Effect of Long-term Fenofibrate Therapy on Serum Creatinine and Its Reversibility in Hypertriglyceridemic Patients with Hypertension

Gyu Tae Park; Moonki Jung; Young Kim; Iksung Cho; Hoyoun Won; Seung Yong Shin; Wang-Soo Lee; Kwang Je Lee; Sang-Wook Kim; Tae Ho Kim; Chee Jeong Kim

doi:10.12997/jla.2017.6.2.89

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Park, Jung, Kim, Cho, Won, Shin, Lee, Lee, Kim, Kim, and Kim: Effect of Long-term Fenofibrate Therapy on Serum Creatinine and Its Reversibility in Hypertriglyceridemic Patients with Hypertension

Original Article

J Lipid Atheroscler 2017;6(2):89-96.

Published online: 31 December 2017

DOI: https://doi.org/10.12997/jla.2017.6.2.89

Effect of Long-term Fenofibrate Therapy on Serum Creatinine and Its Reversibility in Hypertriglyceridemic Patients with Hypertension

Gyu Tae Park, Moonki Jung, Young Kim, Iksung Cho, Hoyoun Won, Seung Yong Shin, Wang-Soo Lee, Kwang Je Lee, Sang-Wook Kim, Tae Ho Kim, Chee Jeong Kim

Division of Cardiology, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Korea

Corresponding Author: Chee Jeong Kim, Division of Cardiology, Department of Internal Medicine, Chung-Ang University Hospital, 102 Heukseok-ro, Dongjak-gu, Seoul 06973, Korea Tel: +82-2-6299-1398, Fax: +82-2-822-2769, E-mail: cjkim@cau.ac.kr

Received 20 October 2017 Revised 11 December 2017 Accepted 14 December 2017

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.

Abstract

Objective

Previous studies have shown that fenofibrate therapy increases serum creatinine level and that there is a return of serum creatinine to baseline level after the discontinuation of the drug. We evaluated the effect of long-term fenofibrate therapy on creatinine levels and its reversibility in patients with hypertension and hypertriglyceridemia.

Methods

This retrospective study enrolled 54 hypertensive and hypertriglyceridemic patients taking fenofibrate for 3–6 years (Fenofibrate group) and 30 control patients with similar age, sex, follow-up duration, and creatinine levels (Control group). In 23 patients taking fenofibrate with low triglyceride level and/or with high creatinine levels, fenofibrate was discontinued, and creatinine levels were measured after 2 months.

Results

Creatinine levels increased in both the fenofibrate group (from 0.91±0.18 mg/dL to 1.09±0.23 mg/dL, p<0.001) and the control group (from 0.94±0.16 mg/dL to 0.98±0.16 mg/dL, p=0.04) compared to baseline. However, the elevation was more pronounced in the fenofibrate group than in the control group (21.1±15.4% vs. 4.5±11.3%, p<0.001). The discontinuation of fenofibrate lowered creatinine levels (from 1.39±0.32 mg/dL to 1.15±0.24 mg/dL, p<0.001) which were still higher than pre-treatment levels (p=0.013).

Conclusion

Long-term fenofibrate therapy significantly increased creatinine levels in hypertensive and hypertriglyceridemic patients. The effect of fenofibrate on creatinine level was partially reversible. This finding suggests that follow-up creatinine level is necessary with fenofibrate therapy.

Keywords: Fenofibrate, Creatinine, Hypertension, Hypertriglyceridemia, Nephrotoxicity

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Fig. 1.

Changes in creatinine levels of patients in the fenofibrate group with available levels after medication for 1-3 years (solid) and in the control group (dotted). ^*; p<0.05 versus baseline levels

Fig. 2.

Comparisons of creatinine levels at baseline, fenofibrate therapy for 5.4 years, and withdrawal of fenofibrate for 2 months. ^*; p<0.05 versus baseline levels, ^**; p<0.05 versus levels after fenofibrate therapy

Table 1.

Comparisons of Baseline Demographic and Clinical Characteristics between the Control and Fenofibrate Groups

	Control (n=30)	Fenofibrate (n=54)	p value
Men/women	16/14	34/20	0.49
Age (years)	59.0±9.5	56.1±10.0	0.21
Body mass index (kg/m²)	25.7±2.79	25.8±2.98	0.90
Hypertension	100%	100%	1.00
Ischemic heart disease	20%	15%	0.56
Diabetes mellitus	20%	19%	1.00
Alcohol	40%	50%	0.49
Smoking	17%	28%	0.30
Medications
Aspirin	47%	30%	0.16
Ca channel blocker	57%	65%	0.49
Diuretics	53%	59%	0.65
Beta blocker	33%	52%	0.12
ACEI or ARB	50%	59%	0.49
Statin	23%	15%	0.38
Metformin	3%	11%	0.41
Sulfonylurea	10%	13%	1.00
Nitrate	13%	9%	0.72
Follow-up duration (years)	4.08±0.58	4.22±0.85	0.43
Creatinine (mg/dL)	0.94±0.16	0.91±0.18	0.38
BUN (mg/dL)	14.8±3.66	15.5±5.12	0.49
Cholesterol (mg/dL)	203±39.0	208±33.8	0.56
HDL-C (mg/dL)	43.3±7.59	40.4±7.78	0.10
nHDL-C (mg/dL)	160±35.5	168±32.1	0.28
LDL-C (mg/dL)	97.5±36.3	99.6±25.4	0.79
Triglyceride (mg/dL)	334±127	369±163	0.14
AST (IU/L)	31.3±12.9	25.6±7.92	0.033
ALT (IU/L)	33.0±17.8	30.2±13.4	0.41
Creatine kinase (IU/L)	91±33.6	100±47.3	0.37

ACEI; angiotensin converting enzyme inhibitor, ARB; angiotensin receptor blocker, BUN; blood urea nitrogen, HDL-C; high density lipoprotein cholesterol, nHDL-C; non-high density lipoprotein cholesterol, LDL-C; low density lipoprotein cholesterol, AST; aspartate aminotransferase, ALT; alanine aminotransferase

Table 2.

Comparisons of percent changes in renal functions and lipid profiles between the control and fenofibrate groups

	Fenofibrate (n=54)		Control (n=30)		p value^*
	Percent change	p value^**	Percent change	p value^**
Creatinine	21.1±15.4	0.000	4.5±11.3	0.04	0.000
BUN	19.0±37.1	0.025	25.4±28.0	0.000	0.30
Cholesterol	-6.9±17.7	0.001	-6.2±18.3	0.021	0.93
HDL-C	18.6±21.5	0.000	8.4±22.4	0.12	0.024
nHDL-C	-12.5±21.4	0.000	-9.1±23.1	0.006	0.52
LDL-C^***	25.3±34.6	0.000	22.7±53.0	0.39	0.40
Triglyceride	-56.1±24.7	0.000	-16.8±58.3	0.003	0.000

BUN; blood urea nitrogen, HDL-C; high density lipoprotein cholesterol, nHDL-C; non-high density lipoprotein cholesterol, LDL-C; low density lipoprotein cholesterol

^* ; control versus fenofibrate groups,

^** ; baseline versus follow-up,

^*** ; in patients with TG<400 mg/dL

Table 3.

Parameters associated with percent changes of creatinine levels

	Total		Control group		Fenofibrate group
	r	p value	r	p value	r	p value
Sex	0.20	0.063	0.10	0.60	0.29	0.031
Age	-0.08	0.45	-0.04	0.84	0.01	0.94
Body mass index	0.14	0.22	0.20	0.29	0.13	0.34
Alcohol	0.12	0.29	0.20	0.29	0.18	0.19
Smoking	0.22	0.045	0.14	0.46	0.28	0.040
Diabetes mellitus	0.25	0.023	0.15	0.44	0.36	0.007
IHD	0.02	0.82	0.35	0.060	0.12	0.40
Cholesterol	-0.08	0.49	0.17	0.36	-0.26	0.061
HDL-C	-0.10	0.36	0.25	0.18	-0.11	0.43
nHDL-C	-0.05	0.67	0.13	0.49	-0.24	0.076
LDL-C	-0.10	0.45	0.20	0.32	-0.34	0.037
Triglyceride	0.03	0.77	-0.04	0.84	-0.02	0.87
AST	-0.10	0.36	-0.03	0.88	0.09	0.54
ALT	0.05	0.65	0.05	0.81	0.15	0.27
BUN	0.12	0.29	-0.27	0.15	0.19	0.18
Creatinine	-0.06	0.62	-0.24	0.21	0.06	0.64
Follow-up duration	0.10	0.39	0.23	0.22	0.01	0.96
Fenofibrate therapy	0.50	0.000	-	-	-	-

IHD; Ischemic heart disease, HDL-C; high density lipoprotein cholesterol, nHDL-C; non-high density lipoprotein cholesterol, AST; aspartate aminotransferase, ALT; alanine aminotransferase, BUN; blood urea nitrogen, FU; follow-up

Table 4.

Comparisons of parameter according to change of creatinine levels

	<0.2 mg/dL (n=52)	≥0.2 mg/dL (n=32)	p value
Men/women	30/22	20/12	0.82
Age (years)	57.0±10.4	57.4±9.1	0.85
Body mass index (kg/m²)	25.4±2.94	26.5±2.74	0.09
Ischemic heart disease	19%	13%	0.55
Diabetes mellitus	14%	28%	0.10
Alcohol	46%	47%	1.00
Smoking	17%	34%	0.11
Follow-up duration (years)	4.02±0.78	4.21±0.77	0.31
Creatinine (mg/dL)	0.94±0.16	0.88±0.19	0.10
BUN (mg/dL)	14.9±5.14	15.9±3.68	0.33
Cholesterol (mg/dL)	204±35.5	211±35.8	0.41
HDL-C (mg/dL)	41.4±6.95	41.5±9.12	0.95
nHDL-C (mg/dL)	163±34.4	169±32.6	0.40
LDL-C (mg/dL)	96.7±30.8	102±28.9	0.48
Triglyceride (mg/dL)	357±169	357±120	0.30
AST (IU/L)	28.3±11.2	26.6±8.7	0.48
ALT (IU/L)	30.9±16.2	31.7±13.2	0.82
Fenofibrate therapy	46%	94%	0.000

BUN; blood urea nitrogen, HDL-C; high density lipoprotein cholesterol, nHDL-C; non-high density lipoprotein cholesterol, AST; aspartate aminotransferase, ALT; alanine aminotransferase

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