Incidence Of Worsening Renal Function Research Articles

Randomized trial assessing worsening renal function with dapagliflozin addition in acute decompensated heart failure: ROAD-ADHF trial

Abstract Background Dapagliflozin (DAPA), a sodium-glucose co-transporter 2 inhibitor, has shown to reduce cardiovascular mortality in patients with chronic heart failure.1) In addition, DAPA can enhance diuresis in patients with acute decompensated heart failure (ADHF).2) However, there is little known how early initiation of DAPA might impact the worsening renal function (WRF) when combined with standard decongestive therapy for ADHF. Purpose We aimed to evaluate the impact of initiating DAPA within 24 hours after ADHF admission on WRF, compared to standard decongestive therapy with loop diuretics alone. Methods We enrolled consecutive ADHF patients with a left ventricular ejection fraction (LVEF) less than 50%. The patients were prospectively randomized to either the DAPA group who received DAPA at a dose of 10 mg once daily within 24 hours of admission or the conventional therapy group (CON group) who received loop diuretics alone. Furosemide, loop diuretic, dosage was adjusted by increase or decrease of 10 mg to maintain urine output between a 1-2 mL/kg/hour.3) The primary endpoint was the incidence of WRF, which was defined as an increase in the serum creatinine of ≥ 0.3 mg/dL from baseline within 7 days of admission.4) Additionally, right heart catheterization (RHC) was performed before discharge if the consent was obtained. Results From May 2021 to May 2023, we analyzed a total of 114 patients (56 in the DAPA group and 58 in the CON group). The mean age was 73 years, 35% were female, and the mean LVEF was 32.5%. There was no significant difference in the incidence of WRF between two groups (16.1% in the DAPA group vs. 12.1% in the CON group, P=0.54, Figure 1). The cumulative loop diuretics dose over 7 days was lower in the DAPA group than CON group (184 ± 9.64 mg vs. 214 ± 9.81 mg, P=0.03, Figure 2). RHC before discharge was performed in 54 patients (96.4%) in the DAPA group and in 54 (93.1%) in the CON group. There were no significant differences in the pulmonary artery wedge pressure, pulmonary artery pressure, right atrial pressure, and cardiac index by the thermodilution method or the Fick method between two groups. Conclusion This randomized prospective trial revealed the early initiation of DAPA within 24 hours of admission for ADHF reduced loop diuretic demand without inducing WRF compared to standard decongestive therapy.Figure 1Figure 2

Impact of worsening renal function in patients with incident heart failure across the spectrum of ejection fraction: a population-based longitudinal study

Abstract Background Renal dysfunction is a common occurrence in patients with heart failure (HF) and may impact on HF treatment and outcomes. HF clinical trial data suggest that worsening renal function (WRF) is associated with worse prognosis, however many of the medications used in HF cause a short-term decline in renal function that may improve in the longer-term. The real-world incidence and implications of WRF following an initial diagnosis of HF across the spectrum of ejection have not been well-characterised. Purpose The present study was designed to establish the incidence and outcomes associated with WRF in patients with incident HF on the risk of mortality and HF hospitalisation (hHF) in a real-world setting. Methods Electronic health records were linked to echocardiography data between 2016 to 2021 to define incident HF with reduced/mildly reduced/preserved EF (HFrEF/HFmrEF/HFpEF). Incidence of WRF at 6 months was determined as a composite endpoint of (i) having two consecutive eGFR declined by 40% or greater; (ii) having an eGFR <15 mL/min/1.73m^2; (iii) on sustained dialysis; or (iv) receiving kidney transplantation. Incidence of hHF and all-cause mortality were compared in HF patients with versus without WRF. We performed a stratified analysis according to baseline renal function (eGFR: >60, 45-59, 30-44, 15-29, or <15 mL/min/1.73m2). Results 4254 individuals were identified, 1100 HFrEF, 650 HFmrEF, 1252 HFpEF, and 1252 HF with unknown EF. Within 6 months of HF diagnosis, 592 patients died and 349 had WRF. Baseline eGFR <60 was present in 32% of individuals with HFrEF, 32% in HFpEF, 27% in HFmrEF, and 37% in HF with unknown EF. The incidence of WRF was similar in HFrEF (20.7 [95% CI: 16.9 – 25.1] per 100 person-years) and in HF with unknown EF (20.9 [17.1 – 25.3]), but was significantly lower in HFmrEF (13.6 [9.8 – 18.4]) and HFpEF (16.8 [13.7 – 20.5]). Patients with WRF were more likely to be female (adjusted hazard ratio [aHR]: 1.32 [1.06 – 1.64], p=0.014), having diabetes (1.34 [1.07 – 1.69], p = 0.012), and with lower baseline renal function (eGFR categories 45-59, 30-44, 15-29, or <15 compared with >60: aHR 1.75 [1.29 – 2.38], p<0.001; 1.64 [1.12 – 2.42], p=0.012; 5.65 [4.06 – 7.87], p<0.001; 90.74 [63.2 – 130.28], p<0.001). Individuals with WRF had significantly higher incidence of subsequent hHF (HR adjusted for age, sex, baseline renal function, and diabetes: 1.79 [1.35 – 2.39], p<0.001) and all-cause death (2.18 [1.66 – 2.88], p<0.001), compared to those without WRF. This was driven by patients diagnosed with HFrEF (2.46 [1.45 – 4.18], p<0.001) or HFpEF (3.45 [2.21 – 5.40], p<0.001), but was not seen in HFmrEF (1.91 [0.91 – 3.99], p=0.086) or HF within unknown EF (1.28 [0.65 – 2.52], p=0.484). Conclusion WRF is an important and common consequence following initial diagnosis of HF across the spectrum of EF with associated severe clinical outcomes in HF. Priority should be given to prevention of WRF in patients with incident HF.Impact of WRF on Clinical Outcomes

Incidence, Predictors, and Outcomes Associated With Worsening Renal Function in Patients With Heart Failure and Secondary Mitral Regurgitation: The COAPT Trial.

Background The incidence and implications of worsening renal function (WRF) after mitral valve transcatheter edge-to-edge repair (TEER) in patients with heart failure (HF) are unknown. Therefore, the aim of this study was to determine the proportion of patients with HF and secondary mitral regurgitation who develop persistent WRF within 30 days following TEER, and whether this development portends a worse prognosis. Methods and Results In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial, 614 patients with HF and severe secondary mitral regurgitation were randomized to TEER with the MitraClip plus guideline-directed medical therapy (GDMT) versus GDMT alone. WRF was defined as serum creatinine increase ≥1.5× or ≥0.3 mg/dL from baseline persisting to day 30 or requiring renal replacement therapy. All-cause death and HF hospitalization rates between 30 days and 2 years were compared in patients with and without WRF. WRF at 30 days was present in 11.3% of patients (9.7% in the TEER plus GDMT group and 13.1% in the GDMT alone group; P=0.23). WRF was associated with all-cause death (hazard ratio [HR], 1.98 [95% CI, 1.3-3.03]; P=0.001) but not HF hospitalization (HR, 1.47 [ 95% CI, 0.97-2.24]; P=0.07) between 30 days and 2 years. Compared with GDMT alone, TEER reduced both death and HF hospitalization consistently in patients with and without WRF (Pinteraction=0.53 and 0.57, respectively). Conclusions Among patients with HF and severe secondary mitral regurgitation, the incidence of WRF at 30 days was not increased after TEER compared with GDMT alone. WRF was associated with greater 2-year mortality but did not attenuate the treatment benefits of TEER in reducing death and HF hospitalization compared with GDMT alone. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01626079.

Albuminuria predicts worsening renal function after transcatheter aortic valve replacement

BackgroundThe impact of albuminuria on worsening renal function (WRF) and clinical outcomes after transcatheter aortic valve replacement (TAVR) is unknown. MethodsOverall, 142 patients who underwent TAVR for severe aortic stenosis were divided into two groups based on the preoperative urinary albumin-to-creatinine ratio (ACR): high (ACR ≥30 mg/g) and low (ACR <30 mg/g). The incidence of WRF (an absolute increase in serum creatinine level of ≥0.3 mg/dL or ≥1.5-fold from baseline or dialysis initiation) at 6 months after TAVR and the incidence of all-cause death and heart failure readmission during follow-up were investigated. ResultsHalf of the examined patients [n=71/142 (50.0%)] had a high ACR. Patients with a high ACR more frequently had WRF at 6 months than those with a low ACR (17.6% vs. 2.9%, p=0.004). Multivariate analysis showed a high ACR was independently associated with WRF (odds ratio, 7.76; 95% confidence interval, 1.62–37.30; p=0.01), whereas baseline estimated glomerular filtration rate <60 mL/min/1.73m² was not (odds ratio, 0.34; 95% confidence interval, 0.08–1.50; p=0.15). Patients with a high ACR had a higher risk of composite outcomes of all-cause death and heart failure readmission (p=0.002). ConclusionsPreoperative albuminuria (ACR ≥30 mg/g) was independently associated with WRF at 6 months after TAVR. Furthermore, patients with an ACR ≥30 mg/g had higher risks of all-cause death and heart failure readmission than those with an ACR <30 mg/g.

B-type natriuretic peptide trend predicts clinical significance of worsening renal function in acute heart failure.

In acute heart failure (AHF), relationships between changes in B-type natriuretic peptide (BNP) and worsening renal function (WRF) and its prognostic implications have not been fully determined. We investigated the relationship between WRF and a decrease in BNP with in-hospital and 1-year mortality in AHF. The Acute Kidney Injury NGAL Evaluation of Symptomatic heart faIlure Study (AKINESIS) was a prospective, international, multicentre study of AHF patients. Severe WRF (sWRF) was a sustained increase of ≥44.2 μmol/L (0.5mg/dL) or ≥50% in creatinine, non-severe WRF (nsWRF) was a non-sustained increase of ≥26.5μmol/L (0.3mg/dL) or ≥50% in creatinine, and WRF with clinical deterioration was nsWRF with renal replacement therapy, inotrope use, or mechanical ventilation. Decreased BNP was defined as a ≥30% reduction in the last measured BNP compared to admission BNP. Among 814 patients, the incidence of WRF was not different between patients with or without decreased BNP (nsWRF: 33% vs. 31%, P=0.549; sWRF: 11% vs. 9%, P=0.551; WRF with clinical deterioration: 8% vs. 10%, P=0.425). Decreased BNP was associated with better in-hospital and 1-year mortality regardless of WRF, while WRF was associated with worse outcomes only in patients without decreased BNP. In multivariate Cox regression analysis, decreased BNP, sWRF, and WRF with clinical deterioration were significantly associated with 1-year mortality. Decreased BNP was associated with better in-hospital and long-term outcomes. WRF was only associated with adverse outcomes in patients without decreased BNP.

4330Effect of empagliflozin as add-on therapy on decongestion and renal function in diabetic patients hospitalized for acute decompensated heart failure: a prospective randomized controlled study

Abstract Background The mainstay of treatment of acute decompensated heart failure (ADHF) is decongestion by diuretic therapy. Empagliflozin has been shown to reduce the risk of hospitalization for heart failure in patients (pts) with type 2 diabetes mellitus (T2D) and cardiovascular disease. This may be explained by natriuresis and osmotic diuresis caused by empagliflozin, leading to plasma volume (PV) contraction and decongestion. However, little is known about the therapeutic effect of empagliflozin on decongestion and its association with renal function in T2D pts with ADHF. Purpose We sought to elucidate the effect of empagliflozin as add-on therapy on plasma B-type natriuretic peptide (BNP) level, hemoconcentration, PV contraction and renal function in T2D pts with ADHF. Methods We enrolled 38 consecutive T2D pts admitted for ADHF. On admission, enrolled pts were randomly assigned in a 1:1 ratio to either empagliflozin add-on therapy (EMPA(+)) or conventional glucose-lowering therapy (EMPA(−)). All pts in EMPA(+) group received empagliflozin (10mg/day) throughout the study period. Left ventricular ejection fraction (LVEF) was measured at baseline using echocardiography. Body weight and vital signs, such as blood pressure and heart rate, were measured, and blood and urine samples were collected at baseline and 1, 2, 3 and 7 days after randomization. Hemoconcentration was defined as a ≥3% absolute increase in hematocrit (Hct). Percent change in PV between admission and subsequent timepoints (%ΔPV) was calculated using the Strauss formula as follows: %ΔPV = ([(Hb1/Hb2) × ((100 − Hct2)/(100 − Hct1))] − 1) × 100 (%), where 1 = baseline values and 2 = subsequent values. Worsening renal function (WRF) was defined as an increase in serum creatinine ≥0.3 mg/dL above baseline within 7 days of randomization. Results Twenty pts were assigned to the EMPA(+) group, and 18 pts were assigned to the EMPA(−) group. There were no significant baseline differences in LVEF, plasma BNP level, Hct or serum creatinine level between the EMPA(+) and EMPA(−) groups. Seven days after randomization, plasma BNP level was significantly lower in the EMPA(+) group than in the EMPA(−) group (median 213 [IQR 116–360] pg/mL vs 362 [226–776] pg/mL, p=0.0437) and hemoconcentration was more frequently observed in the EMPA(+) group than in the EMPA(−) group (53% vs 12%, p=0.0105). The decrease in %ΔPV was larger in the EMPA(+) group than in the EMPA(−) group 2 days (−8.74±9.92% vs 1.14±14.71%, p=0.0228), 3 days (−11.28±10.65% vs −0.02±14.70%, p=0.0121) and 7 days after randomization (−10.62±14.89% vs 0.97±13.72%, p=0.0211). The incidence of WRF did not significantly differ between the EMPA(+) and EMPA(−) groups (15% vs 22%). Conclusions This study demonstrated that empagliflozin as add-on therapy can achieve effective decongestion without an increased risk of WRF in T2D pts with ADHF.

Hyperkalemia, Worsening Renal Function, Acute Kidney Injury and Clinical Outcomes in Acute Heart Failure

Background Kidney dysfunction and hyperkalemia are commonly observed in heart failure (HF). Their relationship has not been fully investigated in acute HF (AHF), especially in relation to worsening renal function (WRF) and acute kidney injury (AKI). Purpose: We aimed to investigate the relationship between changes in potassium, WRF and AKI and its prognostic implication in AHF. Methods We retrospectively analyzed the AKINESIS, which is a multicenter, prospective cohort study of AHF patients. Levels of serum potassium and creatinine were recorded each day during hospitalization. Urine neutrophil gelatinase-associated lipocalin (NGAL) was measured at admission, 4-hour, day 1, 2, 3 and discharge. Patients were classified into 3 groups; hyperkalemia (> 5mEq/l) on admission, an increasing trend (≤ 5 mEq/l on admission and increased to > 5mEq/l during hospitalization) and non-hyperkalemia (≤ 5 mEq/l during hospitalization). WRF was defined as an increase of ≥ 0.3 mg/dl or ≥ 50% in creatinine. Clinical outcome was one-year mortality. Results Among 912 patients analyzed, hyperkalemia on admission and an increasing trend were observed in 10% and 7.8%, respectively. The incidence of WRF in patients with hyperkalemia on admission, an increasing trend and non-hyperkalemia were 41%, 59% and 27%, respectively (p Conclusions Hyperkalemia was associated with WRF and AKI in AHF. An increase in potassium during hospitalization but not a higher level on admission was associated with poor prognosis independent of WRF and AKI.

Can Tolvaptan Protect Renal Function in the Early Postoperative Period of Cardiac Surgery? - Results of a Single-Center Randomized Controlled Study.

Oral administration of tolvaptan, a vasopressin V2receptor antagonist, significantly reduces deterioration of renal function, which has recently been highlighted as an exacerbating factor for adverse events in patients with acute heart failure. In the present study we tested the hypothesis that concomitant administration of tolvaptan with a conventional diuretic is beneficial for perioperative body fluid management in patients who have undergone cardiac surgery.Methods and Results:In all, 280 patients who underwent cardiac surgery were prospectively randomized to concomitant treatment with tolvaptan and a conventional diuretic (tolvaptan group; 147 patients) or treatment with a conventional diuretic alone (control group; 133 patients). Groups were compared in terms of the time required to restore preoperative body weight and the incidence of worsening renal function (WRF), defined as an increase in the serum creatinine level ≥0.3 mg/dL. The time required to restore preoperative body weight was significantly shorter in the tolvaptan than control group (mean [±SD] 3.97±1.95 vs. 5.02±2.83 days, respectively; P<0.001). The incidence of WRF was significantly lower in the tolvaptan than control group (n=11 [7.5%] vs. n=25 [18.8%], respectively; P=0.011). Administration of tolvaptan with conventional diuretics in the early postoperative period after cardiac surgery could be beneficial in maintaining urine output without affecting renal function and may thus help avoid WRF.

Tolvaptan Reduces the Risk of Worsening Renal Function in Patients With Acute Decompensated Heart Failure and Preserved Left Ventricular Ejection Fraction - Prospective Randomized Controlled Study.

Although the mainstay of treatment for acute decompensated heart failure (ADHF) is decongestion by diuretic therapy, it is often associated with worsening renal function (WRF). The effect of tolvaptan, a selective V2 receptor antagonist, on WRF in ADHF patients with preserved left ventricular ejection fraction (LVEF) is unknown.Methods and Results:We enrolled 50 consecutive ADHF patients whose LVEF on admission was ≥45%. Patients were randomly assigned to either tolvaptan add-on (n=26) or conventional diuretic therapy (n=24). The primary endpoint was the incidence of WRF, defined as an increase in serum creatinine (Cr) ≥0.3 mg/dL or 50% above baseline within 48 h of randomization. There was no significant difference between the 2 groups in the change in body weight or the total urine volume during 48 h. However, the change in Cr (∆Cr) at 24 and 48 h after randomization and the incidence of WRF (12% vs. 42%, P=0.0236) were significantly lower, and the fractional excretion of urea (FEUN) at 24 and 48 h after randomization was significantly higher in the tolvaptan group. There was an inverse correlation between ∆Cr and FEUN at 48 h after randomization. Tolvaptan can alleviate congestion with a significantly lower risk of WRF in ADHF patients with preserved LVEF, presumably through maintenance of renal perfusion.

Cystatin C as Marker of Cardiorenal Syndrome and Poor Prognosis in Patients Hospitalized with Acute Heart Failure and Normal Renal Function

Background: The development of renal dysfunction in patients hospitalized for acute heart failure is known as cardiorenal syndrome type 1 (CRS). Worsening renal function (WRF) during hospitalization is associated with poor prognosis. Cystatin C has emerged as an alternative renal function marker to creatinine.Objective: The aim of this study was to demonstrate the usefulness of cystatin C as predictor of WRF and prognostic factor in patients with acute heart failure and normal renal function assessed by creatinine level on admission.Methods: A prospective, observational study was performed on consecutive patients with acute heart failure and normal renal function defined as serum creatinine <1.3 mg/dL on admission. Cystatin C was measured on admission. The primary endpoint was WRF, and secondary endpoints were in-hospital mortality, total mortality and rehospitalization for heart failure.Results: A total of 166 patients were included in the study. Median age was 85 years (IQR 77.7- 89 years). The incidence of WRF was 29.7%, with in-hospital mortality of 3.1% and total mortality of 24.4%. Median follow-up was 193 days. Serum cystatin C was significantly higher in patients who developed WRF (1.72±0.58 mg/dL vs. 1.51±0.41 mg/dL, p=0.03) and in patients who died during follow up (1.76±0.49 vs. 1.51±0.46, p=0.004). Multivariate analysis showed that cystatin C was an independent predictor of mortality (OR 3.03, 95% CI 1.22-7.47) and WRF (OR 2.38, 95% CI 1.02-5.5). The optimal cystatin C cutoff point was 1.6 mg/dL, with 61.22% sensitivity and 60.34% specificity for the development of WRF, and 61.54% sensitivity and 61.98% specificity for total mortality.Conclusions: Cystatin C on admission is a predictor of in-hospital WRF and increased mortality in this population hospitalized with acute heart failure and preserved renal function.

Abstract 10772: Could Tolvaptan Protect Renal Function in the Early Postoperative Period After Cardiac Surgery?

Introduction: Tolvaptan (TV), a vasopressin V2 inhibitor, has a strong diuretic effect, which is beneficial for body fluid management in patients with acute heart failure (AHF). Several studies have reported that TV significantly reduces worsening renal function (WRF), which has recently been highlighted as an exacerbation factor in the treatment of AHF. We hypothesized that concomitant administration of TV with conventional diuretic treatment is beneficial for perioperative body fluid management in patients who have undergone cardiac surgery. In this study, we prospectively randomized the patients into the TV group, in which TV was administered in addition to conventional diuretics, and the control group, in which the patients received conventional diuretics only. Methods: A total of 176 patients who underwent cardiac surgery were divided into 2 groups, which were the TV group (TV + furosemide, 90 patients) and conventional diuretic treatment group (Control [C], furosemide with or without spironolactone, 86 patients). We compared urine output for 3 days after surgery, the time required to restore the preoperative body weight, and the incidence of WRF between the 2 groups. In the TV group, patients received TV 7.5mg/day orally starting on POD1 and continued to take TV up to POD 5. WRF was defined as a rise in the serum creatinine level (Cr) of ≥0.3 mg/dL. Results: The mean daily urine output from POD1 to POD 3 of the TV group (2672 ± 769 mL/day) was higher than that of the C group (2240 ± 529 mL/day) (p = 0.001). The time required to restore preoperative body weight was shorter in the TV group (3.8 ± 1.4 days) than in the C group (4.8 ± 2.0 days) (p=0.003). While the highest postoperative Cr of the TV group (1.01 ± 0.50 mg/dL) was the same as that of the C group (1.16 ± 0.91 mg/dL) (p=0.25), the incidence of WRF in the TV group (9 patients, 10%) was significantly lower than in the C group (24 patients, 28%) (p=0.007), which might indicate the protective effect of TV against WRF in the patients undergoing cardiac surgery. Conclusions: Administration of TV with conventional diuretics in the early postoperative period after cardiac surgery could be beneficial in maintaining urine output without affecting renal function, which may help to avoid WRF after cardiac surgery.

Renal effects of the angiotensin receptor neprilysin inhibitor LCZ696 in patients with heart failure and preserved ejection fraction.

Increases in serum creatinine with renin-angiotensin-aldosterone system (RAAS) inhibitors can lead to unnecessary discontinuation of these agents. The dual-acting angiotensin receptor neprilysin inhibitor LCZ696 improves clinical outcome patients with heart failure with reduced ejection fraction, and pilot data suggest potential benefit in heart failure with preserved ejection fraction (HFpEF). The effects of LCZ696 on renal function have not been assessed. A total of 301 HFpEF patients were randomly assigned to LCZ696 or valsartan in the PARAMOUNT trial. We studied renal function [creatinine, estimated glomerular filtration rate (eGFR), cystatin C, and urinary albumin to creatinine ratio (UACR)] at baseline, 12 weeks, and after 36 weeks of treatment. Worsening renal function (WRF) was determined as an serum creatinine increase of >0.3 mg/dL and/or >25% between two time-points. Mean eGFR at baseline was 65.4 ± 20.4 mL/min per 1.73 m(2) . The eGFR declined less in the LCZ696 group than in the valsartan group (-1.5 vs. -5.2 mL/min per 1.73 m(2) ; P = 0.002). The incidence of WRF was lower in the LCZ696 group (12%) than in the valsartan group (18%) at any time-point, but this difference was not statistically significant (P = 0.18). Over 36 weeks, the geometric mean of UACR increased in the LCZ696 group (2.4-2.9 mg/mmol), whereas it remained stable in the valsartan group (2.1-2.0 mg/mmol; P for difference between groups = 0.016). In patients with HFpEF, therapy with LCZ696 for 36 weeks was associated with preservation of eGFR compared with valsartan therapy, but an increase in UACR.

Abstract 15174: Higher Plasma Osmolality as an Independent Determinant of In-hospital Worsening Renal Function in Acute Decompensated Heart Failure

Backgrounds: Previous studies showed that worsening renal function (WRF) was associated with poor clinical outcome in acute decompensated heart failure (ADHF) patients. Hyperosmolarity is known to cause direct renal cell injury and decreases in renal blood flow and glomerular filtration rate. In ADHF setting, the plasma osmolality can be changed dramatically. However, the prognostic significance of plasma osmolality for the development of WRF in ADHF patients is unclear. Methods: We examined 320 consecutive ADHF patients who admitted to our institution between January 2013 and January 2014 from prospective registry. Patients who had acute coronary syndrome and without complete data-set at admission were excluded. Finally, 303 patients were divided into two groups according to lower plasma osmolality (below 297 mOsm/kg H2O, the cut-off value based on ROC analysis) or higher plasma osmolality (above 297 mOsm/kg H2O) at admission. WRF was defined as ≥ 0.3 mg/dl increase in serum creatinine from baseline to discharge. Results: During follow-up period (median 21 days, interquartile range 14-29), WRF was occurred in 58 patients (19.6 %). Patients with higher plasma osmolality had significantly higher incidence of WRF compared with those without (32.3% vs 13.6%, P&lt;0.01). Higher plasma osmolality was associated with more use of diuretics, higher serum creatinine level and lower hemoglobin level. There were no significant differences between the two groups in terms of age, sex, body mass index, NYHA functional class, left ventricular ejection fraction (LVEF), blood pressure, etiology of HF, cardiovascular medications other than diuretics, plasma brain natriuretic peptide (BNP) level on admission. Multivariate logistic regression analyses showed that higher plasma osmolality (OR 2.00, 95% CI 1.00-3.98, P=0.049), as well as lower hemoglobin (OR 1.22, 95% CI 1.04-1.42, P=0.012), was an independent determinant of WRF, although other variables including age, sex, serum creatinine level and use of diuretics on admission were not. Conclusions: In patients with ADHF, higher plasma osmolality on admission was an independent predictor of in-hospital WRF, suggesting the measurement of plasma osmolality might be useful for identifying patients at risk for WRF.

Tolvaptan reduces the risk of worsening renal function in patients with acute decompensated heart failure in high-risk population

BackgroundAlthough tolvaptan is a recently approved drug for heart failure and causes aquaresis without affecting renal function, its clinical efficacy for patients with acute decompensated heart failure (ADHF) is yet to be elucidated. Methods and resultsWe conducted a prospective observational study in patients with ADHF and high risk for worsening renal function (WRF). Risk stratification for WRF was done by scoring system. Of 174 patients, 114 patients were included as high-risk population for WRF. Incidence of WRF, urine output within 24h and 48h, and changes in brain natriuretic peptide (BNP) were recorded in 44 patients treated with tolvaptan plus conventional therapy, and 70 patients with only conventional therapy. Urine output at 24h and 48h after admission were both significantly higher in the tolvaptan group (p=0.001 and <0.001, respectively), and changes in BNP were not significantly different (p=0.351). However, the incidence of WRF was significantly lower in the tolvaptan group compared to the conventional group (22.7% vs 41.4%, p=0.045). Logistic regression analysis showed that treatment with tolvaptan was an independent factor for reducing WRF (hazard ratio 0.28, 95% confidence interval; 0.10–0.84; p=0.023). ConclusionIn patients with ADHF with high risk of WRF, treatment with tolvaptan could prevent WRF compared to conventional therapy.

Incidence, clinical predictors, and prognostic impact of worsening renal function in elderly patients with chronic heart failure on intensive medical therapy

Incidence, predictors, and prognostic impact of worsening renal function (WRF) in elderly patients with chronic heart failure (HF) undergoing intensive contemporary medical therapy are unknown. In 566 patients (age 77 ± 8 years) included in the TIME-CHF, serum creatinine (sCr) was repeatedly measured up to 6 months. Worsening renal function was classified as increase in sCr by 0.2 to 0.3 (WRFI), 0.3 to 0.5 (WRFII), or ≥0.5 mg/dL (WRFIII) within the first 6 months. Outcome events were assessed for 18 months. The incidence of WRF I, II, and III was 12%, 19%, and 22%, respectively. Worsening renal function III was associated with increased mortality (hazard ratio 1.98 [95% CI 1.27-3.07, P = .002] vs no WRF), whereas WRF I/II was not. History of renal failure, spironolactone treatment, higher baseline dose, and higher maximal increase in loop diuretic dose were independently associated with the occurrence of WRF III, whereas angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, and β-blocker use and allocation to N-terminal pro-B-type natriuretic peptide-guided management were not. Worsening renal function III was an independent predictor of death, death or hospitalization, and death or HF hospitalization also after adjusting for baseline characteristics. One fifth of elderly patients with chronic HF experienced WRF III on 6-month intensive HF treatment. These patients had higher mortality, whereas patients with smaller sCr rises did not. Occurrence of WRF III was associated with high doses of loop diuretics and spironolactone use but not with other treatments.

Effect of nesiritide on renal function in patients admitted for decompensated heart failure

Studies addressing the effect of nesiritide on renal function in patients hospitalized for decompensated heart failure (HF) are limited, with conflicting results. To study the effect of nesiritide on renal function in patients admitted for acute decompensated HF. We retrospectively reviewed charts of patients admitted with decompensated HF, comparing those who received nesiritide along with conventional therapy vs. those who received conventional therapy alone. Serum creatinine levels and body weight were measured on admission, and were compared with levels at day 3 to estimate deterioration in renal function. Worsening renal function (WRF) was defined as a rise in serum creatinine of > or =0.3 mg/dl from baseline, with final creatinine level >1.5 mg/dl. We reviewed 206 charts (116 controls, 90 nesiritide group). WRF developed in 28/90 (31.1%) in the nesiritide group and 37/116 (31.9%) controls (p = 1.0). Mean change in creatinine in the nesiritide group was 0.15 +/- 0.37 mg/dl, compared to 0.17 +/- 0.25 mg/dl in controls (p = 0.75). Using an alternative cut-off increase in serum creatinine of > or =0.5 mg/dl, 16/90 (17.7%) patients in the nesiritide group developed WRF compared to 18/116 (15.5%) controls (p = 0.80). If WRF was defined as elevation in serum creatinine levels by > or =0.3 mg/dl anytime during hospitalization, the incidence of WRF in the nesiritide group remained similar to that of controls (42.2% vs. 41.3%, p = 0.90). On multivariate analysis, nesiritide therapy was not associated with WRF (OR 0.8, 95% CI 0.4-1.6, p = 0.48). We failed to detect any significant risk of WRF in patients treated with nesiritide compared to conventional therapy in patients with decompensated HF during index hospitalization. Larger randomized, placebo-controlled trials are required to further elucidate the effect of nesiritide on renal function in these patients.

Secular Trends in Renal Dysfunction and Outcomes in Hospitalized Heart Failure Patients

Background Renal dysfunction and worsening renal function (WRF) during heart failure (HF) therapy predict outcomes. We determined whether the severity of renal dysfunction, the incidence of WRF or outcomes have changed over time (secular trends) in patients hospitalized for HF therapy. Methods and Results A total of 6440 consecutive unique patients admitted for HF to Mayo Clinic Hospitals Rochester, MN, January 1, 1987, to December 31, 2002, were identified and data extracted from electronic databases. Over the study period, age and admission creatinine increased, whereas estimated glomerular filtration rate and hemoglobin decreased ( P < .0001 for all). The prevalence of hypertension and diabetes among HF patients also increased over time ( P < .0001). The incidence of WRF was stable. Renal dysfunction and development of WRF were associated with mortality. When adjusted for the changes in baseline characteristics of HF patients, mortality declined over the study period. Conclusion Hospitalized HF patients are increasingly elderly, have a greater prevalence of diseases that lead to renal dysfunction, and have more severe renal dysfunction and anemia on admission. However, adjusting for these secular trends in patient characteristics, mortality after HF admission is improving. These data enhance our understanding of the changing natural history of HF.