Renal Infarction

Etiology

The causes of renal infarction can be grouped into the following categories:

• Cardioembolic sources
• Renal artery thrombosis
• Trauma or mechanical injury
• Aortic or renal artery dissection
• Hypercoagulability
• Atheroembolic disease [6][7][8][9][10] 

Cardioembolic Disorders

Cardioembolic disorders are the most common etiology of renal infarction, accounting for up to 55% of cases. Within this group, between 64% to 75% are noted to have atrial fibrillation.[7] Renal infarction may be the first sign of atrial fibrillation. Also, many patients with atrial fibrillation who develop renal infarction are found to be subtherapeutic with anticoagulation. Renal infarction due to cardiac emboli tends to occur in the older age group, often in the sixth to eighth decade of life. Other cardiac causes include cardiac emboli due to rheumatic mitral stenosis, myocardial infarction, and prosthetic or native valve endocarditis. Renal infarction can also occur from an embolus originating from an atrial myxoma or thrombus in the left ventricle apex.[11] 

Renal Artery Thrombosis

Arterial causes of renal infarction include atherosclerotic thrombosis originating from the aorta or renal artery. Aneurysms of the thoracic or suprarenal abdominal aorta can also increase the risk of renal infarctions by favoring thrombi development. Treatment is aimed at treating risk factors such as hyperlipidemia and hypertension.[12] 

Trauma or Mechanical Injury

Renal infarction can occur from a blunt abdominal injury leading to dissection or occlusion of the renal artery, which may result from direct trauma or retroperitoneal bleeding compressing renal vasculature. Surgery or endovascular repair may be indicated depending on the nature of the injury. 

Aortic or Renal Artery Dissection

Mechanical instrumentation is the most common cause of renal artery dissection, most often due to endovascular or surgical procedures involving the aorta or its branches. Aortic dissection can also involve 1 or both renal arteries, and endovascular stent placement during aortic repair can also affect the renal artery supply. Spontaneous renal artery dissection is very rare but can have significant sequelae in otherwise healthy patients. Clinicians should assess each patient for risk and individualize surgical or nonsurgical management determinations.[13][14]

Fibromuscular dysplasia occurs primarily in women younger than 50 and usually involves the renal arteries, about half the time, bilaterally.[15] Fibromuscular dysplasia affects small and medium-sized arteries, causing stenosis, aneurysm, or dissection. Renal infarctions can occur due to thrombus formation in the poststenotic, dilated portion of the artery, which usually manifests initially as hypertension.[16][17] See StatPearls' companion reference, "Fibromuscular Dysplasia," for further information.[18] Renal artery dissection can occur spontaneously in fibromuscular dysplasia, Marfan syndrome, and Ehler-Danlos syndrome.[19][20]

Hypercoagulable State

Heritable coagulation disorders like protein C and protein S deficiency, hyperhomocysteinemia, systemic lupus erythematous, polycythemia vera, Factor V Leiden mutation, prothrombin gene mutation, and antithrombin III deficiency can also lead to renal artery blockage. Renal infarction may also be seen with oral contraceptive use, COVID-19 infection, malignancy, sickle cell disease, anabolic steroid abuse, and cocaine use.[21][22]

Atheroembolic Disease

The majority of patients who receive angiography have significant atherosclerotic disease, which puts them at higher risk for atherosclerotic plaque emboli, resulting in renal artery occlusion and infarction. The incidence of acute kidney injury (AKI) in patients older than 60 years due to biopsy-confirmed renal atheroemboli has been reported at 7%, which can be reduced using a brachial rather than an iliofemoral approach for arterial access.[23][24] 

In contrast to other causes of AKI, atheroembolic disease can present with renal injury gradually and weeks after the initial insult.[25] Symptoms are generally less severe because atheroemboli often have irregular shapes and do not typically cause complete occlusion, as do thromboemboli.[26] Over time, this results in a narrowed arterial lumen and some degree of renal injury over several weeks.[27][28] 

Idiopathic

Despite extensive evaluation, many patients do not have an identifiable cause of renal infarction. About 20% to 30% of cases remain idiopathic, with a median age of approximately 50 years in these patients.[6][7][10] The infarction may represent poor vascular health in general, and all secondary risk factors, including hypertension, hyperlipidemia, and diabetic control, should be aggressively treated.[29] A study found that patients with idiopathic causes were more likely to be younger and smokers, suggesting targets for secondary prevention.[30]

Epidemiology

Autopsy studies suggest the incidence of renal infarction is 14 per 1000, or 1.4%.[6] Other retrospective studies of ER admissions found an incidence of 0.004% to 0.007%.[30][31] Many renal infarctions are diagnosed late or misdiagnosed; therefore, autopsy studies may be more accurate.[30][32] A study found unilateral renal involvement in 81% of cases and bilateral involvement in 19%.[9] Patients with hypercoagulability may be more likely to have multiple and bilateral infarcts.[6] The mean age of patients who present with renal infarction is thought to be approximately 63 years, with no significant difference in sex distribution.[9][19] Risk factors for renal infarction include atrial fibrillation, hypertension, diabetes, and prior embolic infarction.[9][30]

Pathophysiology

Thrombotic mechanisms involve endothelial injury, which activates in-situ thrombus formation. Another ischemic mechanism occurs when emboli from the heart in atrial fibrillation become dislodged and eventually occlude the renal artery. All renal segmental arteries are end-arteries, so a complete or partial reduction in vascular flow due to embolic or thrombotic occlusion leads to renal ischemia and infarction with focal tissue necrosis of the kidney (see Image. Renal Tissue Necrosis). The consequent impairment in renal function can manifest as elevated creatinine levels and decreased glomerular filtration rates (GFR), leading to AKI, chronic kidney disease (CKD), and sometimes end-stage renal failure. 

Atheroemboli is more irregular than thrombus-based emboli, but the crystals are smaller. They are, therefore, more likely to produce an incomplete renal arterial blockage than thromboemboli and tend to affect smaller branches.[26] The atheroemboli eventually cause a foreign body reaction with giant cell formation, narrowing the arterial lumen and reducing renal blood flow, resulting in renovascular hypertension and reduced GFR.[27][28]

An infarction of the main renal artery jeopardizes the function of the entire organ. Segmental arterial occlusion can lead to reduced function of a large portion of the kidney, which is especially significant when associated with preexisting renal failure or solitary kidneys. Blockage of a subsegmental artery leads to the classic "wedge-shaped" diffusion defect of the renal parenchyma seen on contrast-enhanced CT scans of the abdomen.

History and Physical

Clinical Features

Patients with acute renal infarctions typically present with a sudden onset of abdominal or flank pain along with associated symptoms, including nausea, vomiting, hematuria, and occasionally fever. On physical examination, abdominal or loin tenderness findings may be present.[5][6] Skin color changes are noted in approximately one-third of cases (eg, "blue toe" syndrome or livedo reticularis).[33][34] 

Unfortunately, the clinical presentation is often nonspecific or suggestive of alternative, more common disorders, including ureteral colic, a "passed" kidney stone, pyelonephritis, or gastroenteritis. This confusion often leads to a delay, with fewer than 50% of patients receiving the correct diagnosis within 2 days of their initial presentation.[35] Signs of acute kidney injury may only appear several weeks after the actual injurious event. The triad of sudden abdominal or flank pain, elevated lactate dehydrogenase (LDH), and hematuria and proteinuria suggest renal infarction.[31]

Since these cases often present with vague symptoms, a high index of suspicion is necessary for accurate diagnosis. Risk factors for general atherosclerotic disease include male gender, significant smoking history, hypertension, hypercholesterolemia, diabetes, and older age. Atrial fibrillation is a pervasive source of emboli causing renal infarction.[36][37] Fundoscopic examination is suggested in suspected cases of atherosclerotic emboli to identify retinal abnormalities.[38]

Acute loss of renal arterial supply can lead to new-onset, renin-mediated hypertension noted at the time of initial presentation, which usually improves with treatment.[4] Unfortunately, this hypertension is often attributed to a pain response and frequently goes unrecognized.[8] Some patients may be asymptomatic, further contributing to the underdiagnosis of renal infarction. Asymptomatic renal infarction can also be detected incidentally in patients undergoing imaging for unrelated reasons.[39] Atherosclerotic renal emboli as a cause of renal infarction is suggested by the following clinical features: 

• History of a precipitating event in the past 6 months (eg, angiography); the most significant risk factor for cholesterol emboli
• Acute or subacute kidney injury
• Skin color changes [33][34] 
• Cholesterol crystals found in the retina (ie, Hollenhorst plaques) on fundoscopic examination [38]

Evaluation

Laboratory Studies

Laboratory findings in renal infarction include leukocytosis, elevated C-reactive protein (CRP), very high LDH, macroscopic or microscopic hematuria, and proteinuria.[35][40] Other possible lab findings are elevated creatinine and creatine kinase values. The rise in creatinine is more evident in patients with a particularly large renal infarct or bilateral involvement of both kidneys.[6] A careful assessment of coagulation disorders should also be performed if cardiac and renal arterial pathology have been eliminated as causative factors of renal infarction or if surgical revascularization is being considered. LDH is a marker of cell necrosis and can rise to 4 or 5 times the normal value with no similar rise in serum aspartate aminotransferase (AST) and alanine transaminase (ALT) in renal infarction; this does not occur with other etiologies (eg, urolithiasis, renal colic, or pyelonephritis).[4][41][42] Elevated LDH also occurs with myocardial infarction, hemolysis, and renal transplant rejection, which are usually clinically distinguishable from renal infarctions.[42] LDH can remain elevated up to 15 days after the first clinical symptoms.[6] 

Cholesterol emboli causing renal infarction are often associated with eosinophilia, eosinophiluria, and low serum complement in the acute phase. However, these findings dissipate after about 1 week from the time of the injury.[43][44][45] Focal neurological defects, mental confusion, localized cyanosis, and retinal Hollenhorst plaques suggest atherosclerotic emboli.[1] Atheroemboli also tend to produce a slow and often subacute decrease in renal function, which typically plateaus at 3 to 8 weeks.[27] Clinical diagnosis of atheroembolic disease is often missed; renal biopsy can be necessary for a definitive diagnosis. Atheroemboli is detected in over 75% of cases. Intraluminal cholesterol crystals appear as biconvex, needle-shaped defects, or "ghosts" as the cholesterol dissolves during the fixation process.[46][47] Significant vascular intimal inflammation and possibly eosinophilic infiltration.[44] Focal glomerulosclerosis may also be seen.[47][48]

Imaging Studies

Noninvasive imaging studies in patients presenting with acute flank pain, vomiting, and hematuria usually start with a noncontrast CT scan of the abdomen and pelvis to rule out urolithiasis and pyelonephritis, which are the most common reasons for such a clinical presentation.[49] However, with renal infarction, noncontrast CT may show only perinephric stranding, mild renal swelling, or no significant abnormality (see Image. Renal Infarction). If a noncontrast CT is not diagnostic, a contrast-enhanced abdominal CT should be performed to look for renal infarction.[19][20] Clinicians should consider renal infarction in patients with a high risk of thromboembolic events, high LDH levels, or hematuria.[30] 

CT with contrast often shows a clear hypodensity or wedge-shaped perfusion defect in the kidney, best appreciated in the arterial phase. With a segmental infarct, there may be a thin rim of the renal cortex paralleling the wedge-shaped area of the infarct, presenting with normal enhancement. This finding is called the cortical rim sign, which is seen in about half of the cases of renal infarction.[50][51] The cortical rim sign may become evident several days after a renal infarction due to preserved perfusion of the capsule by perforating branches of the renal capsular artery, receiving collateral circulation from branches of the suprarenal, ureteral, and lumbar vessels.[52] If there is total occlusion of the main renal artery, there can be nonenhancement of the entire kidney. In a traumatic transection of the renal artery, CT of the abdomen may reveal a hematoma starting at the hilum of the renal artery. Intervention is likely ineffective if the kidney is atrophic or scarred. Renal CT arteriography is the gold standard investigation for renal infarction and makes the definitive diagnosis, allowing for proper treatment decision-making.[19] Renal magnetic resonance imaging (MRI) arteriography is equally helpful, but the examination takes much longer, so CT imaging is usually preferred. Other investigations used to confirm the diagnosis of renal infarction are dimercaptosuccinic acid (DMSA) radioisotope scans.

Renal artery dopplers are often used to evaluate for renal artery stenosis but cannot assess nonstenotic lesions and determine etiology.[29] Image quality can also be significantly affected by body habitus. A color Doppler scan may also be beneficial in demonstrating decreased or absent blood flow to the infarcted area. An intravenous pyelogram (IVP) in a renal infarction demonstrates nonvisualization of the infarcted renal parenchyma. A DMSA radioisotope scan will reveal decreased or no tracer uptake in the affected area.[4] 

Invasive vascular ultrasound (IVUS) is a newer modality to add diagnostic accuracy for renal infarctions. This method adds information regarding the arterial walls that are not always visualized by arteriography, which primarily images the arterial lumens. IVUS can also help differentiate thrombosis, dissection, and fibromuscular dysplasia. This modality has been used primarily in cardiovascular evaluations, and further study is needed for renal artery imaging.[29][53]

Additional Cardiac Studies

Cardiac studies, including an ECG or Holter monitoring, should evaluate for atrial fibrillation in all patients diagnosed with renal infarction without an apparent cause. A transthoracic or transesophageal echocardiogram can determine the possibility of cardiac thromboembolic disease and thrombi.[52]

Treatment / Management

CT renal angiography is performed to better evaluate the vasculature, identify the specific vessels involved, and determine the degree of occlusion. Revascularization is not useful if imaging demonstrates a shrunken, atrophic kidney or a clearly demarcated, dense wedge-shaped scar suggesting an old infarction. Treating renal infarction can be broadly categorized into catheter-directed thrombolysis, systemic thrombolysis, anticoagulation, surgery, and experimental treatment.

The factors used to determine if a patient would benefit from revascularization procedures include the time since ischemia onset, current kidney function, renal infarct size and extent, the presence of arterial dissection, contralateral kidney function, the precise vessels involved, and whether renal artery occlusion is partial or complete. Determining the time of the infarction onset may not always be straightforward. Acute symptoms (eg, flank pain, nausea, vomiting, and hypertension) suggest a more recent onset of 1 week or less. Typically, even complete occlusions of ≤6 hours are considered potentially reversible. Patients with normal kidney function may not initially show an elevated BUN and creatinine even with complete, acute, unilateral renal arterial occlusion. The degree of renal arterial blockage can be determined by CT renal angiography. Partial occlusion with some degree of visualized parenchymal perfusion suggests potential recovery.

Catheter-Directed Thrombolysis 

Catheter-directed thrombolysis, or percutaneous endovascular therapy, is used to revascularize proximal or bilateral renal artery occlusions and restore perfusion in a solitary kidney. Catheter-directed thrombolysis may also be considered for selected patients with significant segmental artery occlusions. Modalities, including local intraarterial thrombolysis, thrombectomy, angioplasty, or stenting, are more effective when performed as close to the onset of clinical symptoms.[54] Most patients show complete or at least partial vascular reperfusion if diagnosed and treated promptly, and case reports have shown successful revascularization for up to 96 hours after presentation.[55][56][57][58] Following catheter-directed thrombolysis, laboratory markers of renal recovery may lag behind functional kidney improvement. One study demonstrated long-term recovery of renal function despite no significant improvement in the BUN and creatinine at the time of hospital discharge. Likely, some renal tissue was reperfused and recovered over time, similar to "myocardial stunning."[37](B3)

One published protocol attempts thrombectomy first; if unsuccessful, a bolus injection of 250,000 IU of urokinase is given directly into the affected artery. If results are not deemed adequate, the catheter is left in place, and a continuous infusion of urokinase at a rate of 50,000 IU per hour is utilized for up to 72 hours. Daily renal angiograms are done while the urokinase infusion is administered, and the patients are carefully monitored for possible complications. If the infarction remains unchanged after 72 hours, the treatment is ineffective and discontinued.[37] Other thrombolytic agents like urokinase, streptokinase, or tissue plasminogen activator have also been used. If thrombolysis is ineffective, angioplasty with or without stenting can be considered, but no definitive guidelines exist. The complications of catheter-directed thrombolysis include bleeding, pseudoaneurysm formation, and acute mesenteric embolism with ischemia.[59] Typically, patients who undergo angioplasty or stenting receive 3 to 6 months of aspirin and clopidogrel. Ultrasound-enhanced catheter-directed thrombolysis is a novel treatment option for renal artery thrombosis, wherein the ultrasound waves allow better penetration of thrombolytic agents by acoustic streaming.[60] Following endovascular therapy, patients are maintained on aspirin and clopidogrel; the clopidogrel can be discontinued after 3 months.[60](B3)

Systemic Thrombolysis 

Systemic thrombolysis can be attempted if catheter-directed thrombolysis is not available.[61][62] However, the risk of systemic bleeding is higher in systemic fibrinolytic therapy than in catheter-directed thrombolysis.[4] Compared to systemic fibrinolysis, catheter-directed thrombolysis has the advantage of a lower dosage of thrombolytic agents and easier deliverability to the target blood vessels.[60] Reperfusion injury is a potential complication of thrombolysis. (B3)

Anticoagulation or antiplatelet agents are considered the treatment of choice for patients who present several days or longer after a renal infarction, as revascularization therapy is not likely to be beneficial. Long-term anticoagulation is initiated for those with underlying hypercoagulation disorders or cardioembolic disease. The duration of anticoagulation is typically at least 6 months if the patient does not have risk factors for repeat embolization. Intravenous heparin, followed by warfarin, with a target INR of 2 to 3, is commonly used. In patients already on warfarin with a therapeutic INR before their renal infarct, an increased INR target of 2.5 to 3.5 is suggested. Direct oral anticoagulants (eg, Factor Xa inhibitors) are frequently used for anticoagulation indications and do not require the frequent monitoring associated with long-term warfarin therapy. If anticoagulants are stopped after 6 months, life-long aspirin has been recommended for patients with renal infarction, even if no specific hypercoagulable state has been identified. Aspirin may also benefit those with asymptomatic remote renal infarctions who present with an atrophic kidney.

Surgical Therapy

Open surgery is mostly attempted in the event of trauma-related renal artery injury and aortic dissection extending into the renal artery. Various surgical options include arteriotomy with embolectomy, aorto-renal, ileo-renal, or splenorenal bypass procedures.[40] Clinicians should refer patients with underlying fibromuscular dysplasia to specialists for possible percutaneous transluminal angioplasty or vascular reconstructive surgery. Surgical intervention has not proven effective in thrombotic and embolic etiologies and is associated with significant risks.[37](B3)

Antihypertensive Medications 

Antihypertensive medications inhibiting the renin-angiotensin axis are preferred for renovascular hypertension, which often develops in the first week after a renal infarction due to increased renin levels. The associated hypertension frequently subsides in the following weeks unless underlying essential hypertension exists.[37][39] Long-term management of high blood pressure should be the same as for any hypertensive patient.[37]

Atherosclerotic Emboli Therapy

Atherosclerotic emboli treatment in the renal arteries is primarily supportive.[63][64] Scheduled angiographic and vascular procedures should be canceled, postponed, or delayed. Patients with renal infarcts due to atheroemboli have a relatively poor overall prognosis due to the severity of their underlying atherosclerotic disease. However, patients without significant comorbidities or complications can see their renal function improve over time, as shown in a study where 24% fully recovered.[27] Patients should follow general measures, including aspirin use, smoking cessation, hypertension control, weight management, and glycemic control.[1][65] (B2)

Surveillance Recommendations

Long-term follow-up for patients with thromboembolic renal infarctions has not been standardized. Monitoring patients for complications related to ongoing therapy (eg, bleeding episodes) and regularly checking renal function is reasonable. Lifelong aspirin therapy is typically recommended as well.[10][66] 

Follow-up imaging is recommended, and some experts have suggested serial abdominal imaging, preferably with MRI, at 6 and 12 months. If no new lesions or concerns are found, further surveillance imaging may not be necessary. Patients with underlying renal or cardiac issues will require closer and longer-term monitoring. 

Differential Diagnosis

Diagnoses in the differential for renal infarction include the following: aortic aneurysm, aortic dissection, appendicitis, diverticulitis, gastroenteritis, mesenteric ischemia, nephrolithiasis, pyelonephritis, renal cell carcinoma, and gynecologic disorders. Nephrolithiasis and pyelonephritis are commonly confused for renal infarction. Failure to consider renal infarction as a differential in a case of flank pain initially suspected as renal colic could delay diagnosis and make renal function unsalvageable with reperfusion therapy. Significant LDH elevation is not seen in pyelonephritis or nephrolithiasis and can be used to help distinguish these disorders from renal infarction, especially if serum transaminases are low. A contrast-enhanced CT scan of the abdomen is crucial to help differentiate renal infarction from extrarenal causes of abdominal pain. Clinicians should exclude mesenteric ischemia because systemic embolization in a patient with atrial fibrillation or hypercoagulable disorder could potentially occlude the blood vessels supplying the intestine, leading to acute bowel infarction; angiography may be required for evaluation.

Prognosis

One large retrospective review found approximately 20% of patients diagnosed with renal infarction had died at 40 months; however, only 2% of these patients progressed to ESRD. The poor prognosis suggests that renal infarction is indicative of cardiac and other mortality. [29] Prognosis is improved with early diagnosis. Warm ischemia time, collateral flow, and preexisting kidney disease tend to influence prognosis following treatment with catheter-directed thrombolysis.[55] Prognosis can also be influenced by embolic infarction in other organs like the spleen, intestine, liver, and lungs.[19] The presence of extrarenal embolisms increases the duration of hospital stay as well as the overall morbidity and mortality.[11]

Complications

Common complications include acute kidney injury, chronic kidney disease, and hypertension. The progression to CKD from AKI correlates with the magnitude of the infarction.[67] The main risk factors for CKD are advanced age and a higher degree of AKI. Up to 58% of renal infarction patients developed CKD, as detected in follow-up renal scintigraphy.[67][68][69]