Dyslipidemia and transplantation History: An 8-year-old boy presented with generalized edema and hypertension. A renal biopsy confirmed a diagnosis of focal segmental glomerulosclerosis (FSGS). After his

More information

The legally binding text is the original French version TRANSPARENCY COMMITTEE OPINION. 30 November 2011

The legally binding text is the original French version TRANSPARENCY COMMITTEE OPINION. 30 November 2011 The legally binding text is the original French version TRANSPARENCY COMMITTEE OPINION 30 November 2011 NULOJIX 250 mg, powder for concentrate for solution for infusion B/1 (CIP code: 580 415-7) B/2 (CIP

More information

Combination of a Calcineurin Inhibitor and a Mammalian Target of Rapamycin Inhibitor: Not So Nephrotoxic As We Thought?

Combination of a Calcineurin Inhibitor and a Mammalian Target of Rapamycin Inhibitor: Not So Nephrotoxic As We Thought? Trends in Transplant. 2011;5:49-56Helio Tedesco Silva Junior: Calcineurin and mtor inhibitor nephrotoxicity Combination of a Calcineurin Inhibitor and a Mammalian Target of Rapamycin Inhibitor: Not So

More information

Cover Page. The handle holds various files of this Leiden University dissertation.

Cover Page. The handle   holds various files of this Leiden University dissertation. Cover Page The handle http://hdl.handle.net/1887/29755 holds various files of this Leiden University dissertation. Author: Moes, Dirk Jan Alie Roelof Title: Optimizing immunosuppression with mtor inhibitors

More information

Chapter 6: Idiopathic focal segmental glomerulosclerosis in adults Kidney International Supplements (2012) 2, ; doi: /kisup.2012.

Chapter 6: Idiopathic focal segmental glomerulosclerosis in adults Kidney International Supplements (2012) 2, ; doi: /kisup.2012. http://www.kidney-international.org chapter 6 & 2012 KDIGO Chapter 6: Idiopathic focal segmental glomerulosclerosis in adults Kidney International Supplements (2012) 2, 181 185; doi:10.1038/kisup.2012.19

More information

clevelandclinic.org/transplant

clevelandclinic.org/transplant carolyn spiotta Pancreas/Kidney Transplant Recipient I feel so fortunate and thankful that I have received a second chance at life. Carolyn Spiotta, 44, Pittsburgh. Carolyn needed a new pancreas and kidney

More information

Risk factors associated with the deterioration of renal function after kidney transplantation

Risk factors associated with the deterioration of renal function after kidney transplantation Kidney International, Vol. 68, Supplement 99 (2005), pp. S113 S117 Risk factors associated with the deterioration of renal function after kidney transplantation DANIEL SERÓN, XAVIER FULLADOSA, and FRANCESC

More information

Analytical Methods: the Kidney Early Evaluation Program (KEEP) The Kidney Early Evaluation program (KEEP) is a free, community based health

Analytical Methods: the Kidney Early Evaluation Program (KEEP) The Kidney Early Evaluation program (KEEP) is a free, community based health Analytical Methods: the Kidney Early Evaluation Program (KEEP) 2000 2006 Database Design and Study Participants The Kidney Early Evaluation program (KEEP) is a free, community based health screening program

More information

Chapter 4: Steroid-resistant nephrotic syndrome in children Kidney International Supplements (2012) 2, ; doi: /kisup.2012.

Chapter 4: Steroid-resistant nephrotic syndrome in children Kidney International Supplements (2012) 2, ; doi: /kisup.2012. http://www.kidney-international.org & 2012 KDIGO Chapter 4: Steroid-resistant nephrotic syndrome in children Kidney International Supplements (2012) 2, 172 176; doi:10.1038/kisup.2012.17 INTRODUCTION This

More information

Immunosuppressants. Assistant Prof. Dr. Najlaa Saadi PhD Pharmacology Faculty of Pharmacy University of Philadelphia

Immunosuppressants. Assistant Prof. Dr. Najlaa Saadi PhD Pharmacology Faculty of Pharmacy University of Philadelphia Immunosuppressants Assistant Prof. Dr. Najlaa Saadi PhD Pharmacology Faculty of Pharmacy University of Philadelphia Immunosuppressive Agents Very useful in minimizing the occurrence of exaggerated or inappropriate

More information

Why Do We Need New Immunosuppressive Agents

Why Do We Need New Immunosuppressive Agents Why Do We Need New Immunosuppressive Agents 1 Reducing acute rejection rates has not transplanted into better long-term graft survival Incidence of early acute rejection episodes by era Relative risk for

More information

The Histology of Solitary Renal Allografts at 1 and 5 Years After Transplantation

The Histology of Solitary Renal Allografts at 1 and 5 Years After Transplantation American Journal of Transplantation 2011; 11: 698 707 Wiley Periodicals Inc. C 2010 CSIRO C 2010 The Authors Journal compilation C 2010 The American Society of Transplantation and the American Society

More information

Original Article. Introduction

Original Article. Introduction Nephrol Dial Transplant (26) 21: 3252 3257 doi:1.193/ndt/gfl447 Advance Access publication 5 September 26 Original Article of proteinuria after conversion from calcineurin inhibitor to sirolimus-based

More information

CHAPTER 14. Renal Transplantation

CHAPTER 14. Renal Transplantation 15th Report of the Malaysian RENAL TRANSPLANTATION CHAPTER 14 Renal Transplantation Editor: Dr. Goh Bak Leong Expert Panel: : Dato Dr. Dato Zaki Dr. Morad Zaik Morad Mohd (Chair) Zaher (Chair) Dr. Goh

More information

Chronic Kidney Disease & Transplantation. Paediatrics : 2004 FRACP

Chronic Kidney Disease & Transplantation. Paediatrics : 2004 FRACP Chronic Kidney Disease & Transplantation Paediatrics : 2004 FRACP ANZDATA Registry Mode of First Treatment - Paediatric 14 12 10 8 6 4 2 0 0-4 y 5-9 y 10-14 y 15-19 y Hospital CAPD Hospital HD Hospital

More information

Better than Google- Click on Immunosuppression Renal Transplant. David Landsberg Oct

Better than Google- Click on Immunosuppression Renal Transplant. David Landsberg Oct Better than Google- Click on Immunosuppression Renal Transplant David Landsberg Oct 3 2008 OUTLINE History of Immunosuppression Trends in Immunosupression FK vs CYA Steroid Minimization CNI Avoidance Sirolimus

More information

Special Challenges and Co-Morbidities

Special Challenges and Co-Morbidities Special Challenges and Co-Morbidities Renal Disease/ Hypertension/ Diabetes in African-Americans M. Keith Rawlings, MD Medical Director Peabody Health Center AIDS Arms, Inc Dallas, TX Chair, Internal Medicine

More information

CHAPTER 5 RENAL TRANSPLANTATION. Editor: Dr Goh Bak Leong

CHAPTER 5 RENAL TRANSPLANTATION. Editor: Dr Goh Bak Leong CHAPTER 5 RENAL TRANSPLANTATION Editor: Dr Goh Bak Leong Expert Panel: Dr Goh Bak Leong (Chair) Dato Dr (Mr) Rohan Malek Dr Wong Hin Seng Dr Fan Kin Sing Dr Rosnawati Yahya Dr S Prasad Menon Dr Tan Si

More information

Effect of long-term steroid withdrawal in renal transplant recipients: a retrospective cohort study

Effect of long-term steroid withdrawal in renal transplant recipients: a retrospective cohort study NDT Plus (2010) 3 [Suppl 2]: ii32 ii36 doi: 10.1093/ndtplus/sfq064 Effect of long-term steroid withdrawal in renal transplant recipients: a retrospective cohort study Miguel Gonzalez-Molina 1, Miguel Angel

More information

Serum samples from recipients were obtained within 48 hours before transplantation. Pre-transplant

Serum samples from recipients were obtained within 48 hours before transplantation. Pre-transplant SDC, Patients and Methods Complement-dependent lymphocytotoxic crossmatch test () Serum samples from recipients were obtained within 48 hours before transplantation. Pre-transplant donor-specific CXM was

More information

Victims of success: Do we still need clinical trials? Robert S. Gaston, MD CTI Clinical Trials and Consulting University of Alabama at Birmingham

Victims of success: Do we still need clinical trials? Robert S. Gaston, MD CTI Clinical Trials and Consulting University of Alabama at Birmingham Victims of success: Do we still need clinical trials? Robert S. Gaston, MD CTI Clinical Trials and Consulting University of Alabama at Birmingham Disclosure Employee: CTI Clinical Trials and Consulting

More information

Case Presentation Turki Al-Hussain, MD

Case Presentation Turki Al-Hussain, MD Case Presentation Turki Al-Hussain, MD Director, Renal Pathology Chapter Saudi Society of Nephrology & Transplantation Consultant Nephropathologist & Urological Pathologist Department of Pathology & Laboratory

More information

New-onset diabetes after transplantation. Christophe Legendre Université Paris Descartes & Hôpital Necker, Paris.

New-onset diabetes after transplantation. Christophe Legendre Université Paris Descartes & Hôpital Necker, Paris. New-onset diabetes after transplantation Christophe Legendre Université Paris Descartes & Hôpital Necker, Paris. Actualités Jean Hamburger Paris, 23-24 avril 2012 NODAT IFG IGT CJ Yates et al, Am J Transplant

More information

Management of Rejection

Management of Rejection Management of Rejection I have no disclosures Disclosures (relevant or otherwise) Deborah B Adey, MD Professor of Medicine University of California, San Francisco Kidney and Pancreas Transplant Center

More information

Cover Page. The handle holds various files of this Leiden University dissertation.

Cover Page. The handle   holds various files of this Leiden University dissertation. Cover Page The handle http://hdl.handle.net/1887/29755 holds various files of this Leiden University dissertation. Author: Moes, Dirk Jan Alie Roelof Title: Optimizing immunosuppression with mtor inhibitors

More information

Belatacept: An Update of Ongoing Clinical Trials

Belatacept: An Update of Ongoing Clinical Trials Belatacept: An Update of Ongoing Clinical Trials Michael D. Rizzari, MD University of Wisconsin Madison School of Medicine and Public Health, Madison, Wisconsin Abstract Belatacept is a fusion protein

More information

CHAPTER 5 RENAL TRANSPLANTATION. Editor: Dr Goh Bak Leong

CHAPTER 5 RENAL TRANSPLANTATION. Editor: Dr Goh Bak Leong CHAPTER 5 RENAL TRANSPLANTATION Editor: Dr Goh Bak Leong Expert Panel: Dr Goh Bak Leong (Chair) Dato Dr Zaki Morad Mohd Zaher Dato Dr (Mr) Rohan Malek Dr Fan Kin Sing Dr Lily Mushahar Dr Lim Soo Kun Dr

More information

ATHLETES & PRESCRIBING PHYSICIANS PLEASE READ

ATHLETES & PRESCRIBING PHYSICIANS PLEASE READ ATHLETES & PRESCRIBING PHYSICIANS PLEASE READ USADA can grant a Therapeutic Use Exemption (TUE) in compliance with the World Anti- Doping Agency International Standard for TUEs. The TUE application process

More information

Clinical decisions regarding immunosuppressive

Clinical decisions regarding immunosuppressive PHARMACOLOGIC THERAPIES AND RATIONALES * Stuart D. Russell, MD ABSTRACT This article reviews evidence related to the use of induction therapy and longer-term combination immunosuppressive drug regimens

More information

Clinical Outcomes of Renal Transplantation in Hepatitis C Virus Positive Recipients

Clinical Outcomes of Renal Transplantation in Hepatitis C Virus Positive Recipients Original Research Article Clinical Outcomes of Renal Transplantation in Hepatitis C Virus Positive Recipients Surendran Sujit 1*, N. Gopalakrishnan 2 1 Assistant Professor, 2 Professor and Head Department

More information

How to improve long term outcome after liver transplantation?

How to improve long term outcome after liver transplantation? How to improve long term outcome after liver transplantation? François Durand Hepatology & Liver Intensive Care University Paris Diderot INSERM U1149 Hôpital Beaujon, Clichy PHC 2018 www.aphc.info Long

More information

OBJECTIVES. Phases of Transplantation and Immunosuppression

OBJECTIVES. Phases of Transplantation and Immunosuppression Transplant and Immunosuppression: Texas Transplant Center April 29, 2017 Regina L. Ramirez, Pharm.D., BCPS PGY1 Pharmacy Residency Program Director Clinical Practice Specialist Solid Organ Transplant and

More information

Reduced graft function (with or without dialysis) vs immediate graft function a comparison of long-term renal allograft survival

Reduced graft function (with or without dialysis) vs immediate graft function a comparison of long-term renal allograft survival Nephrol Dial Transplant (2006) 21: 2270 2274 doi:10.1093/ndt/gfl103 Advance Access publication 22 May 2006 Original Article Reduced graft function (with or without dialysis) vs immediate graft function

More information

RENAL EVENING SPECIALTY CONFERENCE

RENAL EVENING SPECIALTY CONFERENCE RENAL EVENING SPECIALTY CONFERENCE Harsharan K. Singh, MD The University of North Carolina at Chapel Hill Disclosure of Relevant Financial Relationships No conflicts of interest to disclose. CLINICAL HISTORY

More information

Chronic Kidney Disease (CKD) Stages. CHRONIC KIDNEY DISEASE Treatment Options. Incident counts & adjusted rates, by primary diagnosis Figure 2.

Chronic Kidney Disease (CKD) Stages. CHRONIC KIDNEY DISEASE Treatment Options. Incident counts & adjusted rates, by primary diagnosis Figure 2. Chronic Kidney Disease (CKD) Stages Stage 1 GFR > 90 (evidence of renal disease) Stage 2 GFR 60-89 Stage 3 GFR 30-59 Stage 4 GFR 15-29 Stage 5 GFR

More information

Pleiotropic effects of mtor inhibitors : cardiovascular and cancer. Dr Paolo Malvezzi Clinique de Néphrologie CHU Grenoble

Pleiotropic effects of mtor inhibitors : cardiovascular and cancer. Dr Paolo Malvezzi Clinique de Néphrologie CHU Grenoble Pleiotropic effects of mtor inhibitors : cardiovascular and cancer Dr Paolo Malvezzi Clinique de Néphrologie CHU Grenoble Tehran August 2016 Why this topic? Since last year very little news in the immunosuppressive

More information

Summary of Results for Laypersons

Summary of Results for Laypersons What was the Study Called? Summary of Results for Laypersons A Multi-center, Randomized, Open-label, Pilot and Exploratory Study Investigating Safety and Efficacy in OPTIMIZEd Dosing of Advagraf Kidney

More information

European Risk Management Plan. Measures impairment. Retreatment after Discontinuation

European Risk Management Plan. Measures impairment. Retreatment after Discontinuation European Risk Management Plan Table 6.1.4-1: Safety Concern 55024.1 Summary of Risk Minimization Measures Routine Risk Minimization Measures Additional Risk Minimization Measures impairment. Retreatment

More information

The CARI Guidelines Caring for Australasians with Renal Impairment. Specific management of IgA nephropathy: role of steroid therapy GUIDELINES

The CARI Guidelines Caring for Australasians with Renal Impairment. Specific management of IgA nephropathy: role of steroid therapy GUIDELINES Specific management of IgA nephropathy: role of steroid therapy Date written: July 2005 Final submission: September 2005 Author: Merlin Thomas GUIDELINES Steroid therapy may protect against progressive

More information

Progress in Pediatric Kidney Transplantation

Progress in Pediatric Kidney Transplantation Send Orders for Reprints to reprints@benthamscience.net The Open Urology & Nephrology Journal, 214, 7, (Suppl 2: M2) 115-122 115 Progress in Pediatric Kidney Transplantation Jodi M. Smith *,1 and Vikas

More information

Are the current chronic allograft nephropathy grading systems sufficient to predict renal allograft survival?

Are the current chronic allograft nephropathy grading systems sufficient to predict renal allograft survival? Chronic Brazilian allograft Journal nephropathy of Medical and grading Biological system Research Online Ahead of Print ISSN 0100-879X Are the current chronic allograft nephropathy grading systems sufficient

More information

Ten-year outcomes in a randomized phase II study of kidney transplant recipients administered belatacept 4-weekly or 8-weekly

Ten-year outcomes in a randomized phase II study of kidney transplant recipients administered belatacept 4-weekly or 8-weekly Ten-year outcomes in a randomized phase II study of kidney transplant recipients administered belatacept 4-weekly or 8-weekly F. Vincenti, University of California, San Francisco G. Blancho, University

More information

Organ rejection is one of the serious

Organ rejection is one of the serious Original Article Outcomes of Late Corticosteroid Withdrawal after Renal Transplantation in Patients Exposed to Tacrolimus and/or Mycophenolate Mofetil: Meta-Analysis of Randomized Controlled Trials A.

More information

The Natural History of Chronic Allograft Nephropathy

The Natural History of Chronic Allograft Nephropathy The new england journal of medicine original article The Natural History of Chronic Allograft Nephropathy Brian J. Nankivell, M.D., Ph.D., Richard J. Borrows, M.B., B.Chir., Caroline L.-S. Fung, M.B.,

More information

Risk Factors in Long Term Immunosuppressive Use and Advagraf. Daniel Serón Nephrology department Hospital Universitari Vall d Hebron

Risk Factors in Long Term Immunosuppressive Use and Advagraf. Daniel Serón Nephrology department Hospital Universitari Vall d Hebron Risk Factors in Long Term Immunosuppressive Use and Advagraf Daniel Serón Nephrology department Hospital Universitari Vall d Hebron Progressive well defined diseases ABMR GN Polyoma Non-specific Findings

More information

Innovation In Transplantation:

Innovation In Transplantation: Innovation In Transplantation: Improving outcomes Thomas C. Pearson Department of Surgery Emory Transplant Center CHOA Symposium October 22, 2016 Disclosures Belatacept preclinical and clinical trial were

More information

Relationship between Post-kidney Transplantation Antithymocyte Globulin Therapy and Wound Healing Complications

Relationship between Post-kidney Transplantation Antithymocyte Globulin Therapy and Wound Healing Complications Original Article Relationship between Post-kidney Transplantation Antithymocyte Globulin Therapy and Wound Healing Complications G. R. Pourmand 1, S. Dehghani 1*, A. Saraji 1, S. Khaki 1,2, S. H. Mortazavi

More information

Low toxicity immunosuppressive protocols in renal transplantation. Ron Shapiro

Low toxicity immunosuppressive protocols in renal transplantation. Ron Shapiro LECTURE Low toxicity immunosuppressive protocols in renal transplantation Ron Shapiro Department of Surgery, Director, Renal Transplantation, Thomas E. Starzl, Transplantation Institute University of Pittsburgh,

More information

This study is currently recruiting participants.

This study is currently recruiting participants. A Two Part, Phase 1/2, Safety, PK and PD Study of TOL101, an Anti-TCR Monoclonal Antibody for Prophylaxis of Acute Organ Rejection in Patients Receiving Renal Transplantation This study is currently recruiting

More information

Additional file 2: Details of cohort studies and randomised trials

Additional file 2: Details of cohort studies and randomised trials Reference Randomised trials Ye et al. 2001 Abstract 274 R=1 WD=0 Design, numbers, treatments, duration Randomised open comparison of: (45 patients) 1.5 g for 3, 1 g for 3, then 0.5 to 0.75 g IV cyclophosphamide

More information

Transplantation: Year in Review

Transplantation: Year in Review Transplantation: Year in Review Alexander Wiseman, MD Medical Director, Kidney and Pancreas Transplant Program Associate Professor, Division of Renal Diseases and Hypertension University of Colorado Outline:

More information

RECURRENT AND DE NOVO RENAL DISEASES IN THE ALLOGRAFT. J. H. Helderman,MD,FACP,FAST

RECURRENT AND DE NOVO RENAL DISEASES IN THE ALLOGRAFT. J. H. Helderman,MD,FACP,FAST RECURRENT AND DE NOVO RENAL DISEASES IN THE ALLOGRAFT J. H. Helderman,MD,FACP,FAST Vanderbilt University Medical Center Professor of Medicine, Pathology and Immunology Medical Director, Vanderbilt Transplant

More information

Minimal change nephropathy: an update (for adults) Dr. CC Szeto Department of Medicine & Therapeutics The Chinese University of Hong Kong

Minimal change nephropathy: an update (for adults) Dr. CC Szeto Department of Medicine & Therapeutics The Chinese University of Hong Kong Minimal change nephropathy: an update (for adults) Dr. CC Szeto Department of Medicine & Therapeutics The Chinese University of Hong Kong First, it is not uncommon Cameron JS. Am J Kidney Dis 10: 157 171,

More information

CHAPTER 5 RENAL TRANSPLANTATION

CHAPTER 5 RENAL TRANSPLANTATION CHAPTER 5 RENAL TRANSPLANTATION Editor: Dr. Goh Bak Leong Expert Panel: Dato Dr. Zaki Morad b Mohd Zaher (Chair) Dr. Goh Bak Leong (Co-Chair) Dr. Fan Kin Sing Dr. Lily Mushahar Mr. Rohan Malek Dr. S. Prasad

More information

Utility of Urine Eosinophils in the Diagnosis of Acute Interstitial Nephritis

Utility of Urine Eosinophils in the Diagnosis of Acute Interstitial Nephritis Article Utility of Urine Eosinophils in the Diagnosis of Acute Interstitial Nephritis Angela K. Muriithi,* Samih H. Nasr, and Nelson Leung* Summary Background and objectives Urine eosinophils (UEs) have

More information

Sirolimus in Kidney Transplantation: A Pilot Study in Chinese Patients

Sirolimus in Kidney Transplantation: A Pilot Study in Chinese Patients Original Article Sirolimus in Kidney Transplantation: A Pilot Study in Chinese Patients Man-Fai Lam, Terence Pok-Siu Yip, Kai-Chung Tse, Fu-Keung Li, Sing-Leung Lui, Kar-Neng Lai, Tak-Mao Chan We conducted

More information

BK Virus (BKV) Management Guideline: July 2017

BK Virus (BKV) Management Guideline: July 2017 BK Virus (BKV) Management Guideline: July 2017 BK virus has up to a 60-80% seroprevalence rate in adults due to a primary oral or respiratory exposure in childhood. In the immumocompromised renal transplant

More information

Pathological back-ground of renal transplant pathology and important mile-stones of the Banff classification

Pathological back-ground of renal transplant pathology and important mile-stones of the Banff classification Banff 1 Banff Pathological back-ground of renal transplant pathology and important mile-stones of the Banff classification Department of Nephrology, Japanese Red Cross Nagoya Daini Hospital Morozumi Kunio,

More information