Clearance and beyond: the complementary roles of GFR measurement and injury biomarkers in acute kidney injury (AKI)

Abstract

Acute kidney injury (AKI) is a common and frequently fatal illness in critically ill patients. The reliance on daily measurements of serum creatinine as a surrogate of glomerular filtration rate (GFR) not only delays diagnosis and development of successful therapies but also hinders insight into the pathophysiology of human AKI. Measurement of GFR under non-steady-state conditions remains an elusive gold standard against which biomarkers of renal injury need to be judged. Approaches to the rapid (near real-time) measurement of GFR are explored. Even if real-time GFR was available, absent baseline information will always limit diagnosis of AKI based on GFR or serum creatinine to a detection of change. Biomarkers of renal cellular injury have provided new strategies to facilitate detection and early intervention in AKI. However, the diagnostic and predictive performance of urinary biomarkers of injury vary, depending on both the time after renal injury and on the preinjury GFR. Progress in understanding the role of each novel biomarker in the causal pathways of AKI promises to enhance their diagnostic potential. We predict that combining rapid measures of GFR with biomarkers of renal injury will yield substantive progress in the treatment of AKI.

Serum Creatinine Changes Associated with Critical Illness and Detection of Persistent Renal Dysfunction after AKI

“…Therefore, it seems plausible that the observed falls in serum creatinine across critical illness occur as the result of loss of muscle mass and reduced creatinine generation, potentially combined with reduced hepatic creatinine production and dietary changes. These changes would also compromise the use of creatinine as a measure of renal function during hospital admission (24). In addition, we would predict that use of final or lowest hospital creatinine as a surrogate for baseline creatinine in post hoc AKI diagnosis might lead to overestimation of AKI diagnosis, which was reported by other investigators (25).…”

Acute kidney disease and renal recovery: consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup

“…Alternative or complementary measures of kidney function, including other filtration markers such as cystatin C and timed urine clearance measurements, could hold promise for improved phenotyping of functional recovery from AKD but require further validation before recommending their routine adoption into clinical practice 35,[63][64][65][66] . Methods to assess glomerular functional reserve (for example, by assessing the effect of a protein load on GFR) or tubular functional reserve (for example, through furosemide stress testing or the administration of intravenous creatinine) have also been developed in the CKD setting but have yet to be applied to patients with AKD 67,68 .…”

Acute kidney injury in the perioperative period and in intensive care units (excluding renal replacement therapies)

“…Currently, no curative strategies enable clinicians to treat such established damage, and AKI is clearly associated with an increased independent risk of in-hospital mortality and CRI within a few years following AKI [16][17][18][19][20][21]. Therefore, current data strongly suggest the need to research risk factors for AKI and to detect early kidney attack episodes [1,[22][23][24]. Consequently, over the last 10 years multiple renal biomarkers capable of detecting early acute kidney attacks have been developed.…”