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Original article
Effect of pitavastatin on erythrocyte membrane fatty acid content in patients with chronic kidney disease: two-arm parallel randomized controlled trial
Minna Kim1orcid, Seong Eun Kim1orcid, Su Mi Lee1orcid, Won Suk An1,2orcid

DOI: https://doi.org/10.12701/jyms.2024.00094
Published online: May 8, 2024

1Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea

2Medical Science Research Center, Dong-A University, Busan, Korea

Corresponding author: Won Suk An, MD, PhD Department of Internal Medicine, Dong-A University College of Medicine, 32 Daesingongwon-ro, Seo-gu, Busan 49201, Korea Tel: +82-51-240-2811 • Fax: +82-51-242-5852 • E-mail: anws@dau.ac.kr
• Received: January 26, 2024   • Revised: March 26, 2024   • Accepted: April 2, 2024

© 2024 Yeungnam University College of Medicine, Yeungnam University Institute of Medical Science

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • Background
    Statins reduce the risk of cardiovascular events in patients with chronic kidney disease (CKD). Although diabetes mellitus (DM) is a reported side effect of statin treatment, some studies have indicated that pitavastatin does not cause DM. The present study investigated the effect of pitavastatin on the fatty acid (FA) content of erythrocyte membranes, which affects the occurrence of DM and cardiovascular diseases. In addition, changes in adiponectin and glycated hemoglobin (HbA1c) levels were evaluated after pitavastatin treatment.
  • Methods
    A total of 45 patients were enrolled, 28 of whom completed the study. Over 24 weeks, 16 patients received 2 mg pitavastatin and 12 patients received 10 mg atorvastatin. Dosages were adjusted after 12 weeks if additional lipid control was required. There were 10 and nine patients with DM in the pitavastatin and atorvastatin groups, respectively. Erythrocyte membrane FAs and adiponectin levels were measured using gas chromatography and enzyme-linked immunosorbent assay, respectively.
  • Results
    In both groups, saturated FAs, palmitic acid, trans-oleic acid, total cholesterol, and low-density lipoprotein cholesterol levels were significantly lower than those at baseline. The arachidonic acid (AA) content in the erythrocyte membrane increased significantly in the pitavastatin group, but adiponectin levels were unaffected. HbA1c levels decreased in patients treated with pitavastatin. No adverse effects were associated with statin treatment.
  • Conclusion
    Pitavastatin treatment in patients with CKD may improve glucose metabolism by altering erythrocyte membrane AA levels. In addition, pitavastatin did not adversely affect glucose control in patients with CKD and DM.
Patients with chronic kidney disease (CKD) have a higher mortality rate than the general population, and the mortality rate is even higher in patients with diabetes mellitus (DM) [1,2]. This is because patients with CKD have traditional risk factors for cardiovascular complications, such as DM, hypertension, and dyslipidemia, as well as nontraditional risk factors such as microalbuminuria and decreased hemoglobin levels [3]. The use of statins before dialysis in patients with CKD reduces the incidence of cardiovascular disease. Therefore, it is crucial to measure and treat lipid levels at the time of CKD diagnosis [4,5].
A critical side effect of statins is the development of new-onset DM. Reports suggest that atorvastatin and simvastatin can increase the incidence of type 2 DM [6]. However, pitavastatin has not been reported to contribute to the development of type 2 DM [7]. Because the mechanisms underlying statin-induced DM remain unclear, each statin characteristic related to glucose metabolism should be evaluated.
Erythrocyte membrane fatty acids (FAs) are associated with changes in blood glucose levels and risk of developing type 2 DM [8]. Pitavastatin has been reported to modulate the FA content in erythrocyte membranes [9,10]. Further studies are required to investigate the effects of pitavastatin on erythrocyte membrane FAs and its potential role in the development of DM.
This study primarily aimed to examine the changes in erythrocyte membrane FA content in patients with CKD after pitavastatin therapy. We also assessed the effect of pitavastatin on elevating adiponectin and glycated hemoglobin (HbA1c) levels, which are reported effects of other statins.
Ethical statements: This study was approved by the Institutional Review Board (IRB) of Dong-A University Hospital (IRB No: DAUHIRB-15-153), and written informed consent was obtained from all participants.
1. Study design and patients
We conducted a two-arm parallel randomized controlled trial. Random allocation was performed at the beginning of the study. After entering the assigned codes into the Research Randomizer, participant numbers were automatically generated and randomly allocated to the treatment and control groups. During random allocation, considerations were given to the institution and sex. A predetermined random allocation table was used, and an additional random allocation was conducted based on an estimated glomerular filtration rate (eGFR) threshold of 60 mL/min/1.73 m2. This study was registered at ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT02863185).

1) Inclusion criteria

Forty-five patients were enrolled in this randomized controlled study, of whom 28 successfully completed the study. Patients aged 20 to 80 years with CKD stages 1 to 5 who were not receiving dialysis were enrolled in this study. The inclusion criteria were as follows: (1) not currently taking statins and (2) having coronary artery disease or equivalent risk factors with low-density lipoprotein (LDL) cholesterol levels ≥100 mg/dL, having two or more cardiovascular risk factors with LDL cholesterol levels ≥130 mg/dL, or having LDL cholesterol levels >160 mg/dL.

2) Exclusion criteria

The exclusion criteria were a history of taking statins or omega-3 FAs; taking sevelamer hydrochloride within 3 months; a history of statin-associated side effects; hospitalization due to cardiovascular disease, infection, or acute kidney injury within 3 months; pregnant or about to become pregnant; examination using a contrast agent within 2 weeks; dyslipidemia due to nephrotic syndrome; a history of liver cirrhosis or malignancy; and an albumin level <3.0 g/dL.

3) Withdrawal criteria

The withdrawal criteria were intake of other lipid-lowering drugs (e.g., other statin drugs, omega-3 FAs, or sevelamer hydrochloride) during the study period, withdrawal of consent, hospitalization for more than 1 month during the research period, severe muscle pain or dark brown urine after taking the drug, aspartate transaminase (AST) or alanine transaminase (ALT) level increased more than three times the upper limit, decreased renal function by >30%, discontinuation of the study drug for more than 2 months.
After excluding patients who withdrew or dropped out, 28 of the 45 patients successfully completed this study. Specifically, six patients declined to provide final samples, three patients discontinued their participation, the blood samples of four patients were lost, and four patients were excluded from the analysis due to acute kidney injury, which was determined to be unrelated to statin treatment (Fig. 1). Of the remaining 28 patients, 16 received 2 mg pitavastatin and 12 received 10 mg atorvastatin for 24 weeks. In cases where LDL cholesterol levels were not well controlled at the 12-week mark of the study, the doses were increased to 4 mg for pitavastatin and 20 mg for atorvastatin. Ten patients in the pitavastatin group and nine in the atorvastatin group had DM.
2. Clinical outcomes

1) Biochemical and hematologic evaluation

eGFR was calculated using dietary modifications of the renal disease formula using age- and sex-adjusted serum creatinine (sCr) as follows: eGFR (mL/min/1.73 m2)=175×sCr−1.154×age−0.203×0.742 (in women)×1.21. Cystatin C-based eGFR was calculated for women with serum cystatin C levels ≤0.8 mg/dL as follows: eGFR=133×(serum cystatin C/0.8)−0.499×(0.996)×age×0.932. For women with serum cystatin C levels >0.8 mg/L, eGFR was calculated as follows: eGFR=133×(serum cystatin C/0.8)−1.328×(0.996)×age×0.932. For men with serum cystatin C levels ≤0.8 mg/dL, eGFR was calculated as follows: eGFR=133×(serum cystatin C/0.8)−0.499×(0.996)×age. For men with serum cystatin C levels >0.8 mg/L, eGFR was calculated as follows: eGFR=133×(serum cystatin C/0.8)−1.328×(0.996)×age.

2) Laboratory measurements

We analyzed the serum levels of total cholesterol, triglycerides, LDL cholesterol, high-density lipoprotein (HDL) cholesterol, and HbA1c. Proteinuria was measured using the random spot urine test, and adiponectin levels were measured using an enzyme-linked immunosorbent assay (BioVendor Laboratory Medicine, Modřice, Czech Republic).

3) Gas chromatography

The erythrocyte membrane FA content was measured at baseline and after 24 weeks by gas chromatography (Shimadzu 2010AF, Shimadzu Scientific Instrument, Kyoto, Japan). The isolated erythrocytes underwent methylation by adding boron trifluoride methanol-benzene for 10 minutes at 100°C. FAs were identified by comparison with known standards (GLC-727; Nu-Chek Prep, Elysian, MN, USA). FA methyl esters were analyzed by gas chromatography using a 100 m SP-2560 capillary column (Supelco, Bellefonte, PA, USA). The omega-3 index is a measure of eicosapentaenoic acid and docosahexaenoic acid (DHA) content in erythrocyte membranes, and the erythrocyte membrane FA content is expressed as a percentage of the total FA weight.
3. Statistical outcomes
In previous studies, the average change in oleic acid levels among erythrocyte membrane FAs after omega-3 FA administration in patients with CKD undergoing dialysis was 2.5 weight %. The standard deviation was 2.0 weight %, and we estimated that the value with pitavastatin was less than that with omega-3 FAs. To detect an effective mean difference in erythrocyte membrane oleic acid content of 1.5±2.0 weight % at a two-sided significance level of 0.05, a sample size of 18 patients per group was required to achieve a minimum power of 80% and an expected dropout rate of 20%. The participants were divided into two equal groups based on an eGFR threshold of 60 mL/min/1.73 m2 and were subsequently analyzed. Data are expressed as mean±standard deviation. The differences between the two groups were analyzed using the Mann-Whitney U-test. The Wilcoxon rank sum test was used for initial data and changes after 24 weeks, and the chi-square test was used for qualitative variables. All analyses were performed using SPSS ver. 18.0 for Windows (SPSS Inc., Chicago, IL, USA). Statistical significance was set at p<0.05.
1. Baseline characteristics and changes in biochemical laboratory data
The pitavastatin and atorvastatin treatment groups underwent blood biochemical analyses and examination of erythrocyte membrane FA content before starting treatment, and there were no significant differences between the two groups.
Regardless of the type of statin used, both groups showed a significant decrease in total cholesterol (p<0.001) and LDL cholesterol (p<0.001) compared to baseline; however, there were no significant changes in the levels of adiponectin. Patients with DM showed a significant decrease in HbA1c levels from 7.6%±1.5% to 7.3%±1.3% (p=0.038) (Table 1). In patients with and without DM, there was a significant decrease in total cholesterol and LDL cholesterol levels after statin treatment. Regardless of baseline eGFR, there was a significant decrease in total cholesterol and HDL cholesterol levels in both patient groups receiving statin treatment. There were no significant changes in HbA1c or adiponectin levels according to baseline eGFR.
2. Changes in erythrocyte membrane fatty acid content
Table 2 shows the changes in the composition of erythrocyte membrane FAs after statin treatment, irrespective of the type of statin. There was a significant decrease in the content of saturated FAs, palmitic acid, and trans-oleic acid (p=0.016, p<0.001, and p=0.015, respectively), while arachidonic acid (AA) content showed a significant increase compared with its baseline level (p=0.006).
3. Changes in biochemical parameters and erythrocyte membrane fatty acid content according to the type of statin
There was a significant decrease in the levels of total cholesterol, LDL cholesterol, and ALT (p<0.001, p<0.001, and p=0.031, respectively) in the patients treated with pitavastatin (Table 3). Patients with DM treated with pitavastatin for 24 weeks showed a significant decrease in HbA1c levels (p=0.045) (Fig. 2). Patients treated with atorvastatin had significantly lower total cholesterol, LDL cholesterol, and uric acid levels (p=0.005, p=0.002, and p=0.045, respectively). Patients treated with pitavastatin showed a significant increase in AA content (p=0.020), whereas those treated with atorvastatin showed a significant decrease in palmitic acid content (p=0.005) (Table 4). Fig. 3 shows that AA content significantly increased only in patients treated with pitavastatin. No significant changes were observed in the AA/DHA ratio or total trans-FA levels in either patient group. In patients with eGFR ≥60 mL/min/1.73 m2, there was a significant decrease in the levels of saturated FAs, palmitic acid, lignoceric acid, trans-oleic acid, and total trans-FAs after statin treatment (p=0.023, p=0.033, p=0.046, p=0.023, and p=0.039, respectively). Only palmitic acid was significantly decreased in patients with eGFR <60 mL/min/1.73 m2 (Supplementary Table 1). Neither group showed significant changes in AA content or the AA/DHA ratio compared to the baseline.
4. Adverse effects and dropout
Pitavastatin did not cause any significant adverse effects. During the analysis, four patients withdrew due to acute kidney injury, which was determined to be unrelated to statin use. In patients treated with pitavastatin or atorvastatin, there was a significant increase in AST (p=0.008) and ALT levels (p=0.030) after 24 weeks (Table 1), which could have been a side effect of statin treatment; however, there were no serious adverse effects that required treatment discontinuation.
This study found that statin treatment modified the FA composition of erythrocyte membranes in patients with CKD. The levels of saturated FAs, palmitic acid, and trans-oleic acid in the erythrocyte membrane decreased, similar to the decrease in total cholesterol and LDL cholesterol levels. It is widely acknowledged that saturated FAs raise levels of LDL cholesterol, and the consumption of trans-FAs is associated with an increased risk of cardiovascular disease [11-14]. Based on these observations, pitavastatin and atorvastatin may reduce the risk of cardiovascular disease by reducing LDL cholesterol and saturated FA levels.
There are several hypotheses for statin-induced new-onset DM, including reduced 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, decreased adiponectin levels, increased insulin resistance, and impaired pancreatic beta cell function [15]. However, unlike other statins, pitavastatin has been reported to have no effect on serum glucose levels [16]. Pitavastatin was found to increase AA levels and decrease DHA/AA ratios [9]. Previous studies have demonstrated that AA and DHA prevent DM by regulating insulin secretion [17]. In our study, patients who received pitavastatin showed a significant increase in AA levels and a decrease in HbA1c levels. Although there were no significant changes in the AA/DHA ratio, our findings indicate that pitavastatin treatment may reduce HbA1c levels by increasing AA levels. In a meta-analysis of 13 prospective randomized controlled trials involving 91,140 patients without DM treated with statins, a mean follow-up period of 4 years was conducted to observe the occurrence of DM [18]. Since there was a significant decrease in HbA1c levels among the 10 patients with DM treated with pravastatin and no significant change in HbA1c levels among the nine patients treated with atorvastatin, pitavastatin may not be harmful to glucose control.
Decreased adiponectin levels are closely associated with worsening insulin resistance, which is associated with the onset of DM [19]. A previous study reported that after 6 months of pitavastatin treatment in 117 patients with hyperlipidemia, there was a significant decrease in total cholesterol and LDL cholesterol and an increase in adiponectin levels [20]. Our study showed no significant changes in adiponectin levels in patients treated with pitavastatin; however, the reason for this is unclear. Due to the limited number of enrolled patients in our study, we suspect that there may not have been sufficient observations to adequately assess changes in adiponectin levels.
Studies have suggested that atorvastatin significantly reduces serum uric acid levels compared to other statins [21,22]. In our study, we also observed a significant reduction in serum uric acid levels after 24 weeks of atorvastatin treatment; however, such changes were not observed with pitavastatin treatment. It is unclear why there is a difference between atorvastatin and pitavastatin in terms of the changes in uric acid levels. A possible cause may be decreased uric acid production due to atorvastatin. Decreasing uric acid levels with atorvastatin treatment may be beneficial for preserving renal function in patients with CKD.
Adverse effects can occur in patients treated with statins; myopathy is the most commonly observed side effect, but hepatotoxicity can also occur [23,24]. In our study, there was a significant increase in ALT and AST levels after statin use. No cases of myopathy were observed in this study. Although the increase in liver enzyme levels was not severe enough to discontinue treatment, careful monitoring is necessary to avoid possible side effects.
This study had several limitations. First, our study included an inadequate sample size. We planned to recruit 72 participants; however, only 45 patients were enrolled and 28 completed the study. Enrollment was stopped due to insufficient recruitment and a prolonged recruitment period. This insufficient enrollment may have affected our results. Second, we did not initially plan to assess insulin resistance. Third, we did not check for glycated albumin, and HbA1c is not reliable in patients with anemia and a lower eGFR.
In conclusion, pitavastatin and atorvastatin treatments controlled cholesterol levels and modified FA content, thereby reducing cardiovascular risk. Although our study did not show significant changes in adiponectin levels, we observed a decrease in HbA1c levels and an increase in AA levels in the pitavastatin group. Based on these findings, we believe that pitavastatin use in patients with CKD may benefit glucose metabolism and alter erythrocyte membrane AA levels, and that pitavastatin does not have detrimental effects on glucose control in patients with CKD and DM.
Supplementary Table 1 can be found at https://doi.org/10.12701/jyms.2024.00094.
Supplementary Table 1.
Comparison of erythrocyte membrane fatty acids content according to kidney function
jyms-2024-00094-Supplementary-Table-1.pdf

Conflicts of interest

No potential conflict of interest relevant to this article was reported.

Funding

This study was supported by the Dong-A University Research Fund.

Author contributions

Conceptualization, Supervision: SEK, WSA; Data curation: SML, WSA; Formal analysis: SEK, SML, WSA; Funding acquisition, Investigation: WSA; Methodology: MK; Writing-original draft: MK, WSA; Writing-review & editing: all authors.

Fig. 1.
Consort diagram of the study population. AKI, acute kidney injury.
jyms-2024-00094f1.jpg
Fig. 2.
Changes in HbA1c before and after the administration of pitavastatin to patients with hyperlipidemia and diabetes mellitus. HbA1c, glycated hemoglobin. *p<0.05, mean values are significantly different from the baseline data.
jyms-2024-00094f2.jpg
Fig. 3.
Changes in arachidonic acid in erythrocyte membrane fatty acids after receiving (A) 24 weeks of pitavastatin and (B) 24 weeks of atorvastatin. *p<0.05, mean values are significantly different from the baseline data.
jyms-2024-00094f3.jpg
Table 1.
Baseline clinical and biochemical characteristics of the subjects
Characteristic Baseline (n=28) 24 weeks (n=28) p-value
Age (yr) 63.0±9.0
Male sex 14 (50.0)
Diabetes mellitus 19 (67.9)
Systolic BP (mmHg) 131.1±17.1 132.8±14.1 0.543
Diastolic BP (mmHg) 72.9±11.7 72.8±8.7 0.974
Calcium (mg/dL) 9.2±0.6 9.2±0.5 0.774
Phosphorus (mg/dL) 3.7±0.5 3.6±0.6 0.789
Glucose (mg/dL) 149.2±83.8 127.9±39.5 0.228
BUN (mg/dL) 21.1±8.0 22.1±10.4 0.391
Creatinine (mg/dL) 1.3±0.6 1.4±0.7 0.210
eGFR (mL/min/1.73 m2) 61.8±27.2 62.8±28.1 0.504
CKD-EPI (mL/min/1.73 m2) 60.1±25.5 60.9±26.7 0.551
Uric acid (mg/dL) 6.3±1.8 5.8±1.5 0.012a)
Total cholesterol (mg/dL) 222.7±43.4 157.9±25.7 <0.001a)
Albumin (g/dL) 4.2±0.5 4.2±0.4 0.301
AST (U/L) 20.8±7.7 23.9±8.1 0.008a)
ALT (U/L) 17.4±9.5 20.4±7.1 0.030a)
Triglyceride (mg/dL) 224.2±128.2 189.0±135.2 0.156
HDL (mg/dL) 47.3±8.9 47.3±8.9 0.906
LDL (mg/dL) 154.8±24.5 96.7±19.0 <0.001a)
Cystatin C (mg/L) 1.4±0.6 1.5±0.7 0.079
Cystatin C GFR (mL/min/1.73 m2) 58.3±25.8 57.3±25.6 0.339
CRP (mg/dL) 0.2±0.1 0.2±0.2 0.658
UPCR (g/g) 1.0±1.7 1.3±2.3 0.083
HbA1c (%) 7.6±1.5 7.3±1.3 0.038a)
Adiponectin (μg/mL) 10.4±5.3 10.0±5.2 0.192

Values are presented as mean±standard deviation or number (%).

BP, blood pressure; BUN, blood urea nitrogen; eGFR, estimated glomerular filtration rate; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; AST, aspartate aminotransferase; ALT, alanine aminotransferase; HDL, high-density lipoprotein; LDL, low-density lipoprotein; CRP, C-reactive protein; UPCR, urine protein-creatinine ratio; HbA1c, glycated hemoglobin.

a) p<0.05, mean values are significantly different from the baseline data.

Table 2.
Change in erythrocyte membrane fatty acid content after statin treatment
Variable Baseline (n=28) 24 weeks (n=28) p-value
Saturated 41.3±2.2 40.3±1.9 0.016a)
 Myristic 0.3±0.1 0.3±0.1 0.458
 Palmitic 23.4±1.4 22.3±1.2 <0.001a)
 Stearic 16.4±0.9 16.8±1.0 0.827
 Lignoceric 0.5±0.2 0.4±0.1 0.787
Monounsaturated 17.1±1.1 17.1±1.2 0.370
 Palmitoleic 0.5±0.2 0.2±0.2 0.501
 Trans-oleic 0.2±0.1 0.2±0.0 0.015a)
 Oleic 14.9±1.3 15.1±1.6 0.282
Polyunsaturated 42.1±3.3 42.9±3.3 0.178
Omega-6 28.6±2.7 29.2±2.7 0.067
 Linoleic 10.7±1.2 10.4±1.8 0.244
 AA 13.6±1.8 14.3±1.5 0.006a)
Omega-3 13.5±2.3 13.7±2.8 0.697
 Alpha-linolenic 0.2±0.1 0.3±0.1 0.287
 EPA 1.8±0.8 1.7±0.8 0.714
 DHA 8.9±1.6 9.1±1.6 0.577
Omega-3 index 10.7±2.1 10.9±2.2 0.745
AA/EPA 9.1±4.3 10.4±5.2 0.053
AA/DHA 1.56±0.3 1.62±0.3 0.255
Omega-6/omega-3 2.2±0.5 2.3±0.6 0.544
Total trans-fatty acid 0.5±0.1 0.4±0.1 0.227

Values are presented as mean±standard deviation.

AA, arachidonic acid; EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid.

a) p<0.05, mean values are significantly different from the baseline data.

Table 3.
Clinical blood biochemical analyses according to pitavastatin or atorvastatin treatment
Variable Pitavastatin (n=16)
Atorvastatin (n=12)
Baseline 24 weeks p-value Baseline 24 weeks p-value
Age (yr) 60.4±9.1 66.4±8.0
Male sex 8 (50.0) 6 (50.0)
Diabetes mellitus 10 (62.5) 9 (75.0)
Systolic BP (mmHg) 129.6±19.6 132.8±15.6 0.518 133.2±13.6 132.8±12.5 0.937
Diastolic BP (mmHg) 71.7±12.1 72.5±8.7 0.717 74.5±11.4 73.3±9.2 0.906
Calcium (mg/dL) 9.3±0.5 9.2±0.5 0.448 9.1±0.7 9.1±0.5 0.721
Phosphorus (mg/dL) 3.7±0.5 3.7±0.6 0.900 3.6±0.5 3.6±0.7 0.906
Glucose (mg/dL) 151.9±106.5 118.2±36.1 0.570 145.5±41.8 140.8±41.6 0.480
BUN (mg/dL) 20.1±8.4 22.6±10.1 0.163 22.4±7.7 21.5±11.4 0.637
Creatinine (mg/dL) 1.2±0.6 1.3±0.7 0.162 1.4±0.6 1.5±0.8 0.657
eGFR (mL/min/1.73 m2) 68.5±30.7 68.4±31.3 0.796 52.9±19.3 55.3±22.2 0.272
CKD-EPI (mL/min/1.73 m2) 66.5±28.2 66.2±29.3 0.623 51.5±19.2 53.8±22.1 0.346
Uric acid (mg/dL) 6.0±2.0 5.6±1.5 0.468 6.7±1.4 6.1±1.5 0.045a)
Total cholesterol (mg/dL) 232.4±37.0 164.3±22.5 <0.001a) 209.8±49.4 149.3±28.0 0.005a)
Albumin (g/dL) 4.2±0.4 4.3±0.4 0.243 4.0±0.5 4.1±0.4 0.878
AST (U/L) 20.4±5.4 23.2±5.4 0.069 21.2±10.3 24.8±11.0 0.090
ALT (U/L) 17.2±6.0 20.0±6.1 0.031a) 17.8±13.2 20.8±8.4 0.068
Triglyceride (mg/dL) 210.6±113.7 188.0±153.2 0.423 242.3±148.6 190.4±113.2 0.099
HDL (mg/dL) 49.1±11.0 48.4±9.2 0.776 45.3±7.4 45.8±8.5 0.789
LDL (mg/dL) 159.9±24.8 98.9±16.8 <0.001a) 147.9±23.4 93.8±22.1 0.002a)
Cystatin C (mg/L) 1.3±0.6 1.4±0.7 0.222 1.5±0.5 1.6±0.7 0.480
Cystatin C GFR (mL/min/1.73 m2) 65.1±30.2 63.3±29.5 0.233 49.9±16.4 49.8±18.4 0.724
CRP (mg/dL) 0.1±0.1 0.2±0.2 0.268 0.2±0.1 0.1±0.1 0.789
UPCR (g/g) 1.1±2.0 1.5±2.7 0.349 0.7±1.1 0.9±1.5 0.146
HbA1c (%) 7.6±1.4 7.1±1.2 0.045a) 7.7±1.6 7.4±1.4 0.237
Adiponectin (μg/mL) 9.3±4.9 8.9±4.2 0.410 11.9±5.7 11.4±6.1 0.638

Values are presented as means±standard deviation or number (%).

BP, blood pressure; BUN, blood urea nitrogen; eGFR, estimated glomerular filtration rate; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; AST, aspartate aminotransferase; ALT, alanine aminotransferase; HDL, high-density lipoprotein; LDL, low-density lipoprotein; CRP, C-reactive protein; UPCR, urine protein-creatinine ratio; HbA1c, glycated hemoglobin.

a) p<0.05, mean values are significantly different from the baseline data.

Table 4.
Change in erythrocyte membrane fatty acid content after pitavastatin or atorvastatin treatment
Variable Pitavastatin (n=16)
Atorvastatin (n=12)
Baseline 24 weeks p-value Baseline 24 weeks p-value
Saturated 41.2±2.3 40.4±2.2 0.088 41.3±2.0 40.3±1.9 0.084
 Myristic 0.3±0.1 0.3±0.1 0.959 0.4±0.1 0.3±0.1 0.308
 Palmitic 23.3±1.3 22.6±1.3 0.088 23.4±1.6 22.0±1.0 0.005a)
 Stearic 17.1±1.2 16.9±1.3 0.918 17.0±1.0 17.3±0.9 0.209
 Lignoceric 0.5±0.1 0.5±0.1 0.642 0.5±0.2 0.5±0.2 >0.999
Monounsaturated 16.0±1.4 16.2±1.8 >0.999 15.9±1.6 16.2±1.9 0.433
 Palmitoleic 0.4±0.1 0.5±0.2 0.605 0.6±0.2 0.5±0.2 0.209
Trans-oleic 0.20±0.07 0.16±0.02 0.056 0.2±0.0 0.2±0.0 0.099
 Oleic 15.0±1.3 15.2±1.6 0.717 14.7±1.4 15.1±1.7 0.347
Polyunsaturated 42.0±3.4 42.8±3.5 0.278 42.2±3.3 43.0±3.2 0.347
Omega-6 28.1±2.8 29.1±2.7 0.070 29.3±2.6 29.4±2.9 0.480
 Linoleic 10.8±1.4 10.5±2.0 0.215 10.6±0.9 10.3±1.5 0.209
 AA 13.3±1.7 14.3±1.4 0.020a) 13.9±1.9 14.4±1.6 0.209
Omega-3 13.9±2.7 13.7±2.8 0.877 12.9±1.5 13.6±2.8 0.583
 Alpha-linolenic 0.2±0.1 0.3±0.2 0.918 0.2±0.1 0.2±0.1 0.308
 EPA 1.9±0.9 1.9±0.8 0.918 1.7±0.7 1.5±0.9 0.754
 DHA 9.3±1.7 9.0±1.7 0.438 8.4±1.2 9.2±1.5 0.117
Omega-3 index 11.2±2.4 10.9±2.3 0.756 10.1±1.3 10.7±2.2 0.433
AA/EPA 8.4±3.7 9.3±5.0 0.255 9.9±4.9 11.9±5.2 0.209
AA/DHA 1.5±0.4 1.6±0.3 0.063 1.7±0.3 1.6±0.3 0.530
Omega-6/omega-3 2.1±0.6 2.2±0.7 0.642 2.3±0.3 2.3±0.5 0.814
Total trans-fatty acid 0.5±0.1 0.4±0.1 0.148 0.5±0.1 0.5±0.1 0.875

Values are presented as means±standard deviation.

AA, arachidonic acid; EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid.

a) p<0.05, mean values are significantly different from the baseline data.

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