Tubular proteinuria in acute kidney injury: a critical evaluation of current status and future promise

Abstract

The diagnosis and prognosis of acute kidney injury (AKI) by current clinical means is inadequate. Biomarkers of kidney injury that are easily measured and unaffected by physiological variables could revolutionize the management of AKI. Our objective was to systematically review the diagnostic and prognostic utility of urine and serum biomarkers of AKI in humans. We searched MEDLINE, PubMed and EMBASE databases (January 2000-August 2009) for biomarker studies that could be classified into the following categories: (a) confirmation of the diagnosis of established AKI, (b) early prediction of AKI, and (c) prognostication of AKI. We identified 54 manuscripts published since 2000 that met our inclusion and exclusion criteria. Urinary interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and Nacetyl-b-D-glucosaminidase (NAG) are potentially useful biomarkers for the diagnosis of established AKI. Urinary NGAL, IL-18, and liver-type fatty acid binding protein, and serum NGAL and cystatin C represent the most promising biomarkers for early prediction of AKI. Urinary cystatin C, a1-microglobulin, NAG and retinol-binding protein may be useful to predict severity and outcomes of AKI. In conclusion, we identified several studies of promising biomarkers for the diagnosis, prediction and prognostication of AKI. However, we note several limitations, including small sample sizes, inadequate gold standard, exclusion of patients with chronic kidney disease, incomplete statistical analyses, utilization of research-based assays and a paucity of studies examining prediction for clinical outcomes. Future studies will need to address these limitations in order for further progress to be made.

Urinary Biomarkers of AKI and Mortality 3 Years after Cardiac Surgery

“…Most studies of urinary biomarkers have only focused on short-term outcomes. 3,4,6 Ralib et al Oliguria is defined as a patient who had ,125 ml or ,500 ml urine output in 6 or 24 hours, respectively. e Peak indicates the highest biomarker value through the third postoperative day.…”

“…Several urinary biomarkers of structural kidney injury have been investigated in human cohorts in an effort to identify AKI earlier, improve the diagnosis of AKI, and to aid in risk stratification. 3 It is largely unknown, however, whether kidney injury biomarkers associate with long-term outcomes, including mortality, and whether these biomarkers add useful prognostic information beyond the standard measure to detect AKI (e.g., peak change in serum creatinine). Some data suggest that "subclinical AKI," as evidenced by elevations in urinary kidney injury biomarkers in the absence of a rise in serum creatinine, associates with worse in-hospital clinical outcomes.…”

Acute Kidney Injury – An Underestimated Problem In Pediatric Intensive Care / Akûts Nieru Bojâjums — Nenovçrtçta Problçma Bçrnu Intensîvajâ Terapijâ

“…Serum Cystatin C levels show high correlation to established AKI and are used by some urologists as a marker of disease progression after kidney transplantation. Kidney injury molecule-1, interleukin-18, and liver fatty acid-binding protein have been shown to be associated with kidney ischemia (Parikh et al, 2010). Clinical studies indicate urinea nd serum neutrophil gelatinase-associated lipocalin (NGAL) as highly sensitive, specific, and predictive of AKI in many different disease processes (Williams et al, 2002).…”

Effects of Preterm Birth on the Kidney

“…As Rosner (2009) describes, it would be optimal if a biomarker could be developed to: 1) assess the response to, and any adverse effects of therapeutic interventions 2) indicate the severity of renal injury 3) inform on the etiology of the injury and 4) identify the location of injured cells. In a systematic review of the current literature, Parikh et al (2010) determined that the molecules with the most promise for the diagnosis of established AKI include interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), N-acetyl-beta-D-glucosaminidase (NAG) and neutrophil gelatinaseassociated lipocalin (NGAL). NGAL, IL-18, fatty acid binding protein (FABP), and cystatin-C are the most encouraging biomarkers for the early diagnosis of AKI, given that the upregulation of these molecules following injury onset precedes the rise in serum creatinine by many hours (Parikh et al, 2010).…”

“…In a systematic review of the current literature, Parikh et al (2010) determined that the molecules with the most promise for the diagnosis of established AKI include interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), N-acetyl-beta-D-glucosaminidase (NAG) and neutrophil gelatinaseassociated lipocalin (NGAL). NGAL, IL-18, fatty acid binding protein (FABP), and cystatin-C are the most encouraging biomarkers for the early diagnosis of AKI, given that the upregulation of these molecules following injury onset precedes the rise in serum creatinine by many hours (Parikh et al, 2010). In the preterm neonate, a small number of studies have been conducted for the assessment of urinary NGAL levels, with mixed results.…”