Department of Physiology, Functional Renal Explorations Department, AP-HP (Public Assistance Hospitals of Paris), Georges Pompidou European Hospital, Paris Descartes University, Paris, France.
INSERM UMRS 1138, Paris, France.
BJU Int. 2019 Nov;124(5):849-861. doi: 10.1111/bju.14721. Epub 2019 Mar 25.
To evaluate medical treatments, in terms of adverse events (AEs) and therapeutic goals, in a large series of patients with cystinuria.
Data from 442 patients with cystinuria were recorded retrospectively. Crystalluria was studied in 89 patients. A mixed-effects logistic regression model was used to estimate how urine pH, specific gravity and cysteine-binding thiols (CBT) correlate with risk of cystine crystalluria.
Alkalizing agents and CBT agents were given to 88.8% (n = 381) and 55.3% (n = 238) of patients, respectively. Gastrointestinal AEs were reported in 12.3%, 10.4% and 2.6% of patients treated with potassium bicarbonate, potassium citrate and sodium bicarbonate, respectively (P = 0.008). The percentages of patients who experienced at least one AE with tiopronin (24.6%) and with D-penicillamine (29.5%) were similar (P = 0.45). Increasing urine pH and decreasing urine specific gravity significantly reduced the risk of cystine crystalluria, whereas D-penicillamine and tiopronin treatments did not reduce this risk (odds ratio [OR] 1 for pH ≤6.5; OR 0.52 [95% confidence interval {95% CI} 0.28-0.95] for 7.0 <pH ≤7.5, P = 0.03; OR 0.26 [95% CI 0.13-0.53] for 7.5 < pH ≤8.0, P <0.001; OR 1 for specific gravity ≤1.005 OR 5.76 [95% CI 1.45-22.85] for 1.006 ≤ specific gravity ≤1.010, P = 0.01; and OR 11.06 [95% CI 2.76-44.26] for 1.011 ≤ specific gravity ≤ 1.014, P < 0.001). Increased urine pH significantly increased the risk of calcium phosphate crystalluria (OR 1 for pH≤ 6.5; OR 6.09 [95% CI 2.15-17.25] for pH >8.0, P <0.001).
Adverse events were frequent with D-penicillamine and tiopronin. Alkaline hyperdiuresis was well tolerated and reduced cystine crystalluria. Urine specific gravity ≤1.005 and urine pH >7.5, while warning about calcium-phosphate crystallization, should be the goals of medical therapy.
评估胱氨酸尿症患者中大量病例的治疗方法（不良事件和治疗目标）。
回顾性记录了 442 例胱氨酸尿症患者的数据。对 89 例患者进行了结晶尿研究。采用混合效应逻辑回归模型来评估尿液 pH 值、比重和半胱氨酸结合硫醇（CBT）与胱氨酸结晶尿风险的相关性。
分别有 88.8%（n=381）和 55.3%（n=238）的患者接受了碱化剂和 CBT 治疗。接受碳酸氢钾、柠檬酸钾和碳酸氢钠治疗的患者分别有 12.3%、10.4%和 2.6%出现胃肠道不良事件（P=0.008）。使用硫普罗宁（24.6%）和青霉胺（29.5%）治疗的患者至少出现一次不良事件的比例相似（P=0.45）。尿液 pH 值升高和比重降低显著降低了胱氨酸结晶尿的风险，而青霉胺和硫普罗宁治疗并未降低这种风险（pH 值≤6.5 时比值比[OR]为 1；pH 值为 7.0<pH 值≤7.5 时 OR 为 0.52[95%置信区间{95%CI}0.28-0.95]，P=0.03；pH 值为 7.5<pH 值≤8.0 时 OR 为 0.26[95%CI 0.13-0.53]，P<0.001；尿液比重≤1.005 时 OR 为 1；1.006≤尿液比重≤1.010 时 OR 为 5.76[95%CI 1.45-22.85]，P=0.01；尿液比重为 1.011≤尿液比重≤1.014 时 OR 为 11.06[95%CI 2.76-44.26]，P<0.001）。尿液 pH 值升高显著增加了磷酸钙结晶尿的风险（pH 值≤6.5 时 OR 为 1；pH 值>8.0 时 OR 为 6.09[95%CI 2.15-17.25]，P<0.001）。
青霉胺和硫普罗宁的不良反应较为频繁。碱性高渗利尿反应良好，降低了胱氨酸结晶尿的风险。尿液比重≤1.005 和尿液 pH 值>7.5 虽然提示可能出现钙磷结晶，但应作为医学治疗的目标。
