Simultaneous Heart and Kidney Transplantation: A Systematic Review and Proportional Meta-Analysis of Its Characteristics and Long-Term Variables.

Patients with end-stage heart disease who undergo a heart transplant frequently have simultaneous kidney insufficiency, therefore simultaneous heart and kidney transplantation is an option and it is necessary to understand its characteristics and long-term variables. The recipient characteristics and operative and long-term variables were assessed in a meta-analysis. A total of 781 studies were screened, and 33 were thoroughly reviewed. 15 retrospective cohort studies and 376 patients were included. The recipient's mean age was 51.1 years (95% CI 48.52-53.67) and 84% (95% CI 80-87) were male. 71% (95% CI 59-83) of the recipients were dialysis dependent. The most common indication was ischemic cardiomyopathy [47% (95% CI 41-53)] and cardiorenal syndrome [22% (95% CI 9-35)]. Also, 33% (95% CI 20-46) of the patients presented with delayed graft function. During the mean follow-up period of 67.49 months (95% CI 45.64-89.33), simultaneous rejection episodes of both organ allografts were described in 5 cases only. Overall survival was 95% (95% CI 88-100) at 30 days, 81% (95% CI 76-86) at 1 year, 79% (95% CI 71-87) at 3, and 71% (95% CI 59-83) at 5 years. Simultaneous heart and kidney transplantation is an important option for concurrent cardiac and renal dysfunction and has acceptable rejection and survival rates.

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 Factors Associated with Renal Outcome After Heart Transplantation.

Cardiorenal syndrome (CRS) frequently occurs in end-stage heart failure patients waiting for heart transplantation (HT). Decision-making regarding simultaneous heart and kidney transplantation is an unresolved issue in these patients. We investigated clinical factors associated with renal outcome after HT. A total of 180 patients who received HT from 1996 to 2015 were included. Factors associated with early post-HT chronic kidney disease (CKD, estimated glomerular filtration rate [eGFR] < 60 mL/minute/1.73 m2 within 1 year post-HT), post-HT end-stage kidney disease (ESKD), and significant renal function improvement (%ΔeGFR > 15%) at 1 year post-HT were analyzed. Early post-HT CKD and post-HT ESKD developed in 61 (33.9%) and 8 (4.4%) of 180 patients, respectively. Old age was only independently associated with early post-HT CKD and preexisting CKD tended to be associated with early post-HT CKD. Old age and preexisting CKD were independently associated with post-HT ESKD. Low pre-HT eGFR and preoperative renal replacement therapy were not associated with early post-HT CKD or post-HT ESKD. Young age, low pre-HT eGFR, and high %ΔeGFR 1 month post-HT were independently associated with significant renal function improvement. Preoperative renal function, including preoperative RRT, was not associated with post-HT mortality. In conclusion, preexisting CKD may impact renal outcomes after HT, but preoperative severe renal dysfunction, even that severe enough to require RRT, may not be a contraindication for HT alone. Our data suggest the necessity of early HT in end-stage heart failure patients with CRS and the importance of careful management during the early postoperative period.

Emergency TAVI in cardiogenic shock and cardiorenal syndrome secondary to severe bicuspid aortic stenosis.

A 78-year man with severe aortic stenosis awaiting elective surgical aortic valve replacement presented with worsening New York Heart Association IV shortness of breath. Despite appropriate heart failure treatment, he deteriorated and developed cardiogenic shock and cardiorenal syndrome which progressed despite inotropic support. A non-contrast-gated CT coronary angiogram was arranged in light of acute renal failure which revealed a bicuspid aortic valve. Three-dimensional transoesophageal echocardiography guidance was used to assist annulus sizing. An emergency transcatheter aortic valve replacement (eTAVI) was carried out 5 days into admission with a 34 mm Core Valve Evolut Pro valve with a no contrast technique. The patient's blood pressure and urine output improved and no procedural complications were encountered. He was discharged after 21 days and has remained well subsequently. This case highlights the utility of eTAVI and demonstrates the feasibility of a no contrast approach.

The involvement of renal afferents in the maintenance of cardiorenal diseases.

Elevated sympathetic vasomotor activity is a common feature of cardiorenal diseases. Therefore, the sympathetic nervous system is an important therapeutic target, particularly the fibers innervating the kidneys. In fact, renal denervation has been applied clinically and shown promising results in patients with hypertension and chronic kidney disease. However, the underlying mechanisms involved in the cardiorenal protection induced by renal denervation have not yet been fully clarified. This mini-review highlights historical and recent aspects related to the role of renal sensory fibers in the control of cardiorenal function under normal conditions and in experimental models of cardiovascular disease. Results have demonstrated that alterations in renal sensory function participate in the maintenance of elevated sympathetic vasomotor activity and cardiorenal changes; as such, renal sensory fibers may be a potential therapeutic target for the treatment of cardiorenal diseases. Although it has not yet been applied in clinical practice, selective afferent renal denervation may be promising, since such an approach maintains efferent activity and can provide more refined control of renal function compared with total renal denervation. However, more studies are needed to understand the mechanisms by which renal afferents partially contribute to such changes, in addition to the need to evaluate the safety and advantages of the approach for application in the clinical practice.

Reversal of stage 5 chronic kidney disease by aortic valve replacement in kidney transplant recipient: a case report.

BACKGROUND: Cardiorenal syndrome (CRS) is a group of pathophysiological disorders affecting heart and kidneys. CASE PRESENTATION: We present 44-year-old kidney transplant recipient with acute-on-chronic graft failure in the course of CRS due to acutely decompensated heart failure associated with severe aortic regurgitation successfully treated with aortic valve replacement. Because of graft failure progression and difficult to eradicate infections he was treated with dialysis and radical minimization of immunosuppression. After 74 days of renal replacement therapy the patient regained graft function after successful aortic valve replacement. The dialysis could be stopped and immunosuppressive therapy was reintroduced. Heart and renal function are stable and patient is doing well without dialysis for 3 years. CONCLUSIONS: The return of kidney graft function can occur even after a long period of dialysis therapy due to improved cardiovascular function. Therefore, distinguishing an acute-on-chronic CRS subtype is mandatory to enable specific patient approach.

[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.

Concomitant coronary and renal revascularization improves left ventricular hypertrophy more than coronary stenting alone in patients with ischemic heart and renal disease.

Percutaneous transluminal renal artery stenting (PTRAS) has been proved to have no more benefit than medication alone in treating atherosclerotic renal artery stenosis (ARAS). Whether PTRAS could improve left ventricular hypertrophy (LVH) and reduce adverse events when based on percutaneous coronary intervention (PCI) for patients with coronary artery disease (CAD) and ARAS is still unclear. A retrospective study was conducted, which explored the effect of concomitant PCI and PTRAS versus PCI alone for patients with CAD and ARAS complicated by heart failure with preserved ejection fraction (HFpEF). A total of 228 patients meeting inclusion criteria were divided into two groups: (1) the HFpEF-I group, with PCI and PTRAS; (2) the HFpEF-II group, with PCI alone. Both groups had a two-year follow-up. The left ventricular mass index (LVMI) and other clinical characteristics were compared between groups. During the follow-up period, a substantial decrease in systolic blood pressure (SBP) was observed in the HFpEF-I group, but not in the HFpEF-II group. There was marked decrease in LVMI in both groups, but the HFpEF-I group showed a greater decrease than the HFpEF-II group. Regression analysis demonstrated that PTRAS was significantly associated with LVMI reduction and fewer adverse events after adjusting for other factors. In HFpEF patients with both CAD and ARAS, concomitant PCI and PTRAS can improve LVH and decrease the incidence of adverse events more than PCI alone. This study highlights the beneficial effect of ARAS revascularization, as a new and more aggressive revascularization strategy for such high-risk patients.

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.

Renal impairment an impediment to heart transplantation?

Chronic kidney disease and chronic heart failure are now recognized as closely intertwined entities. The noxious interactions between the heart and kidney systems as part of the so-called cardiorenal syndrome is a matter of great concern for heart transplant candidates. Not only is chronic kidney disease a commonly associated comorbidity, but its detrimental effect on the outcome of heart transplantation is now well established. In the more advanced stages of kidney disease, it may even deter physicians from carrying out heart transplantation in potential candidates. This review offers insights on epidemiological issues regarding chronic kidney disease among patients awaiting heart transplantation as well as its impact on the outcomes related with heart transplantations. Finally, emerging therapeutic opportunities which may benefit heart transplant candidates with the most severe renal impairment will be reviewed with a special emphasis on combined heart-kidney transplantation.

Renal denervation: a novel non-pharmacological approach in heart failure.

Heart failure is associated with activation of the sympathetic nervous system which presumably results in a progression of the syndrome and thereby in poor outcome. Renal denervation has shown to be effective in conditions with enhanced sympathetic activity like resistant hypertension and metabolic syndrome associated with sleep apnea. The first pilot trials assessing the effect of renal denervation on signs and symptoms of heart failure in patients with both preserved and reduced left ventricular ejection fraction are presently ongoing. The results of these studies will determine whether to proceed with larger prospective outcome trials. Altogether, renal denervation is a promising novel technique that may improve the outcome of patients with sympathetic hyperactivity and cardiovascular diseases.

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.

The evidence of occult hypervolemia; improvement of cardiac functions after kidney transplantation.

The term cardiorenal syndrome (CRS) has been used to define interactions between acute or chronic dysfunction of the heart or kidney. When primary chronic kidney disease contribute to cardiac dysfunction, it is classified as type 4 CRS. Cardiac dilatation, valve regurgitations, and left ventricular dysfunction are observed in end-stage renal failure patients with uremic cardiomyopathy. Because of perioperative risks in these patients, they may not be considered a candidate for kidney transplantation. However, uremic cardiomyopathy can be corrected when volume control is achieved by appropriate dose and duration of ultrafiltration. By presenting two cases with occult hypervolemia in uremic cardiomyopathy whose cardiac functions improved early after kidney transplantation, attention is drawn to the importance of kidney transplantation on cardiac function in such patients primarily and the importance of strict volume control on cardiac function in dialysis patients waiting for kidney transplantation.