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Nephrology (Saint-Petersburg)

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Vol 27, No 3 (2023)
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REVIEWS AND LECTURES

11-22 1402
Abstract

There is an increase in the prevalence of chronic kidney disease in the world. This is primarily due to the increase in the incidence of diabetes mellitus and arterial hypertension as the main etiological factors. A progressive decline in the excretory function of the kidneys is associated with metabolic disorders such as metabolic acidosis, hyperuricemia, hyperparathyroidism, oxidative and inflammatory stress, etc. This leads, in turn, to a decrease in the body weight of patients, primarily due to the loss of muscle mass. Such changes have an adverse effect, including on the synthesis of sex hormones, in particular, on the level of testosterone, the production of which decreases in the cohort of patients under discussion. Hormonal imbalance in the form of hypogonadism can play a significant role in increasing cardiovascular risk. Renal replacement therapy may be an independent risk factor for the development and progression of hypogonadism. At the same time, the problems of impaired regulation, synthesis and balance of sex hormones, as well as the issues of correction of secondary hypogonadism in patients with chronic kidney disease remain poorly understood and are of scientific interest.

23-31 373
Abstract

The literature review summarizes information about the current nomenclature and classification of amyloidosis, the features of the etiology, pathogenesis, course, diagnosis and treatment of systemic secondary AA-amyloidosis in children and adult patients. Among the systemic forms of amyloidosis, secondary AA-amyloidosis accounts for 40–60 % of cases. The literature data on the features of the development of secondary AA-amyloidosis in familial Mediterranean fever (periodic illness) due to homozygous or heterozygous mutation of the MEFV gene in children are presented.

ORIGINAL ARTICLES. CLINICAL INVESTIGATIONS

32-43 417
Abstract

Background. One of the components of the metabolome that performs multifaceted functions in homeostasis is blood albumin. The albumin molecule has a pronounced hydrophilicity, due to which it plays an important role in maintaining oncotic blood pressure. Thus, the expansion of knowledge about the interrelationships of traditional biochemical information about the concentration of albumin and the biophysical properties of its derivatives complements the idea of the pharmacological effect of albumin transfusions. THE AIM: to study of the biophysical properties of albumin in patients with chronic kidney disease on programmed hemodialysis.

Patients and Methods. The study included 29 patients with chronic renal failure treated with programmed bicarbonate hemodialysis for an average of 110 months. To assess the condition of patients, a complex of laboratory studies was used, including hematological examination on Beckman Coulter analyzers; clinical assessment of nutritional status based on data from the analysis of medical histories; assessment of colloidal osmotic blood pressure by calculation, as well as by direct measurement on a BMT 923 oncometer; measurement of particle size in blood plasma by dynamic light scattering on a Photocor Compact spectrometer- Z. Statistical analysis of the material was performed using the Statistica for Windows v.6.0 software package. The null statistical hypothesis of the absence of differences and connections was rejected at p<0.05. RESULTS. The average correlation coefficient of oncotic pressure was 0.94 for total protein and 0.90 for albumin. Measurement of colloidal osmotic pressure showed a significant increase in pressure in each of the postdialysis samples. The hydrodynamic radius of the albumin peak for the predialysis sample is significantly higher, which may indicate a change in the sorption properties of the albumin surface. CONCLUSION. The calculation of oncotic pressure by the concentration of total protein, as a rule, provides clinical needs, however, with a significant concentration of toxins, clinical situations are possible in which a moderate decrease in the concentration of the "total protein" of the blood is detected, hence the main oncotic component – albumin is noted but there is a development pronounced edematous syndrome due to a significant decrease in oncotic pressure as a result of a conformational change in albumin molecules. In such situations, it is necessary to directly determine the oncotic pressure of the blood. Keywords: albumin, oncotic pressure, hydrodynamic radius, dialysis>˂0.05.

Results. The average correlation coefficient of oncotic pressure was 0.94 for total protein and 0.90 for albumin. Measurement of colloidal osmotic pressure showed a significant increase in pressure in each of the postdialysis samples. The hydrodynamic radius of the albumin peak for the predialysis sample is significantly higher, which may indicate a change in the sorption properties of the albumin surface.

Conclusion. The calculation of oncotic pressure by the concentration of total protein, as a rule, provides clinical needs, however, with a significant concentration of toxins, clinical situations are possible in which a moderate decrease in the concentration of the "total protein" of the blood is detected, hence the main oncotic component – albumin is noted but there is a development pronounced edematous syndrome due to a significant decrease in oncotic pressure as a result of a conformational change in albumin molecules. In such situations, it is necessary to directly determine the oncotic pressure of the blood.

44-52 235
Abstract

Background. The use of direct acting antiviral drugs (DAАs) leads to the achievement of a stable virological response (SVR) in 95–100 % of patients with HCV-associated cryoglobulinemic vasculitis (HCV-CV). However, in some patients, despite the eradication of the virus, clinical and immunological markers of vasculitis still remain.

The aim: to evaluate clinical and immunological responses in patients with HCV-CV in comparison with patients with "asymptomatic" HCV- associated cryoglobulinemia (HCV- СG) after achieving SVR with the help of DAАs with long-term dynamic observation (12 months).

Patients and Methods: The study included 45 patients: 23 with HCV-CV and 22 with "asymptomatic" HCV-CG, who underwent antiviral therapy with DAAs. Clinical-immunological, virological data were evaluated: before treatment, 12 weeks (3 months) and 48 weeks (12 months) after the end of treatment.

Results: After a course of DAAs, SVR was diagnosed in all 45 (100 % of patients). In patients with HCV-CV, an immunological response (complete and partial) was observed by week 12 (SVR12) – in 56.5 % and by week 48 (SVR48) – in 73.9 % patients. In 6 patients (26.1 %), the immunological response was not achieved by SVR48. The rate of complete and partial clinical response 12 weeks after the end of treatment at the SVR12 period in patients with HCV-CV was 65.2 %, to the time of SVR48 amounted to 78.3 % patients. In 5 (21.7 %) individual manifestations of CV persisted and/or relapsed. In patients with HCV-CG, the frequency of complete and partial immunological responses after DAAs therapy was 77.3 % – by SVR12 and 86.3 % – by SVR48, respectively. No response was observed in 3 patients and it was characterized by trace-level of cryoglobulinemia.

Conclusion: In most patients with HCV-CV eradication of HCV with help of DAAs leads to the achievement of clinical and immunological remission of the disease. However, in 20 % of patients manifestations of HCV-CV persist / recur immediately after the end of treatment or later relapses are observed. Based on these observations, patients with HCV-CV, especially those with severe underlying skin and kidney disease, are required long-term monitoring after SVR is achieved.

53-58 280
Abstract

Background. Diabetic nephropathy is a condition marked by persistent proteinuria, hypertension, and a progressive loss of renal function. End-stage kidney disease needing continuous renal replacement treatment is now primarily caused by diabetes. According to Kimmelstiel and Wilson, the hallmark lesion of diabetic nephropathy is nodular glomerulosclerosis. Diabetic nephropathy or Nondiabetic renal disease, or the coexistence of both can be seen in renal histopathology and in differentiating between these diagnostic groups can have an impact on patient care and prognosis.

Patients and Methods. Total of 21 cases of Diabetic nephropathy were included in the study. Clinical details and laboratory parameters like diastolic blood pressure, creatinine level, 24 hrs urinary protein level and HbA1C% were recorded in pretested performa in all cases. The biopsy specimens were stained with hematoxylin & eosin and special stains.

Results. Among the total DM cases only 21 patients have done renal biopsy, 11 cases (52.3 %) showed KW lesion (Class III) while 06 cases (28.5 %) showed diffuse diabetic glomerulosclerosis (Class IV). The remaining 04 cases (19 %) showed a mild increase in mesangial matrix and slight thickening of glomerular basement membrane (Class II). When compared with clinical parameters, they were more raised in Nodular diabetic glomerulosclerosis type (Class III) lesion as compared to diffuse diabetic glomerulosclerosis.

Conclusion. Nodular diabetic glomerulosclerosis was the most common lesion in renal biopsy of type II diabetes mellitus patients. This KW lesion is responsible for more severe clinical and biochemical renal abnormality in most patients with type II diabetes mellitus.

59-67 220
Abstract

The aim: to determine the phenotype of kidney damage characteristic of resistant arterial hypertension by MRI, including the volume of renal parenchyma, and its association with biomarkers of renal dysfunction.

Patients and methods. The main group included 35 patients with resistant arterial hypertension (RAH), average age 57.6±8.4 years. The comparison group consisted of 20 men and women without cardiovascular pathology, comparable in gender and age. To determine the qualitative and quantitative changes in the kidneys, MRI was performed (1.5 Tesla, Titan vantage, Toshiba). Kidney volumes (TKV, TCV) were calculated using the ellipsoid formula. Kidney volumes indexed for height, BMI and body surface area were calculated. Renal dysfunction was assessed by the level of serum creatinine and cystatin C, as well as by the value of eGFR (CKD-EPI).

Results. The MR phenotype of kidney changes in resistant hypertension is described – renal cortex surface roughness, renal cortex thinning, decreased kidney sizes, and rounded kidney shape. The relationship of the renal parenchyma volume indexed for height with the level of cystatin C (r=-0.36), creatinine (r=-0.48) and eGFR (r=0.49) was revealed.

Conclusion. The hypertensive renal MRI-phenotype includes a decreased in kidney size, thinning of the renal cortex, renal cortex surface roughness and rounded shape of the kidneys. The total volume of the renal cortex indexed for height has a close relationship with serum biomarkers of renal dysfunction, and is recommended for use as a non-invasive marker reflecting the state of the kidneys in resistant arterial hypertension.

68-75 344
Abstract

Background. Vascular calcification underlies cardiovascular complications, which remain the leading cause of high mortality in chronic kidney disease (CKD). Uremic toxins, including the advanced glycation end products, play a significant role in the formation of this process.

The Aim of the study is to clarify the role of the advanced glycation end products (AGEs) and inflammationproducts in the processes of vascular calcification at different stages of CKD.

Patients and Methods. 105 patients aged 18 to 66 years at different stages of CKD C1-C5D were examined, 75 of which were caused by diabetic nephropathy (DN), 30 by other nosological forms. Serum concentrations of AGEs, IL6, TNF-α, troponin I, parathyroid hormone (PTH) were determined by enzyme immunoassay (ELISA). To study the AGEs concentration, the serum was separated by centrifugation (in Eppendorf tubes). The samples were stored at – 70 °C. The left ventricular myocardial mass index (LVMI) was determined. Left ventricular hypertrophy (LVH) was diagnosed with LVH>115 g/m2 for men and >95 g/m2 for women. The peak systolic velocity of blood flow in the aortic arch (Vps) was studied by duplex scanning using the Doppler effect.

Results. A significant increase in serum phosphorus concentration (p < 0.05) and PTH (p< 0.01) was revealed as the glomerular filtration rate decreased. An increase in the concentration of AGEs, IL6 and TNF-α was found at all stages of CKD, most pronounced at the later stages – C4-C5D ((p< 0.01, p< 0.05, p<0.05, respectively). Pronounced changes in LVMI and Vps were associated with high levels of AGEs, IL6 and TNF-α. CONCLUSION. An increase in the level of glycation end products and inflammatory factors directly and reliably correlated with the severity of uremia and the severity of morphofunctional changes in the heart and aorta, which confirms their significant role in the development of cardiovascular complications in CKD. Keywords: advanced glycation end products, inflammation, vascular calcification, chronic kidney disease>˂0.05, respectively). Pronounced changes in LVMI and Vps were associated with high levels of AGEs, IL6 and TNF-α.

Conclusion. An increase in the level of glycation end products and inflammatory factors directly and reliably correlated with the severity of uremia and the severity of morphofunctional changes in the heart and aorta, which confirms their significant role in the development of cardiovascular complications in CKD.

76-85 523
Abstract

The aim: to study the relationship of beta-2-microglobulin (beta-2 MG) with clinical and laboratory manifestations of chronic kidney disease (CKD).

Patients and Methods. The results of a comprehensive examination of 284 people (118 males and 166 females) aged 18 to 86 years with various types of socially significant diseases were studied. All patients underwent thorough collection of clinical and anamnestic data, laboratory monitoring with the determination of the level of systolic and diastolic blood pressure (BP), body mass index, red blood, beta-2-microglobulin (B2M), lipid profile and proteinuria. Kidney function was assessed according to the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula using serum creatinine. The main group included 113 patients (55 men and 58 women, mean age 50.9±15.8 years), diagnosed with chronic kidney disease (CKD). The control group consisted of 171 people (63 men and 108 women) with various forms of socially significant diseases, but without signs of CKD. Statistical analysis was carried out using the programs Statistica 10.0 (StatSoft Inc., USA) and Microsoft Office Excel 2010 (Microsoft Corp., USA).

Results. In the subgroup of patients with CKD, signs of renal failure were observed in 46 people in 40.7 % of cases. As CKD progressed, the signs of impaired metabolism of B2M were more severe: its serum level was 8.646 (7.892; 12.231) mg/l at C4 and 18.444 (11.225; 23.717) mg/l at C5 stages of CKD, and urinary excretion was 2.502 (0.305; 6.313) mg/l at C4 and 2.614 (1.535; 25.812) mg/l at C5 stages of CKD. Regardless of renal dysfunction, the median serum B2M level was clinically significantly higher in females (p>0.05). Single-factor one-way correlation analysis showed statistically highly significant relationship was between serum B2M and creatinine levels both in the subgroup of patients with CKD (r = 0.905; p = 0.001) and in the total sample (r = 0.749; p = 0.001). There was a strong negative relationship between serum B2M levels and estimated glomerular filtration rate (GFR) (r = -0.717; p = 0.001). In individuals without CKD, an increase in serum creatinine was closely associated with an increase in urinary excretion of B2M (r=0.252; p=0.005). Simultaneously, in this category of patients, there was a close correlation between estimated GFR with serum B2M level (r= -0.433; p=0.002) and its urinary excretion (r= -0.247; p=0.005). A direct relationship between an increase in serum B2M and an increase in diastolic blood pressure (r=0.274; p=0.034) among CKD patients was established. In the total sample, a direct relationship between the value of systolic BP and serum B2M level (r= 0.223; p=0.01) was registered, as well as between diastolic BP (r= 0.268; p=0.01) and urinary excretion of B2M.

Conclusion. As a result of the study, metabolism of B2M and its relationship with the clinical and laboratory manifestations of CKD were evaluated. The data obtained show high prognostic potential of changes in metabolism of B2M in the population of patients with various forms of socially significant diseases, as well as CKD, which allows to identify among them groups of patients with high and/or very high renal and cardiovascular risk, in order to take timely targeted therapy.

ORIGINAL ARTICLES. EXPERIMENTAL INVESTIGATION

86-91 356
Abstract

Background. Rheumatoid arthritis is a disease that is accompanied by impaired kidney function in most patients, which attracts the attention of researchers to this problem. Both in the joints and in the kidneys, hyaluronic acid plays an important role, the degree of polymerization of which depends on the functioning of these organs. The degradation of hyaluronic acid by hyaluronidases may be a factor involved in the development of the inflammatory process in rheumatoid arthritis as well as in the realization of osmoregulatory functions of the body. In this regard, the purpose of this work was to find out whether the development of this pathology can affect on the hyaluronidase activity in the kidneys. THE AIM: to clarify is in the experiment formation of inflammatory changes in the joints accompanied by a change in the cortico-papillary ratio of hyaluronidase activity in the kidneys.

Materials and Methods. A model of rheumatoid arthritis was created in Wistar rats by a single administration of a complete Freund adjuvant. After 7 weeks after injection, the degree of pathological changes in the joints was assessed by radiographic method and the hyaluronidase activity in various kidney zones was determined using zymography.

Results. It was revealed that in the cortex and papillary zone of the kidneys, hyaluronidase activity was characteristic of proteins with a molecular weight of 63 and 73 kDa. It has been shown that the development of the inflammatory process is accompanied by a change in the corticopapillary ratio of hyaluronidase activity in the kidneys. In the papillary zone, a decrease in hyaluronidase activity was observed, on average, by 1.6 times, while in the renal cortex, hyaluronidase activity increased by 1.5 times.

Conclusion. Such a redistribution of hyaluronidase activity in the cortical and papillary zones of the kidneys in rheumatoid arthritis can lead to a decrease in the effectiveness of the mechanism of osmotic concentration of urine and impaired kidney function. 

PROGRAM ON CONTINUOUS POSTGRADUATE EDUCATION ON NEPHROLOGY

92-96 209
Abstract

The structure of the pathology of the kidneys of a traumatic nature was studied, revealed in the injured living persons sent by the investigation and the court for forensic medical examination. The studied material was data on 49 cases of traumatic kidney injuries among 4,200 forensic medical examinations performed in 2021 in the department of examination of victims, accused and other persons of the St. Petersburg Bureau of Forensic Medical Examination. It was found that kidney injury is a rare (1.2 %) pathology in the forensic medical examination of living persons. Such injuries, as a rule, are formed with a massive combined injury to the body (car, falling from a height). In cases of local injuries of the abdomen, lower back or pelvis (even with fractures of the pelvic bones), kidney damage is extremely rare. The diagnosis of "kidney injury" made in the clinic is not objectively confirmed in all cases of forensic medical examinations. This is due to the lack of a full description in medical documents of objective diagnostic signs of renal pathology.

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