Morphological picture of acute kidney injury in patients with severe acute decompensation heart failure and its relation to clinical, functional and biochemical parameters

Background: There are no biological markers to predict the onset of acute kidney injury (AKI) in patients with acute decompensated heart failure (ADHF). Liver-type fatty acid-binding protein (L-FABP) levels are markedly upregulated in the proximal tubules after renal ischemia. We investigated whether urinary L-FABP is a suitable marker to predict AKI in ADHF patients. Methods: We examined 281 consecutive patients with ADHF. Serum creatinine (Cr) and L-FABP levels were measured at admission and 24 and 48 h after admission. Results: AKI developed in 104 patients (37%). Urinary L-FABP levels at admission were significantly higher in patients with AKI than in those without (33.0 vs. 5.2 μg/g Cr; p < 0.001). Multivariate analysis showed that baseline urinary L-FABP level was an independent predictor of AKI in ADHF patients (odds ratio 1.08, 95% confidence interval 1.05-1.12; p < 0.001). Receiver operating characteristic analysis showed that baseline urinary L-FABP level exhibited 94.2% sensitivity and 87.0% specificity at a cutoff value of 12.5 μg/g Cr. Conclusions: Urinary L-FABP level is useful for predicting the onset of AKI in patients with ADHF. The results of our study could help clinicians diagnose AKI in ADHF patients earlier, leading to possible improvements in the treatment of this group of patients.

Cardiorenal Syndrome in Critical Care: The Acute Cardiorenal and Renocardiac Syndromes

Background: Acute decompensation of chronic heart failure (ADHF) is frequently complicated by acute kidney injury (AKI), which worsens prognosis and increases the risk of adverse outcomes. Understanding the impact of AKI on combined renal and cardiovascular outcomes in ADHF patients remains critical for improving long-term management strategies. Objective: The objective of this study was To evaluate the prognostic value of acute kidney injury in patients hospitalized with acute decompensation of chronic heart failure (ADHF) in relation to combined renal and cardiovascular outcomes during 1 year of follow-up. Methods: One hundred and eight patients hospitalized with attention deficit hyperactivity disorder (ADHD) (mean age 68.3 ± 10.0 years, 60% men) were included in a single-center prospective study. All patients included in the study underwent a standard physical and laboratory instrumental examination, including an assessment of the clinical condition on the SHOCS scale, determination of serum creatinine levels, glomerular filtrate rate (GFR) according to the chronic kidney disease-epidemiology formula, albumin-to-creatinine ratio in urine, and NTproBNP upon admission and discharge. The diagnosis of acute kidney injury (AKI) was established on the basis of generally accepted criteria. The total rate of total mortality and repeated hospitalizations from all causes was estimated as cardiovascular outcomes. Renal outcomes included deterioration of renal function in the form of a decrease in GFR &gt;15% of baseline and a decrease in GFR &lt;30 mL/min/1.73 kg2. Combined renal and cardiovascular outcomes were assessed during outpatient visits 3, 6, and 12 months after discharge. Results: The incidence of AKI during hospitalization in patients with CHF was 14% (n = 15). The groups with and without AKI were comparable in terms of clinical and demographic parameters and clinical assessment scale parameters. However, patients in the AKI group were characterized by higher baseline values of NT-proBNP and more pronounced impaired renal function, which persisted for 6–12 months of follow-up. There were no significant differences in the patient’s clinical condition and the level of NT-proBNP during 1 year of follow-up. In patients with ADHF, the presence of AKI during hospitalization leads to a significant increase in the risk of combined renal and cardiovascular outcomes during 1 year of follow-up (heart rate = 7.6; 95% confidence interval = 2–29; P = 0.003). Conclusion: The development of AKI during hospitalization in patients with ADHD is a predictor of an unfavorable prognosis for combined renal and cardiovascular outcomes during 1 year of follow-up.

AimsIn this prospective, placebo‐controlled, double‐blind, exploratory study, we examined early and more delayed effects of empagliflozin treatment on haemodynamic parameters (primary endpoint: cardiac output) and kidney function including parameters of acute kidney injury (AKI) in patients with acute decompensated heart failure (HF).Methods and resultsPatients with acute decompensated HF with or without diabetes were randomized to empagliflozin 10 mg or placebo for 30 days. Haemodynamic, laboratory, and urinary parameters were assessed after 6 h, 1 day, 3 days, 7 days, and 30 days of treatment. Median time between hospital admission and randomization was 72 h. Baseline characteristics were not different in the empagliflozin (n = 10) and placebo (n = 9) groups. Empagliflozin led to a significant increase in urinary glucose excretion throughout the study (baseline: 37 ± 15 mg/24 h; Day 1: 14 565 ± 8663 mg/24 h; P = 0.001). Empagliflozin did not affect the primary endpoint of cardiac index or on systemic vascular resistance index at any time point. However, empagliflozin significantly reduced parameters of AKI (urinary TIMP‐2 and IGFBP7 by NephroCheck® as indicators of tubular kidney damage), which became significant after 3 days of treatment [placebo: 1.1 ± 1.1 (ng/mL)2/1000; empagliflozin: 0.3 ± 0.2 (ng/mL)2/1000; P = 0.02] and remained significant at the 7 day time point [placebo: 2.5 ± 3.8 (ng/mL)2/1000; empagliflozin: 0.3 ± 0.2 (ng/mL)2/1000; P = 0.003].ConclusionsIn this study, empagliflozin treatment did not affect haemodynamic parameters but significantly reduced markers of tubular injury in patients with acute decompensated HF.

Elevated plasma levels of fibroblast growth factor 23 (FGF23) have emerged as a predictor for the development of acute kidney injury (AKI) in patients undergoing cardiac surgery and those with critical illnesses. However, accurate data in cases involving acute decompensated heart failure (ADHF) remains limited. Single centre cohort study was performed in patients admitted for ADHF. Plasma c-terminal FGF23 (c-FGF23) was measured at baseline and 24 hours after being diagnosed with ADHF. AKI was defined by KDIGO 2012 criteria. The study enrolled 62 patients diagnosed with ADHF. The incidence of AKI was 45% and significantly increased the risk of death. Patients developing AKI had significantly higher levels of plasma c-FGF23 at baseline in comparison with those not developing AKI [median value 1258.5 (57.2, 15 850) vs 230.2 (68.515 850) RU/mL, P = .005]. During the first 24 hours, plasma c-FGF23 levels decreased in both groups, and the levels of c-FGF23 at 24 hours were consistent with the baseline [861.8 (75.7, 15 850) vs 226.3 (56, 5450.8) RU/mL, P = .006]. Receiver operating characteristic analysis of both first time and second time for plasma c-FGF23 collection yielded an area under curve of 0.71 for the prediction of AKI incidence. With the cut-off point at 450 RU/mL, the sensitivity and specificity of plasma c-FGF23 at the baseline for predicting AKI were 71.4% and 61.8% respectively. Plasma c-FGF23 may serve as a novel biomarker for development of AKI in patients with ADHF. These results should be revalidated in larger-scale, cohort studies.

Although hypoalbuminemia at admission is a risk for acute kidney injury (AKI) and mortality in patients with acute decompensated heart failure (ADHF), the clinical significance of decreased serum albumin levels (DAL) during ADHF therapy has not been elucidated. This study aimed to evaluate whether DAL was associated with AKI, and whether intravenous atrial natriuretic peptide (ANP) administration, which provides an effective treatment for ADHF but promotes albumin extravasation, was associated with DAL and AKI. A total of 231 consecutive patients with ADHF were enrolled. AKI was defined as ≥0.3mg/dl absolute or 1.5-fold increase in serum creatinine levels within 48h. AKI occurred in 73 (32%) of the 231 patients during ADHF therapy. The median value of decreases in serum albumin levels was 0.3g/dl at 7days after admission. When DAL was defined as ≥0.3g/dl decrease in serum albumin levels, DAL occurred in 113 patients, and was independently associated with AKI. Of the 231 patients, 73 (32%) were treated with intravenous ANP. DAL occurred more frequently in patients receiving ANP than in those not receiving ANP (77 vs. 36%, p < 0.001), and ANP was independently associated with DAL. The incidence of AKI was higher in patients receiving ANP than in those not receiving ANP (48 vs. 24%, p < 0.001). ANP was independently associated with AKI. In conclusion, DAL is associated with AKI. Intravenous ANP administration may be one of the promoting factors of DAL, which leads to AKI, indicating a possible novel mechanism of AKI.

ObjectiveThis retrospective multicentre observational study was performed to assess the predictors of acute kidney injury (AKI) in patients with acute decompensated heart failure (ADHF) in emergency departments in China.MethodsIn total, 1743 consecutive patients with ADHF were recruited from August 2017 to January 2018. Clinical characteristics and outcomes were compared between patients with and without AKI. Predictors of AKI occurrence and underdiagnosis were assessed in multivariate regression analyses.ResultsOf the 1743 patients, 593 (34.0%) had AKI. AKI was partly associated with short-term all-cause mortality and cost. Cardiovascular comorbidities such as coronary heart disease, diabetes mellitus, and hypertension remained significant predictors of AKI in the univariate analysis. AKI was significantly more likely to occur in patients with a lower arterial pH, lower albumin concentration, higher creatinine concentration, and higher N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration. Patients treated with inotropic agents were significantly more likely to develop AKI during their hospital stay.ConclusionThis study suggests that cardiovascular comorbidities, arterial pH, the albumin concentration, the creatinine concentration, the NT-proBNP concentration, and use of inotropic agents are predictors of AKI in patients with ADHF.

We investigated the utility of the preprocedural red cell distribution width (RDW) for predicting contrast-induced acute kidney injury (CI-AKI) in patients with ST-segment-elevation myocardial infarction (STEMI) who underwent a primary percutaneous coronary intervention. A total of 630 consecutive patients who were routinely referred to coronary angiography for STEMI were included in the present study. CI-AKI was observed in 79 patients (12.5%). The RDW, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and the mean platelet volume were significantly higher in the CI-AKI group than in the non-CI-AKI group (P<0.001, P=032, P=0.025, and P=0.039, respectively). Serum total bilirubin and direct bilirubin levels were not different among the study groups. Using multivariate logistic regression analysis, we found that left ventricular ejection fraction [odds ratio (OR)=0.972, 95% confidence interval (CI) 0.945-0.998, P=0.033], estimated glomerular filtration rate (OR=0.970, 95% CI 0.959-0.981, P<0.001), contrast volume (OR=1.007, 95% CI 1.002-1.012, P=0.009), and RDW (OR=1.406, 95% CI 1.120-1.792, P=0.005) were independent predictors of CI-AKI. Red blood cell distribution width, an inexpensive and easily measurable laboratory variable, is associated independently with the development of CI-AKI. Our data suggest that RDW may be a useful marker in CI-AKI risk stratification.

To investigate the prognostic value of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) in the development of acute kidney injury (AKI) in patients with acute decompensated chronic heart failure (ADCHF). Eighty-three patients (55 (66%) men and 28 (34%) women; mean age, 65±11 years) with ADCHF were examined. AKI was diagnosed and classified according to the 2012 Kidney Disease Improving Global Outcomes Clinical Practice guidelines. To rule out contrast-induced AKI, the investigation enrolled only patients in whom radiopague agents had not been injected 7 days before and during hospitalization. Enzyme immunoassay was used to determine serum NT-proBNP concentrations in all the patients upon hospital admission. AKI was diagnosed in 18 (22%) patients, 13 (16%) had Stage I, 4 (5%) had Stage II, and 1 (1%) had Stage III. The serum concentration of NT-proBNP was significantly higher in patients with AKI than that in the other patients [1512.1 (981.0; 2246.2) and 861.8 (499.0; 1383.6) pg/ml (p=0.008). The rise in NT-proBNP concentrations of more than 942 pg/ml was established to be associated with a considerable increase in the risk of AKI (relative risk (RR) was 4.3; 95% confidence interval (CI), 1.27-14.90; p=0.02). RОС analysis indicated that a NT-proBNP level of >942 pg/ml allows prediction of AKI with a sensitivity of 78% (52; 94) and a specificity of 55% (44; 69) (AUC=0.70; p=0.006). Four (5%) patients died in hospital. NT-proBNP levels in all the dead were greater than 942 pg/ml. Two of the 4 deceased patients had AKI. A high level of NT-proBNP in a patient with ADCHF during hospitalization can serve as a biomarker for high risk of AKI and for high mortality rates.

Aim. To study the effect of acute kidney injury in patients hospitalized with acute decompensation of chronic heart failure (ADCHF) in relation to combined renal and cardiovascular outcomes during 1 year of follow-up.Materials and methods. A total of 108 patients hospitalized with ADCHF (mean age 68.3 ± 10.0 years, 60% men) were included in a single-center prospective study. All patients included in the study underwent a standard physical and laboratory instrumental examination, including an assessment of the clinical condition according to the Rating Scale of Clinical State (RSCS) and laboratory tests (including serum creatinine level, glomerular filtration rate (GFR) using the CKD-EPI 2021 equation, albumin to creatinine ratio in urine, natriuretic peptide (NT-proBNP) upon admission and discharge. Acute kidney injury (AKI) was diagnosed based on the KDIGO guidelines (Kidney Disease: Improving Global Outcomes). The total rate of all-cause mortality and repeated hospitalizations from ADCHF was evaluated as cardiovascular outcomes. Renal outcomes included deterioration of renal function in the form of a decrease in GFR &gt;15% of baseline and a decrease in GFR &lt; 30 ml/min/1.73 m2. Combined renal and cardiovascular outcomes were assessed during outpatient visits 3, 6, 12 months after discharge.Results. The incidence of AKI during hospitalization in patients with ADCHF was 14% (n = 15). The groups with and without AKI were comparable in terms of clinical and demographic parameters and clinical assessment scale parameters. However, patients in the AKI group had higher baseline values of NT-proBNP and more pronounced impaired renal function, which persisted for 6–12 months of follow-up. There were no differences in clinical and laboratory data during the follow-up period. In patients with ADCHF, the presence of AKI during hospitalization significantly increases the risk of combined renal and cardiovascular outcomes during 1 year of follow-up (HR = 7.6; 95%CI = 2–29; p = 0.003).Conclusion. The development of AKI during hospitalization in patients with ADCHF is a predictor of an unfavorable prognosis for combined renal and cardiovascular outcomes during 1 year of follow-up.

Cardiorenal syndrome type I (CRS I) is defined as the development of acute kidney injury (AKI) following acute decompensated heart failure (ADHF). The clinical significance of endothelial markers in ADHF-associated AKI has yet to be clarified. This study therefore investigated the biological processes linking ADHF and AKI with the aim of determining whether the plasma markers of endothelial injury and activation are associated with AKI in patients with ADHF. The study prospectively recruited 125 consecutive patients admitted to a coronary critical unit due to ADHF. Patients with and without AKI were compared in terms of soluble thrombomodulin (sTM), angiopoietin (Ang)-1 and −2 plasma levels as well as baseline characteristics. Among the study population, 14 (11.2%) patients developed CRS within 7 days after admission. The hemoglobin levels (median [IQR]11.3[10.8–12.6] vs. 13.5 [12.2–15.0] g/dL, p = 0.003) and baseline eGFR (66.5[35.7–87.9] vs. 78.5 [64.9–107.5] mL/minute/1.73m2, p = 0.044) of patients with CRS were lower than those of patients without CRS. Patients with CRS also presented elevated plasma levels of BNP (1317.5 [222.6–3375.5] vs. 258.2 [63.2–925.8] pg/mL, p = 0.008), Ang-2 (3993.0 [1561.3–15722.7] vs. 1805.9 [1196.9–3302.3] pg/mL, p = 0.006), and sTM (6665.7 [4707.1–11947.3] vs. 4132.2 [3338.0–5531.8] ng/mL, p < 0.001), compared to patients without CRS. Multivariate logistic regression analysis based on forward stepwise method identified that log sTM was the only independent risk factor for AKI (OR, 13.83; 3.02–63.28, p = 0.001). Furthermore, higher sTM levels were associated with AKI in patients with ADHF. These findings suggest a novel approach to dealing with kidney injury in the context of ADHF, involving the use of baseline biomarker profiles to identify individuals at risk of developing AKI. KEY MESSAGES The clinical significance of endothelial markers in acute decompensated heart failure (ADHF)-associated acute kidney injury (AKI) has not previously been clarified. This study revealed that markers of endothelial injury (i.e. plasma soluble thrombomodulin (sTM) levels) were higher in ADHF patients with AKI than in those without AKI. Multivariate analysis identified sTM level > cutoff value of 4,855.2 pg/mL as an independent factor associated with the development of AKI. sTM could potentially be used as a biomarker to predict the development of AKI in patients with heart failure. These findings suggest a novel approach to dealing with kidney injury in the context of ADHF, involving the use of baseline biomarker profiles to identify individuals at risk of developing AKI.

To evaluate the clinical significance of serum and urinary microRNA-423-5p in the prediction of acute kidney injury onset and survival in patients with acute decompensated heart failure. A total of 180 acute decompensated heart failure patients, including 57 acute kidney injury cases and 123 non-acute kidney injury cases, were included in this study. Serum and urinary neutrophil gelatinase-associated lipocalin, a biomarker of renal injury of acute kidney injury, was detected using an enzyme-linked immunosorbent assay. Expression of microRNA-423-5p in serum and urine samples was examined using quantitative real-time polymerase chain reaction. The clinical significance of microRNA-423-5p was evaluated using receiver operating characteristic curve and Kaplan-Meier survival analysis. The levels of neutrophil gelatinase-associated lipocalin and microRNA-423-5p in serum and urine samples were elevated in patients with acute kidney injury compared with the non-acute kidney injury cases (all P<0.05). Serum and urinary microRNA-423-5p had relatively high predictive performance for acute kidney injury onset in acute decompensated heart failure patients, and this predictive value was more significant when combined with urinary neutrophil gelatinase-associated lipocalin. In addition, serum and urinary elevated levels of microRNA-423-5p predicted a poor 180-day survival in the acute kidney injury group. Increased serum and urinary microRNA-423-5p can predict the occurrence of acute kidney injury in acute decompensated heart failure patients, and is associated with poor survival of acute kidney injury patients. In addition, the diagnostic value of urine neutrophil gelatinase-associated lipocalin for the early screening of acute kidney injury from acute decompensated heart failure patients might be improved by considering the changes in urinary microRNA-423-5p.

Acute Kidney Injury in Alcohol-Associated Hepatitis: More than a Bystander

Acute kidney injury is a serious condition, occurring in up to two-thirds of intensive care unit patients, and 8.8-55% of patients with acute cardiac conditions. Renal replacement therapy is used in about 5-10% of intensive care unit patients. The term cardiorenal syndrome refers to combined heart and kidney failure; three types of acute cardiorenal syndrome have been described: acute cardiorenal syndrome or cardiorenal syndrome type 1, acute renocardiac syndrome or cardiorenal syndrome type 3, and acute cardiorenal syndrome type 5 (cardiac and renal injury secondary to a third entity such as sepsis). Acute kidney injury replaced the previously used term ‘acute renal failure’ and comprises the entire spectrum of the disease, from small changes in function to the requirement of renal replacement therapy. Not only failure, but also minor and less severe decreases, in kidney function are of clinical significance both in the short and long-term. The most recent definition for acute kidney injury is proposed by the Kidney Disease: Improving Global Outcomes clinical practice guidelines workgroup. This definition is a modification of the RIFLE and AKIN definitions and staging criteria, and it stages patients according to changes in the urine output and serum creatinine (see Tables 68.1 and 68.2). Acute kidney injury is a heterogeneous syndrome with different and multiple aetiologies, often with several insults occurring in the same individual. The underlying processes include nephrotoxicity, and neurohormonal, haemodynamic, autoimmune, and inflammatory abnormalities. The most frequent cause for acute kidney injury in intensive cardiac care patients are low cardiac output with an impaired kidney perfusion (cardiogenic shock) and/or a marked increase in venous pressure (acute decompensated heart failure). Predictors for acute kidney injury in these patients include: baseline renal dysfunction, diabetes, anaemia, and hypertension, as well as the administration of high doses of diuretics. In the intensive cardiac care unit, attention must be paid to the prevention of acute kidney injury: monitoring of high-risk patients, prompt resuscitation, maintenance of an adequate mean arterial pressure, cardiac output, and intravascular volume (avoidance of both fluid overload and hypovolaemia), as well as the avoidance or protection against nephrotoxic agents. The treatment of acute kidney injury focuses on the treatment of the underlying aetiology, supportive care, and avoiding further injury from nephrotoxic agents. More specific therapies have not yet demonstrated efficacy. Renal replacement therapy is indicated in life-threatening changes in fluid, electrolyte, and acid-base balance, but there are also arguments for more early initiation.

Acute kidney injury is a serious condition, occurring in up to two-thirds of intensive care unit patients, and 8.8-55% of patients with acute cardiac conditions. Renal replacement therapy is used in about 1.5-15% of intensive care unit patients. The term cardiorenal syndrome refers to combined heart and kidney failure; three types of acute cardiorenal syndrome have been described: acute cardiorenal syndrome or cardiorenal syndrome type 1, acute renocardiac syndrome or cardiorenal syndrome type 3, and acute cardiorenal syndrome type 5 (cardiac and renal injury secondary to a third entity such as sepsis). Acute kidney injury replaced the previously used term 'acute renal failure' and comprises the entire spectrum of the disease, from small changes in function to the requirement of renal replacement therapy. Not only failure, but also minor and less severe decreases, in kidney function are of clinical significance both in the short and long-term. The most recent definition for acute kidney injury is proposed by the Kidney Disease: Improving Global Outcomes clinical practice guidelines workgroup. This definition is a modification of the RIFLE and AKIN definitions and staging criteria, and it stages patients according to changes in the urine output and serum creatinine (see Tables 68.1 and 68.2). Acute kidney injury is a heterogeneous syndrome with different and multiple aetiologies, often with several insults occurring in the same individual. The underlying processes include nephrotoxicity, and neurohormonal, haemodynamic, autoimmune, and inflammatory abnormalities. The most frequent cause for acute kidney injury in intensive cardiac care patients are low cardiac output with an impaired kidney perfusion (cardiogenic shock) and/or a marked increase in venous pressure (acute decompensated heart failure). Predictors for acute kidney injury in these patients include: baseline renal dysfunction, diabetes, anaemia, and hypertension, as well as the administration of high doses of diuretics. In the intensive cardiac care unit, attention must be paid to the prevention of acute kidney injury: monitoring of high-risk patients, prompt resuscitation, maintenance of an adequate mean arterial pressure, cardiac output, and intravascular volume (avoidance of both fluid overload and hypovolaemia), as well as the avoidance or protection against nephrotoxic agents. The treatment of acute kidney injury focuses on the treatment of the underlying aetiology, supportive care, and avoiding further injury from nephrotoxic agents. More specific therapies have not yet demonstrated efficacy. Renal replacement therapy is indicated in life-threatening changes in fluid, electrolyte, and acid-base balance, but there are also arguments for more early initiation.