Abstract
Detecting high-risk patients for early rehospitalization is crucial in heart failure patient care. An association of albuminuria with cardiovascular events is well known. However, its predictive impact on rehospitalization for acute decompensated heart failure (ADHF) remains unknown. In this study, 190 consecutive patients admitted due to ADHF between 2017 and April 2019 who underwent urinalysis were enrolled. Among them, 140 patients from whom urine albumin-to-creatinine ratio (UACR) was measured with spot urine samples on admission were further analyzed. The association between UACR and rehospitalization due to HF during 1 year after discharge was evaluated. The mean age of 140 participants was 77.6 years and 55% were men. Only 18% (n = 25) of patients presented with normoalbuminuria (UACR < 30 mg/g∙creatinine), whereas 59% (n = 83) and 23% (n = 32) showed microalbuminuria (UACR 30–300 mg/g·creatinine) and macroalbuminuria (UACR > 300 mg/g·creatinine), respectively. The level of UACR on admission was correlated with the risk of subsequent rehospitalization due to HF (p = 0.017). The receiver operating characteristic analysis indicated that the best cut-off values for the UACR and B-type natriuretic peptide (BNP) levels to predict ADHF rehospitalization were 50 mg/g·creatinine and 824 pg/ml, respectively. When the patients were divided into four groups using both cut-off values, the individual predictive impacts of UACR and BNP on rehospitalization were comparable. Patients with both elevated UACR and BNP levels had a higher rate of HF rehospitalization than those with elevated BNP levels alone (p < 0.05). The combination of both values enabled more accurate prediction of HF rehospitalization than BNP levels alone. In conclusion, UACR could be a new useful biomarker to predict HF rehospitalization in patients with ADHF, especially in combination with the levels of BNP, and should be further evaluated in a prospective study.
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Chang PP, Chambless LE, Shahar E, Bertoni AG, Russell SD, Ni H, He M, Mosley TH, Wagenknecht LE, Samdarshi TE, Wruck LM, Rosamond WD (2014) Incidence and survival of hospitalized acute decompensated heart failure in four US communities (from the Atherosclerosis Risk in Communities Study). Am J Cardiol 113(3):504–510
Kono Y, Izawa H, Aoyagi Y, Ishikawa A, Sugiura T, Mori E, Yanohara R, Ishiguro T, Yamada R, Okumura S, Fujiwara W, Hayashi M, Saitoh E (2020) Predictive impact of early mobilization on rehospitalization for elderly Japanese heart failure patients. Heart Vessels 35(4):531–536
Butler J, Kalogeropoulos A (2008) Worsening heart failure hospitalization epidemic we do not know how to prevent and we do not know how to treat! J Am Coll Cardiol 52(6):435–437
Cooper LB, Lippmann SJ, DiBello JR, Gorsh B, Curtis LH, Sikirica V, Hernandez AF, Sprecher DL, Laskey WK, Saini R, Fonarow GC, Hammill BG (2019) The burden of congestion in patients hospitalized with acute decompensated heart failure. Am J Cardiol 124(4):545–553
Maggioni AP, Dahlström U, Filippatos G, Chioncel O, Crespo Leiro M, Drozdz J, Fruhwald F, Gullestad L, Logeart D, Fabbri G, Urso R, Metra M, Parissis J, Persson H, Ponikowski P, Rauchhaus M, Voors AA, Nielsen OW, Zannad F, Tavazzi L (2013) EURObservational Research Programme: regional differences and 1-year follow-up results of the Heart Failure Pilot Survey (ESC-HF Pilot). Eur J Heart Fail 15(7):808–817
Omote K, Nagai T, Asakawa N, Kamiya K, Tokuda Y, Aikawa T, Fukushima A, Noguchi K, Kato Y, Komoriyama H, Nishida M, Kudo Y, Iwano H, Yokota T, Anzai T (2019) Impact of admission liver stiffness on long-term clinical outcomes in patients with acute decompensated heart failure. Heart Vessels 34(6):984–991
Stewart S, MacIntyre K, Hole DJ, Capewell S, McMurray JJ (2001) More “malignant” than cancer? Five-year survival following a first admission for heart failure. Eur J Heart Fail 3(3):315–322
Sudharshan S, Novak E, Hock K, Scott MG, Geltman EM (2017) Use of biomarkers to predict readmission for congestive heart failure. Am J Cardiol 119(3):445–451
Briguori C, Betocchi S, Manganelli F, Gigante B, Losi MA, Ciampi Q, Gottilla R, Violante A, Tocchetti CG, Volpe M, Chiariello M (2001) Determinants and clinical significance of natriuretic peptides and hypertrophic cardiomyopathy. Eur Heart J 22(15):1328–1336
Gruden G, Landi A, Bruno G (2014) Natriuretic peptides, heart, and adipose tissue: new findings and future developments for diabetes research. Diabetes Care 37(11):2899–2908
Knudsen CW, Omland T, Clopton P, Westheim A, Wu AH, Duc P, McCord J, Nowak RM, Hollander JE, Storrow AB, Abraham WT, McCullough PA, Maisel A (2005) Impact of atrial fibrillation on the diagnostic performance of B-type natriuretic peptide concentration in dyspneic patients: an analysis from the breathing not properly multinational study. J Am Coll Cardiol 46(5):838–844
Dai Z, Zhang Y, Ye H, Zhang G, Jin H, Chen Z, Yao Y, Tian X, Zhou J, Li P, Liang X, Xie H, Ge S, Zhang Z (2018) Adiponectin is valuable in the diagnosis of acute heart failure with renal insufficiency. Exp Ther Med 16(3):2725–2734
Tang WH, Wu Y, Grodin JL, Hsu AP, Hernandez AF, Butler J, Metra M, Voors AA, Felker GM, Troughton RW, Mills RM, McMurray JJ, Armstrong PW, O’Connor CM, Starling RC (2016) Prognostic value of baseline and changes in circulating soluble ST2 levels and the effects of nesiritide in acute decompensated heart failure. JACC Heart Fail 4(1):68–77
Adler AI, Stevens RJ, Manley SE, Bilous RW, Cull CA, Holman RR (2003) Development and progression of nephropathy in type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS 64). Kidney Int 63(1):225–232
Jackson CE, Solomon SD, Gerstein HC, Zetterstrand S, Olofsson B, Michelson EL, Granger CB, Swedberg K, Pfeffer MA, Yusuf S, McMurray JJ (2009) Albuminuria in chronic heart failure: prevalence and prognostic importance. Lancet 374(9689):543–550
Selvaraj S, Claggett B, Shah SJ, Anand I, Rouleau JL, O'Meara E, Desai AS, Lewis EF, Pitt B, Sweitzer NK, Fang JC, Pfeffer MA, Solomon SD (2018) Prognostic value of albuminuria and influence of spironolactone in heart failure with preserved ejection fraction. Circ Heart Fail 11(11):e005288
Shuvy M, Zwas DR, Lotan C, Keren A, Gotsman I (2020) Albuminuria: associated with heart failure severity and impaired clinical outcomes. Can J Cardiol 36(4):527–534
Bakris GL, Agarwal R, Anker SD, Pitt B, Ruilope LM, Rossing P, Kolkhof P, Nowack C, Schloemer P, Joseph A, Filippatos G (2020) Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med 383(23):2219–2229
Pitt B, Filippatos G, Agarwal R, Anker SD, Bakris GL, Rossing P, Joseph A, Kolkhof P, Nowack C, Schloemer P, Ruilope LM (2021) Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med. https://doi.org/10.1056/NEJMoa2110956
Porter TR, Shillcutt SK, Adams MS, Desjardins G, Glas KE, Olson JJ, Troughton RW (2015) Guidelines for the use of echocardiography as a monitor for therapeutic intervention in adults: a report from the American Society of Echocardiography. J Am Soc Echocardiogr 28(1):40–56
Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A (2009) Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 53(6):982–992
Stehouwer CD, Smulders YM (2006) Microalbuminuria and risk for cardiovascular disease: analysis of potential mechanisms. J Am Soc Nephrol 17(8):2106–2111
Konta T, Hao Z, Abiko H, Ishikawa M, Takahashi T, Ikeda A, Ichikawa K, Takasaki S, Kubota I (2006) Prevalence and risk factor analysis of microalbuminuria in Japanese general population: the Takahata study. Kidney Int 70(4):751–756
Neuen BL, Ohkuma T, Neal B, Matthews DR, de Zeeuw D, Mahaffey KW, Fulcher G, Li Q, Jardine M, Oh R, Heerspink HL, Perkovic V (2019) Effect of canagliflozin on renal and cardiovascular outcomes across different levels of albuminuria: data from the CANVAS program. J Am Soc Nephrol 30(11):2229–2242
Koyama S, Sato Y, Tanada Y, Fujiwara H, Takatsu Y (2013) Early evolution and correlates of urine albumin excretion in patients presenting with acutely decompensated heart failure. Circ Heart Fail 6(2):227–232
Ninomiya T, Perkovic V, de Galan BE, Zoungas S, Pillai A, Jardine M, Patel A, Cass A, Neal B, Poulter N, Mogensen CE, Cooper M, Marre M, Williams B, Hamet P, Mancia G, Woodward M, Macmahon S, Chalmers J (2009) Albuminuria and kidney function independently predict cardiovascular and renal outcomes in diabetes. J Am Soc Nephrol 20(8):1813–1821
van der Velde M, Matsushita K, Coresh J, Astor BC, Woodward M, Levey A, de Jong P, Gansevoort RT, van der Velde M, Matsushita K, Coresh J, Astor BC, Woodward M, Levey AS, de Jong PE, Gansevoort RT, Levey A, El-Nahas M, Eckardt KU, Kasiske BL, Ninomiya T, Chalmers J, Macmahon S, Tonelli M, Hemmelgarn B, Sacks F, Curhan G, Collins AJ, Li S, Chen SC, Hawaii Cohort KP, Lee BJ, Ishani A, Neaton J, Svendsen K, Mann JF, Yusuf S, Teo KK, Gao P, Nelson RG, Knowler WC, Bilo HJ, Joosten H, Kleefstra N, Groenier KH, Auguste P, Veldhuis K, Wang Y, Camarata L, Thomas B, Manley T (2011) Lower estimated glomerular filtration rate and higher albuminuria are associated with all-cause and cardiovascular mortality. A collaborative meta-analysis of high-risk population cohorts. Kidney Int 79(12):1341–1352
Wang Y, Zhao X, Zhai M, Fan C, Huang Y, Zhou Q, Tian P, An T, Zhang Y, Zhang J (2021) Elevated urinary albumin concentration predicts worse clinical outcomes in hospitalized acute decompensated heart failure patients. ESC Heart Fail 8(4):3037–3048
Asanuma K, Yanagida-Asanuma E, Takagi M, Kodama F, Tomino Y (2007) The role of podocytes in proteinuria. Nephrology (Carlton) 12(Suppl 3):S15–S20
Durvasula RV, Petermann AT, Hiromura K, Blonski M, Pippin J, Mundel P, Pichler R, Griffin S, Couser WG, Shankland SJ (2004) Activation of a local tissue angiotensin system in podocytes by mechanical strain. Kidney Int 65(1):30–39
García Donaire JA, Ruilope LM (2007) Angiotensin receptor blockade in diabetic renal disease—focus on candesartan. Diabetes Res Clin Pract 76(Suppl 1):S22–S30
Ross EA (2012) Congestive renal failure: the pathophysiology and treatment of renal venous hypertension. J Card Fail 18(12):930–938
Martens RJ, Henry RM, Houben AJ, van der Kallen CJ, Kroon AA, Schalkwijk CG, Schram MT, Sep SJ, Schaper NC, Dagnelie PC, Muris DM, Gronenschild EH, van der Sande FM, Leunissen KM, Kooman JP, Stehouwer CD (2016) capillary rarefaction associates with albuminuria: the Maastricht study. J Am Soc Nephrol 27(12):3748–3757
Márquez E, Riera M, Pascual J, Soler MJ (2015) Renin-angiotensin system within the diabetic podocyte. Am J Physiol Renal Physiol 308(1):F1–F10
Rafiq K, Noma T, Fujisawa Y, Ishihara Y, Arai Y, Nabi AH, Suzuki F, Nagai Y, Nakano D, Hitomi H, Kitada K, Urushihara M, Kobori H, Kohno M, Nishiyama A (2012) Renal sympathetic denervation suppresses de novo podocyte injury and albuminuria in rats with aortic regurgitation. Circulation 125(11):1402–1413
Vaněčková I, Hojná S, Kadlecová M, Vernerová Z, Kopkan L, Červenka L, Zicha J (2018) Renoprotective effects of ET(A) receptor antagonists therapy in experimental non-diabetic chronic kidney disease: is there still hope for the future? Physiol Res 67(Suppl 1):S55-s67
Smilde TD, Damman K, van der Harst P, Navis G, Westenbrink BD, Voors AA, Boomsma F, van Veldhuisen DJ, Hillege HL (2009) Differential associations between renal function and “modifiable” risk factors in patients with chronic heart failure. Clin Res Cardiol 98(2):121–129
Erkan E, Devarajan P, Schwartz GJ (2007) Mitochondria are the major targets in albumin-induced apoptosis in proximal tubule cells. J Am Soc Nephrol 18(4):1199–1208
Ronco C, Cicoira M, McCullough PA (2012) Cardiorenal syndrome type 1: pathophysiological crosstalk leading to combined heart and kidney dysfunction in the setting of acutely decompensated heart failure. J Am Coll Cardiol 60(12):1031–1042
Mullens W, Abrahams Z, Francis GS, Sokos G, Taylor DO, Starling RC, Young JB, Tang WHW (2009) Importance of venous congestion for worsening of renal function in advanced decompensated heart failure. J Am Coll Cardiol 53(7):589–596
Damman K, Masson S, Hillege Hans L, Voors Adriaan A, van Veldhuisen Dirk J, Rossignol P, Proietti G, Barbuzzi S, Nicolosi Gian L, Tavazzi L, Maggioni Aldo P, Latini R (2013) Tubular damage and worsening renal function in chronic heart failure. JACC Heart Fail 1(5):417–424
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Matsumoto, Y., Orihara, Y., Asakura, M. et al. Urine albumin-to-creatinine ratio on admission predicts early rehospitalization in patients with acute decompensated heart failure. Heart Vessels 37, 1184–1194 (2022). https://doi.org/10.1007/s00380-022-02025-y
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DOI: https://doi.org/10.1007/s00380-022-02025-y