Bjornstad Petter, Maahs David M, Roncal Carlos A, Snell-Bergeon Janet K, Shah Viral N, Milagres Tamara, Ellis Samuel L, Hatch Matthew, Chung Linh T, Rewers Marian J, Garg Satish, Cherney David Z, Pyle Laura, Nadeau Kristen J, Johnson Richard J
Division of Endocrinology, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.
Department of Clinical Research, Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, Colorado.
Diabetes Obes Metab. 2018 Jul;20(7):1776-1780. doi: 10.1111/dom.13274. Epub 2018 Mar 24.
Uricosuria and crystallization are increasingly recognized risk factors for diabetic tubulopathy. This pilot clinical trial aimed to determine the acute effect of urinary alkalinization using oral sodium bicarbonate (NaHCO ) on UA crystals in adults with type 1 diabetes (T1D). Adults with T1D, ages 18 to 65 years (n = 45, 60% female, HbA1c, 7.5 ± 1.2%, 20.2 ± 9.3 years duration) without chronic kidney disease (eGFR ≥60 mL/min/1.73 m and albumin-to-creatinine ratio < 30 mg/g) received 2 doses of 1950 mg oral NaHCO over 24 hours. Fasting urine and serum were collected pre- and post-intervention. UA crystals were identified under polarized microscopy. Urine measurements included: osmolality, pH, UA, creatinine and kidney injury molecule-1 (KIM-1). NaHCO therapy increased mean ± SD urine pH from 6.1 ± 0.7 to 6.5 ± 0.7 (P < .0001). Prior to therapy, 31.0% of participants had UA crystals vs 6.7% post therapy (P = .005). Change in urine pH inversely correlated with change in urine KIM-1 (r:-0.51, P = .0003). In addition, change in urine UA over 24 hours correlated with change in urine KIM-1 (r:0.37, P = .01). In conclusion, oral NaHCO normalized urine pH and decreased UA crystals, and may hold promise as an inexpensive and safe tubulo-protective intervention in individuals with T1D.
尿酸尿症和结晶越来越被认为是糖尿病肾小管病变的风险因素。这项初步临床试验旨在确定口服碳酸氢钠(NaHCO₃)使尿液碱化对1型糖尿病(T1D)成人患者尿酸(UA)结晶的急性影响。年龄在18至65岁的T1D成人患者(n = 45,60%为女性,糖化血红蛋白[HbA1c]为7.5±1.2%,病程20.2±9.3年),无慢性肾脏病(估算肾小球滤过率[eGFR]≥60 mL/min/1.73 m²且白蛋白与肌酐比值<30 mg/g),在24小时内分2剂服用1950 mg口服NaHCO₃。干预前后收集空腹尿液和血清。在偏振显微镜下鉴定UA结晶。尿液检测指标包括:渗透压、pH值、UA、肌酐和肾损伤分子-1(KIM-1)。NaHCO₃治疗使平均±标准差尿液pH值从6.1±0.7升至6.5±0.7(P <.0001)。治疗前,31.0%的参与者有UA结晶,治疗后为6.7%(P =.005)。尿液pH值变化与尿液KIM-1变化呈负相关(r:-0.51,P =.0003)。此外,24小时内尿液UA变化与尿液KIM-1变化相关(r:0.37,P =.01)。总之,口服NaHCO₃可使尿液pH值正常化并减少UA结晶,对于T1D患者而言,有望成为一种廉价且安全的肾小管保护干预措施。