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 developedacute 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 beeither 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 long-term 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 BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow
2 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.
CRP(mg/L) / Leptin
(µg/L) / oxLDL/LDL
(mmol/L AU-1)
eGFR<60 mL/min / 7.0±13.6 / 30.7±25.3 / 28.0±9.7
eGFR ≥60 mL/min / 5.7±16.0 / 15.0±9.0 / 22.7±8.9
P value
/ 0.038 / 0.004 / 0.027Table.
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,MonklandsHospital, 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, MonklandsHospital, 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, CrosshouseHospital, 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.
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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 2006with 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. ListerHospital, 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
1Edinburgh Royal Infirmary, Little France, Edinburgh
2Department of Chemistry, KingsBuilding, University of Edinburgh
3WashingtonUniversitySchool 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.