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RPS Case of the Month

May 2023

Hypertensive urgency with acute

kidney injury – diagnostic possibilities


Anjali Satoskar, MD1

Dalia Y. Ibrahim, MD MSc2

Amy A. Yau, MD1


1. The Ohio State University Wexner Medical Center, Columbus, OH USA 43210
2. 2. University of Toledo Medical Center, Toledo, OH USA 43614

CLINICAL HISTORY

A Caucasian male in his 70s with acute kidney injury and previous history of stenosis of the right carotid artery, bilateral renal artery stenosis, Leriche syndrome, as well as history of malignant secondary renovascular hypertension and chronic kidney disease (CKD) stage IV. His baseline serum creatinine was 2.39 mg/dL. He presents with hypertensive urgency, oliguric acute kidney injury, and subnephrotic proteinuria. Blood pressure 165/73 mm Hg. He weighs 182 pounds with a BMI 24.7 kg/m2. Laboratory workup shows serum creatinine 6.4-7.3 mg/dL. It worsened further prior to the biopsy and was up to the 8-9 mg/dL range. Serum potassium 4.8 mEq/L, serum calcium 8.5 mg/dL and serum phosphorus 4.9 mg/dL. WBC count 15.2 x 109/L, hemoglobin 10.0 g/dL, and platelet count 223K/uL. Urine protein/creatinine ratio was 2.6, and urinalysis showed greater than 300 mg/dL protein, 0-5 WBC per high-power field, and greater than 20 red blood cells per high-power field. Serologies for ANCA, anti-myeloperoxidase, anti-proteinase 3, and ANA are all negative. Cryoglobulin test is negative. There are normal levels of serum C3, C4, haptoglobin, free kappa light chain, free lambda light chain, and kappa to lambda light chain ratio. The patient was started on dialysis, and he was empirically pulsed with steroids for possible glomerulonephritis.

KIDNEY BIOPSY FINDINGS

 

Figure 1: Approximately 35% of the glomeruli in the biopsy are globally sclerosed, and additional glomeruli show periglomerular fibrosis and small poorly perfused capillary tufts. Zonal interstitial fibrosis and tubular atrophy with tubular thyroidization (small tubules with thin walls and distended with hyaline casts) (HE 200x)


 

Figure 2: Zonal interstitial fibrosis and tubular atrophy most likely due to repeated episodes of atheroemboli and obliterative microvascular disease leading to zonal ischemia in the kidney (Trichrome x100)



Figure 3: Arteries show moderate fibrointimal thickening. An arcuate-size artery shows prominent cholesterol clefts (HE x200)


 

Figure 4: Another arcuate-size artery shows prominent cholesterol clefts (HE x400)



FINAL DIAGNOSIS

  • Multiple arteries with cholesterol clefts, consistent with cholesterol embolism (atheroembolism).
  • Zonal cortical scarring and tubular thyroidization with superimposed acute tubular necrosis (ATN).

 

DISCUSSION

In atheroembolic renal disease atheromatous plaque dislodged from major arteries can get repeatedly and persistently lodged in intra-renal arteries, arterioles, and rarely glomerular capillary tufts causing progressive microvascular occlusion, leading to ischemic injury to the parenchyma and progressive renal dysfunction and chronic kidney disease. It may follow intravascular interventions, or can rarely occur spontaneously1.

It was first described by Panum in 1862 2. There are three forms of atheroembolic renal disease. Acute form, in which massive embolization develops within few days of the provoking event. Subacute form, which is the most frequent form, ensues in a stepwise fashion likely caused by recurrent embolization. The third form is often mistaken for nephrosclerosis because it presents as chronic and slowly progressive impairment of renal function due cholesterol crystals slowly released from the atherosclerotic plaque over a period of time 3.

Cholesterol emboli have a predilection to occur in white males older than 50 years. Cholesterol emboli can involve any organ downstream of atherosclerotic plaques. The kidney is the most common site of involvement. Clinical presentation includes acute kidney injury, new onset hypertension, proteinuria, and hematuria. Prognosis is poor, mostly related to the underlying vascular disease and multi-organ damage 4.

Renal biopsy is the gold standard for diagnosis 5. However, because the renal vasculature is not equally affected, the diagnosis may be missed due to sampling bias. Needle shaped, biconvex clefts are seen in the arcuate and interlobular arteries, as the lipids are dissolved during formalin fixation. They can also involve arterioles and rarely reach the glomeruli 6. Acute lesions may be surrounded by red blood cells, fibrin, and leukocytes. In the subacute phase, multinucleated giant cell reaction can be seen surrounding the cleft-like spaces. Chronic lesions show intimal fibrosis around the cholesterol clefts. The obstruction is usually incomplete leading to ischemic atrophy. When unfixed, unstained tissue is air dried and viewed under polarized light, cholesterol crystals are birefringent 1. There is no specific staining seen in immunofluorescence microscopy. Electron microscopy may show foot process effacement.

Differential diagnosis includes:

  1. Acute Thrombotic microangiopathy (TMA): this is characterized by hypertensive urgency and acute kidney injury (AKI).
  2. Chronic TMA or thromboembolism: zonal scarring in the kidney with thyroidization of tubules. It can also cause focal infarcts similar to thromboemboli affecting larger arteries.
  3. Acute glomerulonephritis: there is active urine sediment, AKI, and proteinuria.

Diagnostic clues:

  1. Severe arteriosclerotic disease usually in abdominal aorta and renal arteries. In this case, multiple arteries were affected.
  2. It is usually preceded by invasive vascular procedure such as carotid stenting or abdominal aortic aneurysm repair. But may also be spontaneous as in this case.
  3. Patient has negative autoimmune serologies, normal complements, but sometimes C3 can be low.

 

References

  1. Modi KS, Rao VK. Atheroembolic renal disease. J Am Soc Nephrol. 2001; 12:1781–7. 
  2. Panum PL. Experimentelle Beitrage zur Lehre von der embolie. Virchows Arch Pathol Anat Physiol. 1862; 25:308–10. 
  3. Li X, Bayliss G, Zhuang S. Cholesterol crystal embolism and chronic kidney disease. Int J Mol Sci. 2017; 18:1120. 
  4. lusco et al. AJKD Atlas of Renal Pathology: Cholesterol Emboli. Am J Kidney Dis. 2016;67(4): e23-e24
  5. Sharma A, Hada R, Agrawal RK, Baral A. Favorable outcome in atheroembolic renal disease with pulse steroid therapy. Indian J Nephro l. 2012; 22:473–6. 
  6. Flory CM. Arterial occlusion produced by emboli from eroded aortic atheromatous plaques. Am J Pathol. 1945; 21:549–65. 



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The RPS promotes excellence in diagnosis, fosters basic, clinical and translational research, encourages training and education in renal disease, sponsors US based and international conferences and symposia, and brings news and updates pertaining to renal pathology to its members around the world.

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