Kidney and Pancreas Transplantation : The history of Surgical Techniques and immunosuppression

peer reviewedPancreas Transplantation aims at providing Beta cells replacement in diabetic patients, especially for type 1 diabetes recipients in whom Beta cells had been destroyed by an autoimmune process. The final achievement is to restore a normal physiological control of glucose metabolism in order to halt or reverse the secondary complications of diabetes i.e. retinopathy, neuropathy, nephropathy, micro – and macro - angiopathy [1]. That can be achieved by a vascularised pancreas graft (referred as Pancreas Transplantation, PT) or by islet grafting (referred as Islet Transplantation, IT). The former PT includes transplanting 95% of unuseful cells, the exocrine part from one pancreas, while the last one IP, embolizing into the recipient liver, Islets of Langerhans after digestion and purification of several human pancreases. Three types of PT can be performed: the pancreas and a kidney are simultaneously transplanted with a single induction of immunosuppression (IS) therapy in hoping to correct both uremia and diabetes mellitus (SPK = Simultaneous Pancreas and Kidney Transplantation); the pancreas is transplanted after a successful kidney graft allowing two induction therapies along with the basic IS treatment (PAK = Pancreas After Kidney Transplantation) ; and finally the Pancreas can be transplanted alone in pre-uremic recipients with unawareness hypoglycaemic events or with rapidly evolving secondary complications of diabetes such as proliferative retinopathy, or advanced neuropathy (PTA = Pancreas Transplantation Alone) [1]. Moreover, in SPK, both organs the Pancreas and the Kidney are procured from the same deceased donor, either donor after brain death (DBD) or donor after cardiac death (DCD). In some US institutions, a segmental pancreas and the left kidney, are procured in a living donor [2], using a laparoscopic approach in the more recent year [3]. For PAK, in order to avoid an excessive IS load and two induction therapies, other institutions had proposed whenever possible to keep in stand-by the potential live kidney donor until a cadaver whole pancreatic compatible graft is available [1]. By contrast, the number of PTA remains limited in non uremic recipients with life-threatening complications of diabetes, in whom one might hope to avoid the hypoglycaemic events with a successful graft. That can also be achieved with IT. But except for rare cases, insulin independence with IT requires more than a single human pancreas and is limited over time [1]. Moreover, IT needs costly materials, chambers and rooms for preparation. That’s why IT will not be included in the present report

Increased risk of interstitial fibrosis and tubular atrophy in controlled donation after circulatory death kidney transplantation

Introduction: Comparable transplant outcomes between controlled donation after circulatory death (cDCD) and donation after brain death (DBD) kidney transplantation (KT) have been confirmed. However, few data describes the histology of cDCD-KT which is subjected to prolonged procurement warm ischemia. This study aimed to evaluate the rate of interstitial fibrosis (IF) and tubular atrophy (TA) on the surveillance biopsy performed in our unit between the 2 and 6 months post KT. Acute rejection was considered as secondary endpoint. Patients and Methods: 330 KT (226 DBD and 104 DCD) have been performed between 2008 and 2014. Surveillance or per-cause biopsy was performed in 272 recipients. Among them, the rate of adequate (≥8 glomeruli and ≥1 large-sized artery) was 76.8%. Results: IFTA was found in 11.5% and 25.7% of DBD and cDCD-KT, respectively (p = 0.004). Considering IF and TA separately, the corresponding rates were 20.4% vs 32% (p = 0.04) and 23% vs 36% (p = 0.03), respectively. If acute rejection before routine biopsy was excluded, either IF or TA rate was significantly higher in cDCD- than DBD-KT (12.6% vs 27.1%, p = 0.006; 17.6% vs 31.4%, p = 0.016; and 20.9% vs 35.7%, p = 0.015 in case of IF-TA, IF, and TA, respectively). A cDCD-KT compared to a DBD-KT was 3.11 (95%CI 1.51– 6.43, p = 0.002), 2.34 (95%CI 1.21–4.53, p = 0.011) and 2.29 (95%CI 1.23– 4.27, p = 0.009) times more likely to have IFTA, IF, and TA, respectively. Extended criteria donor (ECD) vs standard criteria donor (SCD) was also an independent risk factor for IFTA (OR = 3.11, 95%CI 1.51–6.43, p = 0.002), IF (OR = 4.86, 95%CI 1.96–12.05, p = 0.001), and TA (OR = 4.09, 95%CI 1.68– 9.93, p = 0.002). The rate of acute rejection diagnosed by SB was 7.1% and 8.9% in DBD and cDCD kidney grafts (p = ns), respectively.Conclusion: KT from cDCD increased the risk of IF-TA between 3 and 6 months post-transplant. Further studies are warranted to investigate the evolution of this phenomenon over time and its effect on graft function

Evolution of Native Kidney Function After Pancreas Transplantation Alone

peer reviewedIntroduction. This study investigated changes in kidney function over time among a cohort of patients undergoing pancreas transplantation alone (PTA) from January 2002 to December 2011. Patients and Methods. Ten of eighteen PTA patients bearing functioning grafts for at least 1 year were recruited for the analysis. Primary endpoints were changes in mean serum creatinine (SCr, mg/L) and mean estimated glomerular filtration rate (eGFR) using the 4-variable Levey-MDRD equation (mL/min/1.73 m2) comparing baseline (pretransplantation) to 6-month, 1-year, 3-year, and 5-year posttransplantation values. Mean follow-up time was 75.7 20.5 months (range, 46–106.5). Results. Baseline eGFR was 89.3 27.9 (range, 58–145). eGFR decreased to 75.7 26.2, 71 20.6, 66.5 14.8, and 62.1 11.2 at 6 months, 1, 3, and 5 years representing 15.2%, 20.5%, 15.8%, and 22.6% percentage decreases respectively (P .05 for all pairwise comparisons). The Baseline SCr was 8.6 2.3 mg/L (range, 5–13). SCr progressively increased to 10.1 3, 10.5 3.1, 10.9 3.1, and 11.3 1.7 at 6 months, 1, 3, and 5 years a 17.1%, 22%, 16.6%, and 19.9% increase respectively (P .05 for all pairwise comparisons). One of ten, 2/8, and 3/7 patients displayed an eGFR 60 at transplantation versus 3 and 5 years thereafter, respectively. No patient developed a SCr 25 mg/L or eGFR 30 or needed dialysis or kidney transplantation. Five of ten patients had micro-albuminuria or proteinuria before transplantation. Tacrolimus levels were within recommended therapeutic ranges over time. Conclusion. Kidney function deteriorated significantly after PTA. Understanding of risk factors for the development of renal impairment is important to preserve kidney function and to select appropriate candidates for PTA

Purpose and scope

Peer reviewe

European Renal Best Practice Guideline on kidney donor and recipient evaluation and perioperative care

The European Best Practice Guideline group (EBPG) issued guidelines on the evaluation and selection of kidney donor and kidney transplant candidates, as well as post-transplant recipient care, in the year 2000 and 2002. The new European Renal Best Practice board decided in 2009 that these guidelines needed updating. In order to avoid duplication of efforts with kidney disease improving global outcomes, which published in 2009 clinical practice guidelines on the post-transplant care of kidney transplant recipients, we did not address these issues in the present guidelines. The guideline was developed following a rigorous methodological approach: (i) identification of clinical questions, (ii) prioritization of questions, (iii) systematic literature review and critical appraisal of available evidence and (iv) formulation of recommendations and grading according to Grades of Recommendation Assessment, Development, and Evaluation (GRADE). The strength of each recommendation is rated 1 or 2, with 1 being a ‘We recommend' statement, and 2 being a ‘We suggest' statement. In addition, each statement is assigned an overall grade for the quality of evidence: A (high), B (moderate), C (low) or D (very low). The guideline makes recommendations for the evaluation of the kidney transplant candidate as well as the potential deceased and living donor, the immunological work-up of kidney donors and recipients and perioperative recipient care. All together, the work group issued 112 statements. There were 51 (45%) recommendations graded ‘1', 18 (16%) were graded ‘2' and 43 (38%) statements were not graded. There were 0 (0%) recommendations graded ‘1A', 15 (13%) were ‘1B', 19 (17%) ‘1C' and 17 (15%) ‘1D'. None (0%) were graded ‘2A', 1 (0.9%) was ‘2B', 8 (7%) were ‘2C' and 9 (8%) ‘2D'. Limitations of the evidence, especially the lack of definitive clinical outcome trials, are discussed and suggestions are provided for future research. We present here the complete recommendations about the evaluation of the kidney transplant candidate as well as the potential deceased and living donor, the immunological work-up of kidney donors and recipients and the perioperative recipient care. We hope that this document will help caregivers to improve the quality of care they deliver to patients. The full version with methods, rationale and references is published in Nephrol Dial Transplant (2013) 28: i1-i71; doi: 10.1093/ndt/gft218 and can be downloaded freely from http://www.oxfordjournals.org/our_journals/ndt/era_edta.htm

First World Consensus Conference on pancreas transplantation: Part II - recommendations.

Funder: Fondazione Pisa, Pisa, Italy; Id: http://dx.doi.org/10.13039/100007368Funder: Tuscany Region, Italy; Id: http://dx.doi.org/10.13039/501100009888Funder: Pisa University Hospital, Pisa, ItalyFunder: University of Pisa, Pisa, Italy; Id: http://dx.doi.org/10.13039/501100007514The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts' recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st-world-consensus-conference-of-pancreas-transplantation/246

The history of kidney transplantation: Past,Present and Future

peer reviewedThe history of kidney transplantation is thought to have originated at the early beginning of the previous century with several attempts of Xenografting, and experimental works on vascular sutures (Küss & Bourget, 1992)1. But it really started more than 60 years ago with first attempts of deceased donor transplantation (DCD) and the first successful kidney transplantation of homozygote twins in Boston (Toledo-Pereyra et al, 2008)2. Belgian surgeons contributed to that field of medicine by performing in the early sixties the first ever organ procurement on a brain dead heart beating donor (DBD) (June 1963) (Squifflet, 2003)3. Later on, in the eighties, they published a first series of living unrelated donor (LURD) transplantations, as well as ABO-Incompatible living donor (ABO-Inc LD) transplantations. With the advent of Cyclosporine A, and later other calcineurin inhibitors such as Tacrolimus, with the advent of more potent immunosuppressive drugs (IS), the gap between the number of renal transplant candidates and the number of transplanted recipients was and is continuously increasing in Belgium and most countries. It opened the search for other sources of organs such as donors after cardiac death (DCD) defined with the Maastricht conference and the extended criteria donors (ECD) compared to standard criteria donors (SCD). In Belgium another source of DCD was identified after the promulgation in 2002 of a law on euthanasia. The Belgian example and all its historical measures could help others to fight against organ shortage and its consequences, organ trafficking, commercialization and tourism