I recently saw a patient in clinic who has type I diabetes and received a kidney transplant from a sibling ~15 yrs ago. His allograft function remains excellent, but recently his diabetic control has been more difficult, despite the use of an insulin pump, and he has now been experiencing increasing number of hypoglycemic episodes. This brought me to wonder whether he would benefit from a pancreas transplant, i.e. pancreas after living donor kidney (PALK). [*Side note: he has a history of primary biliary cirrhosis precluding him from islet transplantation.]
First, the value of a pancreas after kidney transplant (PAK) in terms of survival benefit has been controversial. Venstrom et al. reported an overall relative risk of 1.42 (95% CI, 1.03-1.94; p=0.03) for PAK transplant compared with conventional therapy alone. 1- and 4-yr survival rates were 95.3% and 84.5% for PAK transplant compared to 97.1% and 88.1% for patients who received a kidney transplant and were on the waitlist for a pancreas. In contrast, Gruessner et. al showed that the overall mortality between PAK and those on the waitlist was not increased after transplantation. But besides the debate regarding survival benefit, there are also theoretical concerns that further antigenic challenge can lead to increased rates of rejection in both the existing kidney allograft as well as the newly placed pancreas. Higher immunosuppression increases the risk of infection/cancer and nephrotoxicity in the case of CNI use. On the other hand, pancreas transplantation restores euglycemia even after 10 yrs and, in doing so, can prevent diabetic nephropathy within the allograft and even partially reverse diabetic complications such as retinopathy, neuropathy and most notably atherosclerosis.
So the question is, would patients who have received a prior living donor kidney benefit from a subsequent pancreas transplant? A recent study by Sampaio et al. sought to address this. They analyzed OPTN/UNOS data to assess the impact of mortality and graft survival in type I diabetic patients receiving a pancreas after living donor kidney, compared to recipients of a living donor kidney transplant alone who were listed on the pancreas transplant waitlist but had yet to receive one. From 1997-2007, 4649 T1DM ESRD patients received a living donor kidney transplant and were placed on the pancreas transplantation list. Of these, 1026 subsequently received a PALK (75% of them received it within the first 2 yrs after their kidney transplant). These patients had superior patient and graft survival compared to those who did not receive a subsequent pancreas transplant at the 8yr follow-up (patient survival was 85% vs 75%, and overall graft survival was 75% vs 62%). However, because this was a retrospective, observational study, there was an inherent selection bias in choosing recipients for a subsequent pancreas transplant. For example, in order to receive a PALK, patients had to demonstrate acceptable kidney function and peri-operative risk assessment may have favoured transplanting those with less comorbidities.Indeed, the PALK group were younger, had a shorter pre-transplant dialysis time, and showed less “immunological risk” (fewer African Americans and lower PRA levels). These patients also had fewer episodes of DGF and acute rejection episodes.
So it appears that, at least based on this data, PALK does confer a longterm survival benefit in type I diabetics.
First, the value of a pancreas after kidney transplant (PAK) in terms of survival benefit has been controversial. Venstrom et al. reported an overall relative risk of 1.42 (95% CI, 1.03-1.94; p=0.03) for PAK transplant compared with conventional therapy alone. 1- and 4-yr survival rates were 95.3% and 84.5% for PAK transplant compared to 97.1% and 88.1% for patients who received a kidney transplant and were on the waitlist for a pancreas. In contrast, Gruessner et. al showed that the overall mortality between PAK and those on the waitlist was not increased after transplantation. But besides the debate regarding survival benefit, there are also theoretical concerns that further antigenic challenge can lead to increased rates of rejection in both the existing kidney allograft as well as the newly placed pancreas. Higher immunosuppression increases the risk of infection/cancer and nephrotoxicity in the case of CNI use. On the other hand, pancreas transplantation restores euglycemia even after 10 yrs and, in doing so, can prevent diabetic nephropathy within the allograft and even partially reverse diabetic complications such as retinopathy, neuropathy and most notably atherosclerosis.
So the question is, would patients who have received a prior living donor kidney benefit from a subsequent pancreas transplant? A recent study by Sampaio et al. sought to address this. They analyzed OPTN/UNOS data to assess the impact of mortality and graft survival in type I diabetic patients receiving a pancreas after living donor kidney, compared to recipients of a living donor kidney transplant alone who were listed on the pancreas transplant waitlist but had yet to receive one. From 1997-2007, 4649 T1DM ESRD patients received a living donor kidney transplant and were placed on the pancreas transplantation list. Of these, 1026 subsequently received a PALK (75% of them received it within the first 2 yrs after their kidney transplant). These patients had superior patient and graft survival compared to those who did not receive a subsequent pancreas transplant at the 8yr follow-up (patient survival was 85% vs 75%, and overall graft survival was 75% vs 62%). However, because this was a retrospective, observational study, there was an inherent selection bias in choosing recipients for a subsequent pancreas transplant. For example, in order to receive a PALK, patients had to demonstrate acceptable kidney function and peri-operative risk assessment may have favoured transplanting those with less comorbidities.Indeed, the PALK group were younger, had a shorter pre-transplant dialysis time, and showed less “immunological risk” (fewer African Americans and lower PRA levels). These patients also had fewer episodes of DGF and acute rejection episodes.
So it appears that, at least based on this data, PALK does confer a longterm survival benefit in type I diabetics.
Posted by Melissa Yeung M.D.
i was wondering if you had a chance to compare this data to SPK transplant?
ReplyDeleteASG