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Cyclosporine – A Withdrawal in renal transplantation
Indian J Transplant 2008; 2: 32-50
Everolimus and Low Dose Cyclosporine combination in DeNovo Kidney Transplant patients Sailaja, Sahariah. S, Umamaheshwar Rao. Ch
45 has allowed safe reduction in Cya dose with improved graft function. However, Optimization of the dosages and levels of Everolimus and Cya in our population needed further follow-up. Further Follow-up is needed for long term outcome.
Global Hospital and Organ Transplant Institute, Hyderabad
Everolimus is a semi synthetic Proliferation signal inhibitor, inhibits growth factor stimulated proliferation and prevents vascular remodeling, a key factor of progressive allograft dysfunction. The efficacy, tolerability and clinical information of Everolimus, low dose cyclosporine and Prednisolone combination in denovo kidney transplant patients in Indian population are limited. Here we present our experience on this ongoing, no comparative study on allograft function in renal transplant patients.
Cyclosporine - A Withdrawal in renal transplantation Lakshminarayana G, Rajesh R, G Background : Cyclosporine - A (Cys-A) is considered as short-term friend and long-term foe for renal allograft as it can cause nephrotoxicity and is implicated as a causative factor for chronic allograft nephropathy, which is a major cause for long-term graft loss.
Fifteen denovo kidney transplant recipients(7 cadaver and 8 live unrelated/related donors) age ranging from 21 to 51 years were enrolled in the study. Nine patients received Injection Daclizimab 50 mg in 2 doses on day 0 and 14 post operative day as induction therapy. All the patients received Everolimus 0. 5 mg B. D. Cya 100 mg B. D and Prednisolone 20 mg B. D as initial therapy. Cya was reduced to 50 mg B. D at the end of 3rd month maintaining the mean C2 levels ranging in between 600700 μg /ml. Prednisolone was tapered gradually. All the renal parameters, Everolimus, Cya levels, lipids and blood sugar levels were monitored at regular intervals.
Withdrawal of Cys-A and replacement with less nephrotoxic drugs may be a solution.
Patient and Graft survival was 100% after 6 months follow up. Adverse events noted in the study are delayed wound healing in 1 patient, acute rejection in 2 patients(13%), who responded well to the conservative treatment. 1 Patient developed PTDM. And a biopsy proven CNI toxicity noted in 1 patient with peak serum Creatnine reaching 2. 8 μg /ml. Hyperlipidimia was observed in 10 patients.
All 108 recipients received standard triple immunosupression (Cys-A, azathioprine, prednisolone) according to our standard protocol. Cys-A was withdrawn in 38 % in the first 6 (mean 4) months, 22 % at 6 – 10 months (mean 9) and in 40 % at more than 10 (mean 18) months after transplantation. All the early withdrawals were started on Sirolimus. Hirsutism (26 %) was the most common indication for Cys-A withdrawal followed by
The mean dose of Everolimus, Cya at 6 months is 0. 53±0. 11 mg BD and 109±25 mg/day. The mean serum Creatnine levels, Everolimus trough levels and Cya C2 levels at 6 months were 1. 5±0. 21, 6. 44±4. 2 μg /ml and 452±276 μg /ml respectively.
post-transplant diabetes (20 %), graft dysfunction (CysA toxicity or chronic allograft nephropathy) (20 %) and post-transplant erythrocytosis (PTE) (9 %); financial constraints or uncontrolled hypertension was the indication in the remaining patients. There was improvement in glycemic control, PTE, hypertension in all patients. Graft function (s. creatinine) improved after Cys-A withdrawal by 25 % in 20 % of recipients, < 25 % in 50 % recipients and no improvement was seen in the remaining 30 %. Acute rejection (AR) after Cys-A withdrawal was seen only in 3 patients within 12 weeks after withdrawal and another 4 patients had AR beyond 12 weeks. The incidence of AR was not related to the time of withdrawal; recipients with a better the HLA match had a lesser chance of rejection after stopping Cys-A.
The mean Creatnine clearance at the end of 6 months is 61. 6 ml/mins and 24 hr urinary protein level of 281. 7 mg/day which were improved when compared to 3rd month levels of 51. 5 ml/mt 388 mg/day respectively. There was gradual improvement in the GFR as reflected by CCT levels. Hyperlipidimia was controlled after treatment with statins.
Conclusion : This regime has proved to be effective in achieving good outcome with few side effects in denovo renal transplant patients including cadaver transplantation. Everolimus
Objective of the study: To study the Cys-A withdrawal patterns and its effects in renal allograft recipients at our center.
Methods : It is a retrospective study, which included 108 live related renal allograft recipients, in whom Cys-A was withdrawn with a follow-up period of 4 to 71 (mean 30) months.
Summary of results :
Conclusion : Most common indication for Cys-A withdrawal was Copyright © 2008 by The Indian Society of Organ Transplantation
46
Indian Journal of Transplantation
hirsutism. Significant improvement in glycemic control, PTE, hypertension and graft function was noted after Cys-A withdrawal. The incidence of AR was not related to the time of withdrawal. Hence patients may be considered for early (six months) Cys-A withdrawal & replacement with lesser nephrotoxic drugs.
Indian J Transplant 2008; 2: 32-50
Mycophenolate Versus Azathioprine as Primary Immunosuppression In Renal Transplantation - A Case Control Study Annapandian VM1, Basu G1, Neelakantan N2, Fleming DH3, Mathew BS3, Varughese S1, John GT1
Anemia in Renal Transplant Recipients Praveen Murlidharan, N K Hase, Arun Halankar
Departments of 1Nephrology, 2Biostatistics, 3Clinical Pharmacology. Christian Medical College, Vellore, India.
Registrar in Nephrology, Department of Nephrology, Seth GS Medical College & KEM Hospital
Aim :
Anemia, a potentially correctable cardiovascular risk factor, continues to be a major problem in kidneytransplant patients. The nature of post transplant anemia is multifactorial, and the prevalence and predictors of post transplant anemia vary between different studies. Awareness of factors associated with lower hemoglobin may prompt better anemia screening and management. We performed a retrospective analysis of 100 consecutive adult kidney transplant recipients, on regular follow up, for presence of anemia (defined as per the WHO criteria of Hemoglobin <13gm/dl in men and <12gm/ dl in women, 3 months after transplantation; significant anemia was defined as < 12g/dl in men & 11gm/dl in women). Patients within last 3 months of transplant were excluded from the study. The prevalence of anemia was 46 %( M: 32%, F=14%) with 65. 2% of these patients having significant anemia. Mean hemoglobin in the studied population was 10. 89+/ -1. 83 g/dl. Mean time post transplantation was 5. 8+/-3. 2 years and mean estimated MDRD GFR was 44. 25+/18. 2 ml/min. The most common immunosuppressants in patients with anemia was cyclosporine / azathioprine / prednisolone combination (43. 47%). 26% of the anemic patients on ACE inhibitors/ARBs or both. The mean age was 34. 47+/- 8. 47yrs (M/F: 35. 87+/-8. 8yrs: 31. 28+/-6. 68yrs). 30. 43% of patients had episodes of acute rejection, ATN or slow/delayed graft function. There was a strong association between hemoglobin and graft function determined by GFR; the mean GFR was significantly lower (38. 36+/-3. 8ml/mt) in the 65. 2% patients who had significant anemia (p< 0. 005). On urivariate analysis, factors associated with significantly higher risk for anemia included higher age, GFR, episodes of acute rejection and use of ACE inhibitors/ ARBs. Factors not associated with anemia included sex, type of immunosuppression, pre transplant hemoglobin and years post transplant. There was no significant correlation with the severity of anemia and the use of ACE inhibitors/ ARBs. Multivariate analysis revealed GFR (p-0. 004) as the only independent variable for anemia. Other risk factors tested included age, gender, immunosuppressive therapy, pretransplant hemoglobin, episodes of AR, but they showed no significant correlation with anemia. Copyright © 2008 by The Indian Society of Organ Transplantation
The aim of the study is to compare the safety and efficacy of mycophenolate (MPA) and azathioprine (AZA) in renal transplant patients.
Background : MPA and AZA decrease acute rejection after renal transplantation, and MPA has been associated with better patient and graft survival than AZA.
Patients and methods : We studied 102 patients who had renal transplant from 2002-2006 using a case-control design. The controls were selected, matched for age ± 10 years, sex, live/cadaver donor, HLA matches, CNI, cor ticosteroids, and transplantation within a year of the case. 51 patients received MPA (cases) dose tailored to AUC 30-60 mg. h/ L. and 51 received AZA (controls) as the primary immunosuppressant. Results: Both cases and controls had equal patient and graft survival, whereas MPA was associated with trend towards lower creatinine than AZA (p= 0. 05). There was no significant difference in acute rejection of both groups (17. 6% vs. 27. 5%; p=0. 23), but MPA was associated with lower rates of late acute rejection (0% vs. 9. 8%; P=0. 02). Urinary tract infections (UTI) were frequent among the MPA compared to AZA group (33. 33% vs. 21. 6%; p=0. 18), but incidence of recurrent UTI was lower in MPA group (29. 4% vs 63. 7%; p=0. 07). Though cytomegalovirus (CMV) infection in the MPA group was marginally higher than in the AZA group (23. 5% vs. 19. 6%; p=0. 63), recurrent CMV infection was observed only in AZA group (10%). Incidence of bacterial, tuberculous, and viral infections were not significantly different in the two groups though they tend to occur less frequently in the MPA group. Leucopenia was common with AZA (43. 1% vs. 21. 6%; p=0. 0203) whereas transient diarrhea (9. 8%) was observed only with MPA.
Conclusion : MPA was associated with better graft function and marginally lower rejection rates, bacterial infections and leucopenia when compared to AZA. But both groups have similar patient and graft survival.
Everolimus and Low Dose Cyclosporine combination in DeNovo Kidney Transplant patients Sailaja, Sahariah. S, Umamaheshwar Rao. Ch
45 has allowed safe reduction in Cya dose with improved graft function. However, Optimization of the dosages and levels of Everolimus and Cya in our population needed further follow-up. Further Follow-up is needed for long term outcome.
Global Hospital and Organ Transplant Institute, Hyderabad
Everolimus is a semi synthetic Proliferation signal inhibitor, inhibits growth factor stimulated proliferation and prevents vascular remodeling, a key factor of progressive allograft dysfunction. The efficacy, tolerability and clinical information of Everolimus, low dose cyclosporine and Prednisolone combination in denovo kidney transplant patients in Indian population are limited. Here we present our experience on this ongoing, no comparative study on allograft function in renal transplant patients.
Cyclosporine - A Withdrawal in renal transplantation Lakshminarayana G, Rajesh R, G Background : Cyclosporine - A (Cys-A) is considered as short-term friend and long-term foe for renal allograft as it can cause nephrotoxicity and is implicated as a causative factor for chronic allograft nephropathy, which is a major cause for long-term graft loss.
Fifteen denovo kidney transplant recipients(7 cadaver and 8 live unrelated/related donors) age ranging from 21 to 51 years were enrolled in the study. Nine patients received Injection Daclizimab 50 mg in 2 doses on day 0 and 14 post operative day as induction therapy. All the patients received Everolimus 0. 5 mg B. D. Cya 100 mg B. D and Prednisolone 20 mg B. D as initial therapy. Cya was reduced to 50 mg B. D at the end of 3rd month maintaining the mean C2 levels ranging in between 600700 μg /ml. Prednisolone was tapered gradually. All the renal parameters, Everolimus, Cya levels, lipids and blood sugar levels were monitored at regular intervals.
Withdrawal of Cys-A and replacement with less nephrotoxic drugs may be a solution.
Patient and Graft survival was 100% after 6 months follow up. Adverse events noted in the study are delayed wound healing in 1 patient, acute rejection in 2 patients(13%), who responded well to the conservative treatment. 1 Patient developed PTDM. And a biopsy proven CNI toxicity noted in 1 patient with peak serum Creatnine reaching 2. 8 μg /ml. Hyperlipidimia was observed in 10 patients.
All 108 recipients received standard triple immunosupression (Cys-A, azathioprine, prednisolone) according to our standard protocol. Cys-A was withdrawn in 38 % in the first 6 (mean 4) months, 22 % at 6 – 10 months (mean 9) and in 40 % at more than 10 (mean 18) months after transplantation. All the early withdrawals were started on Sirolimus. Hirsutism (26 %) was the most common indication for Cys-A withdrawal followed by
The mean dose of Everolimus, Cya at 6 months is 0. 53±0. 11 mg BD and 109±25 mg/day. The mean serum Creatnine levels, Everolimus trough levels and Cya C2 levels at 6 months were 1. 5±0. 21, 6. 44±4. 2 μg /ml and 452±276 μg /ml respectively.
post-transplant diabetes (20 %), graft dysfunction (CysA toxicity or chronic allograft nephropathy) (20 %) and post-transplant erythrocytosis (PTE) (9 %); financial constraints or uncontrolled hypertension was the indication in the remaining patients. There was improvement in glycemic control, PTE, hypertension in all patients. Graft function (s. creatinine) improved after Cys-A withdrawal by 25 % in 20 % of recipients, < 25 % in 50 % recipients and no improvement was seen in the remaining 30 %. Acute rejection (AR) after Cys-A withdrawal was seen only in 3 patients within 12 weeks after withdrawal and another 4 patients had AR beyond 12 weeks. The incidence of AR was not related to the time of withdrawal; recipients with a better the HLA match had a lesser chance of rejection after stopping Cys-A.
The mean Creatnine clearance at the end of 6 months is 61. 6 ml/mins and 24 hr urinary protein level of 281. 7 mg/day which were improved when compared to 3rd month levels of 51. 5 ml/mt 388 mg/day respectively. There was gradual improvement in the GFR as reflected by CCT levels. Hyperlipidimia was controlled after treatment with statins.
Conclusion : This regime has proved to be effective in achieving good outcome with few side effects in denovo renal transplant patients including cadaver transplantation. Everolimus
Objective of the study: To study the Cys-A withdrawal patterns and its effects in renal allograft recipients at our center.
Methods : It is a retrospective study, which included 108 live related renal allograft recipients, in whom Cys-A was withdrawn with a follow-up period of 4 to 71 (mean 30) months.
Summary of results :
Conclusion : Most common indication for Cys-A withdrawal was Copyright © 2008 by The Indian Society of Organ Transplantation
46
Indian Journal of Transplantation
hirsutism. Significant improvement in glycemic control, PTE, hypertension and graft function was noted after Cys-A withdrawal. The incidence of AR was not related to the time of withdrawal. Hence patients may be considered for early (six months) Cys-A withdrawal & replacement with lesser nephrotoxic drugs.
Indian J Transplant 2008; 2: 32-50
Mycophenolate Versus Azathioprine as Primary Immunosuppression In Renal Transplantation - A Case Control Study Annapandian VM1, Basu G1, Neelakantan N2, Fleming DH3, Mathew BS3, Varughese S1, John GT1
Anemia in Renal Transplant Recipients Praveen Murlidharan, N K Hase, Arun Halankar
Departments of 1Nephrology, 2Biostatistics, 3Clinical Pharmacology. Christian Medical College, Vellore, India.
Registrar in Nephrology, Department of Nephrology, Seth GS Medical College & KEM Hospital
Aim :
Anemia, a potentially correctable cardiovascular risk factor, continues to be a major problem in kidneytransplant patients. The nature of post transplant anemia is multifactorial, and the prevalence and predictors of post transplant anemia vary between different studies. Awareness of factors associated with lower hemoglobin may prompt better anemia screening and management. We performed a retrospective analysis of 100 consecutive adult kidney transplant recipients, on regular follow up, for presence of anemia (defined as per the WHO criteria of Hemoglobin <13gm/dl in men and <12gm/ dl in women, 3 months after transplantation; significant anemia was defined as < 12g/dl in men & 11gm/dl in women). Patients within last 3 months of transplant were excluded from the study. The prevalence of anemia was 46 %( M: 32%, F=14%) with 65. 2% of these patients having significant anemia. Mean hemoglobin in the studied population was 10. 89+/ -1. 83 g/dl. Mean time post transplantation was 5. 8+/-3. 2 years and mean estimated MDRD GFR was 44. 25+/18. 2 ml/min. The most common immunosuppressants in patients with anemia was cyclosporine / azathioprine / prednisolone combination (43. 47%). 26% of the anemic patients on ACE inhibitors/ARBs or both. The mean age was 34. 47+/- 8. 47yrs (M/F: 35. 87+/-8. 8yrs: 31. 28+/-6. 68yrs). 30. 43% of patients had episodes of acute rejection, ATN or slow/delayed graft function. There was a strong association between hemoglobin and graft function determined by GFR; the mean GFR was significantly lower (38. 36+/-3. 8ml/mt) in the 65. 2% patients who had significant anemia (p< 0. 005). On urivariate analysis, factors associated with significantly higher risk for anemia included higher age, GFR, episodes of acute rejection and use of ACE inhibitors/ ARBs. Factors not associated with anemia included sex, type of immunosuppression, pre transplant hemoglobin and years post transplant. There was no significant correlation with the severity of anemia and the use of ACE inhibitors/ ARBs. Multivariate analysis revealed GFR (p-0. 004) as the only independent variable for anemia. Other risk factors tested included age, gender, immunosuppressive therapy, pretransplant hemoglobin, episodes of AR, but they showed no significant correlation with anemia. Copyright © 2008 by The Indian Society of Organ Transplantation
The aim of the study is to compare the safety and efficacy of mycophenolate (MPA) and azathioprine (AZA) in renal transplant patients.
Background : MPA and AZA decrease acute rejection after renal transplantation, and MPA has been associated with better patient and graft survival than AZA.
Patients and methods : We studied 102 patients who had renal transplant from 2002-2006 using a case-control design. The controls were selected, matched for age ± 10 years, sex, live/cadaver donor, HLA matches, CNI, cor ticosteroids, and transplantation within a year of the case. 51 patients received MPA (cases) dose tailored to AUC 30-60 mg. h/ L. and 51 received AZA (controls) as the primary immunosuppressant. Results: Both cases and controls had equal patient and graft survival, whereas MPA was associated with trend towards lower creatinine than AZA (p= 0. 05). There was no significant difference in acute rejection of both groups (17. 6% vs. 27. 5%; p=0. 23), but MPA was associated with lower rates of late acute rejection (0% vs. 9. 8%; P=0. 02). Urinary tract infections (UTI) were frequent among the MPA compared to AZA group (33. 33% vs. 21. 6%; p=0. 18), but incidence of recurrent UTI was lower in MPA group (29. 4% vs 63. 7%; p=0. 07). Though cytomegalovirus (CMV) infection in the MPA group was marginally higher than in the AZA group (23. 5% vs. 19. 6%; p=0. 63), recurrent CMV infection was observed only in AZA group (10%). Incidence of bacterial, tuberculous, and viral infections were not significantly different in the two groups though they tend to occur less frequently in the MPA group. Leucopenia was common with AZA (43. 1% vs. 21. 6%; p=0. 0203) whereas transient diarrhea (9. 8%) was observed only with MPA.
Conclusion : MPA was associated with better graft function and marginally lower rejection rates, bacterial infections and leucopenia when compared to AZA. But both groups have similar patient and graft survival.