ISSN 2415-3060 (print), ISSN 2522-4972 (online)
  • 25 of 50
УЖМБС 2021, 6(3): 192–198
Clinical Medicine

Anti-Inflammatory Effect of Nephroprotective Therapy in Patients with Diabetic Nephropathy

Topchii I. I., Savicheva K. O., Semenovykh P. S., Galchinska V. Yu.

Diabetic kidney disease develops in approximately 40% of patients who are diabetic and is the leading cause of chronic kidney disease worldwide. The majority of patients actually die from cardiovascular diseases and infections before needing kidney replacement therapy. The progression of fibrotic processes in the diabetic kidneys occurs with the participation of universal mediators of inflammation. Given the clinical and social significance of diabetic kidney damage, the determination of interleukin-1β and interleukin-6 in blood serum may expand the understanding of this problem, as well as help in the development of individualized therapeutic approaches. The purpose of the study is to investigate interleukin-1β and interleukin-6 levels in the serum of patients with type 2 diabetes mellitus, depending on kidney functional state in the dynamics of therapy and with additional prescription of dapagliflozin. Materials and methods. 72 patients with type 2 diabetes were examined. The control group consisted of 20 healthy individuals. The patients were divided into the following groups: group I – type 2 diabetic patients with normal glomerular filtration rate and without albuminuria (n = 25); group II – patients with type 2 diabetes with normal glomerular filtration rate and albuminuria (n = 23); group III – patients with type 2 diabetes with decreased glomerular filtration rate and albuminuria (n = 24). The complex pathogenetic therapy of patients of group 1 included renin-angiotensin-aldosterone system blockers, metformin and hypolipidemic agents. Patients of group 2 were additionally prescribed dapagliflozin. The control was carried out after 6 months. Results and discussion. According to the results of the study, the development of diabetic nephropathy in patients with type 2 diabetes is accompanied by a significant increase in the level of interleukin-1β and interleukin-6 in the blood plasma compared with the control and in patients with diabetes without signs of nephropathy. Nephroprotective therapy contributed to a significant decrease of interleukin-1β and interleukin-6 levels in the blood serum in all groups of patients. The highest response to treatment was observed in patients with diabetic nephropathy and albuminuria. Most significant decrease of albuminuria, normalization of blood pressure and lipid spectrum improvement were observed in patients with the initial stages of the disease. Additional using of dapagliflozin leads to a more significant decrease in the content of proinflammatory cytokines in the blood serum of patients with type 2 diabetes mellitus with diabetic nephropathy. Conclusion. The results of the study indicate the advisability of using interleukin-1β and interleukin-6 as a diagnostic marker of cardiac disorders, assessment of prognosis, and improvement of the cardionephroprotective strategy in diabetic patients. The therapeutic potential of dapagliflozin in the treatment of diabetic nephropathy and the prevention of cardiovascular events in patients with diabetes is of great scientific interest and requires further research

Keywords: diabetes mellitus, diabetic nephropathy, interleukin-1ß, interleukin-6, proinflammatory cytokines, dapagliflozin

Full text: PDF (Ukr) 292K

  1. Fox CS, Matsushita K, Woodward M, Bilo HJ, Chalmers J, Heerspink HJ,et al. Chronic Kidney Disease Prognosis Consortium. Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis. Lancet. 2012; 380: 1662–73.
  2. Einarson TR, Acs A, Ludwig C, Panton UH. Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007–2017. Cardiovascular Diabetology. 2018; 17(1): 83. PMid: 29884191. PMCid: PMC5994068.
  3. Ketlynskyy SA, Symbyrtsev AS. Tsitokiny [Cytokines]. SPb: Foliant; 2008. 552 s. [Russian]
  4. Kovalchuk LV, Ygnatevoy GA, Gankovskoy LV. Immunologiya [Immunology]. Ucheb posobye. M:GEOTAR-Medya; 2014. 174 s. [Russian]
  5. Alaveras AE, Thomas SM, Sagriotis A, Viberti GC. Promoters of progression of diabetic nephropathy: The relative roles of blood glucose and blood pressure control. Nephrol Dial Transplant. 1997; 12(2): 71-4.
  6. Viberti G, Wheeldon NM. Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus: A blood pressure independent effect. Circulation. 2002; 106: 672-8. PMid: 12163426.
  7. Karalliedde J, Gnudi L. ACCORD and ADVANCE: A tale of two studies on the merits of glycaemic control in type 2 diabetic patients. Nephrol Dial Transplant. 2008; 23: 1796-8. PMid: 18403430.
  8. Chaturvedi N. Randomised placebocontrolled trial of lisinopril in normotensive patients with insulindependent diabetes and normoalbuminuria or microalbuminuri. Lancet. 1997; 349: 1787-92.
  9. Zaccardi F, Webb DR, Htike ZZ, Youssef D, Khunti K, Davies MJ. Efficacy and safety of sodium-glucose cotransporter 2 inhibitors in type 2 diabetes mellitus: Systematic review and network meta-analysis. Diabetes Obes Metab. 2016; 18(8): 783-94. PMid: 27059700.
  10. Ma Q, Steiger S, Anders HJ. Sodium glucose transporter-2 inhibition has no renoprotective effects on non-diabetic chronic kidney disease. Physiol Rep. 2017; 5(7): PMid: 28364032. PMCid: PMC5392518.
  11. Zhang Y, Thai K, Kepecs DM, Gilbert RE. Sodium-Glucose Linked Cotransporter-2 Inhibition Does Not Attenuate Disease Progression in the Rat Remnant Kidney Model of Chronic Kidney Disease. PLoS One. 2016; 11(1). PMid: 26741142. PMCid: PMC4711803.
  12. Demyanov AV, Kotov AYu, Symbyrtsev AS. Dyagnostycheskaya tsennost yssledovanyya urovney tsytokynov v klynycheskoy praktyke [Diagnostic value of research of cytokine levels in clinical practice]. Vrachu obshchey praktyky. 2003; 2(3): 20-35. [Russian]
  13. Leng W, Ouyang X, Lei X. The SGLT-2 Inhibitor Dapagliflozin Has a Therapeutic Effect on Atherosclerosis in Diabetic ApoE -/- Mice. Mediators Inflamm. 2016; 2016: 6305735. PMid: 28104929. PMCid: PMC5220517.