Renal Function In Heart Failure Research Articles

Assessment of Biomarkers of Myocardial injury, Inflammation, and Renal Function in Heart Failure With Reduced Ejection Fraction: The VICTORIA Biomarker Substudy

BackgroundCirculating biomarkers may be useful in understanding prognosis and treatment efficacy in heart failure with reduced ejection fraction. In the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial, vericiguat, a soluble guanylate cyclase stimulator, decreased the primary outcome of cardiovascular death or heart failure hospitalization in heart failure with reduced ejection fraction. We evaluated biomarkers of cardiac injury, inflammation, and renal function for associations with outcomes and vericiguat treatment effect. Methods and ResultsHigh-sensitivity cardiac troponin T (hs-cTnT), growth differentiation factor-15 (GDF-15), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and cystatin C were measured at baseline and 16 weeks. Associations of biomarkers with the primary outcome and its components were estimated. Interaction with study treatment was tested. Changes in biomarkers over time were examined by study treatment. One or more biomarkers were measured in 4652 (92%) of 5050 participants at baseline and 4063 (81%) at 16 weeks. After adjustment, higher values of hs-cTnT, growth differentiation factor-15, and interleukin-6 were associated with the primary outcome, independent of N-terminal pro-B-type natriuretic peptide. Higher hs-cTnT values were associated with a hazard ratio per log standard deviation of 1.21 (95% confidence interval 1.14–1.27). A treatment interaction with vericiguat was evident with hs-cTnT and cardiovascular death (P = .04), but not HF hospitalization (P = .38). All biomarkers except cystatin C decreased over 16 weeks and no relationship between treatment assignment and changes in biomarker levels was observed. Conclusionshs-cTnT, growth differentiation factor-15, and interleukin-6 levels were associated with risk of the primary outcome in VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction). Uniquely, lower hs-cTnT was associated with a lower rate of cardiovascular death but not HF hospitalization after treatment with vericiguat.

PS-BPC07-4: RENOPROTECTIVE EFFECTS OF SGLT2 INHIBITORS AND RELATED FACTORS IN CHRONIC HEART FAILURE PATIENTS WITH DIABETES

Objective: Large-scale clinical trials have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors have beneficial effects on not only cardiovascular and renal outcomes but also the preservation of renal function in patients with diabetes mellitus and/or chronic kidney disease. However, the effect of SGLT2 inhibitors on renal function in heart failure remains to be fully elucidated. The present study investigated whether SGLT2 inhibitors exert renoprotective effects in chronic heart failure patients with diabetes, by comparing serial changes in estimated glomerular filtration rate (eGFR) for years before and after SGLT2 inhibitor administration. In addition, if SGLT2 inhibitors had a favorable effect on renal function, we examined what cardiac/hemodynamic and noncardiac factors were involved in its effect. Design and method: Methods: From 83 outpatients with chronic heart failure and type-2 diabetes mellitus taking both SGLT2 inhibitors and loop diuretics, 50 patients whose eGFR levels were continuously measured for more than 6 months both before and after administration of SGLT2 inhibitors were selected. In this longitudinal observational study, eligible patients were retrospectively followed up before and after SGLT2 inhibitor administration. Clinical data such as body weight, blood pressure, heart rate, blood (hematological and biochemical) parameters, echocardiographic parameters, and medical treatment were collected at respective ends of the follow-up periods before and after SGLT2 inhibitor administration. All eGFR values were separately plotted before and after the initiation of treatment with SGLT2 inhibitors along the time course axis and the slope of the linear regression curve was calculated as an annual change in eGFR. Results: The mean follow-up periods before and after SGLT2 inhibitor administration were 2.6 and 1.9 years, respectively. Changing rates of eGFR per year were significantly improved after treatment with SGLT2 inhibitors (mean ± SD, -5.78 ± 7.67 to -0.43 ± 10.81 mL/min/1.73m2/year, p = 0.006). The daily doses of loop diuretics were not altered after SGLT2 inhibitor administration. Body weight decreased and hematocrit and hemoglobin increased by SGLT2 inhibitor administration, but neither change was not associated with the change in eGFR slope before and after SGLT2 inhibitor administration. While, the decrease in inferior vena cava diameter was significantly correlated with the improvement of eGFR decline slope after SGLT2 inhibitor administration (r = -0.428, p = 0.004). Conclusions: This study demonstrated that long-term treatment with SGLT2 inhibitors ameliorated annual decline in eGFR in Japanese patients with chronic heart failure. The observed renoprotective effect may have been mediated by improved venous congestion.

Global warming, renal function and heart failure: a 20-year follow-up study

Abstract Background There is a growing concern about the possible effects of global warming on human health. In HF outpatients, renal function significantly worsens during summer. More specific analyses on the impact of increasing temperatures on body homeostasis are lacking. Purpose We investigated the relationship between the trend of temperatures from 2002 to 2021 and renal function in heart failure (HF) outpatients. Methods All creatinine and estimated glomerular filtration rate (eGFR) values of HF outpatients followed at one tertiary hospital in a Mediterranean area of Spain were retrieved from electronic health records. eGFR was calculated through the CKD-EPI formula. Temperature data from the local municipality were derived from the Meteocat service; as temperatures from the years 2004–2005 were not available, these years were not analysed. Summer was defined as the timespan from June to September included. We calculated average values of creatinine and eGFR during summer and the rest of the same year, considering each patient and each year. Similarly, we averaged temperature values during summer and the rest of the same year. Results We derived 6,307 couples of average creatinine/eGFR values in summer and in the rest of the year from 2,194 patients. Across all the years (2002–2003 and 2006–2021), creatinine was slightly higher in summer than in the rest of the year (1.26 vs. 1.21 mg/dL, p<0.001), and eGFR was lower (65 vs. 67 mL/min/1.73 m2, p<0.001). Temperatures in summer and the rest of the year increased gradually, albeit not linearly, from 2002 to 2021 (Figure 1). The absolute (Δ) and percent changes (Δ%) in median temperatures between summer and the rest of the year increased across years (r=0.149, p=0.001 and r=0.144, p=0.002, respectively), as well as Δ and Δ% of the monthly median of maximal temperatures (r=0.119, p<0.001 and r=0.052, p<0.001, respectively) (Figure 1). The Δ and Δ% temperatures between summer and the rest of the year displayed several significant correlations with Δ and Δ% creatinine and eGFR after adjusting for several variables including age, sex, HF therapies, and creatinine outside of summer (Figure 2). Conclusions Over a 20-year timespan there has been an increase in 1) temperatures in summer and in the rest of the year, and 2) the temperature excursion between summer and the rest of the year. Changes in temperatures between summer and the rest of the year correlated with the magnitude of the decrease in renal function during summer, likely because of worse dehydration with higher temperatures. Therefore, the progressive rise in temperature may have detrimental effects on renal function during summer in HF outpatients. Funding Acknowledgement Type of funding sources: None.

Global warming, renal function and heart failure over 20 years

BackgroundThe impact of increasing temperatures on renal function in heart failure (HF) outpatients has never been specifically analyzed. MethodsWe retrieved creatinine and estimated glomerular filtration rate (eGFR) values of all HF outpatients followed at a HF clinic and temperature data from 2002 to 2021. For each patient and each year we averaged values of creatinine, eGFR and monthly temperatures during summer and the rest of the year. ResultsThe study cohort included 2167 HF patients undergoing 25,865 elective visits, with a median of 14 visits for each patient (interquartile range 7–23). At the first visit, patients (70% men) had an age of 67 ± 13 years, and a left ventricular ejection fraction of 35 ± 14%. Creatinine was 1.25 ± 0.51 mg/dL, and eGFR was 65 ± 25 mL/min/1.73 m2. When pooling together all average values of creatinine and eGFR measured during summer or in the rest of the year, creatinine was significantly higher in summer (difference 0.04, 95% confidence interval [CI] 0.04 to 0.05, p < 0.001), and eGFR was slightly lower (difference − 2.0, 95% CI -2.3 to −1.8, p < 0.001). Temperature rise during summer increased from 2002 to 2021. The absolute (Δ) and percent (Δ%) elevation in temperature during summer displayed independent associations with Δ and Δ% creatinine and eGFR after adjusting for age, sex, plasma creatinine, and HF therapies. ConclusionsThe magnitude of temperature elevation during summer has increased over 20 years. This elevation correlates with the decline in renal function during summer. This might be an example of how global warming is affecting human health.

Soluble ST2 and renal function in ischemic heart failure with atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: None. Soluble ST2 (sST2) is a novel cardiac biomarker whose concentration rises in response to myocardial strain. The aim of this study was to analyse the relationship between soluble ST2 (sST2) level and renal function in heart failure (HF) patients with atrial fibrillation (AF). Methods The study involved 113 (83.2% men) patients with mean age 60.0 [54.0-67.0] years with II-IV functional class (recommendations of the New York Heart Association) is due to ischemic heart disease. Serum levels of N-terminal proBNP (NT-proBNP), sST2, TIMP-1 and Cystatine C (CysC) were quantified by ELISA of 33 patients with HF and AF and 80 patients with HF without AF. Echocardiography was performed according to the American Society of Echocardiography/European Association of Echocardiography recommendations. Estimated glomerular filtration rate (eGFR) was calculated by MDRD formula. Nonparametric Mann-Whitney U-test for independent data, Spearman’s rank correlation and multiple linear regression coefficients were calculated. Results Patients with HF and AF characterized significantly higher concentration of sST2 (1453.2 [1184.3-1945.7] vs 1279.7 [1110.9-1616.6] pg/ml, p = 0.05), as well as the marker of kidney dysfunction CysC (1375 [1111.7-1867.4] vs 1136.4 [955-1386.4] ng/ml, p = 0.02) and was significantly lower eGFR (67.7 [60.6-77.2] vs 79.3 [70.9-88.0] ml/min/1.73m2; p = 0.0002). sST2 correlated with TIMP-1 (r = 0.56; p = 0.004) E/e’ (r = 0.87; p = 0.002), as well as CysC with NT-proBNP (r = 0.56; p = 0.002), with age (r = 0.49; p = 0.009) in patients with HF and AF. At multivariate linear regression analysis, only TIMP-1 (β=0.63) and left atrial volume index (β=0.22) were independently associated with sST2 (R2 = 0.58; p = 0.002). Conclusions In patients with ischemic HF and atrial fibrillation elevation sST2, associated with high level cystatine C and correlated with TIMP-1, E/e’, markers which showed abnormal collagen homeostasis and significant diastolic dysfunction LV. Multivariate analysis shows, that sST2 independently associated with TIMP-1 and LAVi. Further studies are needed to clarify the prognostic role of marker renal function (CysC) and cardiovascular stress (sST2) in ischemic HF patients with atrial fibrillation.

Long-term administration of tolvaptan ameliorates annual decline in estimated glomerular filtration rate in outpatients with chronic heart failure.

Protective effects of tolvaptan against worsening renal function in acute heart failure have been shown. However, long-term effects of its agent on renal function remain to be elucidated. The present study investigated retrospectively whether long-term treatment with tolvaptan exerts renoprotective effects in patients with chronic heart failure, by comparing serial changes in estimated glomerular filtration rate (eGFR) for years before and after tolvaptan administration. From 63 outpatients with chronic heart failure taking diuretics including tolvaptan, 34 patients whose eGFR levels were continuously measured for more than 6months both before and after administration of tolvaptan (average dose, 7.8mg/day at the end of the follow-up period) were selected as eligible for the present analyses. All eGFR values were separately plotted before and after the initiation of treatment with tolvaptan (except hospitalization periods) along the time course axis and the slope of the linear regression curve was calculated as an annual change in eGFR. The mean follow-up periods before and after tolvaptan administration were 1197 and 784days (3.3 and 2.1years), respectively. Changing rates of eGFR per year were significantly ameliorated after treatment with tolvaptan (mean ± SD, -8.02 ± 9.35 to -1.62 ± 5.09mL/min/1.73m2/year, P = 0.001). In echocardiographic parameters, inferior vena cava (IVC) diameter significantly decreased after tolvaptan administration, and the decrease in IVC diameter was correlated with the improvement of eGFR decline slope after administration of tolvaptan (P = 0.0075). This longitudinal observational study indicated that long-term treatment with tolvaptan ameliorated annual decline in eGFR in outpatients with chronic heart failure. Our findings suggest that tolvaptan has a protective effect against chronically worsening renal function in heart failure patients.

LCZ696 and preservation of renal function in heart failure: A meta-analysis of 6 randomized trials.

Patients with heart failure (HF) are prone to combine with renal insufficiency. Recently, LCZ696 has been used in the treatment of HF, but whether LCZ696 is better than angiotensin converting enzyme inhibitors/angiotensin receptor antagonists (ACEI/ARB) in renal protection for HF patients has not been investigated. Therefore, we conducted a meta-analysis focusing on LCZ696 and its role in preservation of renal function in HF patients. Embase, PubMed, the Cochrane Library and ClinicalTrials.gov databases were electronically searched for available randomized controlled trials (RCTs). HF patients taking LCZ696 or ACEI/ARB were assessed for renal adverse events. The last search date was Sep 20, 2019. A total of 14959 patients from 6 trials were included in this meta-analysis. As compared to ACEI/ARB, LCZ696 significantly reduced the risk of renal function deterioration (odds ratio 0.77, 95% confidence interval 0.61-0.97, P = 0.02). In summary, LCZ696 may have superior renal protection in HF patients compared with ACEI/ARB.

Incidence of, Associations With and Prognostic Impact of Worsening Renal Function in Heart Failure With Different Ejection Fraction Categories

There are no studies of long-term worsening renal function (WRF) in heart failure (HF) with different ejection fraction (EF) groups. The aim was to compare incidence of, associations with and prognostic impact of WRF in HF with preserved (HFpEF), mid-range (HFmrEF), and reduced EF (HFrEF). The Swedish Heart Failure Registry (SwedeHF) was merged with the Stockholm Creatinine Measurement (SCREAM) registry 2006 to 2010. The associations between EF and WRF (≥25% decrease in eGFR) and the associations between WRF25-49% and WRF≥50% within year one and subsequent all-cause mortality were all assessed with multiadjusted Cox regression. Of 7,154 patients, 41.6% of HFpEF versus 34.5% and 35.4% of HFmrEF and HFrEF patients developed WRF≥25% during year one. The WRF risk was higher in HFpEF (reference) than in HFmrEF, hazard ratio (95% confidence interval) 0.890 (0.794 to 0.997) and HFrEF 0.870 (0.784 to 0.965). WRF within year one was strongly associated with subsequent long-term mortality in all EF groups, yielding adjusted HRs with WRF25-49% and WRF≥50%: HFpEF, 1.101 (0.913 to 1.328) and 2.096 (1.652 to 2.659), in HFmrEF 1.654 (1.353 to 2.022) and 2.375 (1.807 to 3.122) and in HFrEF 1.212 (1.060 to 1.386) and 1.694 (1.412 to 2.033). In conclusion, the long-term WRF risk was high in HF and highest in HFpEF. WRF was strongly associated with mortality in all EF groups, although in HFpEF only with the most severe WRF.

Augmented Endothelial Specific Cationic Amino Acid Transporter‐1 Expression Prevents Renal Fibrosis and Inflammation and Loss of Renal Function in Heart Failure

INTRODUCTIONIt is now well established that impaired renal function associated with heart failure (HF) increases morbidity and mortality in HF patients. There are no effective treatments to rescue renal function in HF and the precise mechanisms that drive renal injury in HF remain elusive. Transport of L‐arginine via cationic amino acid transporter‐1 (CAT‐1) influences renal nitric oxide bioavailability. We hypothesised that impaired L‐arginine transport via CAT‐1 is central to the development of renal dysfunction in HF.METHODSAdult male 18–26 week old wild‐type mice (WT), transgenic mice with dilated cardiomyopathy (DCM) and double transgenic mice with DCM and endothelial‐specific overexpression of CAT1 (HFCAT‐1) were used (n=8 per group). Transgenic mice with dilated cardiomyopathy (DCM) have cardiac specific overexpression of Mammalian sterile 20‐like kinase‐1 (Mst1) which leads to apoptosis and DCM. The double transgenic HFCAT‐1 mouse model has endothelial specific overexpression of CAT1 driven by the Tie‐2 promotor and cardiac specific overexpression of Mst1. Cardiac and renal function were assessed via echocardiography and via calculating the albumin to creatinine ratio, respectively. Fibrosis was assessed via Masson's trichrome staining. Renal inflammation was assessed via expression of pro‐ and anti‐inflammatory gene expression. Plasma nitrate and nitrite levels were assessed via ELISA. Isolated renal cells from WT mice (n=3) were incubated with CAT1 antisense (2.5 μM) or its scrambled oligonucleotide for a period of 4‐h and then CAT1, collagen III and collagen IV expression were measured by PCR.RESULTSExpression of renal CAT1 was less in DCM mice (by 21%) compared to WT mice (P=0.04) and this was restored in HFCAT1 mice. Urinary albumin/creatinine ratio was greater in DCM mice (by 72%) compared to WT (P=0.04). Urinary albumin/creatinine ratio was normalized in HFCAT1 mice. Renal mRNA expression of Il6 was less in HFCAT‐1 mice than DCM mice (P=0.03). Renal mRNA expression of Il10 was 57% less in DCM mice than in WT mice and this was restored in HFCAT‐1 mice (P&lt;0.05). Renal mRNA expression of Pai1 was greater in DCM mice (by 42%), but not HFCAT‐1 mice, compared to WT mice (P=0.01). Tubulointerstitial and glomerular fibrosis were 89% and 76% greater respectively in DCM mice than in WT mice (P&lt;0.05). Tubulointerstitial and glomerular fibrosis were normalized in HFCAT‐1 mice. CAT1 antisense reduced the expression of CAT1 mRNA in isolated renal cells by 46% and collagen III expression in these cells was 8 fold greater compared to control. Ejection fraction was 33% less in DCM mice than in WT (P&lt;0.01) and this was not restored in HFCAT1 mice (P=0.24).CONCLUSIONRestoration of endothelial specific CAT1 expression normalizes renal inflammation and fibrosis and prevents the loss of GFR in experimental HF.Support or Funding InformationNHMRC Program grant (DK) and Baker Heart and Diabetes Institute Early Career Grant (NR)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Selective abdominal venous congestion induces adverse renal and hepatic morphological and functional alterations despite a preserved cardiac function

Venous congestion is an important contributor to worsening renal function in heart failure and the cardiorenal syndrome. In patients, it is difficult to study the effects of isolated venous congestion on organ function. In this study, the consequences of isolated abdominal venous congestion on morphology and function of the kidneys, liver and heart were studied in a rat model. Twelve sham-operated (SHAM) male Sprague Dawley rats were compared to eleven inferior vena cava-constricted (IVCc) rats for twenty-one weeks. Abdominal venous pressure was significantly higher in the IVCc versus SHAM group (p < 0.0001). Indices of liver and kidney weight, function and morphology, inflammation as well as collagen deposition were significantly increased in the IVCc compared to SHAM group, (p < 0.05). Echocardiographic and hemodynamic parameters were largely unaffected by abdominal venous congestion. In this rat model of isolated abdominal venous congestion, retrogradely conducted glomerular hypertension without a concomitant change in glomerular filtration rate was observed. Adverse short-term hepatic morphological alterations were developed which explain the observed organ function dysfunction. Importantly, cardiac function remained comparable between both groups. This study provides relevant insight in the pathophysiology of abdominal congestion on organ function.

Relation of Renal Function with Left Ventricular Systolic Function and NT-proBNP Level and Its Prognostic Implication in Heart Failure with Preserved versus Reduced Ejection Fraction: an analysis from the Korean Heart Failure (KorHF) Registry.

Background and ObjectivesThe relationship between ejection fraction (EF), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and renal function is unknown as stratified by heart failure (HF) type. We investigated their relation and the prognostic value of renal function in heart failure with preserved ejection fraction (HFpEF) vs. reduced ejection fraction (HFrEF).Materials and MethodsNT-proBNP, glomerular filtration rate (GFR), and EF were obtained in 1,932 acute heart failure (AHF) patients. HFrEF was defined as EF<50%, and renal dysfunction as GFR<60 mL/min/1.73 m2 (mild renal dysfunction: 30≤GFR<60 mL/min/1.73 m2; severe renal dysfunction: GFR<30 mL/min/1.73 m2). The primary outcome was 12-month all-cause death.ResultsThere was an inverse correlation between GFR and log NT-proBNP level (r=−0.298, p<0.001), and between EF and log NT-proBNP (r=−0.238, p<0.001), but no correlation between EF and GFR (r=0.017, p=0.458). Interestingly, the prevalence of renal dysfunction did not differ between HFpEF and HFrEF (49% vs. 52%, p=0.210). Patients with renal dysfunction had higher 12-month mortality in both HFpEF (7.9% vs. 15.2%, log-rank p=0.008) and HFrEF (8.6% vs. 16.8%, log-rank p<0.001). Multivariate analysis showed severe renal dysfunction was an independent predictor of 12-month mortality (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.40–3.11). When stratified according to EF: the prognostic value of severe renal dysfunction was attenuated in HFpEF patients (HR, 1.46; 95% CI, 0.66–3.21) contrary to HFrEF patients (HR, 2.43; 95% CI, 1.52–3.89).ConclusionIn AHF patients, the prevalence of renal dysfunction did not differ between HFpEF and HFrEF patients. However, the prognostic value of renal dysfunction was attenuated in HFpEF patients.

Plasma neutrophil gelatinase-associated lipocalin (NGAL) predicts renal function in hospitalized patients with heart failure

Objective To explore the prognostic value of baseline plasma neutrophil gelatinase-associated the lipocalin(NGAL ) for worsening renal function in heart failure (HF). Methods We consecutively enrolled 396 patients hospitalized with HF and used chronic kidney disease epidemiology collaboration (CKD-EPI) formula to calculate estimated glomerular filtration rate (eGFR). All patients were divided into 2 groups: cardiorenal syndrome (CRS) group [eGFR<60 ml/(min·1.73 m2), n=97] and non-CRS group [eGFR ≥ 60 ml/(min·1.73 m2), n=299], indicators measuring the concentration of NGAL two groups of patients, N-terminal pro-brain natriuretic peptide (NT-proBNP), creatinine, serum urea nitrogen (BUN). Results In correlation analysis, r value between NGAL and NT-proBNP, creatine, BUN was 0.194, 0.527, and 0.433, respectively (P<0.01). The area under the receiver operating characteristic (ROC) curve of NGAL, NT-proBNP, BUN to evaluate worsening renal function was 0.863, 0.681, and 0.828, respectively (P<0.01). Conclusions Plasma NGAL was an independent worsening renal function predictor for hospitalized patients with heart failure. Key words: Lipocalins/ME; Gelatinases/ME; Heart failure/CO/ME; Kidney diseases/CO/ME

Intensification of Medication Therapy for Cardiorenal Syndrome in Acute Decompensated Heart Failure

BackgroundWorsening renal function in heart failure may be related to increased venous congestion, decreased cardiac output, or both. Diuretics are universally used in acute decompensated heart failure, but they may be ineffective and may lead to azotemia. We aimed to compare the decongestive properties of a urine output–guided diuretic adjustment and standard therapy for the management of cardiorenal syndrome in acute decompensated heart failure. Methods and ResultsData were pooled from subjects randomized to the stepwise pharmacologic care algorithm (SPCA) in the CARRESS-HF trial and those who developed cardiorenal syndrome (rise in creatinine >0.3 mg/dL) in the DOSE-AHF and ROSE-AHF trials. Patients treated with SPCA (n = 94) were compared with patients treated with standard decongestive therapy (SDT) that included intravenous loop diuretic use (DOSE-AHF and ROSE-AHF; n = 107) at the time of cardiorenal syndrome and followed for net fluid balance, weight loss, and changing renal function. The SPCA group had higher degrees of jugular venous pressure (P < .0001) at the time of cardiorenal syndrome. The group that received SPCA had more weight change (−3.4 ± 5.2 lb) and more net fluid loss (1.705 ± 1.417 L) after 24 hours than the SDT group (−0.8 ± 3.4 lb and 0.892 ± 1.395 L, respectively; P < .001 for both) with a slight improvement in renal function (creatinine change −0.1 ± 0.3 vs 0.0 ± 0.3 mg/dL, respectively; P = .03). ConclusionsCompared with SDT, patients who received an intensification of medication therapy for treating persisting congestion had greater net fluid and weight loss without being associated with renal compromise.

MECHANISM OF PREDNISONE IN LOWERING URIC ACID IN PATIENTS WITH DECOMPENSATED HEART FAILURE

Recently, several randomized clinical trials (RCTs) demonstrated that corticosteroids could potentiate patients’ renal responsiveness to diuretic without impairing renal function in heart failure (HF). One RCT showed prednisone could lower serum uric acid (SUA) in HF patients with hyperuricemia,

Neprilysin inhibitors preserve renal function in heart failure

Neprilysin inhibitors preserve renal function in heart failure

Novel biomarkers assessing renal function in heart failure: relation to inflammatory status and cardiac remodelling.

Patients with heart failure (HF) have a significant decline of renal function. We investigate the association between novel biomarkers of renal dysfunction and indices of inflammatory status and cardiac remodeling in patients with HF. We enrolled 79 consecutive patients with HF and 79 healthy subjects, adjusted for age and sex. Serum levels of neutrophil gelatinase-associated lipocalin (NGAL), cystatin-C, b-type natriuretic peptide (BNP), tumor necrosis factor alpha (TNFα) and matrix metalloproteinase-9 (MMP-9) were measured by ELISA. Creatinine clearance was estimated using Cockcroft-Gault formula (eCcl). Left ventricular ejection fraction was determined by echocardiography. Patients with HF, compared to healthy subjects, had significantly higher NGAL (p=0.007) and cystatin-C levels (p=0.005). In HF patients, NGAL levels were positively correlated with Creatinine levels (r=0.40, p<0.001), TNFa levels (r=0.43, p<0.001), BNP levels (r=0.36, p=0.003), MMP-9 levels (r=0.37, p=0.02) and inversely correlated with left ventricle ejection fraction (r=-0.23, p=0.045). Interestingly, the association between NGAL and MMP-9 levels was independent from confounders such as age, gender, left ventricle ejection fraction, body mass index, TNFα levels, and BNP levels. Moreover, in HF patients, cystatin-C levels were inversely correlated with eCcl (r=-0.21, p=0.04). Cystatin-C levels were not correlated with TNFa, BNP, MMP-9 levels and with left ventricle ejection fraction (p=NS for all). NGAL is associated with left ventricle ejection fraction, and biomarkers of inflammation and cardiac remodeling in patients with HF. These findings highlight a possible common pathogenetic mechanism of renal dysfunction, inflammatory process and cardiac dysfunction in HF.

Prognostic significance of cardiovascular biomarkers and renal dysfunction in outpatients with systolic heart failure: A long term follow-up study

ObjectiveTo assess whether the prognostic significance of cardiovascular (CV) biomarkers, is affected by renal dysfunction (RD) in systolic heart failure (HF). BackgroundIt is unknown, whether the prognostic significance of CV biomarkers, such as N-terminal-pro-brain-natriuretic-peptide (NT-proBNP), high-sensitive troponin T (hsTNT), pro-atrial natriuretic peptide (proANP), copeptin and pro-adrenomedullin (proADM), is affected by renal function in HF. MethodsClinical data and laboratory tests from 424 patients with systolic HF were collected prospectively. The patients were followed for 4.5years (interquartile range: 2–7.7years). CV biomarkers were analyzed on frozen plasma, and renal function was estimated by the Modification of Diet in Renal Disease (MDRD) formula. Cox proportional hazard models for mortality risk were constructed and tests for interaction between each CV biomarker and RD were performed. ResultsMedian age was 73years (51–83), 29% were female, LVEF was 30% (13–45), 74% were NYHA classes I–II and estimated glomerular filtration rate (eGFR) was 68ml/min/1.73m2 (18–157). A total of 252 patients died. All five biomarkers – log(NT-proBNP) (HR: 2.13, 95% CI: 1.57–2.87:, P<0.001), hsTNT (HR: 3.07, 95% CI: 1.90–4.96 P<0.001), proANP (HR: 1.02, 95% CI: 1.01–1.03, P<0.001), copeptin (HR: 1.02, 95% CI: 1.01–1.03, P=0.008) and proADM (HR: 2.37, 95% CI: 1.66–3.38, P<0.001) – were associated with mortality risk, but not affected by RD (P>0.05 for all interactions). ConclusionEstablished and new CV biomarkers are closely associated with renal function in HF. However, their prognostic significance is not affected by RD, and all CV biomarkers can be used for risk stratification independently of renal function.

Renal Effects of Levosimendan: A Consensus Report

Renal dysfunction is common in clinical settings in which cardiac function is compromised such as heart failure, cardiac surgery or sepsis, and is associated with high morbidity and mortality. Levosimendan is a calcium sensitizer and potassium channel opener used in the treatment of acute heart failure. This review describes the effects of the inodilator levosimendan on renal function. A panel of 25 scientists and clinicians from 15 European countries (Austria, Finland, France, Hungary, Germany, Greece, Italy, Portugal, the Netherlands, Slovenia, Spain, Sweden, Turkey, the United Kingdom, and Ukraine) convened and reached a consensus on the current interpretation of the renal effects of levosimendan described both in non-clinical research and in clinical study reports. Most reports on the effect of levosimendan indicate an improvement of renal function in heart failure, sepsis and cardiac surgery settings. However, caution should be applied as study designs differed from randomized, controlled studies to uncontrolled ones. Importantly, in the largest HF study (REVIVE I and II) no significant changes in the renal function were detected. As it regards the mechanism of action, the opening of mitochondrial KATP channels by levosimendan is involved through a preconditioning effect. There is a strong rationale for randomized controlled trials seeking beneficial renal effects of levosimendan. As an example, a study is shortly to commence to assess the role of levosimendan for the prevention of acute organ dysfunction in sepsis (LeoPARDS).

Renal function in heart failure: a disparity between estimating function and predicting mortality risk

To compare the predictive value of estimated renal function calculated by the Chronic Kidney Disease Epidemiology Collaboration (eGFR(CKD-EPI)), four-variable Modification of Diet in Renal Disease (eGFR(MDRD-4)), and Cockcroft-Gault [estimated creatinine clearance (eCcr)] equation in terms of all-cause mortality in heart failure. Renal function is an important prognostic factor in heart failure. Established methods of estimating renal function are known to under-/overestimate true function in certain settings. A total of 800 systolic heart failure outpatients (mean age 57 ± 11.5 years, 82% male) were studied over a median follow-up of 121 (Q1-Q3: 110-130) months. The highest systematic difference was seen between eCcr and eGFR(MDRD-4) [+12.33 points (mean), 95% limits of agreement -22.35 to 47.01; generalized kappa = 0.36]. eGFR(MDRD-4) and eGFR(CKD-EPI) were the most similar [-4.16 points (mean), 95% limits of agreement -11.56 to 3.25; generalized kappa = 0.74]. Up to 35.4% of patients were reclassified into different estimated glomerular filtration rate (eGFR) categories when comparing eGFR(CKD-EPI) with eCcr and eGFR(MDRD-4). eGFR(CKD-EPI) performed marginally better in terms of predicting all-cause mortality than eGFR(MDRD-4), as univariate areas under the time-dependent receiver operating characteristic curves (AUC), marginal and partial proportions of explained variation (PEV), net reclassification improvement (NRI), and the integrated discrimination improvement (IDI) for 5 years of follow-up were significantly higher for eGFR(CKD-EPI) than for eGFR(MDRD-4). In this cohort of heart failure patients, eGFR(CKD-EPI) was marginally better in predicting all-cause mortality than eGFR(MDRD-4). Estimated function differed widely between equations and is likely to have an effect on therapy choice.

Venous congestion and renal function in heart failure … it's complicated

Venous congestion and renal function in heart failure … it's complicated