A controversial renovascular case.
JP Traynor, J Pryce, M Hand and D Kingsmore
A 62-year old female patient with documented history of atheromatous renovasular
disease requiring bilateral renal artery stents developed acute renal failure and pulmonary
oedema after a 1 week history of nausea, vomiting and mild fever. She was admitted
directly to ITU for ventilation and dialysis. Her past medical history included bilateral renal
artery stenting performed in 2005, a possible sub-endothelial MI in 2000, hypertension and
central obesity. Prior to this admission, her baseline creatinine was 118 umol/L and she
was 2 anti-hypertensives although BP control was sub-optimal.
After initial investigations including Doppler ultrasound proved to be either negative or
unhelpful, formal renal angiography was performed (18 days after she presented). This
revealed a patent right renal artery supplying a small kidney, and an occluded renal artery
stent on the left supplying a larger (10.4cm) kidney. The cause of the occlusion was not
clear but was felt to be either neo-intimal hyperplasia or in-situ thrombosis. The renal
artery lesion was successfully angiolastied and 2 further stents placed within the original
stent. She started passing large volumes of urine almost immediately, and other than one
dialysis session immediately after the procedure to minimise contrast nephropathy,
required no further dialysis. She was started on a statin and warfarin and was able to be
discharged shortly after. At follow up 1 month later, her serum creatinine had fallen to 85
umol/L with a BP 120/76 on atenolol only.
In January 2007, she re-presented with acute pulmonary oedema and again required ITU
admission and dialysis. This time she had been completely well until 12 hours prior to
admission. Further angiography revealed that the left renal artery stents had collapsed
although a small amount of contrast filling normal vessels distally. It was felt that this was
providing some renal perfusion although not enough to allow adequate clearance of small
solutes and free water.. Attempted angioplasty from the groin was unsuccessful on 2
occasions. Her long-term dialysis options were limited. Temporary dialysis access had
been extremely difficult to achieve and we were pessimistic about chances of either a
tunnelled semi-permanent catheter or AV fistula. Also, due to her central obesity PD was
not a realistic option. After 10 days of being dialysis-dependent she was therefore referred
for consideration of exploration of the right kidney, and if viable, revascularisation using
either ilio-renal bypass or auto-transplantation to the right iliac fossa, with reconstruction of
the renal artery with either the internal iliac or long saphenous vein, given that the longterm future on dialysis would be a transplant.
RENAL FUNCTION AND VASCULAR STIFFNESS IN CORONARY ARTERY DISEASE
Christian Delles1 Lukas U. Zimmerli1, Kenneth J. MacArthur2, Tracey Steedman1, Henry J. Dargie1,
and Anna F. Dominiczak1
1
2
BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow
Department of Cardiothoracic Surgery, Western Infirmary, Glasgow
Objective. We have previously demonstrated increased vascular stiffness in end-stage renal disease
and in coronary artery disease (CAD). Here we examine whether mild to moderate renal
impairment further increases vascular stiffness in patients with severe CAD.
Design and method: In 72 patients with severe three-vesel CAD (age, 62±9 years) we measured
carotid-femoral pulse wave velocity (PWV; n=52) using the SphygmoCor® Vx system and
compliance of the ascending aorta by cardiac MRI (1.5 T Siemens Sonata; n=49). Glomerular
filtration rate (eGFR) and creatinine clearance (ClCrea) were estimated by 4-variable MDRD formula
and the formula of Cockroft and Gault, respectively.
Results. eGFR ranged from 27 to 103 (mean, 63±14) mL/min and ClCrea from 34 to 129 (mean,
74±23) mL/min. Patients with eGFR <60 mL/min (n=27) had higher PWV (9.2±1.9 vs 7.6±1.8 m/s;
P=0.003) and lower aortic compliance (6.7±3.8 vs 13.0±6.4 µL/mmHg; P<0.001) than patients with
eGFR ≥60 mL/min (n=45). In line with these findings, PWV (r=-0.301; P=0.030) and aortic
compliance (r=0.601; P<0.001) were correlated with ClCrea. eGFR <60 mL/min was associated with
an unfavourable constellation of factors involved in the pathogenesis of atherosclerosis (Table).
Conclusions. In patients with CAD mild to moderate impairment of renal function is associated
with increased vascular stiffness. This may be explained by unfavourable effects of chronic renal
failure on inflammatory and pro-atherogenic factors. Our data support aggressive management of
co-existing conditions such as chronic renal failure in patients with CAD.
eGFR<60 mL/min
eGFR ≥60 mL/min
P value
CRP
(mg/L)
7.0±13.6
5.7±16.0
0.038
Leptin
(µg/L)
30.7±25.3
15.0±9.0
0.004
oxLDL/LDL
(mmol/L AU-1)
28.0±9.7
22.7±8.9
0.027
Table.
oxLDL/LDL denotes ratio between oxidised LDL cholesterol and LDL cholesterol
Source of funding: British Heart Foundation
Conflict of interest: none
Fabry Disease: An overview and case presentation
Dana Kidder and William Smith
Renal Unit, Monklands Hospital, Airdrie
Fabry disease is an under-recognised X- linked lysosomal storage disorder
characterised by the deficiency of alpha-galactosidase A (α-GAL A). This deficiency
leads to the progressive accumulation of globotriaosylceramide (GL-3/Gb3) in the
vascular endothelium and visceral tissues culminating in end organ damage.
The clinical manifestations are variable, from early symptoms in childhood and
adolescence to late life threatening complications such as renal failure, stroke and
cardiovascular events in early and mid adulthood.
Early classic symptoms include acroparathesias, ocular opacities, hypohidrosis and
angiokeratomas. Renal manifestations commonly include proteinuria, progressive
glomerulosclerosis with GL-3 deposition and end stage renal disease.
Recent advances in this condition include enzyme replacement therapy in the form of
agalsidase which is administered by iv infusion every 2 weeks. Results of recent
stage III and IV clinical trials show significant risk reduction for renal, cardiac and
cerebrovascular events with enzyme replacement therapy.
We present a case of proteinuria and haematuria, with classical zebra inclusion bodies
on renal biopsy and negligible α-GAL A activity. The clinical profile, progress,
NSCAG approval and response to enzyme replacement therapy will be discussed.
Cardiac Troponins in Established Renal Failure
Asif Ansari, Graham Smith* and William Smith
Renal Unit, Monklands Hospital, Airdrie; *Department of Statistics and Modelling Science,
University of Strathclyde, Glasgow
Background: Troponin (Tn) proteins are the gold standard of biomarkers in myocardial
injury/infarction. Both TnT and TnI are sensitive and specific in general but can be altered in non
cardiac conditions such as renal failure, sepsis and acute stroke. Cardiovascular disease, left
ventricular hypertrophy, inflammation, sepsis, abnormal protein metabolism and clearance are
common in end stage renal disease. Many hypotheses have been put forward for the elevation of Tn,
in the absence of myocardial injury in dialysis patients. How do we interpret raised Tn, does it have
a diagnostic or prognostic value?
Methods: We studied an unselected haemodialysis population. Analyses were performed on
predialysis monthly bloods for TnT, TnI, CRP, PTH, and cholesterol. All case records were
reviewed for ECG’s and echocardiograms. Bloods for TnT, CRP, and PTH were repeated 6 months
later and patients were followed up for 12 months. Statistical analysis was performed using SPSS.
Results: The study started with 141 patients, mean age 60, mean duration of dialysis 39 months.
ECG’s were reviewed in 89% of patients and 74% had Echo’s. TnT(1) was raised (normal <0.03) in
63 patients (45%), TnT(2) was raised in 56 of 118 patients (48%) and TnI was elevated (normal
<0.2) in 5 of 135 patients (3.7%). TnT, TnI, CRP and PTH were all skewed in distribution and
results are median and (interquartile range).
TnT(1) = 0.028 (0.07), TnT(2) = 0.025 (0.09), TnI = 0.019 (0.04), CRP(1) = 12 (28), CRP(2) = 9.5 (24),
PTH(1) = 26 (30), PTH(2) = 24 (28). Correlations were done with Spearman rho analysis. Strong
correlations were found between Tn measurements, correlation coefficient (cc) >0.6, p at 0.01 level.
Moderate correlations were found between TnT and CRP, age and outcome cc >0.3, p at 0.01.
Weaker correlations were detected between TnT and ECG and Echo results. No significant
correlations were derived between TnT and PTH, cholesterol or duration of dialysis. Mortality at 12
months was 26.2% of which 18.4% had raised TnT.
Conclusion: These preliminary data need cautious interpretation. TnT was very marginally elevated
in almost half of the haemodialysis patients whereas TnI was normal. TnT appears less specific but
a higher accepted cut-off for renal failure patients would correct this apparent false elevation. The
association between TnT and CRP is suggestive that inflammation/infection may be an influential
factor. Elevated TnT appears to be a negative prognostic factor after 12 months follow-up.
The evolution of end stage renal failure in Ayrshire and Arran – the influence of referral
patterns, diabetes and vascular disease.
Andrew Innes, Mark S MacGregor, Nestor Velasco, Pamela M Mackenzie
and Ian G Mackay.
Renal Unit, Crosshouse Hospital, Kilmarnock.
The Renal Unit in Ayrshire was established in 1990 and since then almost 650 patients have
received RRT for chronic renal failure at the Unit. The take-on rate has risen from 53 per million
(1993) to 157 per million in 2006. In the early years between 42% and 58% of patients needed
dialysis less than one month after first seeing a nephrologist but by 2006 this had fallen to 10%.
Similarly, the median creatinine at first presentation to a nephrologist was consistently over
500µmol/l in the early 1990s but was 248µmol/l (eGFR =22 ml/min corrected) in 2006.
The median age at first dialysis has risen from 52 (1990) to 64 (2006) with a peak of 70 years in
2004. Currently, 61% of new RRT patients have either diabetes or pre-existing vascular disease
(32% have diabetes; 44% have vascular antecedents). As in the rest of Scotland, increasing
numbers on RRT have produced a major demand on hospital HD provision (39 patients on hospital
HD in 1994; 134 in 2006). Crosshouse has a flourishing PD programme which has also increased
from 27 in 1994 to 42 in 2006; now with 86% on APD. In the prevalent dialysis population (HD
and PD) 21% are diabetic and 38% have vascular antecedents; almost half (48%) have at least one
of these comorbidities. Of the 59 patients starting RRT in 2006, 12 started PD and 47 HD (10 with
functioning fistulas, 37 with catheters).
As in other parts of Scotland, the relentless increase in numbers of patients starting haemodialysis
places demands on HD spaces. These patients are increasingly elderly and now a sizeable majority
enter dialysis with significant comorbidity in terms of vascular disease and diabetes. The problem
of late referral (and consequent “acute” need for dialysis) appears to be addressed and diminished
by the establishment of a renal unit in an area. Nevertheless, creatinines at the time of referral (of
those who subsequently go on to require dialysis) remain stubbornly around 250µmol/l.
Nephrotic syndrome presenting as venous thromboembolism
Vik Selvarajah, Bill Ambler, Chris Isles
Renal Unit, Dumfries and Galloway Royal Infirmary, Dumfries, DG1 4AP.
A patient presenting with a swollen left leg and pleuritic chest pain was shown to have deep vein
thrombosis by doppler studies. He was anticoagulated but represented six weeks later with swelling
of both legs while on warfarin. No fresh thrombus was seen and warfarin was continued. Three
weeks later he was readmitted with swelling that extended to both upper thighs. A degree of
redness led to a diagnosis of cellulitis and treatment with antibiotics. Urinalysis was not recorded
during one of these admissions, while a positive dipstick result for proteinuria was overlooked
twice. Following his third discharge from hospital, the GP noted heavy proteinuria and referred the
patient directly to the Renal Clinic where urine protein was quantified at 12.3 g/24 hours and a
diagnosis of nephrotic syndrome was confirmed. Renal biopsy showed that this was due to
membranous nephropathy.
We subsequently conducted two audits. The first was of patients with diagnostic discharge codes
for nephrotic syndrome and venous thromboembolism in south west Scotland (population 147,000)
from 1996 to 2006 in order to determine the frequency with which DVT or PE had been the
presenting feature of nephrotic syndrome. We were able to confirm a diagnosis of nephrotic
syndrome in 32 patients, all of whom had oedema, serum albumin < 30 g/l and proteinuria > 3 g/24
hours. No fewer than four (12.5%) of these including the index case had presented with DVT (2) or
PE (2). Three had membranous nephropathy and one had minimal change nephropathy. Renal vein
doppler studies were normal in both patients with PE. The diagnosis of nephrotic syndrome was
made during the first admission to hospital in all patients except the index case. A second audit of
98 consecutive patients with doppler positive lower limb DVT presenting to A&E in Dumfries from
July 2005 to July 2006 showed that the urine had been tested for protein in one case only.
These results support the view that nephrotic syndrome is complicated by venous thromboembolism
sufficiently frequently for the diagnosis to be considered in all patients with DVT or PE. The move
towards managing patients with DVT in the community may mean that patients are even less likely
to have urinalysis performed. The take home message for patients with DVT or PE must simply be
– don’t forget to dip the urine.
Word count: 385
Abstract
Renal Failure in Patients with Multiple Myeloma
Shona Methven, Nicola Joss, Jonathan Fox
Renal Unit, Glasgow Royal Infirmary
Background and aims: Renal disease in multiple myeloma can present in a variety of ways and
predicts outcome. We present data on the severity of renal failure at referral to renal services,
frequency of renal biopsy, frequency of renal replacement therapy (RRT) and survival in patients
diagnosed with multiple myeloma in a single centre.
Methods: Patients attending the Renal Unit, Glasgow Royal Infirmary between 1989 and March
2006 with a diagnosis of multiple myeloma were identified from the electronic patient record.
Results: One hundred and twenty two patients were identified (60.7% males). At referral, the mean
age was 65.5 years (SD 11), median serum creatinine was 400µmol/L (IQR 200,693), and median
estimated glomerular filtration rate (eGFR) by the MDRD formula was 11.5 ml/min (IQR 6,25). 1%
of patients were referred at CKD stage 1, 6% at CKD stage 2, 15% at CKD stage 3, 23% at CKD
stage 4 and 55% at CKD stage 5. Other baseline data were mean serum albumin 32.7 g/L (SD 7.3),
adjusted calcium 2.4 mmol/L (SD 0.3) and haemoglobin 10 g/dL (SD 2.2). 35.3% had serum
albumin less than 30 g/L. Of those who had proteinuria measured (82 patients), 32% had nephrotic
range proteinuria.
Thirty-four patients (27.9%) had a renal biopsy. There was no statistically significant difference in
age, serum creatinine, eGFR, or serum albumin between the biopsy group and the non-biopsy
group. The diagnoses made by renal biopsy were: cast nephropathy n=14, AL amyloidosis n=9,
light chain disease n=5, heavy chain disease n=1, acute interstitial nephritis n=4, acute tubular
necrosis n=2 and ischaemic/hypertensive nephropathy n=2 (some patients had >1 diagnosis).
Fifty-three patients (43.4%) received RRT with 28 patients (52.8%) starting RRT within 1 week of
referral. Fifteen patients who started RRT recovered renal function with a median time to recovery
of 4.0 days. No patients fully recovered renal function (to eGFR > 60ml/min) during follow up. Of
those who did not recover renal function, median survival on RRT was 22.5 months (95%CI
7.5,37.5). Overall, median patient survival from time of referral was 18.7 months (95%CI 10,27.4)
with a 1-year survival of 58.6% and 5-year survival of 25.9%.
Conclusion: Renal failure in patients with multiple myeloma often presents late, frequently requires
renal replacement therapy, and has a poor prognosis. Indications for renal biopsy in patients with
multiple myeloma remain unclear.
Diurnal variation of phosphate is maintained in end-stage renal disease.
Elaine M Spalding & Ken Farrington. Lister Hospital, Stevenage.
Introduction. Marked diurnal variation exists in plasma phosphate concentration in normal
individuals but it is not known if this, or diurnal variation in regulating hormones is maintained in
CRF.
Subjects and Methods. Eight subjects, four with normal renal function and four with CRF were
studied for 24 hours with hourly measurements of phosphate, calcium, bicarbonate, potassium,
albumin and glucose and two hourly measurements of PTH, GH, cortisol and insulin. Analysis of
diurnal variation was by rhythm biometry using cosinor methodology and relationships between
variables were investigated by cross-correlation.
Results. Diurnal variation in phosphate, calcium, phosphate excretion, bicarbonate, PTH and
cortisol is maintained and is well described by harmonic periodic regression. The relationship seen
between phosphate and PTH in normal renal function is maintained in advanced CRF but there are
marked differences in the relationship between calcium and PTH and in acid-base status between
the two groups.
Conclusion. The diurnal variation that is maintained in non-oliguric CRF has implications for the
timing of blood samples when initiating treatment for bone disease or monitoring response to
treatment. There are potential long-term implications for the planning of dialysis schedules.
Conflict of interest: none
Source of funding: unit funds
The provision of accommodation by Roche Pharmaceuticals Clinical Pharmacology Unit, Welwyn
Garden City for the duration of the above study is gratefully acknowledged.
Endothelial cell protection from complement activation – relevance to the pathogenesis of atypical
Haemolytic Uraemic Syndrome
Anna Richards1,3, David Kavanagh2,3, Kathy Liszewski3, John Atkinson3
1
Edinburgh Royal Infirmary, Little France, Edinburgh
2
Department of Chemistry, Kings Building, University of Edinburgh
3
Washington University School of Medicine, St Louis, MO63110, USA
Introduction
Haemolytic uraemic syndrome, the clinical triad of microangiopathic haemolytic anaemia,
thrombocytopenia and acute renal failure, is characterised by damage to microvascular endothelial cells,
particularly in the glomerular and renal arteriolar endothelium. Endothelial cells (EC) are highly
specialised cells capable of producing both anti and pro-inflammatory mediators. The macrovascular EC
line, HUVEC, express the membrane bound complement regulators CD46, CD55 and CD59. They also
synthesise the soluble complement regulators factor H, factor I and the activating components factor B
and C3. Mutations in the alternative pathway complement regulators factor H, factor I and CD46 have
previously been described in atypical HUS (aHUS). More recently, mutations in Factor B and C3 have
been reported. Our aim was to characterise the complement regulatory profile and response to
complement activation of microvascular and glomerular ECs.
Methods
Characterisation of an immortalised human microvascular endothelial cell line (HMEC) and a primary
glomerular endothelial cell (GEC) line was undertaken. Expression of the complement regulators CD46,
CD55 and CD59 was examined using FACS, ELISA and Western blotting. Synthesis of Factor H, C3
and Factor I was assessed by Western blotting. Binding of factor H and factor I to HMEC was assessed
by FACS. A ‘Complement Challenge’ experiment, whereby antibody was used in the presence of human
serum to deposit complement on the endothelial cell surface was developed and the effects of blocking
complement regulators singly, and in combination, examined.
Results
Like HUVEC, HMEC and GEC also express the membrane bound complement regulatory proteins CD46,
CD55 and CD59 on their surface. They do not express CR1. These cells are typical endothelial cells,
expressing a wide range of endothelial cell marker antigens. However differences between HMEC and
GEC can be found, suggesting an important role for specialisation in different endothelial cell beds. Using
EDTA to activate the classical pathway of complement in the Challenge assay, it was possible to show
differential function and effectiveness of the soluble and membrane bound complement regulatory
proteins in down-regulating complement on the HMEC surface. These effects were additive. Using
MgEGTA as a buffer to preferentially activate the alternative pathway it was possible to show a
significant difference in the ease with which the two pathways of complement could be activated on
HMEC.
Conclusions
We have characterised complement regulator protein expression in both a microvascular and renal
endothelial cell systems. We have developed a sensitive and highly modifiable system for assessing the
effects of complement activation on the surface of endothelial cells. Future work will look at Factor B and
C3 synthesis and secretion by HMEC and GEC, which have recently been implicated in the pathogenesis
of aHUS. This system could also be used to look at the effectiveness of pharmacological methods of
protecting endothelial cells from complement-mediated attack.
Characterization of Mutations in Complement Factor I (CFI) Associated with Haemolytic Uraemic
Syndrome
David Kavanagh1, Anna Richards1, Marina Noris2, Judith Goodship3, Veronique FremeauxBacchi4, Giuseppe Remuzzi2, Timothy H. J. Goodship3, John P. Atkinson1*
1
Washington University School of Medicine, St. Louis, U.S.A.
Mario Negri Institute,Bergamo, Italy
3
Institute of Human Genetics, University of Newcastle upon Tyne.
4
Hôpitaux Européen Georges Pompidou, Paris, France
2
Recent studies have identified mutations in the complement regulatory gene factor-I (CFI) that
predispose to atypical haemolytic uraemic syndrome (aHUS).
CFI is a two chain serine protease in which the light chain carries the catalytic domain while the heavy
chain’s function is unclear. CFI downregulates the alternative and classical complement pathways by
cleaving the α chains of C3b and C4b (cofactor activity). Many CFI mutations in aHUS result in low CFI
levels with a consequent quantitative defect in complement regulation. In others, the mutant protein is
present in normal amounts but the presumed functional deficiency has not been defined. In this report we
examine the nature of the functional defect in aHUS-associated CFI mutations.
A representative subset of aHUS associated CFI mutants was chosen for study from our prior genetic
analysis. The aHUS-mutations were introduced into CFI cDNA containing a 6X histidine tag using
Quikchange®. Transient transfections of 293T cells were performed. The recombinant CFI was purified
using an AKTA purifier® with a HisTrap column. C3b and C4b endpoint and kinetic cofactor assays were
then performed.
Three mutations (D506V, D501N, R299W) demonstrated a loss of both C3b and C4b cofactor activity.
In two heavy chain mutants (M120I, G243D) cofactor activity was normal. The L466V+Q467G+W468X
mutant was retained intracellularly consistent with the low serum level of CFI seen in this patient.
Modelling of CFI predicts that both D501 and D506 form part of the walls of the specificity pocket of
the serine protease domain of CFI. Our results provide experimental evidence supporting this modelling
prediction and demonstrate that this region is critically important to the serine protease function of CFI.
R299W resides in part of an unidentified domain region of unknown function between the LDLRa
domain and the serine protease domain. Our experiments demonstrate that the R299W mutation results in a
decrease in C3b and C4b cofactor activity, establishing that this novel region plays a role in C3b and C4b
cleavage.
Mutations in the heavy chain domains CD5 and LDLr did not affect fluid phase cofactor activity. These
mutations may point to an as yet undiscovered function of the non-catalytic domain in the regulation of
complement.
In summary we demonstrate that 4 out of the 6 CFI mutations studied result in a loss of both alternative
and classical pathway cofactor activity.
THE RELATIONSHIP BETWEEN HAEMODIALYSIS CATHETER CHOICE,
CLINICAL OUTCOME AND RECOMMENDED PRACTICE.
Peter C Thomson*, Catherine Stirling**, Scott Morris**,
Robert A Mactier**.
* Research Fellow in Renal Medicine, Renal Unit, Glasgow Royal Infirmary.
** Consultant Nephrologist, Renal Unit, Glasgow Royal Infirmary.
Correspondence to:
Dr Peter Thomson, Renal Unit, 3rd Floor Walton Building, Glasgow Royal Infirmary, 84 Castle
Street, Glasgow, G4 OSF
Tel:
(+44) 141 211 0570
Fax: (+44) 141 211 4843
Introduction
Haemodialysis catheter use can be associated with significant complications. In cases of
suspected catheter thrombosis or low-grade catheter-related bacteraemia in the absence of
subcutaneous tunnel infection, NKF-KDOQI advocate catheter exchange over a guide-wire. This
study compared rates of catheter-related bacteraemia following various types of catheter insertion,
including how catheter-exchange over a guidewire compares with catheter replacement at a
different site.
Methods
We performed a prospective analysis of all incident vascular access haemodialysis catheter
insertions over the period starting 05/08/2005 and ending 05/08/2006. Laboratory and clinical
variables were recorded at catheter insertion and the clinical course was followed up to the point of
catheter removal. The primary outcome measure was catheter-related bacteraemia as defined by
the presence of positive blood cultures, clinical and biochemical evidence of a raised systemic
inflammatory response and the absence of evidence of infection arising from a different site.
Univariate analysis was used to test for association between clinical and laboratory variables and
subsequent outcome. Significant univariates were then put forward for inclusion in a multivariate
model to test for independent association.
Results
15,834 catheter days were accumulated over the study period during which time a total of 206
patients underwent insertion of 131 tunnelled central venous catheters (TCVCs) and 271 nontunnelled central venous catheters (NTCVCs).
Rates of catheter-related bacteraemia per 1000 catheter days were 1.88 in the TCVC group, 7.86
in the internal jugular vein NTCVC group [Hazard Ratio (HR) 2.8, p=0.004], 10.99 in the femoral
vein NTCVC group [HR 5.2, p=0.009], 14.89 in the internal jugular NTCVC guidewire group [HR
6.9, p<0.001] and 45.45 in the femoral vein NTCVC guidewire group [HR 21.7, p<0.001]. These
associations were independent of age, sex, diabetes and length of time on renal replacement
therapy.
Patients who had undergone NTCVC exchange over a guidewire were found to have significantly
higher rates of catheter-related bacteraemia (17.9 v 7.3 per 1000 catheter days, p=0.025) when
compared with those who had undergone NTCVC replacement at a de novo site.
Conclusion
Haemodialysis catheter-exchange over a guidewire was the catheter insertion strategy most
strongly associated with subsequent catheter-related bacteraemia. Guidelines should be amended
to suggest that catheter-exchange over a guidewire only be conducted when catheter replacement
at a de novo site is unachievable. Vascular access catheters remain a significant contributor to
the burden of infection in the haemodialysis population.
Paying The Price For A Transplant - An Unusual Case Of Urinary Sepsis.
Kate Preece1, David Walbaum1, Ian Laurenson2, John Govan2, and Paddy Gibson1
1Renal Unit and 2Department of Microbiology, Royal Infirmary Edinburgh.
A thirty-five year old man who had been on hospital haemodialysis in Edinburgh for two years due
to end stage renal failure secondary to membranous glomerulonephritis, returned from Pakistan
having received a live unrelated renal transplant.
On return to the UK initial graft function was excellent, however he had an episode of
acute cellular rejection confirmed by allograft biopsy on day 15, and was treated with
intravenous corticosteroid and switched from cyclosporine to tacrolimus.
On day 50 he presented with a fever, general malaise and night sweats. He had no urinary
symptoms. Subsequent investigations confirmed a urinary tract infection with the gram
negative bacillus Burkholderia Cepacia.
This unusual pathogen is most frequently found in cystic fibrosis or lung transplant
patients, and is notoriously difficult to eradicate. The only previous reported case of B.
Cepacia in a renal transplant recipient resulted in graft nephrectomy. Our patient was
treated with removal of his ureteric stent and one month of intravenous antibiotics. Two
months later his graft function is satisfactory and his urine free of infection.
No conflict of interest or funding.
Unsuspected Mycotic Aneurysm of Renal Transplant Artery
1
D Henderson, 1A Pall, 2S Chakravarty
1
Departments of Renal Medicine & 2Radiology, Ninewells Hospital & Medical School, Dundee
A 31year old female with ESRD secondary to mesangiocapillary glomerulonephritis type 2 received
a cadaveric renal transplant. Cause of donor death was hypothermia and extradural hamatoma.
Mismatch 210 and crossmatch negative. Protocol immunosuppression was used and consisted of
loading dose IV Methyl Prednisolone followed by maintenance tacrolimus, azathioprine and
prednisolone. Transplant function was satisfactory with serum creatinine 95 umol/L. However the
immediate post-operative period was complicated by a febrile illness but with initial blood and
urine cultures and USS/Doppler of transplant kidney negative. By day 10 she had developed
obvious oropharangeal thrush and blood cultures grew candida albicans. She was initiated on
fluconazole with apparent complete clinical response and negative blood cultures. During the
course of treatment for the candidaemia the serum creatinine increased to 150 umol/L, USS/Doppler
again normal but transplant biopsy confirmed an acute cellular rejection. This was treated with
pulse IV Methyl Prednisolone 250 mg x3 and switch from azathioprine to mycophenolate. Her
subsequent condition remained stable with excellent renal allograft function. However four months
post-transplant she was admitted with subacute bowel obstruction thought to be due to fibrous
adhesions related to abdominal surgery pre-transplant. At this time she was afebrile with stable
allograft function (serum creatinine 100 umol/L), normal CRP and controlled BP. USS abdomen
noted the incidental finding of a transplant artery aneurysm (figure 1). This was confirmed on the
MRA examination which reported a presumed mycotic aneurysm of the transplant artery measuring
4.5 cm diameter and extending to the external iliac artery (figure 2). She underwent transplant
nephrectomy and excision of the aneurysm with saphenous vein patch to the external iliac artery.
She was treated empirically at this time with IV flucytosine and amphoteracin although fungal
cultures from the aneurysm sac and stitches from iliac vessels returned negative. Subsequent
progress was complicated by bleeding from deep circumflex branch of the external iliac artery
controlled by endovascular embolisation and subsequent to this an infected haematoma and false
aneurysm with compromise to left leg circulation, which required surgical repair. One year later she
is well on maintenance haemodialysis and is under consideration for a second renal transplant.
Mycotic aneurysm complicating renal transplantation is rare and often diagnosed at post-mortem
after rupture. A low threshold of suspicion is needed for early detection and should be considered
whenever renal transplantation is complicated by serious fungal infection.
Evolution of B-Lymphocyte Infiltration in Acute Cellular Renal Transplant Rejection (ACR) – an
illuminating case report.
1
A Pall, 1V Sanu, 2S Fleming, 1G Stewart, 1I Henderson
Departments of Renal Medicine1 & Pathology2
Ninewells Hospital & Medical School, Dundee
B-lymphocyte infiltration in ACR of the renal allograft has been recently reported and associated
with steroid resistance and worse graft survival. This is seen without evidence of an allohumoral
response (negative C4d staining and DSA). The underlying mechanism and treatment strategy have
yet to be elucidated. We describe a renal transplant recipient, who provided an opportunity to detail
the evolution of a significant B-lymphocyte infiltration, the clinical and histological response to
rituximab. A 32-y/o male with ESRD secondary to IgA nephropathy on maintenance HD for 2 years
received a LRT from his mother. PRA 0%, luminex & XM negative, MM 101, EBV D+/R+, CMV
D-/R-. He received protocol loading dose MePred, tacrolimus, azathioprine and prednisolone. The
transplant was complicated by DGF and the best se.creatinine achieved was 200 umol/L presumed
because of donor/ recipient size disparity. Progress from day 20 and over the next eight months was
complicated by recurrent ACR. This was of varying intensity but appeared to be steroid responsive
on follow-up biopsies. C4d staining and DSA were negative. During the course of follow-up
maintenance IST was adjusted to SRL/MMF/Pred. He had declined anti-lymphocyte antibody
treatment. However after the fourth course of pulse MePred he suffered a further episode of acute
rejection and the biopsy was stained for B-Lymphocytes. These were found to account for 60% of
the lymphocyte infiltrate. A lymphoid aggregate had been noted on a previous biopsy and stained
negative for EBV with low proliferation rate (evidence against PTLD). Because of the high
proportion of B-lymphocytes it was decided to treat with rituximab 175mg/m2 weekly x2. This
resulted in a sustained B cell depletion and repeat biopsy showed complete resolution of the
infiltrate with no CD20. He was switched back to tacrolimus and maintained on this with MMF and
prednisolone. Allograft function stabilised to serum creatinine 270 umol/L. Retrospective staining
for CD20 of all previous biopsies identified a progressive B-lymphocyte infiltrate also apparent on
the biopsies suggesting resolving ACR after pulse steroids. B-lymphocyte infiltration should be
considered with recurrent episodes of ACR when steroid-resistant but also if follow-up biopsy is
suggestive of resolution. Banff has recently been updated in the context of C4d staining and AMR.
In the future the classification may also need to consider the role of B-lymphocytes. We have
shown that rituximab can clear B-cells from the renal allograft when these constitute a significant
proportion of the lymphocyte infiltrate in ACR. Studies are needed to confirm that this translates
into improved clinical outcome.
Pancreas Transplantation in Scotland.
David Walbaum, Christine Jansen, Murat Akyol and Caroline Whitworth.
Transplant Unit, Royal Infirmary of Edinburgh, Old Dalkeith Road, Edinburgh, EH16 4SA.
The first pancreatic allograft transplant in Scotland took place in April 2000, since when a
total of 77 have been performed. This includes 68 simultaneous pancreas-kidney
transplants, 6 pancreas after kidney transplants and 3 pancreas alone transplants.
Patients have been referred from all ten adult renal units in Scotland, with a significant
number of patients being transplanted pre-emptively, before the need for renal
replacement therapy.
The median waiting time for pancreatic transplantation is significantly shorter than for
cadaveric kidney transplantation, and the donors are younger.
One year patient survival is 96.8%, renal allograft survival is 94% and insulin-free
pancreatic allograft survival is 80%. The rate of biopsy proven renal allograft rejection is
24%. The median in-patient hospital stay following a pancreas transplant is 16 days.
We present a review of pancreatic transplant activity in Scotland.
No conflict of interest or funding.