The Associations of Blood Kidney Injury Molecule-1 and Neutrophil Gelatinase–Associated Lipocalin with Progression from CKD to ESRD

Alderson, Helen; Ritchie, James; Pagano, Sabrina; Middleton, Rachel; Pruijm, Menno; Vuilleumier, Nicolas; Kalra, Philip A.

doi:10.2215/cjn.02670316

Cited by 42 publications

(44 citation statements)

References 33 publications

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“…1,2 Although a variety of novel urinary biomarkers of tubular injury, including neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and renal liver-type fatty acid binding protein, have been proposed to improve the accuracy of predicting the development of CKD, they have not been found to improve predictive models of CKD based on traditional laboratory tests in adults. 8,9 …”

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confidence: 99%

Association of Serum Soluble Urokinase Receptor Levels With Progression of Kidney Disease in Children

et al. 2017

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confidence: 99%

Association of Serum Soluble Urokinase Receptor Levels With Progression of Kidney Disease in Children

et al. 2017

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“…Renal weight, plasma creatinine, and urea were not statistically different between control and CML groups, in either WT or RAGE −/− mice (data not shown). We analyzed the expression of Kim‐1 and Ngal as sensitive markers of kidney injury associated with CKD progression in humans (Alderson et al, ): The expression of these genes was also unaffected by the CML‐rich diet (Supporting Information Figure a‐b).…”

Section: Resultsmentioning

confidence: 99%

Knockout of receptor for advanced glycation end‐products attenuates age‐related renal lesions

et al. 2019

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Pro‐aging effects of endogenous advanced glycation end‐products (AGEs) have been reported, and there is increasing interest in the pro‐inflammatory and ‐fibrotic effects of their binding to RAGE (the main AGE receptor). The role of dietary AGEs in aging remains ill‐defined, but the predominantly renal accumulation of dietary carboxymethyllysine (CML) suggests the kidneys may be particularly affected. We studied the impact of RAGE invalidation and a CML‐enriched diet on renal aging. Two‐month‐old male, wild‐type (WT) and RAGE−/− C57Bl/6 mice were fed a control or a CML‐enriched diet (200 μg CML/gfood) for 18 months. Compared to controls, we observed higher CML levels in the kidneys of both CML WT and CML RAGE−/− mice, with a predominantly tubular localization. The CML‐rich diet had no significant impact on the studied renal parameters, whereby only a trend to worsening glomerular sclerosis was detected. Irrespective of diet, RAGE−/− mice were significantly protected against nephrosclerosis lesions (hyalinosis, tubular atrophy, fibrosis and glomerular sclerosis) and renal senile apolipoprotein A‐II (ApoA‐II) amyloidosis (p < 0.001). A positive linear correlation between sclerosis score and ApoA‐II amyloidosis score (r = 0.92) was observed. Compared with old WT mice, old RAGE−/− mice exhibited lower expression of inflammation markers and activation of AKT, and greater expression of Sod2 and SIRT1. Overall, nephrosclerosis lesions and senile amyloidosis were significantly reduced in RAGE−/− mice, indicating a protective effect of RAGE deletion with respect to renal aging. This could be due to reduced inflammation and oxidative stress in RAGE−/− mice, suggesting RAGE is an important receptor in so‐called inflamm‐aging.

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“…Several reports of both blood and urine biomarkers have shown correlations with acute or chronic kidney injury in the general population . Proteins such as albumin, kidney injury molecule‐1, neutrophil gelatinase‐associated lipocalin, and β‐2 microglobulin, are associated with future GFR deterioration, but mainly in patients with abnormal baseline renal function.…”

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confidence: 99%

Discovery and Validation of a Biomarker Model (PRESERVE) Predictive of Renal Outcomes After Liver Transplantation

Levitsky¹,

Asrani

Klintmalm

et al. 2020

Hepatology

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BaCKgRoUND aND aIMS:A high proportion of patients develop chronic kidney disease (CKD) after liver transplantation (LT). We aimed to develop clinical/protein models to predict future glomerular filtration rate (GFR) deterioration in this population. appRoaCH aND ReSUltS: In independent multicenter discovery (CTOT14) and single-center validation (BUMC) cohorts, we analyzed kidney injury proteins in serum/plasma samples at month 3 after LT in recipients with preserved GFR who demonstrated subsequent GFR deterioration versus preservation by year 1 and year 5 in the BUMC cohort. In CTOT14, we also examined correlations between serial protein levels and GFR over the first year. A month 3 predictive model was constructed from clinical and protein level variables using the CTOT14 cohort (n = 60). Levels of β-2 microglobulin and CD40 antigen and presence of hepatitis C virus (HCV) infection predicted early (year 1) GFR deterioration (area under the curve [AUC], 0.814). We observed excellent validation of this model (AUC, 0.801) in the BUMC cohort (n = 50) who had both early and late (year 5) GFR deterioration. At an optimal threshold, the model had the following performance characteristics in CTOT14 and BUMC, respectively: accuracy (0.75, 0.8), sensitivity (0.71, 0.67), specificity (0.78, 0.88), positive predictive value (0.74, 0.75), and negative predictive value (0.76, 0.82). In the serial CTOT14 analysis, several proteins, including β-2 microglobulin and CD40, correlated with GFR changes over the first year. CoNClUSIoNS:We have validated a clinical/protein model (PRESERVE) that early after LT can predict future renal deterioration versus preservation with high accuracy. This model may help select recipients at higher risk for subsequent CKD for early, proactive renal sparing strategies. (Hepatology

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The Associations of Blood Kidney Injury Molecule-1 and Neutrophil Gelatinase–Associated Lipocalin with Progression from CKD to ESRD

Cited by 42 publications

References 33 publications

Association of Serum Soluble Urokinase Receptor Levels With Progression of Kidney Disease in Children

Association of Serum Soluble Urokinase Receptor Levels With Progression of Kidney Disease in Children

Knockout of receptor for advanced glycation end‐products attenuates age‐related renal lesions

Discovery and Validation of a Biomarker Model (PRESERVE) Predictive of Renal Outcomes After Liver Transplantation

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