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Novel Biomarkers for the Diagnosis, Prognosis and Management of Acute...
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Novel Biomarkers for the Diagnosis, Prognosis and Management of Acute Kidney Injury

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Nephrology & Urology".

Deadline for manuscript submissions: closed (10 September 2021) | Viewed by 11661

Special Issue Editor

Prof. Dr. Yacov Shacham

E-Mail Website
Guest Editor
Cardiology Intensive Care Unit, Tel-Aviv Sourasky Medical Center, Affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 64239, Israel
Interests: primary coronary intervention; heart failure; cardiogenic shock; cardio-renal syndromes; reperfusion injury
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Acute kidney injury (AKI) is a common condition associated with adverse outcomes, even at mildest forms. A major impediment to developing effective therapeutic interventions to combat AKI has been the limited ability to accurately detect significant renal injury in a timely manner. The serum creatinine has been the predominant marker of renal function in clinical practice for more than half a century and its limitations are well documented. Indeed, glomerular filtration rate may decrease by more than 50% from normal before a significant rise in serum creatinine occurs, making creatinine insensitive to small but significant reductions in glomerular filtration rate. This delay affects the preclinical evaluation of potential renal damage and prevents timely patient management decisions. Over the last decade, considerable progress has been made in the discovery and development of new AKI biomarkers both in urine and plasma. Utilization of these biomarkers in clinical practice enabled the early identification of injury, stratification according to injury severity, etiologic specificity for the injury, and provided valuable prognostic information. The aim of this Special Issue is to present clinical and experimental scientific reports that improve our understanding of novel biomarkers of early renal damage and their possible utilization in clinical practice.

Dr. Yacov Shacham
Guest Editor

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Keywords

  • Acute kidney injury
  • Biomarkers
  • Serum creatinine
  • Tubular damage
  • Glomerular filtration rate

Published Papers (6 papers)

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8 pages, 674 KiB  
Article
Relation of Baseline Neutrophil Gelatinase-Associated Lipocalin (NGAL) Levels and Contrast-Induced Nephropathy following Percutaneous Coronary Intervention among Chronic Kidney Disease Patients
by Lior Lupu, Hytham Abukatash, Ariel Banai, Keren-Lee Rozenfeld, Dana Lewit, Ilan Merdler, Itamar Loewenstein, Gil Bornstein, Shmuel Banai and Yacov Shacham
J. Clin. Med. 2021, 10(22), 5403; https://doi.org/10.3390/jcm10225403 - 19 Nov 2021
Cited by 6 | Viewed by 1516
Abstract
Background: The risk of contrast-induced acute kidney injury (CI-AKI) following coronary intervention is particularly high among patients with chronic kidney disease (CKD). Among these patients, baseline neutrophil gelatinase-associated lipocalin (NGAL), a marker of tubular damage, reflects the severity of renal impairment. We evaluated [...] Read more.
Background: The risk of contrast-induced acute kidney injury (CI-AKI) following coronary intervention is particularly high among patients with chronic kidney disease (CKD). Among these patients, baseline neutrophil gelatinase-associated lipocalin (NGAL), a marker of tubular damage, reflects the severity of renal impairment. We evaluated whether the baseline serum NGAL level may be a marker for the development of CI-AKI following percutaneous coronary intervention (PCI). Methods: Eighty-eight CKD patients treated with PCI were included. Serum NGAL levels were drawn upon hospital admission. Receiver operator characteristic (ROC) methods were used to identify the optimal sensitivity and specificity for the observed NGAL level compared with the estimated glomerular filtration rate (eGFR) calculated for patients with CI-AKI. Results: Overall CI-AKI incidence was 43%. Baseline serum NGAL levels were significantly higher in patients with CI-AKI than in patients without CI-AKI (150 vs. 103 ng/mL, p < 0.001). According to the ROC curve, baseline NGAL levels performed better than eGFR to predict CI-AKI (AUC 0.753 vs. 0.604), with the optimal cutoff value for baseline NGAL to predict CI-AKI being 127 ng/mL (sensitivity of 68% and specificity of 68%, p < 0.001). In a multivariate logistic regression model, the NGAL level >127 ng/mL ng/mL was independently associated with CI-AKI (HR 9.84, 95% CI: 1.96–40.3; p = 0.01). Conclusion: Baseline serum NGAL levels in CKD patients may identify a high-risk population for CI-AKI following PCI. Further studies on larger populations are required to validate the potential utility of NGAL measurements in monitoring specific CKD-associated conditions. Full article
(This article belongs to the Special Issue Novel Biomarkers for the Diagnosis, Prognosis and Management of Acute Kidney Injury)
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16 pages, 2377 KiB  
Communication
Diagnostic Value of Multiple Serum Biomarkers for Vancomycin-Induced Kidney Injury
by Sang-Mi Kim, Hyun-Seung Lee, Min-Ji Kim, Hyung-Doo Park and Soo-Youn Lee
J. Clin. Med. 2021, 10(21), 5005; https://doi.org/10.3390/jcm10215005 - 27 Oct 2021
Cited by 7 | Viewed by 2227 | Correction
Abstract
Acute kidney injury (AKI) is a major contributor to in-hospital morbidity and mortality. Vancomycin, one of the most commonly used antibiotics in a clinical setting, is associated with AKI, with its incidence ranging up to 43%. Despite the high demand, few studies have [...] Read more.
Acute kidney injury (AKI) is a major contributor to in-hospital morbidity and mortality. Vancomycin, one of the most commonly used antibiotics in a clinical setting, is associated with AKI, with its incidence ranging up to 43%. Despite the high demand, few studies have investigated serum biomarkers to detect vancomycin-induced kidney injury (VIKI). Here, we evaluated the diagnostic value of nine candidate serum biomarkers for VIKI. A total of 23,182 cases referred for vancomycin concentration measurement from January 2018 to December 2019 were screened and 28 subjects with confirmed VIKI were enrolled (VIKI group). Age- and sex- matched control group consisted of 21 subjects who underwent vancomycin therapy without developing VIKI (non-VIKI group), and 23 healthy controls (HC group). The serum concentrations of clusterin, retinol binding protein 4 (RBP4), interleukin-18 (IL-18), tumor necrosis factor receptor 1 (TNF-R1), C-X-C motif chemokine ligand 10 (CXCL10), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin, trefoil factor-3 (TFF3), and cystatin C were compared among the three groups, and their correlations with estimated glomerular filtration rate (eGFR) and diagnostic values for VIKI were assessed. All of the biomarkers except clusterin and RBP4 exhibited significant elevation in the VIKI group. Serum TFF3, cystatin C, TNF-R1, and osteopontin demonstrated an excellent diagnostic value for VIKI (TFF3, area under the curve (AUC) 0.932; cystatin C, AUC 0.917; TNF-R1, AUC 0.866; osteopontin, AUC 0.787); and except osteopontin, a strong negative correlation with eGFR (TFF3, r = −0.71; cystatin C, r = −0.70; TNF-R1, r = −0.60). IL-18, CXCL10, and NGAL showed weak correlation with eGFR and moderate diagnostic value for VIKI. This study tested multiple serum biomarkers for VIKI and showed that serum TFF3, cystatin C, TNF-R1, and osteopontin could efficiently discriminate VIKI patients. Further studies are warranted to clarify the diagnostic value of these biomarkers in VIKI. Full article
(This article belongs to the Special Issue Novel Biomarkers for the Diagnosis, Prognosis and Management of Acute Kidney Injury)
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15 pages, 1823 KiB  
Article
GDF-15 Predicts In-Hospital Mortality of Critically Ill Patients with Acute Kidney Injury Requiring Continuous Renal Replacement Therapy: A Multicenter Prospective Study
by Jeong-Hoon Lim, Yena Jeon, Ji-Sun Ahn, Sejoong Kim, Dong Ki Kim, Jung Pyo Lee, Dong-Ryeol Ryu, Eun Young Seong, Shin Young Ahn, Seon Ha Baek, Hee-Yeon Jung, Ji-Young Choi, Sun-Hee Park, Chan-Duck Kim, Yong-Lim Kim and Jang-Hee Cho
J. Clin. Med. 2021, 10(16), 3660; https://doi.org/10.3390/jcm10163660 - 18 Aug 2021
Cited by 3 | Viewed by 1927
Abstract
Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine. This study evaluated the association between GDF-15 and in-hospital mortality among patients with severe acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). Among the multicenter prospective CRRT cohort between 2017 and 2019, 66 [...] Read more.
Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine. This study evaluated the association between GDF-15 and in-hospital mortality among patients with severe acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). Among the multicenter prospective CRRT cohort between 2017 and 2019, 66 patients whose blood sample was available were analyzed. Patients were divided into three groups according to the GDF-15 concentrations. The median GDF-15 level was 7865.5 pg/mL (496.9 pg/mL in the healthy control patients). Baseline characteristics were not different among tertile groups except the severity scores and serum lactate level, which were higher in the third tertile. After adjusting for confounding factors, the patients with higher GDF-15 had significantly increased risk of mortality (second tertile: adjusted hazards ratio [aHR], 3.67; 95% confidence interval [CI], 1.05–12.76; p = 0.041; third tertile: aHR, 6.81; 95% CI, 1.98–23.44; p = 0.002). Furthermore, GDF-15 predicted in-hospital mortality (area under the curve, 0.710; 95% CI, 0.585–0.815) better than APACHE II and SOFA scores. Serum GDF-15 concentration was elevated in AKI patients requiring CRRT, higher in more severe patients. GDF-15 is a better independent predictor for in-hospital mortality of critically ill AKI patients than the traditional risk scoring system such as APACHE II and SOFA scores. Full article
(This article belongs to the Special Issue Novel Biomarkers for the Diagnosis, Prognosis and Management of Acute Kidney Injury)
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10 pages, 1161 KiB  
Article
Clinically Significant High-Grade AV Block as a Reversible Cause for Acute Kidney Injury in Hospitalized Patients—A Propensity Score Matched Cohort
by Aviram Hochstadt, Ido Avivi, Merav Ingbir, Yacov Shacham, Ilan Merdler, Yoav Granot, Sami Viskin, Raphael Rosso, Shmuel Banai and Maayan Konigstein
J. Clin. Med. 2021, 10(11), 2424; https://doi.org/10.3390/jcm10112424 - 30 May 2021
Cited by 2 | Viewed by 2531
Abstract
Background. High-grade AV block (HGAVB) is a life-threatening condition. Acute kidney injury (AKI) which is usually caused by renal hypo-perfusion is associated with adverse outcomes. We aimed to investigate the association between AKI and HGAVB. Methods. This is a retrospective cohort comparing the [...] Read more.
Background. High-grade AV block (HGAVB) is a life-threatening condition. Acute kidney injury (AKI) which is usually caused by renal hypo-perfusion is associated with adverse outcomes. We aimed to investigate the association between AKI and HGAVB. Methods. This is a retrospective cohort comparing the incidence of AKI among patients with HGAVB requiring pacemaker implantation compared with propensity score matched controls. Primary outcome was the incidence of AKI at admission. Secondary outcomes were change in creatinine levels, AKI during stay, recovery from AKI, mortality and major adverse kidney events (MAKE). Results. In total, 80 HGAVB patients were compared to 400 controls. HGAVB patients had a higher proportion of admission AKI compared to controls (36.2% versus 21.1%, RR = 1.71 [1.21–2.41], p = 0.004). Creatinine changes from baseline to admission and to maximum during hospitalization, were also higher in HGAVB (p = 0.042 and p = 0.033). Recovery from AKI was more frequent among HGAVB patients (55.2% vs. 25.9%, RR = 2.13 [1.31–3.47], p = 0.004) with hospitalization time, MAKE and crude mortality similar (p > 0.158). Conclusions. AKI occurs in about one third of patients admitted with HGAVB, more frequent compared to controls. Patients with AKI accompanying HGAVB were likelier to recover from AKI. Further studies to explore this relationship could aid in clinical decision making for HGAVB patients. Full article
(This article belongs to the Special Issue Novel Biomarkers for the Diagnosis, Prognosis and Management of Acute Kidney Injury)
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8 pages, 206 KiB  
Article
Detection of Renal Injury Following Primary Coronary Intervention among ST-Segment Elevation Myocardial Infarction Patients: Doubling the Incidence Using Neutrophil Gelatinase-Associated Lipocalin as a Renal Biomarker
by Lior Lupu, Keren-Lee Rozenfeld, David Zahler, Samuel Morgan, Ilan Merdler, Moshe Shtark, Ilana Goldiner, Shmuel Banai and Yacov Shacham
J. Clin. Med. 2021, 10(10), 2120; https://doi.org/10.3390/jcm10102120 - 14 May 2021
Cited by 6 | Viewed by 1584
Abstract
Background: A subgroup of patients with acute kidney injury (AKI) do not fulfil the functional criteria for AKI diagnosis but show elevated levels of new biomarkers reflecting tubular injury, suggesting that these patients suffer “subclinical AKI”. We investigated the incidence and possible implications [...] Read more.
Background: A subgroup of patients with acute kidney injury (AKI) do not fulfil the functional criteria for AKI diagnosis but show elevated levels of new biomarkers reflecting tubular injury, suggesting that these patients suffer “subclinical AKI”. We investigated the incidence and possible implications of “subclinical AKI”, compared to no and clinical AKI among ST elevation myocardial infarction patients (STEMI) treated with primary coronary intervention (PCI). Methods: We included 223 patients with STEMI treated with PCI. Neutrophil gelatinase-associated lipocalin (NGAL) was used as a marker of renal tubular damage in the absence of functional AKI, with NGAL levels ≥100 ng/mL suggesting subclinical AKI. Patients were assessed for the occurrence of in-hospital adverse outcomes. Results: Of the study patients, 45 (25%) had subclinical AKI. These patients were more likely to have left ventricular ejection fraction ≤45% (33% vs. 23%. p = 0.01), in-hospital adverse outcomes (73% vs. 48%; p = 0.005), and a combination of the two. The multivariate regression model demonstrated that subclinical AKI was independently associated with in-hospital adverse outcomes (OR 3.71, 95% CI 1.30–10.62, p = 0.02). Conclusions: Subclinical AKI is common among STEMI patients and is independently associated with adverse outcomes, even in the absence of functional AKI. Full article
(This article belongs to the Special Issue Novel Biomarkers for the Diagnosis, Prognosis and Management of Acute Kidney Injury)

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3 pages, 173 KiB  
Correction
Correction: Kim et al. Diagnostic Value of Multiple Serum Biomarkers for Vancomycin-Induced Kidney Injury. J. Clin. Med. 2021, 10, 5005
by Sang-Mi Kim, Hyun-Seung Lee, Min-Ji Kim, Hyung-Doo Park and Soo-Youn Lee
J. Clin. Med. 2022, 11(6), 1667; https://doi.org/10.3390/jcm11061667 - 17 Mar 2022
Viewed by 1059
Abstract
Error in Table [...] Full article
(This article belongs to the Special Issue Novel Biomarkers for the Diagnosis, Prognosis and Management of Acute Kidney Injury)
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