Pancreas Transplantation: A review of 34 patients between April 2000 and January 2004
C Jansen, IM Pope, JJ Casey, M Akyol
Introduction: Outcome of pancreas transplantation in the UK is unknown. A review of the Scottish Pancreas transplant programme since its inception in Edinburgh is presented.
Results: Between April 2000 and January 2004 34 pancreas transplants were performed (30 SPK, 2 PAK, 2 PTA). 16 patients were female and the mean age at the time of transplant was 44 (range 9 – 48 years). The waiting time to transplantation ranged between 1 – 577 days (median 117). One-year patient, kidney, and pancreas graft survival rates are 94%, 91% and 78%. All patients received routine immunosuppression; Tacrolimus, Prednisolone and MMF with 5 patients receiving Basiliximab at time of transplant. 26 patients remain insulin independent with a mean HbA1c of 5.4% after a follow-up of 45 months (median range 0 – 45). 29 patients remain dialysis free with a mean creatinine of 112 mmol/l. 8 pancreas graft failures occurred day 1 to 29 due to fistula, arterial thrombosis, duodenal breakdown and haemorrhage. 2 patients died within the first 41 days and one further patient died 36 months post transplant.
Conclusion: Outcome comparable to internationally published data has been achieved in a newly established transplant programme.
Kath Brown 1, Gary Campbell 1, Jamie Traynor 1, Ian Galbraith 2, Keith Simpson 3, Karen Newbigging 4, Donna Wallace 5, David Deardon 1, Colin Geddes 1
1. Renal Unit Western Infirmary 2. Tissue typing Lab Glasgow Royal Infirmary 3. Renal Unit Glasgow Royal Infirmary 4. Renal Unit Dumfries Royal Infirmary 5. Renal Unit Monklands Hospital
Analysis of potential living kidney donors who do not subsequently donate.
Improved access to kidney transplant may be achieved by increasing resources to facilitate living kidney donation. There is limited published information to quantify the investigation of potential living donors (PLD) and the reasons for PLD drop-out
The LDT process in our centres involves several steps before transplant: 1) inform PLD and screen for history of known contraindications; 2) establish blood group compatibility; 3) preliminary lymphocyte cross-match; 4) screening blood tests, electrocardiogram, chest radiograph, creatinine clearance, urine protein excretion, nephrologist review; 5) MRA renal arteries, glomerular filtration rate, review by independent physician; 6) transplant surgeon review and final lymphocyte cross match. The PLD proceeds to the next stage if the preceding stages are satisfactory.
The aim of the present study was to examine blood group compatible potential LDT who had a preliminary lymphocyte crossmatch (stage 3) in the 2 years between April 2001 and March 2003 to determine the number of PLD reaching each stage, the number of actual transplants achieved and identify the reasons for PLD drop-out.
149 PLD to 111 potential recipients (PR) reached the stage of having a preliminary lymphocyte cross match (1-3 PLD per PR). 105 PLD reached stage 4; 60 reached stage 5; 41 reached stage 6; 29 PLD in this cohort have donated a kidney, 3 have firm arrangements for LDT in the near future and 5 will probably donate at a suitable time in the future.
The commonest reasons for PLD drop-out were: donor medical issues (n=31), donor or PR withdrew voluntarily (n=23), positive lymphocyte crossmatch (n=17) and other suitable PLD (n=14). 10 PR received a cadaveric transplant and 5 PR died during the PLD investigation.
These data show that when allocating resources to increase the number of LDT it must be acknowledged that only 24% of PLD that are investigated will subsequently donate. The reasons for PLD drop-out deserve further study.
Randomised study comparing cyclosporin with azathioprine one year after renal transplantation- 15 year outcome
N Joss on behalf of the Glasgow Transplant group. Renal Unit, Western Infirmary, Glasgow, Scotland
The introduction of cyclosporin (CsA) has improved the 1-year graft survival and reduced the incidence of acute rejection episodes after renal transplantation. CsA is associated with many side effects including hypertension and nephrotoxicity. Reducing the exposure of this drug after the first year may be beneficial on patient and graft survival. 216 patients were enrolled in a single centre study. After 1 year, if serum creatinine was less than 300μmol/l and there were no acute rejection episodes in the previous 6 months, the patients were randomised to continue cyclosporin (114) or to be converted to azathioprine (102). Analyses were performed on an intention to treat basis and we present follow up data at 15 years post transplant.
The patients were well matched at baseline There was no difference in patient survival at 15 years, 64.3% in the CsA group and 64.4% in the Aza group. Fifteen-year transplant survival (including death with a functioning graft) was 40% for the CsA group and 47.2% for the Aza group (p=0.7). Fifteen year graft survival censoring for death with a functioning graft was 57% in the CsA group and 72% in the Aza group (p=0.5). The graft survival for the patients who remained on their assigned treatment was higher in the Aza group (87%) compared to 65% in the CsA group, although this was not significant (p=0.1). The median (range) cyclosporin dose was 3 (1.4-7.1) mg/kg at randomisation and was 2.6 (1.8-3.9) mg/kg in the patients who remained on cyclosporin at 15 years.
The estimated glomerular filtration rate (EGFR) at year 2, 5 and 10 was significantly lower in the CsA group; however, by 15 years this effect was lost. In the CsA group systolic blood pressure (SBP) was significantly higher at year 5 and 10 and more patients were on antihypertensive agents. Cox regression analysis was performed to determine which factors predicted death and graft failure. EGFR at year 1 (p=0.003, RR 0.97) and age (p=0.003, RR 0.97) predicted graft survival (censoring for death). Age (p<0.001, RR 1.07) and SBP at year 1 (p=0.03 RR 1.01) predicted patient survival Assigned drug had no effect on graft or patient survival.
In conclusion, conversion from CsA to Aza at 1 year after transplantation in patients with a serum creatinine less than 300 μmol/l was not associated with any adverse effects on patient or graft survival at 15 years. The most important factor predicting graft survival was renal function at time of randomisation.
Assessing the utility of estimated GFR using the MDRD formula in patients with low serum albumin
Jamie P Traynor and Jonathan G Fox
The MDRD equation for estimating glomerular filtration rate (GFR) has been used increasingly since first published in 2000. It offers advantages over other methods such as the Cockcroft and Gault method in that it was derived using data from patients with advanced renal failure and does not rely on patient body weight. Instead it relies on serum albumin and urea in addition to serum creatinine, patient age, sex and race.
We wondered if this reliance on serum albumin might be a weakness in patients with very low serum albumin such as those with nephrotic syndrome.
To evaluate this further, we gathered data from the electronic patient record (EPR) at Glasgow Royal Infirmary. We searched the EPR for every result of 24-hour urinary measurement that would allow us to calculate the arithmetic mean of urea and creatinine clearance. This was used as one of the reference measurements in the original MDRD paper.
8736 samples from 2955 patients were recorded in the EPR. For the purpose of analysis, when patients had more than one sample only the most recent one was used. Of the 2955 patients, 189 patients had a serum albumin of less than 30 g/L. Figure 1 below shows the difference between estimated GFR using MDRD and using arithmetic mean or urea and creatinine clearance for different levels of serum albumin
Figure 1. Serum albumin versus the difference between MDRD and mean of urea and creatinine clearance. Positive values indicate where MDRD has over-estimated renal funcrion.
Although it appears that the MDRD tends to over-estimate GFR, there does not appear to be a difference in the magnitude of this potential error even at low levels of serum albumin. We conclude therefore that the MDRD remains valuable in estimating GFR even in patients with very low serum albumin.
Major autoreactive T cells in Goodpasture’s disease are specific for highly protease-scissile peptides exposed on the surface of the autoantigen.
Juan Zou, Mary Coughlan, A. Neil. Turner, Richard. G. Phelps.
The self peptides recognised by autoreactive T cells are evidently presented by antigen presenting cells (APC) at disease induction, so question arises as to why their presentation has not previously established secure self-tolerance whereas constitutive presentation of the vast majority of other self peptides has. ‘Destructive processing’ is a putative responsible mechanism that has received support from an animal model of autoimmunity. During APC processing of myelin basic protein (MBP), the mouse autoantigen in experimental allergic encephalomyelitis, a model of multiple sclerosis, the MBP peptide recognised by most autoreactive T cells is rapidly destroyed by the endosomal protease asparginyl endopeptidase (AEP), preventing its efficient presentation to T cells and therefore preventing efficient establishment of self-tolerance.
To investigate the potential of destructive processing to account for the persistence of Goodpasture antigen (3(IV)NC1)-specific T cells we have examined the interaction of endosomal proteases AEP, and cathepsins D and E with intact 3(IV)NC1 and 3(IV)NC1 peptides. Peptides representative of the major T cell epitopes (stimulated 4-6/6 of patients’ T cells) were all rapidly destroyed by the endosomal proteases, and contained a much higher proportion of the highly endosomal protease-scissile sites in the 3(IV)NC1 sequence than expected by chance (p=0.006). The cleavages in each case were within the portion of the epitope critical for binding to the HLA class II molecule, so would be expected to prevent presentation of the epitopes. The epitope-destroying cleavages by endosomal proteases were also observed during digestion of intact 3(IV)NC1. Analysis of a structure of 3(IV)NC1 reveals that the T cell epitopes are largely on the surface of the 3(IV)NC1 molecule and expose the susceptible peptide bonds to marauding proteases.
Therefore the major T cell epitopes in 3(IV)NC1 are likely to be poorly presented during establishment of self tolerance because they are exquisitely susceptible to rapiddestructive processing by endosomal proteases.
Title.
Acute Renal Failure Following Cancer Associated Haemolytic Uraemic Syndrome – An Unexpectedly Good Outcome.
Authors.
Tara A. Collidge1, Walaa W. Saweirs2, Robin J. Winney2 and David A. S. Jenkins1.
1The Renal Unit. Queen Margaret Hospital. Dunfermline. Fife. KY12 OSU. U.K.
2The Renal Unit. The Royal Infirmary of Edinburgh at Little France. Old Dalkeith Road. Edinburgh. Lothian. EH16 4SA. U.K.
Abstract.
We describe three cases presenting between 1998 and 2002 with acute renal failure as part of the haemolytic uraemic syndrome (HUS). In each case the underlying cause was previously undiagnosed advanced, prostate cancer. All patients required renal replacement therapy (mean of eight days) and recovered good renal function (mean creatinine 105mol/l). Renal function was maintained for an average of twenty-nine months follow up. These cases, together with similar cases reported in the literature, suggest that prostate cancer associated HUS should be recognised as a distinct subset of cancer associated HUS with a relatively good prognosis for renal recovery and life expectancy.
RENAL MASSES IN WEGENER’S GRANULOMATOSIS
D Walbaum, R Kain 1, AP Bayliss 2, DC Kluth, AJ Rees.
Renal Unit, 1Department of Pathology, 2Department of Radiology, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, AB25 2ZD.
Renal involvement in Wegener’s granulomatosis (WG) is common, typically taking the form of a necrotising focal segmental or crescentic glomerulonephritis. Granulomas in the upper and lower airways occur frequently, and may occasionally present as tumour-like mass lesions at other sites. However, there are only rare reports of WG presenting with an isolated renal mass, or multiple renal masses.
Similarly, the association of malignancy and glomerulonephritis is well established. In addition there is evidence for an increased incidence of renal carcinoma in patients presenting with systemic vasculitis affecting the kidney.
We present three cases of incidental renal masses found at the time of diagnosis of WG. They provide an insight into the relation between malignancy and vasculitis; and illustrate important practical issues concerning both diagnosis and management of patients with concurrent cancer and autoimmune disease.
Prophylactic Gentamicin and Heparin Locking of Tunnelled Central Venous Catheters Prevents Catheter Related Infection
SH Lambie, LJ Hulme HJ Pitt and CW McIntyre
Centre for Integrated Systems Biology and Medicine
Derby City General Hospital
Catheter related infection (CRI) is a major cause of morbidity and mortality in patients receiving haemodialysis. We have recently demonstrated the efficacy of using gentamicin and heparin lock in newly inserted catheters in a randomised controlled trial. This showed a reduction in CRI rate and an improvement in response to EPO. The current study examines the introduction of gentamicin and heparin locks on a unit-wide basis, rather than in newly-inserted catheters, and the effect on CRI rates, CRP levels and EPO-responsiveness.
All patients with tunnelled venous catheters at the time of trial initiation were studied. This cohort of patients had had standard heparin locks for at least the preceding four months. There was a two month run-in period continuing to use heparin locks, followed by one month in which the gentamicin and heparin locks were introduced, and a further two month period of observation subsequently. The lock solution (gentamicin 5mg/ml, heparin 5000 iu/ml) was made up by the dialysis unit nursing staff prior to the end of the shift, and instilled after every dialysis session. Data was prospectively gathered on CRI rates, CRP levels, haemoglobin concentration and erythropoeitin dose.
48 patients entered the study, (haemodialysis population 189). Prior to introduction of Gentamcin lock, nine CRIs occurred in eight patients in two months: Four of these were recurrences, thus there were five new CRIs in previously uninfected catheters in five patients. In comparison, in the two months following introduction, two CRIs occurred in two patients: Both of these were a recurrence of previous CRI, thus there were no episodes of new CRI. Overall, CRI rates dropped from 3.12 per 1000 catheter days to 0.76 per 1000 catheter days (p<0.05). New CRI rates dropped from 1.74 to 0 per 1000 catheter days. CRP levels were significantly reduced, from 325 to 203 mg/l (p<0.05). Haemoglobin levels were unchanged, (10.02 to 10.30.2 g/dl p=ns), but the dose of erythropoeitin prescribed increased from 9,400 Units/week to 11,100 units/week (p<0.0001). Two catheters were removed during the study, due to fistula maturation, and two patients died. The organisms identified were: 4 Staph Aureus, 2 Pseudomonas, 3 Gram negative bacilli and 2 episodes were growth negative.
These results further demonstrate the efficacy of gentamicin and heparin locks as a practical proposition in the setting of a busy haemodialysis unit. The reduction in CRI rate seen was very similar to the difference between the two groups in our randomised controlled trial of newly inserted catheters, when CRI rates were 0.3/1000 catheter days compared to 4/1000 catheter days. The reduction in CRP levels further attests to the potential benefit of this strategy in reducing the inflammatory burden faced by patients with tunnelled catheters.
Calcium Exposure and Removal in Haemodialysis
Sigrist M, McIntyre CW
The risks associated with calcium exposure in chronic HD patients are becoming increasingly apparent. K-DOQI guidelines recommend an absolute maximum elemental calcium load of 2000mg/day including calcium containing medication and maximum dialysate Calcium concentration of 1.25mmol to avoid intra-dialytic calcium loading. The aim of this study was to characterise calcium exposure in our haemodialysis population, including the relative contribution of dialysing against a fixed dialysate calcium concentration of 1.25mmol/L.
We studied fifty two patients. Each was requested to complete a three day food diary for analysis of daily calcium intake. 24hr urine collections were taken and analysed for calcium content. All patients underwent HD using Hospal Integra dialysis monitors, bicarbonate buffering and dialysate sodium and calcium concentrations of 134mmol/L and 1.25mmol/L respectively. Blood was sampled pre and post HD for total Calcium, albumin, bicarbonate and phosphate, in addition to ionised calcium level measured at the bedside using a portable electrolyte analyser. Calcium flux was determined from measurements of ionised calcium levels in dialyser inlet samples and those in continuous partial waste dialysis collection, with reference to total waste dialysate and ultrafiltration volumes.
There was marked inter-patient variability of exogenous calcium exposure, the mean was found to be 2345 1758 mg per day. Of this a mean of 581 208 mg was contributed from the diet and the remaining was from calcium containing phosphate binders. Calcium removal was evident in 83% of patients dialysed against a dialysate calcium concentration of 1.25mmol/l. Mean calcium flux was -187232mg (range –486-784mg). Calcium flux across the dialysis membrane was found to have a strong diffusion gradient. Table one shows the gradient of calcium diffusion is dependant upon concentrations of both pre dialysis plasma calcium and dialysate calcium (r2= 0.42 P<0.001). The amount of calcium removed during dialysis was found to be independent of exogenous calcium load.
These data suggest that the majority of HD patients are continually being calcium overloaded, which may have a contributory role in the development of vascular calcification. In contrast to recent K-DOQI recommendations for a blanket dialysate concentration of 1.25mmol/L may not be ideal for every patient. In order to minimise the effects of exogenous calcium overload dialysate concentrations should be prescribed with reference to plasma calcium levels.
Table one
Hypertension, antihypertensive agents and outcomes following renal transplantation
Tutone¹ VK, Mark¹ ² PB, Stewart¹ ² GA, Tan¹ CC, Rodger¹ RSC, Geddes¹ CC,
Jardine¹ ² AC
Renal Unit¹ and Department of Medicine and Cardiovascular Science², Western Infirmary, Glasgow, G11 6NT
Abstract
Hypertension is common following renal transplantation and adversely affects graft and patient survival. However, strategies for antihypertensive drug therapy and target blood pressure have not been clearly defined.