Early Detection of Renal Dysfunction in β Thalassemia with Focus on Novel Biomarkers

2020 ◽  
Author(s):  
Mozhgan Hashemieh
Keyword(s):  
Renal Dysfunction ◽  
Early Recognition ◽  
Binding Protein ◽  
Kidney Injury ◽  
Thalassemia Major ◽  
Retinol Binding Protein ◽  
Fatty Acid Binding ◽  
Novel Biomarkers ◽  
Beta 2 Microglobulin ◽  
Kidney Injury Molecule 1

Improved survival among transfusion dependent thalassemia patients in recent years has led to the manifestation of morbidities such as renal dysfunction. Renal injury is still an underestimated complication in β thalassemia major patients. Chronic anemia, iron overload due to repeated transfusion, and specific iron chelators are the main factors in pathogenesis of renal dysfunction in β thalassemia. Early identification of this morbidity allows us to delay the progression of kidney damage and therefore reduce renal impairment. In recent decades , novel biomarkers for early recognition of renal dysfunction have been studied in thalassemic patients, such as cystatin C, beta 2 microglobulin , alpha 1 microglobulin, N-acetyl beta-D-glucosaminidase (NAG), neutrophil gelatinase associated lipocaline (NGAL) , kidney injury molecule 1 (KIM-1) , liver type fatty acid binding protein (L-FABP), and retinol binding protein (RBP). In this review, renal aspects of thalassemia with focus on novel biomarkers were discussed.

Biomarkers of acute kidney injury: the pathway from discovery to clinical adoption

2017 ◽  
Vol 55 (8) ◽  
pp. 1074-1089 ◽  
Author(s):  
Kianoush Kashani ◽  
Wisit Cheungpasitporn ◽  
Claudio Ronco
Keyword(s):  
Acute Kidney Injury ◽  
Clinical Performance ◽  
Early Recognition ◽  
Binding Protein ◽  
Kidney Injury ◽  
Risk Groups ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Diagnostic Tools ◽  
Fatty Acid Binding ◽  
Prophylactic Measures

Abstract Acute kidney injury (AKI) is a common complication of critical illnesses and has a significant impact on outcomes, including mortality and morbidities. Unfortunately, apart from prophylactic measures, no effective treatment for this syndrome is known. Therefore, early recognition of AKI not only can provide better opportunities for preventive interventions, but also opens many gates for research and development of effective therapeutic options. Over the last few years, several new AKI biomarkers have been discovered and validated to improve early detection, differential diagnosis, and differentiation of patients into risk groups for progressive renal failure, need for renal replacement therapy (RRT), or death. These novel AKI biomarkers complement serum creatinine (SCr) and urine output, which are the standard diagnostic tools for AKI detection. In this article, we review the available literature on characteristics of promising AKI biomarkers that are currently the focus of preclinical and clinical investigations. These biomarkers include neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), liver-type fatty acid-binding protein, interleukin 18 (lL-18), insulin-like growth factor-binding protein 7, tissue inhibitor of metalloproteinase 2 (TIMP-2), calprotectin, urine angiotensinogen (AGT), and urine microRNA. We then describe the clinical performance of these biomarkers for diagnosis and prognostication. We also appraise each AKI biomarker’s advantages and limitations as a tool for early AKI recognition and prediction of clinical outcomes after AKI. Finally, we review the current and future states of implementation of biomarkers in the clinical practice.

scholarly journals Potential Prognostic Markers of Acute Kidney Injury in the Early Phase of Acute Pancreatitis

2019 ◽  
Vol 20 (15) ◽  
pp. 3714 ◽  
Author(s):  
Justyna Wajda ◽  
Paulina Dumnicka ◽  
Małgorzata Maraj ◽  
Piotr Ceranowicz ◽  
Marek Kuźniewski ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Acute Pancreatitis ◽  
Binding Protein ◽  
Kidney Injury ◽  
Current Evidence ◽  
Serum Cystatin C ◽  
Fatty Acid Binding ◽  
Number Of Patients ◽  
Kidney Injury Molecule 1 ◽  
The Impact

Acute kidney injury (AKI) is a serious complication of acute pancreatitis (AP), which occurs in up to 70% of patients with severe AP and significantly increases the risk of mortality. At present, AKI is diagnosed based on dynamic increase in serum creatinine and decreased urine output; however, there is a need for earlier and more accurate biomarkers. The aim of the study was to review current evidence on the laboratory tests that were studied as the potential biomarkers of AKI in AP. We also briefly summarized the knowledge coming from the studies including sepsis or ICU patients since severe acute pancreatitis is associated with systemic inflammation and organ failure. Serum cystatin C and serum or urine NGAL have been shown to predict or diagnose AKI in AP; however, this evidence come from the single center studies of low number of patients. Other markers, such as urinary kidney injury molecule-1, cell cycle arrest biomarkers (tissue inhibitor metalloproteinase-2 and urine insulin-like growth factor-binding protein 7), interleukin-18, liver-type fatty acid-binding protein, or calprotectin have been studied in other populations suffering from systemic inflammatory states. In AP, the potential markers of AKI may be significantly influenced by either dehydration or inflammation, and the impact of these factors may be difficult to distinguish from kidney injury. The subject of AKI complicating AP is understudied. More studies are needed, for both exploratory (to choose the best markers) and clinical (to evaluate the diagnostic accuracy of the chosen markers in real clinical settings).

scholarly journals Established and Emerging Markers of Kidney Function

2012 ◽  
Vol 58 (4) ◽  
pp. 680-689 ◽  
Author(s):  
Michael A Ferguson ◽  
Sushrut S Waikar
Keyword(s):  
Kidney Function ◽  
Clinical Medicine ◽  
Kidney Injury ◽  
Creatinine Concentration ◽  
Fatty Acid Binding ◽  
Additional Information ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Novel Biomarkers ◽  
Kidney Injury Molecule 1 ◽  
And Function

Abstract BACKGROUND The kidney performs a multitude of essential functions to maintain homeostasis. In clinical medicine, glomerular filtration rate (GFR) provides the best index of overall kidney function, and proteinuria adds additional information on renal and nonrenal prognosis. Several novel biomarkers of kidney injury and function are under investigation. CONTENT Plasma creatinine concentration is the most widely used measure for estimation of GFR. Plasma cystatin C and β-trace protein may eventually prove to be superior to creatinine. GFR may be measured directly by use of exogenous filtration markers, although their role is primarily limited to the research setting. Real-time, noninvasive measurement of GFR by using fluorescently labeled markers may be available in the future. Novel biomarkers of tubular injury such as neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, liver-type fatty acid binding protein, N-acetyl-β-(D)-glucosaminidase, and interleukin-18 may enable the early detection of acute kidney injury before or in the absence of a change in GFR. SUMMARY A variety of methods are available to assist clinicians in the assessment of kidney function and injury. Ongoing investigation will help determine the utility of several new markers and clarify their role in the care of patients with and at risk for kidney disease.

scholarly journals Current understanding and future directions in the application of TIMP-2 and IGFBP7 in AKI clinical practice

2019 ◽  
Vol 57 (5) ◽  
pp. 567-576 ◽  
Author(s):  
Weixuan Fan ◽  
Ghada Ankawi ◽  
Jingxiao Zhang ◽  
Kumar Digvijay ◽  
Davide Giavarina ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Binding Protein ◽  
Kidney Injury ◽  
Clinical Work ◽  
The United States ◽  
Future Directions ◽  
Fatty Acid Binding ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Kidney Injury Molecule 1

Abstract NephroCheck® is the commercial name of a combined product of two urinary biomarkers, tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), expressed as [TIMP-2]·[IGFBP7], used to identify patients at high risk of acute kidney injury (AKI). AKI is a common and harmful complication especially in critically-ill patients, which can induce devastating short- and long-term outcomes. Over the past decade, numerous clinical studies have evaluated the utility of several biomarkers (e.g. neutrophil gelatinase-associated lipocalin, interleukin-18, liver-type fatty acid binding protein and kidney injury molecule-1, cystatin C) in the early diagnosis and risk stratification of AKI. Among all these biomarkers, [TIMP-2]·[IGFBP7] was confirmed to be superior in early detection of AKI, before the decrease of renal function is evident. In 2014, the US Food and Drug Administration permitted marketing of NephroCheck® (Astute Medical) (measuring urinary [TIMP-2]·[IGFBP7]) to determine if certain critically-ill patients are at risk of developing moderate to severe AKI. It has since been applied to clinical work in many hospitals of the United States and Europe to improve the diagnostic accuracy and outcomes of AKI patients. Now, more and more research is devoted to the evaluation of its application value, meaning and method in different clinical settings. In this review, we summarize the current research status of [TIMP-2]·[IGFBP7] and point out its future directions.

scholarly journals Urinary Markers of Tubular Injury in Early Diabetic Nephropathy

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Temesgen Fiseha ◽  
Zemenu Tamir
Keyword(s):  
Diabetic Nephropathy ◽  
Binding Protein ◽  
Kidney Injury ◽  
Adverse Outcomes ◽  
Retinol Binding Protein ◽  
Diabetic Patients ◽  
Tubular Injury ◽  
Accurate Identification ◽  
Fatty Acid Binding ◽  
Urinary Markers

Diabetic nephropathy (DN) is a common and serious complication of diabetes associated with adverse outcomes of renal failure, cardiovascular disease, and premature mortality. Early and accurate identification of DN is therefore of critical importance to improve patient outcomes. Albuminuria, a marker of glomerular involvement in early renal damage, cannot always detect early DN. Thus, more sensitive and specific markers in addition to albuminuria are needed to predict the early onset and progression of DN. Tubular injury, as shown by the detection of tubular injury markers in the urine, is a critical component of the early course of DN. These urinary tubular markers may increase in diabetic patients, even before diagnosis of microalbuminuria representing early markers of normoalbuminuric DN. In this review we summarized some new and important urinary markers of tubular injury, such as neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), N-acetyl-beta-glucosaminidase (NAG), alpha-1 microglobulin (A1M), beta 2-microglobulin (B2-M), and retinol binding protein (RBP) associated with early DN.

Abstract P347: Retinol-binding Protein 7 (RBP7) is Required for PPARG-mediated Endothelial Protection via Adiponectin

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Chunyan Hu ◽  
Henry L Keen ◽  
Ko-Ting Lu ◽  
Deborah R Davis ◽  
Xuebo Liu ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Rna Sequencing ◽  
Basilar Artery ◽  
Vascular Function ◽  
Carotid Arteries ◽  
Target Genes ◽  
Binding Protein ◽  
Retinol Binding Protein ◽  
Specific Expression ◽  
Fatty Acid Binding

PPARγ protects against endothelial dysfunction by regulation of unknown target genes. One such target, RBP7, an intracellular fatty acid-binding protein, exhibits endothelium-specific expression, but its effect on vascular function remain unknown. We hypothesize that RBP7 is endothelial protective. We examined vascular responses in basilar artery (pressurized myograph) of RBP7-knockout (KO) and wild type (WT) mice fed normal chow (ND) or high fat diet (HFD) for 8 wks. Endothelium-dependent acetylcholine (ACh)-induced relaxation was significantly impaired in HFD-fed KO mice (ACh, 100μM: 33±7% KO vs 83±10% WT, p<0.05), but not in ND-fed groups. This response was ameliorated by pre-incubation with superoxide scavenger tempol (1mM) or PEG-superoxide dismutase (100 U/ml). Mean arterial pressure (measured by radiotelemetry), body weight, hepatic steatosis, fasting glucose, glucose tolerance, and insulin sensitivity were similar in HFD-fed KO and WT mice. To identify targets downstream of RBP7, RNA-Sequencing was performed on carotid arteries from 8-week HFD-fed WT and KO mice as well as ND-fed age-matched littermates. Adiponectin (AdipoQ), a PPARγ target, was increased ~6-fold in HFD-fed WT mice, a response that was markedly blunted in KO mice. RNA sequencing was confirmed by qPCR. There was no difference in plasma AdipoQ. AdipoQ protein is expressed in endothelial cells of carotid arteries and its level of expression was increased in HFD-fed WT but not KO mice (AdipoQ/CD31: 1.14±0.1 WT-HFD vs 0.82±0.1 WT-ND, p<0.05; 0.79±0.1 KO-HFD vs 0.81±0.04 KO-ND). This led us to hypothesize that AdipoQ is involved in RBP7-mediated endothelial protection. Incubation of basilar artery with mouse full-length AdipoQ protein (5 μg/mL, 4 hours) significantly ameliorated endothelial dysfunction (ACh, 100 μM: 56±6% AdipoQ+KO vs 26±3% KO, p<0.05) and blunted carotid artery superoxide production in HFD-fed KO mice. AdipoQ also protects against endothelial dysfunction caused by subpressor Ang-II in KO mice. We conclude that RBP7 protects the endothelium from oxidative stress-induced dysfunction through an AdipoQ-dependent mechanism. Our evidence suggests RBP7 is an essential cofactor for activation of some PPARγ target genes in the endothelium.

Sign in / Sign up

Export Citation Format

Share Document