Table 3.
Validation score and future perspectives in the development of biomarkers in CKD patients.
| Biomarkers | Validation Criteria | Future Perspectives |
|---|---|---|
| Proteinuria | Analytic validation: +/− | Further studies are needed to establish (1) how this marker should be used for monitoring disease progression considering, among all factors, its variability, and (2) what are the true cut-offs for response to treatments. Inclusion of proteinuria in risk prediction models that include the presence of renal diagnoses is also needed. |
| Clinical proof of concept: + | ||
| Clinical prospective validation: + | ||
| Incremental value of the biomarker: + | ||
| Introduction in clinical trials: + | ||
| eGFRcrea | Analytic validation: + | eGFRcrea is an important marker used to stratify risk in CKD patients. Further studies could refine the assessment of eGFRcrea as a biomarker of response to nephroprotective treatments in clinical trials. Inclusion of eGFRcrea in risk prediction models that include the presence of renal diagnoses is also needed. |
| Clinical proof of concept: + | ||
| Clinical prospective validation: + | ||
| Incremental value of the biomarker: + | ||
| Introduction in clinical trials: +/− | ||
| Markers of oxidative stress, tissue remodeling, and metabolism | Analytic validation: + | The prognostic role of these markers should be evaluated in larger cohort studies. Individual prognostic measures should be provided. Although pilot experimental trials showed promising results, stronger evidence in CKD patients around the changes in these markers after treatment initiation is needed. |
| Clinical proof of concept: + | ||
| Clinical prospective validation: +/− | ||
| Incremental value of the biomarker: − | ||
| Introduction in clinical trials: +/− | ||
| Cardiac markers | Analytic validation: +/− | Although cardiac markers levels are associated with the severity of CKD, their assessment is confounded by the coexistence of CV disease, as well as by the eGFR levels. Further studies are needed to establish the true role of these markers in CKD patients. |
| Clinical proof of concept: + | ||
| Clinical prospective validation: +/− | ||
| Incremental value of the biomarker: +/− | ||
| Introduction in clinical trials: − | ||
| Filtration and urinary markers | Analytic validation: +/− | The prognostic role of these markers should be evaluated in larger studies. Individual risk prediction models that include these parameters and intervention studies assessing their changes over time should be implemented. |
| Clinical proof of concept: + | ||
| Clinical prospective validation: + | ||
| Incremental value of the biomarker: − | ||
| Introduction in clinical trials: − | ||
| Ultrasound markers | Analytic validation: + | RRI was found to be associated with CV and renal events in CKD patients, being a promising marker. However, larger clinical trials evaluating the association between changes (treatment-induced) in RRI and clinical outcomes should be performed in the future. |
| Clinical proof of concept: + | ||
| Clinical prospective validation: + | ||
| Incremental value of the biomarker: +/− | ||
| Introduction in clinical trials: +/− | ||
| Proteomics, metabolomics, and genomics | Analytic validation: + | Omics approaches show useful prognostic and predictive information in addition to traditional risk factors. Improving the inclusion of these markers in clinical trials may inform on their clinical applicability. |
| Clinical proof of concept: + | ||
| Clinical prospective validation: + | ||
| Incremental value of the biomarker: + | ||
| Introduction in clinical trials: +/− |
+, fully present; +/−, partially present; −, absent. CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; RRI, renal resistive index; CV, cardiovascular.