Small dose oral corticosteroid treatment rapidly improved renal function in a patient with an acute aggravation of chronic renal failure due to cholesterol embolism

Hajime Nakahama1 and Katsuhiko Sakaguchi2

1 Division of Hypertension and Nephrology, National Cardiovascular Center, Suita, Japan, 2 Department of Internal Medicine, Sumitomo Hospital, Osaka, Japan

Sir,

Cholesterol embolism is a disease that is attracting growing attention [1]. It typically complicates intravascular catheterization and anticoagulant and thrombolytic therapy, during which atheromatous materials are dislodged from major vascular walls and occlude small arteries of multiple organs. Many organs may be affected, and typical features include a purpuric rash, livedo reticularis, myalgia, and acute renal failure. The development of multifocal ischaemic lesions is ominous, and leads to serious morbidity and mortality of up to 37–90% [2]. Once cholesterol emboli have occurred, therapy is of limited value. Intensive supportive treatments including haemodialysis are usually needed. Information on the use of corticosteroids in this condition is limited and its effects are controversial. We report the case of a 55-year-old man with an acute episode of chronic renal failure in whom clinical signs and laboratory tests suggested cholesterol embolism. A small dose of oral corticosteroid (prednisolone 15 mg/day p.o.) resulted in a rapid improvement of renal function.

Case.

A 55-year-old man was admitted to the surgery department on September 24, 1999. The patient had a long (over 10 years) history of hypertension, diabetes mellitus, renal dysfunction as well as anterior myocardial infarction (in 1991). He developed intermittent claudication in 1995 in the right calf, and recent similar symptoms in the left calf. Angiography of the lower limbs demonstrated multiple occlusive lesions. A saccular abdominal aortic aneurysm was also found following CT. Coronary angiography (performed on October 19) showed severe lesions in the anterior descending artery. A percutaneous transluminal coronary angioplasty (PTCA) with stenting was performed on October 28 prior to the surgery. On November 10, 1999, surgery, consisting of a straight graft replacement of the abdominal aorta, an aorta-to-right exterior iliac artery bypass grafting, and an aorta-to-left common femoral artery bypass grafting, was performed.

The patient's serum creatinine was slightly elevated (2.1 mg/dl) on September 28. It increased to 3.9 mg/dl on November 8, and continued to rise to 5.7 mg/dl on November 22. The patient was transferred to the renal division on November 25. Upon transfer, he was unwell with nausea, right lumbar pain and mild fever. On physical examination, his blood pressure was 154/36 mmHg and his pulse was 92 bpm. The bilateral dorsalis pedis pulse was good. No skin lesions such as livedo reticularis were found. The chest was clear according to percussion and auscultation. Palpation of the abdomen revealed a tenderness at the right hypochondrium. Blood urea nitrogen was 28 mg/dl. The haemoglobin was 10.2 g/dl, and the white blood cell count was slightly increased, at 10 120/mm3 with eosinophilia (23.5% or 2378/mm3). Cold-agglutination antibody, thyroglobulin antibody, microsomal antibody, anti-nuclear antibody, anti-DNA antibody, ASO, RF, P-ANCA and C-ANCA were negative. The sedimentation rate was high, at 78 mm/h. C-reactive protein (CRP) was slightly elevated at 4.18 mg/dl (normal:<0.3 mg/dl). There was a hypocomplimentaemia of CH50 20.8 U/ml (normal: 29–45 U/ml). C3 at 53.9 mg/dl (normal: 70–169 mg/dl), and C4 at 19.1 mg/dl (normal: 10–40 mg/dl). Urine was 2+ positive for protein, and 1+ positive for occult blood. Urine microscopy showed 0–1 red, and 0–1 white cell counts per high-power field, and there were hyaline, hyaline-granular and granular casts. Chest radiography was unremarkable. A renal ultrasonographic study showed bilateral atrophic kidneys (right 8.0 cm, left 9.0 cm) with thin cortices.

A diagnosis of an acute episode of chronic renal failure due to cholesterol embolism was made for the following reasons: (i) an increase of serum creatinine occurred after more than a week following coronary angiography and PTCA, (ii) both peripheral blood eosinophilia and (iii) hypocomplementaemia were observed. As no skin lesions, such as livedo reticularis were present, skin biopsies were not feasible and histopathologic proof of cholesterol emboli was not obtained.

Prednisolone treatment (15 mg/day or 0.3 mg/kg/day p.o.) was begun on December 4, 1999. Serum creatinine levels, which reached a peak of 10.5 mg/dl on December 7, began to decline rapidly following the corticosteroid treatment. Creatinine was 3.9 mg/dl on December 24 (Figure 1Go). The clinical symptoms of mild fever, malaise, abdominal discomfort, and eosinophilia subsided. Prednisolone was tapered to 15 mg/day p.o. on alternate days. Serum creatinine increased to 4.8 mg/dl on January 5, 2000. The prednisolone dose was returned to 15 mg/day p.o. every day. No further increase in serum creatinine level was observed.



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Fig. 1 The temporal course of serum creatinine in a patient with cholesterol embolism treated with prednisolone. {blacksquare}, represents the period when prednisolone, 15 mg p.o., was administered on alternate days. CAG, coronary angiography; PTCA, percutaneous transluminal coronary angioplasty.

 

Comment.

Cholesterol embolism is an important and often underdiagnosed cause of renal insufficiency [1]. Cholesterol crystals originate in large vessels such as the abdominal aorta and then lodge in small arteries, such as the arcuate, interlobular and terminal arterioles of the kidneys. Cholesterol emboli appear as biconcave needle-shaped clefts within the lumen of affected vessels. The subsequent intravascular inflammatory reaction causes tissue ischaemia and ultimately leads to renal failure. Cholesterol embolism also involves the skin, muscles, abdominal organs and central nervous system, resulting in significant morbidity and mortality. Performing a skin, muscle, or renal biopsy often allows an accurate diagnosis. Predisposing factors include vascular surgery, arteriography, angioplasty, anticoagulation and thrombolytic therapy. Unlike in contrast nephropathy, renal failure due to cholesterol embolism develops about a week after the vascular procedure and persists or progresses over weeks and months.

The patient presented here already had moderate renal impairment upon admission. A rapid deterioration of renal function occurred following coronary angiography, PTCA, and abdominal aortic aneurysm resection and graft surgery. Due to a lack of skin lesions and to renal atrophy, no biopsy was feasible. Even without histopathological proof, cholesterol embolism-induced renal failure can be easily diagnosed if an increase in serum creatinine of 0.5 mg/dl or more above baseline occurs at least a week or more after angiography. Diagnosis is made in the absence of any other clinically discernible causes of renal failure in patients who have any two of the following: (i) livedo reticularis/petechiae/digital infarction or gangrene/ purple toe/splinter haemorrhage, (ii) hollenhorst plaques (cholesterol crystals in retinal artery), (iii) peripheral blood eosinophilia, (iv) eosinophiluria, or (v) high sedimentation rate [3]. The present patient had eosinophilia and a high sedimentation rate. He also had hypocomplimentaemia, which is often associated with cholesterol embolism. Based on the presence of predisposing factors, the clinical manipulations, eosinophilia, high sedimentation rate and hypocomplementaemia, a final diagnosis of an acute episode of chronic renal failure due to cholesterol embolism was made.

The prognosis of cholesterol embolism is usually ominous, and information on specific treatments is limited. Measures that are usually recommended include (i) discontinuation of anticoagulant treatment, (ii) avoidance of further aortic catheterization, (iii) control of hypertension, (iv) haemodialysis, and (v) nutritional support.

Corticosteroid therapy has been utilized to reduce the inflammatory response with limited or no success. Two cases showing variable responses to high-dose corticosteroids following acute peripheral embolization have been reported [4]. A recent report from Belenfant et al. was more encouraging [5]. They administered 0.3 mg/kg prednisolone to 18 patients having laboratory evidence of inflammation along with a declining general status and/or new episodes of cholesterol embolism. This treatment resulted in relief of lower limb and/or gastrointestinal pain and a definite improvement in food intake and clinical status. It was not specified in the report to what extent corticosteroid treatment improved renal function nor whether it contributed to the overall improvement of patients' prognoses.

To our knowledge, the cholesterol embolism case presented here is the first showing rapid improvement in renal function and avoidance of haemodialysis following a small dose of oral corticosteroid (prednisolone 0.3 mg/kg). The effect of prednisolone was evident because serum creatinine levels increased when prednisolone was reduced to 15 mg/day on alternate days. Despite this being a single case experiment and the lack of histopathologic diagnosis, our experience suggests that corticosteroid treatment may be warranted in cholesterol embolism. A study with a larger number of patients may give more definitive directions for the use of corticosteroids as a treatment for cholesterol embolism.

References

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