Ohsawa Masato, Tamura Kouichi, Wakui Hiromichi, Kanaoka Tomohiko, Azushima Kengo, Uneda Kazushi, Haku Sona, Kobayashi Ryu, Ohki Kohji, Haruhara Kotaro, Kinguchi Sho, Toya Yoshiyuki, Umemura Satoshi
Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan.
Department of Nephrology, Yokohama Hodogaya Central Hospital, Yokohama, 240-8585, Japan.
Lipids Health Dis. 2015 Dec 9;14:161. doi: 10.1186/s12944-015-0164-5.
In non-dialysis chronic kidney disease (CKD) patients with dyslipidemia, statin therapy is recommended to prevent cardiovascular complications. Dyslipidemia has been also shown to be an independent risk factor for the progression of CKD. However, it is still unclear whether statin therapy exerts an inhibitory effect on renal deterioration in CKD patients with dyslipidemia. The purpose of the present study was to examine possible therapeutic effects of statin add-on therapy on renal function as well as parameters of lipid and glucose metabolism, arterial stiffness and oxidative stress, in comparison to diet therapy, in CKD patients with dyslipidemia.
This study was a randomized, open-label, and parallel-group trial consisted of a 12-months treatment period in non-dialysis CKD patients with alubuminuria and dyslipidemia. Twenty eight patients were randomly assigned either to receive diet counseling alone (diet therapy group) or diet counseling plus pitavastatin (diet-plus-statin therapy group), to achieve the LDL-cholesterol (LDL-C) target of <100 mg/dl.
The statin treatment by pitavastatin was well tolerated in all of the patients without any significant adverse events and the average dose of pitavastatin was 1.0 ± 0.0 mg daily after treatment. After the 12-months treatment period, LDL-C was significantly lower in the diet-plus-statin therapy group compared with the diet therapy group (diet vs diet-plus-statin: LDL-C, 126 ± 5 vs 83 ± 4 mg/dL, P < 0.001). On the other hand, the diet-plus-statin therapy did not significantly reduce albuminuria or delay the decline in eGFR compared with the diet therapy, and there was no relationship between the change in LDL-C and the change in eGFR or albuminuria. However, diet therapy as well as diet-plus-statin therapy exerted similar lowering effects on the pentosidine levels (diet therapy group, baseline vs 12 months: 40 ± 4 vs 24 ± 3 ng/mL, P = 0.001; diet-plus-statin therapy, 46 ± 7 vs 34 ± 6 ng/mL, P = 0.008). Furthermore, the results of multivariate regression analysis indicated that the change in pentosidine was a significant contributor to the change in eGFR (β = -0.536, P = 0.011).
Although statin add-on therapy did not show additive renal protective effects, the diet therapy as well as the diet-plus-statin therapy could contribute to the reduction in plasma pentosidine in CKD patients with albuminuria and dyslipidemia.
在患有血脂异常的非透析慢性肾脏病（CKD）患者中，推荐使用他汀类药物治疗以预防心血管并发症。血脂异常也已被证明是CKD进展的独立危险因素。然而，他汀类药物治疗对患有血脂异常的CKD患者的肾脏恶化是否具有抑制作用仍不清楚。本研究的目的是比较饮食疗法，研究他汀类药物附加疗法对CKD合并血脂异常患者的肾功能、脂质和葡萄糖代谢参数、动脉僵硬度及氧化应激的可能治疗效果。
本研究为一项随机、开放标签、平行组试验，对非透析的白蛋白尿和血脂异常的CKD患者进行为期12个月的治疗。28例患者被随机分配接受单纯饮食咨询（饮食治疗组）或饮食咨询加匹伐他汀（饮食加他汀治疗组），以实现低密度脂蛋白胆固醇（LDL-C）目标<100mg/dl。
所有患者对匹伐他汀的他汀类药物治疗耐受性良好，无任何显著不良事件，治疗后匹伐他汀的平均剂量为每日1.0±0.0mg。经过12个月的治疗期后，饮食加他汀治疗组的LDL-C显著低于饮食治疗组（饮食组与饮食加他汀组：LDL-C，126±5 vs 83±4mg/dL，P<0.001）。另一方面，与饮食治疗相比，饮食加他汀治疗并未显著降低白蛋白尿或延缓估算肾小球滤过率（eGFR）的下降，且LDL-C的变化与eGFR或白蛋白尿的变化之间无相关性。然而，饮食疗法以及饮食加他汀疗法对戊糖苷水平具有相似的降低作用（饮食治疗组，基线时vs 12个月：40±4 vs 24±3ng/mL，P=0.001；饮食加他汀治疗组，46±7 vs 34±6ng/mL，P=0.008）。此外，多变量回归分析结果表明，戊糖苷的变化是eGFR变化的一个重要因素（β=-0.536，P=0.011）。
虽然他汀类药物附加疗法未显示出额外的肾脏保护作用，但饮食疗法以及饮食加他汀疗法有助于降低白蛋白尿和血脂异常的CKD患者的血浆戊糖苷水平。
