Review article: Biomarkers of clinical outcomes in advanced chronic kidney disease

Abstract

Chronic kidney disease (CKD) is a complex condition, where the decrease in kidney function is accompanied by numerous metabolic changes affecting virtually all the organ systems of the human body. Many of the biomarkers characteristic of the individually affected organ systems have been associated with adverse outcomes including higher mortality in advanced CKD, whereas in persons without CKD these biomarkers may have no bearing on survival. It is believed that the high mortality seen in CKD is a result of several abnormalities conspiring to induce or aggravate a heightened degree of cardiovascular morbidity and predisposition to wasting syndrome. Not all the biomarkers may, however, be causally responsible for the adverse outcomes associated with them. We review various biomarkers of protein-energy wasting, inflammation, oxidative stress, potassium disarrays, acid-base disorders, bone and mineral disorders, glycemic status, and anemia. Although all of these biomarkers have shown associations with worsened outcomes in CKD, markers of protein-energy wasting, especially serum albumin, remain the strongest predictor of survival in CKD patients, especially those undergoing maintenance dialysis treatment. We also review the putative pathophysiologic mechanisms behind these associations, and present potential therapeutic interventions that could result in remedies to improve poor clinical outcomes in CKD, pending the results of current and future controlled trials.

Figure 1

Cardiovascular mortality associated with various levels of the calcium-phosphorus product in 58,058 maintenance hemodialysis patients. Based on data from Kalantar-Zadeh et al.

Figure 2

All-cause mortality associated with the ratio of recombinant human erythropoetin dose and blood hemoglobin level in 58,058 maintenance hemodialysis patients. Based on data from Regidor et al.

Figure 3

All-cause mortality associated with various levels of baseline serum cholesterol in 15,859 patients receiving maintenance hemodialysis. Based on data from Kilpatrick et al.