Urinary calprotectin, NGAL, and KIM-1 in the differentiation of primarily inflammatory vs. non-inflammatory stable chronic kidney diseases

Seibert, Felix S.; Sitz, Maximilian; Paßfall, J.; Haesner, Martin; Laschinski, Peter; Buhl, Martin; Bauer, Frederic; Rohn, Benjamin; Babel, Nina; Westhoff, Timm H.

doi:10.1080/0886022x.2021.1885442

Cited by 11 publications

(7 citation statements)

References 34 publications

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“…Plasma levels of Heat-shock protein (Hsp) 60 and 70 (TLR2 and TLR4 ligands) and Calprotectin can predict CV events in the general population ( 16 – 19 ). Notably, CKD-associated tissue injury results in TLR DAMPs production in the kidney ( 20 ), and elevated urinary DAMP levels may serve as biomarkers of kidney damage ( 21 – 23 ). Furthermore, elevated levels of circulating DAMPs including, Calprotectin ( 24 ), S100A12 ( 25 ) and mitochondrial DNA ( 26 ) were also reported in patients on hemodialysis.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic targeting of chronic kidney disease-associated DAMPs differentially contributing to vascular pathology

Mazzarino,

Cetin,

Bartosova

et al. 2023

Front. Immunol.

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Chronic Kidney Disease (CKD) is associated with markedly increased cardiovascular (CV) morbidity and mortality. Chronic inflammation, a hallmark of both CKD and CV diseases (CVD), is believed to drive this association. Pro-inflammatory endogenous TLR agonists, Damage-Associated Molecular Patterns (DAMPs), have been found elevated in CKD patients’ plasma and suggested to promote CVD, however, confirmation of their involvement, the underlying mechanism(s), the extent to which individual DAMPs contribute to vascular pathology in CKD and the evaluation of potential therapeutic strategies, have remained largely undescribed. A multi-TLR inhibitor, soluble TLR2, abrogated chronic vascular inflammatory responses and the increased aortic atherosclerosis-associated gene expression observed in nephropathic mice, without compromising infection clearance. Mechanistically, we confirmed elevation of 4 TLR DAMPs in CKD patients’ plasma, namely Hsp70, Hyaluronic acid, HMGB-1 and Calprotectin, which displayed different abilities to promote key cellular responses associated with vascular inflammation and progression of atherosclerosis in a TLR-dependent manner. These included loss of trans-endothelial resistance, enhanced monocyte migration, increased cytokine production, and foam cell formation by macrophages, the latter via cholesterol efflux inhibition. Calprotectin and Hsp70 most consistently affected these functions. Calprotectin was further elevated in CVD-diagnosed CKD patients and strongly correlated with the predictor of CV events CRP. In nephropathic mice, Calprotectin blockade robustly reduced vascular chronic inflammatory responses and pro-atherosclerotic gene expression in the blood and aorta. Taken together, these findings demonstrated the critical extent to which the DAMP-TLR pathway contributes to vascular inflammatory and atherogenic responses in CKD, revealed the mechanistic contribution of specific DAMPs and described two alternatives therapeutic approaches to reduce chronic vascular inflammation and lower CV pathology in CKD.

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Section: Introductionmentioning

confidence: 99%

Therapeutic targeting of chronic kidney disease-associated DAMPs differentially contributing to vascular pathology

Mazzarino,

Cetin,

Bartosova

et al. 2023

Front. Immunol.

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“…Like serotransferrin, hepcidin is an iron-binding protein, and its urine levels were recorded to increase in lupus nephritis [ 81 ]. Interestingly, the isoform hepcidin-25 was accounted as a prognostic marker for non-AKI outcomes in patients who went through cardiopulmonary bypass surgeries [ 82 ]. In our data, the candidate biomarker associated with the No-AKI group was calprotectin, a complex composed of the proteins S100-A8 (S100A8) and S100-A9 (S100A9).…”

Section: Discussionmentioning

confidence: 99%

“…This pro-inflammatory complex presents a mediator role in inflammation and the immune system and prevents exacerbated tissue damage by scavenging oxidants [ 46 , 47 ]. A decrease in urine calprotectin levels was observed in kidney sclerosis in an autoimmune disease setting [ 83 ], while increased levels were found in chronic kidney disease when compared to healthy controls [ 82 ]. Their abundance in the urine of No-AKI patients may suggest a protective role in Bothrops snakebite envenoming.…”

Section: Discussionmentioning

confidence: 99%

Urinary proteomics reveals biological processes related to acute kidney injury in Bothrops atrox envenomings

Brasileiro-Martins,

Cavalcante,

Nascimento

et al. 2024

PLoS Negl Trop Dis

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Acute kidney injury (AKI) is a critical systemic complication caused by Bothrops envenoming, a neglected health problem in the Brazilian Amazon. Understanding the underlying mechanisms leading to AKI is crucial for effectively mitigating the burden of this complication. This study aimed to characterize the urinary protein profile of Bothrops atrox snakebite victims who developed AKI. We analyzed three groups of samples collected on admission: healthy subjects (controls, n = 10), snakebite victims who developed AKI (AKI, n = 10), and those who did not evolve to AKI (No-AKI, n = 10). Using liquid-chromatography tandem mass spectrometry, we identified and quantified (label-free) 1190 proteins. A panel of 65 proteins was identified exclusively in the urine of snakebite victims, with 32 exclusives to the AKI condition. Proteins more abundant or exclusive in AKI’s urine were associated with acute phase response, endopeptidase inhibition, complement cascade, and inflammation. Notable proteins include serotransferrin, SERPINA-1, alpha-1B-glycoprotein, and NHL repeat-containing protein 3. Furthermore, evaluating previously reported biomarkers candidates for AKI and renal injury, we found retinol-binding protein, beta-2-microglobulin, cystatin-C, and hepcidin to be significant in cases of AKI induced by Bothrops envenoming. This work sheds light on physiological disturbances caused by Bothrops envenoming, highlighting potential biological processes contributing to AKI. Such insights may aid in better understanding and managing this life-threatening complication.

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“…More extensive studies on new biomarkers are needed for predicting the occurrence of CRS-1 as early as possible. Studies tried to use NGAL to differentiate between various types of stable CKD, but failed [ 27 ], whereas pNGAL was proved to be able to predict the AKI occurrence and outcome in ADHF, but the reliability of its predictive value remains controversial [ 6 , 28 ], and more investigations are still needed before its wide application in clinical practice. It is, therefore, necessary to explore more novel biomarkers.…”

Section: Discussionmentioning

confidence: 99%

Urine N-terminal pro-B-type natriuretic peptide and plasma proenkephalin are promising biomarkers for early diagnosis of cardiorenal syndrome type 1 in acute decompensated heart failure: a prospective, double-center, observational study in real-world

Zhao

et al. 2022

Renal Failure

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Background Patients with acute decompensated heart failure (ADHF) show cardiorenal syndrome type 1 (CRS-1) are more likely to have a poor outcome. However, the current criteria often lead to delayed CRS-1 diagnosis. Therefore, we evaluated the predictive value of plasma proenkephalin (pPENK) and urine NT-proBNP (uNT-proBNP) for early diagnosis of CRS-1 and vulnerable-phase prognosis in ADHF patients. Methods The plasma NT-proBNP (pNT-proBNP), pPENK, and uNT-proBNP were measured in 121 ADHF patients on admission. The plasma neutrophil gelatinase-associated lipocalin (pNGAL) was chosen as the reference. Logistic regression was used to determine the predictors of CRS-1. The area under the receiver operating curves (ROCs) was calculated to assess the early diagnostic value of pNGAL, pPENK, and uNT-proBNP/uCr for CRS-1. To evaluate the prognostic risk of factors for the 90-d outcomes of all ADHF patients, the Cox regression was performed and the cumulative risk curve was plotted. Results We found that pPENK [OR 1.093 (95% CI 1.022–1.169), p = 0.010; AUROC = 0.899 (95% CI 0.831–0.946)] and uNT-proBNP/uCr ratio [OR 1.015 (95% CI 1.003–1.028), p = 0.012; AUROC = 0.934 (95% CI 0.874–0.971)] could independently predict the occurrence of CRS-1 in hospitalized patients with ADHF. The pPENK [HR 1.014 (95% CI 1.000–1.042), p = 0.044] and uNT-proBNP/uCr ration [HR 0.998 (95% CI 0.997–1.000), p = 0.045] were also independent predictors of the risk of HF readmission or all-cause death 90 d after discharge in ADHF patients. Conclusions The newly found pPENK and noninvasive test of uNT-proBNP/uCr ratio (pg/nmol) on admission may be two promising novel predictive biomarkers for early diagnosis of CRS-1 occurrence and vulnerable-phase outcomes in ADHF patients.

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Urinary calprotectin, NGAL, and KIM-1 in the differentiation of primarily inflammatory vs. non-inflammatory stable chronic kidney diseases

Cited by 11 publications

References 34 publications

Therapeutic targeting of chronic kidney disease-associated DAMPs differentially contributing to vascular pathology

Therapeutic targeting of chronic kidney disease-associated DAMPs differentially contributing to vascular pathology

Urinary proteomics reveals biological processes related to acute kidney injury in Bothrops atrox envenomings

Urine N-terminal pro-B-type natriuretic peptide and plasma proenkephalin are promising biomarkers for early diagnosis of cardiorenal syndrome type 1 in acute decompensated heart failure: a prospective, double-center, observational study in real-world

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