R. Pararajasingam

Outcome of pancreas transplantation in recipients older than 50 years: a single-centre experience.

Background. Pancreas transplantation (PT) remains the only treatment that can restore insulin independence among insulin-dependent diabetics. An ageing population in developed countries has led to an increasing number of older patients who may be suitable for PT. Some investigators argue that PT in recipients older than 50 years has an inferior outcome compared with the younger group. Methods. The object of this study was to compare the outcomes of 31 PT in patients aged 50 and above 105 PT in recipients below 50 years performed between June 2001 and December 2007. Results. The incidence of general posttransplant complications were similar in both; 60% in less than 50 vs. 58% in more than or equal to 50, P=0.539. So, as the incidence of other surgical complication in the more than or equal to 50 group compared with less than 50 (graft thrombosis 13% vs. 11.5%; bleeding 19% vs. 6.7%; abdominal abscess 23% vs. 19%; pancreatic leak 13% vs. 9.6%). There was no significant difference in the incidence of urinary tract infection and early rejection in either group. However, the incidence of respiratory tract infection was significantly higher in more than or equal to 50 (38.7% in ≥50 vs. 9.6% in <50, P=0.003). One-year patient survival was 88% in more than or equal to 50 vs. 92% in less than 50 group, P=0.399; and pancreas graft survival rate was similar (79% in the ≥50 and 74% in <50, P=0.399). Conclusion. This study demonstrates that it is feasible to safely transplant potentional PT recipients aged 50 and above. However, good medical assessment and careful patient selection is strongly recommended.

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 programmes 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?

Study Type – Therapy (case series)

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.

Biomarkers of Tolerance in Kidney Transplantation: Are We Predicting Tolerance or Response to Immunosuppressive Treatment?

We and others have previously described signatures of tolerance in kidney transplantation showing the differential expression of B cell–related genes and the relative expansions of B cell subsets. However, in all of these studies, the index group—namely, the tolerant recipients—were not receiving immunosuppression (IS) treatment, unlike the rest of the comparator groups. We aimed to assess the confounding effect of these regimens and develop a novel IS‐independent signature of tolerance. Analyzing gene expression in three independent kidney transplant patient cohorts (232 recipients and 14 tolerant patients), we have established that the expression of the previously reported signature was biased by IS regimens, which also influenced transitional B cells. We have defined and validated a new gene expression signature that is independent of drug effects and also differentiates tolerant patients from healthy controls (cross‐validated area under the receiver operating characteristic curve [AUC] = 0.81). In a prospective cohort, we have demonstrated that the new signature remained stable before and after steroid withdrawal. In addition, we report on a validated and highly accurate gene expression signature that can be reliably used to identify patients suitable for IS reduction (approximately 12% of stable patients), irrespective of the IS drugs they are receiving. Only a similar approach will make the conduct of pilot clinical trials for IS minimization safe and hence allow critical improvements in kidney posttransplant management.

Outcomes of Patients Who Develop Symptomatic Clostridium difficile Infection After Solid Organ Transplantation

Clostridium difficile-associated diarrhea is the most common cause of hospital-associated diarrhea in the UK. Infection can produce a spectrum of manifestations from mild diarrhea to toxic megacolon, colonic perforation, and death. The aim of this study was to evaluate the outcomes of patients who developed symptomatic Clostridium difficile infection (CDI) within the first year after solid organ transplantation. Between 2004 and 2007, we performed 682 transplantation: 433 from deceased-donor kidney, 143 live-donor kidney, 18 pancreas-only, and 88 simultaneous kidney and pancreas transplants. Within the first year of transplantation, 24 patients developed symptomatic CDI. No single risk factor or antimicrobial agent was associated with acquiring infection. Among this group, 2 patients developed toxic megacolon requiring subtotal colectomy and recovered. Although 5 patients who developed CDI died within the first year, CDI was not the primary cause of death. The overall mortality of patients who developed CDI within the first year of transplantation accounted for 0.7% of all transplanted patients. Increased awareness of CDI and barrier nursing can minimize the impact of CDI on the morbidity and mortality associated with transplantation. Patients should be informed of the risk of CDI during consenting for transplantation, because the 3.5% incidence is more common than that of graft loss due to thrombosis.

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

BackgroundKidney 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/DesignThe 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.DiscussionLate 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 registrationClinicalTrials.gov, NCT01120028 and ISRCTN88894088

Staged Enteric Conversion After Duodenal Necrosis in Simultaneous Kidney and Pancreas Transplant From a Donor After Cardiac Death: A Case Report

Simultaneous pancreas and kidney transplantation (SPK) is the treatment of choice for insulin-dependent diabetics with end-stage renal failure. The shortage of suitable pancreata has led to the use of donors after cardiac death (DCD). Although more than 20,000 pancreas transplants have been performed worldwide, the experience of pancreas transplantation from DCD remains limited. Factors during recovery, storage, and reperfusion may result in injury to the duodenal segment of the pancreas allograft. Here we have reported a case of duodenal necrosis after reperfusion in a patient who underwent SPK from a DCD. The pancreas was salvaged by excising the duodenum and performing a direct pancreas duct to bladder anastomosis. After recovery of function by the transplanted kidney, the patient developed recurrent urinary sepsis. The bladder-drained pancreas was converted to a direct enteric drainage, which resolved the recurrent urinary sepsis.

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.

Pseudoachalasia of the Esophagus Caused by Encapsulating Peritoneal Sclerosis

Encapsulating peritoneal sclerosis is a severe complication of peritoneal dialysis. Progressive sclerotic thickening of the peritoneum results in tethering and cocooning of the bowel, leading to chronic bowel obstruction, malabsorption, malnutrition, and high mortality. Conservative treatment is often unsuccessful and a surgical enterolysis is required for management. Pseudoachalasia is a rare condition that mimics the clinical and radiological features of achalasia of the cardia. Pseudoachalasia is most commonly caused by infiltrating or metastasizing cancers. In this report, we present a case of pseudoachalasia associated with encapsulating peritoneal sclerosis. The clinical symptoms settled after peritonectomy and enterolysis.