Correction of renal dysfunction in patients with chronic heart failure and reduced left ventricular ejection fraction

Main Article Content

G. Ye. Dudnik
A. S. Solonovych
A. V. Lyashenko

Abstract

The aim – to study the possibilities of correction of renal function parameters in patients with CHF and reduced LV EF on the background of treatment with a fixed combination of meldonium with gamma buterobetaine.
Material and methods. A total of 24 patients with stable CHF and reduced left ventricular ejection fraction
(EF < 40 %), II–IV NYHA classes were examined. Among them, 17 people had CHD, 5 people – dilated cardiomyopathy. All patients underwent general clinical examination, determination of levels of creatinine, blood urea nitrogen, uric acid, microalbuminuria, GFR using the formula CKD-EPI. Ultrasound diagnosis of the vasodilating function of the brachial artery endothelium was performed using a test with reactive hyperemia. Against the background of standard treatment, patients received a fixed combination of meldonium with gamma-butyrobetaine (GBB) at a dose of 2 tablets 3 times a day (every 8 h) for 4 weeks.
Results. Against the background of a 4-week intake of a combination of 360 mg of meldonium and 120 mg of GBB three times a day, patients had a statistically significant improvement in creatinine and GFR. Uric acid levels in the blood plasma of patients did not significantly change. There was no significant effect on the level of heart rate and systolic blood pressure. The levels of daily MAU significantly decreased, as well as blood urea nitrogen. There was a statistically significant improvement in vasodilator function of the endothelium.
Conclusions. In stable patients with CHF and reduced LV EF, addition of meldonium 360 mg with GBB 120 mg to the standard pharmacotherapy is accompanied by improvement of renal function shown by significant reduction of blood creatinine, increase of GFR, decrease of blood urea nitrogen and daily MAU. This treatment improves vasodilator endothelial function.

Article Details

Keywords:

Chronic heart failure, correction of renal function, meldonium, endothelial function.

References

Voronkov LH, Shkurat IA, Besaha YeM. Endothelium-dependent vasodilatation and its prognostic value in patients with chronic heart failure and left ventricular systolic dysfunction. Ukrainskyi kardiolohichnyi zhurnal [Ukraine J of Card.] 2005;6:23–30(in Ukr.)

Voronkov LH, Dudnyk HIe. Renal dysfunction in chronic heart failure. Sertseva nedostatnist [Heart failure]. 2017;2:25–29 (in Ukr.)

Voronkov LH, Mazur ID, Ilnytska MR, Vaida LS. Correction of endothelium dysfunction as a present- day direction in preventive vascular

Medicine. Krovoobih ta hemostaz [Blood circulation and hemostasis].2015;2:5–6. (in Ukr.).

Voronkov LH, Shkurat IA, Besaha YeM. Treatment of endothelial dysfunction as a key link in a cardiovascular and cerebrovascular pharmacotherapy: the urgency of new approaches. Ukr.kard.zhurnal [Ukraine J of Card.] 2006;1:48–5(in Ukr.).

Komarova OV, Smyrnov YE, Kucherenko AH. Endotelian dysfuction in children with chronic kidney dssease. Rossyiskyi pedyatrycheskyi zhurnal. [Russian Pediatric J]. 2012;5:23–26 (in Russ.).

Kudriakova AS. Correction of endothelial dysfunction in patients with chronic kidney disease: avtoref. 2013:3. (in Russ.).

Nefrolohyia: rukovodstvo dlia vrachei / pod red. YE Tareevoi. M.: Medytsyna, 2000. (in Russ.).

Saiakste N.Y, Dzyntare M. Ya., Kalvynsh YIa. The role of NO induction in the mechanism of action of the Kapikor cytoprotector - the original regulator of endothelial function. Medychni perspektyvy [Medical perspectives], 2012. XVII(2):1–7. (in Russ.).

Sirenko YuM, Radchenko HD, Hranich VM. Renal function in patients with arterial hypertension: methods evaluation and treatment strategy. Ukrainskyi kardiolohichnyi zhurnal [Ukraine J of Card]. 2005;4:9–17. (in Ukr.).

Sukhovershyn RA. Metabolyzm arhynyna y eho metylyrovannыkh analohov v fyzyolohycheskykh uslovyiakh y pry ostrom povrezhdenyy pochek u krus: avtoref. 2012;3–4(in Russ.)

Shabalyn AV, Rahyno YuY, Liubymtseva SA. Effect of cytoprotection on oxidative processes and endothelial function in elderly patients with ischemic heart disease. Ratsyonalnaia farmakoterapyia [Rational pharmacotherapy]. 2006;3:32–36 (in Ukr.)

Annuk M, Zilmer M, Lind L, Linde T, Fellström B. Oxidative stress and endothelial function in chronic renal failure. J. Am. Soc. Nephrol. 2001;12: 2747–2750.

Celermajer DS, Sorensen RE, Bull C, Robinson J, Deanfield JE. Endothelium-dependent dilatation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. J Am Coll Cardiol. 1994;24:1468–74.

Cleland JG, Chiswell K, Teerlink JR, Stevens S, Fiusant M, Giverts, MM, Davison BA, Mansoor GA, Ponikovski P, Voors AA, Cotter G, Metra M, Massie BM, O'Connor CM. Predictors of postdischange outcomes from information acquired shortly after admission for acute heart failure: a report from the Placebo-Controlled Randomaized Study of nhe selective A1 Adenosine Receptor Antagonist Rolofilline for patients Hospitalized With Acute Decompensated Yeart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function (PROTECT) Study. Circ Heart Fai. 2014;7:76-87. doi: 10.1016/j.ijcard.2018.01.067

Damman K., Testani J.M. The kidney in heart failure: an update. Europ. Heart J. 2015;6:1437–1444.

Damman K, Valente MA, A Voors AA, O'Connor CM, van Veldhuisen DJ, Hillege HL. Renal impairment, worsening renal function, and outcome in patients with heart failure: an updated meta-analysis. Eur.Heart J.2014;35:455–469. doi.org/10.1093/eurheartj/eht386

Feuerstein GZ, Poste G, Ruffolo RR, Cynthia Perreault-Micale, Roger J Hajjar, Djamel Lebeche, Klara Skiroman, George Jabbour,4Angelia A Doye, Michael X Lee, Nancy Laste, and Judith K Gwathmey Carvedilol update III: rationale for use in congestive heart failure. Drugs Today.1995;31 (Suppl. F):1-23. DOI: 10.1186/1472-6793-3-6

Fisher D, Rossa S, Landmesser U, Spiekermann S, Engberding N, Hornig B, Drexler H. Endothelian dysfunction in patients with chronic heart failure is independently associated with increased incidence of hospitalization or death. Europ. Heart J. 2005;1:65–69. DOI: 10.1093/eurheartj/ehi001

Green D, Kalra P.A. Renal dysfunction. In: Oxford textbook of Heart Failure. Ed.: Mg Donagh T.A., Gardner R.S., Clark A., Dargie H.J. – Oxford Univ. Press, 2011. p.304–312.

Hilledge HL, Girbers AR, de Kam PJ, Boomsma F, de Zeeuw D, Charlesworyh A, Hampton JR, van Veldhuisein DJ. Renal function, neurohormonal activation, and survival in patients with chronic heart failure. Circulation. 2000;102:203–210. DOI:10.1161/CIRCULATIONAHA.105.580506

Ignaro LJ. Experimental evidences of nitric oxide-dependent vasodilatory activity of nebivolol, a third generation beta-blocker. Blood Pressure.2004;13(Suppl.1):2–16. DOI: 10.1345/aph.1G708

Jackson CE, Solomon SD, Gerstein HC, Zetterstrand S, Olofeson B, Michelson EL. Albuminuria in chronic heart failure: prevalence and prognostic importance. Lancet. 2009;374:543–550.

Kang DH, Kanellis J, Hugo C, Truong L, Anderson S, Kerjaschki D, Schreiner GF, Johnson RJ. Role of the microvascular endotheliu in progressive renal disease. J Am SocNephrol. 2002;13:806–816.

Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO Clinical Practice Disease. Kidney inter., 2012;Suppl. 1–150.

Lazarus JM, Bourgoignie JJ, Buckalew VM, Greene T, Levey AS, Milas NC, Paranandi L, Peterson JC, Porush JG, Rauch S, Soucie JM, Stollar C. Achivement and safety of low blood pressure goal in chronic renal disease. Modification of diet in renal disease study. Hypertension. 1997;29:641–650.

Levey AS. A new question to estimate glomerular filtration rate. Ann. Intern. Med. 2009;15:604–612.

Maxwell AP, Ong HY, Nicholls DP. Influence of progressive renal function in chronic heart failure. Eur. J. Heart Failure. 2002;4:125–130. doi: 10.6061/clinics/2013(03)R01

Medcalf EA, Newmann DJ, Gorman ED. Rapid, robust method for measuring low concentration of albumin in urine. Clin Chem. 1999;3:p. 446–449.

Metra M, Gotter G, Gheougihiade M, Cas L, Voors A. The role of the kidney in heart failure. Heart Failure. 2012;33:2135–2142. doi: 10.1093/eurheart/ehs205.

Myers GL, Miller WG, Coresh J, Fleming J, Greenberg N, Greene T, Hostetter T, Levey AS, Panteghini M, Welch M, Eckfeldt JH Reccommtndations for Improving Serum Creatinine Measurement . Clin Chem. 2006;52:5–18. DOI: 10.1373/clinchem.2005.0525144

Nohria A, Hasselblad V, Stebbins A, Pauly DF, Fonarow GC, Shah M, Yancy CW, Califf RM, Stevenson LW, Hill JA. Cardiorenal interactions: insights from the ESCARE trial. J Am Coll Cardiol. 2008;51(13):1268–1274.

Shestakova MV, Gozhenko AI, Kuznetsova HS, Kuznetsova KS, Kuznyetsov SH, Byts TM. The role of the tissue renin-angiotensinaldosterone system in the development of metabolic syndrome, diabetes mellitus and its vascular complications. Diabetes mellitus. 2010; 3:14–19 DOI: https://doi.org/10.22141/2307-1257.7.1.2018.122215.

Silverberg DS. Anemia, chronic renal disease and congestive heart failure – the cardio renal anemia syndrome: the need of cooperation between cardiologists and nephrologists. Int. Urol. Nephrol. 2006;38:295–310.

Smith GL, Lichtman JH, Bracken MB, Shlipak MG, Phillips CO, DiCapua P, Krumholz HM. Renal impairment and outcomes in heart failure: systematic review and meta-analysis J.Am.Coll.Cardiol.2006;47(10):1987–1996. doi:10.1016/j.ccl.2010.04.004

Stehouwer CD, Henry RM, Dekker JM, Nijpels G, Heine RJ, Bouter LM Microalbuminuria is associated with impaired brachial artery, flow-mediated vasodilation in elderly individuals without and with diabetes: further evidence for a link between microalbuminuria and endothelial dysfunction. Kidn. Int Suppl. 2004;92:42–44. DOI: 10.1111/j.1523-1755.2004.09211.x

Testani JM, Cappola TP, Brensinger CM, Shannone RP, Kimmel SE. Interaction between loop diuretic-associated mortality and blood urea nitrogen concentration in chronic heart failure. J Am Coll Cardiol. 2011;58:375–382. doi: [10.1016/j.jacc.2011.01.052

Wal RMA, Asselbergs FW, Plokker HWT, Smild TDJ, Lok D, van Veldhuisen DJ High prevalence of microalbuminuria in chronic heart failure patients. J Card Fail. 2005;11:602–606.

Wayne D. Comper Mechanisms of microalbuminuria. Pathology. 2010;42:19. doi: 10.3109/00313021003600606.

Zima T. Laboratorna diagnostika. Galen. 2002.p.25–28.

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