DYNAMICS OF RENAL FIBROSIS MARKERS IN PATIENTS WITH CHRONIC HEART FAILURE

Determination of collagen IV in urine sediment and pro-inflammatory cytokine tumor necrosis factor‐alpha (TNF-α) in the blood for the purpose of early detection of sclerotic processes in the glomerular membrane of the kidneys in patients with chronic heart failure (CHF). 

The experiment included 225 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, 135 (60%) patients were men, 90 (40%) women. Patients were divided into 3 groups according to their treatment tactics. Group I - 72 patients in complex treatment received additional sacubitril + valsartan 50 mg / day, group II - 77 patients in complex treatment with empagliflozin 10 mg / day, group III - 76 patients - a combination of sacubitril + valsartan and empagliflozin. 

Microalbuminuria was detected in 36.4% of the patients we examined, normoalbuminuria in 53.1%, and macroalbuminuria in 10.1% of patients. Our examination showed that all 100% of patients had collagen IV excretion to varying degrees. When determining the urinary excretion of type IV collagen, some correlations were also identified. Thus, its content in urine is highly negatively correlated with glomerular filtration rate (GFR)  (r = -0.742; P˂0.001) and significantly positively correlates with albuminuria (r = -0.683; P˂0.001). In the group of patients receiving sacubitril-valsartan in combination, TNF-α levels significantly decreased over 3 months from 13.22 to 7.8 pg/ml; in the group of patients receiving empagliflozin in combination, TNF-α levels significantly decreased from 12.6 to 7.2 pg/ml, in the group where both sacubitril-valsartan and empagliflozin were used, the TNF-α indicator significantly decreased from 12.8 to 5.6 pg/ml. Evetually, pathogenetic therapy of CHF leads to stabilization of proinflammatory cytokines. 

The detection of collagen IV in patients with CHF with class II-III in the urine suggests the important role of this marker as an independent predictive factor for the development of glomerulosclerosis. The use of a combination of drugs empagliflozin and sacubitril-valsartan in complex treatment has a beneficial effect on renal filtration by stabilizing pathological processes which can lead to slow down the processes of fibrosis formation and glomerulosclerosis in the basement membrane and renal tubules. TNF-α indicators were significantly reduced with a greater effect in the third group 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.