Evaluation of the clinical value of sodium examination in spot urine in patients presenting with acute heart failure while using SGLT2i – ‘‘SPOT HF STUDY’’

Year 2023, Volume: 9 Issue: 6 - November 2023, 1454 - 1463, 04.11.2023

Onur Aslan , Emre Emrah Demirci

https://doi.org/10.18621/eurj.1349473

Abstract

Objectives: Sodium measurement in spot urine provides important information about the adequacy of the initial dose in acute heart failure (AHF) patients using intravenous diuretic (IV) and makes a guiding contribution to the titration decision. It is not clear whether spot urine sodium measurement has the same clinical value as the effect of sodium-glucose cotransporter 2 inhibitor (SGLT2i) drugs on urinary electrolytes. Our aim in our study is to investigate the clinical value of sodium examination in spot urine in AHF patients while using SGLT2i.

Methods: Our study was conducted retrospectively and single-centered. AHF patients, administered IV diuretics were included in the study. Patients who were using and were not using SGLT2i were examined in two groups. The 2nd and 6th-hour sodium values in spot urine were measured.

Results: Patients using SGLT2i (n = 46) and not using it (n = 54) were included. The mean age was 69.91 ± 11.84 years and 47% were female. The standard deviation value for the sodium in spot urine in patients using SGLT2i was clearly high and its distribution was significantly higher. A weak correlation was found between the sodium value in spot urine and the 24-hour urine volume in this group. Hospitalization history within 1 month after discharge was found to be 39% in the group using SGLT2i, and 51% in the group that did not use it, and this difference was statistically significant.

Conclusions: The measurement of sodium in spot urine does not seem to have the same clinical value in HF patients using SGLT2i. Its correlation with urine volume is also decreasing in this group.

Keywords

Acute heart failure, sodium-glucose cotransporter 2 inhibitor, spot urine

References

• 1. Jencks SF, Williams MV, Coleman EA. Rehospitalizations among patients in the Medicare fee-for-service program. N Eng J Med 2009;360:1418-28.
• 2. Rubio-Gracia J, Demissei BG, Ter Maaten JM, Cleland JG, O’Connor CM, Metra M, et al. Prevalence, predictors and clinical outcome of residual congestion in acute decompensated heart failure. Int J Cardiol 2018;258:185-91.
• 3. Metra M, Davison B, Bettari L, Sun H, Edwards C, Lazzarini V, et al. Is worsening renal function an ominous prognostic sign in patients with acute heart failure? The role of congestion and its interaction with renal function. Circ Heart Fail 2012;5:54-62.
• 4. Mullens W, Damman K, Harjola VP, Mebazaa A, Brunner-La Rocca HP, Martens P, et al. The use of diuretics in heart failure with congestion – a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 2019;21:137-55.
• 5. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. "2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contribution of the Heart Failure Association (HFA) of the ESC." Eur Heart J 2021;42:3599-726.
• 6. Testani JM, Brisco MA, Kociol RD, Jacoby D, Bellumkonda L, Parikh CR, et al. Substantial discrepancy between fluid and weight loss during acute decompensated heart failure treatment. Am J Med 2015;128:776-83.
• 7. Schnermann J. Juxtaglomerular cell complex in the regulation of renal salt excretion. Am J Physiol 1998;274:263-79.
• 8. Testani JM, Brisco MA, Turner JM, Spatz ES, Bellumkonda L, Parikh CR, et al. Loop diuretic efficiency: a metric of diuretic responsiveness with prognostic importance in acute decompensated heart failure. Circ Heart Fail 2014;7:261-70.
• 9. Singh D, Shrestha K, Testani JM, Verbrugge FH, Dupont M, Mullens W, et al. Insufficient natriuretic response to continuous intravenous furosemide is associated with poor long-term outcomes in acute decompensated heart failure. J Card Fail 2014;20:392-9.
• 10. Testani JM, Hanberg JS, Cheng S, Rao V, Onyebeke C, Laur O, et al. Rapid and highly accurate prediction of poor loop diuretic natriuretic response in patients with heart failure. Circ Heart Fail 2016;9:e002370.
• 11. Packer M, Anker SD, Butler J, Flippatos G, Ferreira JP, Pocock SJ, et al. Effect of empagliflozin on the clinical stability of patients with heart failure and a reduced ejection fraction: the EMPEROR-Reduced trial. Circulation 2021;143:326-36.
• 12. McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, et al. DAPA-HF Trial Committees and Investigators. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med 2019;381:1995-2008.
• 13. Cherney DZ, Perkins BA, Soleymanlou N, Maione M, Lai V, Lee A, et al. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation 2014;129:587-97.
• 14. Hodson D, Griffin M, Mahoney D, Raghavenda P, Ahmad T, Turner J, et al. Natriuretic response is highly variable and associated with 6-month survival. JACC Heart Fail 2019;7:383-91.
• 15. Verbrugge FH, Nijst P, Dupont M, Penders J, Tang WH, Mullens W. Urinary composition during decongestive treatment in heart failure with reduced ejection fraction. Circ Heart Fail 2014;7:766-72.
• 16. Ferreira JP, Girerd N, Medeiros PB, Santos M, Carvalho HC, Bettencourt P, et al. Spot urine sodium excretion as prognostic marker in acutely decompensated heart failure: the spironolactone effect. Clin Res Cardiol 2016;105:489-507.
• 17. Mentz RJ, Kjeldsen K, Rossi GP, Voors AA, Cleland JG, Anker SD, et al. Decongestion in acute heart failure. Eur J Heart Fail 2014;16:471-82.
• 18. Brinkley Jr. DM, Burpee LJ, Chaudhry SP, Smallwood JA, Lindenfeld J, Lakdawala NK, et al. Spot urine sodium as triage for effective diuretic infusion in an ambulatory heart failure unit. J Card Fail 2018;24:349-54.
• 19. Packer M, Butler J, Zannad F, Flippatos G, Ferreira JP, Pocock SJ, et al. Effect of empagliflozin on worsening heart failure events in patients with heart failure and preserved ejection fraction: EMPEROR-preserved trial. Circulation 2021;144:1284-94.
• 20. Pessoa TD, Campos LC, Carraro-Lacroix L, Girardi AC, Malnic G. Functional role of glucose metabolism, osmotic stress, and sodium-glucose cotransporter isoform-mediated transport on Na+/H+ exchanger isoform 3 activity in the renal proximal tubule. J Am Soc Nephrol 2014;25:2028-39.
• 21. Alicic RZ, Johnson EJ, Tuttle KR. SGLT2 inhibition for the prevention and treatment of diabetic kidney disease: a review. Am J Kidney Dis 2018;72:267-77.
• 22. McCullough PA, Kluger AY, Tecson KM, Barbin M, Lee AY, Lerma EV, et al. Inhibition of the sodium-proton antiporter (exchanger) is a plausible mechanism of potential benefit and harm for drugs designed to block sodium glucose co-transporter 2. Rev Cardiovasc Med 2018;19:51-63.
• 23. Bjornstad P, Laffel L, Tamborlane WV, Simons G, Hantel S, Von Eynatten M, et al. Acute effect of empagliflozin on fractional excretion of sodium and eGFR in youth with type 2 diabetes. Diabetes Care 2018;41:e129-30.
• 24. Griffin M, Rao VS, Ivey-Miranda J, Fleming J, Mahoney D, Maulion C, et al. Empagliflozin in heart failure: diuretic and cardiorenal effects. Circulation 2020;142:1028-39.
• 25. Damman K, Beusekamp JC, Boorsma EM, Swart HP, Smilde TDJ, Elvan A, et al. Randomized, double-blind, placebo-controlled, multicentre pilot study on the effects of empagliflozin on clinical outcomes in patients with acute decompensated heart failure (EMPA-RESPONSE-AHF). Eur J Heart Fail 2020;22:713-22.
• 26. Boorsma EM, Beusekamp JC, Ter Maaten JM, Figarska SM, Danser AHJ, van Veldhuisen DJ, et al. Effects of empagliflozin on renal sodium and glucose handling in patients with acute heart failure. Eur J Heart Fail 2021;23:68-78.
• 27. Karg MV, Bosch A, Kannenkeril D, Striepe K, Ott C, Schneider MP, et al. SGLT-2-inhibition with dapagliflozin reduces tissue sodium content: a randomised controlled trial. Cardiovasc Diabetol 2018;17:5.
• 28. Lee TI, Chen YC, Lin YK, Chung CC, Lu YY, Kao YH, et al. Empagliflozin attenuates ayocardial sodium and calcium dysregulation and reverses cardiac remodeling in streptozotocin-induced diabetic rats. Int J Mol Sci 2019;20:1680.
• 29. Tanaka H, Takano K, Iijima H, Kubo H, Maruyama N, Hashimoto T, et al. Factors affecting canagliflozin-induced transient urine volume increase in patients with type 2 diabetes mellitus. Adv Ther 2017;34:436-51.
• 30. Damman K, Ter Maaten JM, Coster JE, Krikken JA, van Deursen VM, Krijnen HK, et al. Clinical importance of urinary sodium excretion in acute heart failure. Eur J Heart Fail 2020;22:1438-47.
• 31. Honda S, Nagai T, Nishimura K, Nakai M, Honda Y, Nakano H, et al.; NaDEF Investigators. Long-term prognostic significance of urinary sodium concentration in patients with acute heart failure. Int J Cardiol 2018;254:189-94.
• 32. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015;373:2117-28.
• 33. Neal B, Perkovic V, Mahaffey KW, De Zeeuw D, Fulcher G, Erondu N, et al.; CANVAS Program Collaborative Group. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017;377:644-57.
• 34. Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, et al.; DECLARE–TIMI 58 Investigators. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2019;380:347-57.
• 35. Hallow KM, Helmlinger G, Greasley PJ, McMurray JJ, Boulton DW. Why do SGLT2 inhibitors reduce heart failure hospitalization? A differential volume regulation hypothesis. Diabetes Obes Metab 2018;20:479-87.