1 5045 96 PHARMACOLOGIC EPIGENETIC MODULATORS OF ALKALINE PHOSPHATASE IN CHRONIC KIDNEY DISEASE. PURPOSE OF REVIEW: IN CHRONIC KIDNEY DISEASE (CKD), DISTURBANCE OF SEVERAL METABOLIC REGULATORY MECHANISMS CAUSE PREMATURE AGEING, ACCELERATED CARDIOVASCULAR DISEASE (CVD), AND MORTALITY. SINGLE-TARGET INTERVENTIONS HAVE REPEATEDLY FAILED TO IMPROVE THE PROGNOSIS FOR CKD PATIENTS. EPIGENETIC INTERVENTIONS HAVE THE POTENTIAL TO MODULATE SEVERAL PATHOGENETIC PROCESSES SIMULTANEOUSLY. ALKALINE PHOSPHATASE (ALP) IS A ROBUST PREDICTOR OF CVD AND ALL-CAUSE MORTALITY AND IMPLICATED IN PATHOGENIC PROCESSES ASSOCIATED WITH CVD IN CKD. RECENT FINDINGS: IN EXPERIMENTAL STUDIES, EPIGENETIC MODULATION OF ALP BY MICRORNAS OR BROMODOMAIN AND EXTRATERMINAL (BET) PROTEIN INHIBITION HAS SHOWN PROMISING RESULTS FOR THE TREATMENT OF CVD AND OTHER CHRONIC METABOLIC DISEASES. THE BET INHIBITOR APABETALONE IS CURRENTLY BEING EVALUATED FOR CARDIOVASCULAR RISK REDUCTION IN A PHASE III CLINICAL STUDY IN HIGH-RISK CVD PATIENTS, INCLUDING PATIENTS WITH CKD (CLINICALTRIALS.GOV IDENTIFIER: NCT02586155). PHASE II STUDIES DEMONSTRATE AN ALP-LOWERING POTENTIAL OF APABETALONE, WHICH WAS ASSOCIATED WITH IMPROVED CARDIOVASCULAR AND RENAL OUTCOMES. SUMMARY: ALP IS A PREDICTOR OF CVD AND MORTALITY IN CKD. EPIGENETIC MODULATION OF ALP HAS THE POTENTIAL TO AFFECT SEVERAL PATHOGENETIC PROCESSES IN CKD AND THEREBY IMPROVE CARDIOVASCULAR OUTCOME. 2020 2 1883 36 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 3 587 34 BENEFIT OF APABETALONE ON PLASMA PROTEINS IN RENAL DISEASE. INTRODUCTION: APABETALONE, A SMALL MOLECULE INHIBITOR, TARGETS EPIGENETIC READERS TERMED BET PROTEINS THAT CONTRIBUTE TO GENE DYSREGULATION IN HUMAN DISORDERS. APABETALONE HAS IN VITRO AND IN VIVO ANTI-INFLAMMATORY AND ANTIATHEROSCLEROTIC PROPERTIES. IN PHASE 2 CLINICAL TRIALS, THIS DRUG REDUCED THE INCIDENCE OF MAJOR ADVERSE CARDIAC EVENTS IN PATIENTS WITH CARDIOVASCULAR DISEASE. CHRONIC KIDNEY DISEASE IS ASSOCIATED WITH A PROGRESSIVE LOSS OF RENAL FUNCTION AND A HIGH RISK OF CARDIOVASCULAR DISEASE. WE STUDIED THE IMPACT OF APABETALONE ON THE PLASMA PROTEOME IN PATIENTS WITH IMPAIRED KIDNEY FUNCTION. METHODS: SUBJECTS WITH STAGE 4 OR 5 CHRONIC KIDNEY DISEASE AND MATCHED CONTROLS RECEIVED A SINGLE DOSE OF APABETALONE. PLASMA WAS COLLECTED FOR PHARMACOKINETIC ANALYSIS AND FOR PROTEOMICS PROFILING USING THE SOMASCAN 1.3K PLATFORM. PROTEOMICS DATA WERE ANALYZED WITH INGENUITY PATHWAY ANALYSIS TO IDENTIFY DYSREGULATED PATHWAYS IN DISEASED PATIENTS, WHICH WERE TARGETED BY APABETALONE. RESULTS: AT BASELINE, 169 PLASMA PROTEINS (ADJUSTED P VALUE <0.05) WERE DIFFERENTIALLY ENRICHED IN RENALLY IMPAIRED PATIENTS VERSUS CONTROL SUBJECTS, INCLUDING CYSTATIN C AND BETA(2) MICROGLOBULIN, WHICH CORRELATE WITH RENAL FUNCTION. BIOINFORMATICS ANALYSIS OF THE PLASMA PROTEOME REVEALED A SIGNIFICANT ACTIVATION OF 42 PATHWAYS THAT CONTROL IMMUNITY AND INFLAMMATION, OXIDATIVE STRESS, ENDOTHELIAL DYSFUNCTION, VASCULAR CALCIFICATION, AND COAGULATION. AT 12 HOURS POSTDOSE, APABETALONE COUNTERED THE ACTIVATION OF PATHWAYS ASSOCIATED WITH RENAL DISEASE AND REDUCED THE ABUNDANCE OF DISEASE MARKERS, INCLUDING INTERLEUKIN-6, PLASMINOGEN ACTIVATOR INHIBITOR-1, AND OSTEOPONTIN. CONCLUSION: THESE DATA DEMONSTRATED PLASMA PROTEOME DYSREGULATION IN RENALLY IMPAIRED PATIENTS AND THE BENEFICIAL IMPACT OF APABETALONE ON PATHWAYS LINKED TO CHRONIC KIDNEY DISEASE AND ITS CARDIOVASCULAR COMPLICATIONS. 2018 4 538 26 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 5 2982 32 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 6 462 27 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 7 3095 31 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 8 6510 28 TRANSCRIPTION FACTORS AND EPIGENETIC MODULATION: ITS THERAPEUTIC IMPLICATION IN CHRONIC KIDNEY DISEASE. RECENTLY EMERGING EVIDENCE HAS SHOWN THAT EPIGENETIC MECHANISMS ARE INVOLVED IN INITIATION AND PROGRESSION OF VARIOUS DISEASES, INCLUDING KIDNEY DISEASES. IN THE PRESENT ARTICLE, WE REVIEW THE CURRENT DATA REGARDING THE ROLE OF EPIGENETIC MODULATION IN CHRONIC KIDNEY DISEASE (CKD) AND KIDNEY FIBROSIS, INCLUDING DNA METHYLATION AND HISTONE MODIFICATION. ESPECIALLY WE FOCUSED ON THE ROLE OF TRANSCRIPTION FACTORS IN EPIGENETIC MODULATION AND THE POSSIBILITY OF THERAPEUTIC TARGET OF CKD. WE HAVE RECENTLY REPORTED THAT TRANSCRIPTION FACTOR KRUPPEL-LIKE FACTOR 4 (ALSO KNOWN AS GUT-ENRICHED KRUPPEL-LIKE FACTOR) IS EXPRESSED IN KIDNEY PODOCYTES (VISCERAL EPITHELIAL CELLS) AND MODULATES PODOCYTE PHENOTYPE BY GENE-SELECTIVE EPIGENETIC CONTROL. TARGETING TRANSCRIPTION FACTORS FOR EPIGENETIC MODIFICATION MAY BE A GOOD CANDIDATE FOR REMISSION AND REGRESSION OF CKD. IT IS NECESSARY FOR THE THERAPY OF CKD WITH AN EPIGENETIC-BASED APPROACH TO INVESTIGATE ORGAN-, TISSUE-, OR GENE-SPECIFIC TREATMENT METHODS FOR REDUCTION OF SIDE EFFECTS. 2015 9 1060 28 CLINICAL RELEVANCE OF EPIGENETIC DYSREGULATION IN CHRONIC KIDNEY DISEASE-ASSOCIATED CARDIOVASCULAR DISEASE. ACROSS THE SPECTRUM OF CLINICAL MEDICINE, THE FIELD OF EPIGENETICS HAS GAINED SUBSTANTIAL SCIENTIFIC INTEREST IN RECENT YEARS. EPIGENETICS REFERS TO MODIFICATIONS IN GENE EXPRESSION WHICH ARE NOT EXPLAINED BY CHANGES IN DNA SEQUENCE. CLASSICAL COMPONENTS OF EPIGENETIC REGULATION COMPRISE DNA METHYLATION, HISTONE MODIFICATIONS AND RNA INTERFERENCE. IN CHRONIC KIDNEY DISEASE (CKD), SEVERAL FEATURES OF URAEMIA, SUCH AS HYPERHOMOCYSTEINEMIA AND INFLAMMATION, MAY CONTRIBUTE TO CHANGES IN EPIGENETIC GENE REGULATION. IT HAS BEEN SUGGESTED THAT THESE CHANGES MAY AFFECT GENES RELATED TO CARDIOVASCULAR DISEASE. THEREBY, A URAEMIA-ASSOCIATED DISTURBANCE IN EPIGENETIC REGULATION MAY CONTRIBUTE TO THE SUBSTANTIAL INCREASE IN CARDIOVASCULAR MORBIDITY IN CKD PATIENTS. THE PRESENT REVIEW AIMS TO SUMMARIZE CURRENT KNOWLEDGE OF EPIGENETIC DYSREGULATION IN CARDIOVASCULAR DISEASE FROM A NEPHROLOGICAL PERSPECTIVE, WITH A SPECIAL FOCUS ON DNA METHYLATION. WE FIRST DESCRIBE THE IMPACT OF ALTERED EPIGENETIC REGULATION IN NON-CKD-ASSOCIATED ARTERIOSCLEROSIS, AND NEXT CHARACTERIZE URAEMIC FEATURES WHICH MAY AFFECT EPIGENETIC GENE REGULATION IN THE CONTEXT OF CARDIOVASCULAR DISEASE. FINALLY, WE CONCLUDE THAT SUBSTANTIAL ADDITIONAL WORK IS NEEDED BEFORE EPIGENETIC REGULATORY MECHANISMS MAY BECOME THERAPEUTIC TARGETS IN CKD-ASSOCIATED CARDIOVASCULAR DISEASE. 2013 10 2549 31 EPIGENETICS IN OBESITY AND DIABETES MELLITUS: NEW INSIGHTS. A LONG-TERM COMPLICATION OF OBESITY IS THE DEVELOPMENT OF TYPE 2 DIABETES (T2D). PATIENTS WITH T2D HAVE BEEN DESCRIBED AS HAVING EPIGENETIC MODIFICATIONS. EPIGENETICS IS THE POST-TRANSCRIPTIONAL MODIFICATION OF DNA OR ASSOCIATED FACTORS CONTAINING GENETIC INFORMATION. THESE ENVIRONMENTALLY-INFLUENCED MODIFICATIONS, MAINTAINED DURING CELL DIVISION, CAUSE STABLE CHANGES IN GENE EXPRESSION. EPIGENETIC MODIFICATIONS OF T2D ARE DNA METHYLATION, ACETYLATION, UBIQUITYLATION, SUMOYLATION, AND PHOSPHORYLATION AT THE LYSINE RESIDUE AT THE AMINO TERMINUS OF HISTONES, AFFECTING DNA, HISTONES, AND NON-CODING RNA. DNA METHYLATION HAS BEEN SHOWN IN PANCREATIC ISLETS, ADIPOSE TISSUE, SKELETAL MUSCLE, AND THE LIVER. FURTHERMORE, EPIGENETIC CHANGES HAVE BEEN OBSERVED IN CHRONIC COMPLICATIONS OF T2D, SUCH AS DIABETIC NEPHROPATHY, DIABETIC RETINOPATHY, AND DIABETIC NEUROPATHY. RECENTLY, A NEW DRUG HAS BEEN DEVELOPED WHICH ACTS ON BROMODOMAINS AND EXTRATERMINAL (BET) DOMAIN PROTEINS, WHICH OPERATE LIKE EPIGENETIC READERS AND COMMUNICATE WITH CHROMATIN TO MAKE DNA ACCESSIBLE FOR TRANSCRIPTION BY INHIBITING THEM. THIS DRUG (APABETALONE) IS BEING STUDIED TO PREVENT MAJOR ADVERSE CARDIOVASCULAR EVENTS IN PEOPLE WITH T2D, LOW HDL CHOLESTEROL, CHRONIC KIDNEY FAILURE, AND RECENT CORONARY EVENTS. THIS REVIEW AIMS TO DESCRIBE THE RELATIONSHIP BETWEEN OBESITY, LONG-TERM COMPLICATIONS SUCH AS T2D, AND EPIGENETIC MODIFICATIONS AND THEIR POSSIBLE TREATMENTS. 2023 11 1515 26 DNA METHYLATION AND THE POTENTIAL ROLE OF DEMETHYLATING AGENTS IN PREVENTION OF PROGRESSIVE CHRONIC KIDNEY DISEASE. CHRONIC KIDNEY DISEASE (CKD) IS A GLOBAL EPIDEMIC, AND ITS MAJOR RISK FACTORS INCLUDE OBESITY AND TYPE 2 DIABETES. OBESITY NOT ONLY PROMOTES METABOLIC DYSREGULATION AND THE DEVELOPMENT OF DIABETIC KIDNEY DISEASE BUT ALSO MAY INDEPENDENTLY LEAD TO CKD BY A VARIETY OF MECHANISMS, INCLUDING ENDOCRINE AND METABOLIC DYSFUNCTION, INFLAMMATION, OXIDATIVE STRESS, ALTERED RENAL HEMODYNAMICS, AND LIPOTOXICITY. DELETERIOUS RENAL EFFECTS OF OBESITY CAN ALSO BE TRANSMITTED FROM ONE GENERATION TO THE NEXT, AND IT IS INCREASINGLY RECOGNIZED THAT OFFSPRING OF OBESE MOTHERS ARE PREDISPOSED TO CKD. EPIGENETIC MODIFICATIONS ARE CHANGES THAT REGULATE GENE EXPRESSION WITHOUT ALTERING THE DNA SEQUENCE. OF THESE, DNA METHYLATION IS THE MOST STUDIED. EPIGENETIC IMPRINTS, PARTICULARLY DNA METHYLATION, ARE LAID DOWN DURING CRITICAL PERIODS OF FETAL DEVELOPMENT, AND THEY MAY PROVIDE A MECHANISM BY WHICH MATERNAL-FETAL TRANSMISSION OF CHRONIC DISEASE OCCURS. OUR CURRENT REVIEW EXPLORES THE EVIDENCE FOR THE ROLE OF DNA METHYLATION IN THE DEVELOPMENT OF CKD, DIABETIC KIDNEY DISEASE, DIABETES, AND OBESITY. DNA METHYLATION HAS BEEN IMPLICATED IN RENAL FIBROSIS-THE FINAL PATHOPHYSIOLOGIC PATHWAY IN THE DEVELOPMENT OF END-STAGE KIDNEY DISEASE-WHICH SUPPORTS THE NOTION THAT DEMETHYLATING AGENTS MAY PLAY A POTENTIAL THERAPEUTIC ROLE IN PREVENTING DEVELOPMENT AND PROGRESSION OF CKD.-LARKIN, B. P., GLASTRAS, S. J., CHEN, H., POLLOCK, C. A., SAAD, S. DNA METHYLATION AND THE POTENTIAL ROLE OF DEMETHYLATING AGENTS IN PREVENTION OF PROGRESSIVE CHRONIC KIDNEY DISEASE. 2018 12 6511 29 TRANSCRIPTION FACTORS AS THERAPEUTIC TARGETS IN CHRONIC KIDNEY DISEASE. THE GROWING NUMBER OF PATIENTS WITH CHRONIC KIDNEY DISEASE (CKD) IS RECOGNIZED AS AN EMERGING PROBLEM WORLDWIDE. RECENT STUDIES HAVE INDICATED THAT DEREGULATION OF TRANSCRIPTION FACTORS IS ASSOCIATED WITH THE ONSET OR PROGRESSION OF KIDNEY DISEASE. SEVERAL CLINICAL TRIALS INDICATED THAT REGRESSION OF CKD MAY BE FEASIBLE VIA ACTIVATION OF THE TRANSCRIPTION FACTOR NUCLEAR FACTOR ERYTHROID-2 RELATED FACTOR 2 (NRF2), WHICH SUGGESTS THAT TRANSCRIPTION FACTORS MAY BE POTENTIAL DRUG TARGETS FOR CKD. AGENTS STABILIZING HYPOXIA-INDUCIBLE FACTOR (HIF), WHICH MAY BE BENEFICIAL FOR RENAL ANEMIA AND RENAL PROTECTION, ARE ALSO NOW UNDER CLINICAL TRIAL. RECENTLY, WE HAVE REPORTED THAT THE TRANSCRIPTION FACTOR KRUPPEL-LIKE FACTOR 4 (KLF4) REGULATES THE GLOMERULAR PODOCYTE EPIGENOME, AND THAT THE ANTIPROTEINURIC EFFECT OF THE RENIN(-)ANGIOTENSIN SYSTEM BLOCKADE MAY BE PARTIALLY MEDIATED BY KLF4. KLF4 IS ONE OF THE YAMANAKA FACTORS THAT INDUCES IPS CELLS AND IS REPORTED TO BE INVOLVED IN EPIGENETIC REMODELING. IN THIS ARTICLE, WE SUMMARIZE THE TRANSCRIPTION FACTORS ASSOCIATED WITH CKD AND PARTICULARLY FOCUS ON THE POSSIBILITY OF TRANSCRIPTION FACTORS BEING NOVEL DRUG TARGETS FOR CKD THROUGH EPIGENETIC MODULATION. 2018 13 4120 38 MECHANISMS OF CARDIOVASCULAR DISORDERS IN PATIENTS WITH CHRONIC KIDNEY DISEASE: A PROCESS RELATED TO ACCELERATED SENESCENCE. CARDIOVASCULAR DISEASES (CVDS), ESPECIALLY THOSE INVOLVING A SYSTEMIC INFLAMMATORY PROCESS SUCH AS ATHEROSCLEROSIS, REMAIN THE LEADING CAUSE OF MORBIDITY AND MORTALITY IN PATIENTS WITH CHRONIC KIDNEY DISEASE (CKD). CKD IS A SYSTEMIC CONDITION AFFECTING APPROXIMATELY 10% OF THE GENERAL POPULATION. THE PREVALENCE OF CKD HAS INCREASED OVER THE PAST DECADES BECAUSE OF THE AGING OF THE POPULATION WORLDWIDE. INDEED, CVDS IN PATIENTS WITH CKD CONSTITUTE A PREMATURE FORM OF CVD OBSERVED IN THE GENERAL POPULATION. MULTIPLE STUDIES INDICATE THAT PATIENTS WITH RENAL DISEASE UNDERGO ACCELERATED AGING, WHICH PRECIPITATES THE APPEARANCE OF PATHOLOGIES, INCLUDING CVDS, USUALLY ASSOCIATED WITH ADVANCED AGE. IN THIS REVIEW, WE DISCUSS SEVERAL ASPECTS THAT CHARACTERIZE CKD-ASSOCIATED CVDS, SUCH AS ETIOPATHOGENIC ELEMENTS THAT CKD PATIENTS SHARE WITH THE GENERAL POPULATION, CHANGES IN THE CELLULAR BALANCE OF REACTIVE OXYGEN SPECIES (ROS), AND THE ASSOCIATED PROCESS OF CELLULAR SENESCENCE. UREMIA-ASSOCIATED AGING IS LINKED WITH NUMEROUS CHANGES AT THE CELLULAR AND MOLECULAR LEVEL. THESE CHANGES ARE SIMILAR TO THOSE OBSERVED IN THE NORMAL PROCESS OF PHYSIOLOGIC AGING. WE ALSO DISCUSS NEW PERSPECTIVES IN THE STUDY OF CKD-ASSOCIATED CVDS AND EPIGENETIC ALTERATIONS IN INTERCELLULAR SIGNALING, MEDIATED BY MICRORNAS AND/OR EXTRACELLULAR VESICLES (EVS), WHICH PROMOTE VASCULAR DAMAGE AND SUBSEQUENT DEVELOPMENT OF CVD. UNDERSTANDING THE PROCESSES AND FACTORS INVOLVED IN ACCELERATED SENESCENCE AND OTHER ABNORMAL INTERCELLULAR SIGNALING WILL IDENTIFY NEW THERAPEUTIC TARGETS AND LEAD TO IMPROVED METHODS OF DIAGNOSIS AND MONITORING FOR PATIENTS WITH CKD-ASSOCIATED CVDS. 2020 14 6001 31 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 15 1604 28 DNA METHYLATION SUSTAINS "INFLAMED" MEMORY OF PERIPHERAL IMMUNE CELLS AGGRAVATING KIDNEY INFLAMMATORY RESPONSE IN CHRONIC KIDNEY DISEASE. THE INCIDENCE OF CHRONIC KIDNEY DISEASE (CKD) HAS RAPIDLY INCREASED IN THE PAST DECADES. A PROGRESSIVE LOSS OF KIDNEY FUNCTION CHARACTERIZES A PART OF CKD EVEN WITH INTENSIVE SUPPORTIVE TREATMENT. IRRESPECTIVE OF ITS ETIOLOGY, CKD PROGRESSION IS GENERALLY ACCOMPANIED WITH THE DEVELOPMENT OF CHRONIC KIDNEY INFLAMMATION THAT IS PATHOLOGICALLY FEATURED BY THE LOW-GRADE BUT CHRONIC ACTIVATION OF RECRUITED IMMUNE CELLS. CUMULATIVE EVIDENCE SUPPORT THAT ABERRANT DNA METHYLATION PATTERN OF DIVERSE PERIPHERAL IMMUNE CELLS, INCLUDING T CELLS AND MONOCYTES, IS CLOSELY ASSOCIATED WITH CKD DEVELOPMENT IN MANY CHRONIC DISEASE SETTINGS. THE CHANGE OF DNA METHYLATION PROFILE CAN SUSTAIN FOR A LONG TIME AND AFFECT THE FUTURE GENES EXPRESSION IN THE CIRCULATING IMMUNE CELLS EVEN AFTER THEY MIGRATE FROM THE CIRCULATION INTO THE INVOLVED KIDNEY. IT IS OF CLINICAL INTEREST TO REVEAL THE UNDERLYING MECHANISM OF HOW ALTERED DNA METHYLATION REGULATES THE INTENSITY AND THE TIME LENGTH OF THE INFLAMMATORY RESPONSE IN THE RECRUITED EFFECTOR CELLS. WE AND OTHERS RECENTLY DEMONSTRATED THAT ALTERED DNA METHYLATION OCCURS IN PERIPHERAL IMMUNE CELLS AND PROFOUNDLY CONTRIBUTES TO CKD DEVELOPMENT IN SYSTEMIC CHRONIC DISEASES, SUCH AS DIABETES AND HYPERTENSION. THIS REVIEW WILL SUMMARIZE THE CURRENT FINDINGS ABOUT THE INFLUENCE OF ABERRANT DNA METHYLATION ON CIRCULATING IMMUNE CELLS AND HOW IT POTENTIALLY DETERMINES THE OUTCOME OF CKD. 2021 16 6638 26 UNRAVELING THE EPIGENETIC LANDSCAPE OF GLOMERULAR CELLS IN KIDNEY DISEASE. CHRONIC KIDNEY DISEASE (CKD) IS A MAJOR PUBLIC HEALTH CONCERN AND ITS PREVALENCE AND INCIDENCE ARE RISING QUICKLY. IT IS A NON-COMMUNICABLE DISEASE PRIMARILY CAUSED BY DIABETES AND/OR HYPERTENSION AND IS ASSOCIATED WITH HIGH MORBIDITY AND MORTALITY. DESPITE DECADES OF RESEARCH EFFORTS, THE PATHOGENESIS OF CKD REMAINS A PUZZLE WITH MISSING PIECES. UNDERSTANDING THE CELLULAR AND MOLECULAR MECHANISMS THAT GOVERN THE LOSS OF KIDNEY FUNCTION IS CRUCIAL. ABRUPT REGULATION OF GENE EXPRESSION IN KIDNEY CELLS IS APPARENT IN CKD AND SHOWN TO BE RESPONSIBLE FOR DISEASE ONSET AND PROGRESSION. GENE EXPRESSION REGULATION EXTENDS BEYOND DNA SEQUENCE AND INVOLVES EPIGENETIC MECHANISMS INCLUDING CHANGES IN DNA METHYLATION AND POST-TRANSLATIONAL MODIFICATIONS OF HISTONES, DRIVEN BY THE ACTIVITY OF SPECIFIC ENZYMES. RECENT ADVANCES DEMONSTRATE THE ESSENTIAL PARTICIPATION OF EPIGENETICS IN KIDNEY (PATHO)PHYSIOLOGY, AS ITS ACTIONS REGULATE BOTH THE INTEGRITY OF CELLS BUT ALSO TRIGGERS DELETERIOUS SIGNALING PATHWAYS. HERE, WE REVIEW THE KNOWN EPIGENETIC PROCESSES REGULATING THE COMPLEX FILTRATION UNIT OF THE KIDNEY, THE GLOMERULI. THE REVIEW WILL ELABORATE ON NOVEL INSIGHTS INTO HOW EPIGENETICS CONTRIBUTES TO CELL INJURY IN THE CKD SETTING MAJORLY FOCUSING ON KIDNEY GLOMERULAR CELLS: THE GLOMERULAR ENDOTHELIAL CELLS, THE MESANGIAL CELLS, AND THE SPECIALIZED AND TERMINALLY DIFFERENTIATED PODOCYTE CELLS. 2021 17 1388 19 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 18 1487 26 DNA DAMAGE AND EPIGENETIC CHANGES IN KIDNEY DISEASES - FOCUSED ON TRANSCRIPTION FACTORS IN PODOCYTES. RECENTLY IT HAS BEEN SHOWN THAT EPIGENETIC MECHANISMS ARE INVOLVED IN INITIATION AND PROGRESSION OF CARIDIOVASCULAR AND METABOLIC DISEASES, INCLUDING DIABETES, OBESITY, ATHEROSCLEROSIS, HEART FAILURE, HYPERTENSION AND KIDNEY DISEASES. IN THESE CHRONIC DISEASES, VARIOUS EXOGENOUS AND ENDOGENOUS STRESSES CAUSE DNA DAMAGE, FOLLOWED BY DNA REPAIR PROCESS. ACCUMULATION OF DNA DAMAGES AND IMPAIRED REPAIR PROCESS CAN LEAD TO EPIGENETIC CHANGES, WHICH MAY CONTRIBUTE TO ONSET AND PROGRESSION OF DISEASES. RECENTLY WE HAVE SHOWN THAT THERAPEUTIC EFFECT OF TRANSCRIPTION FACTOR KLF4 (KRUPPEL-LIKE FACTOR 4) IN KIDNEY GLOMERULAR EPITHELIAL CELLS (PODOCYTES) ON PROTEINURIC KIDNEY DISEASES THROUGH EPIGENETIC MECHANISMS. OUR RESULT SUGGESTS THE POSSIBILITY OF TRANSCRIPTION FACTORS AS A TARGET OF SELECTIVE EPIGENETIC THERAPY. MOREOVER, WE HAVE REPORTED THAT RENIN-ANGIOTENSIN SYSTEM (RAS) BLOCKERS, WHICH ARE WIDELY PRESCRIBED FOR THE TREATMENT OF CARDIOVASCULAR DISEASES, CAN RESTORE EPIGENETIC CHANGES THROUGH KLF4 IN PART. THESE RESULTS SUGGEST THAT ACTIVATION OF RAS CAUSES EPIGENETIC CHANGES IN DISEASE STATES, AND ELUCIDATION OF THE PRECISE MECHANISM MAY LEAD TO ESTABLISHMENT OF NOVEL THERAPEUTIC TARGET OF KIDNEY DISEASES. IN THIS REVIEW WE FOCUS ON DNA DAMAGE REPAIR SYSTEM AND EPIGENETIC MODULATORS IN DISEASE STATES, AND SPECULATE A CANDIDATE FOR EPIGENETIC THERAPY OF KIDNEY DISEASES. 2016 19 221 33 ACUTE KIDNEY INJURY TO CHRONIC KIDNEY DISEASE TRANSITION. BACKGROUND: ACUTE KIDNEY INJURY (AKI), EVEN IF FOLLOWED BY RENAL RECOVERY, IS A RISK FACTOR FOR THE FUTURE DEVELOPMENT OF CHRONIC KIDNEY DISEASE (CKD) AND END-STAGE RENAL DISEASE (ESRD). IN THE PREVIOUS YEARS, NOVEL INSIGHTS IN THE PATHOPHYSIOLOGY OF CKD PROGRESSION SUGGESTED A CAUSAL LINK BETWEEN AKI AND CKD DUE TO A MALADAPTIVE REPAIR AFTER SEVERE AND REPEATED INJURY. SUMMARY: SEVERAL PATHOLOGICAL MECHANISMS HAVE BEEN PROPOSED TO CONTRIBUTE TO THE PROGRESSION OF AKI AND TRANSITION TO CKD/ESRD INCLUDING HYPOXIA AND MICROVASCULAR RAREFACTION, ALTERATIONS OF RENAL RESIDENT CELL PHENOTYPES AND FUNCTIONS, CELL CYCLE ARREST IN THE G2/M PHASE, PERSISTENT CHRONIC INFLAMMATION, AND DEVELOPMENT OF INTERSTITIAL FIBROSIS, MITOCHONDRIAL FRAGMENTATION, EPIGENETIC CHANGES, ACTIVATION OF RENIN-ANGIOTENSIN SYSTEM (RAS), CELL AND TISSUE SENESCENCE. FURTHERMORE, SEVERAL CLINICAL FACTORS HAVE BEEN IDENTIFIED SUCH AS SEVERITY OF AKI, AGE, AND COMORBIDITIES. THE IDENTIFICATION OF AKI-TO-CKD BIOMARKERS COULD IMPROVE THE EARLY IDENTIFICATION OF AKI PATIENTS WITH HIGHER RISK FOR CKD PROGRESSION. HOWEVER, ALTHOUGH OUR UNDERSTANDING IN THE PATHOPHYSIOLOGY OF AKI-TO-CKD TRANSITION IS SIGNIFICANTLY IMPROVED, NO NOVEL INTERVENTION HAS BEEN VALIDATED. POTENTIAL THERAPEUTIC APPROACHES TO TREAT AKI AND BLOCK THE TRANSITION TO CKD/ESRD HAVE BEEN RECENTLY REPORTED, BUT THEY NEED FURTHER VALIDATIONS. KEY MESSAGES: MALADAPTIVE REPAIR AFTER AKI IS STRONGLY ASSOCIATED TO THE DEVELOPMENT OF CKD AND LONG-TERM CONSEQUENCES. THE PROMPT IDENTIFICATION OF PATIENTS AT HIGHER RISK FOR LATE CKD PROGRESSION AND THE DEVELOPMENT OF NEW THERAPEUTIC INTERVENTIONS REMAIN CRITICAL RESEARCH GOALS. 2018 20 5660 24 SEX-SPECIFIC EPIGENETIC PROGRAMMING IN RENAL FIBROSIS AND INFLAMMATION. THE GROWING PREVALENCE OF HYPERTENSION, HEART DISEASE, DIABETES, AND OBESITY ALONG WITH AN AGING POPULATION, IS LEADING TO HIGHER INCIDENCE OF RENAL DISEASES IN THE SOCIETY. CHRONIC KIDNEY DISEASE (CKD) IS CHARACTERIZED MAINLY BY PERSISTENT INFLAMMATION, FIBROSIS, AND GRADUAL LOSS OF RENAL FUNCTION LEADING TO RENAL FAILURE. SEX IS A KNOWN CONTRIBUTOR TO THE DIFFERENCES IN INCIDENCE AND PROGRESSION OF CKD. EPIGENETIC PROGRAMMING IS AN ESSENTIAL REGULATOR OF RENAL PHYSIOLOGY AND IS CRITICALLY INVOLVED IN THE PATHOPHYSIOLOGY OF RENAL INJURY AND FIBROSIS. EPIGENETIC SIGNALING INTEGRATES INTRINSIC AND EXTRINSIC SIGNALS ONTO THE GENOME, AND VARIOUS ENVIRONMENTAL AND HORMONAL STIMULI, INCLUDING SEX HORMONES, WHICH REGULATE GENE EXPRESSION AND DOWNSTREAM CELLULAR RESPONSES. THE MOST EXTENSIVELY STUDIED EPIGENETIC ALTERATIONS THAT PLAY A CRITICAL ROLE IN RENAL DAMAGE INCLUDE HISTONE MODIFICATIONS AND DNA METHYLATION. NOTABLY, THESE EPIGENETIC ALTERATIONS ARE REVERSIBLE, MAKING THEM CANDIDATES FOR POTENTIAL THERAPEUTIC TARGETS FOR THE TREATMENT OF RENAL DISEASES. HERE, WE WILL SUMMARIZE THE CURRENT KNOWLEDGE ON SEX-DIFFERENCES IN EPIGENETIC MODULATION OF RENAL FIBROSIS AND INFLAMMATION AND HIGHLIGHT SOME POSSIBLE EPIGENETIC THERAPEUTIC STRATEGIES FOR CKD TREATMENT. 2023