Urinary Cystatin C and NGAL as Early Biomarkers for Assessment of Renal Ischemia-Reperfusion Injury: A Serum Marker to Replace Creatinine?

Woodson, Benjamin; Wang, Liang; Mandava, Sree Harsha; Lee, Benjamin R.

doi:10.1089/end.2013.0198

Cited by 20 publications

(14 citation statements)

References 15 publications

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“…[16][17][18] Increased expression of these biomarkers was observed in our experiments, and KIM-1 was significantly elevated after IRI compared to off-clamp PN. This biomarker has been proven to be more sensitive than serum creatinine for AKI diagnosis and it may be a better method of evaluating renal function in the setting of IRI.…”

Section: Discussionsupporting

confidence: 70%

A novel approach to off-clamp partial nephrectomy demonstrates significant improvements in renal injury in an experimental porcine model

Olvera‐Posada

Lin

Aboalsamh

et al. 2017

CUAJ

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Introduction: We sought to design a partial nephrectomy (PN) with contralateral total nephrectomy porcine model and assess the underlying mechanisms of ischemia reperfusion injury (IRI) after PN using a novel, clinically approved resection device. Methods: Domestic male pigs (n=9) underwent left lower pole PN, allocated to either standard (Group 1) or no ischemia PN (Group 2), followed by contralateral nephrectomy. Biochemical studies were performed at baseline, Day 2, and Day 7; after sacrifice, kidneys were processed for histological analysis. Apoptotic markers were measured by Western blot analyses. Urinary biomarkers were measured to assess acute kidney injury. Results: At Day 2 following PN, there was a significant rise in serum creatinine in Group 1 compared to Group 2 (355 vs. 136 mmol/L; p=0.008). Intra-renal tissue oxygen saturation after PN was inversely correlated with postoperative creatinine (r s -0.75; p=0.012) and the grade of acute tubular necrosis (r s -0.70; p=0.036). We observed a rise in expression of pro-apoptotic markers and pro-inflammatory markers in Group 1 following PN compared to Group 2. Histological analysis revealed higher grade of apoptosis in Group 1. Conclusions: IRI associated with standard PN has a deleterious impact on acute renal function, markers of tissue injury, and histological parameters, compared to off-clamp PN using the ALTRUS device. We identified several intraoperative and postoperative markers that may be used as predictors for functional and histological injury following PN.

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Section: Discussionsupporting

confidence: 70%

A novel approach to off-clamp partial nephrectomy demonstrates significant improvements in renal injury in an experimental porcine model

Olvera‐Posada

Lin

Aboalsamh

et al. 2017

CUAJ

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“…To date, there have been no objective clinical predictors for quantifying the degree of AKI and long-term renal function; until recently, NGAL has been reported as a useful marker for the early identification of ischemic and/or tubular damage [ 10 , 17 – 22 ]. However, not many human studies have documented the efficacy of NGAL in quantifying AKI following PN in patients with normal contralateral kidney.…”

Section: Discussionmentioning

confidence: 99%

Accuracy of Urinary Neutrophil Gelatinase-Associated Lipocalin in Quantifying Acute Kidney Injury after Partial Nephrectomy in Patients with Normal Contralateral Kidney

et al. 2015

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BackgroundTo evaluate the efficacy of urinary neutrophil gelatinase-associated lipocalin (uNGAL) for predicting the degree of acute kidney injury (AKI) in patients following partial nephrectomy (PN).MethodsThis prospective study included 176 patients who underwent open or laparoscopic PN for solid renal tumors between June 2013 and May 2014. Urine samples were collected preoperatively and at 3, 24, and 48 h after renal pedicle clamp removal. Changes in uNGAL levels were analyzed for all patients and between subgroups that were dichotomized based on preoperative eGFR values of <60 and ≥60 mL/min/1.73m2, open and laparoscopic surgery, and according to the onset of AKI. Linear mixed models were used to investigate preoperative and perioperative features associated with postoperative uNGAL and eGFR changes at 6 months postoperatively.ResultsAmong 146 patients included in the final analysis, 10 (6.8%) patients had preoperative eGFR <60 mL/min/1.73m2. In the overall group, uNGAL levels increased following PN. However, all subgroups demonstrated comparable changes in uNGAL levels over time. Multivariate analyses failed to reveal any correctable clinical features associated with postoperative uNGAL changes, whereas preoperative serum creatinine levels and the onset of AKI correlated with eGFR at 6 months postoperatively.ConclusionsuNGAL levels may increase following PN. However, it does not appear to be a useful marker for quantifying the degree of AKI or predicting postoperative renal function in patients with normal contralateral kidney and relatively good preoperative renal function. Further analysis is necessary to assess the usefulness of uNGAL in patients with poor preoperative renal function.

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“…Song et al [32] found that RIPC produced by 3 cycles of intestinal brief ischemia protected against renal IRI in a rat model. Novel biomarkers (such as NGAL and cystatin C) have been proposed as early indicators of an upcoming renal failure [33]. NGAL is a protein belonging to the lipocalin superfamily initially found in activated neutrophils in accordance with its role as an innate antibacterial factor [34].…”

Section: Discussionmentioning

confidence: 99%

“…In a meta-analysis of diagnostic test studies, Haase et al [35] concluded that the NGAL level appears to be of diagnostic and prognostic value for acute kidney injury. Recently, Woodson et al [33] suggested that NGAL with cystatin C can be used as early biomarkers for the assessment of renal IRI in rats. In our model there is evidence that the RIPC II protocol has a better protective effect on IRI as NGAL serum levels were significantly lower than in RIPC I.…”

Section: Discussionmentioning

confidence: 99%

“…It is produced by karyocytes, freely filtered by the glomerulus, and reabsorbed and catabolized in the tubules [36]. Cystatin C is a potential precise marker for renal ischemic injury [33]. Recently, urinary cystatin C was described as an early biomarker of acute kidney injury after open and endovascular abdominal aortic aneurysm repair in humans [37].…”

Section: Discussionmentioning

confidence: 99%

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Remote Ischemic Preconditioning May Attenuate Renal Ischemia-Reperfusion Injury in a Porcine Model of Supraceliac Aortic Cross-Clamping

Athanasiadis

Kapelouzou²,

Martikos³

et al. 2015

J Vasc Res

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Aim: The effect of remote ischemic preconditioning (RIPC) in decreasing renal ischemia-reperfusion injury (IRI) during a suprarenal aortic cross-clamping was examined in a swine model. Materials and Methods: Four groups of pigs were examined: (a) ischemia-reperfusion (IR) group, renal IRI produced by 30 min of supraceliac aortic cross-clamping; (b) RIPC I group, the same renal IRI following RIPC by brief occlusion of the infrarenal aorta (15 min ischemia and 15 min reperfusion); (c) RIPC II group, the same renal IRI following RIPC by brief occlusion of the infrarenal aorta (3 cycles of 5 min ischemia and 5 min reperfusion); (d) sham group. Renal function was assessed before and after IRI by examining creatinine, neutrophil gelatinase-associated lipocalin (NGAL), TNF-α, malondialdehyde (MDA), cystatin C and C-reactive protein (CRP) from renal vein blood samples at specific time intervals. Results: Both RIPC groups presented significantly less impaired results compared to the IR group when considering MDA, cystatin C, CRP and creatinine. Between the two RIPC groups, RIPC II presented a better response with regard to CRP, NGAL, TNF-α, MDA and cystatin C. Conclusions: Remote IR protocols and mainly repetitive short periods of cycles of IR ameliorate the biochemical kidney effects of IRI in a model of suprarenal aortic aneurysm repair.

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Urinary Cystatin C and NGAL as Early Biomarkers for Assessment of Renal Ischemia-Reperfusion Injury: A Serum Marker to Replace Creatinine?

Abstract: Cystatin C and NGAL both appear to be useful biomarkers of renal injury. Studies with larger numbers are needed, however. Also, allopurinol does exhibit renoprotective effects against ischemic injury.

Cited by 20 publications

References 15 publications

A novel approach to off-clamp partial nephrectomy demonstrates significant improvements in renal injury in an experimental porcine model

A novel approach to off-clamp partial nephrectomy demonstrates significant improvements in renal injury in an experimental porcine model

Accuracy of Urinary Neutrophil Gelatinase-Associated Lipocalin in Quantifying Acute Kidney Injury after Partial Nephrectomy in Patients with Normal Contralateral Kidney

Remote Ischemic Preconditioning May Attenuate Renal Ischemia-Reperfusion Injury in a Porcine Model of Supraceliac Aortic Cross-Clamping

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