Mortality in diabetes: pancreas transplantation is associated with significant survival benefit.

BACKGROUND: Pancreas transplantation in complicated type 1 (insulin dependent) diabetes mellitus improves the quality of life, increases longevity and stabilizes diabetic complications. There may be clinician reticence due to perceived poor outcomes with published associated mortality rates of 5-8% due to significant co-morbidities, particularly cardiovascular impairment. METHODS: Retrospective analysis was performed on patients undergoing pancreas transplantation in a single centre since the programme's initiation [simultaneous pancreas kidney (SPK) = 148, pancreas after kidney (PAK) = 33 and pancreas transplant alone (PTA) = 11] compared with a control group accepted contemporaneously onto the waiting list. The primary endpoint was patient mortality. The risk factors including medical and diabetic history, demographics, transplant type and waiting time were analysed. RESULTS: The waiting list mortality was 30% (35 of 120) compared with a mortality of 9% (20 of 193) post-transplantation (P < 0.001). Deaths on the waiting list compared with transplantation up to 1 year had a relative risk of 2.67 (95% CI: 0.81-3.51; P = 0.19), whilst those surviving >1 year had a relative risk of 5.89 of dying on the waiting list (95% CI: 1.70-3.20; P < 0.0005). There were no differences in terms of cardiovascular or renal-associated risk factors, nor in other potential confounding factors other than duration of diabetes (P = 0.02). Median survival from listing was shorter in younger patients (<50; P < 0.0001). CONCLUSIONS: Type 1 diabetics with renal failure listed for pancreas transplantation are at a significant risk of mortality even without surgery. Transplantation offers considerable survival benefits, despite associated surgical and immunosuppressive risks. In selected patients, pancreas transplantation remains the benchmark treatment for type 1 diabetes mellitus.

Native nephrectomy for autosomal dominant polycystic kidney disease: before or after kidney transplantation?

UNLABELLED: Study Type - Therapy (case series). LEVEL OF EVIDENCE: 4. What's known on the subject? and What does the study add? The indications and timing of native nephrectomy in patients with autosomal dominant polycystic kidney disease (ADPKD) is controversial, especially for those undergoing renal transplantation. Post-transplant unilateral native nephrectomy appears to be the preferred intervention compared to pre-transplant native nephrectomy. There seems to be substantial additive risk to bilateral over unilateral nephrectomy, especially prior to transplantation. Pre-transplant native nephrectomy should only be carried out when there are clear indications such as massive size preventing allograft placement, severe pain, early satiety, recurrent bleeding and infections, or suspected malignancy. OBJECTIVE: To analyse indications, timing and outcomes of native nephrectomy in autosomal dominant polycystic kidney disease (ADPKD) patients listed for kidney transplantation. PATIENTS AND METHODS: A retrospective analysis of all ADPKD patients who had a native nephrectomy prior to or following transplantation between January 2003 and December 2009 at a single centre, including those undergoing the sandwich technique (removal of the most severely affected native kidney prior to transplantation, and the other afterwards), was undertaken. RESULTS: There were 35 individuals in our cohort (M : F = 16 : 19), with a median age of 51.5 years (range 43-65). Twenty patients were in the pre-transplant nephrectomy group, 12 in the post-transplant group, and three underwent the sandwich technique. Indications for nephrectomy varied but were most commonly pain/discomfort, space for transplantation, ongoing haematuria, recurrent infections, and gastrointestinal pressure symptoms (early satiety). Seven individuals in the pre-transplant group and three in the post-transplant group required critical care admission after nephrectomy. Transient renal graft dysfunction occurred in two post-transplant bilateral nephrectomy patients. Two patients in the bilateral nephrectomy pre-transplant group and one in the bilateral nephrectomy post-transplant group died in the immediate post-operative period. No complications were noted in the sandwich technique group. CONCLUSION: Native nephrectomy in ADPKD is a major undertaking associated with significant morbidity especially in the pre-transplant group. Post-transplant unilateral nephrectomy appears to be the safest approach with fewest complications.

Management of transplant renal artery stenosis and its impact on long-term allograft survival: a single-centre experience.

BACKGROUND: Transplant renal artery stenosis (TRAS) is a recognized complication resulting in post-transplant hypertension associated with allograft dysfunction. It is a commonly missed but potentially treatable complication that may present from months to years after transplant surgery. In this retrospective study, we compared management strategies and outcomes of TRAS from 1990 to 2005. METHODS: Case notes of transplant recipients with TRAS demonstrated by angiography were reviewed. Angiography and was carried out when there was a clinical or Doppler ultrasound suspicion of TRAS. The clinical diagnosis of TRAS was based on uncontrolled refractory/new-onset hypertension and/or unexplained graft dysfunction in the absence of another diagnosis, such as rejection, obstruction or infection. The two-tailed Student t-test was used to analyse the differences between mean arterial pressure, serum creatinine, and estimated glomerular filtration rate before and after the intervention. RESULTS: Sixty-seven patients with angiogram-confirmed TRAS were included. Forty-four, 9 and 14 patients were managed with primary percutaneous transluminal renal angioplasty (PTRA), surgical intervention and conservative treatment, respectively. Uncontrolled hypertension was the most common presentation noted in 74.62%. Post-anastamotic single stenosis was the commonest occurrence (n = 53). Angioplasty had the highest 1- and 5-year graft survival rate of 91% and 86%, respectively. The worst prognosis was noted in patients treated with secondary PTRA after failed surgery or secondary surgery after failed primary PTRA. CONCLUSIONS: TRAS is a recognized complication resulting in loss of renal allografts. Early Doppler ultrasound is a good primary diagnostic tool. Early intervention is associated with a good long-term graft function.

Negative pressure wound therapy used to heal complex urinary fistula wounds following renal transplantation into an ileal conduit.

Transplantation into an ileal conduit is an established option for patients with end-stage renal failure and a nonfunctioning urinary tract. Urinary fistulae are more common following these complex transplants. Urinary fistula in this scenario can cause substantial morbidity and even result in graft loss. The management options depend on the viability of the transplant ureter, the level of local sepsis and the overall condition of the patient. Urinary diversion with a nephrostomy and ureteric stents has been described in aiding the healing of urinary leaks in renal transplants into a functioning urinary tract. We describe the successful use of negative wound pressure therapy to eradicate the local sepsis and help the healing of a recurrent urinary fistula following kidney transplantation into an ileal conduit. To our knowledge these are the first such cases reported in the literature.

Rabbit anti-thymocyte globulin (rATG) versus IL-2 receptor antagonist induction therapies in tacrolimus-based immunosuppression era: a meta-analysis.

BACKGROUND: The aim of this meta-analysis is to explore the effect of IL-2RA vs rATG on the rate of acute rejection, post-transplant infections, and graft as well as patient's survival in standard- and high-risk renal transplant patients receiving tacrolimus-based maintenance immunotherapy. METHODS: Random effects model was the method used for identifying risk difference. Confidence interval including the value 1 was used as evidence for statistically significant risk difference. Heterogeneity was assessed using Der Simonian analysis. Heterogeneity was evident at the level of P value < 0.1 RESULTS: The random effects model showed no significant differences in both acute rejection rates between IL-2RA and rATG induction therapies with relative risk of 1.24 graft survival with relative risk 0.90. Patient survival also did not demonstrate any significant difference with a relative risk of 1.19. Random effects for CMV infection showed a lesser tendency for CMV infection in IL-2RA group compared to ATG group the with a relative risk of 0.73.In subgroup analysis, the random effects model for acute rejection rates in high-risk transplants showed a higher risk of acute rejection in the IL-2RA group compared to rATG (relative risk equals 1.55) In standard-risk transplants, there were no significant differences between both groups with relative risk equals 1.02 CONCLUSIONS: This meta-analysis revealed no significant difference in patient and graft survival when using IL-2RA vs rATG with the tacrolimus-based maintenance immunosuppression era. However, subgroup analysis showed less incidence of rejection in high-risk renal transplant recipient's population using rATG compared to IL-2RA.

Pancreatic transplantation: Brief review of the current evidence.

Kidney transplantation is the treatment of choice for management of end-stage renal disease. However, in diabetic patients, the underlying metabolic disturbance will persist and even may get worse after isolated kidney transplantation. Pancreatic transplantation in humans was first introduced in 1966. The initial outcome was disappointing. However, this was changed after the improvement of surgical techniques together with better patient selection and the availability of potent and better-tolerated immune-suppression like cyclosporine and induction antibodies. Combined kidney and pancreas transplantation will not only solve the problem of organ failure, but it will also stabilise or even reverse the metabolic complications of diabetes. Combined kidney and pancreas transplantation have the best long term outcome in diabetic cases with renal failure. Nevertheless, at the cost of an initial increase in morbidity and risk of mortality. Other transplantation options include pancreas after kidney transplantation and islet cell transplantation. We aim by this work to explore various options which can be offered to a diabetic patient with advanced chronic kidney disease. Our work will provide a simplified, yet up-to-date information regarding the different management options for those diabetic chronic kidney failure patients.

Comparison of Ipsilateral and Contralateral Simultaneous Pancreas and Kidney Transplantation: A Single-Center Analysis with 5-Year Outcome.

BACKGROUND It is routine to implant the pancreas on the right and the renal graft on the left iliac fossa during a simultaneous kidney and pancreas transplant (cSPK). Ipsilateral placement of both organs on the same side raises concerns that the pancreas graft might compromise the distally placed kidney. However, ipsilateral SPK (iSPK) can be faster than the conventional contralateral graft placement and allows for preservation of the other side for future transplants. MATERIAL AND METHODS In a single unit, 67 SPK transplantations (cSPK n=49, iSPK n=18) were performed from 2008 to 2011. The decision for graft placement was made during the procedure. Donor and recipient demographics, surgical complications, reoperations, surgical time, and patient and graft survival with 5-year follow-up were compared between the 2 groups. RESULTS Duration of operation was shorter in the iSPK group. Recipient and donor demographics were comparable, apart from more females receiving ipsilateral graft placement. The broader female pelvis was probably the determining factor contributing to this outcome. The iSPK group included marginally younger recipients. The ipsilateral group also demonstrated a trend to improved survival of patient, pancreas, and kidney graft, at 1- and 5-year follow-up. There was no difference in complication rates between the 2 groups. CONCLUSIONS There were no significant differences in overall outcomes. iSPK is a safe procedure, which proves similar patient and graft survival as with cSPK. Both procedures have comparable surgical complication rates. iSPK is a safe and quicker procedure that allows for preservation of the contralateral side for potential subsequent transplants.

Transperitoneal Enucleation of a Kidney Transplant Allograft Renal Cell Carcinoma.

Development of malignancy after solid-organ trans?lant is a well-known long-term complication of immunosuppressive therapy. Thus far, there are no specific oncologic recommendations regarding management of de novo tumors in transplanted kidneys. Here, we present the case of a 63-year-old male patient who developed a de novo renal cell carcinoma 6 years after the transplant procedure. The patient underwent nephron-sparing surgery with transperitoneal enucleation of the tumor. We discuss the decision-making process and the operative challenges that we faced. We conclude that this technique should be considered as a therapeutic strategy for selected patients so that transplant nephrectomy can be avoided.

Steroid regulation: An overlooked aspect of tolerance and chronic rejection in kidney transplantation.

Steroid conversion (HSD11B1, HSD11B2, H6PD) and receptor genes (NR3C1, NR3C2) were examined in kidney-transplant recipients with "operational tolerance" and chronic rejection (CR), independently and within the context of 88 tolerance-associated genes. Associations with cellular types were explored. Peripheral whole-blood gene-expression levels (RT-qPCR-based) and cell counts were adjusted for immunosuppressant drug intake. Tolerant (n = 17), stable (n = 190) and CR patients (n = 37) were compared. Healthy controls (n = 14) were used as reference. The anti-inflammatory glucocorticoid receptor (NR3C1) and the cortisol-activating HSD11B1 and H6PD genes were up-regulated in CR and were lowest in tolerant patients. The pro-inflammatory mineralocorticoid gene (NR3C2) was downregulated in stable and CR patients. NR3C1 was associated with neutrophils and NR3C2 with T-cells. Steroid conversion and receptor genes, alone, enabled classification of tolerant patients and were major contributors to gene-expression signatures of both, tolerance and CR, alongside known tolerance-associated genes, revealing a key role of steroid regulation and response in kidney transplantation.

Outcome of kidney transplant with double ureter: a multicenter study.

OBJECTIVES: Renal transplant with double ureters is uncommon. However, with increasing numbers of en bloc and dual transplants from marginal donors, we frequently observe 2 ureters for implant. The current study reviewed our experience with 76 double-ureter renal transplants. MATERIALS AND METHODS: We performed a retrospective analysis of renal transplant performed in 2 institutes from 1996 to 2011. We recorded the outcomes of renal transplants with double ureters including complications. We compared outcomes with renal transplants with single ureters. RESULTS: Irrespective of the technique used for implant, we recorded no significant risk of complications of double, compared with single, ureter renal transplants. There were no significant differences in patient and graft survival. CONCLUSIONS: We believe that double-ureter transplant does not require additional risk discussion with the recipient because it is safe. However, when ureteral stents are used, we should ensure that a mechanism is in place for both stents to be removed postoperatively.

Incidence and Histologic Features of Transplant Graft Pancreatitis: A Single Center Experience.

OBJECTIVES: Pancreas transplant is an effective long-term treatment modality for complicated type 1 diabetes mellitus. However, allograft failure or severe concomitant rejection remain an obstacle to successful transplant outcome, occurring in approximately 21% of recipients within 1 year. Most histologic studies investigating the cause of pancreas transplant failure have concentrated on the presence and severity of acute and chronic cellular or vascular rejection. After vascular thrombosis, graft pancreatitis is the second most frequent complication after transplant. MATERIALS AND METHODS: We conducted a retrospective analysis, collecting information from a contemporaneously maintained database of patients after pancreas transplant. RESULTS: We identified 44 patients with rejected allografts from a database of 196 pancreas transplant patients (44/196, 22%). In these identified rejected allografts, 27 patients (61%) had histopathology reports containing 1 or more terms associated with pancreatitis, with the most common histologic finding was being fat necrosis (21/27, 83%), followed by inflammatory or neutrophil infiltrate (13/27, 48%). Sixteen of these patients (60%) had two 2 or more terms histology terms descriptive of pancreatitis records. Ten of the 44 rejected allografts, 10 patients had histologic evidence of vascular or cellular rejection. There was no significant difference in the proportions showing evidence of rejection between groups with (2/27 patients [26%]) and without (3/17 patients [18%]) descriptions of pancreatitis in their medical records (P = .70). When time from transplant to pancreatectomy was analyzed, a larger proportion of pancreatectomies occurred late for patients with descriptions of pancreatitis in their medical records versus patients without (17/26 [65%] vs 4/16 [25%]; P = .05). CONCLUSIONS: This case series demonstrates that 61% of rejected allografts over a span of 13 years at a single center had histologic features of graft pancreatitis, suggesting that pancreatitis may be a contributory mechanism to graft failure.

Anthropometrics Identify Wasting in Patients Undergoing Surgery for Encapsulating Peritoneal Sclerosis.

UNLABELLED: ♦ INTRODUCTION: Encapsulating peritoneal sclerosis (EPS) is a serious complication of peritoneal dialysis in which gastrointestinal (GI) symptoms reduce appetite and dietary intake. Adequate nutrition is important, especially if surgery is required. Although the incidence of EPS is low, the present report is able to detail preoperative nutrition status and treatment in a large cohort of patients from a national EPS referral center. ♦ METHODS: Of 51 patients admitted to this EPS specialist center hospital for their first peritonectomy in the study period, 50 had a preoperative dietetic assessment, and 49 underwent upper-arm anthropometry. ♦ RESULTS: Mean body mass index (BMI) was 20.6 kg/m(2). Mean weight loss was 14% of body weight in the preceding 6 months, with 35 of 50 patients losing more than 10%. On anthropometry, 25 of 49 patients were below the 5th percentile for mid-arm circumference (MAC), 17 of 49 were below for triceps skinfold thickness (TSF), and 21 of 49 were below for mid-arm muscle circumference (MAMC). Mean handgrip strength (HGS) was 60% of normal, with 43 of 49 patients being below 85% of normal. Appetite was poor in 21 of 50 patients, and 37 of 50 had upper and 40 of 50 had lower GI symptoms. By subjective global assessment, 27 of 51 patients were graded as severely malnourished, and 5 of 51, as well-nourished. Mean serum albumin was 28 g/L and did not correlate with BMI, MAC, TSF, MAMC, or HGS. In most patients, C-reactive protein was elevated (mean: 111 mg/L). Preoperative parenteral nutrition was given to 46 of 51 patients for a mean of 21 days. ♦ DISCUSSION: Our findings demonstrate the poor nutrition status of patients admitted for EPS surgical intervention. Anthropometrics reveal depleted fat and lean body mass in EPS patients, which might be a result of anorexia and inflammation, and the reason that albumin was not an accurate marker of nutrition. Poor nutrition status is likely to negatively affect outcome in this patient group. ♦ CONCLUSIONS: Early recognition of GI symptoms may herald a diagnosis of EPS. Optimization of preoperative nutrition status with intensive nutrition support is needed.

Arteritis in the appendix: an unusual cause of right iliac fossa pain.

Many conditions can cause or mimic appendicitis, of which necrotising arteritis remains an unusual cause. Its significance stems from its association with the vasculitides in general. We describe here a 15-year-old-girl with an incidental finding of a focal arteritis in the vasculature of the appendix and with right iliac fossa pain. There was no evidence of suppurative inflammation of the appendix, and she made a good recovery following laparoscopic appendicectomy.

Campath, calcineurin inhibitor reduction and chronic allograft nephropathy (3C) study: background, rationale, and study protocol.

BACKGROUND: Kidney transplantation is the best treatment for patients with end-stage renal failure, but uncertainty remains about the best immunosuppression strategy. Long-term graft survival has not improved substantially, and one possible explanation is calcineurin inhibitor (CNI) nephrotoxicity. CNI exposure could be minimized by using more potent induction therapy or alternative maintenance therapy to remove CNIs completely. However, the safety and efficacy of such strategies are unknown. METHODS/DESIGN: The Campath, Calcineurin inhibitor reduction and Chronic allograft nephropathy (3C) Study is a multicentre, open-label, randomized controlled trial with 852 participants which is addressing two important questions in kidney transplantation. The first question is whether a Campath (alemtuzumab)-based induction therapy strategy is superior to basiliximab-based therapy, and the second is whether, from 6 months after transplantation, a sirolimus-based maintenance therapy strategy is superior to tacrolimus-based therapy. Recruitment is complete, and follow-up will continue for around 5 years post-transplant. The primary endpoint for the induction therapy comparison is biopsy-proven acute rejection by 6 months, and the primary endpoint for the maintenance therapy comparison is change in estimated glomerular filtration rate from baseline to 2 years after transplantation. The study is sponsored by the University of Oxford and endorsed by the British Transplantation Society, and 18 centers for adult kidney transplant are participating. DISCUSSION: Late graft failure is a major issue for kidney-transplant recipients. If our hypothesis that minimizing CNI exposure with Campath-based induction therapy and/or an elective conversion to sirolimus-based maintenance therapy can improve long-term graft function and survival is correct, then patients should experience better graft function for longer. A positive outcome could change clinical practice in kidney transplantation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01120028 and ISRCTN88894088.

Successful en bloc renal transplant from a 19-month-old nonheart-beating donor into an adult recipient: case report.

Worldwide, there is a shortage of organs available for transplant into patients with end-stage renal failure. This has led to donor selection of the most-marginal donors. These strategies, so far, have failed to meet the requirements. Further adaptations are required to maximize the donor pool. One such pool is nonheart-beating pediatric donors less than 2 years of age. This report highlights a successful en bloc renal transplant using a 19-month-old nonheart-beating pediatric donor kidney into an adult recipient. Renal transplant from a nonheart-beating pediatric donor kidney can be a way forward toward increasing the organ donor pool.

Transplantation in adults with primary hyperoxaluria: single unit experience and treatment algorithm.

BACKGROUND: Kidney transplantation alone in Primary Hyperoxaluria is associated with a high rate of recurrence and in many cases early graft loss. Liver transplantation offers the possibility of correcting the metabolic defect. MATERIAL/METHODS: A retrospective review of five cases of Primary Hyperoxaluria managed at a major transplant unit was performed. RESULTS: The 5 patients had a mean age of 32.2 years (range 28-40) at time of first transplantation. 3 patients had kidney only transplants (one live donor, 2 deceased donor) and 2 had segmental liver followed by delayed kidney transplantation. All 3 kidney alone failed and one is now awaiting a live donor transplant, one underwent kidney alone retransplantation (failed 5 years later) and one had a combined deceased donor liver and kidney transplantation (remains well at 4 years). The 2 segmental liver sequential kidney transplant recipients remain well at 1 year and 3 years. CONCLUSIONS: Combined liver-kidney transplantation may be a better choice as the primary transplant procedure. The indication and timing for pre-emptive liver or liver followed by delayed kidney transplantation remains a matter of debate.