Synthesizing Markers of Kidney Injury in Acute Decompensated Heart Failure: Should We Even Keep Looking?

Manguba, A; Parada, Xavier Vela; Coca, Steven G.

doi:10.1007/s11897-019-00448-9

Cited by 5 publications

(6 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus far, research into candidate protein biomarkers in the specific context of AKI following ADHF has produced mixed and inconclusive results, in part due to the complex and potentially confounding factors inherent in observational patient cohorts [19]. A strength of the present study is the elimination of confounding factors such as age, gender, ethnicity, comorbidities, and decongestive therapy through the use of an established ovine model of ADHF [52,53].…”

Section: Discussionmentioning

confidence: 98%

“…While the utility of TIMP-2, IGFPB7, and L-FABP for the prediction of AKI within 1-7 days of ADHF onset has been investigated [13][14][15][16][17], no markers have sufficient sensitivity and specificity for routine clinical use, with several studies presenting mixed and inconclusive results [19]. This is in part due to variations in methodologies, heterogeneous study populations and clinical settings, and the lack of universal definitions of kidney impairment employed in research [19]. Consequently, the current body of evidence for the prognostic and diagnostic utility of various protein biomarkers for kidney injury in ADHF is insufficient to support their routine clinical use [19].…”

Section: Introductionmentioning

confidence: 99%

“…This is in part due to variations in methodologies, heterogeneous study populations and clinical settings, and the lack of universal definitions of kidney impairment employed in research [19]. Consequently, the current body of evidence for the prognostic and diagnostic utility of various protein biomarkers for kidney injury in ADHF is insufficient to support their routine clinical use [19].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Identifying Candidate Protein Markers of Acute Kidney Injury in Acute Decompensated Heart Failure

Templeton

Lassé

Kleffmann

et al. 2022

IJMS

View full text Add to dashboard Cite

One-quarter of patients with acute decompensated heart failure (ADHF) experience acute kidney injury (AKI)—an abrupt reduction or loss of kidney function associated with increased long-term mortality. There is a critical need to identify early and real-time markers of AKI in ADHF; however, to date, no protein biomarkers have exhibited sufficient diagnostic or prognostic performance for widespread clinical uptake. We aimed to identify novel protein biomarkers of AKI associated with ADHF by quantifying changes in protein abundance in the kidneys that occur during ADHF development and recovery in an ovine model. Relative quantitative protein profiling was performed using sequential window acquisition of all theoretical fragment ion spectra–mass spectrometry (SWATH–MS) in kidney cortices from control sheep (n = 5), sheep with established rapid-pacing-induced ADHF (n = 8), and sheep after ~4 weeks recovery from ADHF (n = 7). Of the 790 proteins quantified, we identified 17 candidate kidney injury markers in ADHF, 1 potential kidney marker of ADHF recovery, and 2 potential markers of long-term renal impairment (differential abundance between groups of 1.2–2.6-fold, adjusted p < 0.05). Among these 20 candidate protein markers of kidney injury were 6 candidates supported by existing evidence and 14 novel candidates not previously implicated in AKI. Proteins of differential abundance were enriched in pro-inflammatory signalling pathways: glycoprotein VI (activated during ADHF development; adjusted p < 0.01) and acute phase response (repressed during recovery from ADHF; adjusted p < 0.01). New biomarkers for the early detection of AKI in ADHF may help us to evaluate effective treatment strategies to prevent mortality and improve outcomes for patients.

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Identifying Candidate Protein Markers of Acute Kidney Injury in Acute Decompensated Heart Failure

Templeton

Lassé

Kleffmann

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…Deterioration of kidney function is frequently recognised by the rise of serum creatinine levels or by the decline of glomerular filtration rate (GFR). However, creatinine levels can also be influenced by several factors such as advanced age, sex, excessive protein intake, muscle mass, medication, or intense exercise ( 9 ). Nowadays, early changes in other molecular components have been suggested including kidney injury molecule 1 (KIM-1), Cystatin C (CysC), or neutrophil gelatinase-associated lipocalin (NGAL) ( 10 – 13 ), but their usefulness for detecting early pathological changes is controversial, and their value has not been consistently proven ( 14 , 15 ).…”

Section: Introductionmentioning

confidence: 99%

Vitamin D Binding Protein and Renal Injury in Acute Decompensated Heart Failure

Diaz-Riera

García-Arguinzonis

López

et al. 2022

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

BackgroundRenal function in acute decompensated heart faiulre (ADHF) is a strong predictor of disease evolution and poor outcome. Current biomarkers for early diagnostic of renal injury in the setting of ADHF are still controversial, and their association to early pathological changes needs to be established. By applying a proteomic approach, we aimed to identify early changes in the differential urine protein signature associated with development of renal injury in patients hospitalised due to ADHF.Materials and MethodsPatients (71 [64–77] years old) admitted at the emergency room with ADHF and hospitalised were investigated (N = 64). Samples (urine/serum) were collected at hospital admission (day 0) and 72 h later (day 3). Differential serum proteome was analysed by two-dimensional electrophoresis and matrix-assisted laser desorption/ionisation-time of flight (MALDI-ToF/ToF). Validation studies were performed using ELISA.ResultsProteomic analysis depicted urinary vitamin D binding protein (uVDBP) as a two spots protein with increased intensity in ADHF and significant differences depending on the glomerular filtration rate (GFR). Urinary VDBP in patients with ADHF at hospitalisation was > threefold higher than in healthy subjects, with the highest levels in those patients with ADHF already presenting renal dysfunction. At day 3, urine VDBP levels in patients maintaining normal renal function dropped to normal values (P = 0.03 vs. day 0). In contrast, urine VDBP levels remained elevated in the group developing renal injury, with values twofold above the normal range (P < 0.05), while serum creatinine and GF levels were within the physiological range in this group. Urinary VDBP in ADHF positively correlated with markers of renal injury such as cystatin C and Kidney Injury Molecule 1 (KIM-1). By ROC analysis, urinary VDBP, when added to cystatin C and KIM-1, improved the prediction of renal injury in patients with ADHF.ConclusionWe showed increased urine VDBP in patients with ADHF at hospital admission and a differential uVDBP evolution pattern at early stage of renal dysfunction, before pathological worsening of GFR is evidenced.

show abstract

“…FABP1 (also known as liver type‐FABP, L‐FABP) is a 14 kDa cytosolic protein that is predominantly expressed in the liver and, to a lesser extent, in the kidney, intestine, stomach, and lung [ 5 , 6 ]. Urinary FABP1 levels are elevated in several acute kidney diseases such as ischemia reperfusion injury/hypoperfusion, acute decompensated heart failure [ 7 , 8 , 9 ], cardiac surgery [ 10 ], kidney transplantation [ 3 , 11 ], sepsis [ 12 ], and contrast‐ 13 , 14 ] and nephrotoxin‐induced AKI [ 3 , 15 ]. Several studies have reported that urinary FABP1 is useful for the early detection and prediction of prognosis [ 3 , 4 , 11 , 16 , 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Urinary FABP1 is a biomarker for impaired proximal tubular protein reabsorption and is synergistically enhanced by concurrent liver injury

Kawakami

Matsui

Konno

et al. 2021

The Journal of Pathology

View full text Add to dashboard Cite

Urinary fatty acid binding protein 1 (FABP1, also known as liver-type FABP) has been implicated as a biomarker of acute kidney injury (AKI) in humans. However, the precise biological mechanisms underlying its elevation remain elusive. Here, we show that urinary FABP1 primarily reflects impaired protein reabsorption in proximal tubule epithelial cells (PTECs). Bilateral nephrectomy resulted in a marked increase in serum FABP1 levels, suggesting that the kidney is an essential organ for removing serum FABP1. Injected recombinant FABP1 was filtered through the glomeruli and robustly reabsorbed via the apical membrane of PTECs. Urinary FABP1 was significantly elevated in mice devoid of megalin, a giant endocytic receptor for protein reabsorption. Elevation of urinary FABP1 was also observed in patients with Dent disease, a rare genetic disease characterized by defective megalin function in PTECs. Urinary FABP1 levels were exponentially increased following acetaminophen overdose, with both nephrotoxicity and hepatotoxicity observed. FABP1-deficient mice with liver-specific overexpression of FABP1 showed a massive increase in urinary FABP1 levels upon acetaminophen injection, indicating that urinary FABP1 is liver-derived. Lastly, we employed transgenic mice expressing diphtheria toxin receptor (DT-R) either in a hepatocyte-or in a PTEC-specific manner, or both. Upon administration of diphtheria toxin (DT), massive excretion of urinary FABP1 was induced in mice with both kidney and liver injury, while mice with either injury type showed marginal excretion. Collectively, our data demonstrated that intact PTECs have a considerable capacity to reabsorb liver-derived FABP1 through a megalin-mediated mechanism. Thus, urinary FABP1, which is synergistically enhanced by concurrent liver injury, is a biomarker for impaired protein reabsorption in AKI. These findings address the use of urinary FABP1 as a biomarker of histologically injured PTECs that secrete FABP1 into primary urine, and suggest the use of this biomarker to simultaneously monitor impaired tubular reabsorption and liver function.

show abstract

Synthesizing Markers of Kidney Injury in Acute Decompensated Heart Failure: Should We Even Keep Looking?

Cited by 5 publications

References 89 publications

Identifying Candidate Protein Markers of Acute Kidney Injury in Acute Decompensated Heart Failure

Identifying Candidate Protein Markers of Acute Kidney Injury in Acute Decompensated Heart Failure

Vitamin D Binding Protein and Renal Injury in Acute Decompensated Heart Failure

Urinary FABP1 is a biomarker for impaired proximal tubular protein reabsorption and is synergistically enhanced by concurrent liver injury

Contact Info

Product

Resources

About