Genetic polymorphisms in ABCB1 are correlated with the increased risk of atorvastatin-induced muscle side effects: a cross-sectional study.

Genetic factors are recognized as risk factors for statin-associated muscle symptoms (SAMS), which are the most common cause of statin intolerance. The aim of this study was to determine whether there is an association between polymorphisms 1236C > T, 2677G > T/A, and 3435C > T in the ABCB1 gene, encoding the efflux transporter of statins, and SAMS, as results on this topic are still controversial. A cross-sectional study was conducted on patients with or without SAMS using atorvastatin. The influence of non-genetic variables on SAMS was also evaluated. Our results show that patients with TT genotype in 1236C > T, 2677G > T/A, and 3435C > T polymorphisms had higher risk of developing SAMS, compared to wild type and heterozygous carriers together (OR 4.292 p = 0.0093, OR 5.897 p = 0.0023 and OR 3.547 p = 0.0122, respectively). Furthermore, TTT/TTT diplotype was also associated with a higher risk of SAMS, OR 9.234 (p = 0.0028). Only family history of cardiovascular disease was found to be a risk factor for SAMS, in addition to the known non-genetic variables. We believe that ABCB1 genotyping has great potential to be incorporated into clinical practice to identify high-risk patients in a timely manner.

Association of multiple retinal nodular hamartomas and "confetti" skin lesions with end-stage renal disease in patients with tuberous sclerosis.

PURPOSE: The main purpose of this study is to explore characteristics of patients with chronic kidney disease in tuberous sclerosis (TSC) and to underline differences in clinical characteristics between end-stage renal disease (ESRD) patients and patients in earlier stages of chronic kidney disease. METHODS: This multicentric, retrospective study included data for 48 patients from seven South-Eastern European countries (Albania, Bosnia and Herzegovina, Croatia, Greece, Montenegro, Serbia, Slovenia) in the period from February to August 2020. Researchers collected data from local and national nephrological and neurological registries and offered clinical and laboratory results from medical histories in follow-up periods. RESULTS: This study enrolled 48 patients with a median age of 32.3 years (range, 18-46 years), and predominant female gender (60.45%). The percentage of patients with chronic kidney disease (CKD) diagnosis of the total number of patients was 66.90%, with end-stage renal disease development in 39.6%. The most prevalent renal lesions leading to chronic kidney disease were angiomyolipomas (AMLs) in 76.6%, while multiple renal cysts were present in 42.6% of patients. Nephrectomy was performed in 43% of patients, while the mTOR inhibitors were used in 18 patients (37.5%). The majority of patients had cutaneous manifestations of tuberous sclerosis-83.30% had hypomelanotic cutaneous lesions, and 68.80% had angiofibromas. Multiple retinal nodular hamartomas and "confetti" skin lesions were more frequent in end-stage renal disease (ESRD) than in patients with earlier stages of chronic kidney disease (p-0.033 and 0.03, respectively). CONCLUSION: Our study has also shown that retinal hamartomas and "confetti" skin lesions are more frequent in end-stage renal diseases (ESRD) patients than in other chronic kidney disease (CKD) patients. Usage of mTOR inhibitors can also reduce the number of complications and associated with tuberous sclerosis, such as dermatological manifestations and retinal hamartoma, which are more common in the terminal stage of chronic kidney disease.

Malnutrition inflammation score (MIS) is stronger predictor of mortality in hemodialysis patients than waist-to-hip ratio (WHR)-4-year follow-up.

PURPOSE: The main purpose of this study is to correlate the significance of the malnutrition inflammation score (MIS) and the waist-to-hip ratio (WHR) in the prediction of mortality in hemodialysis patients. METHODS: The study was conducted from March 2016 to April 2020, covering 100 hemodialysis patients. Anthropometric measures (Waist circumference (WC), Hip circumference (HC), Waist-to-hip ratio (WHR), Caliper and BMI) and biomarkers of inflammation (IL6, hsCRP) and nutrition (Transfferin, Albumin) were determined and for the above-mentioned biomarkers, we monitored all-cause mortality for 4 years. The hemodialysis patients were divided in three groups based on their MIS score. RESULTS: In this prospective, longitudinal study, we enrolled 100 patients (54 males and 46 females) with a median age of 58 (51-65) years. All patients were divided into three groups according to MIS score values. We performed univariate Cox regression survival analysis for a period of 4 years, and then included for multivariate survival Cox regression analysis well-defined nutritional markers: BMI, mid-arm circumference, WHR and MIS score. The MIS score was demonstrated to be the best independent predictor of 4-year mortality in our study (p < 0.001). CONCLUSION: The results of our study have shown that there is no significance of WHR in the prediction of mortality in hemodialysis patients, but that the MIS score is a strong, independent predictor of all-cause 4-year mortality.

Machine learning approach in mortality rate prediction for hemodialysis patients.

Kernel support vector machine algorithm and K-means clustering algorithm are used to determine the expected mortality rate for hemodialysis patients. The national nephrology database of Montenegro has been used to conduct this research. Mortality rate prediction is realized with accuracy up to 94.12% and up to 96.77%, when a complete database is observed and when a reduced database (that contains data for the three most common basic diseases) is observed, respectively. Additionally, it is shown that just a few parameters, most of which are collected during the sole patient examination, are enough for satisfying results.

Relationship between insulin-like growth factor-1, insulin resistance and metabolic profile with pre-obesity and obesity in children.

OBJECTIVES: Childhood obesity is a serious medical condition with alarmingly high rates worldwide. There is controversy regarding the relationship between insulin-like growth factor-1 (IGF-1) and pediatric obesity. We investigated the relationship between IGF-1, insulin resistance and metabolic profile with childhood pre-obesity/obesity. METHODS: The study involved 201 children aged 7-15 years, divided in three groups according to their nutritional status (International Obesity Task Force criteria): normal-weight (n=84), pre-obese (n=82), obese (n=35). Laboratory IGF-1, insulin, fasting blood glucose (FBG), lipid profile, alanine-aminotransferase (ALT), uric acid (UA), anthropometric and body composition parameters were analyzed. Body mass index and IGF-1 standard deviation score (SDS), waist-to-height ratio (WtHR) and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) score were calculated. RESULTS: Pre-obese/obese children had significantly higher IGF-1 SDS, FBG, insulin, HOMA-IR, UA, ALT, triglycerides, and lower high-density lipoprotein cholesterol (HDL-c); obese group had higher WtHR and low-density lipoprotein cholesterol (LDL-c) compared to controls (p<0.05). In obese group, IGF-1 SDS was positively correlated with fat free/muscle mass, total body water (p<0.05) and negatively correlated with LDL-c (p<0.05). In pre-obese/obese HOMA-IR and insulin were positively correlated with age, total body fat (TBF) (p<0.05) and negatively correlated with HDL-c (pre-obese) (p<0.05). Multivariate ordinal logistic regression analyses showed that IGF-1 SDS (OR=1.94; 95%CI: 1.21-3.11), TBF (OR=1.37; 95%CI: 1.21-1.54) were predictors of nutritional status (p<0.001). FBG (OR=42.39; 95%CI: 2.31-77.2) and UA (OR=1.03; 95%CI: 1.01-1.05) were predictors of IR (p<0.001). CONCLUSIONS: IGF-1 SDS and TBF were predictors of nutritional status. Further studies are required to clarify the role of IGF-1 in pathophysiology of obesity and its comorbidities.

Decreased insulin-like growth factor-1 (IGF-1) concentration correlates with reduced left-ventricle ejection fraction (LVEF) in hemodialysis patients.

PURPOSE: The main purpose of this study is to determine the correlation between the serum IGF-1 concentration and certain cardiac indexes in hemodialysis patients. METHODS: The study was conducted at the Clinical Center of Montenegro and three regional hemodialysis centers. The echocardiographic studies were performed the day after the hemodialysis sessions. Blood samples were taken before dialysis for the measurement of IGF1 and PTH. RESULTS: A total of 102 patients were divided into two groups according to their left-ventricular ejection fraction (EF). Patients in the group with the higher EF had higher IGF-1 concentration (p = 0.024). IGF-1 was positively correlated with EF (ρ = 0.251, p = 0.012), and negatively correlated with LVMI (ρ = - 0.621, p < 0.001), SW (ρ = - 0.632, p < 0.001), and LW (ρ = - 0.632, p < 0.001). Multiple linear regression analysis was performed to determine the possible independent association between the EF and IGF-1 and the clinical data. The age of patients, their gender, and smoking habits did not have any combined influence on EF, but IGF-1 had a strong influence and was independently associated with the ejection fraction. CONCLUSION: Our results may indicate the possible protective role of IGF-1 in the maintenance of heart structure and function in hemodialysis patients.

Age and Assay Related Changes of Laboratory Thyroid Function Tests in the Reference Female Population.

BACKGROUND: Laboratory thyroid function tests play a central role in the diagnosis of thyroid disorders. The aim of our cross-sectional study was to determine reference values for thyroid tests in a rigorously selected group of Montenegrin females, investigate the impact of possible age-related changes and the influence of the interassay bias between three frequently used immunoassays. METHODS: Female subjects were randomly selected, aged between 20 and 69 and 946 of them met the selection criteria. TSH, fT3, fT4, thyroid peroxidase and thyroglobulin antibodies were measured. Eighty samples were further analyzed on two other immunochemistry platforms. RESULTS: Median TSH progressively increased with age, there was no difference in fT3, while fT4 was significantly higher in the two oldest groups compared to the others. When using the age-related 97.5 percentile of TSH the percentage of reclassification was highest in the 20-29 years of age group (5.2%, p<0.05). In the oldest band, 7.7% had TSH values above cohort-specific and below the age-related upper reference limit. Bland-Altman bias plots revealed the highest interassay absolute mean difference between compared TSH assays of 24.5% and for fT4 assays of 13.8%. CONCLUSIONS: The correlation coefficients between fT3 assays from different manufacturers were low. Serum TSH and fT4 concentrations increased with age and the implementation of age-specific TSH reference intervals would be of interest. The bias between the three commercial immunoassays indicated that the standardization of thyroid function tests is a task of great importance.

Increased Serum Level of IGF-1 Correlates With Better Cognitive Status in End-Stage Renal Disease Patients Undergoing Hemodialysis.

Prevalence of cognitive function decline in end stage renal disease (ESRD) patients undergoing hemodialysis is higher than in the general population. We analyzed risk factors for cognitive function decline in those patients. This study included 93 ESRD patients undergoing hemodialysis two or three times a week in three centers for hemodialysis in Montenegro. The cognitive status of patients was assessed using the mini mental score examination (MMSE) test. All 93 patients have been divided into three groups according to the results of MMSE. Patients in the first group had severe cognitive impairment and MMSE score below 17 (26.88%), patients in the second group with MMSE score 18-23 had moderate cognitive impairment (40.86%) and third group of patients have MMSE >24 and no cognitive impairment (32.26%). There were no significant differences between groups for gender, smoking habits and level of parathyroid hormone. Level of schooling was significantly different between groups of patients (P < 0.001). Laboratory markers observed in this study with significant differences between groups were: IGF 1, IGFBP 3, erythrocytes and hemoglobin (P < 0.001, P = 0.004, P < 0.001, P = 0.002, respectively). IGF 1 proved to be of great importance for evaluating cognitive status in our study. This marker was statistically different between groups (P < 0.001) and Tukey post hoc analysis showed significant differences between all three groups (first and second group P = 0.045, second and third group P = 0.015, first and third group P < 0.001). Our data suggest that IGF 1 can be considered as novel biomarker for assessment of cognitive functioning in CKD patients, which can be of huge clinical importance.

Prooxidant-antioxidant balance, hsTnI and hsCRP: mortality prediction in haemodialysis patients, two-year follow-up.

Oxidative stress and inflammation are highly intertwined pathophysiological processes. We analyzed the markers of these processes and high-sensitive troponin I (hsTnI) for mortality prediction in patients on haemodialysis. This study enrolled a total of 62 patients on regular haemodialysis. The patients were monitored for two years, and the observed outcomes were all-cause and cardiovascular mortality. Blood samples were taken before one dialysis session for analysis of the baseline concentrations of prooxidant-antioxidant balance (PAB), total antioxidant status (TAS), total oxidative status (TOS), hsTnI, hsCRP and resistin. The overall all-cause mortality was 37.1% and CVD mortality 16.1%. By univariate and multivariate logistic regression, our findings suggest that good predictors of all-cause mortality include hsCRP and PAB (p < .05) and of CVD mortality hsCRP (p < .05) and hsTnI (p < .001). To evaluate the relationship between the combined parameter measurements and all-cause/CVD mortality risk, patients were divided into three groups according to their PAB, hsCRP and hsTnI concentrations. The cutoffs for hsCRP and hsTnI and the median for PAB were used. Kaplan-Meier survival curves pointed out that the highest mortality risk of all-cause mortality was in the group with hsCRP levels above the cutoff and PAB levels above the median (p < .001). The highest risk of CVD mortality was found in the group with hsCRP and hsTnI levels above the cutoff levels (p = .001). Our data suggest that hsCRP and PAB are very good predictors of all-cause mortality. For CVD complications and mortality prediction in HD patients, the most sensitive parameters appear to be hsTnI and hsCRP.

High uric acid and low superoxide dismutase as possible predictors of all-cause and cardiovascular mortality in hemodialysis patients.

PURPOSE: We investigated the role of serum uric acid (sUA) and superoxide dismutase (SOD) as predictive factors for mortality in hemodialysis (HD) patients. METHODS: SOD, butyrylcholinesterase, and malondialdehyde were estimated spectrophotometrically and the other parameters by standard procedures. High-sensitive C-reactive protein was assayed by a sandwich ELISA method. RESULTS: sUA among survivors (112.1 ± 13.82 µmol/L) was significantly lower than in deceased (160.8 ± 16.81 µmol/L, p < 0.001), while SOD was higher in survivors (31.8 ± 6.61 kU/L) than among deceased (20.2 ± 3.03, p < 0.05). Kaplan-Meier survival curves showed the greatest mortality risk in the highest tertile of basal sUA concentration (≥ 127.11 µmol/L, p < 0.001), and for SOD in the lowest tertile (≤ 23.83 kU/L, p < 0.05). CONCLUSION: Our results suggest that high sUA and low SOD may predict all-cause and cardiovascular mortality in HD patients.