REVIEWS AND LECTURES
The gut microbiota is an essential part of the human organism, which plays a crucial role in maintaining its homeostasis. Peaceful coexistence with trillions of microorganisms mainly depends on the normal functioning of cellular and extracellular components of the intestinal mucosa, often called the "intestinal barrier". This barrier protects the organism against pathogenic infections while and at the same time satisfying its requirements for digestion and absorption of nutrients. It is not surprising that structural and functional intestinal barrier abnormalities are involved in the pathogenesis of many diseases including various nephropathies. The pathogenetic interconnection between the intestine and the kidneys is bidirectional. On the one hand, uremia affects the microbiota composition and the integrity of the intestinal epithelium. On the other hand, uremic toxins translocation, formed as a result of abnormal microbial metabolism, from the intestine into circulation through the ultra-permeable barrier contributes to the progression of renal dysfunction. Furthermore, according to a number of researchers, dysbiosis and the leaky gut syndrome are considered as one of the possible causes of anemia, nutritional disorders, cardiovascular and many other complications, often diagnosed in patients with chronic renal disease. The first part of the review reflects modern data about normal intestinal barrier structure and physiology, as well as methods for studying the intestinal wall integrity and permeability. The significant role of microbiota in the regulation of the barrier properties of the intestinal mucous and epithelial layer is emphasizing. The main differences between the intestinal microflora of patients with nephropathies from healthy people are presented, possible causes of their occurrence are discussed.
ORIGINAL ARTICLES. CLINICAL INVESTIGATIONS
THE AIM. To study the key homeostatic physicochemical parameters of blood serum characterizing the patient's state with COVID-19 of varying severity. Patients and methods. The study involved 94 patients with COVID-19, age from 24 to 102 years, median – 67 years, men – 43, women – 51. Patients were divided into 3 groups: 1st – 40 patients with a relatively mild course, 2nd – 22 patients with a severe course of the disease, after treatment they were discharged from the clinic, the 3rd – 32 patients with a very severe course of COVID-19 and a fatal outcome. The concentration of ions in blood serum was measured on a Gem Premier 3000 (Instrumentation Laboratory, USA), clinical analysis was performed on a BC-5380c Mindray hematology analyzer (Mindray, China), biochemical studies were performed on an Architech c4000 analyzer (Abbott Laboratories, USA).
RESULTS. The harbingers of a serious impairment in patients with COVID-19 were an increase in the Na+/K+ ratio in blood serum from 32,7±0,8 to 44,7 ± 2.1 (p<0,01), a decrease in the concentration of ionized Ca2+ from 1,08 ± 0,01 to 0,9 ± 0,03 mmol/l (p<0,01), a sharp increase in the concentration of C-reactive protein from 43,6±8,6 to 175 ± 14,7 mg/l (p<0,01). Within the reference values with COVID-19 the concentration of bilirubin and creatinine in the blood serum remained normal; the concentration of total protein was at the lower limits of the normal range, the glucose level was slightly higher than normal, and ferritin was increased compared to the reference values.
CONCLUSION. Harbingers of a sharp impairment in COVID-19 are an increase in the Na+/K+ ratio in the blood serum, a decrease of the of ionized Ca2+ concentration, a sharp increase in C-reactive protein concentration.
BACKGROUND. The presence and drug correction of arterial hypertension (AH) with inhibitors of the renin-angiotensin system (RAS), as well as chronic kidney disease (CKD) and its role in the regulation of RAS, can significantly affect the condition of a person with COVID-19.
OBJECTIVE: to study the features of the functional state of the kidneys in patients with grade 1-2 hypertension who have fallen ill with COVID-19.
PATIENTS AND METHODS. A subanalysis of patients with CKD, participants in the BIRCOV study (ARB, ACEi, DRi in COVID-19) is presented: 112 outpatient patients with grade 1-2 hypertension, 83 of whom had CKD. The participants were divided into groups receiving ACE inhibitors (group 1 – 39 %), ARBs (group 2 – 32 %), or a direct renin inhibitor (PIR) (group 3 – 29 %) as the main therapy of hypertension. The value of blood pressure, eGFR, albuminuria level were analyzed at the debut of COVID-19 and at 2, 4, 12, 24 weeks from the onset of the disease.
RESULTS. In the first two weeks of COVID-19, there was a decrease in blood pressure with a gradual return to baseline values in patients of group 1 and group 3 (to a lesser extent). The use of ACE inhibitors in the treatment of hypertension increased the risk of withdrawal compared to PIR and ARBs due to COVID-19. In patients with CKD, higher values of mean blood pressure were obtained with similar dynamics. A synchronous decrease in eGFR and systolic blood pressure has been documented, more pronounced in patients with CKD, especially when taking aCEI. The decrease in eGFR correlated with the stage of CKD. With stable renal function in patients with CKD during the first 12 weeks of COVID-19, the urine albumin/creatinine ratio (UAC) increased without further normalization. By the second week of the disease, eGFR decreased with a reciprocal increase in the level of uric acid in the blood. The use of dexamethasone was accompanied by a decrease in eGFR in CKD stages 3b-4.
CONCLUSION. When taking ACE inhibitors, the effect of lowering blood pressure was comparable to a double block of RAS: ACE inhibitors + ARBs.
BACKGROUND. Chronic kidney disease leads to a significant increase in the risk of fractures, which increases even more after kidney transplantation.
THE AIM. The goal of this study was to develop simple, accessible criteria for predicting the risk of fracture in patients with a functioning kidney transplant.
PATIENTS AND METHODS. The prospective study included 131 kidney transplant recipients (men-55, women-76) (average age 39.7±11.7 years). The duration of follow-up was 40.7±21.2 months. Bone mineral density was assessed using dual-energy x-ray absorptiometry. To determine the prognostic significance of variables, we used stepwise regression (Cox model) analysis. p < 0.05 was considered statistically significant.
RESULTS. During the follow-up period, fractures were registered in 47 patients (35.9 %). Fractures were detected more often in women (42 %) than in men (27.3 %). All patients with fractures had lower bone mineral density and longer-term renal replacement therapy. Stepwise multivariate regression analysis showed that the combination of bone mineral density scores of lumbar vertebra and duration of renal replacement therapy best predicts the overall fracture risk. Adding the other variables to the analysis did not increase significantly their predictive value. A comparative analysis of the cumulative proportion of males and females with fractures confirmed a greater susceptibility of female transplant recipients to fractures.
CONCLUSIONS. The combination of bone mineral density scores of the lumbar vertebra with the duration of renal replacement therapy best predict the risk of fracture in patients with kidney transplants and can be used in the choice of prevention measures.
THE AIM: to evaluate the efficacy, safety, and tolerability of the preparation of calcium polystyrene sulfonate (Kalimate ® ), clinical observation was conducted in patients with chronic kidney disease who do not need dialysis, using different dosages of the drug with incomplete effectiveness of the hypokalemic diet as monotherapy for hyperkalemia.
PATIENTS AND METHODS: the study included 70 patients suffering from chronic kidney disease who do not need renal replacement therapy, and with a plasma potassium level of 5.5 mmol/l or higher, after the use of hypokalemic diet therapy was ineffective. The patients were divided into 4 groups depending on the dose of calcium polystyrene sulfate. The 3 groups differed in the dose of the drug taken, the 4th group consisted of patients with reduced nutrition. Patients in all groups underwent control studies of serum potassium concentration before the start of the study, after 1 week, after 2 weeks, after 1 month, after 3, and after 6 months of treatment.
RESULTS: The decrease in the level of potassium in the blood serum of group 1 patients for 6 months was 24.15 % (95 % CI 16.32-31.4 %), which in absolute value was 1.485± 0.513 mmol/l. Similar parameters for groups 2, 3 and 4 were, respectively: 22.59 % (95 %CI 15.57–31.12 %) and 1.38±0.487 mmol/L, 19.72 % (95 %CI 12.08–25.32 %) and 1.215±0.45 mmol/L, 25.24 % (95 % CI 17.86–30.24 %) and 1.58±0.502 mmol/l.
CONCLUSION: the effectiveness of reducing serum potassium levels in patients with hyperkalemia on the background of chronic kidney disease who do not receive dialysis and follow only a hypokalemic diet, when using the drug polystyrene sulfate according to the instructions for 15-30 grams per day for at least 1 week with subsequent dose adjustment is an effective way of treating and correcting hyperkalemia.
Hemodiafiltration on-line (HDF OL) cannot be considered sufficiently studied in terms of its effect on the outcome.
THE AIM. To identify the possible relationship of individual anthropometric, laboratory data and parameters of the prescribed treatment regimen with better survival when using the HDF OL.
PATIENTS AND METHODS. A retrospective study of the EuCliD database of patients treated with HDF OL in 27 Fresenius Medical Care centers in the Russian Federation during 2014 was conducted. All patients received postdilution HDF OL procedures at least 3 times a week, lasting at least 12 hours a week, with adequacy of Kt/V procedures of at least 1,4. Data from survivors (9616) and deceased (370) patients were compared. The analyzed indicators were: gender, age, treatment experience, body weight, body mass index (BMI), body surface area (BSA), total body water volume (TBW), the volume of distribution (V Urea BCM), presence of diabetes mellitus, coronary heart disease, heart failure, as well as the parameters of the procedure: effective weekly dialysis time, Kt/V, effective in-fusion volume (EIV), effective convection volume (ECV).
RESULTS. Risk factors for death in patients with CKD 5D treated with HDF OL include male gender, older age, con-comitant diseases, lower body weight, and BMI, shorter effective weekly dialysis time, lower EIV and ECV values, Kt/V, higher hypercalcemia, hypoalbuminemia, lower hemoglobin levels, higher b2-microglobulin levels, and CRP. Сomparing the normalized BMI, BSA, TBW, V Urea BCM indicators, we identified those that were associated with a high risk of mortality in the population of dialysis patients.
CONCLUSION. As a result of this work, two normalized ratios were identified (the median ratio of effective infusion volume to body surface area and the median ratio of effective convection volume to body surface area), which were associated with a high risk of mortality in the population of dialysis patients.
BACKGROUND. Uromodulin (UMO) is a multifunctional glycoprotein expressed in epithelial cells of the thick ascending part of the loop of Henle. Currently, enough information has been accumulated about the participation of this glycoprotein in a number of important physiological and pathological processes. THE AIM: to evaluate the relationship between the level of urine uromodulin (Umo) and the intake of angiotensin converting enzyme (ACE) inhibitors in chronic kidney disease.
PATIENTS AND METHODS. 96 patients aged 43.6±15.4 years were examined. (M:W = 46:50). The presence of kidney disease in all cases is confirmed morphologically. The main criterion for the inclusion of patients in the study was the presence of CKD C1-C3. The exclusion criteria were age over 70 years, the presence of diabetes mellitus, immunosuppressive therapy at the time of examination, taking diuretics. Umo concentrations in blood serum (SUmo) and urine (UUmo) were measured by enzyme immunoassay. Serum and urinary concentrations of creatinine, potassium, sodium, chlorine, calcium, and inorganic phosphorus, as well as protein levels in urine, were also determined. The glomerular filtration rate (eGFR) was calculated using the formula CKD-EPI. The values of daily excretion, clearance, and fractional excretion were calculated for all ions.
RESULTS. The patients were divided into two groups: group 1 – 20 people who did not take ACE inhibitors; group 2 – 78 people who took ACE inhibitors. The content of Umo in urine correlated in the first group with the value of systolic and diastolic blood pressure and serum Umo. In the second group, associations of the concentration of Umo in urine with age, eGFR, the excreted fraction of sodium and chlorine, and serum Umo were noted.
CONCLUSION. The data obtained suggest that the nephroprotective properties of ACE inhibitors are broader than is commonly thought. Our data allow us to talk about their protective effect at the level of the tubular apparatus. The authors believe that the information currently available is quite sufficient to discuss the need to introduce the definitions of SUmo and UUmo into real clinical practice.
ORIGINAL ARTICLES. EXPERIMENTAL INVESTIGATION
THE AIM: to evaluate the effect of a high-salt diet on the level of miRNA expression in urine and the mechanisms of endothelium-dependent vascular dilatation in rats.
MATERIALS AND METHODS: 20 Wistar rats were divided into two equal groups. The high salt (HS) group received 8 % NaCl in the diet, the control (NS) received the standard diet (0.34 % NaCl). After 4 months, blood pressure (BP), left ventricular mass index (IMLV) were assessed in rats, and relative expression levels of miRNA-21, miRNA-133, and miRNA-203 were determined in urine. The reactivity of the rings of the aorta and the superior mesenteric artery (SMA) to acetylcholine (ACh) was assessed in vitro in isometric mode.
RESULTS: there was no significant difference between the groups in terms of mean blood pressure (p> 0.05). However, in HS-rats an increase in IMLV was noted. The relative levels of expression of miRNA-21, miRNA-133, and miRNA-203 in the urine of rats fed a high-salt diet increased significantly as compared to the values of control animals. A high-salt diet resulted in a decrease in the reactivity of vascular segments precontracted with phenylephrine to ACh. A high-salt diet resulted in a decrease in the reactivity of vascular segments precontracted with phenylephrine to ACh. In the HS-group, the decrease in the amplitude of vasodilation under the action of ACh under conditions of blockade of NO-synthase (with the use of L-NIO) was less compared to the reaction in the absence of the blocker, than the NS-group: in the SMA of the HS group – by 45 %, NS group – by 69.4 %, in the aorta HS-group – by 49.4 %, NS-group – by 80.7 %. In contrast to the aorta, blockade of Ca2+-sensitive K+-channels in SMA (under the conditions of administration of tetraethylammonium, TRAM-34, or apamin) weakened ACh-induced relaxation, and in HS-rats, the decrease in vasodilation was more pronounced.
CONCLUSION: consumption of a high-salt diet, without changing blood pressure, increases IMLV and the level of miRNA expression in the urine, and also reduces endothelium-dependent vascular relaxation, mediated, in particular, by impaired endothelial NO production, which is more pronounced in the aorta than in the SMA.
PRACTICAL NOTES
Fibronectin glomerulopathy (FNGP) is an extremely rare glomerulopathy with an autosomal dominant pattern of inheritance. Sporadic cases of the disease are also described. Currently, several types of FN1 gene mutations are known that underlie conformational changes in the fibronectin molecule and lead to its deposition in the renal tissue. The clinical manifestations of FNGP may be very heterogeneous, but in most cases are characterized by proteinuria, microscopic hematuria, arterial hypertension, and long-term progressive renal failure. Renal biopsy is the main method for diagnosing the disease. Histologically, GFND is characterized by a lobular glomerular architecture with mesangial expansion and obliteration of capillary loops due to the accumulation of an acellular, periodic acid–Schiff positive, silver Jones-negative material. Immunofluorescence is usually negative. Electron microscopy shows finely granular or fibrillary mesangial and subendothelial electron-dense deposits. At higher magnifications, the fibrils have a diameter of 12-16 nm and are randomly arranged. Standard protocols for the etiopathogenetic therapy of FNGP are not currently developed. Improvement of clinical status and prognosis can be achieved by optimizing blood pressure and proteinuria control by renin–angiotensin–aldosterone system blockers. The recurrence risk of FNGP after renal transplantation remains uncertain due to the rare prevalence of the pathology. In this article, we report a 25-year-old man with nephrotic syndrome, which occurred after a previous upper respiratory tract infection. Histological changes specific to FNGP were found in the kidney biopsy. Genetic analysis was not performed. The absence of a family history of kidney disease suggests that this is a sporadic case of FNGP.
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