Major R W, Shepherd D, Brunskill N J: Reclassification of Chronic Kidney Disease Stage, Eligibility for Cystatin-C and Its Associated Costs in a UK Primary Care Cohort. Nephron 2018;139:39–46
The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guidelines recommend confirmatory testing for estimated glomerular filtration rate (eGFR) using cystatin C or cystatin C + creatinine eGFR formulas when eGFR is between 45 and 59 ml/min/1.73m2 (CKD category 3A), when proteinuria is absent (category A1), or when no co-morbid diseases (such as diabetes) is present that might explain the presence of CKD. If the eGFR is < 60ml/min/1.73m2 with one or the other of the “confirmatory” tests, then CKD may be diagnosed. The utility and cost-effectiveness of these recommendations have not been well studied, especially in a primary care practice situation largely involving older adults. The prevalence of category G3a without abnormal proteinuria (CKD G3a/A1) is likely to be affected by the type of eGFR equation (Modification of Diet in Renal Disease (MDRD) vs CKD-EPI creatinine vs other equations) in such a population.
Major and co-workers in the United Kingdom sought to remedy this gap in knowledge by conducting a study in 353,256 adult patients (over 18 years of age) enrolled in 49 primary care practices. Initially, a total of 21,544 individuals (6.1 %) had at least two eGFR values (MDRD equation) < 60ml/min/1.73m2 three months apart, of which 10,031 (46.6 %) had CKD category G3a/A1. As expected, patients identified as having CKD were older adults (average age 75 years), predominantly female (61 %), and 22 % had diabetes. Reclassification of the patients using the CKD-EPI equation reduced the number of subjects with category G3a/A1 CKD from 10,031 to 8762 (about -12 %) and increased the number categorized with more severe CKD (category G3b/A1) from 2213 to 3095 (about 40 %). See Table:
Classification of CKD at the study’s baseline by MDRD, CKD-EPI and proteinuria stage and reclassification of CKD stages between MDRD and CKD-EP (From Nephron 2018;139:39–46)
Thus, use of CKD-EPI-creatinine actually decreases “eligibility” of patients for confirmatory cystatin C eGFR testing by virtue of its effect of worsening the CKD severity category in those originally defined as having CKD by the MDRD eGFR equation. But since the cohort was originally constructed by inclusion of only those subjects with any CKD by eGFR criteria using MDRD values, the overall impact of using a CKD-EPI creatinine equation for assessment of CKD could not be evaluated, but suggests the possibility that more patients will be classified as having CKD, by KDIGO criteria, if a CKD-EPI creatinine equation is used as the “classifier” in an elderly cohort of patients being seen in primary care practice. It is generally agreed that the prevalence of CKD (by KDIGO criteria) in the elderly highly depends on the formula used to estimate GFR. No formulas for eGFR other than CKD-EPI creatinine or MDRD were examined in this study. Applying these data to the entire UK adult population (51.3 million in 2015, all ages > 18 years) it was estimated about 1.27 million subjects (2.5 %) would be eligible for “confirmatory” cystatin C eGFR determinations (fewer using CKD-EPI creatinine compared to MDRD). When visits and primary care consultation costs were included in addition to the serum cystatin C determination cost a total of 67.5 million Euros (USD 81 million) would be required for implementation of a serum cystatin C confirmation program if 100 % of adults in the UK were screened for CKD using eGFR MDRD or CKD-EPI creatinine determinations. Comparable costs in the USA are unknown but might approximate USD 500 million.
This study provides no insights into the cost-benefit relationships of confirmatory cystatin C eGFR testing in the G3a/A1 CKD population, but raises some serious issues about its application in defined populations, about selection of the optimum GFR formulas for determining eligibility for such confirmational testing, and the need for additional “refinement” of the eligibility criteria if such confirmatory testing is deemed to have clinical utility.