Timing of Worsening Renal Function in Patients Hospitalized for Heart Failure Exacerbation Who Were Being Treated With Intravenous Diuretic Therapy.

BACKGROUND: This retrospective observational study investigated the incidence of worsening renal function (WRF) in patients hospitalized for heart failure (HF) and treated with intravenous diuretics in Japan. METHODS AND RESULTS: Associations between WRF at any point and HF treatments, and the effects of WRF on outcomes were evaluated (Diagnosis Procedure Combination database). Of 1,788 patients analyzed (mean [±SD] age 80.5±10.2 years; 54.4% male), 641 (35.9%) had WRF during a course of hospitalization for worsening HF: 208 (32.4%) presented with WRF before admission (BA-WRF; estimated glomerular filtration rate decreased by ≥25% from baseline at least once between 30 days prior to admission and admission); 44 (6.9%) had WRF that persisted before and after admission (P-WRF); and 389 (60.7%) had WRF develop after admission (AA-WRF). Delayed initial diuretic administration, higher maximum doses of intravenous diuretics during hospitalization, and diuretic readministration during hospitalization were associated with a significantly higher incidence of AA-WRF. Patients with WRF at any time point were at higher risk of death during hospitalization compared with patients without WRF, with adjusted hazard ratios of 3.56 (95% confidence interval [CI] 2.23-5.69) for BA-WRF, 3.23 (95% CI 2.21-4.71) for AA-WRF, and 13.16 (95% CI 8.19-21.15) for P-WRF (all P<0.0001). CONCLUSIONS: Forty percent of WRF occurred before admission for acute HF; there was no difference in mortality between patients with BA-WRF and AA-WRF.

Abdominal obesity is associated with increased worsening renal function risk in patients with heart failure with preserved ejection fraction.

BACKGROUND: Worsening renal function (WRF) is a frequent comorbidity of heart failure with preserved ejection fraction (HFpEF). However, its relationship with abdominal obesity in terms of HFpEF remains unclear. This study aimed to evaluate the value of waist circumference (WC) and body mass index (BMI) in predicting WRF and examine the correlation between abdominal obesity and the risk of WRF in the HFpEF population. METHODS: Data were obtained from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial. Abdominal obesity was defined as WC ≥ 102 cm for men and ≥ 88 cm for women. WRF was defined as doubling of serum creatinine concentration from baseline. Restricted cubic splines and receiver operating characteristic curves were used to evaluate the value of WC and BMI in predicting WRF. Cumulative incidence curves and cox proportional-hazards models were used to compare patients with and without abdominal obesity. RESULTS: We included 2,806 patients with HFpEF in our study (abdominal obesity, n: 2,065). Although baseline creatinine concentrations did not differ, patients with abdominal obesity had higher concentrations during a median follow-up time of 40.9 months. Unlike BMI, WC exhibited a steady linear association with WRF and was a superior WRF predictor. Patients with abdominal obesity exhibited a higher risk of WRF after multivariable adjustment (hazard ratio: 1.632; 95% confidence interval: 1.015-2.621; P: 0.043). CONCLUSIONS: Abdominal obesity is associated with an increased risk of WRF in the HFpEF population. TRIAL REGISTRATION: URL: https://beta. CLINICALTRIALS: gov . Unique identifier: NCT00094302.

Renal resistive index in patients supported with a durable continuous flow left ventricular assist device.

BACKGROUND: The impact of continuous flow resulting from contemporary left ventricular assist devices (LVAD) on renal vascular physiology is unknown. Renal resistive index (RRI) reflects arterial compliance, as well as renal vascular resistance, contributed by afferent and efferent arteriolar tone, the renal interstitium as well as renal venous pressures. METHODS: Prospective, single center study with renal Doppler evaluation at baseline (pre-implant) and at 3-months support. Outcomes assessed include need for post-operative renal replacement therapy (RRT), worsening renal function (WRF) defined as persistent increase from pre-implant KDIGO chronic kidney disease stage, right ventricular (RV) failure, and survival to transplantation. RESULTS: Pre-implant RRI did not predict cardiorenal outcomes including right heart failure, need for renal replacement therapy or worsening renal function. Post-implant RRI was significantly lower than pre-implant RRI, with a distinct Doppler waveform characteristic of continuous flow. Post-implant renal end-diastolic velocity, but not RRI, correlated strongly with LVAD flow (Spearman rho -0.99, p < 0.001), with trend toward correlation with mean arterial pressure (Spearman's rho 0.63, p = 0.129). There was a negative correlation between post-implant RRI and mean pulmonary artery pressure (Spearman's rho -0.81, p = 0.049), likely driven by elevated pulmonary capillary wedge pressure (Spearman's rho -0.83, p = 0.058). CONCLUSION: The hemodynamic contributors to RRI in LVAD supported patients are complex. Higher mean pulmonary artery and pulmonary capillary wedge pressures seen in lower RRI may reflect a smaller difference in systolic and diastolic flow. Future simultaneous Doppler assessment of the LVAD outflow graft and RRI may help understand the hemodynamic interactions contributing to this index.

Changes in estimated glomerular filtration rate before and after the first visit for atrial fibrillation.

BACKGROUND: Although the development of atrial fibrillation (AF) and the progression of chronic kidney disease are known to be interrelated, it remains unclear when and how renal function changes during the clinical course of AF. METHODS: This study retrospectively enrolled 131 patients who were able to collect data on estimated glomerular filtration rate (eGFR) at least five times during the 500 days before and 500 days after the first visit (baseline) of new-onset AF, respectively. To investigate the temporal relationship between the development of AF and the beginning of worsening renal function (WRF), a piecewise regression model was applied to the eGFR time series data. The time point at which the slopes of the two regression lines changed (inflection -point), the slope before and after the inflection-point (ß1 and ß2, respectively), and the difference in slope (Δß) were estimated. The presence of WRF was defined as having the inflection-point at which both Δß and ß2 were < - 0.0083 mL/min/1.73 m2/day (corresponding to 3.03 mL/min/1.73 m2/year), and the corresponding the inflection-point was defined as the beginning of WRF. RESULTS: WRF was detected in 54 (41.2%) patients. The beginning of WRF were distributed at various times, but most frequently (23 of 54 patients) within 100 days before and after baseline. The presence of WRF was not associated with age, heart failure, or baseline eGFR, but was associated with positive ß1 (odds ratio 30.5, 95% confidence interval 11.1-83.9, P < 0.01). CONCLUSION: In nearly half of AF patients with WRF, the beginning of WRF was observed within a few months before or after the first visit for AF. Patients with a positive eGFR slope before the onset of AF are more likely to develop WRF after the onset of AF, suggesting that potential kidney damage may be underlying.

Renal function and decongestion with acetazolamide in acute decompensated heart failure: the ADVOR trial.

BACKGROUND AND AIMS: In the ADVOR trial, acetazolamide improved decongestion in acute decompensated heart failure (ADHF). Whether the beneficial effects of acetazolamide are consistent across the entire range of renal function remains unclear. METHODS: This is a pre-specified analysis of the ADVOR trial that randomized 519 patients with ADHF to intravenous acetazolamide or matching placebo on top of intravenous loop diuretics. The main endpoints of decongestion, diuresis, natriuresis, and clinical outcomes are assessed according to baseline renal function. Changes in renal function are evaluated between treatment arms. RESULTS: On admission, median estimated glomerular filtration rate (eGFR) was 40 (30-52) mL/min/1.73 m². Acetazolamide consistently increased the likelihood of decongestion across the entire spectrum of eGFR (P-interaction = .977). Overall, natriuresis and diuresis were higher with acetazolamide, with a higher treatment effect for patients with low eGFR (both P-interaction < .007). Acetazolamide was associated with a higher incidence of worsening renal function (WRF; rise in creatinine ≥ 0.3 mg/dL) during the treatment period (40.5% vs. 18.9%; P < .001), but there was no difference in creatinine after 3 months (P = .565). This was not associated with a higher incidence of heart failure hospitalizations and mortality (P-interaction = .467). However, decongestion at discharge was associated with a lower incidence of adverse clinical outcomes irrespective of the onset of WRF (P-interaction = .805). CONCLUSIONS: Acetazolamide is associated with a higher rate of successful decongestion across the entire range of renal function with more pronounced effects regarding natriuresis and diuresis in patients with a lower eGFR. While WRF occurred more frequently with acetazolamide, this was not associated with adverse clinical outcomes. CLINICALTRIALS.GOV IDENTIFIER: NCT03505788.

Relationship between early drop in systolic blood pressure, worsening renal function, and in-hospital mortality in patients with heart failure: a retrospective, observational study.

This study aimed to determine the optimal cut-off value of the early drop in systolic blood pressure (SBP) for worsening renal function (WRF) in hospitalized patients with heart failure (HF) and analyze predictors of WRF and the early drop in SBP at that threshold. We retrospectively enrolled 396 patients with acute decompensated HF. The early drop in SBP was defined as the difference between baseline and SBP measured 24 h after hospitalization. We performed receiver operating characteristic (ROC) analysis to determine the optimal cut-off value of the early drop in SBP for WRF and evaluated the effect of the early drop in SBP on in-hospital mortality by multivariate logistic regression analyses. The mean age of the patients was 73.4 ± 14.7 years, and 61.2% were men. A 14.0% drop in SBP was identified as the optimal cut-off value for WRF from the ROC curve analysis. An early drop in SBP ≥ 14.0% was associated with WRF in multivariate logistic regression analysis (odds ratio 7.84; 95% confidence interval 4.06-15.14; P < 0.0001). The dose of intravenous furosemide within 24 h of admission was one of the predictors of the early drop in SBP ≥ 14.0%, while no early drop in SBP was a predictor of in-hospital mortality in multivariate logistic regression models. In conclusion, the optimal cut-off value for WRF in patients with HF was a 14.0% drop in SBP within 24 h of admission. The early drop in SBP ≥ 14.0% was one of the predictors of WRF in patients with HF. However, no early drop in SBP was associated with in-hospital mortality. This study was registered with the University Hospital Medical Information Network in Japan (UMIN000035989).

Admission free-fatty acid level is a predictor of the mid-term worsening renal function in patients with ST-segment elevation myocardial infarction.

Whether free fatty acids (FFAs), which are generators of reactive oxygen species and substrates of cytotoxic lipid peroxidation products in proximal tubules of the kidney, can be a predictor of worsening renal function (WRF) is not fully elucidated. A total of 110 patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention within 24 h after symptom onset were included. The exclusion criteria were out-of-hospital cardiac arrest, vasospastic angina, hemodialysis, and/or lack of data. FFAs and serum cystatin C were measured on admission, and urinary liver-type fatty acid-binding protein (L-FABP) was measured 3 h after admission. WRF, defined as an increase in serum creatinine by ≥ 0.3 mg/dL for 2-year follow-up, was observed in 16 patients (15%). A multivariate logistic regression analysis (a stepwise algorithm) revealed that the FFA level was an independent predictor of WRF (P = 0.024). The FFA level was associated with WRF adjusted after serum cystatin C (odds ratio [OR]: 1.378 per 1 mEq/L, P = 0.017), L-FABP (OR: 1.370 per 1 mEq/L, P = 0.016), or the Mehran contrast-induced nephropathy (CIN) risk score (OR: 1.362 per 1 mEq/L, P = 0.021). The FFA level was inversely associated with the change in estimated glomerular filtration rate level for 2 years (R2 = 0.051, P = 0.018). The FFA level on admission was associated with the mid-term WRF in patients with STEMI.

Efficacy of tolvaptan on advanced chronic kidney disease with heart failure: a randomized controlled trial.

BACKGROUND: Tolvaptan (TLV) is reported to improve diuretic effects in patients with chronic kidney disease (CKD) when furosemide (FUR) is not sufficiently effective. However, it is not clear whether TLV addition is effective for advanced CKD patients with heart failure. METHODS: An open-label, parallel-group randomized trial was performed. The subjects were 33 patients with CKD stage G3-G5 who had fluid overload despite taking 20-100 mg/day FUR. They were divided into two groups: a group administered 15 mg/day TLV plus their original FUR dose for 7 days (TLV group), and a group administered 120-200 mg/day FUR (i.e., 100 mg/day over their previous dose) for 7 days (FUR group). RESULTS: The mean change in urine volume was significantly higher in the TLV group compared to the FUR group (637 ml vs 119 ml; p < 0.05). The difference was greater when the urine osmolality before treatment was high. Serum creatinine was increased only in the FUR group. The incidence of worsening renal function (WRF) was significantly lower in the TLV group (18.8% vs 58.8%; p < 0.05). Serum sodium decreased significantly in the FUR group, but did not change in the TLV group. CONCLUSIONS: In patients with advanced CKD with fluid overload, the addition of TLV achieved a significantly higher urine volume with less adverse effects on renal function compared with increasing the dose of FUR. The efficacy and safety of TLV were higher in patients who had higher urine osmolality and lower serum sodium before treatment. CLINICAL TRIAL REGISTRATION: UMIN000014763.

Potential Utility of Cardiorenal Biomarkers for Prediction and Prognostication of Worsening Renal Function in Acute Heart Failure.

BACKGROUND: Multiple different pathophysiologic processes can contribute to worsening renal function (WRF) in acute heart failure. METHODS AND RESULTS: We retrospectively analyzed 787 patients with acute heart failure for the relationship between changes in serum creatinine and biomarkers including brain natriuretic peptide, high sensitivity cardiac troponin I, galectin 3, serum neutrophil gelatinase-associated lipocalin, and urine neutrophil gelatinase-associated lipocalin. WRF was defined as an increase of greater than or equal to 0.3 mg/dL or 50% in creatinine within first 5 days of hospitalization. WRF was observed in 25% of patients. Changes in biomarkers and creatinine were poorly correlated (r ≤ 0.21) and no biomarker predicted WRF better than creatinine. In the multivariable Cox analysis, brain natriuretic peptide and high sensitivity cardiac troponin I, but not WRF, were significantly associated with the 1-year composite of death or heart failure hospitalization. WRF with an increasing urine neutrophil gelatinase-associated lipocalin predicted an increased risk of heart failure hospitalization. CONCLUSIONS: Biomarkers were not able to predict WRF better than creatinine. The 1-year outcomes were associated with biomarkers of cardiac stress and injury but not with WRF, whereas a kidney injury biomarker may prognosticate WRF for heart failure hospitalization.

Worsening Renal Function during Index Hospitalization Does Not Predict Prognosis in Heart Failure with Preserved Ejection Fraction Patients.

INTRODUCTION: Worsening renal function (WRF) predicts poor prognosis in patients with left ventricular systolic dysfunction. The effect of WRF in heart failure with preserved ejection fraction (HFpEF) is unclear. OBJECTIVE: The objective of this study was to determine whether WRF during index hospitalization for HFpEF is associated with increased death or readmission for heart failure. METHODS: National Veterans Affairs electronic medical data recorded between January 1, 2002, and December 31, 2014, were screened to identify index hospitalizations for HFpEF using an iterative algorithm. Patients were divided into 3 groups based on changes in serum Cr (sCr) during this admission. WRF was defined as a rise in sCr ≥0.3 mg/dL. Group 1 had no evidence of WRF, group 2 had transient WRF, and group 3 had persistent WRF at the time of discharge. RESULTS: A total of 10,902 patients with index hospitalizations for HFpEF were identified (mean age 72, 97% male). Twenty-nine percent had WRF during this hospital admission, with 48% showing recovery of sCr and 52% with no recovery at discharge. The mortality rate over a mean follow-up duration of 3.26 years was 72%. Compared to group 1, groups 2 and 3 showed no significant difference in risk of death from any cause (hazard ratio [HR] = 0.95 [95% confidence interval [CI]: 0.87, 1.03] and 1.02 [95% CI: 0.93, 1.11], respectively), days hospitalized for any cause (incidence density ratio [IDR] = 1.01 [95% CI: 0.92, 1.11] and 1.01 [95% CI: 0.93, 1.11], respectively), or days hospitalized for heart failure (IDR = 0.94 [95% CI: 0.80, 1.10] and 0.94 [95% CI: 0.81, 1.09], respectively) in analyses adjusted for covariates affecting renal function and outcomes. CONCLUSIONS: While there is a high incidence of WRF during index hospitalizations for HFpEF, WRF is not associated with an increased risk of death or hospitalization. This suggests that WRF alone should not influence decisions regarding heart failure management.

Worsening renal function after transcatheter aortic valve replacement and surgical aortic valve replacement.

Several prior reports have investigated worsening renal function around transcatheter aortic valve replacement (TAVR) procedures. However, in clinical practice, it seems more important to evaluate changes associated with TAVR-related procedures, including preoperative enhanced computed tomography (CT), as well as the TAVR procedure itself, as CT assessment is considered essential for safe TAVR. This study evaluated worsening renal function during the TAVR perioperative period, from the preoperative enhanced CT to 1 month after TAVR, and then compared the incidence with that in patients undergoing surgical aortic valve replacement (SAVR). This retrospective single-center study investigated 123 TAVR patients and 130 SAVR patients. We evaluated baseline renal function before enhanced CT in TAVR patients and before operation in SAVR patients, and again at 1 month post-operatively. We defined worsening renal function at 1 month according to three definitions: (1) an increase in serum creatinine ≥ 0.3 mg/dL or ≥ 1.5-fold from baseline or initiation of dialysis, (2) a decline in eGFR at 1 month ≥ 20% from baseline or initiation of dialysis, (3) a decline in eGFR at 1 month ≥ 30% from baseline or initiation of dialysis. TAVR patients were significantly older and had higher surgical risk scores than SAVR patients. In TAVR patients, serum creatinine levels were 1.00 ± 0.32 mg/dL at baseline and 1.01 ± 0.40 mg/dL at 1 month post-operatively (p = 0.58), while in SAVR patients, these levels were 0.99 ± 0.51 mg/dL and 0.98 ± 0.49 mg/dL, respectively (p = 0.59). In TAVR patients, 7 (5.7%), 14 (11.4%), and 3 (2.4%) patients experienced worsening renal function according to the three definitions, respectively, but there were no significant differences from those in SAVR patients, for any definition. Worsening renal function after TAVR was uncommon, and the incidence rate was comparable to that in SAVR patients, even though TAVR patients had worse baseline characteristics.

Worsening renal function during hospitalization in elderly patients with heart failure: an independent factor of activities of daily living decline.

This study aimed to clarify the effects of worsening renal function (WRF) during hospitalization on activities of daily living (ADL) at discharge of elderly heart failure (HF) patients. We included 323 consecutive patients hospitalized for HF who were prescribed phase I cardiac rehabilitation (CR) from November 2017 to April 2019. WRF was defined as a relative increase from baseline in serum creatinine of 25% or that in serum creatinine ≥ 0.3 mg/dL during hospitalization. The indices of ADL and physical function were the functional independence measure (FIM), short physical performance battery (SPPB) and 10-m comfortable gait speed as assessed at discharge. We compared background factors, clinical parameters, walking level before hospitalization, physical function, and FIM in two groups. Multiple regression analysis was performed with FIM at discharge as the dependent variable and items with P < 0.05 in bivariate correlation as independent variables. Ultimately, 160 patients were included and divided into the WRF group (n = 72) and non-WRF group (n = 88). FIM, SPPB, and 10-m comfortable walking speed were significantly lower in the WRF group. Moreover, even after adjustment for confounding factors (age, Hb, eGFR, CKD, GNRI, start day of standing), eGFR on admission (ß = 0.12), WRF (ß = - 6.42) and walking level before hospitalization (ß = - 10.00) were independent factors of ADL decline at discharge (adjusted R2 = 0.46). WRF during hospitalization of elderly HF patients was a factor affecting ADL decline at discharge along with walking level before hospitalization and renal function at admission.

Combined evaluation of plasma B-type natriuretic peptide and urinary liver-type fatty acid-binding protein/creatinine ratio is related to worsening renal function in patients undergoing elective percutaneous coronary intervention.

BACKGROUND: There are few reports on the significance for the combined evaluation of blood humoral factors and urinary biomarkers in terms of worsening renal function (WRF) after coronary angiography (CAG)/percutaneous coronary arterial intervention (PCI). METHOD AND RESULTS: Urinary liver type-fatty acid-binding protein (L-FABP), neutrophil gelatinase associated lipocalin (NGAL), and adrenomedullin (AM) were measured less than 24 h before and 3 h, 6 h, 1 day, and 2 days after CAG/PCI. WRF was defined as a > 20% decrease in the estimated GFR. WRF occurred in seven of 100 patients and the increase in L-FABP/creatinine (Cr) at 1 day after CAG/PCI was significantly higher in the WRF group than in the non-WRF group. Plasma B-type natriuretic peptide (BNP) before CAG/PCI and L-FABP/Cr at 1 day after CAG/PCI were independent predictors for WRF. The areas under the receiver-operating characteristic curves were as follows: 0.760 for BNP before CAG/PCI, 0.731 for L-FABP/Cr at 1 day after CAG/PCI, and 0.892 for BNP and L-FABP/Cr. Urinary AM levels after PCI/CAG were negatively correlated only to serum potassium levels. Gene expressions of AM and AM-receptor were detectable in renal tubule epithelial cells. AM increased intracellular second messenger levels in a dose-dependent manner. CONCLUSIONS: Our results suggest that combined evaluation of plasma BNP and urinary L-FABP/Cr is useful as a predictor of renal dysfunction in CAG/PCI patients.

Impact of worsening renal function on peak oxygen uptake in patients with acute myocardial infarction.

AIM: Worsening renal function (WRF) induced by acute myocardial infarction (AMI) is a strong predictor of cardiovascular events and mortality. Peak oxygen uptake may contribute to prognosis in AMI patients with WRF, however, the impact of WRF on peak oxygen uptake is unclear. METHODS: Among 154 patients with AMI who underwent emergency percutaneous coronary intervention and participated in phase II cardiac rehabilitation, those who underwent cardiopulmonary exercise testing were consecutively enrolled. WRF was defined as a ≥20% decrease in estimated glomerular filtration rate (eGFR [ml/min/1.73 m2 ]) from admission to that at cardiopulmonary exercise testing. The association of WRF with peak oxygen uptake was evaluated by multivariate regression analysis. The non-WRF group was divided into two subgroups according to eGFR <60/≥60 at cardiopulmonary exercise testing, and eGFR at cardiopulmonary exercise testing and peak oxygen uptake of all three groups were compared. RESULTS: Ninety-four patients were enrolled in the final analysis. Multiple linear regression analysis showed that WRF was associated with peak oxygen uptake (p = .003). Comparing the non-WRF group with eGFR at cardiopulmonary exercise testing <60 and the WRF group, although eGFR at cardiopulmonary exercise testing was similar (p = 1.000), peak oxygen uptake in the WRF group was significantly lower (p = .026). CONCLUSION: WRF, not eGFR at cardiopulmonary exercise testing was significantly associated with peak oxygen uptake in patients with AMI. This result suggests that when considering the relationship between renal function and peak oxygen uptake, WRF must be taken into account.

Renal outcomes of idiopathic and atypical membranous nephropathy in adult Chinese patients: a single center retrospective cohort study.

BACKGROUND: Membranous nephropathy (MN) is mainly classified into idiopathic MN (iMN) and secondary MN in etiology. In recent years, a new kind of membranous nephropathy, atypical membranous nephropathy (aMN) which shows "full house" in immunofluorescence but without definite etiology was paid more attention. In a single center cohort, the renal outcomes of iMN and aMN were compared. METHODS: iMN and aMN patients were selected from renal pathology databank from January 2006 to December 2015. Patients' demographics, laboratory values, induction regimens and patients' responses were recorded. Specially, creatinine, eGFR, albumin and 24 h urinary protein excretion were recorded at 6th month after the induction of immunosuppressive (IS) treatment and at the end of follow up. Complete proteinuria remission was defined as urinary protein < 0.3 g/d, partial proteinuria remission was defined as urinary protein between 0.3 g/d ~ 3.5 g/d and decreased > 50 % from the baseline. The primary outcome was worsening renal function, defined as a 30 % or more decrease in eGFR or end-stage renal disease (eGFR < 15ml/min/1.73m2). COX proportional hazard models were used to test if aMN was a risk factor of worsening renal function compared with iMN. RESULTS: There were 298 patients diagnosed with MN and followed in our center for 1 year or more, including 145 iMN patients with an average follow-up time of 4.5 ± 2.6 years, and 153 aMN patients with 4.1 ± 2.0 years (p = 0.109). The average age of iMN patients was older than aMN patients (56.1 ± 12.2 versus 47.2 ± 16.2 years old, p < 0.001). There were 99 iMN patients and 105 aMN patients with nephrotic range proteinuria and without previous immunosuppressive treatment. 93 (93.9 %) and 95 (90.5 %) patients underwent immunosuppressive treatment in iMN and aMN group, and there was no significant difference of the overall proteinuria remission rates at 6th month (59.1 % vs. 52.0 %, p = 0.334) and endpoint (73.7 % vs. 69.5 %, p = 0.505) between the two groups. 25 (25.3 %) patients in iMN group and 21 (20.0 %) patients in aMN group reached primary endpoint (X2 = 0.056, p = 0.812). Multivariate COX regression showed that after demographics, baseline laboratory values and remission status at 6th month were adjusted, aMN group had similar renal outcome compared with iMN group, the HR of primary outcome was 0.735 (95 % CI 0.360 ~ 1.503, p = 0.399). CONCLUSIONS: The proteinuria remission rates and renal outcomes were similar in iMN and aMN patients after covariables were adjusted.

Any heart failure treatments associated with worsening renal function in patients admitted due to acute heart failure?

BACKGROUND: Worsening renal function (WRF) occurs in approximately 25% of acute heart failure patients, and both baseline characteristics and heart failure treatment may increase the risk of WRF. This study aimed to evaluate additional risk factors for WRF in acute heart failure, particularly those related to heart failure treatment. METHODS: This was a retrospective, observational, analytical study. The inclusion criteria were age 18 years or over, hospital admission due to acute heart failure, and having undergone at least two serum creatinine tests during admission. The eligible patients were classified into two groups: WRF and non-WRF. Predictors for WRF (including treatment parameters) were determined using logistic regression analysis. RESULTS: During the study period, there were 301 eligible patients who met the study criteria. Of those, 82 (27.24%) had WRF. There were two independent factors associated with WRF occurrence: baseline diastolic blood pressure and beta blocker treatment, with adjusted odds ratios (95% confidence interval) of 1.060 (1.008, 1.114) and 0.064 (0.006, 0.634), respectively. The Hosmer-Lemeshow Chi square for the final model was 6.11 (p = .634). CONCLUSIONS: After examining several heart failure treatments and baseline factors, we found that beta blocker treatment results improvement in kidney function.

Effect of Loop Diuretics on the Fractional Excretion of Urea in Decompensated Heart Failure.

BACKGROUND: Fractional excretion of urea (FEUrea) is often used to understand the etiology of acute kidney injury (AKI) in patients receiving diuretics. Although FEUrea demonstrates diagnostic superiority over fractional excretion of sodium (FENa), clinicians often assume FEUrea is not affected by diuretics. OBJECTIVE: To assess the intravenous loop diuretic effect on FEUrea. METHODS: We analyzed a prospective cohort (n=297) hospitalized with hypervolemic heart failure at Yale New Haven Hospital System. FENa and FEUrea were calculated at baseline and serially after diuretics. The change in FEUrea at peak diuresis was compared with the pre-diuretic baseline. RESULTS: Mean baseline FEUrea was 35.2% ± 10.5% and increased by a mean 5.6% ± 10.5% following 80 mg (40-160 mg) of furosemide equivalents (P < .001). The magnitude of change in FEUrea was clinically important as the distribution of change in FEUrea was similar to the overall distribution of baseline FEUrea. Change in FEUrea was related to the diuretic response (r = 0.61, P < .001), with a larger FEUrea increase in diuretic responders (8.8%, interquartile range [IQR]: 1.8-16.9) than non-responders (1.2%, IQR: -3.2 to 5.5; P < .001). Diuretic administration reclassified 27% of patients between low and high FEUrea groups across a 35% threshold. Neither change in FEUrea nor percentage reclassified out of a low FEUrea category differed between patients with and without AKI (P > .63 for both). CONCLUSIONS: FEUrea is meaningfully affected by loop diuretics. The degree of change in FEUrea is highly variable between patients and commonly of a magnitude that could reclassify across categories of FEUrea.

The role of the kidney in acute and chronic heart failure.

Renal dysfunction affects approximately 30 to 50% of heart failure (HF) patients. The unfavourable relationship between heart and kidney dysfunction contributes to worse outcomes through several mechanisms such as inflammation, oxidative stress, impaired hydrosaline homeostasis, and diuretic resistance. Renal dysfunction not only carries important prognostic value both in acute and in chronic HF, but also is a potential precipitating factor after the first diagnosis. Because renal dysfunction encompasses different etiologies, a better understanding of its definition, incidence, and pathophysiology provides additional information. Although old and novel available biomarkers for the detection of renal dysfunction have been recently proposed, there is no general consensus regarding the terminology and definition of renal dysfunction in HF. Due to some specific pathophysiological mechanisms, renal impairment seems to be different on an individual patient level and, recognizing it in acute and chronic settings, could be useful to optimize decongestive treatment. For these reasons, in this review, we aim to describe and evaluate different phenotypes of renal dysfunction in acute and chronic HF and the possible management in these settings. KEY MESSAGES: • Chronic kidney dysfunction and worsening renal function are highly prevalent in acute heart failure and chronic heart failure and associated with poor outcomes. • This association is modified by the context in which it occurs, i.e. worsening renal function in the context of adequate decongestion in acute heart failure, or worsening renal function after initiation of neurohormonal blockers in chronic heart failure. • Future research should be aimed at elucidating the mechanisms involved in these differenct contexts, as well as alternative treatment approaches in the case of true worsening renal function.

Exercise intervention in hospitalized heart failure patients, with emphasis on congestion-related complications: a review.

The importance of physical activity has become evident since a sedentary lifestyle drives cardiovascular disease progression and is associated with increased morbidity and mortality. The favorable effects of exercise training in chronic heart failure (HF) and chronic kidney disease (CKD) are widely recognized and exercise training is recommended by European and American guidelines. However, the application of exercise intervention in HF patients hospitalized for acute decompensation or acute worsening in cardiac function has not been explored extensively and, as a result, knowledge about the effects of exercise training in the inpatient setting of acute HF is limited. Acute HF is often accompanied by signs and symptoms of congestion, termed acute decompensated heart failure (ADHF), which leads to worsening renal function (WRF) and eventually negatively affects both thoracic and abdominal organs. Therefore, we first provide a comprehensive overview of the impact of exercise training in hospitalized patients demonstrating acute decompensating HF. In the second part, we will focus on the effects of exercise training on congestion in a setting of ADHF complicated by renal dysfunction. This review suggests that exercise intervention is beneficial in the inpatient setting of acute HF, but that more clinical studies focusing on the application of exercise training to counteract venous congestion are needed.

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.