The two leading causes of renal infarction are thromboembolism and in situ thrombosis. The former is an obstruction of a blood vessel by a blood clot from the heart, among which atrial fibrillation is the most common cause[5, 6]. It is reported that the incidence rate of renal arterial thromboembolism is about 2% in a series of almost 29862 patients(14 917 men and 14 945 women, 50 to 89 years old) with AF following for up to 13 years[7], and other series reported of the prevalence of acute renal infarction(ARI) in paitents from emergency department was 0.013 % and 70% of the patients had atrial fibrillation in a single center in Japan[8]. While a multicentric survey in Turkey reported in 121 renal infarction patients, only 36(about 30%) patients had thromboemboli due to atrial fibrillation[9]. It seems the incident of ARI varies depending on the characteristics of the cohort (age, gender, comorbidities etc) and the length of follow-up.
Patients with acute renal infarction usually complain of an acute attack of osphyalgia or diffuse abdominal pain, often accompanied by nausea, vomit, and occasionally fever. The majority of patients may have hematuresis and slightly elevated WBC and C-reactive protein, as well as elevated lactate dehydrogenase levels[4]. Because the symptoms of renal infarction are not specific, it is often not diagnosed immediately after the onset, usually more than two days[3, 10].
For a patient with osphyalgia, a general CT scan is a preferred initial test, and inflammation, urolithiasis, and other common acute abdominal diseases should be ruled out prior to the diagnosis of renal infarction, because renal infarction is a relatively rare disease in a paitent with osphyalgia or celialgia. On this occasion, if physical examination, CBC, laboratory biochemical analysis, urinalysis, and abdominal B-ultrasound could not confirm the cause of abdominal pain, contrast-enhanced CT examination is essential for the diagnosis[4].
In a Turkey survey, the patients enrolled was mainly of middle age, and the final mean creatinine was found to be 1.69 ± 0.16 mg/dl[9]. As for this elderly patient, her creatinine increased significantly up to 2.38mg/dl during 3 years’ follow-up. This difference of final serum creatinine may be related to the severity of infarction and the different compensatory ability of the unilateral normal kidney between elderly and middle-aged people. It was reported that acute renal infarction causes irreversible loss of renal mass, but it rarely leads to end-stage renal disease or long-term mortality [11].
In most series studies of thromboembolic renal infarction, the majority of patients received anticoagulation therapy, in which many patients had other anticoagulation indications like AF[3, 12, 13]. Intravenous heparin or subcutaneous injection of low-molecular-weight heparin(LMWH) followed by oral warfarin is a common approach. This patient received LMWH followed by oral warfarin and maintained INR between 2.0 to 2.5, which is a standard therapy for renal infarction.
Beyond the diagnosis of renal infarction, the most important problem is what can we learn from this case? If the renal infarction can be avoided or prevented? Is there a better choice of treatment for this patient before thromboembolism happened?
According to ACCP guidelines, the recommendation[14] of antithrombotic therapy for atrial fibrillation for patients with AF, including those with paroxysmal AF, who are at high risk of stroke (eg, CHADS2 score = 2), oral anticoagulation rather than no therapy was recommended in Grade 1A class. This patient had a score of 3(age ≥ 75, history of hypertension, and congestive heart failure). The CHA2DS2-VASc score also estimates the risk of thromboembolism in patients with atrial fibrillation[15]. Patients with a CHA2DS2-VASc score of 4 to 5 are considered moderate risk[5–10% annual risk of venous thrombus embolism(VTE)]. And for this patient, congestive heart failure(+ 1), hypertension(+ 1), and age ≥ 75 years(+ 2), female(+ 1), made a score of 5 in total. CHADS2 and CHA2DS2-VASc scores both suggested that this patient had a moderate to high risk of thromboembolism, which means anticoagulation therapy should be given when AF first onset, even considering perioperation of ICD. At the mean time, bleeding risk should also be estimated when antithrombolic therapy should be given. The HAS-BLED score is used to predict the risk of bleeding for anticoagulation therapy in patients with non-valvular atrial fibrillation[16, 17]. This patient had a score of 2, meaning she was not of high bleeding risk.
As for anticoagulation strategies during cardiac rhythm device periprocedure, it is recommended for unfractionated heparin(UFH) or LMWH as a bridging therapy by American College of Chest Physicians(ACCP) 9th Edition guidelines[14] and American College of Surgeons' Guidelines[18]. However, there are some different results published these years. BRUISE CONTROL study is the largest randomized controlled trial to evaluate antithrombotic strategies in patients with Cardiac implantable electronic device(CIED) implantation[16], it showed in 681 patients with an annual risk of thromboembolic events of 5% or more, compared with the heparin bridging strategy(HBS), continued warfarin treatment during CIED surgery markedly reduced the incidence of clinically significant device-pocket hematoma.
There are several meta-analysis published focusing on the evaluation of bleeding and thromboembolic rate of vitamin K antagonist and heparin bridging therapy in patients receiving cardiac rhythm devices. In a meta-analysis involving thirteen articles and 5978 patients, the results demonstrated that compared with holding or continuing anticoagulant (AC), HBS significantly increased bleeding events[19]. In another review which included 34 studies with 1 randomized trial, the meta-analysis showed there was no difference in the risk of thromboembolic events compared with the bridged and nonbridged groups, and patients receiving perioperational HBS appeared to have an increased risk of overall and major bleeding, and a similar risk of thromboembolic events compared with non-HBS patients[20]. Ghanbari et al. identified 8 studies enrolling 2,321 patients in a meta-analysis[21], compared with heparin-bridging therapy, a strategy of continuous warfarin therapy throughout CIEDs implantation is associated with a decreased risk of bleeding without increased risk of thromboembolic events. In another meta-analysis evaluating patients on chronic oral anticoagulant (OAC) therapy undergoing CIEDs implantation, it is indicated that implantation of CIEDs with uninterrupted OAC therapy seemed better than both of HBS and OAC interruption therapy for lowering the bleeding risk[22]. In a comparation of continuous oral anticoagulant vesus HBS in patients undergoing CIED surgery, seven studies with totaling 2,191 patients were included in a meta-analysis, continous OAC was associated with a significantly lower risk of postprecedure bleeding risk compared with HBS, and there was no difference in the thromboembolic events between two strategies[23].
Network meta-analysis (NMA) has some advantages over traditional meta-analysis. A network meta-analysis of observational studies tested the antithrombotic therapy during the CIED implantation, in which thirty-one observational studies, 41,174 patients were included. Continued warfarin, interrupted warfarin, and interrupted NOACs all reduced the risk of bleeding compared with HBS, and interrupted NOACs therapy might be the optimal anticoagulation strategy for the perioperative period of CIED implantation[24].
As can be seen from the above random controlled study and meta-analysis, continuous oral anticoagulation does not increase the bleeding risk and may reduce thromboembolic events, it may be the best option for perioperative CIED implantation. Some authors suggested HBS was given only in patients at high risk of stroke when anticoagulation was interrupted.