Comparative cardioprotective effects of carvedilol versus atenolol in a rat model of cardiorenal syndrome type 4.

The incidence of chronic kidney disease is escalating; cardiorenal syndrome (CRS) type 4 is gaining a major health concern causing significant morbidity and mortality, putting major burdens on the healthcare system. This study was designed to compare the cardioprotective effects of carvedilol versus atenolol against CRS type 4 induced by subtotal 5/6 nephrectomy in rats and to explore the underlying mechanisms. Immediately after surgery, carvedilol (20 mg/kg/day) or atenolol (20 mg/kg/day) was added to drinking water for 10 weeks. Carvedilol was more effective than atenolol in improving kidney functions, decreasing elevated blood pressures, attenuating cardiac hypertrophy, reducing serum brain natriuretic peptide, and diminished cardiac fibrous tissue deposition. However, carvedilol was equivalent to atenolol in modulating ß1-adrenergic receptors (ß1ARs) and cardiac diacylglycerol (DAG) signaling, but carvedilol was superior in modulating ß-arrestin2, phosphatidyl inositol 4,5 bisphosphates (PIP2), and caspase 3 levels. Carvedilol has superior cardioprotective effects than atenolol in a rat model of CRS type 4. These protective effects are mediated through modulating cardiac ß1ARs/ß-arrestin2/PIP2/DAG as well as abating cardiac apoptotic signaling pathways (caspase3/pS473 protein kinase B (Akt)).

[Clinical features and outcomes of patients with the cardio-renal syndrome admitting to a surgical intensive care unit].

OBJECTIVE: To investigate the clinical features and risk factors on outcomes of patients with cardio-renal syndrome (CRS) in surgical intensive care unit (SICU). METHODS: The clinical data of the patients admitted to SICU of Peking University People's Hospital from January 1st 2017 to December 31st 2017 were analyzed retrospectively, including gender, age, severity of the disease, underlying diseases, type of CRS, precipitating factors of CRS, cardiac and renal function [cardiac troponin I (cTnI), B-type natriuretic peptide (BNP), serum creatinine (SCr), glomerular filtration rate (eGFR)], outcomes [secondary outcomes, duration of mechanical ventilation, the length of ICU stay, the length of hospital stay, 28-day mortality and hospital mortality]. Patients were grouped according to CRS classification or hospitalization prognosis, the clinical features within different CRS types were analyzed, and risk factors on outcomes of the CRS patients were analysed by Logistic regression. RESULTS: 86 (7.3%) of the 1 172 patients during the study period had CRS. (1) CRS clinical features: CRS 1-5 type patients accounted for 24.4% (21 cases), 1.2% (1 case), 20.9% (18 cases), 1.2% (1 case) and 52.3% (45 cases) respectively, CRS type 1, 3 and 5 were the main types (i.e. acute cardiac and renal dysfunction), while type 5 CRS was the highest (i.e. organ dysfunction caused by simultaneous involvement of cardiac and renal functions secondary to systemic diseases was the most common). Baseline BNP (Z = 11.365, P = 0.023), SCr peak (Z = 13.405, P = 0.009) and baseline eGFR (F = 2.648, P = 0.037) were significantly different within the CRS 5 types. The basic cardiac function of type 1 CRS patients was significantly worse than that of type 3 and type 5 CRS patients [baseline BNP (µg/L): 434.2 (187.0, 1 252.0) vs. 154.9 (66.4, 272.5), 268.5 (124.1, 486.6), both P < 0.05]. The basic renal function of type 3 CRS patients was significantly worse than that of type 5 CRS patients [baseline eGFR (mL/min): 71.0±30.3 vs. 88.3±29.0, P < 0.05]. The severity of acute kidney injury (AKI) in type 3 CRS patients was significantly higher than that in type 1 and type 5 CRS patients [SCr peak (µmol/L): 285.0 (171.5, 420.6) vs. 143.0 (99.5, 213.5), 189.0 (105.5, 280.5), both P < 0.01]. There were no significant differences in gender, age, department, acute physiology and chronic health evaluation II (APACHE II), intraoperative blood loss, basic cTnI and SCr levels, BNP peak, AKI staging and prognostic indicators among patients with various types of CRS. (2) Death risk analysis: 43 (50%) of the 86 CRS patients died during the hospital stay. Compared with the survival patients, CRS death patients were older [years old: 72 (57, 80) vs. 62 (50, 73)] and had higher APACHE II score [22 (17, 29) vs. 18 (15, 21)], with higher proportion of cerebrovascular disease (9.3% vs. 0). Regarding to precipitating factors of CRS, sepsis/septic shock (41.9% vs. 18.6%) and surgery stress (9.3% vs. 0) were remarkably increased in death patients. Death patients had higher cTnI and SCr peak [cTnI peak (µg/L): 1.155 (0.192, 5.125) vs. 0.122 (0.045, 0.610), SCr peak (µmol/L): 208 (143, 295) vs. 146 (101, 289)] and also high proportion of AKI stage 3 (41.9% vs. 20.9%), higher rate of secondary infection (67.4% vs. 30.2%), prolonged duration of mechanical ventilation and the length of ICU stay [hours: 179 (61, 470) vs. 37 (7, 134); days: 10 (4, 24) vs. 5 (2, 11)], with statistically significant differences (all P < 0.05). Logistic regression analysis showed that the elderly [odds ratio (OR) = 1.053, 95% confidence interval (95%CI) = 1.003-1.094, P = 0.010], high APACHE II score (OR = 1.165, 95%CI = 1.057-1.285, P = 0.002), sepsis/septic shock (OR = 4.561, 95%CI = 1.351-15.391, P = 0.014) and AKI stage 3 (OR = 5.468, 95%CI = 1.457-20.530, P = 0.012) were independent risk factors for hospital death in CRS patients. CONCLUSIONS: Surgical ICU patients with CRS are characterized by acute cardiac and renal dysfunction. CRS type 5 is the most common and has a high fatality rate. Age, severity of illness, sepsis/septic shock and AKI stage 3 are independent risk factors of death.

Biomarkers and echocardiography for evaluating the improvement of the ventricular diastolic function after surgical relief of hydronephrosis.

The pathophysiology of cardio-renal syndrome (CRS) is complex. Hydronephrosis caused by urolithiasis may cause cytokine release and lead to cardiac dysfunction. The aim of this study was to evaluate cardiac function changes observed in patients who received double J placement using feasible biomarkers and echocardiography. This was a prospective, single-center study. Eighty-seven patients who presented with acute unilateral hydronephrosis and received ureteroscope stone manipulation were enrolled. Echocardiography and cytokines were measured on the day of the operation and 24 hours after the procedure. Changes before and after surgery were assessed by the paired t-test and Wilcoxon test. Correlation analyses between echocardiographic diastolic indices and cytokine levels were performed using Pearson's correlation coefficients. Patients with hydronephrosis showed a higher left atrium volume index (LAVI), decreased E', and increased E/ E' ratio, which indicated diastolic dysfunction. Patients with hydronephrosis also exhibited decreased global strain rates during isovolumetric relaxation (SRIVR) and E/ SRIVR, which confirmed the diastolic dysfunction. Significant reductions in LAVI, increases in SRIVR and decreases in E/ SRIVR were observed after the operation. Biomarkers, such as TGF-ß and serum NT-proBNP, were significantly decreased after surgery. In addition, a significant correlation was observed between the post-surgical decrease in TGF-ß1 and increase in SRIVR. Unilateral hydronephrosis causes cardiac diastolic dysfunction, and relieving hydronephrosis could improve diastolic function. Improvements in cardiac dysfunction can be evaluated by echocardiography and measuring cytokine levels. The results of this study will inform efforts to improve the early diagnosis of CRS and prevent further deterioration of cardiac function when treating patients with hydronephrosis.

Acute cardiac tamponade: an unusual cause of acute renal failure in a renal transplant recipient.

We report a case of slow graft function in a renal transplant recipient caused by uremic acute pericardial effusion with tamponade. Urgent pericardiocentesis was done with an improvement in blood pressure, immediate diuresis, and quick recovery of renal function back to baseline. Pericardial tamponade should be included in consideration of causes of type 1 cardiorenal syndrome in renal transplant recipients.

Combined heart-kidney transplant improves post-transplant survival compared with isolated heart transplant in recipients with reduced glomerular filtration rate: Analysis of 593 combined heart-kidney transplants from the United Network Organ Sharing Database.

OBJECTIVE: Criteria for simultaneous heart-kidney transplant (HKTx) recipients are unclear. We characterized the evolution of combined HKTx in the United States over time compared with isolated heart transplantation (HTx) and determined factors maximizing post-transplant survival. We focused on whether a threshold estimated glomerular filtration rate (eGFR) could be identified that justified combined transplantation. METHODS: A supplemented United Network Organ Sharing Dataset identified HTx and HKTx recipients from 2000 to 2010. eGFR was calculated for HTx and recipients were grouped into eGFR quintiles. Time-related mortality was compared among recipients, with multivariable factors sought using Cox proportional hazard regression models. RESULTS: We identified 26,183 HTx recipients, of whom 593 were HKTx recipients. HTx increased modestly over time (3.6%), whereas prevalence of HKTx increased dramatically (147%). Risk-unadjusted survival was similar among HTx recipients (8.4 ± 0.04 years) and HKTx recipients (7.7 ± 0.2 years) (P = .76). Isolated HTx recipients in the lowest eGFR quintile had decreased survival (P < .001), but those in the third eGFR quintile had superior survival, suggesting a benefit in this subgroup. HTx recipients in the lowest eGFR quintile (eGFR less than mean 37 mL/minute) had worse survival than combined HKTx recipients (7.1 ± 0.07 vs 7.7 ± 0.2; P < .001). Multivariable factors for increased mortality among HTx recipients included lower eGFR, higher recent panel reactive antibody score, older age, African American race, diabetes, longer ischemic time, and certain diagnoses. CONCLUSIONS: Performance of combined HKTx is increasing out of proportion to isolated HTx. eGFR is an important determinant of improved HTx survival. Combined HKTx recovers post-transplant survival in patients with eGFR <37 mL/minute and can be recommended in this subgroup.

Use of ventricular assist device as bridge to simultaneous heart and kidney transplantation in patients with cardiac and renal failure.

BACKGROUND: Ventricular assist device (VAD) implantation as a bridge to cardiac transplantation is an effective treatment option for end-stage heart failure. Renal dysfunction is not uncommon but is considered to be a poor prognostic factor. We present our experience with 6 patients who had combined heart and kidney transplantation (HKT) after VAD implantation for advanced cardiac and renal failure. METHODS: Of 74 patients who underwent VAD implantation as a bridge to transplant from May 2001 to September 2009, 28 patients developed renal failure, and of these, 6 (5 male, 1 female, ages 40-64 years) had HKT. All required hemodialysis because of renal failure before HKT. Immunosuppression consisted of anti-thymocyte globulin followed by triple drug therapy consisting of calcineurin inhibitors, mycophenolate, and corticosteroids. RESULTS: Of the 6 HKT patients, 5 (83%) were alive without hemodialysis at 1 and 2 years; of the 22 patients with renal failure after VAD implantation without subsequent transplant, 1- and 2-year survivals were zero. Interval from VAD implantation to HKT ranged from 36 to 366 days (133 ± 127 days). At 6 months after HKT (100% alive), left ventricular ejection fraction was 60.2 ± 5.8% and serum creatinine 1.1 ± 0.2 mg/dL. Three HKT patients required temporary hemodialysis after surgery. Endomyocardial biopsy showed absence of ISHLT grade 2R-3A or greater cellular rejection, and none showed evidence of definite antibody-mediated rejection. CONCLUSIONS: Based on our initial experience, simultaneous HKT is a safe treatment option with excellent outcomes for patients with advanced heart failure and persistent renal dysfunction after VAD implantation.

Acute cardiorenal syndrome by high flow arteriovenous fistula after kidney transplantation.

PURPOSE: The aim of this work was to increase recognition of high flow arteriovenous fistulas in kidney transplant patients. CASE: Here, we report the case of a 22-year-old man with repeated hospitalizations for cardiomegaly and chronic pericardial effusion after kidney transplantation. Eventually, high flow of his arteriovenous fistula was recognized 5.5 years after transplantation when he developed acute cardiorenal syndrome. Access flow reduction markedly improved kidney graft function along with reversion of cardiomegaly, which was impressively demonstrated by follow-up chest-x-rays. CONCLUSION: Arteriovenous fistulas should be monitored regularly after kidney transplantation to avoid congestive heart failure and other serious complications.