Neutrophil gelatinase‐associated lipocalin in dogs with chronic kidney disease, carcinoma, lymphoma and endotoxaemia

Cobrin, A. R.; Blois, Shauna L.; Abrams‐Ogg, Anthony; Kruth, Stephen A.; Dewey, Cate; Holowaychuk, Marie K.; Gauthier, Vincent

doi:10.1111/jsap.12481

Cited by 12 publications

(13 citation statements)

References 55 publications

(95 reference statements)

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“…In a prospective longitudinal study of 15 dogs with sepsis, of the 9 dogs with uNGALC above the upper limit only 2 developed AKI and none developed azotemia; the study was not able to conclude whether the increase in uNGALC was caused by subclinical AKI or to the septic process . Increments in serum and urine NGAL also were reported in dogs with neoplasia and endotoxemia, challenging its specificity as a marker of AKI only . Our results also highlight the strong influence of the inflammatory response on uNGAL results, pointing out that this biomarker must be interpreted carefully in critically ill dogs with systemic inflammation.…”

Section: Discussionmentioning

confidence: 99%

Urine neutrophil gelatinase‐associated lipocalin to diagnose and characterize acute kidney injury in dogs

Monari

Troìa

Magna

et al. 2019

Veterinary Internal Medicne

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Background: Urine neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker of acute kidney injury (AKI) in dogs.Objectives: To evaluate the utility of urinary NGAL for characterizing AKI according to volume responsiveness, presence of inflammation and sepsis, and prognosis.Animals: Dogs with AKI (n = 76) and healthy controls (n = 10).Methods: Prospective study. Clinical and clinicopathologic data including absolute urine NGAL concentration (uNGAL) and NGAL normalized to urine creatinine concentration (uNGALC) were measured upon admission. Dogs were graded according to International Renal Interest Society (IRIS) AKI guidelines and compared based on AKI features: volume-responsive (VR-) AKI vs. intrinsic (I-) AKI based on IRIS criteria; VR-AKI and I-AKI based on urine chemistry; inflammatory versus noninflammatory; septic versus nonseptic; and survivors versus nonsurvivors. Nonparametric statistics were calculated, and significance set at P < .05.Results: Urinary NGAL was significantly higher in dogs with AKI compared to controls, regardless of AKI grade. Urinary NGAL did not differ between dogs with VR-AKI and I-AKI based on IRIS criteria, whereas higher uNGALC was recorded in dogs with I-AKI based on urine chemistry. Urinary NGAL was significantly higher in dogs with inflammatory AKI, whereas no difference with respect to sepsis or outcome was identified.Conclusions and Clinical Importance: Urinary NGAL is a sensitive marker for AKI in dogs, but its specificity is affected by systemic inflammation. Increased urinary NGAL in both I-AKI and VR-AKI also suggests the presence of tubular damage in transient AKI.Combining urine chemistry data with IRIS criteria could facilitate AKI characterization in dogs. K E Y W O R D Sintrinsic AKI, systemic inflammation, tubular damage, urine chemistry, volume-responsive AKI Abbreviations: AKI, acute kidney injury; CKD, chronic kidney disease; FENa, fractional excretion of sodium; I-AKI, intrinsic acute kidney injury; ICU, intensive care unit; IRIS, International Renal Interest Society; MAT, microagglutination test; NGAL, neutrophil gelatinase-associated lipocalin; sCr, serum creatinine concentration; sCRP, serum C-reactive protein concentration; uCr, urine creatinine concentration; uCr/sCr, urine creatinine to serum creatinine ratio; uNa, urine sodium concentration; uNGAL, urine neutrophil gelatinase-associated lipocalin concentration; uNGALC, urine neutrophil gelatinase-associated lipocalin to urine creatinine ratio; UO, urinary output; VR-AKI, volume-responsive acute kidney injury; VUH, veterinary university hospital; WBC, white blood cell.

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Section: Discussionmentioning

confidence: 99%

Urine neutrophil gelatinase‐associated lipocalin to diagnose and characterize acute kidney injury in dogs

Monari

Troìa

Magna

et al. 2019

Veterinary Internal Medicne

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“…These findings indirectly demonstrate that the feline monomer uNGAL seems to originate from the kidneys, and feline dimeric uNGAL appears to originate from inflammation of lower urinary tract. Increased uNGAL has been reported to be associated with neoplasia and endotoxaemia [13]. In this study, monomeric NGAL is the predominant molecular form in the urine of the cats that form the non-RP group (data not shown).…”

Section: Discussionmentioning

confidence: 54%

“…In veterinary medicine, NGAL has been proved to be a novel and promising biomarker. An increased level of NGAL in dogs has been found to be associated with various different urinary diseases [5, 10–13]. Among cats with naturally occurring kidney diseases, urine NGAL (uNGAL) levels and the urine NGAL to creatinine ratio (UNCR) are thought to be a useful biomarkers when detecting chronic renal damage and when predicting the clinical progression of cats with CKD [14].…”

Section: Introductionmentioning

confidence: 99%

Identification of urine neutrophil gelatinase-associated lipocalin molecular forms and their association with different urinary diseases in cats

Hsu

Tsai

et al. 2019

BMC Vet Res

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Background Neutrophil gelatinase-associated lipocalin (NGAL), a promising renal biomarker, can exists as a monomer, a dimer and/or in a NGAL/matrix metalloproteinase-9 (MMP-9) complex form when associated with different urinary diseases in humans and dogs. In this study, the presence of the various different molecular forms of NGAL in cat urine (uNGAL) was examined and whether these forms are correlated with different urinary diseases was explored. Results One hundred and fifty-nine urine samples from cats with various different diseases, including acute kidney injury (AKI, 22 cats), chronic kidney disease (CKD, 55 cats), pyuria (44 cats) and other non-renal and non-pyuria diseases (non-RP, 26 cats), as well as healthy animals (12 cats), were collected. The molecular forms of and concentrations of urinary NGAL in these cats were analyzed, and their uNGAL-to-creatinine ratio (UNCR) were determined. The cats with AKI had the highest UNCR (median: 2.92 × 10 − 6 ), which was followed by pyuria (median: 1.43 × 10 − 6 ) and CKD (median: 0.56 × 10 − 6 ); all of the above were significantly higher than the healthy controls (median: 0.17 × 10 − 6 ) ( p < 0.05). Three different NGAL molecular forms as well as the MMP-9 monomer were able to be detected in the cat urine samples. Moreover, the cases where urine NGAL monomer were present also had significantly higher levels of BUN (median: 18.9 vs 9.6 mmol/L) and creatinine (327.1 vs 168 umol/L). The presence of dimeric NGAL was found to be associated with urinary tract infections. Most cats in the present study (126/159, 79.2%) and more than half of healthy cats (7/12, 58.3%) had detectable NGAL/MMP-9 complex present in their urine. Conclusions The monomeric and dimeric molecular forms of uNGAL suggest upper and lower urinary tract origins of disease, respectively, whereas the presence of the uNGAL/MMP-9 complex is able to be detected in most cats, including seemingly healthy ones.

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“…rossi-infected dogs. Why NGAL appears to be more specific for kidney injury in the current study compared to other studies (Cortellini et al, 2015;Cobrin et al, 2016), may be explained by the fact that all dogs in our study were infected with the same organism which causes a disease in which neutrophilia is uncommon (Scheepers et al, 2011), thus reducing the impact of NGAL originating from circulating neutrophils (Mårtensson and Bellomo, 2014).…”

Section: Discussionmentioning

confidence: 55%

“…In a previous study, uNGAL was also increased in dogs with AKI Grade I, showing its potential as a sensitive biomarker of milder forms of AKI (Segev et al, 2013). However, in human medicine (Mårtensson and Bellomo, 2014) and more recently also in veterinary medicine (Cortellini et al, 2015;Cobrin et al, 2016), the specificity of NGAL for AKI has been questioned. It is important to realize that competition for tubular reabsorption between NGAL and other filtered proteins could result in increased uNGAL and u/pNGAL 10 ratio as well, independent of the presence of tubular injury (Nejat et al, 2012).…”

Section: Discussionmentioning

confidence: 97%

Evaluation of acute kidney injury in dogs with complicated or uncomplicated Babesia rossi infection

Defauw

Schoeman

Leisewitz

et al. 2020

Ticks and Tick-borne Diseases

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Dogs with babesiosis can present with multiple complications, including acute kidney injury (AKI). The objective of this study was to characterize AKI in dogs with babesiosis caused by Babesia rossi at presentation and after treatment. Thirty-five client-owned dogs with B. rossi infection and 10 control dogs were included in this prospective observational study. Blood and urine were collected in Babesiainfected dogs at presentation (T0, n=35), after 24 hours (T24h, n=11), and after 1 month (T1m, n=9). The following urinary kidney injury biomarkers were assessed: urinary protein to creatinine ratio (UPC), urinary glomerular injury biomarkers (immunoglobulin G (uIgG) and C-reactive protein (uCRP)), and urinary tubular injury biomarkers (retinol-binding protein (uRBP) and neutrophil gelatinase-associated lipocalin (uNGAL)). Serum functional renal biomarkers were creatinine (sCr) and symmetric dimethylarginine (sSDMA). Post-mortem kidney biopsies were analyzed by light and transmission electron microscopy. At T0, all kidney injury biomarkers were significantly higher in Babesia-infected dogs compared to healthy controls (P<0.001), while functional renal biomarkers were not significantly different (P>0.05). At T24h, all urinary tubular injury biomarkers and UPC decreased significantly (P<0.01), while glomerular injury biomarkers did not (P=0.084). At T1m, all urinary kidney injury biomarkers decreased to values not significantly different from healthy controls (P>0.5). Significant changes in functional renal biomarkers were not seen after treatment (P>0.05). Dogs with complicated babesiosis had significantly higher glomerular injury biomarkers, UPC, and sSDMA compared to uncomplicated cases (P<0.05), while all tubular injury biomarkers and sCr were not significantly different (P>0.1). Dogs with babesiosis caused by B. rossi showed transient kidney injury, which was detected by all kidney injury biomarkers, but remained undetected by functional biomarkers. All infected dogs, irrespective of disease severity, suffered comparable kidney injury based on tubular injury biomarker concentrations, while loss of function was seen more often in dogs with complicated babesiosis based on sSDMA results.

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Neutrophil gelatinase‐associated lipocalin in dogs with chronic kidney disease, carcinoma, lymphoma and endotoxaemia

Abstract: NGAL can be elevated by chronic kidney disease and neoplasia, compared with healthy controls. Further research is needed to determine if uNGAL or uNGAL-to-creatinine ratio is more specific than serum levels to detect chronic kidney disease.

Cited by 12 publications

References 55 publications

Urine neutrophil gelatinase‐associated lipocalin to diagnose and characterize acute kidney injury in dogs

Urine neutrophil gelatinase‐associated lipocalin to diagnose and characterize acute kidney injury in dogs

Identification of urine neutrophil gelatinase-associated lipocalin molecular forms and their association with different urinary diseases in cats

Evaluation of acute kidney injury in dogs with complicated or uncomplicated Babesia rossi infection

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