Reduced Albuminuria and Potassemia Indicate Early Renal Repair Processes after Resynchronization Therapy in Cardiorenal Syndrome Type 2

Agnieszka Gala-Błądzińska, Janusz Romanek, Danuta Mazur, Tomasz Stepek, Marcin Braun, Piotr Szafarz, Marcin Chlebuś, Andrzej Przybylski, Agnieszka Gala-Błądzińska, Janusz Romanek, Danuta Mazur, Tomasz Stepek, Marcin Braun, Piotr Szafarz, Marcin Chlebuś, Andrzej Przybylski

Abstract

Background: Patients with chronic cardiorenal syndrome type 2 (T2-CRS) who qualify for resynchronization therapy (CRT) are exposed perioperatively to potentially nephrotoxic factors including contrast agents and blood loss.

Methods: The objective of this prospective interventional study was to assess the effects of CRT on renal function in patients with T2-CRS within the first 48 hours following implantation. Initially, 76 patients (15% female; aged 69 ± 9.56 years) with heart failure (New York Heart Association classes II-IV), ejection fraction ≤ 35%, and QRS > 130 ms were included in the study. During CRT implantation, a nonionic contrast agent (72.2 ± 44.9 mL) was administered. Prior to and 48 hours following implantation, renal function was evaluated using the following serum biomarkers: creatinine (sCr), estimated glomerular filtration rate (using the Chronic Kidney Disease Epidemiology Collaboration equation [eGFRCKD-EPI]), and the electrolyte and urine biomarkers albumin (uAlb), albumin/creatinine ratio (UACR), and neutrophil gelatinase-associated lipocalin (uNGAL).

Results: Before CRT, patients classified as NYHA class III or IV had higher uNGAL levels in comparison to uNGAL levels after CRT (43.63 ± 60.02 versus 16.63 ± 18.19; p=0.041). After CRT implantation, uAlb, UACR, and potassium levels were reduced (p < 0.05), and uNGAL, sCr, and eGFRCKD-EPI were unchanged. The contrast medium volume did not correlate with the test biomarkers (p > 0.05).

Conclusions: In patients with T2-CRS, uNGAL is a biomarker of kidney injury that correlates with the NYHA classes. A stable uNGAL value before and after CRT implantation confirms the lack of risk of contrast-induced nephropathy. Reduced albuminuria and blood potassium are biomarkers of improving T2-CRS in the early post-CRT period.

Conflict of interest statement

The authors declare that there are no conflicts of interest regarding the publication of this paper.

Copyright © 2020 Agnieszka Gala-Błądzińska et al.

Figures

Figure 1
Figure 1
Algorithm for qualifying patients with chronic cardiorenal syndrome type 2, including indications for CRT implantation.
Figure 2
Figure 2
Graph showing the correlation of uNGAL with NYHA heart failure classes in the study group prior to CRT implantation; abbreviations: NYHA, New York Heart Association class; uNGAL, lipocalin associated with neutrophil gelatinase in a single sample of urine.
Figure 3
Figure 3
Impact of CRT implantation on selected renal parameters across the entire group of patients 48 hours following implantation. (a) uAlb, urinary albumin concentration in a single morning sample of urine prior to CRT implantation; uAlb 48, albumin concentration in a single morning sample of urine 48 hours following CRT implantation. (b) uACR, urinary albumin to creatinine ratio prior to CRT implantation; uACR 48, urinary albumin to creatinine ratio 48 hours following CRT implantation. (c) uNGAL, lipocalin associated with neutrophil gelatinase in a single morning sample of urine prior to CRT implantation; uNGAL 48, lipocalin associated with neutrophil gelatinase in a single morning sample of urine 48 hours following CRT implantation. (d) uNCR, urinary NGAL to creatinine ratio prior to CRT implantation; uNCR 48, urinary NGAL to creatinine ratio 48 hours following CRT implantation. (e) eGFR, estimated glomerular filtration rate calculated using Chronic Kidney Disease Epidemiology Collaboration prior to CRT implantation; eGFR 48, estimated glomerular filtration rate calculated using Chronic Kidney Disease Epidemiology Collaboration 48 hours following CRT implantation. (f) K, serum potassium concentration prior to CRT implantation; K 48, serum potassium concentration 48 hours following CRT implantation.

References

    1. Levin A., Stevens P. E., Bilous R. W., et al. Kidney disease: improving global outcomes (KDIGO) CKD work group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney International Supplements. 2013;3(1):1–150.
    1. Mills K. T., Xu Y., Zhang W., et al. A systematic analysis of worldwide population-based data on the global burden of chronic kidney disease in 2010. Kidney International. 2015;88(5):950–957. doi: 10.1038/ki.2015.230.
    1. Matsushita K., van der Velde M., Astor B. C., et al. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet. 2010;375(9731):2073–2081. doi: 10.1016/S0140-6736(10)60674-5.
    1. Go A. S., Chertow G. M., Fan D., McCulloch C. E., Hsu C.-y. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. New England Journal of Medicine. 2004;351(13):1296–1305. doi: 10.1056/nejmoa041031.
    1. Takahama H., Kitakaze M. Pathophysiology of cardiorenal syndrome in patients with heart failure: potential therapeutic targets. American Journal of Physiology-Heart and Circulatory Physiology. 2017;313(4):H715–H721. doi: 10.1152/ajpheart.00215.2017.
    1. Di Lullo L., Bellasi A., Barbera V., et al. Pathophysiology of the cardio-renal syndromes types 1-5: an uptodate. Indian Heart Journal. 2017;69(2):255–265. doi: 10.1016/j.ihj.2017.01.005.
    1. Dries D. L., Exner D. V., Domanski M. J., Greenberg B., Stevenson L. W. The prognostic implications of renal insufficiency in asymptomatic and symptomatic patients with left ventricular systolic dysfunction. Journal of the American College of Cardiology. 2000;35(3):681–689. doi: 10.1016/s0735-1097(99)00608-7.
    1. Bazoukis G., Letsas K. P., Korantzopoulos P., et al. Impact of baseline renal function on all-cause mortality in patients who underwent cardiac resynchronization therapy: a systematic review and meta-analysis. Journal of Arrhythmia. 2017;33(5):417–423. doi: 10.1016/j.joa.2017.04.005.
    1. Seferovic P. M., Ponikowski P., Anker S. D., et al. Clinical practice update on heart failure 2019: pharmacotherapy, procedures, devices and patient management. An expert consensus meeting report of the Heart Failure Association of the European Society of Cardiology. European Journal of Heart Failure. 2019;21(10):1169–1186. doi: 10.1002/ejhf.1531.
    1. Shurrab M., Ko D. T., Zayed Y., et al. Outcomes of ICDs and CRTs in patients with chronic kidney disease: a meta-analysis of 21,000 patients. Journal of Interventional Cardiac Electrophysiology. 2018;53(1):123–129. doi: 10.1007/s10840-018-0424-1.
    1. Cannizzaro L. A., Piccini J. P., Patel U. D., Hernandez A. F. Device therapy in heart failure patients with chronic kidney disease. Journal of the American College of Cardiology. 2011;58(9):889–896. doi: 10.1016/j.jacc.2011.05.024.
    1. Moreira R. I., Cunha P. S., Rio P., et al. Response and outcomes of cardiac resynchronization therapy in patients with renal dysfunction. Journal of Interventional Cardiac Electrophysiology. 2018;51(3):237–244. doi: 10.1007/s10840-018-0330-6.
    1. Kowalczyk J., Lenarczyk R., Oskar K., et al. Contrast-induced acute kidney injury in patients undergoing cardiac resynchronization therapy-incidence and prognostic importance. Sub-analysis of data from randomized TRUST CRT trial. Journal of Interventional Cardiac Electrophysiology. 2014;40(1):1–8. doi: 10.1007/s10840-014-9887-x.
    1. Ponikowski P., Voors A. A., Anker S. D., et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. European Heart Journal. 2016;37(27):2129–2200. doi: 10.1093/eurheartj/ehw128.
    1. Dolgin M., New York Heart Association . Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels. 9th. Boston, MA, USA: Little Brown & Co.; 1994. pp. 253–256.
    1. Kellum J. A., Lameire N., Aspelin P., et al. Kidney disease: improving global outcomes (KDIGO) acute kidney injury work group. KDIGO clinical practice guideline for acute kidney injury. Kidney International Supplements. 2012;2(1):1–138.
    1. Mehran R., Aymong E. D., Nikolsky E., et al. A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention. Journal of the American College of Cardiology. 2004;44(7):1393–1399. doi: 10.1016/s0735-1097(04)01445-7.
    1. Ronco C., Di Lullo L. Cardiorenal syndrome. Heart Failure Clinics. 2014;10(2):251–280. doi: 10.1016/j.hfc.2013.12.003.
    1. Rangaswami J., Bhalla V., Blair J. E. A., et al. Cardiorenal syndrome: classification, pathophysiology, diagnosis, and treatment strategies: a scientific statement from the American heart association. Circulation. 2019;139(16):e840–e878. doi: 10.1161/CIR.0000000000000664.
    1. Brignole M., Auricchio A., Baron-Esquivias G., et al. 2013 ESC guidelines on cardiac pacing and cardiac resynchronization therapy: the task force on cardiac pacing and resynchronization therapy of the European Society of Cardiology (ESC). Developed in collaboration with the European Heart Rhythm Association (EHRA) Europace Heart Journal. 2013;34(29):2281–2329. doi: 10.1093/eurheartj/eht150.
    1. Flower D. R. Experimentally determined lipocalin structures. Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology. 2000;1482(1-2):46–56. doi: 10.1016/s0167-4838(00)00147-3.
    1. Mishra J., Ma Q., Prada A., Mitsnefes M., et al. Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. Journal of the American Society of Nephrology. 2003;14(10):2534–2543. doi: 10.1097/01.asn.0000088027.54400.c6.
    1. Hirsch R., Dent C., Pfriem H., et al. NGAL is an early predictive biomarker of contrast-induced nephropathy in children. Pediatric Nephrology. 2007;22(12):2089–2095. doi: 10.1007/s00467-007-0601-4.
    1. Haase M., Bellomo R., Devarajan P., Schlattmann P., Haase-Fielitz A. Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: a systematic review and meta-analysis. American Journal of Kidney Diseases. 2009;54(6):1012–1024. doi: 10.1053/j.ajkd.2009.07.020.
    1. Damman K., Masson S., Hillege H. L., et al. Clinical outcome of renal tubular damage in chronic heart failure†. European Heart Journal. 2011;32(21):2705–2712. doi: 10.1093/eurheartj/ehr190.
    1. Jackson C. E., Solomon S. D., Gerstein H. C., et al. Albuminuria in chronic heart failure: prevalence and prognostic importance. The Lancet. 2009;374(9689):543–550. doi: 10.1016/S0140-6736(09)61378-7.
    1. Masson S., Latini R., Milani V., et al. Prevalence and prognostic value of elevated urinary albumin excretion in patients with chronic heart failure. Circulation: Heart Failure. 2010;3(1):65–72. doi: 10.1161/CIRCHEARTFAILURE.109.881805.
    1. Sarnak M. J., Levey A. S., Schoolwerth A. C., et al. Kidney disease as a risk factor for development of cardiovascular disease. Circulation. 2003;108(17):2154–2169. doi: 10.1161/01.cir.0000095676.90936.80.
    1. Mangiavacchi M., Gasparini M., Genovese S., et al. Insulin-treated type 2 diabetes is associated with a decreased survival in heart failure patients after cardiac resynchronization therapy. Pacing and Clinical Electrophysiology. 2008;31(11):1425–1432. doi: 10.1111/j.1540-8159.2008.01206.x.
    1. Haase M., Devarajan P., Haase-Fielitz A., et al. The outcome of neutrophil gelatinase-associated lipocalin-positive subclinical acute kidney injury: a multicenter pooled analysis of prospective studies. J Am Coll Cardiol. 2011;57(17):1752–1761. doi: 10.1016/j.jacc.2010.11.051.
    1. Annamalai S. K., Kapur N. K. Contrast induced nephropathy after coronary or vascular intervention: more biomarkers than answers. Catheterization and Cardiovascular Interventions. 2018;91(7):1192–1193. doi: 10.1002/ccd.27671.
    1. Sato A., Hoshi T., Kakefuda Y., et al. Effect of the Mehran risk score for the prediction of clinical outcomes after percutaneous coronary intervention. Journal of Cardiology. 2015;66(5):417–422. doi: 10.1016/j.jjcc.2014.12.016.
    1. DeFilippis E. M., Desai A. S. Treatment of hyperkalemia in heart failure. Current Heart Failure Reports. 2017;14(4):266–274. doi: 10.1007/s11897-017-0341-0.

Source: PubMed

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