Immunosuppressive Therapy as a Determinant of Transplantation Outcomes

Evans, Roger W.; Manninen, Diane L.; Dong, Frederick B.; Ascher, Nancy L.; Frist, William H.; Hansen, John A.; Kirklin, James K.; Perkins, James D.; Pirsch, John D.; Sanfilippo, Fred

doi:10.1097/00007890-199306000-00017

Cited by 25 publications

(4 citation statements)

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“…Some centers even begin with a qua druple immunosuppressive therapy also containing anti thymocyte globulin or monoclonal antibodies against T lymphocytes. Brayman et al [6] pointed out that a more aggressive immunosuppressive induction treatment can positively affect the outcome of these patients and a simi lar conclusion was reported from a US survey [7], Our rejection rate seems to demonstrate that triple-drug thera py as induction treatment is sufficient and alllows us to keep infectious complications at an acceptable level. The latter fact should be carefully considered since infections may not only affect patient survival but also the incidence of rejection [8].…”

Section: Discussionmentioning

confidence: 56%

Experience with 100 Combined Pancreatic Renal Transplantations in a Single Center

Landro

Koenigsrainer²,

Oefner³

et al. 1996

Nephron

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Compared to the still increasing number of kidney, liver and heart transplants performed worldwide, pancreas transplantation remains a rare occurrence. At our center a pancreas transplant program was began in late 1979. Since then a total of 113 pancreas transplants were performed in 106 patients, 100 of them also received a kidney from the same donor. The first group consisted of 5 patients with immediate duct occlusion (IDO). In the second group (n = 8) the pancreatic juice of the segmental graft was diverted into a Roux-Y loop of jejunum. Because of two fatal technique-associated complications, delayed duct occlusion was introduced and applied in 15 patients. Because of a prolonged hospitalization period due to local complications, the surgical technique was changed again. From 1987, 72 segmental pancreatic transplants with bladder drainage were performed and finally one whole organ with a duodenal segment was transplanted. Immunosuppression consisted of cyclosporine A, azathioprine and prednisolone from 1984 on. Rejection episodes were treated with high-dose methylprednisolone on 3 consecutive days and steroid-resistant rejections with ATG. The overall patient survival at 6 years was 80%, renal allograft survival 72% and pancreas graft survival 63% for the entire group. In the delayed duct occlusion group, 1-year patient and kidney graft survival of 93% each and 79% for the pancreas was calculated. One-year survival in the most recent and largest group with bladder drainage was 89% for patients, 86% for the kidney and 75 % for the pancreas. Excellent metabolic control was achieved in the majority of patients with mean C-peptide levels and HbA1C levels at 6 months of 1.46 pmol/ml and 5.6%, respectively. Successful pancreas transplants with normalization of carbohydrate metabolism seem to have a beneficial effect on secondary complications of diabetes, contributing to the high degree of rehabilitation of these patients.

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Section: Discussionmentioning

confidence: 56%

Experience with 100 Combined Pancreatic Renal Transplantations in a Single Center

Landro

Koenigsrainer²,

Oefner³

et al. 1996

Nephron

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“…It has been documented that performing more transplants is associated with better outcomes (24). Transplant centers may also systematically differ in prescribing practices (25), which could translate into artifactual differences (type 1 error) or, conversely, lack of differences when there really are drug related differences (type 2 error). Finally, in this observational study, associations between therapy and outcome are determined, but no causal conclusions can be made about drug treatment and outcome.…”

Section: Discussionmentioning

confidence: 99%

Mycophenolate mofetil vs. azathioprine is associated with decreased acute rejection, late acute rejection, and risk for cardiovascular death in renal transplant recipients with pre‐transplant diabetes

David¹,

Morris²,

Steffen³

et al. 2005

Clinical Transplantation

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Outcomes specifically in mycophenolate mofetil (MMF)-treated diabetic renal transplant patients have not been previously reported. This study compared acute rejection (AR), late acute rejection (LAR), patient survival [and specifically death from cardiovascular (CV), infectious and malignant causes], incidence of post-transplant malignancies, and graft loss in MMF- or azathioprine (AZA)-treated renal transplant patients with pre-transplant diabetes. Outcomes were compared between MMF- (n = 14 144) and AZA- (n = 3001) treated diabetic patients using the Scientific Registry of Transplant Recipients data on all U.S. adult renal transplants performed between 1995 and 2002. Statistical analyses included Kaplan-Meier survival analysis, Cox multivariable regression and chi-square tests. MMF patients had less AR compared with AZA-treated patients (23.5% vs. 28.3%, p < 0.001) and less risk for LAR over 4 yr [hazard ratio (HR): 0.64, 95% CI 0.44, 0.92; p = 0.02]. While time to any-cause death did not differ between the groups, MMF treatment was associated with a 20% decreased risk of CV death (HR: 0.80, 95% CI 0.67, 0.97; p = 0.020) compared with AZA treatment. MMF patients also had a lower incidence of malignancies than AZA patients (2.2% vs. 3.7%, p < 0.001). These results suggest treatment with MMF compared with treatment with AZA in diabetic transplant patients is associated with less AR, less risk of LAR, a decreased risk of CV death, and a lower incidence of malignancies.

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“…Intravenous mega doses (e.g., three 1‐g pulses) of methylprednisolone (MP) succinate are currently the treatment of choice, and the most widely used protocol, for the treatment of acute cellular rejection1–4 that occurs in 60–80% of liver transplant patients 2, 5. However, this treatment has been fatal in several cases6–11 and/or associated with severe life‐threatening toxicities related to the cardiovascular system (cardiac arrest and arrhythmia),8, 10–12 central nervous system (seizure and blindness),6, 13–16 severe infections (viral and bacterial),2, 3, 5, 17 or metabolic complications (hypokalamia) 18.…”

Section: Introductionmentioning

confidence: 99%

Plasma Pharmacokinetics and Tissue Disposition of Novel Dextran–Methylprednisolone Conjugates With Peptide Linkers in Rats

Penugonda

Agarwal

Parang

et al. 2010

Journal of Pharmaceutical Sciences

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The plasma and tissue disposition of two novel dextran prodrugs of methylprednisolone (MP) containing one (DMP-1) or five (DMP-5) amino acids as linkers were studied in rats. Single 5-mg/kg doses (MP equivalent) of each prodrug or MP were administered intravenously, and blood and tissue samples were collected. Prodrug and drug concentrations were quantitated using HPLC, and non-compartmental pharmacokinetic parameters were estimated. Whereas conjugation of MP with dextran in both prodrugs substantially decreased the clearance of the drug by ~200 fold, the accumulations of the drug in the liver, spleen, and kidneys were significantly increased by conjugation. However, the extent of accumulation of DMP-1 in these tissues was substantially greater than that for DMP-5. Substantial amounts of MP were regenerated from both prodrugs in the liver and spleen, with the rate of release from DMP-5 being twice as fast as that from DMP-1. However, the AUCs of MP regenerated from DMP-1 in the liver and spleen were substantially higher than those after DMP-5. In contrast, in the kidneys, the AUC of MP regenerated from DMP-5 was higher than that after DMP-1 administration. These data suggest that DMP-1 may be more suitable than DMP-5 for targeting immunosuppression to the liver and spleen.

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Immunosuppressive Therapy as a Determinant of Transplantation Outcomes

Cited by 25 publications

References 0 publications

Experience with 100 Combined Pancreatic Renal Transplantations in a Single Center

Experience with 100 Combined Pancreatic Renal Transplantations in a Single Center

Mycophenolate mofetil vs. azathioprine is associated with decreased acute rejection, late acute rejection, and risk for cardiovascular death in renal transplant recipients with pre‐transplant diabetes

Plasma Pharmacokinetics and Tissue Disposition of Novel Dextran–Methylprednisolone Conjugates With Peptide Linkers in Rats

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