Biomarkers Of Renal Disease Research Articles

Validation of Candidate Phospholipid Biomarkers of Chronic Kidney Disease in Hyperglycemic Individuals and Their Organ-Specific Exploration in Leptin Receptor-Deficient db/db Mouse

Biological exploration of early biomarkers for chronic kidney disease (CKD) in (pre)diabetic individuals is crucial for personalized management of diabetes. Here, we evaluated two candidate biomarkers of incident CKD (sphingomyelin (SM) C18:1 and phosphatidylcholine diacyl (PC aa) C38:0) concerning kidney function in hyperglycemic participants of the Cooperative Health Research in the Region of Augsburg (KORA) cohort, and in two biofluids and six organs of leptin receptor-deficient (db/db) mice and wild type controls. Higher serum concentrations of SM C18:1 and PC aa C38:0 in hyperglycemic individuals were found to be associated with lower estimated glomerular filtration rate (eGFR) and higher odds of CKD. In db/db mice, both metabolites had a significantly lower concentration in urine and adipose tissue, but higher in the lungs. Additionally, db/db mice had significantly higher SM C18:1 levels in plasma and liver, and PC aa C38:0 in adrenal glands. This cross-sectional human study confirms that SM C18:1 and PC aa C38:0 associate with kidney dysfunction in pre(diabetic) individuals, and the animal study suggests a potential implication of liver, lungs, adrenal glands, and visceral fat in their systemic regulation. Our results support further validation of the two phospholipids as early biomarkers of renal disease in patients with (pre)diabetes.

Urinary Extracellular Vesicles as Biomarkers of Kidney Disease

Extracellular vesicles (EVs) are membrane-bound vesicles produced and released into the extracellular fluid by cells under physiological and stressful conditions. They play a role as intracellular communicators by carrying and delivering biomolecules, such as proteins, lipids, or nucleic acids. Urinary EVs have gained important recognition as potential diagnostic biomarkers in renal disease, as they can originate from diverse cell types, including glomerular podocytes, tubular epithelial cells, or endothelial cells. Accumulating evidence has emphasized the feasibility of using EVs as biomarkers for diagnostic, prognostic, and therapeutic purposes in several forms of renal disease, such as acute kidney injury, glomerulonephritis, and renal transplantation. In this review, we introduce recent studies that attempt to identify urinary EVs as candidate biomarkers for human kidney diseases and consider their potential implications as a therapeutic option in significant kidney diseases.

Urinary DPP4 correlates with renal dysfunction, and DPP4 inhibition protects against the reduction in megalin and podocin expression in experimental CKD.

This study investigated the molecular mechanisms underlying the antiproteinuric effect of DPP4 inhibition in 5/6 renal ablation rats and tested the hypothesis that the urinary activity of DPP4 correlates with chronic kidney disease (CKD) progression. Experiments were conducted in male Wistar rats who underwent 5/6 nephrectomy (Nx) or sham operation followed by 8 wk of treatment with the DPP4 inhibitor (DPP4i) sitagliptin or vehicle. Proteinuria increased progressively in Nx rats throughout the observation period. This increase was remarkably mitigated by sitagliptin. Higher levels of proteinuria in Nx rats compared to control rats were accompanied by higher urinary excretion of retinol-binding protein 4, a marker of tubular proteinuria, as well as higher urinary levels of podocin, a marker of glomerular proteinuria. Retinol-binding protein 4 and podocin were not detected in the urine of Nx + DPP4i rats. Tubular and glomerular proteinuria was associated with the reduced expression of megalin and podocin in the renal cortex of Nx rats. Sitagliptin treatment partially prevented this decrease. Besides, the angiotensin II renal content was significantly reduced in the Nx rats that received sitagliptin compared to vehicle-treated Nx rats. Interestingly, both urinary DPP4 activity and abundance increased progressively in Nx rats. Additionally, urinary DPP4 activity correlated positively with serum creatinine levels, proteinuria, and blood pressure. Collectively, these results suggest that DPP4 inhibition ameliorated both tubular and glomerular proteinuria and prevented the reduction of megalin and podocin expression in CKD rats. Furthermore, these findings suggest that urinary DPP4 activity may serve as a biomarker of renal disease and progression.

CO2 laser photoacoustic spectrometer for measuring ethylene, acetone, and ammonia in the breath of patients with renal disease

We applied our lab-built CO2 laser photoacoustic spectrometer, which has a multi-component measurement capability, for measuring the ammonia, acetone, and ethylene trace gases in the breath of 10 renal disease patients and 30 healthy volunteers. We argue that not only ammonia but also acetone and ethylene can become potential biomarkers for renal disease. We found that the breath ammonia and acetone concentrations from the renal disease patients are significantly higher than that of the healthy volunteers. While for ethylene, we found that the breath ethylene concentration from renal disease patients is not significantly higher than in the healthy volunteer. Besides a reconfirmation of the breath ammonia concentration as a biomarker for renal disease, our results open up a possibility for the breath acetone to be a possible biomarker for renal disease.

Extracellular vesicles: a novel window into kidney function and disease.

There has been an increasing interest in extracellular vesicles as potential diagnostic, prognostic or therapeutic biomarkers for various kidney diseases, as extracellular vesicles mediate cell-cell or intercellular communication. This review explores the current state of knowledge regarding extracellular vesicles as a tool for examining kidney physiology and disease. Urinary extracellular vesicles may be useful as biomarkers to detect abnormal function in renal endothelial and tubular cells as well as podocytes. Recent studies suggest that urinary extracellular vesicles may facilitate early diagnosis and/or monitoring in acute kidney injury, glomerular disease, autosomal dominanat polycyst kidney disease and urinary tract malignancies. Circulating extracellular vesicles may serve as biomarkers to assess cardiovascular disease. Urinary and circulating extracellular vesicles have gained significant interest as potential biomarkers of renal diseases. Analysis of extracellular vesicles may serve as a logical diagnostic approach for nephrologists as well as provide information about disease pathophysiology.

Biomarkers associated with early stages of kidney disease in adolescents with type 1 diabetes.

To identify biomarkers of renal disease in adolescents with type 1 diabetes (T1D) and to compare findings in adults with T1D. Twenty-five serum biomarkers were measured, using a Luminex platform, in 553 adolescents (median [interquartile range] age: 13.9 [12.6, 15.2] years), recruited to the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial. Associations with baseline and final estimated glomerular filtration rate (eGFR), rapid decliner and rapid increaser phenotypes (eGFR slopes <-3 and > 3 mL/min/1.73m2 /year, respectively), and albumin-creatinine ratio (ACR) were assessed. Results were also compared with those obtained in 859 adults (age: 55.5 [46.1, 64.4) years) from the Scottish Diabetes Research Network Type 1 Bioresource. In the adolescent cohort, baseline eGFR was negatively associated with trefoil factor-3, cystatin C, and beta-2 microglobulin (B2M) (B coefficient[95%CI]: -0.19 [-0.27, -0.12], P = 7.0 × 10-7 ; -0.18 [-0.26, -0.11], P = 5.1 × 10-6 ; -0.12 [-0.20, -0.05], P = 1.6 × 10-3 ), in addition to clinical covariates. Final eGFR was negatively associated with osteopontin (-0.21 [-0.28, -0.14], P = 2.3 × 10-8 ) and cystatin C (-0.16 [-0.22, -0.09], P = 1.6 × 10-6 ). Rapid decliner phenotype was associated with osteopontin (OR: 1.83 [1.42, 2.41], P = 7.3 × 10-6 ), whereas rapid increaser phenotype was associated with fibroblast growth factor-23 (FGF-23) (1.59 [1.23, 2.04], P = 2.6 × 10-4 ). ACR was not associated with any of the biomarkers. In the adult cohort similar associations with eGFR were found; however, several additional biomarkers were associated with eGFR and ACR. In this young population with T1D and high rates of hyperfiltration, osteopontin was the most consistent biomarker associated with prospective changes in eGFR. FGF-23 was associated with eGFR increases, whereas trefoil factor-3, cystatin C, and B2M were associated with baseline eGFR.

Performance of creatinine- and cystatin C-based formulas to estimate glomerular filtration rate

Chronic kidney disease (CKD) affects 8-16% of the population worldwide and is a huge global health issue, given its strong association with higher cardiovascular morbidity and mortality, progression towards end-stage renal disease, and other complications including cognitive decline, mineral bone disease and anaemia [ [1] Gentile G. Remuzzi G. Novel biomarkers for renal diseases? None for the moment (but one). J Biomol Screen. 2016; 21: 655-670 Crossref PubMed Scopus (27) Google Scholar ]. Despite huge efforts to identify novel and more specific kidney biomarkers [ [2] Perico L. Perico N. Benigni A. The incessant search for renal biomarkers: is it really justified?. Curr Opin Nephrol Hypertens. 2019; 28: 195-202 Crossref PubMed Scopus (2) Google Scholar ], estimation of glomerular filtration rate (GFR) remains the mainstay of initial CKD diagnosis, its staging, and its subsequent management. Several international guidelines recommend the usage of different estimation formulas, including the 4- and 6-variable Modification of Diet in Renal Disease (MDRD) formulas [ [3] Levey A.S. Bosch J.P. Lewis J.B. Greene T. Rogers N. Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999; 130: 461-470 Crossref PubMed Scopus (12525) Google Scholar ] and, more recently, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, based on serum creatinine (CKD-EPIcrea) [ [4] Levey A.S. Stevens L.A. Schmid C.H. Zhang Y.L. Castro 3rd, A.F. Feldman H.I. et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009; 150: 604-612 Crossref PubMed Scopus (13708) Google Scholar ], cystatin C (CKD-EPIcys), or both (CKD-EPIcrea/cys), which are more reliable in people with estimated GFR higher than 60 mL/min/1.73 m2. In this issue of the Journal, the timely systematic review by Zou and colleagues provides original insights on the performance of GFR estimating equations. The analysis included 35 studies, relevant to primary care, with 23,667 adult participants, aimed to establish the bias, accuracy and precision of estimated GFR using the three CKD-EPI equations [ [5] Zou L.-X. Sun L. Nicholas S.B. Lu Y. K S.S. Hua R. Comparison of bias and accuracy using cystatin C and creatinine in CKD-EPI equations for GFR estimation. Eur J Inter Med. 2020; https://doi.org/10.1016/j.ejim.2020.04.044 Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar ]. The mean bias was expressed as the difference between measured GFR and estimated GFR by the CKD-EPIcrea, CKD-EPIcys, and CKD-EPIcrea/cys formulas, in mL/min/1.73 m2. Accuracy was expressed as percentage of eGFR readings within 30% of measured GFR, or P30. Specifically, the Authors assessed the different accuracy of the three CKD-EPI formulas in people with measured GFR above or below 60 mL/min/1.73 m2, aged < 70 versus ≥ 70 years, or Asians versus non-Asians. Precision was assessed by the coefficient of correlation (R) between measured GFR and estimated GFR.

P0664CKDSENS, A NOVEL HEALTHCARE PLATFORM FOR CHRONIC KIDNEY DISEASE

Abstract Background and Aims The 10% of the global adult population, more than 730 million people, suffers from some degree of chronic kidney disease (CKD). From that population, a 30% is suffering from an advanced stage of the disease. Approximately 38 million of the European population is affected by an advanced stage renal disease with 1 million of new cases every year. These patients require close monitoring, which increase the burden of the disease. New tools and methods are required to improve the patients’ well-being, the perception and management of their disease, decrease the impact of the complications, as well as to delay of the progression of the disease. Method Seven partners have joined in the CKDSens consortium and are contributing to the project with different expertise and technical resources (medical, technological, educational, business and management): CreatSens Health SL, Hospital Clínic de Barcelona – Fundació Privada Clínic per a la Recerca Biomèdica, Genesis Biomed, Eurecat, Universitat de Barcelona, Universidad Politécnica de Madrid, and Madopa. This consortium is a novel and unique technological platform, combining in vitro diagnostic devices and software components, that connects patients with CKD and healthcare professionals to improve the well-being of people and the efficiency of the healthcare system by monitoring relevant biomarkers out of the hospital in a simple and cost- effective connected paper-based sensors. The proposal aims to increase the quality of life of CKD patients through early diagnostics, real time monitoring and personalization of therapies. Results The CKDSens consortium is developing a novel technological platform for real-time and low-cost diagnostics for two key biomarkers in renal diseases (creatinine and potassium), which include a new point-of-care device that allows monitoring by remote control these biomarkers. The technology has been patented for both biomarkers, and it has been transferred to CreatSens, a spinoff from Universitat Rovira i Virgili. The product integrates paper-based sensors in a drop of blood analysis, wireless connectivity and a digital platform as data analytics. The aim of the consortium is to validate the use of a new medical device as a product that can fit and truly generate value and business. Through that perspective, the optimization, manufacturing and validation of the tool and the business case will be performed as a first step, while usability, end user interaction and regulatory pathway will be developed in the second step. CKDSens will afford a novel approach to embed healthcare in daily life and routine. This new strategy implies production and commercialization for prevention and diagnose where markets are well known and validated. The aim is to mimic a well-known business model such as glucometer, translating this one into renal diseases. CKDSens has risen funding for this purpose through a grant of the European Institute of Innovation and Technology (EIT Health, ID Project 19579), and it is working to have validated this device at the end of the year. This requires also a clinical validation, which will be performed in a clinical trial in the second half of the year. Conclusion CKDSens consortium has been created as a novel technological platform to develop and validate a new medical device for a remote control of patients with CKD, in order to increase the quality of life of CKD patients through early diagnostics, real time monitoring and personalization of therapies. It is expected to have this device designed and validated by the end of the year 2020 and ready for further commercialization.

Urinary Extracellular Vesicles as Biomarkers of Kidney Disease: From Diagnostics to Therapeutics.

Cell-derived extracellular vesicles (EVs) can be isolated from various body fluids, including urine. Urinary EVs have gained important recognition as potential diagnostic biomarkers in renal disease since their cargo includes nucleic acids, proteins, and other cellular components, which likely mirror the physiological and possibly pathophysiological state of cells along the nephron. Accumulating evidence highlights the feasibility of using EVs as biomarkers for diagnostic, prognostic, and therapeutic purposes in several forms of renal disease, such as acute kidney injury, glomerulonephritis, and renal transplantation. Additionally, exogenous delivery of EVs released in vitro by cells in culture may have salutary benefits for renal diseases. In this review, we introduce recent studies that attempt to identify urinary EVs as candidate biomarkers for human kidney diseases and consider their potential implication as a therapeutic option in key kidney diseases.

Circular RNA in renal diseases.

Circular RNA (circRNA) is a newly described type of non‐coding RNA. Active research is greatly enriching the current understanding of the expression and role of circRNA, and a large amount of evidence has implicated circRNA in the pathogenesis of certain renal diseases, such as renal cell carcinoma, acute kidney injury, diabetic nephropathy and lupus nephritis. Studies have found evidence that circRNAs regulate programmed cell death, invasion, and metastasis and serve as biomarkers in renal diseases. Recently, circRNAs were identified in exosomes secreted by the kidneys. Nevertheless, the function of circRNA in renal diseases remains ambiguous. Given that circRNAs are regulators of gene expression, they may be involved in the pathology of multiple renal diseases. Additionally, emerging evidence is showing that circulating circRNAs may serve as novel biomarkers for renal disease. In this review, we have summarized the identification, biogenesis, degradation, and functions of circRNA and have evaluated the roles of circRNA in renal diseases.

Urinary MicroRNAs in Environmental Health: Biomarkers of Emergent Kidney Injury and Disease

There is a critical need for sensitive biomarkers of renal disease and progression. Micro(mi)RNAs are attractive as next-generation biomarkers in kidney disease, particularly as urine miRNAs can inform kidney function and cellular integrity. This review summarizes recent epidemiologic and toxicologic advances using urinary miRNAs and exosomal miRNAs as novel biomarkers of chemical exposure and of kidney damage and disease. Urine miRNA biomarkers offer improved stability over protein in stored samples, relative ease of collection and quantitation, and conserved sequence homology across species. Particularly in the case of emergent environmental health threats such as chronic kidney disease of unknown origin, urinary miRNAs hold promise as biomarkers of disease and/or exposure. We present evidence to address scientific knowledge gaps, comment on the relevance of urine-derived miRNAs in environmental health research, and discuss limitations and recommendations for future directions needed to advance miRNA biomarker strategies.

Assessment of Urinary MicroRNAs by Quantitative Polymerase Chain Reaction in Diabetic Nephropathy Patients.

Urinary microRNAs show promise as noninvasive biomarkers in renal disease. Here, we describe a detailed protocol for the column-based extraction and quantification of miRNAs by reverse-transcription quantitative polymerase chain reaction (RT-qPCR) from urine samples.

Consensus-based technical recommendations for clinical translation of renal diffusion-weighted MRI

ObjectivesStandardization is an important milestone in the validation of DWI-based parameters as imaging biomarkers for renal disease. Here, we propose technical recommendations on three variants of renal DWI, monoexponential DWI, IVIM and DTI, as well as associated MRI biomarkers (ADC, D, D*, f, FA and MD) to aid ongoing international efforts on methodological harmonization.Materials and methodsReported DWI biomarkers from 194 prior renal DWI studies were extracted and Pearson correlations between diffusion biomarkers and protocol parameters were computed. Based on the literature review, surveys were designed for the consensus building. Survey data were collected via Delphi consensus process on renal DWI preparation, acquisition, analysis, and reporting. Consensus was defined as ≥ 75% agreement.ResultsCorrelations were observed between reported diffusion biomarkers and protocol parameters. Out of 87 survey questions, 57 achieved consensus resolution, while many of the remaining questions were resolved by preference (65–74% agreement). Summary of the literature and survey data as well as recommendations for the preparation, acquisition, processing and reporting of renal DWI were provided.DiscussionThe consensus-based technical recommendations for renal DWI aim to facilitate inter-site harmonization and increase clinical impact of the technique on a larger scale by setting a framework for acquisition protocols for future renal DWI studies. We anticipate an iterative process with continuous updating of the recommendations according to progress in the field.

MicroRNAs as non-invasive biomarkers of renal disease.

MicroRNAs as non-invasive biomarkers of renal disease.

Role of hypoxia-inducible factor 1α as a potential biomarker for renal diseases-A systematic review.

Renal cells need oxygen for homeostasis; it is known for adjusting cellular functioning and the energy obtainment have a broad relationship with cellular respiration, through the O2 bioavailability. O2 homeostasis regulation in the kidney is mediated by hypoxia-inducible factors (HIFs). HIF is divided into three α isoforms, represented by HIF-1α, HIF-2α, and HIF-3α in addition to three paralogs of HIF-1β; these are involved in some metabolic processes, as well as in the pathogenesis of several diseases. Renal biopsy analyses of patients and experimental animal models aim to understand the relationship between HIF and protection against developing renal diseases or the induction of their onset, being thus this molecule can be considered a potential biomarker of renal disease. We carried out a systematic review to which we included studies on HIF-1α and renal disease in the last 5years (2013-2018) in researches with humans and/or animal model through searches in three databases: LILACS, PubMed, and SciELO by two researchers. We obtained 22 articles that discussed the relationship with HIF as inductor or protector against renal disease and no relation between HIF and renal. We observed controversies remain regarding the relation between of HIF with renal diseases; this may be related to the different intracellular pathways mediated by HIF-1α, thereby determining differentiated cellular responses.

Renal ADAM10 and 17: Their Physiological and Medical Meanings.

A disintegrin and metalloproteinases (ADAMs) are a Zn2+-dependent transmembrane and secreted metalloprotease superfamily, so-called “molecular scissors,” and they consist of an N-terminal signal sequence, a prodomain, zinc-binding metalloprotease domain, disintegrin domain, cysteine-rich domain, transmembrane domain and cytoplasmic tail. ADAMs perform proteolytic processing of the ectodomains of diverse transmembrane molecules into bioactive mediators. This review summarizes on their most well-known members, ADAM10 and 17, focusing on the kidneys. ADAM10 is expressed in renal tubular cells and affects the expression of specific brush border genes, and its activation is involved in some renal diseases. ADAM17 is weakly expressed in normal kidneys, but its expression is markedly induced in the tubules, capillaries, glomeruli, and mesangium, and it is involved in interstitial fibrosis and tubular atrophy. So far, the various substrates have been identified in the kidneys. Shedding fragments become released ligands, such as Notch and EGFR ligands, and act as the chemoattractant factors including CXCL16. Their ectodomain shedding is closely correlated with pathological factors, which include inflammation, interstitial fibrosis, and renal injury. Also, the substrates of both ADAMs contain the molecules that play important roles at the plasma membrane, such as meaprin, E-cadherin, Klotho, and CADM1. By being released into urine, the shedding products could be useful for biomarkers of renal diseases, but ADAM10 and 17 per se are also notable as biomarkers. Furthermore, ADAM10 and/or 17 inhibitions based on various strategies such as small molecules, antibodies, and their recombinant prodomains are valuable, because they potentially protect renal tissues and promote renal regeneration. Although temporal and spatial regulations of inhibitors are problems to be solved, their inhibitors could be useful for renal diseases.

Traditional Renal Biomarkers and New Approaches to Diagnostics

Traditional biomarkers of renal disease have a number of limitations, whether evaluating veterinary patients or performing preclinical toxicity studies. Serum creatinine and urea nitrogen are affected by nonrenal influences that limit their usefulness for detecting small but significant decreases in glomerular filtration rate (GFR) in veterinary patients. These nonrenal influences can be more controlled in preclinical studies than in clinical patients; however, because of its high functional reserve, these estimates of GFR are insensitive for detecting kidney injury prior to loss of a substantial proportion of functioning nephrons. Urine biomarkers can be highly sensitive for tubular or glomerular injury that might lead to irreversible damage to the nephron. Several proteins are qualified by the Food and Drug Administration for nonclinical application as urinary biomarkers of drug-induced nephrotoxicity, and many of these also have preliminary data supporting their usefulness for kidney injury in dogs and cats. In addition to these relatively recently identified biomarkers, efforts are underway to discover new renal biomarkers using a variety of techniques including liquid chromatography-mass spectrometry and small RNA sequencing. Ultimately, the interplay between preclinical studies and clinical patients in discovery and validation of renal biomarkers is critical to their successful implementation.

Novel finding of caveolin-2 in apical membranes of proximal tubule and first detection of caveolin-2 in urine: A promising biomarker of renal disease.

Caveolin-2 (Cav-2) is expressed in a variety of cell tissue, and it has also been found in renal tissue. The expression of Cav-2 in proximal tubules is still unclear. The aim of this study was to carry out a complete evaluation of the expression pattern of Cav-2 in rat renal cortex to clarify and deepen the knowledge about the localization of Cav-2 in the proximal tubules and also to evaluate its presence in urine. Male Wistar rats were used to assess Cav-2 expression by Western blot analysis in homogenates, apical, and basolateral membranes from kidney cortex, in lysates and total plasma membranes from renal cortical cell suspensions, in urine, and in urinary exosomes. Cav-2 was clearly expressed in renal cortex homogenates and in both apical and basolateral membranes isolated from kidney cortex, with a greater expression on the former membranes. It was also observed in lysates and in plasma membranes from cortical cell suspensions. Moreover, Cav-2 was found in urine and in its exosomal fraction. These results confirmed the presence of Cav-2 in proximal tubule cells in the kidney of healthy rats, and showed for the first time its expression at the apical membrane of these cells and in urine. Besides, urinary exosomal pathway could be involved in Cav-2 urinary excretion under normal conditions. We observed an increase in the urinary abundance of Cav-2 in two models of acute kidney injury, and thus we proposed the urinary excretion of Cav-2 as a potential biomarker of kidney injury.

Urinary angiostatin, CXCL4 and VCAM-1 as biomarkers of lupus nephritis

BackgroundThe aim was to study urinary angiostatin, CXC chemokine ligand 4 (CXCL4) and vascular cell adhesion molecule-1 (VCAM-1) as biomarkers of renal disease in systemic lupus erythematosus (SLE).MethodPatients who fulfilled ≥ 4 American College of Rheumatology (ACR) criteria for SLE with active renal, active non-renal or inactive disease, and a group of healthy controls were studied. Urine samples were assayed for angiostatin, CXCL4 and VCAM-1 by ELISA, and normalized by creatinine. Receiver operating characteristic analysis was performed to obtain the best cutoff values to calculate the performance of these markers in differentiating the different groups of patients as compared to anti-double-stranded DNA (anti-dsDNA) and complement C3. Correlation between these urinary biomarkers and various renal parameters was also tested.ResultsPatients with SLE (n = 227; 80 with inactive SLE, 67 with active non-renal disease and 80 with active renal disease; 94% women; age 39.2 ± 13.8 years) and 53 controls (96% women) were studied. All were ethnic Chinese. Urinary angiostatin, CXCL4 and VCAM-1 (normalized for creatinine) were significantly higher in patients with active renal disease than in patients with active non-renal disease, patients with inactive SLE and controls. These markers correlated significantly with total SLE disease activity index (SLEDAI) and renal SLEDAI scores, and with the urinary protein-to-creatinine ratio. Urine angiostatin exhibited higher specificity and sensitivity in differentiating active renal from active non-renal SLE (area under the curve (AUC) 0.87) than serum anti-dsDNA/C3. Urine CXCL4 (AUC 0.64) and VCAM-1 (AUC 0.73), on the other hand, performed similarly to anti-dsDNA/C3. All three markers performed comparably to anti-dsDNA/C3 in distinguishing active from inactive SLE. In a subgroup of 68 patients with paired renal biopsy, the urinary levels of these proteins did not differ significantly between the proliferative and non-proliferative types of lupus nephritis. Urinary CXCL4 and VCAM-1 correlated significantly with the histologic activity score, and urinary angiostatin correlated significantly with proteinuria in this subgroup.ConclusionsUrinary angiostatin, CXCL4 and VCAM-1 are potential biomarkers for SLE, in particular lupus nephritis. Further longitudinal studies are necessary to delineate the performance of these markers in predicting renal flares and prognosis in SLE patients.

Novel Biomarkers in the Diagnosis of Chronic Kidney Disease and the Prediction of Its Outcome

In its early stages, symptoms of chronic kidney disease (CKD) are usually not apparent. Significant reduction of the kidney function is the first obvious sign of disease. If diagnosed early (stages 1 to 3), the progression of CKD can be altered and complications reduced. In stages 4 and 5 extensive kidney damage is observed, which usually results in end-stage renal failure. Currently, the diagnosis of CKD is made usually on the levels of blood urea and serum creatinine (sCr), however, sCr has been shown to be lacking high predictive value. Due to the development of genomics, epigenetics, transcriptomics, proteomics, and metabolomics, the introduction of novel techniques will allow for the identification of novel biomarkers in renal diseases. This review presents some new possible biomarkers in the diagnosis of CKD and in the prediction of outcome, including asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), uromodulin, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), miRNA, ncRNA, and lincRNA biomarkers and proteomic and metabolomic biomarkers. Complicated pathomechanisms of CKD development and progression require not a single marker but their combination in order to mirror all types of alterations occurring in the course of this disease. It seems that in the not so distant future, conventional markers may be exchanged for new ones, however, confirmation of their efficacy, sensitivity and specificity as well as the reduction of analysis costs are required.