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. Fifteenyear 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.
100
80
60
40
2
MDRD minus Mean
R = 0.0052
20
0
0
10
20
30
40
50
-20
-40
-60
-80
-100
Serum Albumin
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.
60
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 selftolerance.
To investigate the potential of destructive processing to account for the persistence of
-specific T cells we have examined the interaction
V)NC1 and
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
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 epitopedestroying cleavages by endosomal proteases were also observed during digestion of
susceptible peptide bonds to marauding proteases.
during establishment of self tolerance because they are exquisitely susceptible to rapid
destructive 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.
1
The Renal Unit. Queen Margaret Hospital. Dunfermline. Fife. KY12 OSU. U.K.
2
The 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
. 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 EPOresponsiveness.
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 325 to 203 mg/l
(p<0.05). Haemoglobin levels were unchanged, (10.02 to 10.30.2 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 -187232mg (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
Determinants of calcium
removal on dialysis
0.50
0.25
-750
-500
-250
250
500
750
-0.25
-0.50
Ca removed during dialysis (mg)
Plasma-Dialysate Ca
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.
Aim: To assess the influence of achieved blood pressure and antihypertension drug
therapy on graft and patient survival with the aim of identifying targets and event
rates for future intervention studies.
Methods: We undertook a prospective study of 634 renal transplant patients. Patients
were surveyed in December 1994 and followed up after 102 months. Blood pressure
(BP) was determined from mean of three clinic readings and antihypertensive drug
therapy recorded.
Results: Complete follow up data were available for analysis on 622 patients (57.2%
male; mean age 45.2 +/-13.0 years). There were 158 (25.4%) deaths and 115 (18.5%)
death-censored graft failures. Univariate analysis showed age (hazard ratio (HR)
1.066, P<0.01), serum creatinine (HR 1.002, P<0.05), diabetes (HR 3.989, P<0.01),
and pulse pressure (HR 1.013, P<0.01) to be predictors of patient survival. Serum
creatinine (HR 1.012, P<0.001), duration of renal replacement therapy, number of
antihypertensive agents (HR 1.413, P<0.01) and pulse pressure (HR 1.018, P<0.05)
were predictors of graft survival. Patient survival was reduced with increasing number
of antihypertensives (p<0.05), as was graft survival (p<0.05). Reduced patient and
graft survival was seen in patients prescribed calcium channel antagonists (p<0.01).
There was no increased patient mortality in those patients on beta- blockers or ACE
inhibitors.
Conclusion. Hypertension is a risk factor for reduced patient and graft survival. This
risk remains despite use of anti-hypertensives. Beta-blockers may have a beneficial
effect on cardiovascular mortality, and ACE inhibitors a beneficial effect on both
patient and graft survival. There is a pressing need for interventional studies to assess
the impact of blood pressure targets on patient and graft survival and the effect of
individual agents on these outcomes.
Acute renal failure requiring renal replacement therapy in Scottish
Intensive Care Units
Jyoti Baharani1 Gordon Prescott2 W C Smith2 K Simpson3 A MacLeod1 and I Khan1
1 Department
of Medicine and Therapeutics, University of Aberdeen, 2 Department of Public
Health, University of Aberdeen, 3Scottish Renal Registry Glasgow
The epidemiology of acute renal failure (ARF) requiring renal replacement
therapy (RRT) has seen an increasing shift towards the intensive care unit
(ITU) in recent years, with 5-20% of all admissions to ITU developing ARF
often in the context of multi organ failure (MOF). 21 of the 26 ITU’S in
Scotland provide RRT for patients with ARF but little is known about the
outcome of these patients.
As part of the acute renal failure in Scotland study (ARFS) we registered all
patients who received RRT for ARF in all Scottish ITU’s over a 36- week
period. All patients were registered at the time of first of first RRT and followed
up for 90 days or to the time they died. All data was collected on site from
patients case notes as well as the Ward Watcher PC based software.
Over the 36-week period of data collection, 417 patients were registered
(average age 58.2 years, 62|% male). Just fewer than 10% of registered
patients had a degree of underlying renal dysfunction. 62% of the patients had
sepsis and a third of all patients were post op. 7% of all patients dialysed had
received Nephrotoxins prior to their first RRT.
Less than 1% of all ARF patients had a renal biopsy performed in ITU.
More than half the patients were treated with continuous renal replacement
therapy (CRRT) and no patients were treated with peritoneal dialysis. 41.7%
of all patients received renal consultation prior to RRT.
90-day mortality was 62%. Of the survivors, only 8% remained dialysis
dependant at
90 days.