Background and Objectives: Nowadays, every tenth adult in the world suffers from diabetes mellitus (DM). Diabetic retinopathy (DR) is the most common microvascular complication of type 2 DM (T2DM) and a leading cause of acquired blindness in middle-aged individuals in many countries. Previous studies have identified associations of several gene polymorphisms with susceptibility to microvascular complications of DM in various worldwide populations. In our study, we aimed to test the hypothesis of the associations of single nucleotide polymorphisms (SNP) of the VEGF (−2549I/D), RAGE (−429T/C and −374T/A), TCF7L2 (rs7903146), and ITGA2 (BglII) genes with a predisposition to DR among T2DM patients in the Kazakhstan population. Materials and Methods: We conducted a case–control study comparing the genotype distribution and allele frequencies between groups of DR patients (N = 94), diabetic patients without DR (N = 94), and healthy controls (N = 51). Genotypes were identified using the PCR-RFLP method. Results: In all cases, the genotype distribution corresponded to the Hardy–Weinberg equilibrium. The groups of diabetic patients with and without DR did not significantly differ in the genotype distribution of the SNPs studied. Differences between both groups of diabetic patients and healthy controls in four out of five SNPs were also not significant. At the same time, both groups of diabetic patients differed significantly from healthy controls in genotype distribution (p = 0.042 and 0.005, respectively) and allele frequencies (p = 0.021 and 0.002, respectively) of the BglII polymorphism in the ITGA2 gene. After adjusting for multiple comparisons, the differences between the group of diabetic patients without DR and the control group remained significant (pBonf = 0.027 for genotypes and pBonf = 0.009 for alleles). The BglII− allele was associated with diabetes: OR = 1.81 [1.09–2.99] for DR patients, and OR = 2.24 [1.34–3.75] for diabetic patients without DR. The association was also observed in the subset of Kazakhs. Conclusions: This study shows that the BglII polymorphism in the ITGA2 gene can be associated with T2DM but not with DR. According to our data, the risk allele for diabetes is the wild BglII− allele, and not the minor BglII+, which is considered as risky for DR.
Blindness and low vision, as a social medical problem, occupy one of the leading places in both healthcare and the state economy. Diabetic retinopathy (DR) is a vision-threatening microvascular disease, the most common diabetes complication that affects the retina, causing blindness among working-age adults in developed countries. Difficulties in determining the starting, key pathogenetic links and early diagnosis of this disease do not allow to accurately determine the initial moment of occurrence, and known treatment methods are aimed, as a rule, at slowing down the pathological process. Purpose. Analysis of literature data on the clinical and diagnostic features of diabetic retinopathy. Material and methods. To analyze the literature, information was searched on this problem up to 10 years deep in PubMed / MEDLINE, PMC, Web of Since. For the search, the following terms were used individually or in combination: "diabetes mellitus", "diabetic retinopathy", "diabetic vasculopathy", "optical coherence tomography", "fluorescence angiography", "complications". The search criteria were key studies related to diabetic retinopathy, vasculopathy: meta-analyzes, original studies, retrospective and cohort studies. Results and discussions. Oxygen from the capillary layer of the choroid through the Bruch membrane and retinal pigment epithelium (RPE) gets to the outer retinal layers. Due to complications in the bloodstream, nutrition is impaired which leads to diabetic retinal changes. It is advisable and necessary to study changes in the structures of the choroid in large samples using angio-OCT, since changes in the choroid can be the primary prognostic markers of the development of diabetes in the absence of clinical manifestations of diabetic retinopathy. Conclusion. Changes in the structure of the choroid can become a marker for predicting the development of DR in patients with type 2 diabetes, more accurately and quickly establish a diagnosis in the early stages of the disease, and prescribe appropriate therapy in a timely manner. As a result, patients receive timely care and treatment costs will decrease. Keywords: diabetes mellitus, diabetic retinopathy, choroid, diabetic choriopathy, OCT angiography, choroid structures.
BACKGROUND AND AIMS Chronic kidney disease (CKD) is a complex medical and social problem worldwide due to high prevalence and mortality rates. According to the ESPN/ERA-EDTA, the prevalence of CKD stages 3–5 in children is about 55–60 pmarp [1]. Moreover, CKD usually causes different severe complications, including pathologic changes in the cardiovascular system, which significantly affect long-term survival. Unlike many complications of CKD, hypertension can be present in the earliest stages of the disease [2]. Nowadays, there has been a scientific and practical interest in Fibroblast growth factor 23 (FGF-23) which is mostly considered as a phosphate-regulating biomarker [3]. There are some speculations that FGF-23 affects blood pressure (BP) in adults due to the impact on the renin-angiotensin-aldosterone system (RAAS) by decreasing calcitriol [4] and the direct effect of FGF-23 on sodium reabsorption, which has been demonstrated in experimental models [5]. Therefore, the aim of our study was to investigate the link between FGF-23 and BP in children with CKD. METHOD There were 73 children with CKD stages 1–5, mean age was 9.79 ± 0.58 years. BP was determined by 3 times measurement and calculating the mean value. Received results were compared with percentile norms according to age and gender in order to divide patients into two groups: normotensive and hypertensive. FGF-23 was determined in serum by multimatrix ELISA kit (Biomedica Medizinprodukte GmbH, Austria). Statistical analysis was performed using SPSS version 26 (IBM, USA). RESULTS In the group with normal BP the median of FGF-23 in serum was 1.8 [0.7–3.4] pmol/L. In comparison, in the group with a hypertensive level of BP median indicator of FGF-23 was 7.6 (1.98–18.5) pmol/L (P < .001). The prevalence of elevated FGF-23 in children with high BP predominates 1.6 times [95% confidence interval (95% CI): 1.2–2.1]. It is also noticed that pulse BP positively correlated with FGF-23 level in serum (r = 0.402, P < .001). CONCLUSION Our findings confirm that FGF-23 is linked to BP in children with CKD what makes us conclude that more careful attention to children with a high level of FGF-23 is needed in relation to hypertension and as a consequence cardiovascular complications. However, more investigations should be done in order to establish a causal relationship.
Background and Aims Chronic kidney disease (CKD) is considered a global medical and public health issue. CKD takes a special place among non-infectious diseases because of its prevalence (6-20% according to different surveys and studies) and is associated with a poor life quality, complications and high risk of mortality. In recent years, there have been new biomarkers requiring more research in this area. One of these biomarkers is Fibroblast growth factor-23 (FGF-23) which is found as a bone derived hormone and might be a predictor of progression. However, the role of FGF-23 in CKD progression in children has not been adequately studied, especially on the early stages. Nowadays, the study of FGF-23 in children and the question of the clinical importance of this marker are relevant. Therefore, the aim of our study was to establish the role of FGF-23 in CKD progression in children. Method A prospective study was conducted on 73 children with different stages of CKD and 14 healthy individuals (control group) matched by age and gender. There were approximately equal numbers of patients in study groups. An average age was 9.61±1.05 years. Exclusion criteria: active inflammatory, bone, infectious, oncological, immunological diseases, taking steroids and vitamin D supplements. Laboratory measurements included all common clinical and biochemical indicators. Serum concentration of intact FGF-23 was assessed by using the ELISA method (Biomedica Medizinprodukte GmbH, Austria). Statistical analysis was conducted in MS Excel 2016 and SPSS 18.0. Results The normal range of FGF-23 for this kit was 0.1-1.5 pmol/l. The average value of FGF-23 in the control group was 0.69±0.12 pmol/l. Further studies in the groups with different stages of CKD revealed that FGF-23 concentration gradually rose in parallel with stages of CKD, and it reached the maximum on the last stage. It should be noticed that the level of FGF-23 concentration on the first stage of CKD was normal (0.73±0.14 pmol/l) and the comparison with healthy individuals revealed no significant differences. What is remarkable, despite the fact that the average value of the second stage patients was normal (1.36±0.2 pmol/l), there was a statistically significant difference with the control group (p=0.008). The levels of FGF-23 on the next stages were 2.52±0.52 pmol/l, 5.42±1.61 pmol/l, and 12.16±1.55 pmol/l, respectively. The differences were considerable and proved by statistical analysis (p<0.01). Conclusion Our study showed that there is an upward trend of FGF-23 as CKD progresses from early to advanced stages. The results on the second and third stages indicate that FGF-23 should be considered as one of early biomarkers of CKD progression in children. Thus, there is a need for more studies in this area.
Ablepsia and hypovision as a social medical problem occupies one of the leading places, both in health care and the economy of the state. Uveitis associated with systemic diseases occur in up to 40% of the population and require an interdisciplinary approach, as they are characterized by polymorphism of clinical manifestations, which makes it difficult to diagnose and treat early, leads to rapid development of complications and disability. Aim. Analysis of literature data on epidemiological and clinical features of uveitis associated with systemic diseases. Material and methods. To analyze the literature, we searched for information about this problem for a period up to 10 years in PubMed/ MEDLINE, PMC, Web of Since. The following terms were used separately or in combination for the search: “uveitis”, “non-infectious uveitis”, “spondylarthritis”, “systemic connective tissue diseases”, “systemic vasculitis”, “complications”, “anti-TNF-α”. The search criteria were key studies related to uveitis and systemic diseases: meta-analyses, original studies, retrospective and cohort studies. Results and discussion. In everyday clinical practice, only close cooperation between rheumatologist and ophthalmologist considering carefully collected anamnestic information, clinical features and course of disease, data of additional examinations contribute to early diagnosis, selection of optimal strategy of treatment, prevention of recurrence and the reduction of visual impairment. Conclusion. All patients with ocular inflammation, especially in the presence of systemic diseases, require the professional attention of clinical medicine specialists. Keywords: inflammatory eye diseases, uveitis, systemic diseases, complications, spondylarthritis, systemic vasculitis, Behcet's syndrome, SLE.
To this date, uveitis associated with connective tissue diseases remain relevant due to serious complications that significantly reduce vision and thus worsen the quality of life of patients. Aim. To study the frequency and prevalence, as well as clinical manifestations of ophthalmopathology in connective tissue diseases. Material and methods. A retrospective and prospective study of 534 patients (144 men and 390 women) with connective tissue diseases was conducted, in which ophthalmological disorders were detected. The patients underwent standard rheumatological examination in the department. And also, ophthalmological examination with the determination of visual acuity, intraocular pressure and the use of biomicroscopy, ophthalmoscopy (or cycloscopy). If necessary and possible, additional studies were performed such as: ultrasound B-scan, optical coherence tomography, perimetry. The study examined the type of common disease, age of onset and gender of the patient. Of particular interest were patients with uveal inflammation, in which the localization and nature of the course of inflammation were evaluated. Results and discussion. The most common diseases with eye damage were rheumatoid arthritis (RA) – 129 (24.1%), systemic lupus erythematosus (SLE) – 92 (17.2%), inflammatory bowel disease (IBD) – 95 (17.8%), systemic scleroderma (SDS) – 54 (10.1%) and spondylarthritis (Spa) – 41 (7.8%). In a small percentage of cases, other connective tissue diseases were diagnosed, such as: mixed connective tissue diseases (MCTS) – 24 (4.5%), Overlap syndrome – 21 (3.9%), systemic vasculitis – 23 (4.3%), Behcet's syndrome -18 (3.4%), Sjogren disease – 14 (2.6%) and juvenile idiopathic arthritis - 7 (1.3%). All ophthalmic disorders were divided into four general groups and distributed as follows: inflammatory 27.7%, degenerative 4.9%, vascular 48.7%, side effects of glucocorticoids 18.7%. Uveitis accounted for 52 (9.7%) of all ophthalmopathology, occurring in connective tissue diseases. Unilateral acute anterior uveitis (AAU) was diagnosed in 13 (25%) patients with ankylosing spondylitis, of which 4 (7.8%) had a relapse in the paired eye. Simultaneously, bilateral AAU was detected in 3 (5.7%) patients with Behcet's syndrome. Chronic, recurrent posterior uveitis was diagnosed in 13 (25%) patients with Behcet's systemic vasculitis. All patients with Behcet's syndrome were male at the age of 31±3.1 years. The uveal process approximately started 3.2±1.16 years after the onset of systemic disease. Generalization of inflammation in all departments of uvea was detected in patients with PSA-5 (9.6%), AC – 3 (5.7%), DS – 2 (3.8%) and SLE – 2 (3.8%). In 5 (9.6%) patients, the process was bilateral. Inflammation of the paired eye by the type of AAU was observed in 1 patient and posterior uveitis - in 2 patients. Conclusions. Ophthalmic disorders in the structure of systemic diseases make up 20.2% and vary widely in their clinical manifestations. Chronic blepharoconjunctivitis, combined with rheumatoid arthritis (46%) is a common inflammation of the accessory structures of the eye. About 20% of patients have complications from general immunosuppressive therapy, leading to impaired visual function. The frequency of uveitis in the structure of ophthalmopathology associated with connective tissue disease is 9.7%. Uveitis associated with ankylosing spondylitis and systemic vasculitis of Behcet occurs in men at a younger age and is 31%. More than half (63%) of patients with uveitis have a severe course with the development of panuveitis and neuropathy. An increase in the thickness of the choroid (up to 2 mm) according to two-dimensional ultrasound is an early diagnostic criterion for the development of uveitis and the underlying disease of connective tissue. Keywords: inflammatory eye diseases, uveitis, connective tissue diseases, spondyloarthritis, Behcet's syndrome, complications.
Background and Aims In recent years there has been a growth in the number of patients with chronic kidney disease (CKD). As it is known, one of the most severe complications of CKD is mineral and bone disorder (MBD). MBD, which develops in childhood, contributes not only to the development of degenerative bone disease, but also to the growth of vascular morbidity and mortality in adulthood. Therefore, adequate control of bone and mineral metabolism is one of the goals in the treatment of children with CKD. Due to the recently discovered FGF-23, a significant role in the pathogenesis of MBD is given to hyperphosphatemia as the initiator of the process. However, changes in value of phosphorus and parathyroid hormone (PTH) are revealed only on the last stages of the disease. FGF-23 is a protein, which produced in bone cells and nowadays it is considered to be the central regulator of mineral-bone metabolism. It increases the loss of phosphorus in the urine due to the blockade of the sodium-phosphorus transporter in the proximal tubule of the nephron. FGF-23 also inhibits 1α-hydroxylase and stimulates 24-hydroxylase, leading to accelerated degradation of the active form of vitamin D. Thus, the aim of our study was to investigate the relation between FGF-23 and other markers of bone metabolism such as phosphorus and parathyroid hormone. Method The study was conducted on 73 children (38 boys and 35 girls) with different stages of CKD. An average age of the patients was 9.89 ± 0.57 years. Exclusion criteria: active inflammatory, bone, infectious, oncological, immunological diseases; taking steroids and vitamin D supplements. We performed further laboratory tests: phosphorus, PTH, vitamin D and FGF-23. Serum concentration of intact FGF-23 was assessed by using the kit for ELISA method (Biomedica Medizinprodukte GmbH, Austria). This study was approved by the local scientific ethics committee of National medical university. Ethical standards and rights of patients were not violated. Descriptive statistics and correlation analysis were performed in MS Excel 2016 and SPSS 18.0. Results The laboratory tests results revealed that the mean value of phosphorus was 1.77±0.04 mmol/l among all patients with different stages of CKD. There were 29 (33.3%) children with hyperphosphatemia. The most of these patients were ESRD and they needed a renal replacement therapy. No patients with CKD 1-3 stages had high level of phosphorus. The values of PTH increase as CKD progresses. The patients with the first and second stages had absolutely normal PTH value and only 2 patients with the third stage had slightly elevated level. Only 1 out of 17 patients on dialysis (both hemodialysis and peritoneal dialysis) had an acceptable PTH value. By contrast, there was a vitamin D deficiency (a mean value was 22.4±1.64 ng/ml). The results of identification FGF-23 by the ELISA kit showed that there was also a gradual increase in its level depending on the stage of the disease. Moreover, there were 14 (19.2%) children with elevated FGF-23 concentration though other markers of bone metabolism were normal. The correlation analysis revealed positively significant associations between FGF-23 and phosphorus (r=0.60, p=0.00), FGF-23 and PTH (r=0.68, p=0.00). Conclusion Overall, our investigation proved that FGF-23 is positively correlated to phosphorus and PTH. Furthermore, in most cases, FGF-23 responds much sooner than other markers of mineral and bone metabolism and its increased value might be an early predictor of mineral and bone disorder. However, more research is required in this area.
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