Successful Management of Acute Renal Artery Thromboembolism by Intra-arterial Thrombolytic Therapy with Recombinant Tissue Plasminogen Activator

Abstract

Acute renal artery thromboembolism (ARAT), a rare event in native kidneys, potentially result in severe renal injury if it is not appropriately managed. The optimal therapy still remains controversial today even though various methods of managements for ARTA were applied in these decades including surgical intervention and medical approach such as thrombolytic therapy. Recombinant tissue plasminogen activator (rt-PA) reveals a better bioavailability and lower incidence of adverse effects and it has been widely used to treat a number of clinical conditions but only very few cases have been reported where rt-PA was used to treat ARAT. We described a case of ARAT, which was successfully treated by the administration of rt-PA via intra-arterial infusion within a period of 60 min without residual renal impairment. It may be a useful choice for ARAT and renal infarction sufferers.

• Acute renal artery thromboembolism
• Recombinant tissue plasminogen activator (rt-PA)
• Intra-arterial thrombolytic therapy

Introduction

Acute renal artery thromboembolism (ARAT) is a rare event in native kidneys,[[1]], [[2]], [[3]] it potentially resulting in severe renal injury if it is not appropriately managed. Owing to the rather low ischemic tolerance of the kidneys, an accurate early diagnosis of this condition and prompt treatment are crucial.[[1]], [[4]] Surgical intervention, anticoagulant therapy, systemic and selective thrombolytic infusion using streptokinase or urokinase have previously been applied for treating ARAT,[[3]], [[4]], [[5]], [[6]], [[7]] yet the optimal therapy still remains controversial. Since recombinant tissue plasminogen activator (rt-PA) reveals a better bioavailability and lower incidence of adverse effects, it has been widely used to treat a number of clinical conditions.[[8]], [[9]], [[10]] Herein, we described a case of ARAT, which was successfully treated by the administration 50 mg rt-PA via intra-arterial infusion within a period of 60 min, and it may be a useful choice for ARAT and renal infarction sufferers.

Case Report

A 33-year-old previously healthy man was admitted to our hospital due to the sudden onset of left flank pain that had arisen 12 h prior to presentation. The pain was reported to have been sharp, spasmodic and unrelated to any patient positional change, he denying any previous history of urolithiasis.

Upon examinations, the patient appeared distressed, he demonstrating the following: an axillary temperature of 36.5°C, an irregular heart rate of 126/min, whilst his respiratory rate was 18 breaths/min, his blood pressure was 104/80 mmHg. Chest radiography did not reveal the presence of any active cardiopulmonary lesion, although an electrocardiogram (ECG) did indicate an irregular sinus rhythm. Urinalysis exhibited the following: protein = 25 mg/dL, WBC = 1–3/HFP, and RBC = 0–2/HPF. A hemogram revealed: white blood cell = 12300/mm³, hemoglobin = 15.2 g/dL, and platelets = 201,000/mm³. Laboratory data indicated: blood urea nitrogen (BUN) = 10 mg/dL, serum creatinine (Scr) = 1.5 mg/dL, glucose = 130 mg/dL, amylase = 41 U/L, and lipase = 42 U/L. Anticardiolipin antibody, rheumatic factor, protein C, protein S, anti-thrombin III, and thyroid function tests all provided results within the normal range. Abdominal computed tomography (CT) revealed a filling defect in the left renal artery. Under the impression of acute left renal arterial thromboembolism related to atrial fibrillation, systemic anticoagulation with unfractionated heparin was administered with a maintenance infusion dose intended to maintain an activated partial thromboplastin time value of 1.5–2.0 times the control value subsequent to an initial bolus of 5000U of heparin, although the patient still experienced left flank pain despite continuous treatment for 12 h. As a sequence, renal arteriogram was performed, and thrombosis of the left mid-portion lobar renal artery with a markedly decreased renal arterial perfusion was revealed (Fig. 1). A bolus of 15 mg recombinant tissue plasminogen activator (rt- PA; Actilyse, Boehringer Ingelheim, Germany) was administered, followed by an infusion of 35 mg rt-PA diluted in 35 mL saline continued over a period of 60 min at the site of the clot via the angiography catheter. Within 30 min of rt-PA thrombolytic therapy, the patient's left flank pain ceased. Subsequent left renal arteriogram performed two hours later revealed virtual complete lysis of the embolus and resumption of vascularity over the previously hypoperfused area (Fig. 2). Following thrombolytic therapy, unfractionated heparin was continuously infused and was subsequently replaced by warfarin from the fourth day post-admission. ⁹⁹Tc^m dimer-captosuccinate (⁹⁹Tc^m DMSA) plus ⁹⁹Tc^m diethylene triamine tetraacetic acid (⁹⁹Tc^m DTPA) administered on day seven revealed normal blood flow levels to both kidneys and the count ratio of the left kidney to the total flow was 41.3%. The patient was discharged on day eleven revealing a Scr level of 1.0 mg/dL. During the entire course of hospitalization, no systemic hemostatic side effects were noted. The follow-up Scr level was 1.0 mg/dL in the sixth month post-discharge.

Figure 1. Digital left renal angiogram shows total occlusion of mid-portion lobar artery of anterior division of the left renal artery.

Figure 2. Follow-up angiogram after intra-arterial thrombolytic therapy shows complete lysis of the thrombus and good reperfusion of the left renal mid-portion arterial branches.

Discussion

ARAT is an uncommon event among native kidneys.[[1]], [[2]], [[3]] It is primarily associated with cardiac disease and arrhythmia, atrial fibrillation being the most common example.[[1]], [[3]], [[4]], [[5]], [[6]], [[7]] Other etiologies including thrombosis related to atherosclerosis, collagen vascular disease, tumor, trauma, or iatrogenic causes have been previously noted.[[2]] The clinical presentations of ARAT are characterized by a variety of symptoms including flank pain, hematuria, proteinuria, and fever and chills.[[1]], [[6]], [[7]] An early diagnosis often proves to be difficult due to the variable nature of associated symptoms and, frequently, the presence of non-specific laboratory findings, such that a specific diagnosis is dependent upon arteriography.

The duration of tolerance for a human ischemic kidney appears to be unknown, but it could be as short as 1–3 h at body temperature as indicated by appropriate animal studies, with any ensuing renal parenchymal damage usually developed during the ischemic period.[[5]] Therefore, the prompt and safe restoration of renal blood flow is important in order to avoid subsequent acute or chronic renal failure. Various methods for treating ARAT including surgical intervention, anticoagulant therapy, and systemic and selective thrombolytic infusion have been reviewed in a series of literature-cited reports pertaining to the resolution of ARAT.[[6]], [[7]], [[8]], [[9]] With respect to the higher mortality rate and no evidence of any better renal function recovery following embolectomy or vascular reconstruction, medical treatments are generally preferred.[[4]], [[6]], [[7]] Intravenous unfractionated heparin administration followed by warfarin has been reported to be useful for this condition.[[6]] However, unfractionated heparin and warfarin have the disadvantages of having a less predictable thrombolytic response and being associated with certain complications including bleeding, thrombocytopenia, and osteoporosis. Since the 1980s, the availability of thrombolytic agents such as streptokinase, urokinase, and rt-PA has diversified the therapeutic approach to ARAT.[[6]], [[7]], [[8]], [[9]], [[11]] Streptokinase is an enzyme derived from certain bacteria, and urokinase is an enzyme derived from cultured human kidney cells. Both agents demonstrate a more substantial antigenic property and a lower affinity to fibrin or fibrin-bound plasminogen as compared with rt-PA.[[8]], [[10]] Recombinant tissue plasminogen activator, a naturally occurring enzyme derived from DNA technology, exhibits a more-pronounced bioavailability, a more-potent enzymatic activity of plasminogen activator and the presentation of a reduced suite of side effects such as bleeding and anaphylactoid reactions when compared with streptokinase and urokinase therapy.[[8]], [[9]], [[10]] The successful use of rt-PA for the treatment of acute coronary occlusion, acute cerebrovascular accidents, bypass graft occlusions, peripheral arterial occlusions and acute pulmonary embolism has previously been reported.[[9]], [[12]], [[13]] However, only very few cases have been reported where rt-PA was used to treat ARAT, especially by way of an intra-arterial infusion. In 1990, Mügge et al. reported a case of a hypertensive man suffering atrial fibrillation who exhibited an acute embolic occlusion of the right renal artery, the condition being successfully treated by lysing the embolus using an intra-arterial bolus of 10 mg of rt-PA, followed by an infusion of 20 mg of rt-PA over a period of 12 h, but the patient's renal function was not fully restored.[[11]] For our case, that of ARAT for a 33-year-old man with atrial fibrillation, the condition was successfully managed 28 h subsequent to the onset of symptoms by way of the administration of a bolus of 15 mg rt- PA, followed by a 35 mg infusion of rt-PA over a period of 60 min delivered directly at the site of the clot via the angiography catheter. Arteriography provided an accurate diagnosis and the intra-arterial catheter offered a route for immediate rt-PA local infusion. The associated timely local administration of rt-PA via an infusion contributed to the patient's optimal anatomical resolution and functional salvage. The optimal dosage for the selective infusion of rt-PA for the treatment of ARAT appears to be uncertain presently, since no evidence-based literature appears to be available for review currently, although the successful application of low dosage rt-PA, as, for example, with the administration of 15 mg rt-PA via an intravenous bolus over a 30 min time period followed by the infusion of 35 mg rt-PA over the subsequent 60 min period for treating acute coronary syndrome and acute ischemic stroke have been previously established.[[14]], [[15]] It is based upon such facts that we elected to utilize a selective infusion of 50 mg rt-PA in order to treat our patient's ARAT.

In conclusion, early diagnosis and immediate therapy is clearly desirable for maximal salvage of renal function for ARAT patients. Our case, described here, demonstrates that intra-arterial thrombolytic therapy with a low dosage of 50 mg rt-PA may be an effective and safe strategy for the treatment of ARAT, despite the period of ischemia being as long as 28 h.