Abstract：
BACKGROUND: The beneficial effects of oral supplements with alkalinizing agents in patients with chronic kidney disease (CKD) have been limited to the severe stages. We investigated whether two types of supplements, sodium bicarbonate (SB) and potassium citrate/sodium citrate (PCSC), could maintain renal function in patients with mild-stage CKD.
METHODS: This was a single-center, open-labeled, randomized cohort trial. Study participants with CKD stages G2, G3a, and G3b were enrolled between March 2013 and January 2019 and randomly assigned by stratification according to age, sex, estimated glomerular filtration rate (eGFR), and diabetes. They were followed up for 6 months (short-term study) for the primary endpoints and extended to 2 years (long-term study) for the secondary endpoints. Supplementary doses were adjusted to achieve an early morning urinary pH of 6.8-7.2. We observed renal dysfunction or new-onset cerebrovascular disease and evaluated urinary surrogate markers for renal injury.
RESULTS: Overall, 101 participants were registered and allocated to three groups: standard (n = 32), SB (n = 34), and PCSC (n = 35). Two patients in the standard group attained the primary endpoints (renal stones and overt proteinuria) but were not statistically significant. There was one patient in the standard reduced eGFR during the long-term study (p = 0.042 by ANOVA). SB increased proteinuria (p = 0.0139, baseline vs. 6 months), whereas PCSC significantly reduced proteinuria (p = 0.0061, baseline vs. 1 year, or p = 0.0186, vs. 2 years) and urinary excretion of 8-hydroxy-2\'-deoxyguanosine (p = 0.0481, baseline vs. 6 months).
CONCLUSIONS: This study is the first to report supplementation of PCSC reduced intrarenal oxidative stress in patients with mild-stage CKD.
METHODS: This was a single-center, open-labeled, randomized cohort trial. Study participants with CKD stages G2, G3a, and G3b were enrolled between March 2013 and January 2019 and randomly assigned by stratification according to age, sex, estimated glomerular filtration rate (eGFR), and diabetes. They were followed up for 6 months (short-term study) for the primary endpoints and extended to 2 years (long-term study) for the secondary endpoints. Supplementary doses were adjusted to achieve an early morning urinary pH of 6.8-7.2. We observed renal dysfunction or new-onset cerebrovascular disease and evaluated urinary surrogate markers for renal injury.
RESULTS: Overall, 101 participants were registered and allocated to three groups: standard (n = 32), SB (n = 34), and PCSC (n = 35). Two patients in the standard group attained the primary endpoints (renal stones and overt proteinuria) but were not statistically significant. There was one patient in the standard reduced eGFR during the long-term study (p = 0.042 by ANOVA). SB increased proteinuria (p = 0.0139, baseline vs. 6 months), whereas PCSC significantly reduced proteinuria (p = 0.0061, baseline vs. 1 year, or p = 0.0186, vs. 2 years) and urinary excretion of 8-hydroxy-2\'-deoxyguanosine (p = 0.0481, baseline vs. 6 months).
CONCLUSIONS: This study is the first to report supplementation of PCSC reduced intrarenal oxidative stress in patients with mild-stage CKD.
摘要：
背景：含碱化剂的口服补充剂对慢性肾病（CKD）患者的有益作用仅限于严重阶段。我们调查了两种类型的补充剂，碳酸氢钠（SB）和柠檬酸钾/柠檬酸钠（PCSC），可以维持轻度CKD患者的肾功能。
方法：这是一个单中心，开放标签，随机队列试验。CKD阶段G2、G3a、和G3b在2013年3月至2019年1月期间纳入，并根据年龄分层随机分配，性别,估计肾小球滤过率(eGFR)，和糖尿病。主要终点随访6个月（短期研究），次要终点随访2年（长期研究）。调整补充剂量以达到早晨尿液pH值为6.8-7.2。我们观察到肾功能障碍或新发脑血管疾病，并评估了肾脏损伤的尿替代标志物。
结果：总体而言，101名参与者被登记并分配到三组：标准(n=32)，SB（n=34），和PCSC(n=35)。标准组中的两名患者达到了主要终点（肾结石和明显的蛋白尿），但没有统计学意义。在长期研究中，有一名患者的标准eGFR降低（通过ANOVA，p=0.042）。SB增加蛋白尿（p=0.0139，基线与6个月),而PCSC显着减少蛋白尿（p=0.0061，基线与1年,或p=0.0186，与2年）和8-羟基-2'-脱氧鸟苷的尿排泄（p=0.0481，基线与6个月）。
结论：本研究首次报道补充PCSC可降低轻度CKD患者的肾内氧化应激。
方法：这是一个单中心，开放标签，随机队列试验。CKD阶段G2、G3a、和G3b在2013年3月至2019年1月期间纳入，并根据年龄分层随机分配，性别,估计肾小球滤过率(eGFR)，和糖尿病。主要终点随访6个月（短期研究），次要终点随访2年（长期研究）。调整补充剂量以达到早晨尿液pH值为6.8-7.2。我们观察到肾功能障碍或新发脑血管疾病，并评估了肾脏损伤的尿替代标志物。
结果：总体而言，101名参与者被登记并分配到三组：标准(n=32)，SB（n=34），和PCSC(n=35)。标准组中的两名患者达到了主要终点（肾结石和明显的蛋白尿），但没有统计学意义。在长期研究中，有一名患者的标准eGFR降低（通过ANOVA，p=0.042）。SB增加蛋白尿（p=0.0139，基线与6个月),而PCSC显着减少蛋白尿（p=0.0061，基线与1年,或p=0.0186，与2年）和8-羟基-2'-脱氧鸟苷的尿排泄（p=0.0481，基线与6个月）。
结论：本研究首次报道补充PCSC可降低轻度CKD患者的肾内氧化应激。
