Department of Renal Medicine, Leeds General Infirmary, Leeds, UK
Keywords: cardiac transplantation; renal artery stenosis
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Introduction |
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Atherosclerotic renovascular disease is an increasingly common cause of renal failure in the general population, and is associated with those features that also predict dysfunction after cardiac transplantation. In addition, the histopathological changes found in association with renal-artery stenosis are similar to those presumed to be secondary to CsA toxicity. However, the studies of renal failure following cardiac allografting have not looked for renal-artery disease in sufficient detail to exclude this as a possible cause for the decline in glomerular filtration rate and associated renal morphological abnormalities.
We present four patients who developed renal impairment after receiving cardiac transplants, and were subsequently found to have renovascular disease. We suggest that the cardiac transplant population is at risk of atheromatous renal-artery stenosis, and they should be investigated with accurate imaging techniques before they are presumed to suffer from the effects of CsA.
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Cases |
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Case 2
A 53-year-old man with a history of peripheral vascular disease underwent cardiac transplantation following an anterior myocardial infarction complicated by bi-ventricular dysfunction. Preoperatively his creatinine was 133 µmol/l, and a renal-tract ultrasound scan was unremarkable. He was maintained on CsA and azathioprine. He developed hypertension, which was well controlled on two agents. Renal function remained normal for 1 year post-transplantation but then steadily deteriorated, thought to be due to a combination of CsA toxicity and possible renovascular disease. Eight years after he had received his transplant, and with a creatinine of approximately 600 µmol/l, the renal vessels were imaged with CE-MRA, which demonstrated an occluded right renal artery and a tight proximal left renal-artery stenosis; this was stented. Following this procedure, renal function deteriorated rapidly, such that the patient required dialysis within 2 weeks. He was maintained on haemodialysis until he died 2 years later.
Case 3
In 1993, a 54-year-old smoker with a history of insulin- treated diabetes mellitus and cerebrovascular disease received a cardiac allograft for ischaemic cardiomyopathy. He had suffered a myocardial infarction 4 years earlier and required coronary artery bypass grafting. Pre-operatively his renal function fluctuated (creatinine 150230 µmol/l), probably related to diuretic therapy. A renal ultrasound scan did not demonstrate any abnormalities. Following transplantation, maintenance immunosuppression included prednisolone, azathioprine and CsA. His renal function remained impaired but stable, with a creatinine of 225 µmol/l. He developed an episode of acute renal failure following elective repair of an abdominal aortic aneurysm, although this recovered, and his creatinine was 263 µmol/l at the beginning of 1996. The patient then failed to attend any clinic appointments for 1 year, and was then admitted with increasing pulmonary oedema. Renal function had deteriorated markedly (creatinine 803 µmol/l), and he required two sessions of haemodialysis. CE-MRA demonstrated significant bilateral renal-artery stenosis, and the patient underwent successful bilateral renal-artery stenting. The creatinine fell to 562 µmol/l over the next 3 days; however, the patient then died unexpectedly. The post-mortem examination revealed widespread coronary-artery atherosclerosis and cardiomegaly, and renal histological abnormalities included diabetic glomerulosclerosis, arteriosclerosis, and interstitial fibrosis.
Case 4
A 43-year-old man with cardiomyopathy complicated by ventricular dysrhythmias underwent cardiac transplantation. He had a history of excess alcohol consumption, but a cardiac biopsy revealed non-specific changes. There was no evidence of coronary-artery atheroma on coronary angiography. Renal function was normal with a creatinine of 111 µmol/l. Three years after transplantation the patient developed nephrotic syndrome associated with a 24 h urine protein level of 4.24 g. His creatinine was elevated at 222 µmol/l. Renal ultrasound and renal arterial duplex scanning were normal. A renal biopsy revealed widespread global glomerulosclerosis and interstitial fibrosis. Subsequently, renal function continued to decline and he underwent further investigations for renovascular disease. CE-MRA scanning demonstrated a tight right proximal renal-artery stenosis, which was stented. Initial progress was satisfactory with the creatinine improving from 360 to 260 µmol/l over a period of 4 weeks. However, renal function then began to deteriorate rapidly. A renal Doppler ultrasound scan showed no evidence of arterial insufficiency and it was felt that little would be gained by repeat angiography. He was started on dialysis 4 months later and remained on haemodialysis for 9 months before receiving a cadaveric renal transplant. He has remained well over the past 18 months.
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Discussion |
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We have reported four cardiac allograft recipients who developed renal impairment following transplantation and were found to have renal-artery stenosis. Three of our patients demonstrated temporary improvement of renal function following stenting, and it is likely that in these cases arterial insufficiency contributed toward the renal dysfunction. The lack of sustained improvement is not entirely surprising as the renal parenchymal injury often comprises not only ischaemic damage consequent on a haemodynamically significant stenosis, but also intra-renal atheroma, cholesterol embolization, and hypertension. Therefore, the response to revascularization is highly variable [5]. Although the biopsy findings in our cases could be attributed to cyclosporin toxicity [4], very similar renal parenchymal changes are found in association with renal-artery stenosis [6].
We believe that renovascular disease should be readily suspected following cardiac transplantation, as the demographic and co-morbid features of these patients place them at risk. Significant renal vascular lesions are commonly found in patients with coronary-artery disease. The extent of coronary-artery lesions and the presence of congestive cardiac failure are independently associated with significant renal-artery disease [7]. As patients with ischaemic cardiomyopathy represent about 40% of all those receiving a cardiac transplant [8], this group is particularly prone to ischaemic nephropathy and renal dysfunction. This association has been demonstrated [2], although the finding has not been universal [1]. It is also known that after cardiac transplantation, peripheral vascular disease, commonly found in association with renal-arterial disease, occurs 1015 years earlier than would be expected in the general population [9]. It is possible that immunosuppression accelerates the atherosclerotic process, and patients may develop renal-artery stenosis even in the absence of traditional risk factors. Our patient in Case 4 illustrates the point further. He had no evidence of coronary-artery disease and was relatively young. We have reviewed our population of over 200 patients undergoing contrast magnetic resonance angiography to diagnose renal-artery stenosis, and of 19 patients below the age of 50 years, no other patient had a positive scan (unpublished data).
Although searching for renal-artery stenosis has been advocated [3], there has been no accurate assessment of the renal arteries in any of the relevant literature. Van Gelder et al. [1] investigated those patients progressing to end-stage renal failure with Doppler ultrasound scanning. However, this technique can be an inaccurate diagnostic tool [10], and their findings confirm thistwo patients with suspected renal-artery stenosis following duplex scanning subsequently had negative intra-arterial contrast angiograms.
We conclude that renal-artery stenosis should be considered before the assumption is made that renal dysfunction following cardiac transplantation is entirely due to the effects of CsA, as there are potential benefits of intervention. CsA undoubtedly has a deleterious effect on renal function, but it is not the only aetiological factor contributing toward renal damage following cardiac transplantation. Future studies should also address this, to allow further understanding of a common complication of cardiac transplantation.
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Notes |
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References |
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