Role of comorbidities in heart failure prognosis Part 2: Chronic kidney disease, elevated serum uric acid

Despite improvements in pharmacotherapy, morbidity and mortality rates in community-based populations with chronic heart failure still remain high. The increase in medical complexity among patients with heart failure may be reflected by an increase in concomitant non-cardiovascular comorbidities, which are recognized as independent prognostic factors in this population. Heart failure and chronic kidney disease share many risk factors, and often coexist. The presence of kidney failure is associated with incremented risk of cardiovascular and non-cardiovascular mortality in heart failure patients. Chronic kidney disease is also linked with underutilization of evidence-based heart failure therapy that may reduce morbidity and mortality. More targeted therapies would be important to improve the prognosis of patients with these diseases. In recent years, serum uric acid as a determinant of cardiovascular risk has gained interest. Epidemiological, experimental and clinical data show that patients with hyperuricaemia are at increased risk of cardiac, renal and vascular damage and cardiovascular events. Moreover, elevated serum uric acid predicts worse outcome in both acute and chronic heart failure. While studies have raised the possibility of preventing heart failure through the use of uric acid lowering agents, the literature is still inconclusive on whether the reduction in uric acid will result in a measurable clinical benefit. Available evidences suggest that chronic kidney disease and elevated uric acid could worsen heart failure patients’ prognosis. The aim of this review is to analyse a possible utilization of these comorbidities in risk stratification and as a therapeutic target to get a prognostic improvement in heart failure patients.

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MO491ASSOCIATION BETWEEN SERUM URIC ACID LEVEL AND CHRONIC KIDNEY DISEASE INCIDENCE STRATIFIED BY SEX IN MIDDLE-AGED ADULTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab087.0011 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Shingo Nakayama ◽

Michihiro Satoh ◽

Takahisa Murakami ◽

Yukako Tatsumi ◽

Tomoko Muroya ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Uric Acid ◽

Kidney Disease ◽

Serum Uric Acid ◽

Health Check ◽

Middle Aged ◽

Men And Women ◽

Increased Risk ◽

The Mean ◽

Middle Aged Adults

Abstract Background and Aims While previous studies have reported the association between serum uric acid (SUA) and chronic kidney disease (CKD) incidence, the sex differences in this association remain controversial. Therefore, we examined the association between SUA levels and CKD incidence in middle-aged adults stratified by sex using data from a large-scale health check-up. Method We analyzed information from the JMDC database, which included the annual health check-up data of Japanese employees and their dependents aged <75 years. Among those individuals, we analyzed data from 138,511 individuals without CKD, kidney disease, or a history of cardiovascular disease at baseline. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and/or proteinuria. We divided the participants into 9 and 7 groups according to SUA levels for men and women, respectively. A Cox model was applied to assess the adjusted hazard ratios (HRs) for CKD incidence in each SUA level group using an SUA concentration of 4.0–4.9 mg/dL as the reference after adjusting for age, body mass index, current or ex-smoker, current or ex-drinker, diabetes mellitus, dyslipidemia, systolic blood pressure, use of anti-hyperuricemic drugs, and baseline eGFR. Results The mean participant age was 44.1 years, and 29.6% were women. The mean SUA levels were 5.9 mg/dL and 4.1 mg/dL in men and women, respectively. During the mean follow-up period of 4.68 years, 12,589 participants developed CKD. The age-standardized incidence rates for CKD were 17.88/17.80 per 1000 person-years in men/women with SUA concentrations of 4.0–4.9 mg/dL, 209.76 per 1000 person-years in men with SUA ≥11.0 mg/dL, and 73.38 per 1000 person-years in women with SUA ≥ 9.0 mg/dL. The fully adjusted HRs (95% confidence interval [CI], P value) for CKD incidence in the groups with SUA concentrations of <4.0, 10.0–10.9, and ≥11.0 mg/dL compared with those with SUA of 4.0–4.9 mg/dL among men were 1.13 (1.01–1.26, P=0.030), 1.98 (1.32–2.97, P=0.0010), and 3.74 (1.68–8.35, P=0.0013), respectively. In women, the fully adjusted HRs for CKD incidence in the groups with SUA concentrations of <4.0, 8.0–8.9, and ≥9.0 mg/dL were 1.08 (1.01–1.16, P=0.032), 2.39 (1.07–5.35, P=0.034), and 3.20 (0.80–12.8, P=0.10), respectively. Similar results were observed when we performed the sensitivity analysis excluding 8,411 individuals with hypertensive treatment from the main analysis. The HRs for the outcomes caused by the onset of eGFR <60 mL/min/1.73 m2 or proteinuria separately were similar to those for the main results. Conclusion The results of the present study demonstrated an increased risk of CKD in men with SUA concentrations of <4.0 and ≥10.0 mg/dL and <4.0 and ≥8.0 mg/dL in women compared to those with SUA concentrations of 4.0–4.9 mg/dL after adjusting for various covariates. Both high and low SUA levels were risk factors for CKD in middle-aged men and women. Hyperuricemia was demonstrated to cause renal injury due to the intraluminal deposition of uric acid crystals in the renal collecting duct. Hyperuricemia may also induce endothelial dysfunction, activation of the renin-angiotensin system, and induction of inflammation and stimulation of vascular smooth muscle cell proliferation by the induction of cyclooxygenase-2. However, as uric acid is one of the most important antioxidants in human plasma, low SUA levels may increase the risk of CKD incidence through decreased antioxidant activity. These mechanisms are implicated in the pathogenesis of CKD caused by high and low SUA levels. In addition, the SUA levels and ranges associated with increased risks of CKD incidence differed by sex.

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P4735Xanthine oxidase activation in chronic heart failure patients with concomitant chronic kidney disease

European Heart Journal ◽

10.1093/eurheartj/ehy563.p4735 ◽

2018 ◽

Vol 39 (suppl_1) ◽

Author(s):

M Kolomiiets ◽

A Bilchenko

Keyword(s):

Heart Failure ◽

Chronic Kidney Disease ◽

Chronic Heart Failure ◽

Kidney Disease ◽

Heart Failure Patients

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Elevated Serum Uric Acid Predicts Chronic Kidney Disease

The American Journal of the Medical Sciences ◽

10.1097/maj.0b013e318218bd89 ◽

2011 ◽

Vol 342 (6) ◽

pp. 461-466 ◽

Cited By ~ 20

Author(s):

Tamaki Yamada ◽

Mitsuru Fukatsu ◽

Tsuneya Wada ◽

Sadao Suzuki ◽

Takashi Joh

Keyword(s):

Chronic Kidney Disease ◽

Uric Acid ◽

Kidney Disease ◽

Serum Uric Acid ◽

Elevated Serum

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Renal arterial pulsatility predicts progression of chronic kidney disease in chronic heart failure patients

International Journal of Cardiology ◽

10.1016/j.ijcard.2012.11.088 ◽

2013 ◽

Vol 167 (6) ◽

pp. 3050-3051 ◽

Cited By ~ 3

Author(s):

Mariantonietta Cicoira ◽

Luca Conte ◽

Andrea Rossi ◽

Stefano Bonapace ◽

Giulia D'Agostini ◽

...

Keyword(s):

Heart Failure ◽

Chronic Kidney Disease ◽

Chronic Heart Failure ◽

Kidney Disease ◽

Heart Failure Patients

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Hyperuricemia and Hypertension, Coronary Artery Disease, Kidney Disease: From Concept to Practice

International Journal of Molecular Sciences ◽

10.3390/ijms21114066 ◽

2020 ◽

Vol 21 (11) ◽

pp. 4066 ◽

Cited By ~ 1

Author(s):

Mélanie Gaubert ◽

Thomas Bardin ◽

Alain Cohen-Solal ◽

François Diévart ◽

Jean-Pierre Fauvel ◽

...

Keyword(s):

Coronary Artery Disease ◽

Renal Function ◽

Uric Acid ◽

Coronary Artery ◽

Kidney Disease ◽

Serum Uric Acid ◽

Elevated Serum ◽

Renal Diseases ◽

Increased Risk ◽

Artery Disease

Since the publication of the Framingham Heart Study, which suggested that uric acid should no longer be associated with coronary heart disease after additional adjustment for cardiovascular disease risk factors, the number of publications challenging this statement has dramatically increased. The aim of this paper was to review and discuss the most recent studies addressing the possible relation between sustained elevated serum uric acid levels and the onset or worsening of cardiovascular and renal diseases. Original studies involving American teenagers clearly showed that serum uric acid levels were directly correlated with systolic and diastolic pressures, which has been confirmed in adult cohorts revealing a 2.21-fold increased risk of hypertension. Several studies involving patients with coronary artery disease support a role for serum uric acid level as a marker and/or predictor for future cardiovascular mortality and long-term adverse events in patients with coronary artery disease. Retrospective analyses have shown an inverse relationship between serum uric acid levels and renal function, and even a mild hyperuricemia has been shown to be associated with chronic kidney disease in patients with type 2 diabetes. Interventional studies, although of small size, showed that uric acid (UA)-lowering therapies induced a reduction of blood pressure in teenagers and a protective effect on renal function. Taken together, these studies support a role for high serum uric acid levels (>6 mg/dL or 60 mg/L) in hypertension-associated morbidities and should bring awareness to physicians with regards to patients with chronic hyperuricemia.

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Elevated serum uric acid levels in outpatients with chronic heart failure: side effect or marker of myocardial damage?

Journal of Cardiac Failure ◽

10.1016/s1071-9164(03)00251-3 ◽

2003 ◽

Vol 9 (5) ◽

pp. S91 ◽

Cited By ~ 1

Author(s):

Juan P.Cimbaro Canella ◽

Eduardo R. Perna ◽

Stella M. Macin ◽

Natalia Augier ◽

Jorge Cialzeta ◽

...

Keyword(s):

Heart Failure ◽

Uric Acid ◽

Chronic Heart Failure ◽

Serum Uric Acid ◽

Side Effect ◽

Elevated Serum ◽

Myocardial Damage

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Serum uric acid and risk of incident chronic kidney disease: a national cohort study and updated meta-analysis

Nutrition & Metabolism ◽

10.1186/s12986-021-00618-4 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Nianwei Wu ◽

Jing Xia ◽

Sen Chen ◽

Chuan Yu ◽

Ying Xu ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Uric Acid ◽

Kidney Disease ◽

Cohort Studies ◽

Serum Uric Acid ◽

Meta Analysis ◽

Positive Association ◽

Effect Estimate ◽

Logistic Regression Models ◽

Increased Risk

Abstract Background We prospectively examined the association between serum uric acid (SUA) levels and chronic kidney disease (CKD) in China and updated the evidence through a comprehensive meta-analysis of prospective studies worldwide. Methods Our original analyses were based on data from the China Health and Retirement Longitudinal Study. The primary exposure of interest was SUA at baseline, and the main outcome was incident CKD. Logistic regression models were used to examine the association between SUA levels and incident CKD. A meta-analysis was performed to pool our effect estimate and those from other cohort studies. Results During a 4-year follow-up, 180 participants developed incident CKD. Participants in the highest SUA quartile were 2.73 times as likely to develop incident CKD compared to those in the lowest quartile (multivariable-adjusted OR, 2.73; 95% CI, 1.65–4.50). Each 1 mg/dL increment in the SUA levels was associated with a 49% increased risk of incident CKD (multivariable-adjusted OR, 1.49; 95% CI, 1.28–1.74). In the meta-analysis of 30 cohort studies (including the current study), pooled relative risks (95% CIs) of incident CKD were 1.15 (1.10–1.21) for SUA each 1 mg/dL increment, 1.22 (1.14–1.30) for the highest versus lowest SUA group, and 1.17 (1.12–1.23) for hyperuricemia versus no hyperuricemia. Conclusions Baseline SUA levels were associated with higher risk of incident CKD in middle-aged and elderly Chinese adults, and this positive association was confirmed in the meta-analysis of multiple cohort studies. Our findings may imply that SUA levels need to be routinely monitored for future CKD risk.

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The effect of baseline serum uric acid on chronic kidney disease in normotensive, normoglycemic, and non-obese individuals: A health checkup cohort study

PLoS ONE ◽

10.1371/journal.pone.0244106 ◽

2021 ◽

Vol 16 (1) ◽

pp. e0244106

Author(s):

Young-Bin Son ◽

Ji Hyun Yang ◽

Myung-Gyu Kim ◽

Sang Kyung Jo ◽

Won Yong Cho ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Uric Acid ◽

Risk Factor ◽

Kidney Disease ◽

Serum Uric Acid ◽

Independent Risk Factor ◽

Baseline Serum ◽

Increased Risk ◽

Egfr Decline

Introduction The independent role of serum uric acid (SUA) on kidney disease is controversial due to its association with metabolic syndrome. The objective of this study was to investigate the association of baseline SUA with development of chronic kidney disease and eGFR decline in normotensive, normoglycemic and non-obese individuals during follow up period. Materials and methods We included non-hypertensitive, non-diabetic, and non-obese 13,133 adults with estimated glomerular filtration rate (eGFR) ≥ 60ml/min/1.73m2 who had a voluntary health check-up during 2004–2017. Results SUA was positively related to adjusted means of systolic blood pressure (SBP), triglyceride, body mass index, and body fat percent. SUA was inversely associated with high density lipoprotein HDL (P for trend ≤0.001). SUA was an independent risk factor for the development of diabetes, hypertension, and obesity. During 45.0 [24.0–76.0] months of median follow up, the highest quartiles of SUA showed significant risks of 30% eGFR decline compared than the lowest quartile (RR:3.701; 95% CI: 1.504–9.108). The highest quartile had a 2.2 fold (95% CI: 1.182–4.177) increase in risk for incident chronic kidney disease (CKD). Conclusions SUA is an independent risk factor for the development of diabetes, hypertension, and obesity in the healthy population. High SUA is associated with increased risk of CKD development and eGFR decline in participants with intact renal function.

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