Correspondence *Department of Internal Medicine B, Rambam Health Care Campus, Haifa 31096, Israel

Email nicola.nasser@gmail.com

The case

A 53-year-old man presented to the emergency room of a hospital 2 hours after the abrupt onset of left upper abdominal pain. He had no fever, dysuria, urgency or hematuria. Following a short workup, the patient was treated with analgesics and discharged after 4 hours of observation, with the recommendation to have an ambulatory endoscopy at another center during the following weeks.

As a result of severe left abdominal pain, however, the patient presented to the emergency department of another hospital 2 hours later (i.e. about 8 hours after the onset of pain). His past medical history included hypertension, hypercholesterolemia, heavy smoking (1.5 packs/day for 20 years), and ischemic dilated cardiomyopathy due to recurrent myocardial infarction. His medications at the time of presentation included carvedilol (6.25 mg twice daily), furosemide (40 mg daily), simvastatin (20 mg daily), ramipril (10 mg daily), and aspirin (100 mg daily). Physical examination was unremarkable except for a markedly tender left abdomen with no signs of peritonitis. An electrocardiogram showed a normal sinus rhythm with no signs of ischemia. Laboratory tests revealed a high white blood cell count of 17.8 10⁹/l (83% neutrophils), a mildly elevated blood urea nitrogen (BUN) level of 9.4 mmol/l (26.3 mg/dl), a normal serum creatinine level of 85.7 mol/l (0.97 mg/dl), normal blood sodium and potassium levels, and a markedly elevated lactate dehydrogenase (LDH) level (Table 1). Urinalysis was positive for red blood cells and protein. A contrast-enhanced computed tomography (CECT) scan of the abdomen revealed a thrombus in the left main renal artery, with a resultant infarction of the upper pole of the left kidney (Figure 1). The lower pole of the patient's left kidney, supplied by an accessory left renal artery, showed no signs of infarction. The patient was hospitalized and treated with continuous infusion of unfractionated heparin to increase activated partial thromboplastin time to within a target therapeutic range of 60–80 seconds. Symptomatic relief was achieved after 12 hours of heparin treatment; heparin was then stopped and enoxaparin (60 mg twice daily) was initiated. As there had been a prolonged interval between symptom onset and diagnosis (about 12 hours), thrombolytic therapy was not administered. After 2 days of treatment with enoxaparin, warfarin (5 mg daily) was added and daily measurement of the International Normalized Ratio (INR) was performed aiming for a target INR of between 2 and 3.

Figure 1 Axial contrast-enhanced computed tomography image of the patient's abdomen with maximal intensity projection reconstruction.

The left main renal artery is thrombosed (arrow head), with a resultant infarction of the upper pole of the left kidney (arrow). The unaffected right kidney shows a normal enhancement pattern. Abbreviations: L, liver; S, spleen.

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Table 1 The patient's laboratory values on hospital admission.

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During the fifth day of hospitalization, transesophageal echocardiography was performed (Table 2). The image revealed a severely enlarged left atrium and ventricle, and severely reduced left ventricular function with biatrial spontaneous echocardiographic contrast. The spontaneous echocardiographic contrast in the left atrium was graded as severe (Figure 2). Left atrial spontaneous echocardiographic contrast is the cardiac factor most strongly associated with left atrial appendage thrombus and embolic events.^{1, 2} The patient's blood coagulation profile was normal except for his factor VIII activity level, which was higher than the upper limit of normal (Table 3). High levels of factor VIII activity predispose to venous thrombosis, and might also be associated with arterial thrombosis.³

Figure 2 Transesophageal echocardiogram showing the severely enlarged left atrium and ventricle.

Spontaneous echocardiographic contrast in the left atrium is the cardiac factor most strongly associated with left atrial appendage thrombus and embolic events. Abbreviations: LA, left atrium; LV, left ventricle.

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Table 2 Transesophageal echocardiography findings.

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Table 3 The patient's blood coagulation profile.

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The diagnosis of renal artery thromboembolism resulting from dilated cardiomyopathy, severely reduced cardiac function and an intracardiac thrombus was made. Anticoagulation with enoxaparin was halted on the sixth day of hospitalization when the patient's INR had increased to meet its therapeutic target. The patient was discharged 7 days after admission with an INR of 2.2. He was discharged on warfarin treatment with instructions to perform blood tests and have his family doctor modulate the warfarin dose to maintain his INR between 2 and 3.

One month after discharge, the patient presented to the emergency department with left flank and abdominal pain. His abdomen was tender to palpation with no signs of peritonitis. Blood tests revealed mild leukocytosis (white blood cell count 14.9 10⁹/l), normal hemoglobin (135 g/l), and a markedly prolonged prothrombin time (>120 seconds) most likely to be the result of overtreatment with warfarin. An abdominal CECT scan (Figure 3) showed recanalization of the left main renal artery (Figure 3A). Hypodense areas in the upper pole of the left kidney were revealed in CECT reconstructions (Figure 3B), representing irreversible damage in the site of the previous infarction. The lower pole of the left kidney, supplied by an accessory left renal artery, enhanced normally with contrast (Figure 3B). The patient was hospitalized for observation, and was discharged 6 days later, when his INR had stabilized within the therapeutic range. The patient's BUN and serum creatinine concentrations were within normal ranges throughout this hospitalization and at discharge.

Figure 3 Contrast-enhanced computed tomography images of the patient's abdomen on his second admission to hospital, with maximal intensity projection reconstruction.

(A) The axial plane shows recanalization of the left main renal artery (arrow head) and hypodense areas indicating the previously infarcted upper pole of the left kidney (arrow). (B) The coronal plane shows the recanalized left main renal artery (arrow head) and the previously infarcted upper pole of the left kidney (arrows). The lower pole of the left kidney, supplied by an accessory left renal artery, enhanced normally with contrast.

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Discussion of diagnosis

Acute renal infarction (ARI) is an uncommon disease and its diagnosis is often delayed or missed. The patient described here was evaluated in the emergency room of the first hospital, and discharged without diagnosis. The diagnostic challenge in ARI results from the condition's nonspecific presentation;^{4, 5, 6} there is a paucity of physical and laboratory features specific to ARI. Predisposing factors include atrial fibrillation,⁶ smoking,⁷ prosthetic cardiac valves,⁸ infective endocarditis,⁹ nonbacterial thrombotic (marantic) endocarditis,¹⁰ intracardiac tumors,¹¹ activated protein C resistance,⁶ protein S deficiency,⁶ and drug abuse.¹² Idiopathic cases of ARI have also been reported.¹³ A study by Chu and colleagues found the most common presenting symptom of ARI to be the abrupt onset abdominal or flank pain.¹⁴ Nausea and vomiting occurred in about 50% of patients and fever was reported in around 30% of cases.¹⁴ Presence of fever sometimes leads to a misdiagnosis of pyelonephritis.^{6, 14} Blood analysis of patients with ARI usually reveals an elevated white blood cell count and elevated LDH concentration,^{6, 14} as in the patient presented here. BUN and serum creatinine levels might be elevated¹⁴ or normal.⁶ Urinalysis often reveals hematuria^{6, 14} and proteinuria,^{12, 13} but these urinary findings are not uniformly present.¹⁵

Hazanov et al.¹⁶ summarized the medical records of 44 patients diagnosed with a renal embolus secondary to atrial fibrillation. The average age was 69.5 years; 68% of the patients had abdominal pain, 43% had vomiting, 41% had fever, 54% had hematuria, 45% had proteinuria, and 93% had an elevated LDH concentration. On follow-up, 61% had normal renal function while the remainder continued to have mild to severe renal impairment. Absence of hematuria was associated with an increased occurrence of acute renal failure. Eleven percent of patients in the study died during the first month following diagnosis.

Tsai and colleagues¹⁷ described 18 patients with ARI. Atrial fibrillation was not an inclusion criterion in their study, and the disease etiologies were, therefore, different to those reported by Hazanov and co-workers. The average age of patients in the study by Tsai et al. was 44.7 years. ARI was associated with trauma in four patients (average age 19.5 years) and atrial fibrillation was identified in five patients (average age 56.4 years). Valvular heart disease, previous embolic events or ischemic heart disease were each noted in four cases, and one patient suffered from dilated cardiomyopathy. LDH concentration was elevated in all patients, leukocytosis was present in 72%, and hematuria in 50%. Serum creatinine level was normal or mildly elevated in 89% of patients.

Bolderman et al.¹³ studied 27 patients with ARI. Etiology was related to cardiac disease in 11 (41%) patients, with atrial fibrillation documented in 10 of these. Cardiac disease was not evident in the other 16 patients; etiology was considered idiopathic in these cases. The average age of the idiopathic group was significantly lower than that of the group of patients with cardiac disease (48 years vs 75 years; P = 0.003). Twenty-five patients (93%) presented with pain (the pain was continuous in 23 individuals, and was located in the lumbar region in 16 of these), 17 with nausea, 9 with vomiting, 11 with elevated temperature, 20 with abdominal tenderness, and 17 with lumbar tenderness. In the idiopathic group, the thrombophilia panel detected hyperhomocysteinemia in five patients, protein S deficiency in one patient, factor V Leiden mutation in one patient, and antithrombin deficiency in one patient.

A study by Domanovits et al.¹⁸ investigated 17 patients with ARI (average age 68 years, range 48–74 years). In total, 14 patients had known risk factors for thromboembolic disease. All patients reported abdominal or flank pain, 7 had nausea or vomiting, 2 were anuric, 12 had hematuria, and 10 had proteinuria. Serum LDH levels were elevated in 16 patients on presentation; the other patient had a normal LDH level on presentation but an elevated LDH level at the time of a second measurement 17 hours later.

Discussion of treatment

As a result of the rare incidence of diagnosed ARI, no controlled studies have been performed that could help to guide treatment choices. Management of patients with ARI involves thrombolysis, anticoagulation, and occasionally surgery. Hazanov et al.¹⁶ described seven patients who received thrombolytic therapy with intra-arterial streptokinase or urokinase. On follow-up, four of these patients had normal renal function, one had developed end-stage renal disease, and two had died. Use of local intra-arterial thrombolytic therapy resulted in radiologic improvement in two of five patients in Tsai et al.'s study.¹⁷ Thrombolysis with intra-arterial urokinase⁶ is feasible if the diagnosis of ARI is made within the first 4 hours after symptom onset, and ideally within the first 90 minutes,¹⁹ a situation that rarely occurs.^{17, 19} Anticoagulation with unfractionated heparin, low-molecular-weight heparin and warfarin is usually necessary, and favorable results have been reported in several studies.^{16, 17} Surgical embolectomy is rarely performed, and is mainly reserved for patients with total parenchymal involvement due to bilateral emboli, and those with unilateral main renal artery embolus in a solitary kidney.^{17, 20} Reduction of risk factors (e.g. quitting smoking) and treatment of underlying diseases responsible for the hypercoagulable state might prevent recurrence of organ infarction.

Conclusions

ARI is a rare disease that is often misdiagnosed. Patients with diseases predisposing them to hypercoagulable states, and those presenting with abrupt-onset abdominal or flank pain and elevated LDH levels, with or without hematuria, should be suspected of having ARI. This disease can occur in previously apparently healthy individuals.¹³ Diagnosis of the condition is usually made using CECT, and treatment involves anticoagulation with or without thrombolysis and, in some cases, surgery.

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