Background

To reduce over-diagnosis of chronic kidney disease (CKD) resulting from the inaccuracy of creatinine-based estimates of glomerular filtration rate (GFR), UK and international guidelines recommend that cystatin-C-based estimates of GFR be used to confirm or exclude the diagnosis in people with GFR 45–59 ml/min/1.73 m² and no albuminuria (CKD G3aA1). Whilst there is good evidence for cystatin C being a marker of GFR and risk in people with CKD, its use to define CKD in this manner has not been evaluated in primary care, the setting in which most people with GFR in this range are managed.

Methods and findings

A total of 1,741 people with CKD G3a or G3b defined by 2 estimated GFR (eGFR) values more than 90 days apart were recruited to the Renal Risk in Derby study between June 2008 and March 2010. Using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, we compared GFR estimated from creatinine (eGFR_creat), cystatin C (eGFR_cys), and both (eGFR_creat-cys) at baseline and over 5 years of follow-up. We analysed the proportion of participants with CKD G3aA1 reclassified to ‘no CKD’ or more advanced CKD with the latter two equations. We further assessed the impact of using cystatin-C-based eGFR in risk prediction equations for CKD progression and all-cause mortality and investigated non-GFR determinants of eGFR_cys. Finally, we estimated the cost implications of implementing National Institute for Health and Care Excellence (NICE) guidance to use eGFR_cys to confirm the diagnosis in people classified as CKD G3aA1 by eGFR_creat. Mean eGFR_cys was significantly lower than mean eGFR_creat (45.1 ml/min/1.73 m², 95% CI 44.4 to 45.9, versus 53.6 ml/min/1.73 m², 95% CI 53.0 to 54.1, P < 0.001). eGFR_cys reclassified 7.7% (50 of 653) of those with CKD G3aA1 by eGFR_creat to eGFR ≥ 60 ml/min/1.73 m². However, a much greater proportion (59.0%, 385 of 653) were classified to an eGFR category indicating more severe CKD. A similar pattern was seen using eGFR_creat-cys, but lower proportions were reclassified. Change in eGFR_creat and eGFR_cys over 5 years were weakly correlated (r = 0.33, P < 0.001), but eGFR_cys identified more people as having CKD progression (18.2% versus 10.5%). Multivariable analysis using eGFR_creat as an independent variable identified age, smoking status, body mass index, haemoglobin, serum uric acid, serum albumin, albuminuria, and C reactive protein as non-GFR determinants of eGFR_cys. Use of eGFR_cys or eGFR_creat-cys did not improve discrimination in risk prediction models for CKD progression and all-cause mortality compared to similar models with eGFR_creat. Application of the NICE guidance, which assumed cost savings, to participants with CKD G3aA1 increased the cost of monitoring by £23 per patient, which if extrapolated to be applied throughout England would increase the cost of testing and monitoring CKD by approximately £31 million per year. Limitations of this study include the lack of a measured GFR and the potential lack of ethnic diversity in the study cohort.

Conclusions

Implementation of current guidelines on eGFR_cys testing in our study population of older people in primary care resulted in only a small reduction in diagnosed CKD but classified a greater proportion as having more advanced CKD than eGFR_creat. Use of eGFR_cys did not improve risk prediction in this population and was associated with increased cost. Our data therefore do not support implementation of these recommendations in primary care. Further studies are warranted to define the most appropriate clinical application of eGFR_cys and eGFR_creat-cys.

中文翻译：

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胱抑素C测定在慢性肾脏疾病的诊断和管理中的临床效用和成本影响：一项基层医疗队列研究

背景

为减少因肌酐评估的肾小球滤过率（GFR）的准确性而导致的慢性肾脏疾病（CKD）的过度诊断，英国和国际指南建议将基于胱抑素C的评估的GFR用于确认或排除诊断为GFR 45–59 ml / min / 1.73 m ²且无蛋白尿（CKD G3aA1）的患者。尽管有充分的证据表明胱抑素C是CKD患者GFR和危险的标志物，但在初级保健中尚未评估过以这种方式定义CKD的使用，大多数情况下都可以控制此范围的GFR患者。

方法和发现

在2008年6月至2010年3月之间，共有1741名CKD G3a或G3b由2个估计的GFR（eGFR）值定义，相隔超过90天被招募入德比肾病风险研究。使用慢性肾脏病流行病学协作（CKD-EPI） ）方程，我们比较了基线和超过5年的随访时从肌酐（eGFR _creat），胱抑素C（eGFR _cys）和两者（eGFR _creat-cys）估算的GFR 。我们用后两个方程分析了被归类为“无CKD”或更高级的CKD的CKD G3aA1参与者的比例。我们进一步评估了基于胱抑素C的eGFR在CKD进展和全因死亡率的风险预测方程中的影响，并研究了eGFR _cys的非GFR决定因素。最后，我们估算了实施美国国家卫生与医疗保健研究院（NICE）指导以使用eGFR _cys来确认eGFR _creat分类为CKD G3aA1的人的诊断所涉及的成本。平均数的eGFR_半胱氨酸比平均的eGFR被显著降低_穿心莲（45.1毫升/分钟/1.73米²，95％CI 44.4 45.9，相比之下53.6毫升/分钟/1.73米²，95％CI 53.0至54.1，P < 0.001）。eGFR _cys通过eGFR _creat将CKD G3aA1患儿的7.7％（653个中的50％）重新分类为eGFR≥60 ml / min / 1.73 m ²。但是，更大比例（59.0％，385个中的385个）被归类为eGFR类别，表明CKD更为严重。使用eGFR _creat-cys可以观察到类似的模式，但是将较低的比例重新分类。过去5年中eGFR_创造力和eGFR _cys的变化呈弱相关性（r = 0.33，P < 0.001），但是eGFR _cys识别出更多的人患有CKD进展（18.2％对10.5％）。使用eGFR _creat作为独立变量的多变量分析确定了年龄，吸烟状况，体重指数，血红蛋白，血清尿酸，血清白蛋白，白蛋白尿和C反应蛋白作为eGFR _cys的非GFR决定因素。使用eGFR与具有eGFR _creat的类似模型相比，_cys或eGFR _creats不能改善CKD进展和全因死亡率的风险预测模型中的歧视性。将NICE指南（假定可节省成本）应用于CKD G3aA1的参与者，每位患者的监护成本增加了23英镑，如果推断为在整个英格兰使用，则会使CKD的检测和监测成本每位患者增加约3100万英镑。年。这项研究的局限性包括缺乏可测量的GFR以及研究队列中可能缺乏种族多样性。

结论

在我们研究的初级保健老年人群中实施当前的eGFR _cys检测指南只会导致确诊CKD的减少很小，但是与eGFR _creat相比，CKD的比例更高。使用eGFR _cys不能改善该人群的风险预测，并且与成本增加相关。因此，我们的数据不支持在初级保健中实施这些建议。有必要进行进一步的研究来确定eGFR _cys和eGFR _creat-cys的最合适的临床应用。