1 3095 162 GENOMIC APPROACHES IN THE SEARCH FOR MOLECULAR BIOMARKERS IN CHRONIC KIDNEY DISEASE. BACKGROUND: CHRONIC KIDNEY DISEASE (CKD) IS RECOGNISED AS A GLOBAL PUBLIC HEALTH PROBLEM, MORE PREVALENT IN OLDER PERSONS AND ASSOCIATED WITH MULTIPLE CO-MORBIDITIES. DIABETES MELLITUS AND HYPERTENSION ARE COMMON AETIOLOGIES FOR CKD, BUT IGA GLOMERULONEPHRITIS, MEMBRANOUS GLOMERULONEPHRITIS, LUPUS NEPHRITIS AND AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE ARE ALSO COMMON CAUSES OF CKD. MAIN BODY: CONVENTIONAL BIOMARKERS FOR CKD INVOLVING THE USE OF ESTIMATED GLOMERULAR FILTRATION RATE (EGFR) DERIVED FROM FOUR VARIABLES (SERUM CREATININE, AGE, GENDER AND ETHNICITY) ARE RECOMMENDED BY CLINICAL GUIDELINES FOR THE EVALUATION, CLASSIFICATION, AND STRATIFICATION OF CKD. HOWEVER, THESE CLINICAL BIOMARKERS PRESENT SOME LIMITATIONS, ESPECIALLY FOR EARLY STAGES OF CKD, ELDERLY INDIVIDUALS, EXTREME BODY MASS INDEX VALUES (SERUM CREATININE), OR ARE INFLUENCED BY INFLAMMATION, STEROID TREATMENT AND THYROID DYSFUNCTION (SERUM CYSTATIN C). THERE IS THEREFORE A NEED TO IDENTIFY ADDITIONAL NON-INVASIVE BIOMARKERS THAT ARE USEFUL IN CLINICAL PRACTICE TO HELP IMPROVE CKD DIAGNOSIS, INFORM PROGNOSIS AND GUIDE THERAPEUTIC MANAGEMENT. CONCLUSION: CKD IS A MULTIFACTORIAL DISEASE WITH ASSOCIATED GENETIC AND ENVIRONMENTAL RISK FACTORS. HENCE, MANY STUDIES HAVE EMPLOYED GENETIC, EPIGENETIC AND TRANSCRIPTOMIC APPROACHES TO IDENTIFY BIOMARKERS FOR KIDNEY DISEASE. IN THIS REVIEW, WE HAVE SUMMARISED THE MOST IMPORTANT STUDIES IN HUMANS INVESTIGATING GENOMIC BIOMARKERS FOR CKD IN THE LAST DECADE. SEVERAL GENES, INCLUDING UMOD, SHROOM3 AND ELMO1 HAVE BEEN STRONGLY ASSOCIATED WITH RENAL DISEASES, AND SOME OF THEIR TRAITS, SUCH AS EGFR AND SERUM CREATININE. THE ROLE OF EPIGENETIC AND TRANSCRIPTOMIC BIOMARKERS IN CKD AND RELATED DISEASES IS STILL UNCLEAR. THE COMBINATION OF MULTIPLE BIOMARKERS INTO CLASSIFIERS, INCLUDING GENOMIC, AND/OR EPIGENOMIC, MAY GIVE A MORE COMPLETE PICTURE OF KIDNEY DISEASES.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
2 2982  38 GENETIC CONSIDERATIONS IN PEDIATRIC CHRONIC KIDNEY DISEASE. CHRONIC KIDNEY DISEASE (CKD) IN CHILDREN IS AN IRREVERSIBLE PROCESS THAT, IN SOME CASES, MAY LEAD TO END-STAGE RENAL DISEASE. THE MAJORITY OF CHILDREN WITH CKD HAVE A CONGENITAL DISORDER OF THE KIDNEY OR UROLOGICAL TRACT ARISING FROM BIRTH. THERE IS STRONG EVIDENCE FOR BOTH A GENETIC AND EPIGENETIC COMPONENT TO PROGRESSION OF CKD. UTILIZATION OF GENE-MAPPING STRATEGIES, RANGING FROM GENOME-WIDE ASSOCIATION STUDIES TO SINGLE-NUCLEOTIDE POLYMORPHISM ANALYSIS, SERVES TO IDENTIFY POTENTIAL GENETIC VARIANTS THAT MAY LEND TO DISEASE VARIATION. GENOME-WIDE ASSOCIATION STUDIES EVALUATING POPULATION-BASED DATA HAVE IDENTIFIED DIFFERENT LOCI ASSOCIATED WITH CKD PROGRESSION. ANALYSIS OF SINGLE-NUCLEOTIDE POLYMORPHISMS ON AN INDIVIDUAL LEVEL SUGGESTS THAT SECONDARY SYSTEMIC SEQUELAE OF CKD ARE CLOSELY RELATED TO DYSFUNCTION OF THE CARDIOVASCULAR-INFLAMMATORY AXIS AND MAY LEAD TO ADVANCED CARDIOVASCULAR DISEASE THROUGH ABNORMAL VASCULAR CALCIFICATION AND ACTIVATION OF THE RENIN-ANGIOTENSIN SYSTEM. SIMILARLY, GENETIC VARIANTS AFFECTING CYTOKINE CONTROL, FIBROSIS, AND PARENCHYMAL DEVELOPMENT MAY MODULATE CKD THROUGH DEVELOPMENT AND ACCELERATION OF RENAL INTERSTITIAL FIBROSIS. EPIGENETIC STUDIES EVALUATE MODIFICATION OF THE GENOME THROUGH DNA METHYLATION, HISTONE MODIFICATION, OR RNA INTERFERENCE, WHICH MAY BE DIRECTLY INFLUENCED BY EXTERNAL OR ENVIRONMENTAL FACTORS DIRECTING GENOMIC EXPRESSION. LASTLY, IMPROVED UNDERSTANDING OF THE GENETIC AND EPIGENETIC CONTRIBUTION TO CKD PROGRESSION MAY ALLOW PROVIDERS TO IDENTIFY A POPULATION AT ACCELERATED RISK FOR DISEASE PROGRESSION AND APPLY NOVEL THERAPIES TARGETED AT THE GENETIC MECHANISM OF DISEASE.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
3 2955  47 GENETIC AND EPIGENETIC FACTORS INFLUENCING CHRONIC KIDNEY DISEASE. CHRONIC KIDNEY DISEASE (CKD) HAS BECOME A SERIOUS PUBLIC HEALTH PROBLEM BECAUSE OF ITS ASSOCIATED MORBIDITY, PREMATURE MORTALITY, AND ATTENDANT HEALTHCARE COSTS. THE RISING NUMBER OF PERSONS WITH CKD IS LINKED WITH THE AGING POPULATION STRUCTURE AND AN INCREASED PREVALENCE OF DIABETES, HYPERTENSION, AND OBESITY. THERE IS AN INHERITED RISK ASSOCIATED WITH DEVELOPING CKD, AS EVIDENCED BY FAMILIAL CLUSTERING AND DIFFERING PREVALENCE RATES ACROSS ETHNIC GROUPS. PREVIOUS STUDIES TO DETERMINE THE INHERITED RISK FACTORS FOR CKD RARELY IDENTIFIED GENETIC VARIANTS THAT WERE ROBUSTLY REPLICATED. HOWEVER, IMPROVEMENTS IN GENOTYPING TECHNOLOGIES AND ANALYTIC METHODS ARE NOW HELPING TO IDENTIFY PROMISING GENETIC LOCI AIDED BY INTERNATIONAL COLLABORATION AND MULTICONSORTIA EFFORTS. MORE RECENTLY, EPIGENETIC MODIFICATIONS HAVE BEEN PROPOSED TO PLAY A ROLE IN BOTH THE INHERITED SUSCEPTIBILITY TO CKD AND, IMPORTANTLY, TO EXPLAIN HOW THE ENVIRONMENT DYNAMICALLY INTERACTS WITH THE GENOME TO ALTER AN INDIVIDUAL'S DISEASE RISK. GENOME-WIDE, EPIGENOME-WIDE, AND WHOLE TRANSCRIPTOME STUDIES HAVE BEEN PERFORMED, AND OPTIMAL APPROACHES FOR INTEGRATIVE ANALYSIS ARE BEING DEVELOPED. THIS REVIEW SUMMARIZES RECENT RESEARCH AND THE CURRENT STATUS OF GENETIC AND EPIGENETIC RISK FACTORS INFLUENCING CKD USING POPULATION-BASED INFORMATION.	2014	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
4 1883  49 END-STAGE RENAL DISEASE, INFLAMMATION AND CARDIOVASCULAR OUTCOMES. DESPITE MARKED IMPROVEMENTS IN RENAL REPLACEMENT THERAPY DURING THE LAST 30 YEARS, THE AGE-ADJUSTED MORTALITY RATE IN END-STAGE RENAL DISEASE (ESRD) PATIENTS IS STILL UNACCEPTABLY HIGH AND COMPARABLE TO THAT OF MANY MALIGNANCIES. CARDIOVASCULAR DISEASE (CVD) REMAINS THE MAJOR CAUSE OF MORBIDITY AND MORTALITY IN ESRD PATIENTS. HOWEVER, TRADITIONAL RISK FACTORS CAN ONLY PARTIALLY EXPLAIN THE HIGH PREMATURE CARDIOVASCULAR BURDEN IN THIS POPULATION. NONTRADITIONAL RISK FACTORS, INCLUDING PERSISTENT LOW-GRADE INFLAMMATION, ARE CRITICAL IN THE PATHOGENESIS OF ATHEROSCLEROSIS, VASCULAR CALCIFICATION, AND OTHER CAUSES OF CVD AND MAY ALSO CONTRIBUTE TO PROTEIN-ENERGY WASTING AND OTHER COMPLICATIONS IN CHRONIC KIDNEY DISEASE (CKD) PATIENTS. INFLAMMATORY BIOMARKERS, SUCH AS HIGH SENSITIVITY C-REACTIVE PROTEIN AND INTERLEUKIN-6, INDEPENDENTLY PREDICT MORTALITY IN THESE PATIENTS. THE CAUSES OF INFLAMMATION IN CKD ARE MULTIFACTORIAL AND INCLUDE IMBALANCE BETWEEN INCREASED PRODUCTION (DUE TO MULTIPLE SOURCES OF INFLAMMATORY STIMULI SUCH AS OXIDATIVE STRESS, ACIDOSIS, VOLUME OVERLOAD, CO-MORBIDITIES, ESPECIALLY INFECTIONS, GENETIC AND EPIGENETIC INFLUENCES, AND THE DIALYSIS PROCEDURE) AND INADEQUATE REMOVAL (DUE TO DECREASED GLOMERULAR FILTRATION RATE OR IN ESRD PATIENTS, INADEQUATE DIALYTIC CLEARANCE) OF PRO-INFLAMMATORY CYTOKINES. THOUGH THERE ARE CURRENTLY NO ESTABLISHED GUIDELINES FOR THE TREATMENT OF LOW-GRADE INFLAMMATION IN ESRD PATIENTS, SEVERAL STRATEGIES HAVE BEEN PROPOSED, SUCH AS LIFESTYLE MODIFICATIONS, PHARMACOLOGICAL TREATMENT, AND OPTIMIZATION OF DIALYSIS. FURTHER STUDIES ON PATHWAYS INVOLVED IN PATHOGENIC PROCESSES OF INFLAMMATION IN ESRD, AND LONG-TERM EFFECTS OF ANTI-INFLAMMATORY INTERVENTIONS TARGETING PRODUCTION OR REMOVAL OF CYTOKINES OR BOTH ON PREMATURE CVD AND CLINICAL OUTCOMES IN THIS PATIENT GROUP ARE WARRANTED.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
5 5846  43 STUDY PROTOCOL: RATIONALE AND DESIGN OF THE COMMUNITY-BASED PROSPECTIVE COHORT STUDY OF KIDNEY FUNCTION AND DIABETES IN RURAL NEW MEXICO, THE COMPASS STUDY. BACKGROUND: RURAL AREAS IN THE STATE OF NEW MEXICO HAVE BEEN THE "GROUND-ZERO" FOR THE EPIDEMIC OF DIABETIC CHRONIC KIDNEY DISEASE (CKD) IN THE UNITED STATES. HOWEVER, THERE IS LIMITED RESEARCH ABOUT RISK FACTORS OF DIABETIC CKD IN THIS AREA AND SCARCE DATA REGARDING THE PERFORMANCE OF EMERGING MARKERS OF RENAL FILTRATION AND EPIGENETIC BIOMARKERS OF RENAL FUNCTION AND DIABETES IN THIS AREA WITH ITS UNIQUE ETHNIC/RACIAL POPULATION. WE DESIGNED THE COMPASS STUDY AS A COMMUNITY-BASED PROGRAM IN RURAL NEW MEXICO AIMING TO SCREEN FOR CKD AND TO DISCOVER CKD-RELATED TRANSLATIONAL BIOMARKERS. METHODS/DESIGN: THE STUDY INVOLVES A PROSPECTIVE, LONGITUDINAL COHORT DESIGN INVOLVING INDIVIDUALS LIVING IN RURAL NEW MEXICO. PARTICIPANTS UNDERGO A SCREENING FOR KIDNEY DISEASE USING MARKERS OF ABNORMAL RENAL FILTRATION (IMPAIRED GLOMERULAR FILTRATION RATE) OR DAMAGE (ALBUMINURIA). THOSE FOUND TO HAVE CKD ON THE BASIS OF THESE TESTS OR THOSE AT RISK FOR CKD ARE ENROLLED IN A PROSPECTIVE LONGITUDINAL COHORT. WE MEASURE MARKERS OF RENAL FUNCTION, INSULIN RESISTANCE AND EPIGENETICS (MICRORNAS) ON PATIENTS. INDIVIDUALS ARE INVITED TO PARTICIPATE IN INTERVIEWS AND FOCUS GROUPS IN ORDER TO CHARACTERIZE THEIR ATTITUDES TOWARDS RESEARCH AND BARRIERS OR FACILITATORS TO PARTICIPATION IN FUTURE RESEARCH STUDIES ABOUT KIDNEY DISEASE. DISCUSSION: THIS STUDY WILL PROVIDE IMPORTANT DATA ABOUT THE LOCAL EPIDEMIOLOGY OF KIDNEY DISEASE IN A HIGH-RISK RURAL SETTING AND THE UTILITY OF EMERGING RENAL FILTRATION MARKERS (BETA 2 MICROGLOBULIN AND CYSTATIN C), WHILE GENERATING DATA AND METHODS FOR THE ANALYSES OF MICRORNA BIOMARKERS. THE QUALITATIVE RESEARCH SUBPROJECT WILL IDENTIFY FACTORS ASSOCIATED WITH INCREASED WILLINGNESS TO PARTICIPATE IN FUTURE TRANSLATIONAL RESEARCH PROJECTS. WITH ITS GEOGRAPHICAL FOCUS, THIS STUDY WILL ADDRESS A CRITICAL DISPARITY IN KIDNEY DISEASE RESEARCH, WHILE GENERATING NOVEL EPIGENETIC DATA THAT ARE RELEVANT FOR FUTURE STUDIES IN THE GENERAL POPULATION.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
6  931  37 CHRONIC KIDNEY DISEASE IN CHILDREN AND THE ROLE OF EPIGENETICS: FUTURE THERAPEUTIC TRAJECTORIES. GLOBAL DIFFERENCES IN THE OBSERVED CAUSES OF CHRONIC KIDNEY DISEASE (CKD) IN CHILDREN ARE WELL DOCUMENTED AND ARE ATTRIBUTED TO DISSIMILARITIES IN CLIME, RACE, HEREDITARY, AND ANCESTRY. THUS, FAMILIAL CLUSTERING AND DISPARITIES IN CKD PREVALENCE RATES ACROSS ETHNIC AND RACIAL GROUPS INDICATE THAT THE PROGRESSION OF RENAL DISEASE HAS A STRONG GENETIC COMPONENT. MAMMALIAN STUDIES HAVE DEMONSTRATED A FEASIBLE NEXUS BETWEEN NUTRITION AND NON-GENETIC EXPOSURE (AROUND THE TIME OF CONCEPTION AND IN EPIGENETIC CHANGES) IN THE EXPRESSION OF MAJOR GENES IDENTIFIED IN RENAL ORGANOGENESIS. THE MAJOR CONSEQUENCE IS A REDUCTION IN THE NUMBER OF NEPHRONS, WITH SUBSEQUENT PREDISPOSITION TO HYPERTENSION AND CKD. IDENTIFYING THESE EPIGENETIC CHANGES IS CRUCIAL (DUE TO THEIR POTENTIALLY REVERSIBLE NATURE), AS THEY MAY SERVE AS FUTURE THERAPEUTIC TARGETS TO PREVENT KIDNEY FIBROSIS AND CKD. DESPITE PROGRESS IN THE FIELD OF EPIGENETICS IN ONCOLOGY, RESEARCH IN OTHER SUBSPECIALTIES OF MEDICINE IS LARGELY EXPERIMENTAL WITH FEW EXISTING STUDIES REGARDING THE CLINICAL IMPLICATION OF EPIGENETICS IN RENAL DISEASE. THERAPEUTIC TRAJECTORIES FOR CKD IN CHILDREN BASED ON THE INFLUENCE OF EPIGENETICS MAY EVENTUALLY REVOLUTIONIZE THE MANAGEMENT OF THIS DISEASE. THE AIM OF THE CURRENT NARRATIVE REVIEW IS TO APPRAISE THE ROLE OF EPIGENETICS IN CKD, AND HIGHLIGHT THE POTENTIAL FUTURE THERAPEUTIC PATHWAYS.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
7 1170  54 CONTRIBUTION OF GENETICS AND EPIGENETICS TO PROGRESSION OF KIDNEY FIBROSIS. CHRONIC KIDNEY DISEASE (CKD) WHICH CAN LEAD TO END-STAGE RENAL FAILURE REMAINS A PRINCIPAL CHALLENGE IN NEPHROLOGY. WHILE MECHANISTIC STUDIES PROVIDED EXTENSIVE INSIGHTS INTO THE COMMON PATHWAYS OF FIBROGENESIS WHICH UNDERLIE THE PROGRESSION OF CKD, THESE PRE-CLINICAL STUDIES FAIL TO FULLY EXPLAIN THE VASTLY DIFFERENT PROGRESSION SLOPES OF INDIVIDUAL PATIENTS. RECENT STUDIES PROVIDE EVIDENCE THAT GENETIC POLYMORPHISMS AND EPIGENETIC VARIATIONS DETERMINE THE INDIVIDUAL SUSCEPTIBILITY OF PATIENTS TO DEVELOP CHRONIC PROGRESSIVE KIDNEY DISEASE. HERE, WE REVIEW RECENT INSIGHTS THAT WERE PROVIDED BY GENOME-WIDE ASSOCIATION STUDIES (GWASS), GENE-LINKAGE STUDIES AND EPIGENOME ANALYSIS. THE PROGRESSION OF CKD TOWARDS END-STAGE RENAL FAILURE REMAINS A PRINCIPAL UNSOLVED PROBLEM IN NEPHROLOGY AS EFFECTIVE THERAPIES AND PREDICTIVE TESTS ARE STILL NOT AVAILABLE [ 1, 2]. CHRONIC PROGRESSIVE KIDNEY DISEASE IS CAUSED BY A WIDE RANGE OF DISEASES, WITH DIABETES MELLITUS, HYPERTENSION AND PRIMARY GLOMERULOPATHIES BEING THE MOST COMMON CAUSES IN THE WESTERN WORLD [ 3]. INFECTIONS, PHYSICAL OBSTRUCTION, INTERSTITIAL NEPHRITIDES AND GENETIC CYSTIC KIDNEY DISEASES ARE ALSO COMMON CAUSES OF END-STAGE RENAL DISEASE (ESRD) [ 3]. REGARDLESS OF THE PRIMARY UNDERLYING DISEASE, CHRONICALLY INJURED KIDNEYS ARE HISTOMORPHOLOGICALLY CHARACTERIZED BY TUBULOINTERSTITIAL FIBROSIS [ 1]. IN FACT, THE EXTENT OF TUBULOINTERSTITIAL FIBROSIS IS THE BEST PREDICTOR FOR KIDNEY SURVIVAL, IRRESPECTIVE OF THE UNDERLYING DISEASE. FOR THIS REASON, FIBROSIS IS CONSIDERED THE COMMON PATHWAY OF CHRONIC PROGRESSIVE KIDNEY DISEASE [ 1]. FIBROGENESIS IS A PATHOLOGICAL SCARRING PROCESS WHICH INVOLVES ACCUMULATION OF ACTIVATED FIBROBLASTS, EXCESSIVE DEPOSITION OF EXTRACELLULAR MATRIX, FAILED REGENERATION OF TUBULAR EPITHELIUM, MICROVASCULAR RAREFACTION AND (MOSTLY STERILE) INFLAMMATION [ 4]. FIBROGENESIS DEPENDS ON A COMPLEX INTERACTION OF THE INVOLVED CELL TYPES WHICH IS ORCHESTRATED BY AN EXTENSIVE NETWORK OF GROWTH FACTORS AND SIGNALLING PATHWAYS (WHICH ARE REVIEWED EXTENSIVELY ELSEWHERE) [ 1]. IN VIEW OF THE DETAILED MECHANISTIC KNOWLEDGE OF THE PATHWAYS THAT ORCHESTRATE RENAL FIBROGENESIS, IT IS PUZZLING WHY PROGRESSION RATES OF CKD DIFFER DRAMATICALLY AMONG PATIENTS WITH IDENTICAL UNDERLYING DISEASES [ 1, 2]. THE FIBROTIC PATHWAYS ARE KNOWN, BUT THE SWITCHES THAT CONTROL THEIR INTENSITIES AND WHICH DETERMINE THE SPEED AT WHICH FIBROSIS MOVES ALONG THE PROGRESSION SLOPE ARE NOT YET UNDERSTOOD [ 1, 2]. THE CONCEPT THAT GENETIC POLYMORPHISMS ARE THE BASIS FOR INDIVIDUAL PROGRESSION RATES OF CKD IS AN OBVIOUS AND ATTRACTIVE ONE. DISTINCT SUSCEPTIBILITIES OF DIFFERENT MOUSE AND RAT STRAINS TO EXPERIMENTAL CKD ARE A STRONG TESTAMENT OF THE IMPACT OF GENETIC VARIATIONS ON RENAL FIBROGENESIS. IDENTIFICATION OF THE UNDERLYING GENETIC POLYMORPHISMS AND MECHANISTIC PROOF OF THEIR INVOLVEMENT IN THE PROGRESSION OF CKD, HOWEVER, IS AN ONGOING CHALLENGE. THERE ARE TWO BASIC APPROACHES: ONE STRATEGY IS TO PERFORM UNBIASED SCREENING TO IDENTIFY GENES WHICH ARE ASSOCIATED WITH CHRONIC PROGRESSIVE KIDNEY DISEASE AND TO THEN PROVE THEIR MECHANISTIC RELEVANCE IN EXPERIMENTAL STUDIES ('GENOTYPE TO PHENOTYPE APPROACH'). THE SECOND STRATEGY IS TO SELECTIVELY ANALYSE POLYMORPHISMS OF GENES WHICH HAVE BEEN IDENTIFIED IN MECHANISTIC STUDIES AS DRIVERS OF RENAL FIBROGENESIS WITH REGARD TO THEIR ASSOCIATION WITH CKD (PHENOTYPE TO GENOTYPE APPROACH). THE PUZZLING OBSERVATION, HOWEVER, IS THAT GENETIC ANALYSIS AND MECHANISTIC STUDIES SO FAR RARELY COMPLEMENT EACH OTHER. THE CURRENT STATE OF AFFAIRS IS REVIEWED IN MORE DETAIL BELOW.	2014	

8 1388  34 DIABETIC PATIENTS WITH CHRONIC KIDNEY DISEASE: NON-INVASIVE ASSESSMENT OF CARDIOVASCULAR RISK. THE PREVALENCE AND BURDEN OF DIABETES MELLITUS AND CHRONIC KIDNEY DISEASE ON GLOBAL HEALTH AND SOCIOECONOMIC DEVELOPMENT IS ALREADY HEAVY AND STILL RISING. DIABETES MELLITUS BY ITSELF IS LINKED TO ADVERSE CARDIOVASCULAR EVENTS, AND THE PRESENCE OF CONCOMITANT CHRONIC KIDNEY DISEASE FURTHER AMPLIFIES CARDIOVASCULAR RISK. THE CULMINATION OF TRADITIONAL (MALE GENDER, SMOKING, ADVANCED AGE, OBESITY, ARTERIAL HYPERTENSION AND DYSLIPIDEMIA) AND NON-TRADITIONAL RISK FACTORS (ANEMIA, INFLAMMATION, PROTEINURIA, VOLUME OVERLOAD, MINERAL METABOLISM ABNORMALITIES, OXIDATIVE STRESS, ETC.) CONTRIBUTES TO ADVANCED ATHEROSCLEROSIS AND INCREASED CARDIOVASCULAR RISK. TO DECREASE THE MORBIDITY AND MORTALITY OF THESE PATIENTS DUE TO CARDIOVASCULAR CAUSES, TIMELY AND EFFICIENT CARDIOVASCULAR RISK ASSESSMENT IS OF HUGE IMPORTANCE. CARDIOVASCULAR RISK ASSESSMENT CAN BE BASED ON LABORATORY PARAMETERS, IMAGING TECHNIQUES, ARTERIAL STIFFNESS PARAMETERS, ANKLE-BRACHIAL INDEX AND 24 H BLOOD PRESSURE MEASUREMENTS. NEWER METHODS INCLUDE EPIGENETIC MARKERS, SOLUBLE ADHESION MOLECULES, CYTOKINES AND MARKERS OF OXIDATIVE STRESS. IN THIS REVIEW, THE AUTHORS PRESENT SEVERAL NON-INVASIVE METHODS OF CARDIOVASCULAR RISK ASSESSMENT IN PATIENTS WITH DIABETES MELLITUS AND CHRONIC KIDNEY DISEASE.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
9 6652  43 UPDATE ON INFLAMMATION IN CHRONIC KIDNEY DISEASE. BACKGROUND: DESPITE RECENT ADVANCES IN CHRONIC KIDNEY DISEASE (CKD) AND END-STAGE RENAL DISEASE (ESRD) MANAGEMENT, MORBIDITY AND MORTALITY IN THIS POPULATION REMAIN EXCEPTIONALLY HIGH. PERSISTENT, LOW-GRADE INFLAMMATION HAS BEEN RECOGNIZED AS AN IMPORTANT COMPONENT OF CKD, PLAYING A UNIQUE ROLE IN ITS PATHOPHYSIOLOGY AND BEING ACCOUNTABLE IN PART FOR CARDIOVASCULAR AND ALL-CAUSE MORTALITY, AS WELL AS CONTRIBUTING TO THE DEVELOPMENT OF PROTEIN-ENERGY WASTING. SUMMARY: THE VARIETY OF FACTORS CONTRIBUTE TO CHRONIC INFLAMMATORY STATUS IN CKD, INCLUDING INCREASED PRODUCTION AND DECREASED CLEARANCE OF PRO-INFLAMMATORY CYTOKINES, OXIDATIVE STRESS AND ACIDOSIS, CHRONIC AND RECURRENT INFECTIONS, INCLUDING THOSE RELATED TO DIALYSIS ACCESS, ALTERED METABOLISM OF ADIPOSE TISSUE, AND INTESTINAL DYSBIOSIS. INFLAMMATION DIRECTLY CORRELATES WITH THE GLOMERULAR FILTRATION RATE (GFR) IN CKD AND CULMINATES IN DIALYSIS PATIENTS, WHERE EXTRACORPOREAL FACTORS, SUCH AS IMPURITIES IN DIALYSIS WATER, MICROBIOLOGICAL QUALITY OF THE DIALYSATE, AND BIOINCOMPATIBLE FACTORS IN THE DIALYSIS CIRCUIT PLAY AN ADDITIONAL ROLE. GENETIC AND EPIGENETIC INFLUENCES CONTRIBUTING TO INFLAMMATORY ACTIVATION IN CKD ARE CURRENTLY BEING INTENSIVELY INVESTIGATED. A NUMBER OF INTERVENTIONS HAVE BEEN PROPOSED TO TARGET INFLAMMATION IN CKD, INCLUDING LIFESTYLE MODIFICATIONS, PHARMACOLOGICAL AGENTS, AND OPTIMIZATION OF DIALYSIS. IMPORTANTLY, SOME OF THESE THERAPIES HAVE BEEN RECENTLY TESTED IN RANDOMIZED CONTROLLED TRIALS. KEY MESSAGES: CHRONIC INFLAMMATION SHOULD BE REGARDED AS A COMMON COMORBID CONDITION IN CKD AND ESPECIALLY IN DIALYSIS PATIENTS. A NUMBER OF INTERVENTIONS HAVE BEEN PROVEN TO BE SAFE AND EFFECTIVE IN WELL-DESIGNED CLINICAL STUDIES. THIS INCLUDES SUCH INEXPENSIVE APPROACHES AS MODIFICATION OF PHYSICAL ACTIVITY AND DIETARY SUPPLEMENTATION. FURTHER INVESTIGATIONS ARE NEEDED TO EVALUATE THE EFFECTS OF THESE INTERVENTIONS ON HARD OUTCOMES, AS WELL AS TO BETTER UNDERSTAND THE ROLE OF INFLAMMATION IN SELECTED CKD POPULATIONS (E.G., IN CHILDREN).	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
10  462  42 ARE ALTERATIONS IN DNA METHYLATION RELATED TO CKD DEVELOPMENT? THE MODIFICATIONS IN GENOMIC DNA METHYLATION ARE INVOLVED IN THE REGULATION OF NORMAL AND PATHOLOGICAL CELLULAR PROCESSES. THE EPIGENETIC REGULATION STIMULATES BIOLOGICAL PLASTICITY AS AN ADAPTIVE RESPONSE TO VARIATIONS IN ENVIRONMENTAL FACTORS. THE ROLE OF EPIGENETIC CHANGES IS VITAL FOR THE DEVELOPMENT OF SOME DISEASES, INCLUDING ATHEROGENESIS, CANCERS, AND CHRONIC KIDNEY DISEASE (CKD). THE RESULTS OF STUDIES PRESENTED IN THIS REVIEW HAVE SUGGESTED THAT ALTERED DNA METHYLATION CAN MODULATE THE EXPRESSION OF PRO-INFLAMMATORY AND PRO-FIBROTIC GENES, AS WELL THOSE ESSENTIAL FOR KIDNEY DEVELOPMENT AND FUNCTION, THUS STIMULATING RENAL DISEASE PROGRESSION. ABNORMALLY INCREASED HOMOCYSTEINE, HYPOXIA, AND INFLAMMATION HAVE BEEN SUGGESTED TO ALTER EPIGENETIC REGULATION OF GENE EXPRESSION IN CKD. STUDIES OF RENAL SAMPLES HAVE DEMONSTRATED THE RELATIONSHIP BETWEEN VARIATIONS IN DNA METHYLATION AND FIBROSIS AND VARIATIONS IN ESTIMATED GLOMERULAR FILTRATION RATE (EGFR) IN HUMAN CKD. THE UNRAVELLING OF THE GENETIC-EPIGENETIC PROFILE WOULD ENHANCE OUR UNDERSTANDING OF PROCESSES UNDERLYING THE DEVELOPMENT OF CKD. THE UNDERSTANDING OF MULTIFACETED RELATIONSHIP BETWEEN DNA METHYLATION, GENES EXPRESSION, AND DISEASE DEVELOPMENT AND PROGRESSION COULD IMPROVE THE ABILITY TO IDENTIFY INDIVIDUALS AT RISK OF CKD AND ENABLE THE CHOICE OF APPROPRIATE DISEASE MANAGEMENT.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
11  538  33 ATHEROSCLEROSIS AND EPIGENETIC MODIFICATIONS IN CHRONIC KIDNEY DISEASE. CHRONIC KIDNEY DISEASE (CKD) IS ONE OF THE MOST COMMON CHRONIC DISEASES WORLDWIDE, WITH PREVALENCE CURRENTLY PROJECTED AT 10% AND RISING. CARDIOVASCULAR DISEASE IS THE LEADING CAUSE OF MORBIDITY AND MORTALITY IN CKD PATIENTS AND IS INTEGRALLY LINKED WITH ATHEROGENESIS AND VASCULAR STIFFNESS. ESTIMATED GLOMERULAR FILTRATION RATE AND THE LEVEL OF PROTEINURIA ARE NOT ONLY MARKERS OF KIDNEY FUNCTION BUT OF CARDIOVASCULAR RISK, AS WELL. DESPITE THE EFFORTS, CKD PATIENTS STILL EXPERIENCE EXCESSIVE CARDIOVASCULAR BURDEN. MICRORNAS (MIRNAS) ARE SMALL (18-24 NUCLEOTIDES), SINGLE-STRANDED NON-CODING RNAS THAT REGULATE GENE EXPRESSION BY BLOCKING MESSENGER RNA (MRNA) TRANSLATION AND INITIATING DEGRADATION OF MRNA. STUDIES HAVE CONFIRMED THE IMPERATIVE ROLE OF MIRNA DYSREGULATION IN THE PATHOPHYSIOLOGY OF SEVERAL DISEASES, INCLUDING ATHEROSCLEROSIS AND CKD. THIS ARTICLE SUMMARIZES WHAT IS CURRENTLY KNOWN ABOUT THE ROLE OF MIRNAS IN CKD PATIENTS.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
12 5204  34 PRENATAL PROGRAMMING-EFFECTS ON BLOOD PRESSURE AND RENAL FUNCTION. IMPAIRED INTRAUTERINE NEPHROGENESIS-MOST CLEARLY ILLUSTRATED BY LOW NEPHRON NUMBER-IS FREQUENTLY ASSOCIATED WITH LOW BIRTHWEIGHT AND HAS BEEN RECOGNIZED AS A POWERFUL RISK FACTOR FOR RENAL DISEASE; IT INCREASES THE RISKS OF LOW GLOMERULAR FILTRATION RATE, OF MORE RAPID PROGRESSION OF PRIMARY KIDNEY DISEASE, AND OF INCREASED INCIDENCE OF CHRONIC KIDNEY DISEASE OR END-STAGE RENAL DISEASE. ANOTHER IMPORTANT CONSEQUENCE OF IMPAIRED NEPHROGENESIS IS HYPERTENSION, WHICH FURTHER AMPLIFIES THE RISK OF ONSET AND PROGRESSION OF KIDNEY DISEASE. HYPERTENSION IS ASSOCIATED WITH LOW NEPHRON NUMBERS IN WHITE INDIVIDUALS, BUT THE ASSOCIATION IS NOT UNIVERSAL AND IS NOT SEEN IN INDIVIDUALS OF AFRICAN ORIGIN. THE DERANGEMENT OF INTRAUTERINE KIDNEY DEVELOPMENT IS AN EXAMPLE OF A MORE GENERAL PRINCIPLE THAT ILLUSTRATES THE PARADIGM OF PLASTICITY DURING DEVELOPMENT-THAT IS, THAT TRANSCRIPTION OF THE GENETIC CODE IS MODIFIED BY EPIGENETIC FACTORS (AS HAS INCREASINGLY BEEN DOCUMENTED). THIS REVIEW OUTLINES THE CONCEPT OF PRENATAL PROGRAMMING AND, IN PARTICULAR, DESCRIBES ITS ROLE IN KIDNEY DISEASE AND HYPERTENSION.	2011	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
13 3399  38 HOW CAN GENETICS AND EPIGENETICS HELP THE NEPHROLOGIST IMPROVE THE DIAGNOSIS AND TREATMENT OF CHRONIC KIDNEY DISEASE PATIENTS? DISCOVERY OF NOVEL IMPROVED TOOLS FOR DIAGNOSIS, PREVENTION AND THERAPY OF CHRONIC KIDNEY DISEASE (CKD) IS AN IMPORTANT TASK FOR THE NEPHROLOGY COMMUNITY AND IT IS LIKELY THAT SCIENTIFIC BREAKTHROUGHS, TO A LARGE EXTENT, WILL BE BASED ON GENOMICS. THE RAPID GROWTH OF THE NUMBER OF GENOME-WIDE ASSOCIATION STUDIES, MAJOR ADVANCES IN DNA SEQUENCING AND OMICS PROFILING, AND ACCELERATING BIOMEDICAL RESEARCH EFFORTS IN THIS AREA HAVE GREATLY EXPANDED THE KNOWLEDGE BASE NEEDED FOR APPLIED GENOMICS. HOWEVER, TRANSLATING AND IMPLEMENTING GENOTYPE-PHENOTYPE DATA INTO GENE-BASED MEDICINE IN CKD POPULATIONS IS STILL IN AN EARLY PHASE AND WILL REQUIRE CONTINUOUS RESEARCH EFFORTS WITH INTEGRATED APPROACHES AND INTENSIFIED INVESTIGATIONS THAT FOCUS ON THE BIOLOGICAL PATHWAYS, WHICH CAUSATIVELY LINK A GENETIC VARIANT WITH THE DISEASE PHENOTYPE. IN THIS ARTICLE, WE REVIEW SOME CURRENT STRATEGIES TO UNRAVEL THESE TRANSLATIONAL GAPS AS WELL AS PROSPECTS FOR THE IMPLEMENTATION OF GENETIC AND EPIGENETIC METHODS INTO NOVEL CLINICAL PRACTICE.	2014	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
14 4743  30 NOVEL INSIGHTS FROM GENETIC AND EPIGENETIC STUDIES IN UNDERSTANDING THE COMPLEX URAEMIC PHENOTYPE. LIKE IN MANY OTHER COMMON COMPLEX DISORDERS, STUDIES OF CHRONIC KIDNEY DISEASE (CKD) CAN NOW MAKE USE OF THE INCREASING KNOWLEDGE OF THE HUMAN GENOME, ITS VARIATIONS AND IMPACT ON DISEASE SUSCEPTIBILITY, INITIATION, PROGRESSION AND COMPLICATIONS. SUCH STUDIES ARE FACILITATED BY NOVEL READILY AVAILABLE HIGH THROUGH-PUT GENOTYPING METHODS AND SOPHISTICATED ANALYTICAL APPROACHES TO SCAN THE GENOME FOR DNA VARIATIONS AND EPIGENETIC MODIFICATIONS. HERE, WE REVIEW SOME OF THE RECENT DISCOVERIES THAT HAVE EMERGED FROM THESE STUDIES AND EXPANDED OUR KNOWLEDGE OF GENETIC RISK LOCI AND EPIGENETIC MARKERS IN CKD PATHOPHYSIOLOGY. OBSTACLES AND PRACTICAL ISSUES IN THIS FIELD ARE DISCUSSED.	2014	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
15 3502  60 IDENTIFICATION OF POTENTIAL BIOMARKERS OF CHRONIC KIDNEY DISEASE IN INDIVIDUALS WITH DIABETES: PROTOCOL FOR A CROSS-SECTIONAL OBSERVATIONAL STUDY. BACKGROUND: THE IMPORTANCE OF IDENTIFYING PEOPLE WITH DIABETES AND PROGRESSIVE KIDNEY DYSFUNCTION RELATES TO THE EXCESS MORBIDITY AND MORTALITY OF THIS GROUP. RATES OF CARDIOVASCULAR DISEASE ARE MUCH HIGHER IN PEOPLE WITH BOTH DIABETES AND KIDNEY DYSFUNCTION THAN IN THOSE WITH ONLY ONE OF THESE CONDITIONS. BY THE TIME THESE PEOPLE ARE IDENTIFIED IN CURRENT CLINICAL PRACTICE, PROTEINURIA AND RENAL DYSFUNCTION ARE ALREADY ESTABLISHED, LIMITING THE EFFECTIVENESS OF THERAPEUTIC INTERVENTIONS. THE IDENTIFICATION OF AN EPIGENETIC OR BLOOD METABOLITE SIGNATURE OR GUT MICROBIOME PROFILE MAY IDENTIFY THOSE WITH DIABETES AT RISK OF PROGRESSIVE CHRONIC KIDNEY DISEASE, IN TURN PROVIDING TARGETED INTERVENTION TO IMPROVE PATIENT OUTCOMES. OBJECTIVE: THIS STUDY AIMS TO IDENTIFY POTENTIAL BIOMARKERS IN PEOPLE WITH DIABETES AND CHRONIC KIDNEY DISEASE (CKD) ASSOCIATED WITH PROGRESSIVE RENAL INJURY AND TO DISTINGUISH BETWEEN STAGES OF CHRONIC KIDNEY DISEASE. THREE SOURCES OF BIOMARKERS WILL BE EXPLORED, INCLUDING DNA METHYLATION PROFILES IN BLOOD LYMPHOCYTES, THE METABOLOMIC PROFILE OF BLOOD-DERIVED PLASMA AND URINE, AND THE GUT MICROBIOME. METHODS: THE CROSS-SECTIONAL STUDY RECRUITED 121 PEOPLE WITH DIABETES AND VARYING STAGES (STAGES 1-5) OF CHRONIC KIDNEY DISEASE. SINGLE-POINT DATA COLLECTION INCLUDED BLOOD, URINE, AND FECAL SAMPLES IN ADDITION TO CLINICAL DATA SUCH AS ANTHROPOMETRIC MEASUREMENTS AND BIOCHEMICAL PARAMETERS. ADDITIONAL INFORMATION OBTAINED FROM MEDICAL RECORDS INCLUDED PATIENT DEMOGRAPHICS, MEDICAL COMORBIDITIES, AND MEDICATIONS. RESULTS: DATA COLLECTION COMMENCED IN JANUARY 2018 AND WAS COMPLETED IN JUNE 2018. AT THE TIME OF SUBMISSION, 121 PATIENTS HAD BEEN RECRUITED, AND 119 SAMPLES REMAINED AFTER QUALITY CONTROL. THERE WERE 83 PARTICIPANTS IN THE EARLY DIABETES-ASSOCIATED CKD GROUP WITH A MEAN ESTIMATED GLOMERULAR FILTRATION RATE (EGFR) OF 61.2 ML/MIN/1.73 M2 (EARLY CKD GROUP CONSISTING OF STAGE 1, 2, AND 3A CKD), AND 36 PARTICIPANTS IN THE LATE DIABETIC CKD GROUP WITH A MEAN EGFR OF 23.9 ML/MIN/1.73 M2 (LATE CKD GROUP, CONSISTING OF STAGE 3B, 4, AND 5), P<.001. WE HAVE SUCCESSFULLY OBTAINED DNA FOR METHYLATION AND MICROBIOME ANALYSES USING THE BIOSPECIMENS COLLECTED VIA THIS PROTOCOL AND ARE CURRENTLY ANALYZING THESE RESULTS TOGETHER WITH THE METABOLOME OF THIS COHORT OF INDIVIDUALS WITH DIABETIC CKD. CONCLUSIONS: RECENT ADVANCES HAVE IMPROVED OUR UNDERSTANDING OF THE EPIGENOME, METABOLOMICS, AND THE INFLUENCE OF THE GUT MICROBIOME ON THE INCIDENCE OF DISEASES SUCH AS CANCERS, PARTICULARLY THOSE RELATED TO ENVIRONMENTAL EXPOSURES. HOWEVER, THERE IS A PAUCITY OF LITERATURE SURROUNDING THESE INFLUENCERS IN RENAL DISEASE. THIS STUDY WILL PROVIDE INSIGHT INTO THE FUNDAMENTAL UNDERSTANDING OF THE PATHOPHYSIOLOGY OF CKD IN INDIVIDUALS WITH DIABETES, ESPECIALLY IN NOVEL AREAS SUCH AS EPIGENETICS, METABOLOMICS, AND THE KIDNEY-GUT AXIS. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/16277.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
16   97  27 A PRIMER ON THE EPIGENETICS OF KIDNEY FIBROSIS. DESPITE EXTENSIVE KNOWLEDGE OF THE VARIOUS MOLECULAR PATHWAYS THAT CONTRIBUTE TO TUBULOINTERSTITIAL FIBROSIS, IT REMAINS AN UNSOLVED QUESTION WHY THE PROGRESSION RATE OF CHRONIC KIDNEY DISEASE VARIES SUBSTANTIALLY FROM PATIENT TO PATIENT, EVEN AMONG PATIENTS WITH COMMON UNDERLYING NEPHROPATHIES AND COMORBIDITIES. POSSIBLE EXPLANATIONS FOR DIFFERENT SUSCEPTIBILITIES OF INDIVIDUAL PATIENTS TO DEVELOP END-STAGE RENAL FAILURE INCLUDE GENETIC OR EPIGENETIC VARIATIONS, WHICH MODIFY HOW INDIVIDUAL PATIENTS RESPOND TO KIDNEY INJURY. HERE WE REVIEW PRINCIPLES OF EPIGENETIC MECHANISMS IN CONTEXT OF CHRONIC KIDNEY DISEASE AND DISCUSS HOW SUCH INSIGHTS MAY BE UTILIZED FOR FUTURE THERAPEUTIC STRATEGIES AND MAY LEAD TO NOVEL DIAGNOSTIC TOOLS IN THE FUTURE.	2012	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
17 6001  35 THE ACUTE KIDNEY INJURY TO CHRONIC KIDNEY DISEASE TRANSITION: A POTENTIAL OPPORTUNITY TO IMPROVE CARE IN ACUTE KIDNEY INJURY. RECENT CONTROLLED TRIALS, EPIDEMIOLOGICAL ANALYSES AND BASIC RESEARCH STUDIES OFFER A COMPREHENSIVE VIEW OF THE SHORT AND LONG-TERM CLINICAL REPERCUSSION OF DE NOVO ACUTE KIDNEY INJURY OR AKI. WHILE MOST POST-AKI PATIENTS RECOVER THEIR BASELINE RENAL FUNCTION, A SIGNIFICANT NUMBER, APPROXIMATELY ~20% OF THOSE AFFECTED, WILL GO ON TO DEVELOP LONG TERM ILLNESS CHARACTERIZED BY AN INCREASE IN LATE STAGE CKD, CARDIOVASCULAR COMPLICATIONS, AND INCREASED DEATH RATES. WHEN AKI OCCURS IN HOSPITALIZED PATIENTS, SELECTED DEMOGRAPHIC AND LABORATORY RESULTS CAN BE INCORPORATED INTO RISK CALCULATORS THAT IDENTIFY THOSE AT HIGHER RISK FOR LONG-TERM COMPLICATIONS. THIS REVIEW TOUCHES ON SOME OF THE SALIENT EPIDEMIOLOGICAL STUDIES OF THE AKI TO CKD TRANSITION. IT ALSO FOCUSES ON CERTAIN RECENT ADVANCEMENTS IN OUR UNDERSTANDING OF THE BIOLOGICAL AND FUNCTIONAL IMPACT OF AKI ON THE RENAL TUBULE REPAIR MECHANISM, AS WELL AS THE IMPORTANT ROLE THAT GENETIC, EPIGENETIC, BIOCHEMICAL AND INFLAMMATORY EVENTS, SEEMINGLY BENEFICIAL TO THE RE-ESTABLISHMENT OF NORMAL RENAL FUNCTION, CAN BE OFFSET BY MEDIATORS OF PROGRESSIVE FIBROSIS AND IRREVERSIBLE STRUCTURAL CHANGES. CHARACTERIZATION OF BASIC PROCESSES THAT MEDIATE THE AKI TO CKD TRANSITION REVEALS PROMISING PHARMACOLOGICAL AND BIOLOGICAL AGENTS THAT HOPEFULLY WILL ONE DAY BE USED IN THE EARLY STAGES OF AKI TO PREVENT ITS DEADLY CONSEQUENCES.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
18 6013  41 THE APPLICATIONS OF DNA METHYLATION AS A BIOMARKER IN KIDNEY TRANSPLANTATION: A SYSTEMATIC REVIEW. BACKGROUND: ALTHOUGH KIDNEY TRANSPLANTATION IMPROVES PATIENT SURVIVAL AND QUALITY OF LIFE, LONG-TERM RESULTS ARE HAMPERED BY BOTH IMMUNE- AND NON-IMMUNE-MEDIATED COMPLICATIONS. CURRENT BIOMARKERS OF POST-TRANSPLANT COMPLICATIONS, SUCH AS ALLOGRAFT REJECTION, CHRONIC RENAL ALLOGRAFT DYSFUNCTION, AND CUTANEOUS SQUAMOUS CELL CARCINOMA, HAVE A SUBOPTIMAL PREDICTIVE VALUE. DNA METHYLATION IS AN EPIGENETIC MODIFICATION THAT DIRECTLY AFFECTS GENE EXPRESSION AND PLAYS AN IMPORTANT ROLE IN PROCESSES SUCH AS ISCHEMIA/REPERFUSION INJURY, FIBROSIS, AND ALLOREACTIVE IMMUNE RESPONSE. NOVEL TECHNIQUES CAN QUICKLY ASSESS THE DNA METHYLATION STATUS OF MULTIPLE LOCI IN DIFFERENT CELL TYPES, ALLOWING A DEEP AND INTERESTING STUDY OF CELLS' ACTIVITY AND FUNCTION. THEREFORE, DNA METHYLATION HAS THE POTENTIAL TO BECOME AN IMPORTANT BIOMARKER FOR PREDICTION AND MONITORING IN KIDNEY TRANSPLANTATION. PURPOSE OF THE STUDY: THE AIM OF THIS STUDY WAS TO EVALUATE THE ROLE OF DNA METHYLATION AS A POTENTIAL BIOMARKER OF GRAFT SURVIVAL AND COMPLICATIONS DEVELOPMENT IN KIDNEY TRANSPLANTATION. MATERIAL AND METHODS: A SYSTEMATIC REVIEW OF SEVERAL DATABASES HAS BEEN CONDUCTED. THE NEWCASTLE-OTTAWA SCALE AND THE JADAD SCALE HAVE BEEN USED TO ASSESS THE RISK OF BIAS FOR OBSERVATIONAL AND RANDOMIZED STUDIES, RESPECTIVELY. RESULTS: TWENTY ARTICLES REPORTING ON DNA METHYLATION AS A BIOMARKER FOR KIDNEY TRANSPLANTATION WERE INCLUDED, ALL USING DNA METHYLATION FOR PREDICTION AND MONITORING. DNA METHYLATION PATTERN ALTERATIONS IN CELLS ISOLATED FROM DIFFERENT TISSUES, SUCH AS KIDNEY BIOPSIES, URINE, AND BLOOD, HAVE BEEN ASSOCIATED WITH ISCHEMIA-REPERFUSION INJURY AND CHRONIC RENAL ALLOGRAFT DYSFUNCTION. THESE ALTERATIONS OCCURRED IN DIFFERENT AND SPECIFIC LOCI. DNA METHYLATION STATUS HAS ALSO PROVED TO BE IMPORTANT FOR IMMUNE RESPONSE MODULATION, HAVING A CRUCIAL ROLE IN REGULATORY T CELL DEFINITION AND ACTIVITY. RESEARCH ALSO FOCUSED ON A BETTER UNDERSTANDING OF THE ROLE OF THIS EPIGENETIC MODIFICATION ASSESSMENT FOR REGULATORY T CELLS ISOLATION AND EXPANSION FOR FUTURE TOLERANCE INDUCTION-ORIENTED THERAPIES. CONCLUSIONS: STUDIES INCLUDED IN THIS REVIEW ARE HETEROGENEOUS IN STUDY DESIGN, BIOLOGICAL SAMPLES, AND OUTCOME. MORE COORDINATED INVESTIGATIONS ARE NEEDED TO AFFIRM DNA METHYLATION AS A CLINICALLY RELEVANT BIOMARKER IMPORTANT FOR PREVENTION, MONITORING, AND INTERVENTION.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
19 4830  31 OLD AND NEW BIOMARKERS ASSOCIATED WITH ENDOTHELIAL DYSFUNCTION IN CHRONIC HYPERGLYCEMIA. CHRONIC HYPERGLYCEMIA AND VASCULAR DAMAGE ARE STRICTLY RELATED. BIOMARKERS OF VASCULAR DAMAGE HAVE BEEN INTENSIVELY STUDIED IN THE RECENT YEARS IN THE QUEST OF RELIABLE CARDIOVASCULAR RISK ASSESSMENT TOOLS ABLE TO FACILITATE RISK STRATIFICATION AND EARLY DETECTION OF VASCULAR IMPAIRMENT. THE PRESENT STUDY IS A NARRATIVE REVIEW WITH THE AIM OF REVISING THE AVAILABLE EVIDENCE ON CURRENT AND NOVEL MARKERS OF HYPERGLYCEMIA-INDUCED VASCULAR DAMAGE. AFTER A DISCUSSION OF CLASSIC TOOLS USED TO INVESTIGATE ENDOTHELIAL DYSFUNCTION, WE PROVIDE AN IN-DEPTH DESCRIPTION OF NOVEL CIRCULATING BIOMARKERS (CHEMOKINES, EXTRACELLULAR VESICLES, AND EPIGENETIC AND METABOLOMIC BIOMARKERS). APPROPRIATE USE OF A SINGLE AS WELL AS A CLUSTER OF THE DISCUSSED BIOMARKERS MIGHT ENABLE IN A NEAR FUTURE (A) THE PROMPT IDENTIFICATION OF TARGETED AND CUSTOMIZED TREATMENT STRATEGIES AND (B) THE FOLLOW-UP OF CARDIOVASCULAR TREATMENT EFFICACY OVER TIME IN CLINICAL RESEARCH AND/OR IN CLINICAL PRACTICE.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
20  728  38 CAN WE IDENTIFY PATIENTS WITH HIGH RISK OF OSTEOARTHRITIS PROGRESSION WHO WILL RESPOND TO TREATMENT? A FOCUS ON BIOMARKERS AND FRAILTY. OSTEOARTHRITIS (OA), A DISEASE AFFECTING DIFFERENT PATIENT PHENOTYPES, APPEARS AS AN OPTIMAL CANDIDATE FOR PERSONALIZED HEALTHCARE. THE AIM OF THE DISCUSSIONS OF THE EUROPEAN SOCIETY FOR CLINICAL AND ECONOMIC ASPECTS OF OSTEOPOROSIS AND OSTEOARTHRITIS (ESCEO) WORKING GROUP WAS TO EXPLORE THE VALUE OF MARKERS OF DIFFERENT SOURCES IN DEFINING DIFFERENT PHENOTYPES OF PATIENTS WITH OA. THE ESCEO ORGANIZED A SERIES OF MEETINGS TO EXPLORE THE POSSIBILITY OF IDENTIFYING PATIENTS WHO WOULD MOST BENEFIT FROM TREATMENT FOR OA, ON THE BASIS OF RECENT DATA AND EXPERT OPINION. IN THE FIRST MEETING, PATIENT PHENOTYPES WERE IDENTIFIED ACCORDING TO THE NUMBER OF AFFECTED JOINTS, BIOMECHANICAL FACTORS, AND THE PRESENCE OF LESIONS IN THE SUBCHONDRAL BONE. IN THE SECOND MEETING, SUMMARIZED IN THE PRESENT ARTICLE, THE WORKING GROUP EXPLORED OTHER MARKERS INVOLVED IN OA. PROFILES OF PATIENTS MAY BE DEFINED ACCORDING TO THEIR LEVEL OF PAIN, FUNCTIONAL LIMITATION, AND PRESENCE OF COEXISTENT CHRONIC CONDITIONS INCLUDING FRAILTY STATUS. A CONSIDERABLE AMOUNT OF DATA SUGGESTS THAT MAGNETIC RESONANCE IMAGING MAY ALSO ASSIST IN DELINEATING DIFFERENT PHENOTYPES OF PATIENTS WITH OA. AMONG MULTIPLE BIOCHEMICAL BIOMARKERS IDENTIFIED, NONE IS SUFFICIENTLY VALIDATED AND RECOGNIZED TO IDENTIFY PATIENTS WHO SHOULD BE TREATED. CONSIDERABLE EFFORTS ARE ALSO BEING MADE TO IDENTIFY GENETIC AND EPIGENETIC FACTORS INVOLVED IN OA, BUT RESULTS ARE STILL LIMITED. THE MANY POTENTIAL BIOMARKERS THAT COULD BE USED AS POTENTIAL STRATIFIERS ARE PROMISING, BUT MORE RESEARCH IS NEEDED TO CHARACTERIZE AND QUALIFY THE EXISTING BIOMARKERS AND TO IDENTIFY NEW CANDIDATES.	2015