Albuminuria and Dipstick Proteinuria for Predicting Mortality in Heart Failure: A Systematic Review and Meta-Analysis

Abstract

Background: Research suggest that albuminuria is not only an independent risk factor for the development of heart failure but may also act as a biomarker for predicting adverse outcomes. To date, no study has synthesized evidence on its role as a prognostic indicator. Thus, the current study aimed to quantitatively assess the prognostic utility of albuminuria as well as dipstick proteinuria in predicting mortality in heart failure patients.Methods: PubMed, Embase, ScienceDirect, CENTRAL, and Google Scholar databases were searched up to October 10, 2020. All studies reporting multivariable-adjusted hazard ratios (HR) for albuminuria or dipstick proteinuria for mortality and/or hospitalization in heart failure patients were included.Results: Eleven studies were included. Seven assessed albuminuria and five assessed dipstick proteinuria. Our analysis revealed a statistically significant increased risk of all-cause mortality with microalbuminuria (HR: 1.54; 95% CI, 1.23–1.93; I2 = 79%; p = 0.0002) and macroalbuminuria (HR: 1.76; 95% CI, 1.21–2.56; I2 = 88%; p = 0.003) in heart failure patients. The risk of all-cause mortality and hospitalization was also significantly increased with macroalbuminuria. Microalbuminuria was associated with significantly increased cardiovascular mortality and combined cardiovascular mortality and hospitalization. Positive dipstick test for proteinuria was significantly associated with mortality in heart failure (HR: 1.54; 95% CI, 1.28–1.84; I2 = 67%; p < 0.00001).Conclusion: Both microalbuminuria and macroalbuminuria are predictors of mortality in patients with heart failure. Dipstick proteinuria may be used as a rapid screening test to predict mortality in these patients.

Endothelin type A receptor blockade increases renoprotection in congestive heart failure combined with chronic kidney disease: Studies in 5/6 nephrectomized rats with aorto-caval fistula

“…Nevertheless, the combined treatment displayed marked additional beneficial actions on albuminuria and important renoprotective effects, such as alleviation of the renal glomerular and cortical tubulointerstitial injury. Increased albuminuria is a strong and independent predictor for all-cause mortality in CKD as well as in CHF [3][4][5]7,8,53,55], hence with the prolonged treatment the additive beneficial actions on the course of CKD-and CHF-related mortality could occur. Such reasoning is supported by the favourable actions on renal glomerular and tubulointerstitial morphology: 5/6 + ACF HanSD rats treated within the late treatment protocol with either ET A antagonist alone or ACEi alone showed marked renal glomerular damage, similar as observed in untreated animals.…”

“…Moreover, the combined treatment was the only regimen that reduced left ventricle as well as right ventricle hypertrophy as compared with untreated 5/6 NX + ACF HanSD rats. Since albuminuria and cardiac hypertrophy are regarded as independent risk factors for cardiovascular morbidity and mortality (including CKD-and CHF-related mortality) [2][3][4][55][56][57][58], greater beneficial effects on albuminuria, renal morphology and bilateral cardiac hypertrophy further support the notion that the addition of ET A receptor antagonist to the treatment with ACEi exhibits supplementary protective effects.…”

Association of Dipstick Proteinuria with Long-Term Mortality among Patients with Hypertensive Crisis in the Emergency Department

“…In addition, studies in hypertensive populations indicate that proteinuria is an adverse prognostic indicator of clinical cardiovascular disease and mortality [ 21 , 22 ]. Moreover, proteinuria was associated with all-cause mortality in patients with myocardial infarction [ 23 ], heart failure [ 24 ], and diabetes or pre-diabetes [ 25 ]. In this study, we demonstrated that trace proteinuria showed an HR of 1.91 (95% CI 1.53–2.37) and proteinuria (≥3+) showed an HR of 2.40 (95% CI 1.78–3.24) for all-cause mortality using a fully adjusted model; these increased risks were consistent in most subgroups.…”

ECG and Biomarker Profile in Patients with Acute Heart Failure: A Pilot Study

“…Among them, urinary ACR, microalbuminuria (MAU) and spot urine creatinine were found to have abnormal values in patients with AHF, with statistical significance compared to control group. As other studies show, albuminuria is more common in adults with chronic HF (CHF) than in those without CHF; it has clinical value in improving the accuracy of diagnosis of HFpEF (heart failure with preserved ejection fraction) and is a predictor of mortality in patients with HF [ 52 , 53 , 54 , 55 ]. In particular, Liang W. et al showed, in a meta-analysis published in 2021, that MAU was associated with significantly increased cardiovascular mortality and hospitalization [ 54 ].…”

“…As other studies show, albuminuria is more common in adults with chronic HF (CHF) than in those without CHF; it has clinical value in improving the accuracy of diagnosis of HFpEF (heart failure with preserved ejection fraction) and is a predictor of mortality in patients with HF [ 52 , 53 , 54 , 55 ]. In particular, Liang W. et al showed, in a meta-analysis published in 2021, that MAU was associated with significantly increased cardiovascular mortality and hospitalization [ 54 ]. From this perspective, we believe that the assessment of albuminuria should be part of the biomarker profile in patients with HF.…”