Biomarkers in Progressive Chronic Kidney Disease. Still a Long Way to Go

Ntrinias, Theodoros; Papasotiriou, Marios; Balta, Lamprini; Kalavrizioti, Dimitra; Vamvakas, Sotirios; Papachristou, Evangelos; Goumenos, Dimitrios

doi:10.2478/prilozi-2020-0002

Cited by 24 publications

(26 citation statements)

References 98 publications

(108 reference statements)

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“…A prognostic marker for CKD has been explored for years. A large number of serum and urinary molecules such as NGAL, KIM-1, MCP-1, MMP-9, interleukin-18, clusterin, MMP-9, TIMP-1, Procollagen I alpha 1, FGF-23, suPAR, as well as PTX-2 are under investigation to predict CKD progression ( 8 , 9 ). All these biomarkers have been studied for predicting CKD progression in cohorts of patients with different stages of chronic kidney disease and with various etiologies (proteinuric and non-proteinuric glomerulonephritis, diabetic, hypertensive, and polycystic kidney diseases).…”

Section: Discussionmentioning

confidence: 99%

Pentraxin-2 is Associated with Renal Fibrosis in Patients Undergoing Renal Biopsy

Baştürk¹,

Ojalvo²,

Mazi³

et al. 2020

Clinics

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OBJECTIVES: Progressive renal disease is characterized by histological changes in the kidney and fibrosis is a common outcome. Renal biopsy is the only diagnostic tool to evaluate these histopathological changes. Pentraxin-2 (PTX-2) is an anti-inflammatory constitutive plasma protein associated with the innate immune system. Recently, as a biomarker, the circulating level of PTX-2 is shown to be decreased in chronic fibrotic diseases. In this study, we aimed to investigate the relationship between renal fibrosis severity and serum PTX-2 levels in patients undergoing renal biopsy. METHODS: This cross-sectional study included 45 patients and 16 healthy individuals (HIs). The severity of renal fibrosis was evaluated according to the Banff and Sethi scoring systems by the same pathologist. PTX-2 was measured by an enzyme-linked immunosorbent assay and compared with the demographical, clinical, biochemical, and histopathological data of the patients and HIs. RESULTS: PTX-2 levels were lower in the biopsy group than in the HI group ( p =0.12). Patients with moderate renal fibrosis had significantly lower serum PTX-2 levels than those in patients with minimal and mild fibrosis ( p =0.017 and p =0.010, respectively). PTX-2 concentrations were correlated with serum albumin (r=0.30, p =0.016), and were negatively correlated with serum creatinine levels (rho=-0.42, p =0.01) and body mass index (r=-0.32, p =0.011). CONCLUSIONS: The results indicated that PTX-2 levels are significantly lower in patients with renal fibrosis than HIs, and declining further in patients with severe fibrosis.

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Section: Discussionmentioning

confidence: 99%

Pentraxin-2 is Associated with Renal Fibrosis in Patients Undergoing Renal Biopsy

Baştürk¹,

Ojalvo²,

Mazi³

et al. 2020

Clinics

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“…20 However, once renal filtration reserve is lost, additional renal insults result in further decreases in glomerular filtration and subsequent increases in serum creatinine, limiting the utility of tubular injury biomarkers in patients with diminished renal reserve. 21 Numerous studies have explored whether the recent AKI biomarkers (especially kidney injury molecule 1 [KIM-1] and neutrophil gelatinase-associated lipocalin [NGAL]) could improve upon eGFR and UACR for predicting outcomes in CKD patients (reviewed in the studies [21][22][23][24][25][26][27][28][29][30][31][32] ). Even though many studies have linked KIM-1 and NGAL to deterioration of renal function, there is conflicting evidence that use of KIM-1 or NGAL improves upon risk assessment beyond the standard renal biomarkers.…”

Section: Introductionmentioning

confidence: 99%

“…Even though many studies have linked KIM-1 and NGAL to deterioration of renal function, there is conflicting evidence that use of KIM-1 or NGAL improves upon risk assessment beyond the standard renal biomarkers. 21,22,25 One possibility is that tubular injury biomarkers may have limited utility in patients with diminished renal reserve because of nephron loss. 29 Chronic kidney disease is not a discrete disease entity but rather the common result of diverse disease processes that can occur simultaneously, and it is unlikely that one biomarker will capture all processes.…”

Section: Introductionmentioning

confidence: 99%

“…29 Chronic kidney disease is not a discrete disease entity but rather the common result of diverse disease processes that can occur simultaneously, and it is unlikely that one biomarker will capture all processes. 25 Instead, biomarker panels or disease-specific biomarkers may provide better prognostic utility for CKD. 30,31 In the future, the use of urinary biomarkers in CKD may involve a more personalized medicine approach, for example, by targeting patients undergoing therapy for renal fibrosis prevention or by identifying AKI patients with preserved kidney function who are at risk of progression to CKD.…”

Section: Introductionmentioning

confidence: 99%

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A Review of Specific Biomarkers of Chronic Renal Injury and Their Potential Application in Nonclinical Safety Assessment Studies

et al. 2021

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A host of novel renal biomarkers have been developed over the past few decades which have enhanced monitoring of renal disease and drug-induced kidney injury in both preclinical studies and in humans. Since chronic kidney disease (CKD) and acute kidney injury (AKI) share similar underlying mechanisms and the tubulointerstitial compartment has a functional role in the progression of CKD, urinary biomarkers of AKI may provide predictive information in chronic renal disease. Numerous studies have explored whether the recent AKI biomarkers could improve upon the standard clinical biomarkers, estimated glomerular filtration rate (eGFR), and urinary albumin to creatinine ratio, for predicting outcomes in CKD patients. This review is an introduction to alternative assays that can be utilized in chronic (>3 months duration) nonclinical safety studies to provide information on renal dysfunction and to demonstrate specific situations where these assays could be utilized in nonclinical drug development. Novel biomarkers such as symmetrical dimethyl arginine, dickkopf homolog 3, and cystatin C predict chronic renal injury in animals, act as surrogates for GFR, and may predict changes in GFR in patients over time, ultimately providing a bridge from preclinical to clinical renal monitoring.

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“…First identi ed in 1993 and puri ed from neutrophil granules [11], the neutrophil gelatinase-associated lipocalin (NGAL) is a promising marker for acute kidney injury (AKI) and kidney disease [12]. NGAL is a 25 kDa protein that belongs to the lipocalin superfamily and is encoded by the LCN2 gene.…”

Section: Introductionmentioning

confidence: 99%

Association of significantly elevated serum levels of NGAL and IGFBP4 in patients with diabetic nephropathy

Ali

Abu‐Farha

Alshawaf

et al. 2021

Preprint

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Background: Diabetic nephropathy (DN) is a kidney-related complication affecting approximately 40% of patients with diabetes. Current DN diagnostic criteria predominantly rely on albuminuria and serum creatinine levels; however, the specificity and reliability of both markers are limited. Hence, reliable biomarkers are required to diagnose and effectively manage DN progression. Methods: Here we investigated the expression level and the association between neutrophil gelatinase-associated lipocalin (NGAL), IGFBP-1, IGFBP-3, and IGFBP-4 in patients with DN and compared it to patients with T2D and control participants. A cohort comprise of 159 individuals (DN = 67) was clinically evaluated and circulatory levels of NGAL, IGFBP1, IGFBP3, and IGFBP4 were determined using ELISA. Results: Levels of circulating NGAL were significantly higher in people with DN compared to people with T2D and non-diabetic groups (92.76 ± 7.5, 57.22 ± 8.7, and 52.47 ± 2.9 mg/L, respectively; p < 0.0001). IGFBP4 showed a similar pattern, where it was highest in people with DN (795.61 ng/ml ±130.7) compared to people with T2D and non-diabetic respectively (374.56 ng/ml ±86.8, 273.06 ng/ml ±27.8, ANOVA p<0.01). Our analysis presents a significant positive correlation between NGAL and IGFBP4 in people with DN (ρ =.620, p <0.005). IGFBP4 also correlated positively with creatinine level and negatively with eGFR, in people with DN supporting its involvement in DN. Conclusion: Our results report the association between the rise in NGAL and IGFBP4 levels in DN and suggest them as potential markers to aid DN diagnosis.

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Biomarkers in Progressive Chronic Kidney Disease. Still a Long Way to Go

Cited by 24 publications

References 98 publications

Pentraxin-2 is Associated with Renal Fibrosis in Patients Undergoing Renal Biopsy

Pentraxin-2 is Associated with Renal Fibrosis in Patients Undergoing Renal Biopsy

A Review of Specific Biomarkers of Chronic Renal Injury and Their Potential Application in Nonclinical Safety Assessment Studies

Association of significantly elevated serum levels of NGAL and IGFBP4 in patients with diabetic nephropathy

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