Introduction
Renal infarction (RI) describes the obstruction of the renal artery or its branches from blood clots formed in the vascular system of the patient.[1] It is a rare vascular disease, with an incidence as low as 0.004% to 0.007% of the diagnoses on admissions to the emergency department.[2] Surprisingly, in a study of 14,411 autopsies published in 1940, the incidence of RI was 1.4%.[12]
RI has traditionally been associated with heart diseases, such as atrial fibrillation or valve disorders, as well as with blood and vascular diseases, leading to hypercoagulative conditions. Considering that the kidney comprises end arteries with minimal overlapping of blood supply, it is estimated that 90 min of ischemia can lead to irreversible damage to the renal parenchyma.[34]
Clinical suspicion for this condition is usually low, given the fact that the disease can mimic acute pyelonephritis, renal colic, or other urinary diseases, thus engaging the urologist in the diagnostic process and treatment. The appropriate treatment is also poor defined, and different therapies have historically been applied. Various therapeutic schemes have been reported in the literature with various results in terms of preservation of renal function and survival rates.[12345678910]
Herein, a brief narrative review of RI syndrome is attempted from the urologist's standpoint, and an overview of the diagnostic, therapeutic, and prognostic factors is provided.
Materials and Methods
MEDLINE/PubMed database was reviewed, using the terms renal, kidney, artery, and infarction. All abstracts were screened by the two authors of this manuscript, and relevant articles were identified. Emphasis was given in the more recent advances in the diagnosis and treatment of the disease. Case reports and retrospective case series were the main studies included in this review.
Etiology and predisposing factors
Several factors are involved with RI such as arterial hypertension, hyperlipidemia, atrial fibrillation, congestive heart failure, coronary artery disease, mitral valve disease, and cerebrovascular disease.[91011] Of great importance is the deficiency of protein S and C and the past medical history of an embolic event.[4812] Occasionally, RI has been associated with renal trauma.[413] In some patients, predisposing factors for the disease cannot be identified, and RI is characterized as idiopathic. The rate of idiopathic RI may be as high as 60%.[6] Recently, COVID-19 virus has been implicated in the development of thromboembolic events including the renal artery as well as the renal vein.[1415]
Symptoms signs and laboratory tests
Pain was the most common presenting symptom, located primarily in the lumbar area with detection rates ranging from 32% to 100%, followed by abdominal pain, nausea, vomiting, and fever. Hematuria and proteinuria are also common findings among patients with RI. During the first hours after pain onset, serum biochemistry and urinary studies indicative of tissue or cellular damage (e.g., serum lactate dehydrogenase (LDH) increase, hematuria, or proteinuria) may be absent; therefore, early diagnosis only from the features of the pain cannot be established.[9]
The median time from the onset of pain till the admission to the emergency department has been reported to be 10 h.[9] A median of 8 more hours till the diagnosis of RI was required corresponding to a median overall delay of 18 h.[9] Bolderman et al. reported a 6-h delay in idiopathic (noncardiogenic) population representing a significant improvement compared to older studies.
However, patients usually visited a physician, only after a median of 15 h from the onset of symptoms.[6] Doctors and patients should be aware and cautious about the possibility for RI to be developed. Patients with high-risk history should be instructed to visit the emergency departments, as soon as possible and physicians to promptly evaluate this group of patients with the proper panel of tests.
This panel of tests, apart from the urinalysis or dipstick, should also include total blood count and biochemical examinations including renal biochemistry and nonspecific indexes of tissue damage. However, in other reports the mean or median values of these tests were persistently moderately elevated across all case series.[5] On the contrary, very high levels of LDH have also been persistently published in the literature. Although it is a nonspecific for RI, these very high values could be an alarming finding. In most of the series of [Table 1], the serum LDH was above the threshold of 1000 IU/L, while for most laboratories, the upper normal limit is approximately 280 IU/L.
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Table 1: An overview of the clinical manifestations of renal infarction as derived from the most recent studies
AST/SGOT was also moderately elevated, but the indexes of renal function and particularly of serum creatinine levels were surprisingly almost normal. Similarly, the mean or median estimated glomerular filtration rare was normal ranging from 64 to 76 mL/min/1.73 m2.[25]
Differential diagnosis and imaging modalities
RI is mainly misdiagnosed as renal colic in up to 20% of the cases, followed by acute pyelonephritis and/or urinary tract infection in up to 16% of the patients, obstruction of the mesentery artery in 16% of patients, and biliary tract disorders in 5% of the cases.[7] The disease may also be confused with acute myocardial infarction, congestive heart failure, and acute abdomen disorder. Other researchers have reported that RI can be misdiagnosed as renal colic up to 57%.[1012]
Therefore, the urologist may be actively involved in the management of RI. High index of suspicious is required to avoid any delays in the correct diagnosis and foremost, a prompt and appropriate management to be offered to these patients. For these reasons, apart from the careful medical history taking and the physical examination of all the systems, targeted imaging tests requested.
The ultrasographic examination of the affected the kidney may be initially performed as a mean for early detection of the renal pathology. It may reveal renal lithiasis as a causative factor of the lumbar or abdominal pain or hydronephrosis. Ultrasograpy may also detect malignancies of the parenchyma or the collecting system causing hematuria. In patients presenting with RI, the findings of ultrasography are expected to be unremarkable. Doppler mode, however, performed by an experienced radiologist may define the impairment blood perfusion of the renal unit.[3] With the use of Doppler ultrasound mode the detection rate of RI throughout the literature ranges from 11% to 56%.[716]
Renal isotope scan is another imaging modality used for the diagnosis of RI. Correct diagnosis has been reported to be as high as 97%.[16] However, nuclear laboratory facilities are not always available on 24-h basis. Moreover, lack of perfusion cannot determine the etiology of a filling defect; this finding may be related not only with RI but also with disorders such as renal scarring, simple or complicated parenchymal cysts, or pyelonephritis.[7]
CT is nowadays an excellent modality for the diagnosis of urolithiasis in patients with renal colic. Imaging with or without iv contrast may also be used to determine other etiologies of acute pain such as gastrointestinal tract rupture, biliary tract disorders, and vascular diseases such as aneurysms, appendicitis, or other causes of acute abdomen syndrome. It can also reveal the presence of abdominal malignancies and determine the extent and the etiology of hydronephrosis. In RI cases, though, nonenhanced imaging usually fails to demonstrate the etiology of the pain. In the patients with inconclusive results in non-enhanced CT imaging, the administration of contrast agent could be performed. Apart from the confirmation of the diagnosis of RI, other challenging vascular disorders such as thromboembolism of the superior mesentery artery might be excluded as well.[78]
The typical findings of enhanced CT imaging comprise one or multiple wedge-shaped filling defects of the renal parenchyma or global hypoattenuation of the affected renal unit, compared with the healthy one. Infarcts involving >50% of the renal tissue are considered global. Smaller single or multiples lesions (<50% of the renal unit) are classified as focal or multifocal, respectively.[17]
Enhanced computed tomography (CT) scan is associated with high percentages of detection rate, being reported as high as 97.3%[57] Due to the advantages of CT scan over other imaging modalities, its noninvasive nature, the rapid execution, and the capability of examining the whole body, it should be performed as early as possible should RI is suspected.[9]
Digital subtraction renal arteriography is also a highly sensitive examination with detection rates approaching 100%. It is characterized by great invasiveness[3] and therefore is related with a higher risk of complications. In older series, particularly when CT tomographs were ill available, it was the diagnostic procedure of choice, but in contemporary series, arteriography has lost much of its popularity and is performed in selected cases only.[247] Nevertheless, arteriography may be associated with the delivery of thrombolytic agent directly on the obstructing clot as a measure for achieving recanalization of the artery.[3]
Treatment and Outcome
As mentioned previously, interventional procedures were more frequently performed in the past. Lessman et al. in 1978, apart from the administration of warfarin and heparine, performed embolectomy or nephrectomy in 17.6% of the cases. Nearly 23.5% of the patients died in less than a month from the diagnosis, primarily due to cardiovascular disorders. Therefore, the authors recommended aggressive treatment only in cases with bilateral RI.[10]
Recent studies reveal a shift of the management strategies toward less invasive procedures. As shown in Table 2, thrombolysis with arterial infusion of thrombolytic agents such as streptokinase, urokinase, or tissue plasminogen activator (tPA) is performed in <20% of the cases. More invasive strategies such as arterial bypass or nephrectomy are occasionally implemented too. The availability of the new generation oral and intravenous agents, such as coumarin derivatives, low-molecular-weight heparin, aspirin, and antiplatelet agents received either as monotherapy or in combination, is nowadays the preferred treatments with a reasonable risk of complications.[1578]
Table 2: Overview of the treatment and outcome of renal infarction in the more recent case series
In one of the largest multicenter series originating from France, the treatment of choice was mainly based on noninterventional procedures. Albeit arteriography was performed in one out of three of the patients, concomitant thrombolytic procedures (intra-arterial urokinase infusion, thromboaspiration, and renal artery stenting) were implicated in only 5% of the participants. In these patients, warfarin or coumarin derivatives with or without antiplatelet agents were the preferred treatment. With this therapeutic strategy, a mortality rate of <1% was achieved.[2]
Optimal results have been reported by Bolderman et al. in the subgroup of patients without any history of previous cardiovascular events (idiopathic subgroup comprising the 59% of the total group). With the use of combination of antithrombotic and antiplatelet drugs and without the use of any invasive therapy, renal function was preserved and no deaths were occurred. In this subgroup, RI could be attributed only to smoking and arterial hypertention. On the contrary, those with diabetes mellitus, coronary artery infarction, atrial fibrillation, previous thromboembolic event, and/or cardiovascular family history (41% of the total group) experienced worse outcomes with a mortality rate of 18.2%.[6]
The rate of diagnosis of acute renal injury following RI ranges from 10.9% to 18%. As it is shown in Table 2, the short-term incidence of ESRD was <10%, whereas the midterm rate was almost 20%.[567] Regarding the robust end point of mortality rate, a minimum of 0% up to a maximum of 23.4% is encountered.[5] This maximum value, however, is related with death of any cause after a long-term follow-up.[1] In most of the recent series, the mortality rate is <11% during the 1st year of follow-up.[35678]
Outcome
The ideal treatment of patients with RI is yet to be determined. Intravenous heparin, oral warfarin, with or without rivaroxaban have been examined in respect to the mortality rate and have been compared with a nontreatment group. The treatment scheme exerted a protective role, considering that those who received anticoagulant therapy experienced a 92% improved survival compared to the nontreatment arm (hazard ratio 0.08, 95% confidence interval: 0.02–0.34).[18] Similar studies regarding the possible protective role of thrombolytic agents or surgical interventions has not been performed so far.
Apart from the oral anticoagulants, the outcome of patients with RI may be influenced by the duration of ischemia. The classical teaching supports that, after 90 min of complete normothermic occlusion of the artery, irreversible damage of the renal parenchyma is expected. However, in none of the series, any of the patients has been treated as early as in 90 min from the ischemia onset. In one study, a delay of more than 24 h was recorded in 80% of the patients, whereas in two other studies, the median delay in diagnosis was between 64 h and 5.4 days. However, despite this delay, the morbidity and mortality rates were both acceptable, ranging from 6.3%–10% for end-stage renal disease requiring hemodialysis and from 0% to 11% for 1-month post event mortality [Table 2].[278]
It seems that other factors also determine the outcome. According to an observational study by Gasparini et al., the extent and degree of renal artery occlusion may be an important factor for the preservation of renal function. Surprisingly, in this study, renal function was salvaged in 17% of the patients, when the duration of ischemia was <10 h, whereas for longer ischemia time, the preservation of renal function was over 66%. An explanation for this finding may be that a collateral flow may be developed in the kidney, bridging the renal artery branches with others from the inferior adrenal, ureteral, and capsular arteries.[412]
The long-term outcome of RI is still under investigation. Based on 47 patients with a mean age of 61 years, 19% of the patients experienced recurrent thromboembolic events outside the renal vasculature. Dialysis-free survival rate was approximately 64% at 5 years, after long-term anticoagulation oral therapy. Deaths were related with over vascular disorders including myocardial infarction, congestive heart failure, cerebral infarction, superior mesenteric artery embolism, and gastric cancer. It is assumed that RI is a systematic disease affecting all the cardiovascular system and caution should be undertaken toward avoiding new vascular events. Therefore, these patients should be referred to a physician specialist for vascular diseases (e.g., a vascular surgeon).[1]
This review study represents a nonsystematic evaluation of retrospective single-arm case series. Included studies are based on a limited number of participants, nonstandardized diagnostic procedures, and treatment is based on the preferences of the responsible physicians. Caution should be exercised during comparison of the end points of different studies in respect to renal function preservation, complications rates, and cause of death. Prospective randomized trials have not been conducted so far, and the presented results and recommendations broadly reflect experts' opinions. All the aforementioned should be considered as limitations of this review.
Conclusion
Lumbar and/or abdominal pain and hematuria may be the misleading symptoms in patients with RI, leading to the involvement of the urologist in the management of this disease. Investigation for acute RI should be implemented in patients with relevant history and an inconclusive initial diagnostic workup is inconclusive. High-risk patients should be informed about this rare condition, and the importance of prompt admission to the emergency department. A group of trained physicians should be involved in the management of these patients including a specialist in internal medicine, an interventional radiologist, a vascular surgeon, and perhaps urologist, nephrologist, and intensive care unit specialist. A good cooperation of this multimodal medical team is of utmost importance for avoiding unnecessary diagnostic and therapeutic delays and for the administration of prompt treatment.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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