The prognostic significance of iliac vessel calcification in renal transplantation.

BACKGROUND: Peripheral vascular disease and major extremity amputation are common in patients with established renal failure and are associated with considerable morbidity. Several studies have shown high rates of amputation following simultaneous pancreas-kidney transplantation, but there is minimal literature on the incidence of amputation following renal transplantation. Furthermore, there is little evidence regarding the best method of predicting which patients might be at risk of developing peripheral vascular complications after transplantation. METHODS: We undertook a 5 year follow-up on the cohort of patients who were on our renal transplant waiting list 5 years ago (January 2007). At this time, it was standard practice within our unit for all patients to have routine pelvic x-rays to assess for vascular calcification of the iliac vessels at the time of activation onto the transplant waiting list. Any patients with moderate/severe calcification on x-ray, which may complicate transplantation, were referred for computed tomography angiogram (CTA) of their aorto-iliac vessels. Mortality, transplantation outcomes, and amputation rates at 5 years were correlated with the severity of calcification on preoperative imaging. RESULTS: One hundred eighty-seven patients were on the waiting list for renal transplantation in January 2007 (92 men; mean age, 58.3 +/- 6.2 years). Ninety-three patients received a transplant during the subsequent 5 years. By January 2012, 82 patients had a functioning transplant, 45 remained on the waiting list (5 suspended), 40 patients had died, and 20 were alive but no longer on the waiting list. Seventy-three (39.5%) had moderate or severe calcification on plain x-ray and went on to have CTA. Of these patients, 16 (21.9%) had extensive calcification affecting all the iliac vessels and were removed from the waiting list as a result. Preoperative imaging was useful in determining the side for surgery in a further 18 patients (24.3%). Twenty-two patients developed vascular complications. Nineteen (86.4%) had moderate-severe vascular calcification on imaging. Four of the patients with vascular complications (18.2%) underwent transplantation (2 had below knee amputation (BKA) prior to transplantation; 1 developed distal ischemia on the same side as the transplantation 2 years postoperatively; 1 had bilateral above knee amputation (AKA) approximately 2 years after transplantation). Eleven (50%) of the patients with vascular complications were dead at 5 years of follow-up. Mortality and amputation rates were higher in patients with moderate-severe calcification than minimal calcification (30.1% vs 16.6%; P = .02 and 10.9% vs 1.8%; P = .003, respectively). There was no difference in rates of delayed graft function (DGF), biopsy-proven acute rejection (BPAR), or creatinine at 1 year between patients who underwent transplantation with moderate-severe calcification and those without, however, intraoperative vascular complications (26.7% vs 3%; P < .001), graft loss (28.1% vs 3.4%; P = .01), and death with a functioning transplant (9.7% vs 1.6%; P = .04) rates were higher in patients with extensive calcification compared with those without. CONCLUSIONS: Plain x-ray of the pelvis is a useful screening tool to identify those patients who may require further detailed vascular imaging prior to transplantation. Amputation rates following renal transplantation are low and peripheral vascular disease (PVD) in isolation should not preclude transplantation. Nevertheless, significant vascular calcification is predictive of mortality both with and without transplantation and graft loss in patients with a renal transplant.

An unusual abdominal mass in an elderly patient.

Adult intussusception is rare and is often not included in the differential diagnosis. Patients who have previously undergone some form of gastric bypass procedure are more susceptible. We report a case of retrograde intussusception following a Roux-en-Y gastric bypass in an elderly patient, who presented with an abdominal mass. Her initial provisional diagnosis was bowel obstruction. As the number of bariatric gastric bypass procedures continues to rise, we are likely to see more of this kind of post-operative complication. Hence, it is crucial for surgeons to consider intussusception as a cause of abdominal pain, obstruction or mass in patients who have undergone some form of gastric bypass procedure.

Interpreting regulatory authority guidance on immunosuppressive therapy for renal transplantation: a response to the UK's National Institute for Clinical Excellence (NICE).

AIMS: A group of UK consultant transplant physicians and surgeons (the Consensus Group) met to consider the implications and interpretation of the National Institute for Clinical Excellence's (NICE) Technology Appraisal No. 85 on the use of immunosuppressive therapy for renal transplantation in adults. METHODS: This group considered what the implications of these guidelines might be for clinical practice and consensus was developed on those areas which were potentially open to different interpretations. A wider survey of nephrologists and transplant surgeons throughout the UK was also performed to gauge the impact of the NICE recommendations. RESULTS AND CONCLUSIONS: The outcome of the discussions of the Consensus Group are presented with particular reference to the recommendations of how to respond to calcineurin inhibitor (CNI) intolerance. The survey suggested that the publication of this NICE guidance has resulted in relatively few changes in prescribing practice: UK transplant centers continue to use a wide range of locally developed protocols for immunosuppressive therapy. These include the use of agents such as mycophenolate mofetil (MMF) and sirolimus, despite the fact that both drugs appeared to receive only conditional acceptance in the NICE Guidelines.

Breath ethane peaks during a single haemodialysis session and is associated with time on dialysis.

There is growing evidence that oxidative stress is increased in haemodialysis patients and that dialysis per se is a contributory factor. The elevated oxidant stress, a result of increased production of reactive oxidant species (ROS), may be due to increased pro-inflammatory activity and reduced antioxidant mechanisms. ROS are transitory molecules and therefore surrogate markers of oxidant damage are required. Identification of potential causes of oxidative damage such as dialyser membranes or dialysate has been proposed and therefore assessment of oxidative damage during a single dialysis session would be of interest. We have used breath ethane, a widely accepted marker of oxidative stress, to investigate the cause and extent of the resulting oxidative damage during single dialysis sessions. Our study involved assessment of breath ethane levels during haemodialysis in an end-stage renal failure haemodialysis population (n = 24). Breath samples were collected using discrete sampling techniques and were subsequently analysed using laser spectroscopy. Each patient adopted the role of longitudinal control in this study and his or her breath ethane level was monitored regularly during the dialysis session. Significant breath ethane elevation was observed at the beginning (within the first 10 min) of each dialysis session. This paper provides an in-depth statistical analysis and clinical discussion of the recent findings. A regression analysis of the collected breath ethane data showed a trend towards increased ethane levels for patients on dialysis for a shorter duration of time (r = 0.656, R-Sq = 43.3%, p = 0.001). Multiple linear regression was undertaken to further assess these associations and revealed that peak ethane levels were significantly and independently associated with time period on dialysis (p < 0.000), vascular access (p = 0.013) and male sex (p = 0.005). However, whilst diabetes status had demonstrated a correlation with peak ethane levels (0.525, p = 0.008) this was not independent of vascular access status. This multivariate linear model was significantly associated with Ln peak ethane levels (S = 0.744, R-Sq = 80.8%). The observed rapid rise in oxidative stress during the first few minutes after commencement of dialysis gives new insight into the dynamics of the oxidative damage resulting from dialysis treatment.

Lobar nephronia in a transplanted kidney.

We report a patient who presented with a solid mass in her graft 15 years after renal transplantation. The appearances by ultrasound were consistent with either malignancy or lobar nephronia (focal acute bacterial nephritis). Biopsy confirmed the diagnosis of a lobar nephronia with marked inflammatory infiltrate and frank pus formation. Treatment with antibiotics was associated with resolution of the mass. Lobar nephronia is a diagnosis based upon renal ultrasonography and must be considered in a patient with a solid mass in the kidney.

Random blood glucose measurements and survival in nondiabetic renal transplant recipients.

New-onset diabetes after renal transplantation (PTDM), a common consequence of immunosuppression, is associated with reduced patient survival. However, we know little about the impact of less marked changes in glucose homeostasis. To investigate this problem, we used data on average random blood glucose values during the first, second, and third months posttransplantation, derived from a cohort of 1186 patients who received their first cadaveric or living-donor transplant between 1984 and 2002. We analyzed both patient and death-censored graft survivals, subgrouping recipients into those with end-stage renal failure due to diabetic nephropathy versus those with PTDM versus patients without diabetes. We confirmed that PTDM patients display reduced survival following transplantation, but a long-term survival similar to that of patients with diabetic nephropathy and end-stage renal disease. However, among patients without diabetes, random blood glucose was also a strong determinant of outcome, even when in the low normal range. In contrast, neither the presence of diabetes nor random glucose levels showed a significant impact on graft survival. PTDM is recognized to be an important, potentially modifiable, risk factor for cardiovascular disease in transplant recipients. Our data suggest that there is a gradation of increased risk associated with impaired glycemic control that affects patients who do not have diabetes. These data support the need for improved understanding of glycemic control in transplant recipients and for more detailed screening for impaired glucose tolerance in this population.

Unresectable hepatic tumors in childhood and the role of liver transplantation.

Liver transplantation has been performed in five children with unresectable hepatic tumors who did not have extrahepatic metastases at the time of surgery. Two of the children had hepatoblastomas, one had an infantile hemangioendothelioma, and two had a hepatoma. The two children who had hepatoblastoma are well (37 and 25 months posttransplant) and have no evidence of recurrence. The child with infantile hemangioendothelioma had a successful operation, with good quality of life, but died of tumor recurrence 41 months after transplantation. Both children with hepatomas died, one of graft failure owing to chronic rejection and the other of tumor recurrence 5 months posttransplant. These results suggest that liver transplantation may be successful in children with unresectable hepatic tumors without extrahepatic spread and should be considered particularly for the treatment of hepatoblastoma.

FK 506 versus cyclosporin in the prevention of renal allograft rejection--European pilot study: six-week results.

FK 506 was compared with cyclosporin in a randomised trial in good-risk cadaveric renal transplant recipients. The objective was to evaluate whether oral FK 506 dosing was viable and whether blood concentrations in the range 10-20 ng/ml would prove to be practical. Thirty-one adult patients were randomised to FK 506 and 16 to cyclosporin. Both groups received an identical regimen of azathioprine and corticosteroids. Serum creatinine concentrations decreased rapidly in both groups with mean values below 200 mumol/l within 2 weeks. One graft in the cyclosporin group was lost due to renal vein thrombosis. During the 6-week study period, 19.4% of patients on FK 506 and 31.3% on cyclosporin experienced acute rejection. One patient in each group experienced corticosteroid-resistant rejection that responded to anti-lymphocyte therapy. Infections were reported in 51.6% of the FK 506 group compared with 37.5% of the cyclosporin group. The spectrum of adverse events was similar in both groups. However, minor neurological disorders were more common in the FK 506 group (54.8% versus 6.3%) whereas hypertension was less common (48.8% versus 75.0%). The results indicate that oral FK 506 rapidly achieves therapeutic blood concentrations and is an effective immunosuppressant for the initial treatment of renal allograft recipients.

Steroid withdrawal 3 months after liver transplantation--does FK 506 confer any advantage over cyclosporin?

Eighty-one liver recipients were randomised to FK 506 or cyclosporin (CyA) and azathioprine (AzA), both in combination with steroids. Twenty-seven FK 506 and 29 CyA/AzA patients continued in the trial 3 months after transplantation. Steroids were ceased in 23 (85%) FK 506 patients and in 27 (93%) CyA patients. After steroid withdrawal, 2 FK 506 and 4 CyA patients were excluded from the study, all for reasons other than rejection. The median follow-up was 16 months for the FK 506, and 19 months for CyA group. There were no acute rejection episodes or graft losses in the FK 506 group. None of the CyA patients lost their graft but three (13%) had episodes of acute rejection requiring steroids to be recommenced in two cases. There was no evidence of chronic rejection in any of the annual review biopsies in either group. Our results suggested no advantage of FK 506 over CyA in its steroid-sparing effect.

Metastatic calcification and cytomegalovirus infection.

We report a patient who developed hypercalcaemic metastatic cutaneous calcification in association with a cytomegalovirus infection after a liver transplant. The skin nodules disappeared as the hypercalcaemia resolved and the cytomegalovirus infection subsided.

Importance of cause in the outcome of pancreatic pseudocysts.

Among 100 consecutive patients with pancreatic pseudocysts, a biliary cause for the preceding acute pancreatitis was found in 27, for a mortality rate of 22 percent. Patients with alcohol abuse as the cause had a more favorable prognosis, with a 5 percent mortality rate among 59 patients (p less than 0.05, chi-square test). Despite an age difference between the two groups, we consider that this feature of patients with pancreatic pseudocyst warrants attention and we make recommendations herein with respect to therapy. Pseudocysts developed in 86 patients consequent to an episode of acute pancreatitis, and all 12 deaths (14 percent) were in this group. None of the remaining 14 patients whose pseudocysts were a feature of chronic pancreatitis died. Of the 81 patients in whom amylase levels were measured, 76 percent had an increased level.

Liver transplantation: the first 200 grafts in Birmingham.

Improvements in perioperative management in this series have been balanced by an increase in the proportion of high-risk patients grafted, such that no overall improvement in survival has occurred. We suggest that for each patient 2 separate groups of risk factors are relevant: 1. Risk factors related to the transplant procedure itself: These include previous major upper abdominal surgery, marked cerebral edema due to fulminant hepatic failure, and severe portal hypertension including patients with recent major variceal bleeding. 2. Risk factors related to the recovery phase: These include patients in hepatorenal failure before grafting and those with severe muscle wasting. Greater experience and refinements in surgical technique have improved the outcome for patients with risk factors limited to the first group. However, those with risk factors in both groups remain a difficult problem and a significant proportion of the fatalities occur in patients who have come through the operation only to be lost from complications in the postoperative period. We feel this is one of the most important areas for future efforts if the results of liver replacement are to improve sufficiently to merit a wider application.