Ledinger Dominic, Nussbaumer-Streit Barbara, Piso Brigitte, Dobrescu Andreea, Gadinger Arianna, Klerings Irma, Hohenfellner Katharina, Sommer Isolde
Department for Evidence-based Medicine and Evaluation, University for Continuing Education Krems, Krems, Austria.
Department of Pediatrics, Pediatric Nephrology, RoMed Kliniken, Rosenheim, Germany.
Orphanet J Rare Dis. 2025 Aug 28;20(1):463. doi: 10.1186/s13023-025-03974-z.
Cystinosis is a rare genetic disorder, with the majority of patients suffering from infantile nephropathic cystinosis, the most severe form. If left untreated, cystinosis causes serious morbidity, initially through progressive kidney and eye disease, followed by systemic and multiorgan involvement, ultimately leading to premature death. In this systematic review, we summarize the evidence for cystinosis to support the development of an evidence-based clinical practice guideline (SELECT - S3 guideline for cystinosis).
We searched MEDLINE, Embase, CENTRAL, CINAHL, and other databases for relevant studies published from 1980 onward. We screened literature dually and independently for eligibility. Primary researchers extracted data, rated the risk of bias of included studies, and rated the certainty of the evidence (CoE). Secondary researchers reviewed for completeness and accuracy. We applied a staggered approach, prioritizing available controlled studies and synthesizing results narratively.
We considered 56 studies in our synthesis and assessed findings relevant to 17 of 31 key questions. We identified evidence for 62 of 213 outcomes. Fifty-two outcomes had very low CoE, three low, four moderate, and three high. The moderate and high CoE findings came from indirect comparisons (other chronic multi-organ diseases). There was low evidence that delayed-release cysteamine therapy makes little to no difference on cystine levels compared to immediate-release cysteamine therapy; however, delayed-release cysteamine was associated with a slight increase in adverse events. Starting systemic cysteamine treatment early likely improves renal function compared to a later start. Most included studies lacked a control group, had a high risk of bias, and had a small sample size.
Evidence informing the diagnosis and management of cystinosis is limited, with most findings rated as very low certainty. Few direct comparisons involving only individuals with cystinosis yielded low certainty findings, while moderate to high certainty evidence was found only in indirect comparisons. These findings underscore a critical challenge in managing cystinosis: the balancing act of clinical decision-making in the context of lacking evidence. Nonetheless, this systematic review synthesized the best available data for a clinical practice guideline and highlighted specific areas where future research could strengthen the evidence base.
The online version contains supplementary material available at 10.1186/s13023-025-03974-z.
胱氨酸病是一种罕见的遗传性疾病，大多数患者患有婴儿型肾病性胱氨酸病，这是最严重的一种形式。如果不进行治疗，胱氨酸病会导致严重的发病情况，最初表现为进行性肾病和眼病，随后发展为全身多器官受累，最终导致过早死亡。在本系统评价中，我们总结了胱氨酸病的相关证据，以支持制定基于证据的临床实践指南（SELECT - 胱氨酸病S3指南）。
我们检索了MEDLINE、Embase、CENTRAL、CINAHL和其他数据库，以查找1980年以后发表的相关研究。我们对文献进行了双重独立筛选以确定其是否符合纳入标准。主要研究人员提取数据，评估纳入研究的偏倚风险，并对证据的确定性（CoE）进行评级。次要研究人员对数据的完整性和准确性进行审核。我们采用了一种交错式方法，优先考虑现有的对照研究，并对结果进行叙述性综合。
我们在综合分析中考虑了56项研究，并评估了与31个关键问题中的17个相关的研究结果。我们确定了213项结果中的62项有证据支持。52项结果的证据确定性非常低，3项为低，4项为中等，3项为高。中等和高证据确定性的结果来自间接比较（其他慢性多器官疾病）。有低水平证据表明，与速释半胱胺疗法相比，缓释半胱胺疗法对胱氨酸水平的影响很小或几乎没有影响；然而，缓释半胱胺与不良事件略有增加相关。与较晚开始相比，早期开始全身半胱胺治疗可能会改善肾功能。大多数纳入研究缺乏对照组，偏倚风险高，样本量小。
关于胱氨酸病诊断和管理的证据有限，大多数研究结果的确定性被评为非常低。很少有仅涉及胱氨酸病患者的直接比较得出低确定性的结果，而中等至高确定性的证据仅在间接比较中发现。这些发现凸显了胱氨酸病管理中的一个关键挑战：在缺乏证据的情况下进行临床决策的权衡。尽管如此，本系统评价为临床实践指南综合了现有最佳数据，并突出了未来研究可加强证据基础的特定领域。
在线版本包含可在10.1186/s13023-025-03974-z获取的补充材料。
