在高血压CKD和血清总CO2正常的个体的早期研究中,碳酸氢钠降低了尿TGF-β1水平并保留了肾功能。碳酸氢钠对糖尿病肾病和正常血清总CO2患者肾纤维化和损伤标志物的影响尚不清楚。
我们进行了一项随机研究,双盲,对74名美国1型或2型糖尿病退伍军人进行安慰剂对照研究,eGFR为每1.73m215-89ml/min,尿白蛋白与肌酐之比(UACR)≥30mg/g,血清总CO2为22-28meq/L参与者接受口服碳酸氢钠(每天0.5meq/kg瘦体重;n=35)或安慰剂(n=39)6个月。主要结果是从基线到第3个月和第6个月的尿TGF-β1-肌酐的变化。次要结局包括尿肾损伤分子-1(KIM-1)-肌酐的变化,纤连蛋白肌酸酐,中性粒细胞明胶酶相关脂质运载蛋白(NGAL)与肌酐,从基线到第3个月和第6个月的UACR。
主要基线特征是年龄72±8岁,eGFR为每1.73m251±18ml/min,血清总CO2为24±2meq/L。碳酸氢钠治疗使平均总二氧化碳增加1.2(95%置信区间[95%CI],0.3至2.1)meq/L,尿液pH值增加0.6(95%CI,0.5至0.8),尿氨排泄减少5(95%CI,0至11)meq/d,尿可滴定酸排泄减少11(95%CI,5至18)meq/d。碳酸氢钠没有显著改变尿TGF-β1/肌酐(变化的差异,13%,95%CI,-10%至40%;碳酸氢钠组内部变化,8%,95%CI,-10%至28%;安慰剂组内的变化,-4%,95%CI,-19%至13%)。同样,对KIM-1对肌酐没有显著影响(变化差异,-10%,95%CI,-38%至31%),纤连蛋白与肌酐(8%,95%CI,-15%至37%),NGAL-肌酐(-33%,95%CI,-56%至4%),或UACR(1%,95%CI,-25%至36%)。
在非酸中毒性糖尿病肾病中,碳酸氢钠没有显着降低尿TGF-β1,KIM-1,纤连蛋白,NGAL,或UACR超过6个月。
In early-phase studies of individuals with hypertensive CKD and normal serum total CO2, sodium bicarbonate reduced urinary TGF-β1 levels and preserved kidney function. The effect of sodium bicarbonate on kidney fibrosis and injury markers in individuals with diabetic kidney disease and normal serum total CO2 is unknown.
We conducted a randomized, double-blinded, placebo-controlled
study in 74 United States veterans with type 1 or 2 diabetes mellitus, eGFR of 15-89 ml/min per 1.73 m2, urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g, and serum total CO2 of 22-28 meq/L. Participants received oral sodium bicarbonate (0.5 meq/kg lean body wt per day; n=35) or placebo (n=39) for 6 months. The primary outcome was change in urinary TGF-β1-to-creatinine from baseline to months 3 and 6. Secondary outcomes included changes in urinary kidney injury molecule-1 (KIM-1)-to-creatinine, fibronectin-to-creatinine, neutrophil gelatinase-associated lipocalin (NGAL)-to-creatinine, and UACR from baseline to months 3 and 6.
Key baseline characteristics were age 72±8 years, eGFR of 51±18 ml/min per 1.73 m2, and serum total CO2 of 24±2 meq/L. Sodium bicarbonate treatment increased mean total CO2 by 1.2 (95% confidence interval [95% CI], 0.3 to 2.1) meq/L, increased urinary pH by 0.6 (95% CI, 0.5 to 0.8), and decreased urinary ammonium excretion by 5 (95% CI, 0 to 11) meq/d and urinary titratable acid excretion by 11 (95% CI, 5 to 18) meq/d. Sodium bicarbonate did not significantly change urinary TGF-β1/creatinine (difference in change, 13%, 95% CI, -10% to 40%; change within the sodium bicarbonate group, 8%, 95% CI, -10% to 28%; change within the placebo group, -4%, 95% CI, -19% to 13%). Similarly, no significant effect on KIM-1-to-creatinine (difference in change, -10%, 95% CI, -38% to 31%), fibronectin-to-creatinine (8%, 95% CI, -15% to 37%), NGAL-to-creatinine (-33%, 95% CI, -56% to 4%), or UACR (1%, 95% CI, -25% to 36%) was observed.
In nonacidotic diabetic kidney disease, sodium bicarbonate did not significantly reduce urinary TGF-β1, KIM-1, fibronectin, NGAL, or UACR over 6 months.