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Current treatments involve lowering urinary cystine levels and increasing cystine solubility. This systematic review evaluates the available literature regarding non-surgical interventions for cystinuria.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Key electronic databases were searched for studies that described the clinical management of cystinuria with high\u00a0diuresis, alkalinizing agents and thiol-based drugs that were published between 2000 and 2022. Observational studies were included if they contained clinical investigation with at least one previous or current episode of cystine stones, urine cystine levels\u2009&amp;gt;\u2009250\u00a0mg\/L and patients being managed with urinary dilution, alkalinizing agents\u00a0or other\u00a0pharmacological agents.\u00a0All included studies were assessed for study design, patient characteristics and outcomes. A qualitative and critical analysis was performed whereby study quality was assessed using Methodological Index for Non-Randomized Studies (MINORS).\u00a0Two authors performed the quality assessment\u00a0and excluded the studies with a low MINORS\u00a0score.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fourteen studies met the review inclusion and quality criteria. Of the fourteen studies, two reported treatment using alkalinizing agents, six reported treatment using thiol-based drugs, and six reported combination treatment using alkalinizing agents and thiol-based drugs. These studies indicated that first-line therapies, including high fluid intake and urinary alkalinization, increased urine volume to\u2009&amp;gt;\u20093\u00a0L\/day and urinary pH\u2009&amp;gt;\u20097.0, and were associated with reduced urinary cystine levels and cystine stone formation. Second-line therapy with cystine-binding thiol drugs, such as tiopronin and D-penicillamine, reduced urinary cystine levels, cystine crystal volume and increased cystine solubility, resulting in decreased cystine stone formation and stone recurrence rate. Further, combined intervention with alkalinizing agents and thiol-based drugs synergistically reduced stone recurrence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Cystinuria treatment may require a combined approach of high\u00a0diuresis, alkalinization and pharmacological interventions with regular monitoring of urinary pH, cystine levels, cystine crystal volume and solubility. However, poor adherence to treatment\u00a0is relatively\u00a0frequent, hence the pressing urgency for improved therapies and treatments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s40620-023-01795-6","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T12:02:49Z","timestamp":1699876969000},"page":"293-308","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Pharmacological interventions for the management of cystinuria: a systematic review"],"prefix":"10.1093","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7592-0766","authenticated-orcid":false,"given":"Nirmal Prasad","family":"Bhatt","sequence":"first","affiliation":[{"name":"Department of Immunology, Central Clinical School, Monash University, Melbourne, VIC, Australia 1"},{"name":"Bladder and Kidney Health Discovery Program, Central Clinical School, Monash University, Melbourne, VIC, Australia 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7303-9131","authenticated-orcid":false,"given":"Aniruddh Vijay","family":"Deshpande","sequence":"additional","affiliation":[{"name":"Bladder and Kidney Health Discovery Program, Central Clinical School, Monash University, Melbourne, VIC, Australia 2"},{"name":"Centre for Kidney Research, Children\u2019s Hospital at Westmead, New South Wales, Australia 3"},{"name":"Department of Surgery, Urology Unit, Children\u2019s Hospital at Westmead, Sydney, NSW, Australia 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7359-7464","authenticated-orcid":false,"given":"Malcolm Ronald","family":"Starkey","sequence":"additional","affiliation":[{"name":"Department of Immunology, Central Clinical School, Monash University, Melbourne, VIC, Australia 1"},{"name":"Bladder and Kidney Health Discovery Program, Central Clinical School, Monash University, Melbourne, VIC, Australia 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,11,13]]},"reference":[{"issue":"1","key":"2026012110454495600_CR1","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/s00240-015-0841-x 26614112","article-title":"How should patients with cystine stone disease be evaluated and treated in the twenty-first century?","volume":"44","author":"Andreassen","year":"2016","journal-title":"Urolithiasis"},{"issue":"7","key":"2026012110454495600_CR2","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1038\/nrneph.2010.69 20517292","article-title":"Pathophysiology and treatment of cystinuria","volume":"6","author":"Chillaron","year":"2010","journal-title":"Nat Rev Nephrol"},{"issue":"3","key":"2026012110454495600_CR3","doi-asserted-by":"publisher","first-page":"205","DOI":"10.3109\/00365599009180859 2237297","article-title":"Results of 5035 stone analyses: a contribution to epidemiology of urinary stone disease","volume":"24","author":"Leusmann","year":"1990","journal-title":"Scand J Urol Nephrol"},{"issue":"6","key":"2026012110454495600_CR4","doi-asserted-by":"publisher","first-page":"1516","DOI":"10.1016\/S0022-5347(17)39145-0 2585627","article-title":"Urinary tract stone disease in the united states veteran population. 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