LEADING ARTICLE
As the rate of natural disasters and other devastating events caused by human activities increases, the burden on the health and well-being of those affected by kidney disease has been immeasurable. Health system preparedness, which involves creating a resilient system that is able to deal with the health needs of the entire community during times of unexpected disruptions to usual care, has become globally important. In the wake of the COVID-19 pandemic, there is a heightened awareness of the amplification of negative effects on the renal community. Paradoxically, the complex medical needs of those who have kidney diseases are not met by systems handling crises, often compounded by an acute increase in burden via new patients as a result of the crisis itself. Disruptions in kidney care as a result of unexpected events are becoming more prevalent and likely to increase in the years to come. It is therefore only appropriate that the theme for this year’s World Kidney Day will focus on Kidney Health for All: preparedness for the unexpected in supporting the vulnerable.
REVIEWS AND LECTURES
The transfer of kidney transplant recipients from pediatric to adult healthcare should be a planned process, as it involves various risks, including loss of the transplanted organ and death of the patient. The most critical age for the development of adverse events is the age of 17–24 years. This is because of the peculiarities of the maturation of the brain of adolescents, severe kidney disease and the need for constant medication. At this age, patients experience peer pressure, preoccupation with their appearance, personal development, pursuits and dreams for the future, which may not come true against the background of a long-term chronic illness and lead to low self-esteem, depression and anger. The result of these psycho-emotional experiences may be non-compliance with the regimen of immunosuppressive drugs with the development of rejection, and even loss of a kidney transplant. The transition process should ideally take several years and start early, usually between the ages of 12 and 14. The transfer should be carried out not only after the onset of a certain age, but also based on the existing skills and readiness of the patient. The patient must remain in the pediatric service if severe complications (rejection, infections) develop until they are treated and for at least 1 year after transplantation, even if this period is the age of transition to adult service. Following a transition readiness assessment, a structured plan should be drawn up requiring the integration of medical, educational, behavioral and social strategies both during and after the transition. Establishing transitional clinics or assigning a position of coordinator allows controlling the transition process and minimize possible risks and negative consequences. The development and implementation of programs for the transition of kidney transplant recipients to adult service are aimed at increasing the survival of the kidney transplant and patients, improving their quality of life.
In physiological states, the nervous system and kidneys interact with each other to maintain normal homeostasis in the body. However, pathological conditions such as hypertension, pathology of the kidney itself, both acute and chronic, disrupt this interaction. In acute kidney injury (AKI of various etiologies) and chronic kidney disease (CKD), damaged kidneys can have a significant impact on the function of the central nervous system. CKD is an independent risk factor for the development of cerebrovascular diseases and cognitive impairment due to many factors, including the retention of uremic toxins and phosphates, have been proposed as CKD-specific factors responsible for structural and functional cerebral changes in patients with CKD, however, additional studies are needed to determine the exact pathogenesis. Our review is devoted to the interaction of the kidney and the nervous system in physiological conditions and pathophysiological conditions, we are trying to reveal in detail the mechanisms of dysfunction of the nervous system in kidney pathologies.
Asymptomatic hyperuricemia is frequently seen in patients with kidney disease. A significant number of epidemiological studies suggest that elevated uric acid levels play a causal role in the development and progression of kidney disease. But whether hyperuricemia is simply the result of reduced renal excretion of uric acid or contributes to the progression of renal disease remains controversial. Over the past two decades, numerous experimental studies have expanded the knowledge of the biological effects of uric acid beyond its role in the development of gout. In particular, uric acid induces activation of the immune system and affects not only renal tissue cells but also endothelial cells. All this has led to the presentation of uric acid as a potential and modifying risk factor for kidney disease. This review examines the effects of uric acid on the immune system and further on renal tissue during inflammation.
ORIGINAL ARTICLES. CLINICAL INVESTIGATIONS
THE AIM. To determine the frequency of elevated serum immunoglobulin E (IgE) levels in patients with immunoglobulin A nephropathy (IGAN) and to establish its relation to clinical and morphological, laboratory manifestations and disease course.
PATIENTS AND METHODS. The study enrolled 47 patients with primary IGAN, age 32 (27 ÷ 39) years. Daily proteinuria (PU), hematuria, serum creatinine, degree of arterial hypertension (AH) and glomerular filtration rate (GFR) were analyzed. Blood concentration of total IgE was determined by enzyme immunoassay, and allergen-specific IgE antibodies to 57 allergens (domestic, epidermal, fungal, vegetable, food) using a commercial kit "EUROLINE Atopy Screen (IgE)" ("Euroimmun", Germany).
RESULTS. In patients with IGAN, serum total IgE was found to exceed the normal value in 55 % of cases, with a concentration of 89.4 (47.5 ÷ 198.7) IU/ml and correlation with GFR (R=0.32, p=0.02) and creatinine (R=-0.40, p=0.01) was detected. Patients with elevated IgE levels showed a reduced incidence of AH (p=0.01), tubular atrophy and interstitial fibrosis (T1) (p=0.03). A correlation analysis revealed that the severity of endothelial proliferation decreased with increasing IgE concentration (R=– 0.40, p=0.02). The highest prevalence among allergens was shown for specific IgE to domestic mites Dermatophagoides farinae (42,1 %), specific activity of 31,4 (1,7 ÷ 71,3) u.u. was noted to Dermatophagoides pteronyssinus. There was a correlation between IgE concentration to Dermatophagoides pteronyssinus and PU (R=-0.51, p=0.01) and between the amount of IgE to Dermatophagoides farinae and the percentage of half moon (R=-0.55, p=0.01). The five-year event-free survival rate was 67 ± 19 % in the IgE group within normal limits and 100 % in the IgE group above normal limits (p=0.008).
CONCLUSION. The presence of elevated concentrations of total and specific IgE indicated a more favourable course of IGAN.
BACKGROUND. The problem of steroid-sensitive nephrotic syndrome is the developing of steroid dependency and toxicity.
THE AIM: Evaluate duration of remission of steroid-dependent nephrotic syndrome (NS) after cyclosporine and mycophenolate sodium therapy in children with or without clinical manifestation of allergy.
PATIENTS AND METHODS. Follow-up study with analysis of onset, clinical course and treatment includes 47 children ((31 boys (66 %) и 16 girls (34 %)) with steroid-dependent NS, 34 (72,3 %) had clinical manifestation of allergy, 13 (27,7 %) didn’t have clinical manifestation of allergy. The efficiency of therapy with cyclosporine in 16 patients and mycophenolate sodium in 27 patients with clinical manifestation of allergy is estimated in comparative study by analysis of 6, 12, 24 month remission rate after treatment. Median duration of remission of NS during 2 years after treatment is estimated. Out of 27 children 8 (29,6 %) had mycophenolate sodium treatment after cyclosporine and took part in both groups.
RESULTS. Statistically significant differences in 6, 12, 24 month remission rates after cyclosporine and mycophenolate sodium treatment in children with clinical manifestation of allergy are established. Remission of NS during 6 months after mycophenolate sodium treatment was in 81,5 % (in 22 from 27 patients) unlike of that after cyclosporine – in 40 % (in 6 from 15 patients) in children with clinical manifestation of allergy (р<0,05). Remission of NS during 12 months after mycophenolate sodium treatment was in 55,6 % (in 15 from 27 patients) unlike of that after cyclosporine – 13,3 % (in 2 from 15 patients) (р<0,05) in children with clinical manifestation of allergy. Remission of NS during 24 months after mycophenolate sodium treatment was in 37 % (in 10 from 27 patients) unlike of that after cyclosporine – 6,7 % (in 1 from 15 patients) (р<0,05) in children with clinical manifestation of allergy. Median duration of remission during 2 years after treatment with cyclosporine and mycophenolate sodium in children with clinical manifestation of allergy was 7,0 [2,0-11,0] and 17,0 [6,0-24,0] months, retrospectively, (р<0,05).
CONCLUSION. Remission of steroid-dependent NS during 6 months after therapy with mycophenolate sodium and cyclosporine in children was in 81,5 % and 40,0 % respectively, in children with clinical manifestation of allergy. Remission of steroid-dependent NS during 12 months after therapy with mycophenolate sodium and cyclosporine in children was in 55,6 % and 13,3 % respectively, in children with clinical manifestation of allergy. Remission of steroid-dependent NS during 24 months after therapy with mycophenolate sodium and cyclosporine in children was in 37 % and 6,7 % respectively, in children with clinical manifestation of allergy. Median duration of remission during 2 years after treatment with cyclosporine and mycophenolate sodium in children with clinical manifestation of allergy was 7,0 [2,0-11,0] and 17,0 [6,0-24,0] months, retrospectively. As the result of comparative study duration of remission of steroid-dependent NS in children with clinical manifestation of allergy was statistically significantly longer in children after therapy with mycophenolate sodium.
BACKGROUND. Protein-energy malnutrition (PEM) often develops in patients receiving long-term treatment with programmed haemodialysis (HD). Its main causes are decreased intake of basic nutrients, increased losses, disorders inherent to the terminal renal failure itself (including chronic inflammation), as well as the influence of factors associated with the HD procedure.
THE AIM: to clarify the role of interleukin-6 (IL-6 ) in the pathogenesis of BEN in patients treated with programmed haemodialysis.
PATIENTS AND METHODS. We examined 645 patients receiving HD treatment, including 300 men and 345 women aged 56.8±12.8 years, the duration of renal replacement therapy was 8.4±5.3 years. Nutritional status was assessed according to International Society of Renal Nutrition and Metabolism (ISRNM) recommendations. Serum IL-6 levels were determined by a three-step "sandwich" version of a solid phase enzyme immunoassay using mono- and polyclonal antibodies to IL-6 using a commercial kit "Interleukin-6-IFA-BEST" from Vector-Best, Russia, under the manufacturer's instructions. The reference values for IL-6 are 0-7 pg/ml.
RESULTS. The prevalence of BEN was 24.9 % (160 patients). Mean IL-6 concentration was 6.47±2.64 pg/ml in patients without evidence of BEN, and 23.20±10.40 pg/ml in patients with BEN, p<0.001. Elevated IL-6 levels revealed statistically significantly lower levels of total protein, albumin, prealbumin, total cholesterol, transferrin and blood lymphocyte counts. Patients with elevated IL-6 levels were also characterized by statistically significantly lower values of body mass index, skeletal muscle mass index and skeletal muscle mass index.
CONCLUSION. The results of this study suggest that the high prevalence of PEM in patients treated with HD is closely related to an imbalance of pro- and anti-inflammatory cytokines. An increase in the duration of renal replacement therapy is accompanied by an increase in serum IL-6 levels. Therefore, this cytokine can be considered as a therapeutic target for prevention and treatment of sarcopenia in dialysis patients.
BACKGROUND. In the mechanisms of immune inflammation in chronic glomerulonephritis (CGN), activation of T-cells plays an important role. The role of Th1 and Th2 cells in the pathogenesis of some forms of CGN has been well studied, while the activation of Th17 cells in CGN has been only evaluated in isolated studies. THE AIM: to evaluate the value of determining the level of IL-17 in urine and blood serum in chronic glomerulonephritis.
PATIENTS AND METHODS. Adult patients with active CGN (N=40) were recruited aged from 18 to 75 years. Ten patients had focal segmental glomerulosclerosis, 6 had membranoproliferative glomerulonephritis, 15 had IgA nephropathy, and 9 had membranous nephropathy at histological examination. The control group included 10 healthy subjects. The IL-17A levels in the urine and blood serum were determined by enzyme-linked immunosorbent assay (ELISA). The IL17A levels in the urine were calculated as the ratio to urinary creatinine. The levels of IL-17 in urine and blood serum were compared with the indicators of proteinuria, albumin, creatinine, serum sodium, also the severity of hypertension, edema and daily sodium excretion.
RESULTS. The results of our study showed a significantly higher concentration of IL-17 in urine in patients with a marked decrease in renal function. Also, the levels of IL-17 in urine directly correlated with serum sodium and inversely correlated with eGFR. We also found an association between increase levels of IL-17 in urine with arterial hypertension and the severity of edema. There were no significant correlations of IL-17 in blood serum and other laboratory indicators of nephritis activity.
CONCLUSION. Patients with CGN have increase levels of IL-17 in the urine compared to healthy subjects. A more significant increase of IL-17 in urine is observed in patients with high clinical activity of HCG. IL-17A may participate in the mechanisms of sodium retention, the development of hypertension and edema in patients with nephrotic syndrome.
THE AIM: to study the relationship of blood sclerostin with clinical parameters and its influence on the probability of detection of cardiovascular calcification in patients with CKD C5D.
PATIENTS AND METHODS. The study was a single-stage, cohort study involving 84 patients with stage 5D CKD who received hemodialysis therapy, including 40 (47.6 %) female patients and 44 (52.4 %) male patients. The average age was 55.6±14.9 years. The examination included, in addition to routine studies, echocardioscopy with an assessment of calcification of the heart valves, abdominal radiography in the lateral projection with an assessment of aortic calcification, analysis of indicators that characterize phosphorus-calcium metabolism (serum sclerostin levels, 1.25(OH)D, FGF-23, A-klotho, PTH, P and Cа blood). Statistical analysis was performed using the computer program STATISTICA 12.6 (StatSoft Inc., USA).
RESULTS. It was shown that the level of sclerostin is higher in the elderly, as well as those who have signs of hypoproteinemia and hypoalbuminemia, indirectly indicating the presence of protein-energy deficiency. There is an Association of blood sclerostin with FGF-23 and Alpha-klotho. From the point of view of the probable influence on the processes of cardiovascular calcification, this relationship shows its unidirectionality. Increased blood sclerostin levels have been shown to be associated with the risk of detecting signs of cardiovascular calcification. Moreover, it is shown that the higher the level of sclerostin in the blood, the more pronounced the degree of this calcification. Along with the increase in the level of sclerostin, the ability of a deficit of 1.25(OH)D to lead to the development of calcification was confirmed.
CONCLUSION. A high level of sclerostin in the blood serum of more than 92.5 pmol / l in patients with CKD C5D increases the risk of detecting signs of cardiovascular calcification (calcification of the aortic wall and heart valves). An increase in sclerostin levels occurs in conjunction with an increase in FGF-23 and a decrease in 1.25(OH)D
BACKGROUND. Extragenital diseases, including recurrent urinary tract infections, have an adverse effect on the reproductive health of children and adolescents. Vaginitis and menstrual cycle disorders, including primary oligomenorrhea, predominate in the structure of gynecological morbidity of minors suffering from recurrent UTIs.
THE AIM: to study the role of stress reactions in the genesis of various variants of menstrual cycle disorders in minors suffering from recurrent UTIs to improve the dispensary management of this cohort of patients.
PATIENTS AND METHODS. A prospective study was conducted in 98 adolescent girls aged 16 to 18 years. Taking into account the nature of the clinical course of UTI, all the subjects were divided into 3 groups: group 1 (n=41) – patients with UTI; group 2 (n=27) patients with frequent recurrence of UTI (more than 3 times a year (rIMP); group 3 (n=30) – minors, 1, 2 health groups with no IPM episode. A specialized gynecological examination, functional diagnostic tests, ultrasound examination of the placemark and ovaries, determination of cortisol, norepinephrine, adrenaline by enzyme immunoassay were carried out. Statistical analysis was performed using the program "SPSS Statistics 17.0 for Windows".
RESULTS. Anovulation was observed in patients with frequent recurrence of UTI. Copious and prolonged menstruation, uterine bleeding and primary oligomenorrhea were observed only in patients with recurrent UTIs. In this cohort, inflammatory gynecological diseases take a chronic course. Polycystic ovarian syndrome (40.7 %) and chronic salpingoophoritis (44.4 %) were often detected in patients with frequently recurrent UTI. In patients suffering from UTI, in contrast to the data of the comparison group, there were significant violations of the nature of adaptive reactions, and changes in antistress reactions and their levels differed depending on the variant of the course of the microbial-inflammatory process. In patients with rare relapses of UTI, antistress reactions of a high level of reactivity prevailed, but there were reactions of calm and increased activation, training that took place at low levels of reactivity.
CONCLUSION. Adaptive-compensatory disorders were revealed in almost every patient with recurrent UTI. Considering that stress is especially pathogenic during puberty, when hormonal and psychophysiological restructuring of the body occurs, prevention and complex therapy of microbial-inflammatory diseases of the urinary system in this category of patients should be carried out taking into account the formation of reproductive function and the severity of adaptation reactions.
It is generally accepted that the true-resistant hypertension (RH) currently remains critical issue. At present there is some published evidence that catheter renal denervation prosedure showed effectiveness at randomized clinical trials. The assessment of renal function after the technique is crucial.
THE AIM of the study was to estimate renal function after renal artery denervation procedure in patients with uncontrolled hypertension in 3 – years follow-up.
PATIENTS AND METHODS. The diagnosis of RH was made in the absence of any evidence of secondary hypertension. 40 patients (20 male and и 20 female), aged 55,5± 7,2 years, with office systolic blood pressure (BP) 180 ±26,1 mm Hg, and diastolic BP 107,4±13,9 mm Hg were examined. Glomerular filtration rate (GFR, MDRD) and microalbuminuria level was determined by averaging all measurements performed during hospitalization. Ambulatory blood pressure monitoring (BPM) was performed in all patients.
RESULTS. BPM has revealed the significant decrease of systolic daytime blood pressure (at baseline 161,1±16,9 mm Hg and at follow-up 155,4±20,8 mm Hg; р= 0,024) and decrease of diastolic daytime BP (at baseline 95,6 ±11,8 mmHg and at follow -up 90,2 ±12,4 mm Hg; р=0,002). During 3 -year of follow-up the serum creatinine level has increased at baseline 69,5±16,4 μmol/l and at follow-up 78,7±19,5 μmol/l; р<0,0001). The Glomerular filtration rate has scaled down (at baseline 98,2±18,7 ml/min and at follow-up 85,1±17,9 ml/min; р< 0,0001). The level of daily excretion of albumin has also decreased (at baseline 30,4 [14,6; 52,9] mg and at follow-up 14,1 [11,9; 42,4] mg correspondingly; р= 0,03) .
CONCLUSION. Although BP profile changes have demonstrated the effectiveness of RDN, therefore the future investigation of exact patho-physiological significance of glomerular filtration level after the treatment of RH should be of provided.
The structure of the detected kidney pathology was studied according to the results of a forensic medical examination of corpses in the St. Petersburg Bureau of Forensic Medical Examination (BSME) in 2020–2021. As a result of the research, it turned out that out of the total number of all corpses that were sent by the investigative bodies for forensic medical examination to the St. Petersburg Bureau of Forensic Medical Examination over the years, kidney pathology amounted to 0.7 %. The most frequent (67 %) renal pathology leading to death were malignant kidney diseases. In the group of malignant kidney diseases, the age of the deceased was in the range of 40–90 years (with a pronounced peak of 80–90 years). The age of the majority of those who died from non-malignant kidney diseases was 50-90 years (with a pronounced peak of 80-90 years). Gender differences in the causes of death in the groups of malignant and non-malignant kidney diseases have not been established.
ORIGINAL ARTICLES. EXPERIMENTAL INVESTIGATION
BACKGROUND. One of the most frequently reproduced models of NS is doxorubicin (adriamycin) nephropathy in rats. However, the mechanisms of its development remain insufficiently studied, and it is not entirely clear to which form of NS the nephrotoxicity induced by doxorubicin should be attributed.
THE AIM. Reproduction of doxorubicin nephropathy in rats in an attempt to morphologically identify the resulting pathology and determine the role of free radical oxidation (FRO) in the development of this model of nephrotoxicity.
MATERIALS AND METHODS. Nephropathy was reproduced by a single intravenous administration of doxorubicin to male Wistar rats. In the urine, the content of creatinine, daily proteinuria, and albumin release were determined. Histological examination of the kidneys was performed using a Libra 120 electron microscope (Carl Zeiss, Germany). The total prooxidant activity, total antioxidant activity, the concentration of thiobarbiturate-reactive products, and the activity of antioxidant enzymes were assessed in the blood and kidney.
RESULTS. Against the background of a gradual decrease in the glomerular filtration rate, a significant consistent increase in protein excretion was recorded, largely due to an increase in albumin excretion. Electron microscopic examination revealed a decrease in the number of small (foot) processes of podocytes, their fusion, sclerotic lesions of the elements of the capillary glomerulus, thinning of the GBM, sclerosis of the interstitium. There was a sharp activation of blood OPA and an increase in the content of TBRP. At the same time, such fast-responding antioxidant enzymes as CAT and SOD were activated. The blood TAA decreased in parallel with the decrease in GPO activity.
CONCLUSION. Intravenous administration of doxorubicin to rats induced the development of toxic kidney damage with signs of NS. A characteristic indicator was the development of PU against the background of a decrease in GFR from day 5 and increased many times by the end of the observation period. The greatest contribution to the development of PU was made by an in-crease in albumin excretion. Morphological examination of the kidneys using electron microscopy made it possible to conclude with a high degree of probability that the developed pathology and FSGS are similar. At the same time, FRO activation was recorded, which was expressed in a sig-nificant pro-oxidant effect and a significant decrease in the antioxidant activity of the blood.
PRACTICAL NOTES
The development of the modern world is manifested, inter alia, by an increase in the prevalence of obesity and cardiovascular diseases. Treatment of these conditions is associated with the need to prescribe multicomponent therapy, which complicates the control of drug interactions, leads to a decrease in compliance and polypharmacy. A large number of drugs taken in a particular patient dictates the need to search for drugs, the appointment of which contributes to the control of several diseases at once, can be successfully used in patients with reduced renal function, in the presence of cardiovascular diseases. The presented description of a clinical case demonstrates an example of the use of a type 2 sodium glucose cotransporter inhibitor – dapagliflozin in a patient with type 2 diabetes mellitus, chronic kidney disease, chronic heart failure and gout.
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