Uromodulin as a potential candidate marker for predicting the course of chronic kidney disease

Uromodulin is a nephrospecific protein that is most common in normal urine. And although it has been known for more than 70 years, the function of uromodulin remains unclear. Uromodulin is involved in regulating the transport of salts, protects against urinary tract infections, namely, the mucous membrane of the bladder, and prevents the formation of kidney stones, as well as plays a role in kidney damage and innate immunity. Serum uromodulin and uromodulin of urine, daily excretion and excretion of uromodulin per 1 milliliter of creatinine clearance are actively studied. Complete genome studies of the association have established a correlation between uromodulin gene mutations and autosomal dominant tubulointerstitial kidney disease.

24-h Potassium Excretion Is Associated with Components of the Metabolic Syndrome: Results from a National Survey Based on Urine Collection in Adults

A balanced diet and weight loss are the first lines of treatment for the prevention of metabolic syndrome (MS). Dietary strategies may include changing the composition of macronutrients, adopting a particular dietary pattern as a Mediterranean diet. However, the role of micronutrients, particularly potassium, in the propensity for or treatment of the syndrome is unclear. The study aimed to examine the relationship between the presence of the MS and its risk factors and the 24-h potassium excretion as the most valid proxy for dietary intake. The analyses were performed as part of the national survey estimating sodium and other electrolytes excretion conducted between 2014–2016 in Israel. The survey included urine collection, anthropometric and blood pressure measurements, and a comprehensive medical questionnaire that included details on the intake of medications that may affect electrolyte secretion. A model was constructed to evaluate the probability for the MS. MS score and its probability were examined in relation to potassium excretion at different levels and in stratification to sex. A total of 581 participants were included in the analysis. The mean potassium excretion was 2818 ± 1417 mg. The prevalence of the MS was 18.5% among participants with above-average potassium excretion and about 10.4% among participants with lower-than-average excretion (p = 0.007). A dose–response relationship was observed between MS score and potassium: the higher the score, the lower was the excretion of potassium. Potassium excretion, rather than sodium excretion, correlated with all components of the MS and even predicted MS independently from other variables. This is the first study based on a national survey showing that potassium consumption, as represented by daily excretion in urine, is inversely related to the presence of MS components after adjustment for several leading variables and careful exclusion of participants taking drugs which may interfere in potassium excretion.

The role of fibroblast growth factor 19 in pathogenesis of bile acid diarrhea of the patients who underwent cholecystectomy

The occurrence of chronic diarrhea after cholecystectomy (CCY) has been described by many researchers. However, the main mechanisms of the development of this diarrhea are not fully understood. Supposed that dysregulation of the bile acids (ВA) absorption in the ileum is played a significant role in the development of diarrhea syndrome. Aim. To determine the role of the fibroblast growth factor 19 (FGF19) level in the serum and BA concentration in feces in pathogenesis of bile acid diarrhea (ВАD) in patients after CCY. Materials and methods. Sixty-one patients were examined at various times after CCY: 30 patients with chronic diarrhea that appeared after CCY (group 1) and 31 patients with normal stools (group 2). In all patients, the level of FGF19 in the blood serum, and the daily excretion of BA in the feces were studied. The control group consisted of 28 healthy individuals. Results. In the 1st group we found lower concentrations of FGF19 in the blood serum 86.2 ng/ml (67.8; 117.8) compared with concentrations in the 2nd group 259 ng/ml (170.6; 318.8), p0.001. The daily excretion of bile acids with feces in the 1st group was 657.4 mg/day (524.6; 830.1), which was twice more than in the 2nd group and the control group. It was established an inverse correlation between serum concentration of the FGF19 and the BA excretion in the feces in all examined patients. It indicates a possible relationship between the low concentration of FGF19 in blood serum and malabsorption of the BA. Conclusion. Low level of FGF19 in the blood serum and a high excretion of BA in the feces may be one of the causes of BAD in patients undergoing cholecystectomy. Our results indicate the important role of FGF19 in the development of chronic diarrhea, which can be considered as one of the variants of postcholecystectomy syndrome.

Relationship of Juvenile Diabetic Retinopathy with Thyropathies, Lipid Exchange and Melatonin Production

Progression of diabetic retinopathy is associated with a large number of risk factors, and hyperlipidemia is one of the most common. The work is focused on peculiarities of the progression of juvenile diabetic retinopathy (JDR), depending on the presence of concomitant distyroidism in patients with juvenile diabetes mellitus (JDM), the state of lipid metabolism and melatonin production. The aim. To determine the features of the JDR progression depending on the type of concomitant dysthyroidism, the state of lipid metabolism and production of the hormone melatonin. Materials and methods. The examination of three groups of patients was carried out: group 1 (152 patients) included patients in whom JDM proceeded without thyropathy; group 2 (99 patients) included patients with JDM in combination with autoimmune thyroiditis (AIT); group 3 (111 patients) included patients in whom JDM was accompanied by an increased level of thyroid-stimulating hormone (TSH). Results. It was found that the frequency of proliferative diabetic retinopathy (PDR) in the group with JCD and elevated TSH (21.6%) was 2.7 times higher than the frequency of PDR in the group with JDM and AIT (8.1%) and 3.7 times exceeded the frequency of PDD in JDM without distyroidism (5.9%). The greatest violations of all links of lipid metabolism were found in patients with JDM with an increased level of TSH, which contributes to a more pronounced progression of JDR than in patients without thyropathy or concomitant AIT. The average daily excretion of the hormone melatonin (M) among the studied groups was the lowest in patients with PDD with JCD in combination with increased TSH (38.4 ± 2.7 nmol/day) compared with patients with PDD with JCD without thyropathy (48.3 ± 3.8 nmol/day; p <0.01) and with AIT (42.5 ± 5.6 nmol/day; p <0.01), and compared with the control indicator (52.7 ± 5.8 nmol/day; p <0.001). Conclusions. Based on the results obtained it can be concluded that the combination of type 1 JDM with elevated TSH is accompanied by significant disorders of lipid metabolism and melatonin production and this is a risk factor for accelerated progression of JDR. Keywords: juvenile diabetic retinopathy, thyropathy, melatonin production, lipid metabolism.

Biochemical indices of urine in children with allergic diseases of airways

Currently, unsatisfactory control of the course of allergic diseases of airways (ADA) remains. There is data on the potential involvement of urate and oxalate metabolism in the pathogenesis of ADA, which determines the need to study the corresponding biomarkers. Aim of the work - to evaluate the daily urinary excretion of urates and oxalates in ADA children. Materials and methods. We examined 100 children aged 2 to 9 years, boys - 22, girls - 78, with symptoms of crystalluria. The children were divided into the main group (42 children) and the comparison group (58 people). The main group included patients with established diagnoses of ADA, and the comparison group included patients without ADA. A biochemical study of daily urine was performed in all cases. Results. It was found that the daily excretion of oxalates in ADA patients was significantly increased compared to the control, 26.5 [22.1; 32.6] mg/day and 23.3 [20.1; 27.6] mg/day, respectively. Daily urate excretion in patients of the main group was also significantly increased compared to the control, both in absolute numbers - 1.45 [1.13; 2.13] mmol/day and 1.17 [0.89; 1.5] mmol/day, respectively (p = 0.005), and in normalized to the body surface area units. Conclusion. A statistically significant increase in daily urate excretion was found in ADA children. The clinical and pathogenetic significance of this phenomenon in children with ADA requires further study.

Correlation Between Serum Parathormone Levels With Urinary Magnesium Excretion in Patients With Non-Dialytic Chronic Kidney Disease

Background: Disorders of mineral metabolism occur in most patients with chronic kidney disease (CKD). The aim of this work was to correlate serum parathyroid hormone (PTH) levels with urinary magnesium excretion in patients with non-dialysis CKD. Methods: Cross-sectional study with patients with CKD undergoing non-dialysis treatment in stages 3A, 3B and 4. Concentrations of creatinine, magnesium, calcium, phosphorus, parathyroid hormone, vitamin D and alkaline phosphatase were determined in blood samples. The assessment of urinary magnesium levels was performed by means of total daily excretion and by the excretion fraction (FEMg). Results: The study evaluated 163 patients with mean age of 60.7 ± 11.7 and 51.0% were male. A positive correlation was observed between PTH and alkaline phosphatase (r = 0.26; p = 0.006) and FEMg (r = 0.17; p = 0.020). Calcium (r = -0.23; p = 0.002), magnesium in 24-hour urine (r = -0.18; p = 0.020) and estimated glomerular filtration rate (r = -0.47; p = 0.001) demonstrated negative correlation with PTH. Conclusion: Elevated levels of PTH correlated positively with FEMg, regardless of the presence of serum magnesium alterations, and FEMg can be used as another indicator for the treatment of hyperparathyroidism.

The effect of convulsive syndrome on the metabolic status and survival of patients with alcoholic delirium

The aim of the study was to study the effect of convulsive syndrome in patients with delirium tremens (DT) on the charac teristics of the metabolic status of the body, the severity of clinical manifes tations, and survival of people of different ages. The study involved 753 patients with DT at the age of 20 to 76 years. The metabolic status was studied. One indicator was the urea-creatinine serum index; its low level was considered a sign of anabolic trends in metabolism. Another indicator was the determination of the total protein content in the body by daily excretion of creatinine. It was found that patients with DT with convulsive syndrome had a higher score according to the severity of the disease according to the DRS scale, a longer period of mental disorders, the average number of somatic complications was higher. However, the survival rate of patients with DT with convulsive syndrome and patients with DT without convulsive manifestations was the same. To determine the causes of this, the metabolic status and age of surviving and deceased patients with DT were compared. The highest total protein content in the body is observed in surviving patients with DT with manifestations of convulsive syndrome. Surviving patients with DT with manifestations of convulsive syndrome had a significantly lower level of urea-creatinine index compared with survivors with DT without convulsive syndrome. Among all patients with DT, the average age of survivors with convulsive syndrome was the lowest, and the average age of deceased patients with convulsive syndrome was the highest. In patients with DT without convulsive manifestations, the age of surviving and dead patients did not differ. The age of surviving patients with DT with convulsive syndrome is significantly lower than that of surviving patients without convulsive manifestations. The presence of convulsive syndrome and associated metabolic changes in the body in patients with DT contributes to the survival of a younger part of patients. Key words: alcohol delirium, seizures, aggravation of mental and somatic disorders, anabolic state of metabolism, primary survival of young patients

BIOLOGICAL MARKERS AND MORPHOGENESIS OF ACUTE RENAL INJURY IN RAT DICHLOROETHANE POISONING

The article presents the results of an experimental study on rat poisoning with 1,2-dichloroethane (250 µl / kg, intragastric administration). The aim of this work was to find the relationship between biological markers and morphological changes in acute damage to rat kidneys with dichloroethane. The study of urine samples of experimental animals by gas-liquid chromatography (GLC) revealed 1,2-dichloroethane in the concentration range of 0,05 – 0,90 µg / ml (95% C.I. = 0,09 – 0,90 µg / ml). Daily excretion with urine was 0,60 – 4,50 µg / 16h (95% C.I. = 1,14 – 3,93 µg / ml). Levels of nephron-specific biomarkers in urine were 194,62 ± 9,02 IU / L (NAGase, p = 0,0022) and 2,93 ± 0,38 ng / ml (KIM-1, p = 0,0022), which exceeded those in the control group by 5 and 23 times, respectively. Edema, disorders of intrarenal hemodynamics, leukocyte migration in interstitium, uneven damage to various areas of the kidneys due to adipose dystrophy and necrobiotic changes in the nephrothelium of the proximal tubules mainly in the cortical layer of the kidneys have developed in the kidneys. Positive correlations between the level of 1,2-dichloroethane in the urine and the level of KIM-1 (Spearman r = 0,7427, 95% C.I. 0,2764 – 0,9260, p = 0,0083), -N-acetylglucosaminidase (Spearman r = 0,8248, 95% C.I. 0,4613 – 0,9512, p = 0,0019), the scores on the EGTI scale (Spearman r = 0,8064, 95% C.I. 0,7126 – 0,8719, p < 0.0001); the level of KIM-1 and the scores on the EGTI scale (Spearman r = 0,7427, 95% C.I. 0,2764 – 0,9260, p = 0.0083), -N-acetylglucosaminidase and the scores on the EGTI scale (Spearman R = 0,4684, 95% C.I. 0,2764 – 0,6244, p < 0,0001), the level of the low and medium molecular weight substances in the blood and the scores on the EGTI scale (Spearman R = 0,6909, 95% C.I. 0,5549 – 0,7909, p < 0,0001) were found.