[Anemia of chronic diseases in the early stages of chronic kidney disease as a risk factor for cardiovascular complications in patients with glomerulonephritis].

AIM: To determine biomarkers of anemia of chronic disease (ACD) in patients with glomerulonephritis (GN) in the early stages of CKD, to assess their role as risk factors for cardiovascular complications (CVС). MATERIALS AND METHODS: Seventy nine patients with GN were studied, among them: 40 with primary сhronic GN (CGN), 39 with secondary forms:19 - GN with ANCA-associated systemic vasculitis, 20 - GN with systemic lupus erythematosus (SLE) at early (all I-II) CKD stages. In all patients, the level of serum C-reactive protein (CRP), hepcidin, interferon γ, and the circulating form of protein Klotho (s-Klotho) were determined. When a relative iron deficiency was detected [transferrin iron saturation coefficient (TSAT) <20%], patients were administered parenterally iron [III] sucrose hydroxide complex (Venofer). RESULTS: The frequency of anemia among patients with systemic diseases is 3.2 times higher than among patients with primary CGN. Patients with anemia (group I; n=43) had higher rates of daily proteinuria (p<0.001), systolic blood pressure (p<0.05), serum levels of interferon γ (p<0.001) and hepcidin (p<0.001) and lower values of eGFR (p<0.05) than patients without anemia (group II; n=36). A strong inverse correlation was noted between the level of hepcidin and the content of iron in serum (r=-0.856; p<0.001), between the level of hemoglobin and the level of interferon γ (r=-0.447; p<0.05), hepcidin (r=-0.459; p<0.05) and CRP (r=-0.453; p<0.05). A significant inverse correlation was found between the level of hemoglobin and CVC risk factors - the value of systolic blood pressure (r=-0.512; p<0.05) and the mass index of the left ventricular myocardium (r=-0.619; p<0.01). At the same time, the contribution of 2 from 6 analyzed factors, hepcidin and eGFR, to the development of ACD was 92.5%, of which 86.6% accounted for hepcidin. A strong direct correlation was also found between a decrease in hemoglobin level and a decrease in the level of s-Klotho protein (r=0.645; p<0.001), a decrease in the level of s-Klotho and an increase in the level of serum hepcidin (r=-0.541; p<0.05). The leading value of anemia (beta -0,29; p=0,04) and depression of the s-Klotho level (beta -0,44; p=0,02) as independent cardiovascular risk factors in this group of patients was confirmed by multivariate analysis. In patients with identified deficiency of iron (n=40), after 3-4 weeks of intravenous administration of venofer, the target level of hemoglobin (Нb>120 g/l) and transferrin saturation with iron (TSAT>20%) were achieved. CONCLUSION: Among the biomarkers of ACD in patients with immunoinflammatory diseases of the kidneys (primary and secondary СGN), the increase in the serum level of hepcidin is greatest importance. The concomitant to anemia decrease in s-Klotho is a leading risk factor for CVС in CKD. Early correction of ACD with iron supplements makes it possible to achieve target levels of Hb and TSAT and have subsequently a positive effect on the production of s-Klotho and the severity of left ventricular hypertrophia.

[Soy protein as part of a low-protein diet is a new direction in cardio- and nephroprotection in patients with 3B-4 stages of chronic kidney disease: prospective, randomized, controlled clinical study].

BACKGROUND: It has been established that the use of a low-protein diet (LPD) in combination with ketoanalogues (KA) of essential amino acids can contribute to cardio- and nephroprotection in chronic kidney disease (CKD). Moreover, it has been shown that replacing part of the animal protein with soy protein (SP) in the diet contributed to more pronounced nephro- and cardioprotection in CKD, however, the data, available in the literature, are mainly represented by experimental studies. AIM: To compare the effects of 2 types of diets on the main parameters of nephro- and cardioprotection in patients with CKD. MATERIALS AND METHODS: We have conducted a prospective, randomized, controlled clinical study which included 85 patients with 3B4 stages of CKD, compliant to LPD (0.6 g of protein/kg body weight) + KA (1 tablet/5 kg body weight). 43 patients (Group 1) received LPD with replacing animal protein with soy (60% soy protein + 40% another vegetable proteins) + KA, and 42 patients (control group, Group 2) received LPD (60% animal protein + 40% vegetable protein) + KA, within 12 months. RESULTS: The dietary substitution of animal protein with SP to a greater extent delayed the decrease in glomerular filtration rate (-5.9% vs -13.3%; p=0.048), the increase in left ventricular hypertrophy (+4.7% vs +12.3%; p=0.042), as well as the increase in central systolic blood pressure (+2.6% vs +13.0%; p=0.021), augmentation index (+7.6% vs +23.3%; p=0.010), slowed down the decrease in lean body mass in men (+0.9% vs -11.2%; p=0.017) and women (-1.8% vs -10.3%; p=0.024), increase in phosphorus (-10.3% vs +13.0%; p=0.029), cholesterol (-10.7% vs -3.4%; p=0.047) and urea (+6.3% vs +19.6%; p=0.035) serum levels. CONCLUSION: The use of LPD with substitution of animal protein with soy protein + KA provides a more pronounced effect on nephro- and cardioprotection as well as maintenance of nutritional status, than conventional LPD + KA in patients with 3B4 stages of CKD.

[Diagnostic and treatment difficulties in kidney damage in the patient with generalized sarcoidosis during COVID-19. Case report].

The presented clinical observation reflects the difficulties of differential diagnosis of progressive kidney damage in a patient with sarcoidosis who has undergone a new coronavirus infection. The differential circle included interstitial nephritis as an exacerbation of the underlying disease, acute drug-induced kidney injury, acute glomerulonephritis. Nephrobiopsy confirmed the diagnosis of acute sarcoid tubulointerstitial nephritis with acute tubular necrosis. Timely administration of corticosteroids led to the control of the sarcoidosis process, restoration of kidney function.

[Evaluation of the effectiveness of the compression method for infiltration anesthesia of the mandibular molars]. / Otsenka effektivnosti primeneniya kompressionnogo metoda pri infil'tratsionnoi anestezii dlya obezbolivaniya zhevatel'nykh zubov na nizhnei chelyusti.

AIM: To study the depth of analgesia and the electrical excitability dynamics of the pulp of the tooth under local anesthesia without and with compression on the depot of local anesthetics. MATERIALS AND METHODS: 87 men and 93 women took part in the study, the average age of men was 36.8±5.02 and the average age of women was 30.43±2.14. According to the indications, local anesthesia of infiltration type with and without compression at the depot of local anesthetics was performed. The injection was carried out with a solution of 4% articaine with epinephrine1:100000 or 1:200000. Patients were divided into 2 groups depending on the used concentration of the vasoconstrictor with 4% articaine. The target area thermometry and electroodontometry (EOD) of the first mandibular molar were performed. The criterion for the onset of pulp analgesia was the value from 92 to 100 mA. RESULTS: Dynamics of change in pulp electrical excitability of the first molar with the use of 4% articaine with epinephrine 1:200000 without a compress showed that in the latter case the reduction of pulp electrical excitability to 96.6 µA, which is optimal for painless treatment, was developed by the 5th minute of the study and remained at the limit of 92.2-92.1 µA for 20 minutes. When using 4% articaine 1:100 000 it was noted that also the compression technique allowed to reach the necessary reduction of EOD indices to 93.5 µA by the 5th minute of the study, and to 97.2 µA by the 10th minute. Increased hypothermia in the injection depot area was noted thermographically, especially when high concentrations of epinephrine were used. CONCLUSION: Our own studies reflect the dynamics of change in the electrical excitability of the pulp of the first molar with the use of 4% articaine by compression method more intensively reduces the electrical reacrivity of the dental pulp depending on the concentration of the epinephrine: with the use of 1:100000, the advantage of the pressure technique is 19.3% and 1:200000 - 21.8%.

[Effect of vitamin D receptor activators on serum Klotho levels in 3b-4 stages chronic кidney disease patients: a prospective randomized study].

BACKGROUND: High risk of cardiovascular events is among leading problems in chronic kidney disease (CKD). Serum Klotho is supposed to be cardio- and nephroprotective; modification of its levels may be important in CKD. AIM: To evaluate the impact of vitamin D receptor activators (VDRA) on Klotho serum levels in CKD 3b4 stages patients. MATERIALS AND METHODS: Study included 90 CKD 3b4 stages patients who had elevated serum levels of parathyroid hormone (PTH). From them, 47 patients (group 1) started to treat with the selective VDRA (zemplar 1 mcg/day), and 43 patients (group 2) started to treat with non-selective VDRA (alfacalcidol 0.25 mcg/day). At baseline and after 12 months we conducted routine examination, serum Klotho measurement, and broad cardiovascular examination. RESULTS: The patients who managed to maintain a target serum PTH level, had higher Klotho serum level (p=0.037) at the end of the study. Patients who used selective VDRA significantly more often reached the target PTH level (p=0.032), had higher serum Klotho levels (p=0.037), and glomerular filtration rate (eGFR) level (p=0.048) than patients who used non-selective VDRA. In addition, patients treated with alfacalcidol more than 6 months, more often had hypercalcemia (p=0.047) and hyperphosphatemia (p=0.035). Group 2 showed higher: pulse wave velocity (p=0.051), left ventricular myocardial mass index (p=0.033), and more advanced heart valve calcification (p=0.038). CONCLUSION: Successful parathyroid hormone level control with vitamin D receptor activators was associated with higher serum Klotho, selective agents having shown greater effect. Long-term treatment with selective vitamin D receptor activators may contribute to cardiovascular calcification prevention by modifying Klotho levels.

Autoimmune liver disease (primary biliary cholangitis/autoimmune hepatitis-overlap) associated with sarcoidosis (clinical cases and literature review).

Clinical features of overlap autoimmune hepatitis/primary biliary cholangitis and morphological-proved sarcoid lesions (lungs, lymph nodes, skin) were performed. Data of long-term clinical observation presented in comparison with the results of laboratory datas, instrumental and morphological studies of liver tissue, lungs, skin. The modern aspects of pathogenesis of association autoimmune and granulomatous diseases arediscussed on the example of clinical cases of combination of cholestatic variants of autoimmune hepatitis and generalized sarcoidosis. Keywords: sarcoidosis, autoimmune hepatitis, primary biliary cholangitis, primary biliary cholangitis-autoimmune hepatitis-overlap, extrahepatic manifestations.

Clinical significance of the determination of surfactant proteins A and D in assessing the activity of lung sarcoidosis.

AIM: To study the clinical significance of SP-A, SP-D in assessing the activity of idiopathic pulmonary fibrosis and sarcoidosis. We examined 81 patients with morphologically confirmed diagnoses of idiopathic pulmonary fibrosis (ILF) and sarcoidosis, a control group of 20 healthy individuals. The MSCT of the thoracic organs of the chest was performed, the diffusivity of the lungs was examined, oxygen saturation was determined. In the serum, the surfactant proteins SP-A and SP-D were determined by the enzyme-linked immunosorbent assay. RESULTS: A significant increase in SP-A and SP-D (p<0.05) was observed in patients compared with patients in the control group, a direct correlation was found with signs of activity: SP-A with alveolitis (p<0.05), SP- D with progressive fibrosis (p<0.05), inverse correlation of surfactant proteins with respiratory function indices (p<0.05). CONCLUSION: Serological parameters of SP-A and SP-D reflect the activity of alveolitis and the progression of pulmonary fibrosis in patients with ILF and sarcoidosis.

[Role of the morphogenetic proteins FGF-23 and Klotho and the glycoprotein sclerostin in the assessment of the risk of cardiovascular diseases and the prognosis of chronic kidney disease].

UNLABELLED: AIM. To analyze changes in the serum concentrations of the morphogenetic proteins fibroblast growth factor 23 (FGF-23) and Klotho, as well as sclerostin, an osteocyte-secreted glycoprotein, in relation to the degree of hypertension, left ventricular (LV) hypertrophy, and arterial stiffness in patients with chronic kidney disease (CKD) at its different stages. SUBJECTS AND METHODS: Sixty-five patients (33 men and 32 women) aged 20-65 years, including 25 with chronic glomerulonephritis, 15 with tubulointerstitial nephritis, and 25 with hypertensive nephrosclerosis, were examined. A control group consisted of 15 healthy volunteers matched to the study group patients for age and gender. Serum FGF-23 concentrations and blood pressure (BP) were measured in the all subjects. Patients with BPs > 140/80 mm Hg underwent echocardiography, followed by determination of LV mass (LVM) and calculation of LVM index. Vascular circulation, pulse wave velocity, cardiac and vascular calcifications, and vascular functional properties were estimated. RESULTS: There was a strong direct Correlation between the serum concentration of FGF-23 and the stage of CKD and an inverse correlation between the levels of Klotho and sclerostin and the stage of CKD. As the glomerular filtration rate became lower, the concentration of FGF-23 increased and that of Klotho and sclerostin decreased just in Stage III CKD while hyperphosphatemia and elevated parathyroid hormone levels were noted in Stages IV-V CKD. As CKD progressed, the serum concentrations of Klotho and sclerostin were inversely correlated with the levels of phosphorus and parathyroid hormone. The degree of blood pressure elevation correlated positively with serum FGF-23 concentrations and inversely with Klotho levels. There was no significant correlation of the level of sclerostin with the degree of BP increase. The direct correlation between higher FGF-23 level and higher VLM is most pronounced in hypertensive patients. There was a strong direct relationship between FGF-23 and Klotho levels and a strong inverse relationship between sclerostin levels and pulse wave velocity. Lower Klotho concentrations were associated with the detection rate of calcifications in the heart valves and large arteries (the abdominal aorta). The reduced serum levels of Klotho and sclerostin were also correlated with concentric LV remodeling. CONCLUSION: It was demonstrated that there was a clear link between increased serum FGF-23 and decreased Klotho concentration as CKD progressed, and that between arterial stiffness and calcification and myocardial remodelling regardless of traditional risk factors. More experimental and clinical studies are required to clarify the role of sclerostin in CKD.