A unique case of acute embolus in a renal transplant with salvage by catheter-directed thrombolysis

Introduction

Acute renal arterial embolus can be disastrous in a transplant patient and result in loss of the renal transplant. Unlike renal artery thrombus, which occurs most commonly in the first month after transplantation with an incidence of 0.5%–3.5%, ¹ renal artery embolism is very rare. We describe a case of acute emboli in a 66-year-old female renal transplant patient with successful use of intra-arterial catheter-directed thrombolysis to salvage the transplant.

Case presentation

Following end stage renal failure secondary to adult polycystic kidney disease, a deceased heart-beating donor (DBD) renal transplant was performed in January 2011 with immediate transplant function and no post-operative complications. The recipient had healthy external and distal common iliac arteries, a heavily calcified internal iliac artery with a healthy pliant external iliac vein. The donor was a 24-year-old male patient. The kidney had three arteries; however, these were anastomosed to the recipient on a single patch. The arterial patch was anastomosed onto the proximal external iliac artery end-to-side. There was one vein and one ureter. The vein was anastomosed onto the external iliac vein end-to-side. There were no vascular anastomotic issues at the time of transplant. Routine induction and immunosuppression with Tacrolimus, Mycophenolate Mofetil and Prednisolone was used. Cold ischaemic time was 17 h 45 min and anastomotic time was 35 min. She had excellent transplant function with an average creatinine of 60 µmol/l and an eGFR of 80–90 ml/min. She was on clopidogrel following a previous stroke, having had an upper gastrointestinal bleed on aspirin. This lady had no history of peripheral vascular disease nor of underlying cardiac disease.

In October 2014, she presented with a 24-h history of feeling unwell, vomiting and complaining of right thigh and right-sided transplant pain. This was preceded by palpitations. There was an associated rise in her serum creatinine level and new onset atrial fibrillation (AF) with rapid ventricular response demonstrated on electrocardiogram (ECG).

Admission blood tests showed acute kidney injury (an acute creatinine rise from 60 to 170 µmol/l and then to 258 µmol/l within 12 h). Bedside ultrasound scan demonstrated some transplant perfusion initially. However the symptoms progressed by the following morning with increasing leg pain and the patient was anuric with absent transplant perfusion. There was no palpable right popliteal artery pulse, with acute leg ischaemia distal to this.

Investigations

A renal transplant angiogram was performed via the right (ipsilateral) common femoral artery. This confirmed acute emboli in the branches of the renal transplant arteries arising from the external iliac artery which was occluding over 70% of the kidneys’ arterial supply. There was sparing of an early branch that supplied the upper pole, and a small amount of the lower pole, but the main central and lower pole branches were largely occluded (Figures 1 and 2). Angiography of the right leg demonstrated an acute embolic clot in the right distal popliteal artery occluding the trifurcation, with sluggish reconstitution of the anterior and posterior tibial arteries. She was diagnosed with transplant renal artery and popliteal artery emboli secondary to AF. OPEN IN VIEWER

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Figure 2.

Pre-thrombolysis angiogram demonstrating poor kidney perfusion 0 h.

Management

Attempts to pass an aspiration catheter or Fogarty over-the-wire balloon were unsuccessful due to the tortuosity and small calibre of the renal transplant artery. A Van Schee catheter was placed percutaneously in the origin of the transplant artery, and 3000 units of heparin and 5 mg of the recombinant tissue-type plasminogen activator (tPA) alteplase (Actilyse, Boehringer Ingelheim, Bracknell, UK) were injected in small boluses into both the clot and the renal artery. The catheter was left in the clot and a tPA and heparin infusion was commenced as per the local thrombolysis protocol. The tPA was infused at a rate of 0.5 mg/h via an infusion pump via the intra-arterial catheter and the heparin was injected at a rate of 500 units/h via the side arm of the catheter sheath.

A repeat renal angiogram 24 h later showed significant improvement in appearances with some patchy perfusion in the mid polar aspect of the kidney and improved perfusion in the upper and lower pole vessels. A further repeat angiogram at 36 h showed good perfusion of the upper and lower poles; however, there was still a large central defect (Figures 3 and 4). Despite this, global perfusion was significantly enhanced. Thrombolysis was stopped at 36 h as it was felt there would be minimal ongoing benefit. Surgical embolectomy of the right superficial femoral artery was performed successfully in theatre the following day with good clinical recovery. There was no need for fasciotomy. Intravenous systemic heparin was then infused at a rate consistent with the local hospital protocol keeping a systemic APTT ratio 1.8–2.8 until fully anti-coagulated on warfarin. OPEN IN VIEWER

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Figure 4.

Post-thrombolysis angiogram demonstrating improved kidney perfusion, 36 h.

Outcome

The patient was initially oliguric with a urine output of 100 ml on day 1 but this had improved by day 5 post-thrombolysis to 1210 ml (600 ml day 2, 575 ml day 3, 735 ml day 4, 1210 ml day 5, 1440 ml day 6 and 2540 ml day 7). There was a corresponding fall in the serum creatinine from a peak of 493 µmol/l day 5 to 208 µmol/l by day 12.

Bisoprolol was used for rate control of AF. A transthoracic echo confirmed underlying cardiac disease as a contributory factor for the development of AF. It showed a mildly dilated left atrium with mild calcific mitral stenosis and mild to moderate mitral regurgitation. It also showed moderate left ventricular hypertrophy but good left and right ventricular function and no evidence of pulmonary hypertension. No intracardiac thrombus was seen.

The patient was discharged 12 days after the initial acute episode. Three months post-thrombolysis, good renal transplant function has been regained with a creatinine of 120 µmol/l. She remains on warfarin for anticoagulation and bisoprolol for rate control of AF. She also continues under the follow-up of the cardiologists for her valvular heart disease.

Discussion

Renal artery emboli in transplant patients can be disastrous and result in loss of the transplant. It is a rare occurrence and the incidence is unknown. In native kidneys, the quoted incidence of renal artery emboli is 6.1 patients per million. ² In a systematic literature search of the PubMed database using key words renal transplant, embolus, thrombolysis in varied combinations, we did not find other cases of acute embolus in a renal transplant artery secondary to AF that were treated with intra-arterial catheter-directed thrombolysis.

Our patient presented three and a half years after the initial renal transplant with AF and acute pain in her transplanted kidney and right leg. The reason for transplant pain is difficult to determine as there are no neural connections between the transplant and the brain. Could it be that renal transplant ischaemia leads to swelling which causes pain by compressing adjacent tissues? Many patients do present with pain when there is venous thrombosis as in this situation there is intense swelling from the kidney compressing local structures causing pain. In our patient, there could have been some swelling, but it probably was not as profound as that seen in venous thrombosis. Is the pain related to ischaemia, hypoxia and cellular stress within the transplanted kidney? The body’s reaction to infarction or ischaemia is to initiate an inflammatory response and an ischaemic kidney would likely have a penumbra of inflammation surrounding it. This may incite an inflammatory response in the adjacent visceral peritoneum, with local pain at its location. ³

It is unknown why the embolus lodged in her transplant artery especially given the angle of the arterial anastomosis. The most frequent manifestations of cardiac embolic events are strokes and transient ischaemic attacks.^4,5 However, AF is also a leading cause of peripheral embolism.^4,5,6 Clots that are formed in the left side of the heart account for 55–87% of emboli to peripheral arteries and most emboli to viscera. ⁷ In general, the causes of the varied locations of AF emboli are not known and numerous factors can impact on the location such as the specific anatomical properties of the arterial system.^8,9 With regard to cerebral events, it is thought that the higher prevalence of symptomatic embolisation of carotid arteries compared to subclavian arteries is associated with low-resistance and increased volume flow in cerebral arteries. This hypothesis could also support the fact that embolisation of the splanchnic arteries is most commonly observed in the upper mesenteric and renal arteries, which are characterised by low-resistance and high-volume blood flow. Perhaps the transplant artery from the male donor was larger than the female recipient’s own iliac artery and the rate of flow through the kidney was higher making it more likely for the embolus to lodge here.

If there had been no perfusion at angiography then the sole option would have been nephrectomy. For poor transplant perfusion due to emboli, the options were intra-arterial thrombolysis or surgical embolectomy. In our patient, suction aspiration was attempted initially prior to intra-arterial catheter-directed thrombolysis; however, it was difficult and was abandoned due to an inaccessible transplant renal artery. It was felt that there was a risk of worsening the situation, by dislodging the embolus or damaging the artery, leaving no further options apart from nephrectomy. The objective of the thrombolysis was not solely to treat the embolus but to identify the cause, to dissolve the thrombus which occurs due to low flow as a result of the embolus, therefore restoring perfusion to the kidney and allow for definitive management. Thrombolysis creates less endothelial damage than balloon thrombectomy and restores patency in small inaccessible vessels. ¹⁰ Thrombolysis to the clot allows the tPA to move past the embolus and dissolve into small arteries which would otherwise remain ‘blocked’ if solely embolectomy was performed. tPA is rarely used; however, it was felt appropriate in this case.

We could not find any cases of intra-arterial thrombolysis being used for renal artery embolus in a transplanted kidney. There have also only been a few studies of solely intra-arterial catheter-directed thrombolysis being used for acute renal transplant artery thrombi. One study looked at four patients (ranging between 29 days and 10 years after transplant) and found that two of the four patients were successfully thrombolysed with intra-arterial thrombolysis. ¹¹ Both patients were seven years from transplant and one had renal artery stenosis and the other had undergone angioplasty for stenosis. They concluded thrombolysis may save renal transplants after up to 24 h of arterial thrombotic occlusion. A case report of renal artery thrombosis immediately after live donor transplant, showed satisfactory resolution of renal transplant perfusion after mechanical thrombectomy and administration of intra-arterial tPA intra-operatively. ¹² Although the patient required haemodialysis for 21 days post-thrombectomy, they had satisfactory renal function at four months. A systematic review of intra-arterial thrombolysis in the management of hepatic artery thrombosis following liver transplantation, ranging from 4 h to 120 days showed that thrombolysis using either urokinase or alteplase was successful in 68% of patients. ¹³ It concluded that thrombolysis via the hepatic artery had the advantage of using a highly localised concentration and a smaller thrombolytic dose than would have been used systemically. It was also safer and more effective if the infusion catheter was placed inside the thrombus.

There does not appear to be any consensus on how long intra-arterial thrombolysis should be continued. One study in hepatic artery thrombosis, suggested continuing up to 72 h; however, thrombolysis should be stopped if there was no significant difference in perfusion for a period of 12 h. ¹³ In another study on hepatic artery thrombosis, it concluded that thrombolysis should be terminated if there is persistent thrombus at 36–48 h. ¹⁴ Thrombolysis was stopped at 36 h in our patient as it was felt longer treatment would not improve the outcome. A review of recent trials of catheter-directed intra-arterial thrombolysis and mechanical thrombectomy for acute lower limb ischaemia concluded that thrombolysis was superior to open surgery to treat acute events and the most common complication was bleeding post-operatively including increased risk of haemorrhagic stroke (1–2%). ¹⁵

Conclusion

Consider acute transplant renal artery embolus if a renal transplant patient presents with acute kidney injury, transplant tenderness and cardiac arrhythmia.