BackgroundThe early prediction of acute kidney injury (AKI) by current clinical and laboratory methods remains inadequate. Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as a promisi...

https://journals.sagepub.com/doi/pdf/10.1177/0004563214521795

Neutrophil gelatinase-associated lipocalin as a biomarker of acute kidney injury: a critical evaluation of current status.

Acute kidney injury (AKI) is a common and serious condition, currently diagnosed by functional biomarkers, such as serum creatinine measurements. Unfortunately, creatinine increase is a delayed and unreliable indicator of AKI. The lack of early biomarkers of structural kidney injury has hampered our ability to translate promising experimental therapies to human AKI. The recent discovery, translation and validation of neutrophil gelatinase-associated lipocalin (NGAL), possibly the most promising novel AKI biomarker, is reviewed here. NGAL may be measured by several methods both in plasma and urine for the early diagnosis of AKI and for the prediction of clinical outcomes, such as dialysis requirement and mortality, in several common clinical scenarios, including in the intensive care unit, cardiac surgery and renal damage due the exposition to toxic agent and drugs, and renal transplantation. Furthermore, the predictive properties of NGAL, may play a critical role in expediting the drug development process. A systematic review of literature data indicates that further studies are necessary to establish accurate reference population values according to age, gender and ethnicity, as well as reliable and specific decisional values concerning the more common clinical settings related to AKI. Furthermore, proper randomized clinical trials on renal and systemic outcomes comparing the use of NGAL vs. standard clinical practice are still lacking and accurate cost-benefit and/or cost-utility analyses for NGAL as biomarker of AKI are also needed. However, it is important to note that NGAL, in the absence of diagnostic increases in serum creatinine, is able to detect some patients affected by subclinical AKI who have an increased risk of adverse outcomes. These results also suggest that the concept and definition of AKI might need to be reassessed.

/pdf/neutrophil-gelatinase-associated-lipocalin-ngal-as-biomarker-1rrdzzw6z3.pdf

Neutrophil gelatinase-associated lipocalin (NGAL) as biomarker of acute kidney injury: a review of the laboratory characteristics and clinical evidences.

The recognition that acute kidney injury (AKI) is a significant independent risk factor for morbidity and mortality has resulted in a substantial number of publications over the past 5 years or more. In no small part these have, to a degree, highlighted the inadequacy of conventional markers of renal insufficiency in the acute setting. Much effort has been invested in the identification of early, specific AKI markers in order to aid early diagnosis of AKI and hopefully improve outcome. The search for a 'biomarker' of AKI has seen early promise replaced by a degree of pessimism due to the lack of a clear candidate molecule and variability of results. We outline the major studies described to date as well as discuss potential reasons for the discrepancies observed and suggest that evolution of the field may result in success with ultimately an improvement in patient outcomes.

/pdf/clinical-review-biomarkers-of-acute-kidney-injury-where-are-3sqr6id372.pdf

Clinical review: Biomarkers of acute kidney injury: where are we now?

Neutrophil gelatinase associated lipocalin (NGAL) is a highly predictive biomarker of acute kidney injury. To understand the role of NGAL in renal injury during sepsis, we investigated the temporal changes and biological sources of NGAL in a rat model of acute kidney injury, and explored the relationship between renal inflammation, humoral NGAL and NGAL expression during endotoxemia. To induce acute renal injury, rats were treated with lipopolysaccharide (LPS, 3.5 mg/kg, ip), and the location of NGAL mRNA was evaluated by in situ hybridization. Quantitative RT-PCR was also used to determine the dynamic changes in NGAL, tumor necrosis factor α (TNFα) and interleukin (IL)-6 mRNA expression 1, 3, 6, 12, and 24 hours following LPS treatment. The correlation among NGAL, TNFα and IL-6 was analyzed. Urinary and plasma NGAL (u/pNGAL) levels were measured, and the relationship between humoral NGAL and NGAL expression in the kidney was investigated. Renal function was affected 3–12 hours after LPS. NGAL mRNA was significantly upregulated in tubular epithelia at the same time (P < 0.001). The course of NGAL mRNA upregulation occurred in parallel with renal damage. There was a transient increase in TNFα and IL-6 mRNA levels within 3 hours following LPS administration, and a strong correlation between TNFα and NGAL mRNA (r = 0.995, P <0.001) but not with IL-6 mRNA. Both pNGAL and uNGAL levels were markedly increased compared with those in the control group (P < 0.001); however, only uNGAL levels were correlated with NGAL mRNA (r = 0.850, P <0.001). NGAL upregulation is sensitive to LPS-induced renal TNFα increase and injury, which are observed in the tubular epithelia. Urinary NGAL levels accurately reflect changes in NGAL in the kidney.

/pdf/renal-neutrophil-gelatinase-associated-lipocalin-expression-3nodu0929p.pdf

Renal neutrophil gelatinase associated lipocalin expression in lipopolysaccharide-induced acute kidney injury in the rat

Purpose of reviewAcute kidney injury (AKI) in transplant recipients is a prevalent condition with a broad list of potential inciting causes. This review highlights recent data describing the epidemiology and long-term consequences of transplant AKI, novel interventions in the management of delayed g

Acute kidney injury in kidney transplantation.

BACKGROUND This prospective observational study aimed to assess the relevance of serial postoperative plasma neutrophil gelatinase-associated lipocalin (NGAL) measurements on prediction of early renal transplant function. METHODS Plasma NGAL (pNGAL) was measured (Triage NGAL Test; Biosite Inc., Inverness Medical) in 41 patients scheduled for kidney transplantation from deceased or living donors, immediately before and after surgery, and at 12 hr, day 1, day 3, and day 7. A delayed graft function (DGF) was defined as the need for dialysis during the first week. The results were expressed as median (Q1, Q3). RESULTS Of the 41 consecutive patients enrolled, all had a high preoperative pNGAL level: 453 ng/mL (382, 595). Fifteen (36.6%) presented a DGF. In patients with DGF, pNGAL was significantly higher at 12 hr (571 [467, 634] vs. 242 [158, 299] ng/mL, P<0.0001) and at day 1 (466 [356, 627] vs. 165 [91, 248] ng/mL, P<0.0001). A pNGAL higher than 400 ng/mL 12 hr after transplantation predicted DGF with a sensitivity of 93.3%, a specificity of 88.5%, and an odds ratio of 63.2 (P=0.0004). This predictive performance was higher than for plasma creatinine. CONCLUSIONS pNGAL level early and accurately predicted DGF after renal transplantation. pNGAL measurements allowed monitoring of the renal function in this striking situation of ischemia-reperfusion aggression. Early identification of patients at risk of DGF, before graft lesions are consolidated, opens the field of a precise monitoring of renal injury and the impact of future protective therapeutics.

Plasma neutrophil gelatinase-associated lipocalin in kidney transplantation and early renal function prediction.

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Plasma neutrophil gelatinase-associated lipocalin in kidney transplantation and early renal function prediction.