THE ROLE OF TNF-α AND COLLAGEN IV IN THE PROGRESSION OF RENAL DYSFUNCTION AND FIBROUS FORMATION IN PATIENTS WITH CHRONIC HEART FAILURE

Abstract

One of the mechanisms for the development of fibrosis in the kidneys and glomerulosclerosis in patients with chronic heart failure (CHF) is the activation of pro-inflammatory cytokines, which lead to the synthesis of profibrotic markers and the progression of fibrosis and sclerosis. It has been established that TNF-α is capable of stimulating left ventricular hypertrophy, increasing the content of CRP, stimulating coagulation, worsening the lipid spectrum of the blood, and most importantly, activating fibroblasts and triggering collagen synthesis, which leads to fibrosis both in cardiomyocytes and glomerulosclerosis in the kidneys[1].

Type IV collagen constitutes the main structure of the basement membrane and mesangial matrix of the glomerular kidney, is a high molecular weight fibrillar protein with a molecular weight of approximately 540 kDa, consists of α3, α4 and α5 chains and, as a rule, is not filtered through the glomerular basement membrane. The determination of collagen IV in urine sediment is of great scientific and practical importance for the purpose of early detection of sclerotic processes in the glomerular membrane of the kidneys in patients with CHF[2,4]. In order to examine what the state of the cytokine-inflammatory state and the structure of basement membrane are in patients with FC II-III CHF, the content of the pro-inflammatory cytokine TNF-α and type IV collagen of the studied patients was examined.

Aim. Evaluation of TNF-α and collagen IV in the progression of renal dysfunction and fibrous formation in patients with chronic heart failure.

Materials and methods The study included 67 patients with functional classes (FC) II-III of CHF of ischemic origin with reduced and mid-range ejection fraction (EF) according to the New York Heart Association (NYHA) classification. The average age was 64.3+ 0.62, 40 (60%) patients were men, 27 (40%) women. Patients were divided into 3 groups according to their treatment tactics. Group I - 22 patients in complex treatment received additional sacubitril + valsartan 50 mg / day, group II - 22 patients in complex treatment with empagliflozin 10 mg / day, group III - 23 patients - a combination of sacubitril + valsartan and empagliflozin.

Results As can be seen from the data of our study, TNF-α indicators were significantly reduced with a greater effect in the third subgroup of patients with CHF, where a combination of sacubitril/valsartan and empagliflozin was used. In this connection, we can assume that empagliflazin also has an anti-inflammatory effect and, in combination with sacubitril/valsartan, has a pronounced anti-inflammatory, and subsequently anti-fibrotic effect. In the group of patients who received sacubitril-valsartan in combination, TNF-α levels decreased significantly from 13.2 to 8.4 pg/ml (p˂0.05), in the group of patients who received empagliflozin in combination, the TNF-α level decreased from 12.6 to 8.2 pg/ml (p˂0.05), in the group where the combination of sacubitril-valsartan and empagliflozin was used, the TNF-α indicator significantly decreased from 12.8 to 5.5 pg/ml (p˂0. 01). The level of collagen IV in urine is highly negatively correlated with GFR (r=-0.742; р˂0.001).

Conclusion The use of a combination of empagliflozin and sakabutril/valsartan in complex treatment has a beneficial effect on renal filtration, and it can be assumed that the drugs, by stabilizing pathological processes, can slow down the processes of fibrosis formation and glomerulosclerosis in the basement membrane and renal tubules.