Vol 92, No 6 (2020)

The global burden of chronic kidney disease (CKD) is rapidly increasing with a projection of becoming the 5th most common cause of years of life lost globally by 2040. Aggravatingly, CKD is a major cause of catastrophic health expenditure. The costs of dialysis and transplantation consume up to 3% of the annual healthcare budget in high-income countries. Crucially, however, the onset and progression of CKD is often preventable. In 2020, the World Kidney Day campaign highlights the importance of preventive interventions – be it primary, secondary or tertiary. This complementing article focuses on outlining and analyzing measures that can beimplemented in every country to promote and advance CKD prevention. Primary prevention of kidney disease should focus on the modification of risk factors and addressing structural abnormalities of the kidney and urinary tracts, as well as exposure to environmental risk factors and nephrotoxins. In persons with pre-existing kidney disease, secondary prevention, including blood pressure optimization and glycemic control, should be the main goal of education and clinical interventions. In patients with advanced CKD, management of co-morbidities such as uremia and cardiovascular disease is a highly recommended preventative intervention to avoid or delay dialysis or kidney transplantation. Political efforts are needed to proliferate the preventive approach. While national policies and strategies for non-communicable diseases might be present in a country, specific policies directed toward education and awareness about CKD screening, management and treatment are often lacking. Hence, there is an urgent need to increase the awareness of the importance of preventive measures throughout populations, professionals and policy makers.

We present a case with a rare variant of glomerulonephritis, IgM nephropathy, which occurs mainly with nephrotic syndrome. The clinical features of this variant of kidney damage are characterized; the pathogenetic and the transformation of this form of nephritis into focal segmental glomerulosclerosis are discussed. The development of severe nephrotic syndrome at the beginning of the disease, the formation of secondary steroid resistance have confirmed this hypothesis and have justified the treatment with cyclosporin A aimed at the recovery of the function of the podocyte with remission of nephritis.

A clinical observation is presented of a patient with pulmonary sarcoidosis, who was diagnosed with kidney damage after three years with the development of chronic renal failure and the need for replacement therapy. A histological examination of the renal biopsy revealed a granulomatous process in the interstitial tissue, which was regarded as an extrapulmonary manifestation of sarcoidosis. Pulse therapy with glucocorticoids was prescribed and an attempt was made to reduce hemodialysis sessions.

Aim. An evaluation of the effectiveness of immunosuppressive therapy (IST) and tonsillectomy (TE) in patients with IgA nephropathy (IgAN).

Materials and methods. A retrospective cohort of the study included cases with biopsy proven primary IgAN (n=367, age 34±12 years, men – 55%). We used demographic and clinical and morphological parameters at the time of biopsy. Median followup period was 26 (10; 61) months. Outcomes were remission (complete or partial) and the progression of IgAN (defined as the start of dialysis or a decrease in glomerular filtration rate ≥50% from baseline). All patients received treatment with renin angiotensin system blockers. Evaluation of the effectiveness of therapy was carried out using propensity score (PS) methods – matching, conventional double robust regression models with PS as independent covariate, and inverse probability weighting. Following patient subgroups were used for comparative analyses: with IST (n=176) and without IST (n=191); with TE (n=63) and without TE (n=304); without IST and without TE (IST-TE-; n=162); with TE and without IST (IST-TE+; n=29); with IST and without TE (IST+TE-; n=142); with IST and with TE (IST+ TE+; n=34).

Results. All PS methods used gave close estimates of the comparative effectiveness of treatment in different subgroups: 1) patients on monotherapy with corticosteroids (CS) and combination of CS with other immunosuppressants did not have significant differences in probabilities of IgAN progression (hazard ratio 0.919; 95% CI 0.333–2.950) and remission (odds ratio 0.919; 95% CI 0.379–2.344) and were further combined into a group of IST; 2) IST was significantly associated with the lower risk of disease progression and increased odds ratio for remission; 3) the positive effects of IST were limited to cases with proteinuria >2 g/24 h; 4) the likelihood of IgAN remission and progression did not differ significantly between TE+ and TE-, IST-TE+ and IST-TE- groups. There were no cases of disease progression in the IST+TE+ group. The cumulative renal survival was higher in the IST+TE+ group compared to IST+ TE- group (p=0.010), while the probability of remission did not differ.

Conclusion. IST was associated with a lower risk of IgAN progression and increased probability of remission, while these effects of IST were limited to patients with proteinuria >2 g/24 h. TE in combination with IST is associated with an additional reduction in the risk of disease progression.

Aim. Determine whether bone mineral density (BMD) assessed by dual-energy x-ray absorptiometry can be used as predictor of increased risk of death in hemodialysis patients.

Materials and methods. A prospective study was performed of 516 patients with chronic kidney disease treated with hemodialysis (men – 265, women – 251, mean age 44.8±11.4 years) who were observed for 5.7±3.2 years.

Before inclusion in the study, in all patients was analyzed bone mineral density using dual-energy X-ray absorptiometry in three standard departments: lumbar vertebrae, proximal femur and distal forearm. The probability analysis of the outcome was carried out using the Kaplan–Meier method and Cox.

Results. During follow-up period 111 (21.5%) patients died, 50.5% from cardiovascular events. Survival analysis by Kaplan–Meier method allowed to prove the increased risk of death from cardiovascular pathology in hemodailysis patients with low bone mineral density of all evaluated areas. Step-by-step multivariate Cox regression analysis showed that the T score of the femur, showing the difference of BMD of the patient with normal value of BMD for young adult, had the greatest prognostic significance.

Conclusion. Reduced bone mineral density in patients receiving hemodialysis is associated with an increased risk of death from cardiovascular disease. Dual energy x-ray absorptiometry can be used for assessment of this risk.

Cardiovascular calcification (CVC) makes a significant contribution to the manifestation of cardiovascular complications in patients with chronic kidney disease. Early CVC markers are currently being actively studied to optimize cardio-renoprotective strategies. We performed a prospective comparative analysis of the following factors: FGF-23, a-Klotho, sclecrostin, phosphate, parathyroid hormone, the estimated glomerular filtration rate (eGFR), central systolic pressure as an independent determinant of CVC.

Materials and methods. The study included 131 patients with chronic kidney disease 2–5D st. Serum levels of FGF-23, Klotho, and sclerostin were evaluated using the ELISA method. Vascular augmentation (stiffness) indices, central arterial pressure (using the SphygmoCor device), calcification of heart valves and the degree of aortic calcification (aortic radiography) were also investigated. The observation period was 2 years.

Results. According to the Spearman correlation analysis, the percent of calcification increase and the change in Klotho level are most related. According to ROC analysis, a decrease in serum levels of Klotho by 50 units or more is a significant predictor of an increase in aortic calcification of 50% or more with a sensitivity of 86% and a specificity of 77%. Using logistic regression analysis, it was found that a serum Klotho level <632 pg/L predicts an eGFR below a median level of 48 ml/min/1.73 m² with a sensitivity of 85.5% and a specificity of 78.5%. Wherein OR 17.477 (CI 95% 8.046–37.962; p<0.001).

Conclusion. The factor most associated with CVC is Klotho. Decreased serum level of Klotho is a predictor of aortic calcification. In addition, the initial serum level of Klotho is a predictor of eGFR after 2 years.

Chronic glomerulonephritis (CGN) is a disease with a steadily progressing course, which is based on inflammation with the activation of immune cells. The severity of the inflammatory reaction in the kidney tissue is determined by the balance of locally pro-inflammatory factors and protective mechanisms, which include anti-inflammatory cytokines and T-regulatory lymphocytes (Treg). The study of processes that can modulate the severity of inflammation in the kidney is of particular interest for understanding the basic patterns of CGN progression.

Aim. To determine the clinical significance of the Th17, Th1, and Treg cytokines in urine to assess the activity and progression of chronic glomerulonephritis with nephrotic syndrome (NS).

Materials and methods. The study included 98 patients with CGN – 37 women and 61 men. Patients were divided into two groups according to the degree of CGN activity. Group I consisted of 51 patients with NS. In 21 subjects, a decrease in GFR<60 ml/min was revealed. Group II included 47 patients with proteinuria from 1 to 3 g/day without NS. GFR<60 ml/min/1.73 m² was observed in 26 patients. A kidney biopsy was performed in 65 patients and the hystological diagnosis was verified: 20 had mesangioproliferative GN, 16 had membranous nephropathy, 18 had focal segmental glomerulosclerosis, and 11 had membranoproliferative GN. The control group consisted of 15 healthy people. The levels of IL-6, IL-10, IL-17, tumor necrosis factor a (TNF-a) in the urine were determined using enzyme-linked immunosorbent assay. The number of FoxP3-positive cells in the inflammatory interstitial infiltrate of the cortical layer was determined in 39 patients (in a biopsy sample in a 1.5 mm² area).

Results. In group of patients with CGN, there was an increase in the levels of Th17, Th1, and Treg cytokines in urine – TNF-a and IL-10 compared with healthy individuals. An increase in the levels of IL-6 in the urine of patients with high clinical activity of CGN (with NS and renal dysfunction) was more pronounced than in patients with NS and normal renal function. There was a decrease in the number of Treg cells in the interstitium of the kidney and a decrease in the production of anti-inflammatory IL-10 in CGN patients with NS, compared with patients without NS. The most pronounced changes in the cytokine profile were observed in patients with FSGS with an increase in pro-inflammatory cytokines and a decrease in Treg in the kidney tissue/anti-inflammatory IL-10 in the urine.

Conclusion. An imbalance of cytokines characterized by an increased levels of pro-inflammatory IL-17, IL-6, TNF-a, and a reduced levels of anti-inflammatory IL-10 and T-regulatory cells in the kidney tissue is noted in patients with NS, especially with FSGS. Imbalance of cytokines reflects the high activity of CGN and the risk of the progression of the disease.

Aim. To study the effect of weight loss in the short term after bariatric surgery (BO) on metabolic parameters and glomerular filtration rate (GFR) in patients with morbid obesity.

Materials and methods. We studied 40 adult (over 18 years) patients with morbid obesity who underwent bariatric surgery. Metabolic indices and calculated GFR according to the CKD-EPI formula in patients before and after bariatric surgery were compared.

Results. In the whole group of operated patients, the average body mass index (BMI) after surgery decreased from 45.8 to 30.5 kg/m². In 11 (92%) patients with impaired carbohydrate metabolism, remission of diabetes mellitus was achieved and sugar-lowering drugs were canceled. In patients with baseline GFR≥90 ml/min/1.73 m² after surgery, there is a tendency towards a decrease in GFR, probably due to a decrease in hyperfiltration. In patients with baseline GFR<90 ml/min/1.73 m² after surgery, a statistically significant increase in the level of GFR was noted. The greater metabolic efficacy of combined operations (mini-gastric bypass, biliopancreatic diversion) in relation to the correction of carbohydrate and fat metabolism was revealed.

Conclusion. Obesity is a modifiable risk factor for decreased kidney function and the progression of chronic kidney disease. Bariatric surgery is an effective treatment for morbid obesity. The study proved the positive effect of weight loss after BO on renal function, including by improving the course of diseases associated with obesity.

Aim. To evaluate a 12-week course of combined alloturinol-lowering therapy with a prophylactic anti-inflammatory dose of movalis for the frequency of exacerbations and the quality of life of patients with gout.

Materials and methods. Allopurinol was administered orally, 1 time per day. Every 3 weeks, the dosage of the drug was increased by 50 mg to 300 mg per day under the control of the level of serum uric acid (sUA). The total daily dose of the drug movalis, used in the form of different dosage forms, was 7.5–15 mg. The clinical effectiveness of the treatment was evaluated after 3, 6, 9 and 12 weeks according to physical examination, the dynamics of joint pain at rest, during movement and palpation, according to the visual analogue scale (VAS) in millimeters, Likert scale, EuroQol-5D-5L questionnaire, care for oneself, habitual daily activities, the presence of anxiety and depression, assessment of satisfaction with treatment (on a scale of 1 to 5, where 1 is the complete absence of improvement or worsening, and 5 is a very good result); took into account the period of remission, as well as the time before the onset of relapse of gouty arthritis. An adverse event (AE) was recorded.

Results and discussion. On the background of treatment with movalis 7.5 mg per day more than two-thirds of patients showed no worsening of the articular syndrome with an increase in the dose of allopurinol to 300 mg per day. By the 12th week of observation, a significant difference was found between the severity of gouty arthritis characteristics in the direction of improving mobility, self-care, normal daily activities, reducing soreness, reducing anxiety and depression (p<0.05). In addition, the ESR and sUA levels were significantly different initially and at the final observation point (p<0.05), which indicates a positive effect on the inflammatory process. A 3-month course of combination therapy was not accompanied by significant increases in blood pressure, changes in creatinine clearance in blood serum. There were no adverse events from the gastrointestinal tract. 90.9% of patients rated the treatment result as very good. AE in the form of a skin allergic rash was observed in one patient; it did not require interruption of treatment and completely stopped without consequences after completion of the course.

Conclusion. 12 – a week-long combined therapy of the allopurinol-reducing drug with the anti-inflammatory dose movalis prevents the exacerbation of the articular syndrome and improves the quality of life of patients with gout.

Aim. Conducting a pilot study to assess the effect of thermal heliox on the state of the respiratory tract by studying of the exhaled breath condensate protein composition before the thermal heliox procedure, immediately after and after three hours of relaxation

Materials and methods. A comparative study of the exhaled breath condensates (EBC) protein composition of five non-smoking healthy donors was carried out. The EBC was taken before the respiratory procedure, immediately after a 20-minute inhalation by mixture of He/O₂ gases (70/30) heated to 70°C and 3 hours later. The protein composition was determined by chromatography-mass spectrometric analysis after selective tryptic hydrolysis. The results were processed using the Mascot program and the UniProt database.

Results. After the heliox procedure, the volume of the collected condensate (1–1.5 ml) decreases by an average of 32% and is practically restored after three hours of relaxation. Most proteins were consistent for all samples, regardless of the thermal heliox procedure. These are keratins, several proteins of the immune system (immunoglobulins, compliment proteins), tubulin. In samples after thermal heliox, the appearance of small amounts of additional proteins is observed. These are proteins of muscle metabolism (actin and calmodulin), fibrinogen, traces of hemoglobin, apolipoprotein, type B creatine kinase. After three hours of relaxation, tubulin disappears in the EBC.

Conclusion. Most exhaled proteins are the same before, after the procedure, and for three hours of relaxation. The results obtained demonstrate the relative safety of the use of high temperature heliox as a therapeutic agent.