急性结石事件初始治疗的主要目标是缓解症状,需要时可给与补液和镇痛/止吐。如出现感染的症状和体征,且患者存在肾脏或输尿管结石,应立即请泌尿科会诊,因为结石梗阻情况下的尿路感染是一种急症,需要使用抗生素治疗和解除肾脏压迫,以减少发生危及生命的脓毒性休克的几率。[41]Sammon JD, Ghani KR, Karakiewicz PI, et al. Temporal trends, practice patterns, and treatment outcomes for infected upper urinary tract stones in the United States. Eur Urol. 2013 Jul;64(1):85-92.http://www.ncbi.nlm.nih.gov/pubmed/23031677?tool=bestpractice.com 如果结石患者未出现感染的症状或体征,则可使用阿片类药物和非甾体抗炎药 (NSAID) 进行保守治疗;非甾体抗炎药已被证实能够有效缓解急性肾结石相关的疼痛,并且其副作用少于阿片类药物和对乙酰氨基酚。[42]Pathan SA, Mitra B, Cameron PA. A systematic review and meta-analysis comparing the efficacy of nonsteroidal anti-inflammatory drugs, opioids, and paracetamol in the treatment of acute renal colic. Eur Urol. 2018 Apr;73(4):583-95.http://www.ncbi.nlm.nih.gov/pubmed/29174580?tool=bestpractice.com 如果保守治疗无法控制疼痛,则应考虑肾脏减压或进行结石的确定性治疗。[1]Stoller ML. Urinary stone disease. In: Tanagho EA, McAninch JW, eds. Smith's General Urology, 16th edition. New York, NY: McGraw-Hill: 2004: 256-291. 目前有证据表明,使用药物排石治疗 (medical expulsive therapy ,MET) 即α 受体阻滞剂,可增加 < 10 mm 远端输尿管结石的排出率,并缩短结石排出所需的时间。[43]Eisner BH, Goldfarb DS, Pareek G. Pharmacologic treatment of kidney stone disease. Urol Clin North Am. 2013 Feb;40(1):21-30.http://www.ncbi.nlm.nih.gov/pubmed/23177632?tool=bestpractice.com [
]What are the effects of alpha‐blockers as medical expulsive therapy for people with ureteral stones?https://www.cochranelibrary.com/cca/doi/10.1002/cca.2153/full显示答案 然而,如果已经尝试使用了 4-6 周的药物排石治疗 (MET),但结石未能成功排出,则应进行确定性手术治疗。
针对有结石复发风险或有复发病史的患者应制定二级预防措施,以便消除促进结石形成的基础代谢因素。针对所有此类患者,改善饮食习惯和充分补液是长期治疗方法最重要的方面。
紧急情况:梗阻和感染
患有尿路结石伴有发热和其他感染症状或体征的患者需要就引流和静脉使用抗生素进行泌尿科紧急会诊。若无法迅速行肾脏减压,则可能导致尿脓毒症和死亡。引流的方式有两种。泌尿科医生可在梗阻部位放置一根输尿管支架,实现引流。另外还可通过影像学介入技术进行经皮肾造瘘置管。
结石 < 10 mm 且无并发症的治疗
肾脏和输尿管绞痛的紧急内科治疗包括保守治疗,如补液、镇痛(静脉注射吗啡或非甾体抗炎药物酮咯酸来缓解疼痛)和止吐。 [
]Is there randomized controlled trial evidence to support the use of nonsteroidal anti-inflammatory drugs (NSAIDS) compare with other analgesics and each other in people with acute renal colic?http://cochraneclinicalanswers.com/doi/10.1002/cca.920/full显示答案
输尿管结石 < 10 mm 的新确诊患者,如果没有并发症因素(尿脓毒病、难治性疼痛和/或呕吐、即将出现急性肾功能衰竭、单发或移植肾梗阻或双侧梗阻),则处置效果应该较好。[44]Assimos D, Krambeck A, Miller NL, et al. Surgical management of stones: American Urological Association/Endourological Society Guideline. 2016 [internet publication].http://www.auanet.org/education/guidelines/surgical-management-of-stones.cfm 很多 < 10 mm 的输尿管结石都可自行排出,确切的排出率与结石的大小和位置有关。[45]Jendeberg J, Geijer H, Alshamari M, et al. Size matters: the width and location of a ureteral stone accurately predict the chance of spontaneous passage. Eur Radiol. 2017 Nov;27(11):4775-85.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5635101/http://www.ncbi.nlm.nih.gov/pubmed/28593428?tool=bestpractice.com
使用 α 受体阻滞剂(例如坦索罗辛、阿夫唑嗪或赛洛多辛)的药物排石治疗可能对促进输尿管远端较大结石(但大小仍<10 mm)的排出有帮助;但该类药物的有效率还有待证实。[46]Campschroer T, Zhu X, Vernooij RW, et al. Alpha-blockers as medical expulsive therapy for ureteral stones. Cochrane Database Syst Rev. 2018;(4):CD008509.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD008509.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/29620795?tool=bestpractice.com[47]Sridharan K, Sivaramakrishnan G. Efficacy and safety of alpha blockers in medical expulsive therapy for ureteral stones: a mixed treatment network meta-analysis and trial sequential analysis of randomized controlled clinical trials. Expert Rev Clin Pharmacol. 2018 Mar;11(3):291-307.http://www.ncbi.nlm.nih.gov/pubmed/29334287?tool=bestpractice.com[48]Meltzer AC, Burrows PK, Wolfson AB, et al. Effect of tamsulosin on passage of symptomatic ureteral stones: a randomized clinical trial. JAMA Intern Med. 2018 Aug 1;178(8):1051-7.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082698/http://www.ncbi.nlm.nih.gov/pubmed/29913020?tool=bestpractice.com[49]Hollingsworth JM, Canales BK, Rogers MA, et al. Alpha blockers for treatment of ureteric stones: systematic review and meta-analysis. BMJ. 2016 Dec 1;355:i6112.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5131734/http://www.ncbi.nlm.nih.gov/pubmed/27908918?tool=bestpractice.com[50]Wang RC, Smith-Bindman R, Whitaker E, et al. Effect of tamsulosin on stone passage for ureteral stones: a systematic review and meta-analysis. Ann Emerg Med. 2017 Mar;69(3):353-61.e3.http://www.ncbi.nlm.nih.gov/pubmed/27616037?tool=bestpractice.com[51]El Said NO, El Wakeel L, Kamal KM, et al. Alfuzosin treatment improves the rate and time for stone expulsion in patients with distal uretral stones: a prospective randomized controlled study. Pharmacotherapy. 2015 May;35(5):470-6.http://www.ncbi.nlm.nih.gov/pubmed/26011140?tool=bestpractice.com[52]Sur RL, Shore N, L'Esperance J. Silodosin to facilitate passage of ureteral stones: a multi-institutional, randomized, double-blinded, placebo-controlled trial. Eur Urol. 2015 May;67(5):959-64.http://www.ncbi.nlm.nih.gov/pubmed/25465978?tool=bestpractice.com[53]Yang D, Wu J, Yuan H, et al. The efficacy and safety of silodosin for the treatment of ureteral stones: a systematic review and meta-analysis. BMC Urol. 2016 May 27;16(1):23.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882785/http://www.ncbi.nlm.nih.gov/pubmed/27233621?tool=bestpractice.com [
]What are the effects of alpha‐blockers as medical expulsive therapy for people with ureteral stones?https://www.cochranelibrary.com/cca/doi/10.1002/cca.2153/full显示答案 这些药物可使输尿管平滑肌松弛,并具有抗输尿管痉挛的作用,因而可促进排石。[54]Micali S, Grande M, Sighinolfi MC, et al. Medical therapy of urolithiasis. J Endourol. 2006 Nov;20(11):841-7.http://www.ncbi.nlm.nih.gov/pubmed/17144848?tool=bestpractice.com 患者应注意针对此适应证开具的 α 受体阻滞剂属于超说明书用药。此外,坦索罗辛的使用已被证实与术中虹膜松弛综合征相关,因此如果患者已有白内障手术的计划应禁止开具此药物。
若结石排出为自发性的,绝大多数发生在 4-6 周内。手术干预的适应证为:存在持续梗阻、排石失败、脓毒症、肾绞痛持续或逐渐加重。一般来说,此类患者均应采用腹部平片、肾脏超声或腹部和盆腔 CT 平扫等影像学手段进行定期随访,以监测结石的位置和肾盂积水的程度。
≥ 10 mm 的结石或结石较小但 MET 排石失败后的治疗
除了解剖和临床特征,结石的大小、位置、成分都会影响治疗。较大的结石 (> 10 mm) 或较小但保守治疗无效的结石均需要额外接受手术治疗。过去,开放式手术是清除结石的唯一方法。然而,随着泌尿外科(该术语已用于描述在闭合尿道内进行操作的微创手术技术)的发展并获得成功,目前已很少进行开放式手术。
10-20 mm 结石的一线治疗方法一般为体外冲击波碎石术 (ESWL) 或输尿管镜。但是肾下极结石的 ESWL 结果 (55%) 要劣于上极和中部结石(分别为 71.8% 和 76.5%)。[55]Saw KC, Lingeman JE. Lesson 20: management of calyceal stones. AUA Update Series. 1999;20:154-9. 在 10-20 mm 结石的治疗方面,针对肾下极结石行经皮肾镜取石术 (Percutaneous nephrostolithotomy, PCNL) 的净石率要优于 ESWL(73% 比 57%)。[56]Havel D, Saussine C, Fath C, et al. Single stones of the lower pole of the kidney. Comparative results of extracorporeal shock wave lithotripsy and percutaneous nephrolithotomy. Eur Urol. 1998;33(4):396-400.http://www.ncbi.nlm.nih.gov/pubmed/9612684?tool=bestpractice.com 同样,ESWL 治疗>15-20 mm 的胱氨酸结石和钙磷石结石的效果也较差。[57]Kachel TA, Vijan SR, Dretler SP. Endourological experience with cystine calculi and a treatment algorithm. J Urol. 1991;145:25-28.http://www.ncbi.nlm.nih.gov/pubmed/1984093?tool=bestpractice.com 因此,存在肥胖或身材不适于接受 ESWL,或提示治疗结局较差特征的患者应建议使用 PCNL 或输尿管镜等替代治疗,而这些治疗的结果均较好。[58]Grasso M, Ficazzola M. Retrograde ureteropyeloscopy for lower pole caliceal calculi. J Urol. 1999 Dec;162(6):1904-8.http://www.ncbi.nlm.nih.gov/pubmed/10569534?tool=bestpractice.com 除非具有使用其他治疗方法的特殊适应症,否则>20 mm 的结石均应首先采用 PCNL 治疗。PCNL 是大体积结石的一线治疗方法,但是针对>20 mm(平均 25 mm)的结石,输尿管镜的平均净石率可高达 93.7% (77.0%-96.7%),而且并发症的总体发生率可以接受 (10.1%)。但是,每名患者平均需要 1.6 次输尿管镜手术才能完成净石。[59]Aboumarzouk OM, Monga M, Kata SG, et al. Flexible ureteroscopy and laser lithotripsy for stones >2 cm: a systematic review and meta-analysis. J Endourol. 2012 Oct;26(10):1257-63.http://www.ncbi.nlm.nih.gov/pubmed/22642568?tool=bestpractice.com[60]Kang SK, Cho KS, Kang DH, et al. Systematic review and meta-analysis to compare success rates of retrograde intrarenal surgery versus percutaneous nephrolithotomy for renal stones >2 cm: an update. Medicine (Baltimore). 2017 Dec;96(49):e9119.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5728962/http://www.ncbi.nlm.nih.gov/pubmed/29245347?tool=bestpractice.com
对于<10 mm 的单发肾结石,ESWL 和输尿管镜均是有效的治疗方案。如果 ESWL 失败、存在解剖学异常或其他特殊情况,则可选用输尿管镜或 PCNL。[61]Lingeman JE, Matlaga BR, Evan AP. Surgical management of upper urinary tract calculi. In: Wein AJ, Kavoussi LR, Novick AC, et al., eds. Campbell's urology. 9th ed. Philadelphia, PA: Saunders Elsevier; 2007:1431-1507.
体外冲击波碎石术 (ESWL) 是所有结石确定性治疗中创伤最小的一种方法,适用于绝大多数无并发症的结石患者。ESWL 过程中,外部震波源会发出冲击波,传导至患者的身体内,并在体内传播,直达肾结石。冲击波会通过压力和拉力击碎结石。结石碎片则会通过尿液排出。ESWL 的限制因素包括结石的大小和位置。ESWL 的优点在于,可在静脉镇静或镇痛情况下实施,无需全身麻醉。坦洛新治疗显示可有效地协助肾脏和输尿管结石患者清除结石。[62]Zhu Y, Duijvesz D, Rovers MM, et al. Alpha-blockers to assist stone clearance after extracorporeal shock wave lithotripsy: a meta-analysis. BJU Int. 2010 Jul;106(2):256-61.http://www.ncbi.nlm.nih.gov/pubmed/19889063?tool=bestpractice.com虽然 ESWL 方法治疗肾下极结石的成功率有限,但有证据表明辅助方法(例如振动、利尿和复位)可以提高净石率。[63]Liu LR, Li QJ, Wei Q, et al. Percussion, diuresis, and inversion therapy for the passage of lower pole kidney stones following shock wave lithotripsy. Cochrane Database Syst Rev. 2013;(12):CD008569.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008569.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24318643?tool=bestpractice.comESWL 治疗的禁忌证包括妊娠、严重骨骼畸形、严重肥胖、主动脉和/或肾动脉瘤、高血压控制不良、凝血功能紊乱和尿路感染控制不良。[64]Loughlin KR. Management of urologic problems during pregnancy. Urology. 1994 Aug;44(2):159-69.http://www.ncbi.nlm.nih.gov/pubmed/8048189?tool=bestpractice.com[65]Ignatoff JM, Nelson JB. Use of extracorporeal shock wave lithotripsy in a solitary kidney with renal artery aneurysm. J Urol. 1993 Feb;149(2):359-60.http://www.ncbi.nlm.nih.gov/pubmed/8426419?tool=bestpractice.com
输尿管镜治疗是将一条纤细的半刚性或软性内镜通过尿道置入输尿管和/或肾脏。一旦发现结石,则可使用激光将其击碎,或用网篮套住,并清除。这种操作的创伤性大于 ESWL,但一般认为其净石率更高。进行本操作时会常规使用全麻,操作结束时还可能放置一个输尿管支架。[66]Wang H, Man L, Li G, et al. Meta-analysis of stenting versus non-stenting for the treatment of ureteral stones. PLoS One. 2017 Jan 9;12(1):e0167670.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5221881/http://www.ncbi.nlm.nih.gov/pubmed/28068364?tool=bestpractice.com 在使用钬激光的情况下,凝血功能异常的患者也可安全地接受该手术。
对于需要清除结石的患者,ESWL 和输尿管镜均可被考虑作为输尿管结石的一线手术治疗方法。[44]Assimos D, Krambeck A, Miller NL, et al. Surgical management of stones: American Urological Association/Endourological Society Guideline. 2016 [internet publication].http://www.auanet.org/education/guidelines/surgical-management-of-stones.cfm[67]Türk C, Neisius A, Petrik A, et al. European Association of Urology. Guidelines on urolithiasis. 2018 [internet publication].https://uroweb.org/guideline/urolithiasis/ 对于远端输尿管结石(无论其大小如何)和>10 mm 的近段输尿管结石,输尿管镜的净石率要优于 ESW。[68]Dell'Atti L, Papa S. Ten-year experience in the management of distal ureteral stones greater than 10 mm in size. G Chir. 2016 Jan-Feb;37(1):27-30.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4859772/http://www.ncbi.nlm.nih.gov/pubmed/27142822?tool=bestpractice.com[69]Cui X, Ji F, Yan H, et al. Comparison between extracorporeal shock wave lithotripsy and ureteroscopic lithotripsy for treating large proximal ureteral stones: a meta-analysis. Urology. 2015 Apr;85(4):748-56.http://www.ncbi.nlm.nih.gov/pubmed/25681251?tool=bestpractice.com–但是,输尿管镜清除结石会导致并发症的发生率升高和住院时间延长。[70]Drake T, Grivas N, Dabestani S, et al. What are the benefits and harms of ureteroscopy compared with shock-wave lithotripsy in the treatment of upper ureteral stones? A systematic review. Eur Urol. 2017 Nov;72(5):772-86.http://www.ncbi.nlm.nih.gov/pubmed/28456350?tool=bestpractice.com[71]Aboumarzouk OM, Kata SG, Keeley FX, et al. Extracorporeal shock wave lithotripsy (ESWL) versus ureteroscopic management for ureteric calculi. Cochrane Database Syst Rev. 2012;(5):CD006029.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006029.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/22592707?tool=bestpractice.com
经皮顺行输尿管镜可经皮顺行清除输尿管结石,结石极大 (> 15 mm) 且嵌顿至上段输尿管或逆行方法无法实施的患者可考虑使用该治疗。[72]Maheshwari PN, Oswal AT, Andankar M, et al. Is antegrade ureteroscopy better than retrograde ureteroscopy for impacted large upper ureteral calculi? J Endourol. 1999 Jul-Aug;13(6):441-4.http://www.ncbi.nlm.nih.gov/pubmed/10479011?tool=bestpractice.com[73]el-Nahas AR, Eraky I, el-Assmy AM, et al. Percutaneous treatment of large upper tract stones after urinary diversion. Urology. 2006 Sep;68(3):500-4.http://www.ncbi.nlm.nih.gov/pubmed/16979745?tool=bestpractice.com[74]Wang Q, Guo J, Hu H, et al. Rigid ureteroscopic lithotripsy versus percutaneous nephrolithotomy for large proximal ureteral stones: a meta-analysis. PLoS One. 2017 Feb 9;12(2):e0171478.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5300230/http://www.ncbi.nlm.nih.gov/pubmed/28182718?tool=bestpractice.com
经皮肾镜取石术 (PCNL) 是一种微创治疗,通常用于肾脏和近段输尿管结石(下极结石)及较大结石 (> 20 mm)、使用 ESWL 和输尿管镜治疗失败、或肾脏解剖学构造复杂的患者。[75]Lingeman JE, Matlaga BR, et al. Surgical management of upper urinary tract calculi. In: Walsh P, Retik A, Vaughan ED Jr, Wein A, eds. Campbell's Urology, 8th edition. Philadelphia, PA: WB Saunders; 2002: 1431-1507. 实施本操作时,可通过腰部经皮进入肾脏,并将一根大的鞘管输送置入肾脏。置入成功后,可通过肾镜清除结石。如果结石较大,通常可使用超声碎石技术将结石击碎,并清除。PCNL 通常需要住院,而且其潜在并发症要多于 ESWL 和输尿管镜。如果结石在 20-30 mm 之间,则 ESWL 的净石率会很低 (34%),而 PCNL 的净石率会很高 (90%)。随着结石增大,需要更多次 ESWL 才能清除结石,而且需要辅助治疗措施。[76]Lingeman JE, Coury TA, Newman DM, et al. Comparison of results and morbidity of percutaneous nephrostolithotomy and extracorporeal shock wave lithotripsy. J Urol. 1987 Sep;138(3):485-90.http://www.ncbi.nlm.nih.gov/pubmed/3625845?tool=bestpractice.com
腹腔镜取石是清除输尿管或肾结石的另一种微创治疗方式。然而,其创伤性仍然较大,需要较长时间的住院,而且掌握这项技术的时间要长于输尿管镜和 ESWL。在过去 20 年中,随着 ESWL 和腔内泌尿外科技术(即输尿管镜和 endourological [PCNL])的进展,开放式取石手术的适应症明显缩小。下列罕见情况下可使用腹腔镜或开放式手术取石:ESWL、输尿管镜和经皮输尿管镜失败,或者不太可能成功的患者,解剖结构畸形(妨碍微创手术的使用)的患者;需要同时接受开放式手术、肾盂成形或部分肾切除术的患者或者结石负担较大,需要一次性清除的患者。[44]Assimos D, Krambeck A, Miller NL, et al. Surgical management of stones: American Urological Association/Endourological Society Guideline. 2016 [internet publication].http://www.auanet.org/education/guidelines/surgical-management-of-stones.cfm[67]Türk C, Neisius A, Petrik A, et al. European Association of Urology. Guidelines on urolithiasis. 2018 [internet publication].https://uroweb.org/guideline/urolithiasis/
妊娠期结石
每 200 至 1500 例妊娠中可出现 1 例症状性肾结石,其中有 80%-90% 发生于妊娠中后期。[77]Semins MJ, Matlaga BR. Kidney stones during pregnancy. Nat Rev Urol. 2014 Mar;11(3):163-8.http://www.ncbi.nlm.nih.gov/pubmed/24515090?tool=bestpractice.com 有报道显示,妊娠期间,有 48% 至 80% 的结石可自行排出。[30]Fulgham PF, Assimos DG, Pearle MS, et al. Clinical effectiveness protocols for imaging in the management of ureteral calculous disease: AUA Technology Assessment. J Urol. 2013 Apr;189(4):1203-13.http://www.jurology.com/article/S0022-5347%2812%2905259-7/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/23085059?tool=bestpractice.com[78]Burgess KL, Gettman MT, Rangel LJ, et al. Diagnosis of urolithiasis and rate of spontaneous passage during pregnancy. J Urol. 2011 Dec;186(6):2280-4.http://www.ncbi.nlm.nih.gov/pubmed/22014825?tool=bestpractice.com
如果孕妇的肾绞痛无法通过口服镇痛药控制,或者有结石梗阻并出现了感染体征(发热、尿液分析和/或尿培养提示可能存在尿路感染),则应接受输尿管支架置入或经皮肾造口置管手术。需要强调的是,由于妊娠期的代谢变化,置入的引流管内会很快结痂,因此需要更频繁的更换置管(每 6-8 周更换一次)。如果患者无感染证据,则可使用输尿管镜进行确定性治疗,该方法的安全性已经得到了证实。[79]Semins MJ, Trock BJ, Matlaga BR. The safety of ureteroscopy during pregnancy: a systematic review and meta-analysis. J Urol. 2009 Jan;181(1):139-43.http://www.ncbi.nlm.nih.gov/pubmed/19012926?tool=bestpractice.com 妊娠患者禁止使用 ESWL 和 PCNL。
长期药物疗法及膳食调整
给予诸如枸缘酸钾和碳酸氢钠等药物的口服碱化治疗可能有助于尿酸结石的溶解,并预防尿酸超饱和。因此可用于治疗无需急诊手术处理和无症状的尿酸结石。碱化治疗尿酸结石的理想目标是将尿 pH 值保持在 6.5 至 7.0 之间。枸缘酸钾是一线治疗药物。充血性心力衰竭或肾功能衰竭的患者给予碱化治疗时应格外谨慎。碱化治疗在预防钙性结石和胱氨酸结石形成的过程中也具有重要作用。
长期膳食调节对预防未来结石复发非常重要。调整的主要方式是增加液体摄入量。建议每日排尿量应至少为 2 L,这有助于预防结石的形成。[80]Cheungpasitporn W, Rossetti S, Friend K, et al. Treatment effect, adherence, and safety of high fluid intake for the prevention of incident and recurrent kidney stones: a systematic review and meta-analysis. J Nephrol. 2016 Apr;29(2):211-9.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4831051/http://www.ncbi.nlm.nih.gov/pubmed/26022722?tool=bestpractice.com
结石预防过程中还建议降低膳食中钠、蛋白质和草酸盐的摄入。推荐增加柑橘类水果的摄入以预防结石复发。[81]Pak CY. Kidney stones. Lancet. 1998 Jun 13;351(9118):1797-801.http://www.ncbi.nlm.nih.gov/pubmed/9635968?tool=bestpractice.com 同时建议正常摄入钙(每日 1000-1200 mg)。[81]Pak CY. Kidney stones. Lancet. 1998 Jun 13;351(9118):1797-801.http://www.ncbi.nlm.nih.gov/pubmed/9635968?tool=bestpractice.com 限制膳食中的含钙量可使钙和草酸盐在消化道内的结合减少,促进高草酸尿症,增加结石形成的风险;此外还对骨骼的健康有不良影响。
如果存在明确的代谢异常,而且膳食调节无效,则可能需要特定的预防性治疗。[82]Pearle MS, Goldfarb DS, Assimos DG, et al.; American Urological Association. Medical management of kidney stones: AUA guideline. J Urol. 2014 Aug;192(2):316-24.http://www.jurology.com/article/S0022-5347(14)03532-0/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/24857648?tool=bestpractice.com[83]Gambaro G, Croppi E, Coe F, et al; Consensus Conference Group. Metabolic diagnosis and medical prevention of calcium nephrolithiasis and its systemic manifestations: a consensus statement. J Nephrol. 2016 Dec;29(6):715-34.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5080344/http://www.ncbi.nlm.nih.gov/pubmed/27456839?tool=bestpractice.com这些措施包括:
尿酸结石:采用枸缘酸钾或碳酸氢钠进行尿液碱化。
高尿酸尿症、复发性草酸钙结石且尿钙正常:别嘌呤醇或非布索坦。
美国食品药品监督管理局 (FDA) 建议只能对下列患者开具非布司他:无法耐受别嘌呤醇或别嘌呤醇治疗失败的患者,以及针对心血管疾病风险已接受过咨询的患者。[84]US Food and Drug Administration. FDA adds Boxed Warning for increased risk of death with gout medicine Uloric (febuxostat). 21 February 2019 [internet publication].https://www.fda.gov/Drugs/DrugSafety/ucm631182.htm
针对痛风患者中使用非布司他或别嘌呤醇的心血管安全性的双盲临床试验显示,服用非布司他的患者的心血管死亡率和全因死亡率显著高于服用别嘌呤醇的患者(二者的心血管死亡率为 4.3% vs 3.2%, 风险比 1.34 [95% CI 1.03 to 1.73]; 二者的全因死亡率 7.8% vs 6.4%, HR 1.22 [95% CI 1.01 to 1.47])[85]White WB, Saag KG, Becker MA, et al. Cardiovascular safety of febuxostat or allopurinol in patients with gout. N Engl J Med. 2018 Mar 12;378(13):1200-10.www.doi.org/10.1056/NEJMoa1710895http://www.ncbi.nlm.nih.gov/pubmed/29527974?tool=bestpractice.com 在心血管事件的主要复合结局方面,治疗组间无差异。
高钙尿症和复发性钙性结石:噻嗪类利尿剂,同时补钾或不补钾(枸缘酸钾或氯化钾)。
低枸橼酸尿症和复发性钙性结石:尿液碱化(例如枸缘酸钾,如果患者高钾血症的风险,则可考虑使用碳酸氢钠或枸橼酸钠)。[86]Phillips R, Hanchanale VS, Myatt A, et al. Citrate salts for preventing and treating calcium containing kidney stones in adults. Cochrane Database Syst Rev. 2015;(10):CD010057.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010057.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/26439475?tool=bestpractice.com
高草酸尿症:草酸盐螯合剂(例如钙、镁或考来烯胺)、枸缘酸钾、维生素 B6。
胱氨酸尿:使用枸缘酸钾碱化尿液,或使用硫醇结合制剂(例如硫普罗宁,其耐受性优于 D-青霉胺)。
磷酸铵镁结石:尿素酶抑制剂(例如乙酰氧肟酸),最好用于已经经过多次手术治疗的复杂或复发性磷酸铵镁结石。由于该类药物可能会导致静脉炎和血液高凝状态等重度不良反应,因此应采取二级医疗监护。
以上大多数措施可以用于肾结石患儿中,但针对此年龄段设计良好的临床试验数量有限[87]Kern A, Grimsby G, Mayo H, et al. Medical and dietary interventions for preventing recurrent urinary stones in children. Cochrane Database Syst Rev. 2017;(11):CD011252.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011252.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/29117629?tool=bestpractice.com[88]Barreto L, Jung JH, Abdelrahim A, et al. Medical and surgical interventions for the treatment of urinary stones in children. Cochrane Database Syst Rev. 2018;(6):CD010784.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD010784.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/29859007?tool=bestpractice.com