Biomarkers of renal and hepatic failure

Author(s):  
Mario Plebani ◽  
Monica Maria Mion ◽  
Martina Zaninotto

In the last years, major advances have been achieved in the understanding of the molecular and pathophysiological mechanisms which underlie the complex interactions between the heart and the kidney, as well as between the heart and the liver. According to these new insights, innovative biomarkers have been proposed for better evaluating and monitoring patients affected by cardiovascular diseases. In addition, some biomarkers should be used as risk factors and for an early identification and treatment of these severe diseases. This chapter reviews the most important biomarkers for evaluating the 'cardiorenal syndrome', in particular, the measurement of serum creatinine and its use for calculating the glomerular filtration rate which, with the new and more efficient equation, namely Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), still remains the most widely used biomarker. The role of newer biomarkers will be explored. The measurement of cystatin C, representing additional information, particularly in paediatric age groups and in the early phase of kidney disease, plays an increasing role. Neutrophil gelatinase-associated lipocalin (NGAL) is a recently developed but largely used biomarker for the early diagnosis of acute kidney injury, while the well-known albumin/creatinine ratio has been re-evaluated as a simple and useful tool for an early identification of kidney disease. Regarding liver diseases, a growing body of evidence demonstrates the usefulness of non-invasive makers of hepatic fibrosis that may avoid the need for a liver biopsy in most patients. A promising field of research is represented by the role of non-alcoholic fatty liver disease in the pathogenesis of cardiovascular disease.

Author(s):  
Mario Plebani ◽  
Monica Maria Mion ◽  
Martina Zaninotto

In the last few years, major advances have been achieved in the understanding of the molecular and pathophysiological mechanisms which underlie the complex interactions between the heart and the kidney, as well as between the heart and the liver. According to these new insights, new biomarkers have been proposed for better evaluating and monitoring patients affected by cardiovascular diseases. In addition, some biomarkers should be used as risk factors and for an early identification and treatment of these severe diseases. This chapter reviews the most important biomarkers for evaluating the ‘cardiorenal syndrome’, in particular, the measurement of serum creatinine and its use for calculating the glomerular filtration rate which, with the new and more efficient equation, namely Chronic Kidney Disease Epidemiology Collaboration, still remains the most widely used biomarker. The role of newer biomarkers will be explored. The measurement of cystatin C, representing additional information, particularly in paediatric age groups and in the early phase of kidney disease, plays an increasing role. Neutrophil gelatinase-associated lipocalin is a recently developed and very promising new biomarker for the diagnosis of acute kidney injury, while the well-known albumin/creatinine ratio has been re-evaluated as a simple and useful tool for an early identification of kidney disease. Regarding liver diseases, a growing body of evidence demonstrates the usefulness of non-invasive makers of hepatic fibrosis that may avoid the need for a liver biopsy in most patients. A promising field of research is represented by the role of non-alcoholic fatty liver disease in the pathogenesis of cardiovascular disease.


2019 ◽  
Vol 9 (5) ◽  
pp. 308-315
Author(s):  
Grazia Maria Virzì ◽  
Andrea Breglia ◽  
Ghada Ankawi ◽  
Chiara Bolin ◽  
Massimo de Cal ◽  
...  

Background: Cardiorenal syndrome (CRS) type 1 is characterized by a rapid worsening of cardiac function that leads to acute kidney injury (AKI). This study evaluated the role of lipopolysaccharide (LPS) in the development of AKI in patients with acute heart failure (AHF) and its relationship with renal parameters, to enable a better comprehension of the pathophysiology of CRS type 1. Methods: We enrolled 32 AHF patients, 15 of whom were classified as having CRS type 1. Eight of these 15 exhibited AKI at the time of admission (caused by AHF) and the other 7 developed AKI during their stay in hospital (in the first 48 h). We evaluated the plasmatic LPS concentrations as well as conventional (serum creatinine [sCr] and urea) and unconventional (neutrophil gelatinase-associated lipocalin [NGAL] and cystatin C) renal markers. Results: LPS levels were significantly higher in the CRS type 1 patients. No significant difference in LPS level was found in patients who were admitted with AKI and those developed AKI in hospital, but there was a tendency towards a higher level of LPS in CRS type 1 patients admitted with AKI. The LPS concentrations at admission were similar in CRS type 1 survivors (n = 12) and nonsurvivors (n = 3) (p = 0.22). We observed a positive correlation between LPS level and NGAL, Scr at admission and peak Scr during hospitalization and urea at admission. Conclusion: CRS type 1 patients present with an increased level of LPS and there is a direct correlation between LPS and renal parameters. This pilot research is the first study to explore the premise of LPS as novel pathophysiological factor in CRS type 1.


2020 ◽  
Vol 50 (6) ◽  
pp. 1566-1572
Author(s):  
Didem TURGUT ◽  
Serhan Vahit PİŞKİNPAŞA ◽  
Ezgi COŞKUN YENİGÜN ◽  
Nihal AYDEMİR ◽  
Fatih DEDE

Background/aim: Neutrophil gelatinase-associated lipocalin (NGAL) is used previously to estimate the etiology, severity, and clinical outcomes of acute kidney injury (AKI). However, the role of urinary NGAL (uNGAL) in the postrenal setting is not clear. In our study, we aimed to discover the cut-off value of uNGAL that can be used in the differential diagnosis of underlying AKI etiologies.Materials and methods: In this prospective cross-sectional study, we examined 82 subjects in four groups: patients that had (1) postrenal AKI; (2) AKI other than postrenal etiologies; (3) stable chronic kidney disease; and (4) healthy subjects. A renal function assessment was carried out by measuring serum creatinine (sCr) and uNGAL at the time of diagnosis [0th min (T0)]. We followed the study group for three months. Results: At the time of diagnosis, sCr (T0) was highest in the postrenal AKI and AKI groups in contrast to stable chronic kidney disease patients and healthy subjects (P < 0.001), as expected. T0 median uNGAL was highest in the postrenal group (P < 0.001). Area under curve (AUC) of uNGAL to estimate postrenal AKI presence was 0.957 (95% CI, 0.897–1.000; P < 0.001). The cut-off point of uNGAL was 42.625 ng/mL for this estimation. Conclusion: Patients with AKI must be classified according to the underlying etiologies as soon as possible. uNGAL may be useful to estimate the etiologies, and whether the problem is acute or chronic in the course. In postrenal kidney problems, to plan the urgency of the urologic procedures, it is crucial.


2015 ◽  
Vol 6 (1) ◽  
pp. 61-72 ◽  
Author(s):  
Annalisa Angelini ◽  
Chiara Castellani ◽  
Grazia Maria Virzì ◽  
Marny Fedrigo ◽  
Gaetano Thiene ◽  
...  

Background: In cardiorenal syndrome type 2 (CRS2), the role of systemic congestion in heart failure (HF) is still obscure. We studied a model of CRS2 [monocrotaline (MCT)-treated rats] secondary to pulmonary hypertension and right ventricular (RV) failure in order to evaluate the contribution of prevalent congestion to the development of kidney injury. Methods: Ten animals were treated with MCT for 4 weeks until they developed HF. Eleven animals were taken as controls. Signs of hypertrophy and dilatation of the right ventricle demonstrated the occurrence of HF. Brain natriuretic peptide (BNP), serum creatinine (sCreatinine), both kidney and heart neutrophil gelatinase-associated lipocalin (NGAL), matrix metallopeptidase 9 (MMP9), serum cytokines as well as kidney and heart cell death, as assessed by TUNEL, were studied. Results: Rats with HF showed higher BNP levels [chronic HF (CHF) 4.8 ± 0.5 ng/ml; controls 1.5 ± 0.2 ng/ml; p < 0.0001], marked RV hypertrophy and dilatation (RV mass/RV volume: CHF 1.46 ± 0.31, controls 2.41 ± 0.81; p < 0.01) as well as pleural and peritoneal effusions. A significant increase in proinflammatory cytokines and sCreatinine was observed (CHF 3.06 ± 1.3 pg/ml vs. controls 0.54 ± 0.23 pg/ml; p = 0.04). Serum (CHF 562.7 ± 93.34 ng/ml vs. controls 245.3 ± 58.19 ng/ml; p = 0.02) as well as renal and heart tissue NGAL levels [CHF 70,680 ± 4,337 arbitrary units (AU) vs. controls 32,120 ± 4,961 AU; p = 0.001] rose significantly, and they were found to be complexed with MMP9 in CHF rats. A higher number of kidney TUNEL-positive tubular cells was also detected (CHF 114.01 ± 45.93 vs. controls 16.36 ± 11.60 cells/mm2; p = 0.0004). Conclusion: In this model of CHF with prevalent congestion, kidney injury is characterized by tubular damage and systemic inflammation. The upregulated NGAL complexed with MMP9 perpetuates the vicious circle of kidney/heart damage by enhancing the enzymatic activity of MMP9 with extracellular matrix degradation, worsening heart remodeling.


2020 ◽  
Vol 97 (1) ◽  
pp. 95-105 ◽  
Author(s):  
Katsuyuki Matsushita ◽  
Turgay Saritas ◽  
Mahaba B. Eiwaz ◽  
Nicholas McClellan ◽  
Ian Coe ◽  
...  

2021 ◽  
Vol 10 (11) ◽  
pp. 2353
Author(s):  
Joanna Bagińska ◽  
Agata Korzeniecka-Kozerska

The lack of early biomarkers of renal damage in children with neurogenic bladder (NB) prompts us to investigate the role of promising proteins: neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). This prospective analysis was conducted on 58 children with NB and 25 healthy children. We assessed urinary levels of NGAL and KIM-1 in both groups. Age, sex, anthropometric measurements, activity assessment, renal function, and urodynamics parameters were analyzed. The differences between the median uNGAL and uKIM-1 in the NB group compared to control were recorded. However, only uNGAL levels were statistically significantly higher. Statistically significant correlation was found between gender, recurrent urinary tract infections, bladder trabeculation, its compliance, activity assessment, and uNGAL. To conclude, elevated levels of uNGAL may be considered a biomarker of tubular injury in children with NB due to MMC in contrast to uKIM-1.


2015 ◽  
Vol 6 (1) ◽  
pp. 25-36 ◽  
Author(s):  
Maciej T. Wybraniec ◽  
Katarzyna Mizia-Stec

Background: Contrast-induced acute kidney injury (CI-AKI) remains one of the crucial issues related to the development of invasive cardiology. The massive use of contrast media exposes patients to a great risk of contrast-induced nephropathy and chronic kidney disease development, and increases morbidity and mortality rates. The serum creatinine concentration does not allow for a timely and accurate CI-AKI diagnosis; hence numerous other biomarkers of renal injury have been proposed. Renalase, a novel catecholamine-metabolizing amine oxidase, is synthesized mainly in proximal tubular cells and secreted into urine and blood. It is primarily engaged in the degradation of circulating catecholamines. Notwithstanding its key role in blood pressure regulation, renalase remains a potential CI-AKI biomarker, which was shown to be markedly downregulated in the aftermath of renal injury. In this sense, renalase appears to be the first CI-AKI marker revealing an actual loss of renal function and indicating disease severity. Summary: The purpose of this review is to summarize the contemporary knowledge about the application of novel biomarkers of CI-AKI and to highlight the potential role of renalase as a functional marker of contrast-induced renal injury. Key Messages: Renalase may constitute a missing biochemical link in the mutual interplay between kidney and cardiac pathology known as the cardiorenal syndrome.


2018 ◽  
Vol 24 (9_suppl) ◽  
pp. 314S-322S
Author(s):  
Justin Lee ◽  
Ryan McMillan ◽  
Leonidas Skiadopoulos ◽  
Vinod Bansal ◽  
José Biller ◽  
...  

The prevalence of neurocognitive deficits remains high in patients with stage 5 chronic kidney disease (CKD5D). Major contributors to such deficits include stroke, cervical carotid artery disease (CCAD), and intracranial atherosclerotic disease (ICAD). The risk of developing these dysfunctional vascular processes is facilitated by the chronic inflammation associated with renal failure. Plasma levels of 10 circulating biomarkers in patients with CKD5D (n = 78-90) were quantified using the sandwich enzyme linked immune sorbent assay method. Biomarkers for this study included kidney injury molecule-1, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), neutrophil gelatinase-associated lipocalin, interleukin-18, endothelin 1, calcifediol, parathyroid hormone, platelet-derived growth factor, microparticles-expressing tissue factor, and lipoprotein(a) (Lp(a)). Of the 90 patients with CKD5D, 30 had CCAD, 24 had ICAD, and 22 had stroke. Lp(a) level was significantly elevated in patients with CKD5D with comorbid ICAD compared to those without (125.70 ± 10.03 ng/mL vs 97.16 ± 5.97 ng/mL; P = .0065). NT-proBNP level was also significantly elevated in patients with CKD5D with comorbid stroke diagnosis compared to those without stroke history, once patients with a diagnosis of heart failure (HF) were excluded (14.84 ± 2.80 ng/mL vs 9.06 ± 1.27 ng/mL; P = .0283). Profiling levels of Lp(a) and NT-ProBNP could thus be useful in the risk stratification of ICAD and stroke, respectively, in the CKD5D population.


2021 ◽  
pp. 189-190
Author(s):  
G.G. Kaushik ◽  
Shubham Maheshwari ◽  
Ankita Sharma

Introduction: Serum lipocalin 2 serve as a marker for kidney function. Lipocalin 2 is found in both CKD and kidney injury and it rises in acute kidney injury (AKI) and in patients have faster decline in kidney function. Aims And Objectives: To nd out correlation and assess of serum Neutrophil gelatinase-associated lipocalin 2 (NGAL 2) in patients with stages 2 to 4 of Chronic Kidney disease. The aim of the study was NGAL could represent a novel, sensitive marker of kidney function in adult patients with CKD. Material And Methods: Study involved 120 patients divided in Case group (60 patients) attended medical/ urology OPD or admitted in medical/urology ward of CKD2 – CKD4 while control group – age and sex matched healthy individuals/ stage I CKD patients was taken as control. The plasma/ serum were used for serum urea, creatinine, Cystatin C and lipocalin 2 under all aseptic precaution on receiving consent. Result:The patients of CKD included in study were having glomerulonephritis (46.7%), pyelonephritis (21.7%), diabetic kidney disease (13.3%), polycystic kidney disease (1.7%) and other causes (16.7%). CKD patients demonstrated elevated serum NGAL 159.14 ± 48.73 ng/ml, together with a rise in urea 59.9 ± 17.6 mg/dL, serum creatinine 1.56 ± 0.97 mg/dL and Cystatin C 199 ± 113 ng/ml as compared to control have serum NGAL 76.31 ± 26.34 ng/ml, urea 22.3 ± 5.7 mg/dL, serum creatinine 0.75 ± 0.14 mg/dL and Cystatin C 76 ± 17 ng/ml (P value <0.05). Conclusion: Serum NGAL closely correlates with serum Cystatin C, creatinine, and eGFR, and serve as a potential early and sensitive marker of impaired kidney function/ kidney injury.


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