Role of Estimated Glomerular Filtration Rate in Clinical Research: The Never-Ending Matter

Abstract

Background: Chronic kidney disease (CKD) burden is crucial both on a global scale and at individual patient level, affecting morbidity and mortality directly and through its effect on both cardiovascular damage and CKD progression to end-stage-kidney-disease (ESKD). Unfortunately, the awareness of CKD is poor, with few CKD patients conscious of the severity of their health status. The principal biomarker of kidney function is estimated glomerular filtration rate (eGFR).

Methods: We searched the literature and present a review article with the aim of summarizing the role of eGFR in clinical research. In particular, we report the eGFR role as a prognostic, enrichment and endpoint biomarker and its role in the early detection of CKD.

Results: eGFR has a major role as a biomarker in clinical research. As a prognostic marker, eGFR reduction is associated with cardiovascular events, ESKD and mortality. As an enrichment biomarker, eGFR values are pivotal for selecting patients to be included in randomized and observational studies; it helps to test a pre-defined drug in early CKD or in more advanced CKD allowing also to avoid screening failures and to shorten the duration of clinical trials. Moreover, eGFR decline (expressed as a percentage of reduction from baseline or continuous slope) can be considered a good endpoint in clinic trials overcoming delays whilst waiting for hard endpoints to develop.

Conclusions: eGFR is a strong clinical measure for both observational and intervention studies. It is also helpful in screening the general population for kidney disease and, in particular, to increase awareness of CKD.

Keywords: biomarker; chronic kidney disease; endpoint; enrichment; epidemiology; prognosis.

Fig. 1.

Rate of fatal and non-fatal cardiovascular events (myocardial infarction, stroke, heart failure, peripheral vascular disease) in chronic kidney disease patients stratified by stage [32].

Fig. 2.

Estimated estimated glomerular filtration rate (eGFR) and its association with several pathophysiologic mechanisms. Estimated GFR reduction is associated with the development of several comorbidities (increase in blood toxin levels, electrolyte imbalances such hyperkalaemia and hyposodiemia, inflammation, arterial hypertension and anemia) that, taken together, dramatically increase the risk for future events.