Journal of Artificial Organs

, Volume 18, Issue 1, pp 72–78 | Cite as

Low-density lipoprotein apheresis ameliorates monthly estimated glomerular filtration rate declines in patients with renal cholesterol crystal embolism

  • Keiji Hirai
  • Susumu Ookawara
  • Haruhisa Miyazawa
  • Kiyonori Ito
  • Yuichirou Ueda
  • Yoshio Kaku
  • Taro Hoshino
  • Izumi Yoshida
  • Kaoru Tabei
Original Article Apheresis

Abstract

The incidence of cholesterol crystal embolism (CCE) has increased along with increases in the prevalence of atheromatous diseases and intravascular procedures. CCE frequently results in the deterioration of renal function, which sometimes leads to end-stage renal failure. Although there has been no established therapy for CCE, the possibility that low-density lipoprotein apheresis (LDL-A) is an effective therapy for renal CCE was previously reported. However, whether LDL-A improves renal CCE remains uncertain. This study aimed to evaluate the effectiveness of LDL-A in renal CCE patients. Twelve renal CCE patients (9 men and 3 women, mean age 70.6 ± 1.7 years) were included in this retrospective study. All patients had received LDL-A therapy, and estimated glomerular filtration rate (eGFR) values were examined before and after LDL-A. In addition, monthly changes in eGFR before and after LDL-A were calculated for each patient. At initial diagnosis of renal CCE, the eGFR was 35.2 ± 4.8 mL/min/1.73 m2. At the initiation of LDL-A, the eGFR significantly decreased to 11.0 ± 1.2 mL/min/1.73 m2, and monthly changes in eGFR reached −7.2 ± 2.5 mL/min/1.73 m2/month. After the initiation of LDL-A, the progression of renal dysfunction stabilized in nearly two-thirds of patients, and monthly changes in eGFR after LDL-A significantly diminished to −0.3 ± 0.7 mL/min/1.73 m2/month (p < 0.05 vs. before LDL-A). Although 4 patients had to undergo hemodialysis, all patients were alive over 1 year after the initiation of LDL-A. LDL-A therapy ameliorated renal dysfunction in renal CCE patients.

Keywords

LDL apheresis Cholesterol crystal embolism Renal dysfunction eGFR 

Introduction

Cholesterol crystal embolism (CCE) is a systemic disease caused by cholesterol crystal embolization leading to the occlusion of small arteries in a variety of organs. It may occur spontaneously, or, more often, after intravascular procedures such as coronary angiography and carotid artery stenting, cardiovascular surgery such as coronary artery bypass grafting, or aortic aneurysm surgery [1].

The kidneys were previously reported to be the most frequent target organ for CCE, and renal CCE was found during the course of clinical illness in approximately 50 % of CCE patients [2]. Low-density lipoprotein apheresis (LDL-A), which proved effective in the treatment of various kidney diseases [3], may ameliorate renal dysfunction in renal CCE [4, 5]. LDL-A markedly increases serum bradykinin levels [6]. Moreover, activation of the kinin pathway, including bradykinin, was recently reported to be associated with a renoprotective effect in a salt-sensitive rat model via the improvement of salt sensitivity and reduction of renal fibrosis caused by the suppression of renal transforming growth factor-β (TGF-β) [7]. However, few reports have examined the relationship between the efficacy of LDL-A and the clinical course of renal CCE, and whether LDL-A improves renal CCE remains uncertain.

This study aimed to calculate monthly changes in the estimated glomerular filtration rate (eGFR) before and after LDL-A therapy, and to evaluate the effectiveness of LDL-A in improving renal function in renal CCE patients.

Materials and methods

Patients

We included renal CCE patients treated between 2006 and 2010 who met the following criteria: (a) diagnosed on the basis of renal CCE diagnostic criteria [8], (b) continuous deterioration of renal function even in the presence of blood pressure (BP) management and statin treatment after the onset of renal CCE, and (c) completion of LDL-A therapy.

The diagnosis of renal CCE was made according to the following criteria [8]:
  1. 1.

    Acute or subacute renal failure. Serum creatinine elevation of more than 50 % after the precipitating event.

     
  2. 2.

    Signs of peripheral emboli such as blue toes, livedo reticularis, and digital gangrene.

     
  3. 3.

    A precipitating event or histological confirmation. Intravascular procedures and cardiovascular surgery were precipitating events.

     

On the basis of these criteria, a diagnosis of renal CCE could be made even in the absence of histological confirmation. In addition, the spontaneous form of renal CCE was reportedly diagnosed only when a skin, gastrointestinal, or renal biopsy documented cholesterol clefts without precipitating events [8].

Twelve patients (9 males and 3 females, mean age 70.6 ± 1.7 years) diagnosed with renal CCE were included in this retrospective study. All patients exhibited skin lesions such as livedo reticularis and blue toes. Invasive vascular procedures including angiography or vascular surgery were performed in 10 patients. Renal CCE occurred spontaneously in only 2 patients. Pathological examinations were also performed in 6 patients (skin biopsy in 5 patients and renal biopsy in 1 patient) and showed cholesterol clefts in all 6 patients. The patients’ general characteristics are summarized in Table 1. This study was approved by the Institutional Review Board of Saitama Medical Center, Jichi Medical University, Japan, and conforms to the provisions of the Declaration of Helsinki (as revised in Tokyo, 2004).
Table 1

Patient demographics, clinical characteristics, renal prognosis, and patient’s 1-year survival during the first year after the initiation of LDL-A

Case

Age

Sex

Skin lesions

Biopsy

Findings

HT

DL

DM

Smoking

eGFR prior to renal CCE onset (mL/min/1.73 m2)

CVD

Interventions

Renal prognosis

1 year survival

1

77

F

Livedo reticularis

Kidney

Cholesterol cleft

+

+

27.2

AAA, CI

Y graft replacement

Stabilized

Alive

2

62

M

Blue toes

 

+

+

48.6

PAD

Iliac artery stenting

Stabilized

Alive

3

68

M

Digital gangrene

 

+

+

+

+

44.9

PAD

CAG

Stabilized

Alive

4

68

M

Blue toes

 

+

+

+

No data

MI

PCI

Stabilized

Alive

5

71

M

Livedo reticularis

Skin

Cholesterol cleft

+

+

+

No data

MI

CABG

Stabilized

Alive

6

76

M

Blue toes

Skin

Cholesterol cleft

+

+

+

+

45.9

AP

CABG

Stabilized

Alive

7

82

F

Blue toes

 

+

+

32.3

MI

CABG·CAG

Stabilized

Alive

8

66

F

Livedo reticularis

Skin

Cholesterol cleft

+

+

+

No data

  

Stabilized

Alive

9

76

M

Livedo reticularis

Skin

Cholesterol cleft

+

+

+

+

31.3

 

AVR

HD

Alive

10

68

M

Digital gangrene

Skin

Cholesterol cleft

+

+

+

+

No data

  

HD

Alive

11

68

M

Livedo reticularis

 

+

+

+

+

12.3

AP

PCI

HD

Alive

12

65

M

Blue toes

 

+

+

+

No data

AP

CAG

HD

Alive

AAA abdominal aortic aneurysm, AP angina pectoris, AVR aortic valve replacement, CABG coronary artery bypass graft surgery, CAG coronary angiography, CI cerebral infarction, CVD cardiovascular disease, DL dyslipidemia, DM diabetes mellitus, HT hypertension, MI myocardial infarction, PAD peripheral artery disease, PCI percutaneous coronary intervention

Methods of LDL-A therapy

LDL-A was performed once a week for 10 consecutive weeks using hollow polysulfone fibers (Sulflux, Kaneka, Osaka, Japan) for plasma separation and a dextran sulfate cellulose column (Liposorba 15, Kaneka, Osaka, Japan) as the LDL absorber. Plasma volume was treated at a rate of 50 mL/kg per LDL-A session. The blood flow rate was adjusted to 60–80 mL/min. The anticoagulant agent used was heparin sodium, which was administered as a 1,000-unit priming dose followed by, 1,000 units per hour during hemodialysis (HD).

Evaluation of eGFR

We calculated eGFR values using the following equation [9] and evaluated these values as markers of the progression of renal dysfunction for 3 months before and after LDL-A therapy:
$$ \begin{gathered} \text{eGFR} \left( {\text{mL} /\hbox{min} /1.73\text{m}^{2} } \right) = \, 194 \times \text{S} { - }\text{Cr}^{ - 1.094} \times \text{age}^{ - 0.287} \left( \text {for\,\,men} \right) \hfill \\ \,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\,\, = \, 194 \times \text{S} { - }\text{Cr}^{ - 1.094} \times \text{age}^{ - 0.287} \times 0.739 \, \left( \text {for\,\,women} \right) \hfill \\ \end{gathered} $$
where S-Cr is the serum creatinine concentration (mg/dL).

The decline of renal function was assessed as monthly changes in eGFR using repeated eGFR measurements available at more than 2 time points, and expressed in mL/min/1.73 m2/month. Measurements of eGFR were carried out 5.2 ± 0.7 times during observation before LDL-A and 6.8 ± 0.9 times after the initiation of LDL-A. Monthly changes in eGFR were determined by performing linear regression analysis as the slope per month for each patient before and after LDL-A, respectively [10]. Four out of 12 patients showed a gradual deterioration of renal function even after the initiation of LDL-A therapy, and they had to undergo HD therapy. Even in these patients, LDL-A therapy was completed 10 times regardless of the need for HD, and monthly changes in eGFR after LDL-A were calculated using S-Cr values from the initiation of LDL-A up until the initiation of HD because S-Cr values decreased or fluctuated under the influence of HD therapy.

Statistics

Data are expressed as mean ± standard error (SE). The non-parametric Mann–Whitney U test was used for 2 group comparisons. Comparisons of clinical parameters at the initial diagnosis of renal CCE and before and after LDL-A therapy were evaluated by performing a repeated-measures analysis of variance (ANOVA) using general linear models and Scheffe’s test, respectively. A difference of p < 0.05 was considered statistically significant.

Results

As shown in Table 2, the eGFR value at the initial diagnosis of renal CCE was 35.2 ± 16.5 mL/min/1.73 m2, and 11 out of 12 patients already showed renal dysfunction with CKD stage G3-5 [9]. Renal CCE was treated using antihypertensive agents and statin therapy in all patients, and using steroid therapy in 4 patients. However, renal function continued to deteriorate, and therefore, LDL-A therapy was added consecutively. The duration from the initial diagnosis of renal CCE to the initiation of LDL-A was 118.5 ± 59.0 days. Values of eGFR significantly decreased from 35.2 ± 4.8 to 11.0 ± 1.2 mL/min/1.73 m2 (p < 0.01). Serum LDL concentrations decreased from 120.8 ± 51.0 to 93.2 ± 39.7 mg/dL without significance, while serum high-density lipoprotein (HDL) concentrations also tended to decrease from 37.8 ± 8.2 to 33.1 ± 8.3 mg/dL. Systolic, diastolic, and mean BP values were all elevated before LDL-A as compared to values obtained at the initial diagnosis of renal CCE, despite the increase in the number of antihypertensive medications. After LDL-A therapy, eGFR values stabilized at 12.1 ± 1.7 mL/min/1.73 m2, and serum LDL concentrations further decreased to 80.0 ± 8.8 mg/dL (p < 0.05 vs. initial diagnosis of renal CCE). Furthermore, diastolic and mean BP values significantly decreased compared with those measured before LDL-A (p < 0.05 for each). Although the number of antihypertensive medications was significantly higher after LDL-A than at the initial diagnosis of renal CCE (p < 0.05), it was not significantly different before and after LDL-A. At the end of LDL-A, ARBs were consumed by 8 patients; CCBs, by 11 patients; beta-adrenergic blocking agents, by 11 patients; and a direct renin inhibitor, by 1 patient. Changes of eGFR values in each patient are shown in Fig. 1. Whereas eGFR values rapidly decreased for several months prior to the initiation of LDL-A, they seemed to stabilize after LDL-A therapy. Based on these changes in eGFR values, we calculated monthly changes in eGFR for 3 months before and after LDL-A (Fig. 2). Before LDL-A, the monthly changes in eGFR reached −7.2 ± 2.5 mL/min/1.73 m2, which was considered a very rapid decrease in eGFR. However, these changes were diminished to −0.3 ± 0.7 mL/min/1.73 m2 after LDL-A, which is significantly smaller than the changes observed before LDL-A (p < 0.05). Although LDL-A was considered effective in stabilizing eGFR values in nearly two-thirds of renal CCE patients, HD was necessary in 4 patients because of progression of renal dysfunction. All patients were alive over 1 year after LDL-A therapy even though one-third of the patients required HD therapy (Table 1). Furthermore, we compared the clinical parameters between patients who required HD and those who did not to clarify the factors associated with renal prognosis in this study (Table 3). S-Cr values were significantly higher in patients who required HD than in those who did not, both at the initial diagnosis of renal CCE (2.42 ± 0.68 vs. 1.32 ± 0.06 mg/dL, p < 0.05) and before LDL-A (6.07 ± 0.13 vs. 4.01 ± 0.51 mg/dL, p < 0.05). eGFR values tended to be lower in patients who required HD before HD than in those who did not, although the difference was not significant. However, there were no significant differences according to HD requirement in lipid metabolism, systemic BP levels, number of antihypertensive medicines, days from initial diagnosis of renal CCE to the initiation of LDL-A, and monthly changes in eGFR before LDL-A.
Table 2

Comparison of changes in clinical parameters at the initial diagnosis of renal CCE as well as before and after LDL-A

 

Initial diagnosis of renal CCE

Before LDL-A

After LDL-A

p value

eGFR (mL/min/1.73 m2)

35.2 ± 4.8

11.0 ± 1.2*

12.1 ± 1.7*

<0.01 vs. onset*

LDL (mg/dL)

120.8 ± 14.7

93.2 ± 11.5

80.0 ± 8.8**

<0.05 vs. onset**

HDL (mg/dL)

37.8 ± 2.4

33.1 ± 2.4

41.4 ± 4.0

0.08

Systolic BP (mmHg)

147.8 ± 7.2

156.2 ± 4.9

134.5 ± 5.9

0.06

Diastolic BP (mmHg)

76.1 ± 3.7

82.8 ± 4.7

66.5 ± 4.0**

<0.05 vs. before LDL-A**

Mean BP (mmHg)

100.0 ± 4.5

107.3 ± 4.4

89.2 ± 4.4**

<0.05 vs. before LDL-A**

Number of antihypertensive medicines

1.7 ± 0.5

2.3 ± 0.3

3.0 ± 0.3**

<0.05 vs. onset**

Fig. 1

Changes of eGFR values in each patient before and after LDL-A

Fig. 2

Monthly changes in eGFR before and after LDL-A. *p < 0.05 vs. before LDL-A

Table 3

Comparison of clinical parameters at the initial diagnosis of renal CCE and before LDL-A between patients who received HD and those who did not

n

HD received

Non-HD received

p value

4

8

Initial diagnosis of renal CCE

 Serum creatinine (mg/dL)

2.42 ± 0.68

1.32 ± 0.06

<0.05

 eGFR (mL/min/1.73 m2)

32.2 ± 13.4

36.7 ± 3.8

0.68

 LDL (mg/dL)

85.0 ± 11.2

138.6 ± 18.7

0.09

 HDL (mg/dL)

37.0 ± 2.4

38.3 ± 3.5

0.82

 Systolic BP (mmHg)

150.5 ± 21.0

146.4 ± 5.3

0.80

 Diastolic BP (mmHg)

75.8 ± 11.4

76.3 ± 2.1

0.95

 Mean BP (mmHg)

100.7 ± 14.5

99.6 ± 1.4

0.92

 Number of antihypertensive medicine

2.0 ± 0.8

1.5 ± 0.6

0.64

Before LDL-A

 Serum creatinine (mg/dL)

6.07 ± 0.13

4.01 ± 0.51

<0.05

 eGFR (mL/min/1.73 m2)

8.0 ± 0.2

12.5 ± 1.5

0.06

 LDL (mg/dL)

91.5 ± 21.7

94.0 ± 14.4

0.92

 HDL (mg/dL)

34.5 ± 2.4

32.4 ± 3.5

0.70

 Systolic BP (mmHg)

157.0 ± 10.6

155.8 ± 5.7

0.91

 Diastolic BP (mmHg)

84.3 ± 4.4

82.1 ± 6.9

0.84

 Mean BP (mmHg)

108.5 ± 6.0

106.7 ± 6.1

0.85

 Number of antihypertensive medicines

2.0 ± 0.4

2.5 ± 0.4

0.43

 Days from initial diagnosis of renal CCE to LDL-A initiation

127.0 ± 37.7

114.3 ± 19.2

0.74

 Monthly changes in eGFR (mL/min/1.73 m2/month)

−5.58 ± 1.57

−2.01 ± 3.65

0.66

Discussion

CCE is a systemic disease caused by the occlusion of large arterioles (50–200 μm) by microshowers of cholesterol crystals from aortic atheromatous plaques, and this embolization usually affects the skin, subcutaneous tissue, skeletal muscle, prostate, pancreas, liver, spinal cord, gastrointestinal tract, and kidney [2, 11]. In particular, the kidneys are known to be one of the frequent target organs for CCE, and the frequency of renal clinical manifestations reached approximately 50 % in CCE patients [2]. The occurrence of renal CCE is supposedly high because renal arteries anatomically originate from the abdominal aorta in which rupture or erosion of atheromatous plaques is most likely to occur and they have an enormous amount of blood flowing through the kidneys [11]. The onset of renal CCE cannot be precisely determined because renal CCE sometimes has a smoldering course with renal function declining over a period of several months [2]. In this study, eGFR values had already decreased to 35.2 ± 16.5 mL/min/1.73 m2 at the initial diagnosis of renal CCE. It was previously reported that approximately 80 % of renal CCE patients have S-Cr levels of 2.0 mg/dL or more at the time of initial presentation [12], and our result was nearly consistent with this report.

As an initial treatment for renal CCE, the management of hypertension was enhanced in addition to the use of statins. Renal CCE itself is frequently associated with systemic hypertension, and hypertension directly influences the deterioration of renal function in these conditions. Therefore, normalization of BP would be very important for preventing the progression of renal CCE. In the present study, the management of hypertension was difficult and insufficient even with the increased number of antihypertensive medications before LDL-A therapy, whereas systemic BP markedly improved after LDL-A. Several mechanisms were considered to be associated with the improvement of systemic BP after LDL-A. First, LDL-A has been known to increase serum bradykinin levels [6], and it was recently reported that the activation of the kinin pathway, including bradykinin, lowers systemic BP by promoting vasodilation and natriuresis induced by the inhibition of epithelial Na+ channels at aldosterone-sensitive distal nephron such as the connecting tubule and cortical collecting duct [13]. Although serum bradykinin levels were not measured during LDL-A in this study and we could not directly assess the influence of a serum bradykinin increase on systemic BP, these mechanisms might contribute to the improvement of systemic BP. Second, the ameliorating effect on the progression of renal CCE induced by LDL-A might also contribute to the observed systemic BP improvement. In this study, all patients with renal CCE showed decrease of eGFR values before LDL-A, and the decrease in urinary sodium excretion could be associated with a systemic BP increase. Thus, the protective effect against the progression of renal CCE after LDL-A might lead to systemic BP improvement via the enhancement of renal hemodynamics and the increase of urinary sodium excretion, which induces adequate body-fluid regulation. Finally, an association with the number of antihypertensive medicines was also noted. In this study, the number of antihypertensive medicines used to manage systemic BP significantly increased before and after LDL-A compared with the initial diagnosis of renal CCE, whereas there was no significant difference in the number of antihypertensive medicines used before and after LDL-A. However, the number of these agents tended to increase after LDL-A compared to before LDL-A, and therefore, the effect of increasing the number of antihypertensive medicines for lowering systemic BP after LDL-A cannot be ignored.

Statins, which are lipid-lowering agents, are reported to be effective in renal CCE patients [14]. Furthermore, a prospective study in renal CCE demonstrated that statins have beneficial effects in reducing the risk of end-stage renal disease [15], dialysis, and death [8]. Although these therapies were administered consistently in each patient in our study, renal function did not improve. Therefore, LDL-A, which has been previously shown to be effective in renal CCE [4, 5], was added to these consecutive therapies to prevent further progression of renal CCE. After the addition of LDL-A, monthly changes in eGFR were significantly diminished compared to those observed before the initiation of LDL-A. The precise mechanism for the positive effects of LDL-A in renal CCE remains unclear, but the following effects have been proposed: (a) amelioration of blood rheology, (b) reduction of blood and plasma viscosity, (c) production of vasodilating nitric oxide, eicosanoids, and bradykinin, (d) improvement of endothelial function through the reduction of the concentration of total LDL and oxidized LDL, and (e) reduction of circulating inflammatory cytokines and chemokines [4, 16]. Furthermore, bradykinin has recently shown a direct renoprotective effect such as the inhibition of renal fibrosis via suppression of renal levels of TGF-β in the kidneys [7]. In this study, the significant improvement in monthly changes in eGFR may be associated with the contribution of these various effects induced by LDL-A.

As to the renal prognosis and patient outcomes in our study, 4 out of 12 renal CCE patients (33.3 %) required HD during the first year after LDL-A. Thus far, 25–35 % of renal CCE patients were reported to require HD therapy because of a lack of improvement of acute kidney injury or chronic renal failure [8, 17]. Our results regarding the ratio between renal CCE patients with and without HD are the same as those reported previously. To clarify the factors associated with renal prognosis in renal CCE patients, we compared clinical parameters at the initial diagnosis of renal CCE and before LDL-A between patients who required HD and those who did not. S-Cr concentrations were significantly higher in patients who required HD than in those who did not. Monthly changes in eGFR were significantly diminished after LDL-A therapy compared to before LDL-A therapy, whereas these changes did not improve the renal prognosis of the renal CCE patients in this study. Regarding the correlation between the renal prognosis of patients with renal CCE and the degree of renal dysfunction at the initial diagnosis, S-Cr concentrations were previously reported to be significantly higher in patients who required HD than that in those who did not [18]. Furthermore, a baseline decrease in eGFR (eGFR ≤30 mL/min/1.73 m2) was associated with a significantly increased risk for end-stage renal disease [8]. Considering the results of this and previous studies, an early diagnosis of renal CCE would be important for preventing the progression of renal dysfunction to end-stage renal disease, and LDL-A revealed its protective effect on the progression of renal dysfunction in renal CCE. However, an early initiation of LDL-A cannot be concluded to improve renal prognosis in patients with renal CCE receiving HD in this study. Thus far, no reports have examined the influence of LDL-A on renal prognosis in patients with renal CCE, and whether LDL-A initiation improves the renal prognosis in these patients remains unclear. Therefore, to clarify the relationship between LDL-A initiation and renal prognosis in patients with renal CCE, further prospective randomized studies will be needed. Furthermore, the 1-year mortality rate in renal CCE was reported to be 13–17 %, with an aggressive therapeutic approach including the avoidance of anticoagulation and aortic manipulating procedures, management of hypertension and heart failure, dialytic therapy, and adequate nutritional support [8, 17]. However, in this study, all patients remained alive over 1 year after LDL-A. Although this study cannot refer to the relationship between LDL-A and patient outcomes, LDL-A can potentially favorably influence the prognosis of renal CCE patients.

Regarding the limitations of this study, the sample size was small and there was no control group. In the clinical course of renal CCE, several patterns of renal failure were observed [19]. Therefore, we cannot exclude the possibility that patients in the present study had passed the active phase of renal CCE and that their eGFR would stabilize with or without LDL-A. However, considering the significant stabilization of monthly changes in eGFR after LDL-A, LDL-A appears to exert a renoprotective effect in renal CCE patients. Furthermore, the differentiation between renal CCE and contrast-induced nephropathy is important, but sometimes very difficult. It was previously reported that renal CCE usually developed several weeks to months after an inciting event, whereas contrast-induced nephropathy typically occurs within the first weeks of exposure and resolves within 2 weeks [16]. Patients included in our study had been experiencing the progression of renal dysfunction for several months, and their diagnoses of renal CCE were made according to previously reported criteria [8]. Therefore, the differentiation between renal CCE and contrast-induced nephropathy in this study would have been adequate. Moreover, 4 out of 12 patients had been taking oral steroids for the treatment of renal CCE before and after LDL-A. Thus far, even the use of low-dose steroids (0.3 mg/kg) was reported to provide symptomatic relief in CCE patients [17]. Although we confirmed that steroids did not provide beneficial effects in renal CCE before LDL-A, we cannot exclude the potential long-term effects of steroids on eGFR preservation after LDL-A. Therefore, further studies will be required to confirm the efficacy of LDL-A for preserving eGFR and improving renal prognosis in renal CCE patients.

In conclusion, the findings of this study suggest that LDL-A therapy ameliorated renal dysfunction in renal CCE patients.

Notes

Acknowledgments

We would like to thank Dr. Aizan Hirai for valuable discussions.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© The Japanese Society for Artificial Organs 2014

Authors and Affiliations

  • Keiji Hirai
    • 1
  • Susumu Ookawara
    • 1
  • Haruhisa Miyazawa
    • 1
  • Kiyonori Ito
    • 1
  • Yuichirou Ueda
    • 1
  • Yoshio Kaku
    • 1
  • Taro Hoshino
    • 1
  • Izumi Yoshida
    • 1
  • Kaoru Tabei
    • 1
  1. 1.Division of Nephrology, First Department of Integrated Medicine, Saitama Medical CenterJichi Medical UniversitySaitamaJapan

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