NGAL excretion is higher from the healthy side than from the injured side in unilateral acute kidney injury

Pedersen, Stine Søgaard; Keller, Anna Krarup; Rehling, Michael; Birn, Henrik; Jespersen, Bente

doi:10.3109/00365513.2012.692809

Cited by 4 publications

(4 citation statements)

References 12 publications

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“…To our knowledge, this pattern of NGAL expression has not previously been described, although Pedersen, et al . did find decreased urinary NGAL concentrations with increased length of ischemic time in a porcine model of unilateral renal ischemia 53 . These findings support the idea that NGAL expression may occur primarily in stressed but not highly injured proximal tubules and could help explain some of the inconsistency in NGAL prediction of subsequent AKI seen in recent multicenter clinical studies 15,21 .…”

Section: Discussionmentioning

confidence: 67%

“…Early in the course of ischemia/reperfusion injury NGAL renal expression increases, particularly in the proximal tubule as demonstrated by a series of experiments in rodents 50 . This increased expression leads to elevated urine and serum levels within an hour after CPB, although interpretation of measurements is complicated by alternative sources of NGAL (notably neutrophil production) as well as filtration and reabsorption of soluble NGAL 53 . While data concerning NGAL and AKI in porcine models of kidney ischemia-reperfusion are relatively rare, Goebel, et al .…”

Section: Discussionmentioning

confidence: 99%

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Alkaline Phosphatase Treatment of Acute Kidney Injury in an Infant Piglet Model of Cardiopulmonary Bypass with Deep Hypothermic Circulatory Arrest

Davidson

Khailová

Treece

et al. 2019

Sci Rep

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Acute kidney injury (AKI) is associated with prolonged hospitalization and mortality following infant cardiac surgery, but therapeutic options are limited. Alkaline phosphatase (AP) infusion reduced AKI in phase 2 sepsis trials but has not been evaluated for cardiac surgery-induced AKI. We developed a porcine model of infant cardiopulmonary bypass (CPB) with deep hypothermic circulatory arrest (DHCA) to investigate post-CPB/DHCA AKI, measure serum/renal tissue AP activity with escalating doses of AP infusion, and provide preliminary assessment of AP infusion for prevention of AKI. Infant pigs underwent CPB with DHCA followed by survival for 4 h. Groups were treated with escalating doses of bovine intestinal AP (1, 5, or 25U/kg/hr). Anesthesia controls were mechanically ventilated for 7 h without CPB. CPB/DHCA animals demonstrated histologic and biomarker evidence of AKI as well as decreased serum and renal tissue AP compared to anesthesia controls. Only high dose AP infusion significantly increased serum or renal tissue AP activity. Preliminary efficacy evaluation demonstrated a trend towards decreased AKI in the high dose AP group. The results of this dose-finding study indicate that AP infusion at the dose of 25U/kg/hr corrects serum and tissue AP deficiency and may prevent AKI in this piglet model of infant CPB/DHCA.

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Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Alkaline Phosphatase Treatment of Acute Kidney Injury in an Infant Piglet Model of Cardiopulmonary Bypass with Deep Hypothermic Circulatory Arrest

Davidson

Khailová

Treece

et al. 2019

Sci Rep

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“…NGAL is a 25-kDa molecule that is filtered into the primary urine at the glomerular level. In sepsis, serum levels of NGAL increase exponentially [34,35], even in the absence of AKI [36], which can result in increased urinary levels as well [37]. Once filtered, NGAL is reabsorbed by the tubular epithelium through the megalin receptor, and this through competitive binding [38].…”

Section: Discussionmentioning

confidence: 99%

“…Although a recent study indicated that urinary NGAL stems from local production in the thick ascending limb of the loop of Henle when stress factors are applied, evidence suggests that urinary NGAL can derive from the systemic circulation [37,39]. This indicates that the presence of NGAL in the urine in sepsis patients cannot automatically be considered as a marker of tubular damage per se .…”

Section: Discussionmentioning

confidence: 99%

Urinary output and fractional excretion of sodium and urea as indicators of transient versus intrinsic acute kidney injury during early sepsis

et al. 2013

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IntroductionThe pathophysiology of acute kidney injury (AKI) in sepsis is ill defined. We investigated parameters associated with low glomerular filtration, and their predictive value to discriminate transient from intrinsic septic AKI.MethodsIn 107 sepsis patients, AKI was defined by the Risk, Injury, Failure, Loss of Kidney Function, End-stage renal disease (RIFLE) urinary output or serum creatinine criterion, or both. Transient AKI (TAKI) versus intrinsic AKI was defined as RIFLE R, I, or F on the first day evolving to no AKI or not, respectively, over the following 5 days. Fractional excretion of sodium (FENa), urea (FEUrea), and NGAL (FENGAL) at admission (d0t0), 4 (d0t4), and 24 hours (d1) was determined.ResultsIncluding versus not including the urinary-output criterion of RIFLE increased AKI from 43% to 64.5%. Median uNGAL levels and FENGAL were lower in no AKI versus transient AKI when AKI was defined based on creatinine (P = 0.002 and P = 0.04, respectively), but not when based on urinary output (P = 0.9 and P = 0.49, respectively). FENa < 1% and FEUrea <35% was present in 77.3% and 63.2% of patients. Urinary NGAL was higher (P < 0.001) in those with high versus low fractional sodium excretion, but this was only in patients with transient or intrinsic AKI (P < 0.001 in subgroups), and not in patients without AKI. The negative predictive value for either intrinsic AKI or not restoring diuresis in patients with FENa > 0.36% and FEUrea > 31.5% was 92% and 94.5% respectively.ConclusionsA low FENa and FEUrea is highly prevalent in the first hours of sepsis. In sepsis, oliguria is an earlier sign of impending AKI than increase in serum creatinine. A combination of a high FENa and a low FEUrea is associated with intrinsic AKI, whereas a combined high FENa and FEUrea is strongly predictive of transient AKI.

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Con: Cautionary tales and reservations about the adoption of new technologies and biomarkers for the management of acute kidney injury

Biesen

2017

Nephrology Dialysis Transplantation

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Acute kidney injury (AKI) is an important health-care problem. Over the last decades, many innovative therapies and diagnostic approaches have been tried; however, none of these has been able to confirm consistently that they lead to improved outcomes. Much focus has been placed on intensive care unit (ICU)-associated AKI, whereas the bulk of AKI still concerns patients not in the ICU. Involvement of nephrologists in the care of AKI patients is necessary to further improve outcomes. It is unclear whether new technologies, such as biomarkers, are helpful and could replace nephrology consultation.

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NGAL excretion is higher from the healthy side than from the injured side in unilateral acute kidney injury

Cited by 4 publications

References 12 publications

Alkaline Phosphatase Treatment of Acute Kidney Injury in an Infant Piglet Model of Cardiopulmonary Bypass with Deep Hypothermic Circulatory Arrest

Alkaline Phosphatase Treatment of Acute Kidney Injury in an Infant Piglet Model of Cardiopulmonary Bypass with Deep Hypothermic Circulatory Arrest

Urinary output and fractional excretion of sodium and urea as indicators of transient versus intrinsic acute kidney injury during early sepsis

Con: Cautionary tales and reservations about the adoption of new technologies and biomarkers for the management of acute kidney injury

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