No 2 (2018)

IN PATIENTS WITH MULTIPLE MYELOMA, A NUMBER OF CYTOGENETIC ABNORMALITIES WITH PROGNOSTIC SIGNIFICANCE WERE REVEALED. IMPORTANT FACTORS FOR THE UNFAVORABLE PROGNOSIS IN MULTIPLE MYELOMA INCLUDE DEL 17P, T(4; 14), T( 14; 16), T(14; 20), DEL 1Q21, DEL 13. BRAF, KRAS, NRAS GENE MUTATIONS CHARACTERISTIC FOR DIFFERENT MALIGNANT NEOPLASMS ARE ALSO DETECTED IN PATIENTS WITH MULTIPLE MYELOMA. NEW SEQUENCING METHODS ALLOWED TO DETECT PREVIOUSLY UNKNOWN MUTATIONS OF SP140, ROB0O1, FAM46C AND EGR1 GENES IN PATIENTS WITH MULTIPLE MYELOMA. CRITICAL TO THE PATHOGENESIS AND PROGNOSIS OF MULTIPLE MYELOMA IS c-MYC, PAX and IRF-4 GENE OVEREXPRESSION. THE ACTIVATION OF THE EXPRESSION OF GENES ENCODING TUMOR-ASSOCIATED TESTIS-SPECIFIC ANTIGENS, INCLUDING PRAME, MAGE A1, MAGE A3, NY ES01, HAS THE PROGNOSTIC VALUE FOR MULTIPLE MYELOMA. THE IMMUNOGENICITY OF THESE ANTIGENS ALLOWS TO CONSIDER THEM AS A PROMISING TARGET FOR THE DEVELOPMENT OF IMMUNOTHERAPY FOR MULTIPLE MYELOMA.

PATIENTS WITH MULTIPLE MYELOMA BECOME NOT RARE PATIENTS OF THE NTPHROLOGICAL CLINIC. CLOSE ATTENTION TO THE HEMOSTATIC SYSTEM IS CONSIDERED AS AN IMPORTANT ASPECT OF THEIR MANAGEMENT. MEANWHILE, THROMBOTIC AND HEMORRHAGIC PROBLEMS IN THIS CATEGORY OF PATIENTS ARE QUITE COMMON, AND CHARACTERIZED BY CLINICAL AND PATHOPHYSIOLOGICAL DIVERSITY. ACCORDINGLY, THEY REQUIRE AN INDIVIDUAL APPROACH, BASED ON A CAREFUL LABORATORY MONITORING.

DIALYZERS ARE OPTIMIZED FOR HEMODIALYSIS (HD) AND PROVIDE REMOVAL OF A SIGNIFICANT NUMBER OF SMALL UREMIC MOLECULES, AS WELL AS MEDIUM-SIZED MOLECULES WITH A SMALLER MEMBRANE-TO-BLOOD CONTACT AREA. A RANDOMIZED CONTROLLED TRIAL HAS DEMONSTRATED THAT THE EFFICACY OF DIALYSIS USING REVACLEAR WAS COMPARABLE TO THE EFFICACY ACHIEVED WITH THE USE OF PROPERLY SIZED FRESENIUS MEDICAL CARE'S FX DIALYSERS [1]. ACCORDING TO THE RESULTS OF A COMPARATIVE CLINICAL STUDY OF REVACLEAR AND FX CORDIAX DIALYZERS, THE INTERNAL DIAMETER OF THE PORACTON MEMBRANE OF THE REVACLEAR DIALYZER - 190 μм, PROVIDES EFFECTIVE INTERNAL FILTRATION IN STANDARD HD WITH BETTER ß2-MICROGLOBULIN CLEARANCE [2]. DURING DIALYSIS USING THE REVACLEAR DIALYZER, AN EFFECTIVE CLEARANCE OF HEPCIDIN REGULATING IRON METABOLISM, WHICH WAS RECENTLY RECOGNIZED AS UREMIC TOXIN, WAS DEMONSTRATED [3]. DUE TO THE SPECIAL DESIGN OF THE BOX/COLLEKTOR AND THE HOLLOW FIBER MEMBRANE OF REVACLEAR DIAlYZERS, RHEOLOGY AND HYDRODYNAMICS CREATED SIMPLIFY THE USE OF THE DIALYZER. THIS ALLOWS TO REDUCE THE DIALYSIS FLUID FLOW TO THE BLOOD FLOW RATIO WITHOUT CHANGING THE DIALYSIS DOSE, WHICH IN TURN CAN HELP REDUCE THE VOLUME OF WATER USED DURING DIALYSIS. THE REVACLEAR DIALYZER AND CLINICAL RESULTS OF ITS USE ARE SUPERIOR TO THE USIAL RESULTS OBSERVED WITH HIGH-FLOW HEMODIALYSIS. THE REVACLEAR DIALYZER IS EFFECTIVE AND ECONOMIC FOR A DIALYSIS CLINIC AND EXPANDS THE POSSIBILITIES OF EFFECTIVE HD IN PATIENTS WITH END STAGE RENAL DISEASE (ESRD).

PURPOSE. TO ASSESS THE FUNCTIONAL RENAL STATUS AND THE SIGNIFICANCE OF NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN (NGAL) LEVELS AS A MARKER OF SUBCLINICAL KIDNEY INJURY IN PATIENTS WITH ACUTE CORONARY SYNDROME (ACS). MATERIAL AND METHODS. 111 PATIENTS (80 MEN AND 31 WOMEN, MEAN AGE - 59.5± 10 YEARS) WITH DIAGNOSIS OF ACS WERE EXAMINED. ON THE THIRD DAY OF HOSPITALIZATION, SERUM NGAL (S-NGAL) AND URINE (U-NGAL) LEVELS, SERUM CREATININE (SCR) LEVELS, PRESENCE AND ALBUMINURIA LEVELS (N = 79) WERE DETERMINED. PATIENTS WITH ACS WERE DIVIDED INTO 4 SUBGROUPS DEPENDING ON NGAL (S-NGAL AND U-NGAL) AND SCR LEVELS. THE INCIDENCE OF VARIOUS CARDIOVASCULAR COMPLICATIONS IN THE HOSPITAL AND THE OUTCOME 6 MONTHS AFTER HOSPITAL DISCHARGE WAS ASSESSED. RESULTS. THE U-NGAL LEVELS IN ACS PATIENTS WITH ALBUMINURIA/PROTEINURIA WERE 2-FOLD SIGNIFICANTlY HIGHER 7.28 (2.6-40.6) THAN IN PATIENTS WITH ACS WITHOUT ALBUMINURIA/PROTEINURIA THAT 3.2 (1.5-7.2, P=0.02). THE PRESENCE OF ALBUMINURIA/PROTEINURIA IN ACS WAS ASSOCIATED WITH HIGHER U-NGAL LEVEL (y=0.34, P =0.003). THE INCIDENCE OF SUBCLINICAL ACUTE KIDNEY INJURY (AKI) (NGAL+/SCR-) IN ACS WAS 44.1 AND 6.3% (ACCORDING TO THE S-NGAL AND U-NGAL LEVELS, RESPECTIVELY). ACS PATIENTS WITH SUBCLINICAL AK (S-NGAL+/SCR-) COMPARED WITH PATIENTS IN THE SUBGROUP S-NGAL-/SCR- MORE OFTEN HAD A COMPLICATED HOSPITAL PERIOD (P = 0.04) AND AN UNFAVORABLE OUTCOME IN LONG-TERM (6 MONTHS) (P = 0.03) PERIOD. CONCLUSION. SUBCLINICAL AKI (INCREASE IN THE NGAL LEVEL WITHOUT DIAGNOSTICALLY RELEVANT INCREASE IN SCr) IN ACS PATIENTS WAS MORE OFTEN DETECTED BY THE SERUM NGAL LEVEL. IN ACS PATIENTS WITH SUBCLINICAL AKI (DETERMINED BY SERUM NGAL LEVEL), COMPLICATIONS IN THE HOSPITAL PERIOD AND ENDPOINTS IN THE LONG-TERM (6 MONTHS) PERIOD WERE MORE OFTEN DETECTED THAN IN ACS WITH NGAL LEVEL BELOW THE BOUNDARY VALUE AND REGARDLESS OF SCR LEVELS.

PURPOSE. TO DETERMINE THE CLINICAL SIGNIFICANCE OF URINARY EXCRETION OF THE TRANSFORMING GROWTH FACTOR (TGF-ß, ), ANGIOTENSIN II (Ang II) AND ß2-MICROGLOBULIN (ß2-MG) IN CHILDREN WITH VESICOURETERAL REFLUX (VUR) FOR EARLY DETECTION AND PROGNOSIS OF THE PROGRESSION OF REFLUX NEPHROPATHY (RN). MATERIAL AND METHODS, SEVENTY-NINE PATIENTS WITH VARYING DEGREES OF VUR AGED I TO 14 YEARS (MEAN AGE 5.69±0.44 YEARS), 58 (73.4%) GIRLS. DEPENDING ON THE RESULTS OF DMSA-SCINTIGRAPHY AND THE APPLICATION TASK, THE PATIENTS WERE DIVIDED INTO THE FOLLOWING GROUPS: COMPARISON GROUP (GROUP 1) - PATIENTS WITH DIFFERENT DEGREES OF VUR WITHOUT RN (N=12, MEAN AGE - 1.65±0.31 YEARS), 8 GIRLS (66.7%). THE MAIN GROUP INCLUDED 67 CHILDREN WITH RN (5.64±0.81 YEARS), AND DEPENDING ON THE SEVERITY OF RN WAS DIVIDED INTO 2 GROUPS: GROUP 2-27 CHILDREN WITH MILD (I-II) DEGREE OF RN (5.89±0.77 YEARS), 19 (70.4%) GIRLS, AND GROUP 3-40 CHILDREN WITH SEVERE (III-IV) DEGREE OF RN (5.4 1 ± 1.07 YEARS), 31 (77.5 %) GIRLS. DEPENDING ON THE COURSE OF RN, BOTH GROUPS WERE DIVIDED INTO SUBGROUPS: 2А (WITHOUT PROGRESSION OF RN) - WITH RN OF I-II DEGREES (N= 1 6, MEAN AGE - 5.34±0.23 YEARS), 1 1 (68.8%) GIRLS; 2B (WITH PROGRESSION OF RN) - WITH RN OF I-II DEGREES (N=11, MEAN AGE 6.43±0.86 YEARS), 8 (72.7%) GIRLS; ЗА (WITHOUT PROGRESSION OF RN) - WITH RN OF III-IV DEGREES (N=18, MEAN AGE - 6.17±0.55 YEARS),14 (77.8%) GIRLS; 3B (WITH PROGRESSION) - WITH RN OF III-IV DEGREES (N = 22, AVERAGE AGE - 4.65±0.45 YEARS),17 (72.3%) GIRLS; GROUP 4 (CONTROL) 20 APPARENTLY HEALTHY CHILDREN (6.24±0.31 YEARS), 12 (60%) GIRLS. THE STUDY GROUPS OF PATIENTS DID NOT DIFFER SIGNIFICANTLY IN SEX AND AGE. ALL CHILDREN UNDERWENT EXAMINATION OF URINARY EXCRETION OF ANGlI, TGF-ß,, ß2-MG IN THE MORNING URINE AND REVALUATION RESULTS TO URINARY CREATININE LEVEL. RESULTS. THE URINARY LEVELS OF ANGII, TGF-ß,, ß2-MG WERE SIGNIFICANTLY HIGHER IN THE GROUPS OF CHILDREN WITH RN THAN IN THE CONTROL GROUP. INCREASE IN ANG II AND TGF-ß, LEVELS WAS SIGNIFICANTLY HIGHER IN THE MAIN GROUP THAN IN THE COMPARISON GROUP (P<0.05). THE MOST SENSITIVE MARKERS FOR EARLY DETECTION OF RN ARE ANGlI AND TGF-ß,; GLOMERULAR FILTRATION RATE (GFR) AND ß2-MG REFLECT THE PROGRESSION OF RN. REDUCTION IN GFR IS AN UNFAVORABLE AND MORE CHARACTERISTIC SIGN FOR A SEVERE DEGREE OF RN AND FOR ITS PROGRESSIVE COURSE. CONCLUSION. THE DIRECT CORRELATION REVEALED BETWEEN THE LEVEL OF EXCRETION OF THE STUDIED PRO-FIBROGENIC FACTORS AND THE DEVELOPMENT OF RN INDICATES THE ADVISABILITY AND POTENTIALS FOR THEIR INCLUSION AS DIAGNOSTIC MARKERS OF EARLY DETECTION OF RN. THE URINARY ß2-MG LEVEL IS MORE REFLECTIVE OF THE PROGRESSIVE COURSE OF RN.

ONE OF THE MOST COMMON CAUSES OF THE DEVELOPMENT OF THE END-STAGE RENAL DISEASE IS DIABETIC NEPHROPATHY (DNP). RENAL FIBROSIS, CHARACTERIZED BY THE ACCUMULATION OF EXTRACELLULAR MATRIX (ECM) PROTEINS IN THE GLOMERULAR BASEMENT MEMBRANE AND TUBULOINTERSTITIAL TISSUES, IS THE TERMINAL MANIFESTATION OF DPN. THE SIGNALING PATHWAY OF TGF-ß (TRANSFORMING GROWTH FACTOR BETA) TRIGGERS AN EPITHELIAL-MESENCHYMAL TRANSITION (EMT), WHICH PLAYS A KEY ROLE IN THE ACCUMULATION OF ECM PROTEINS IN DPN. THE STUDIES SHOW THAT DNP CONTINUES TO PROGRESS DESPITE THE GLYCEMIC CONTROL. THIS PHENOMENON IS CALLED "METABOLIC MEMORY" AND MEANS THAT EPIGENETIC FACTORS, IN PARTICULAR HISTONE MODIFICATIONS, ALTER THE TGF-ß,-INDUCED OF RENAL FIBROSIS GENE AND ECM PROTEIN EXPRESSION, AND ALSO PARTICIPATE IN RENAL FIBROSIS DUE TO CAPABILITY TO REGULATE THE EMT PROCESS CAUSED BY TGF-ß SIGNALING. IN THIS REGARD, RESEARCHERS ARE CURRENTLY MAKING EFFORTS TO DEVELOP AGENTS AFFECTING THE HISTONE MODIFICATIONS, IN ORDER TO DELAY, STOP, OR EVEN REVERSE THE DEVELOPMENT OF DPN. THIS REVIEW PRESENTS THE RESULTS OF THE MOST RECENT STUDIES ON THE REGULATION OF HISTONE MODIFICATIONS INVOLVED IN THE PATHOGENESIS OF DPN.