GLP-1 receptor agonists and cardiorenal outcomes in type 2 diabetes: an updated meta-analysis of eight CVOTs.

BACKGROUND: A meta-analysis is presented of cardiovascular outcome trials (CVOTs) comparing glucagon-like peptide-1 receptor agonists (GLP-1RA) versus placebo on cardiorenal outcomes in patients with type 2 diabetes mellitus (T2DM). METHODS: We did an electronic search up to June 30, 2021, for eligible trials. We did a meta-analysis of available trial data using a random-effects model to calculate overall hazard ratios (HRs) and 95% CI (confidence intervals). We included data from 8 CVOTs and 60,080 patients (72.4% with established cardiovascular disease). RESULTS: GLP-1RA reduced major cardiovascular events (MACE) by 14% (HR = 0.86, 95% CI 0.79-0.94, P = 0.006) with a non-significant heterogeneity between subgroups of patients with and without cardiovascular disease (P = 0.127). GLP-1RA also reduced the risk of cardiovascular death by 13% (P = 0.016), nonfatal stroke by 16% (P = 0.007), hospitalization for heart failure by 10% (P = 0.023), all-cause mortality by 12% (P = 0.012), and the broad composite kidney outcome by 17% (P = 0.012), which was driven by a reduction in macroalbuminuria only (HR = 0.74, 0.67-0.82, P < 0.001). CONCLUSIONS: GLP-1RA have moderate benefits on MACE, and also reduce hospitalization for heart failure and all-cause mortality; they also have robust benefits on reducing the incidence of macroalbuminuria.

Improvement of renal function after transcatheter aortic valve replacement and its impact on survival.

BACKGROUND: Chronic kidney disease as well as acute kidney injury are associated with adverse outcomes after transcatheter aortic valve replacement (TAVR). However, little is known about the prognostic implications of an improvement in renal function after TAVR. METHODS: Renal improvement (RI) was defined as a decrease in postprocedural creatinine in µmol/l of ≥1% compared to its preprocedural baseline value. A propensity score representing the likelihood of RI was calculated to define patient groups which were comparable regarding potential confounders (age, sex, BMI, NYHA classification, STS score, log. EuroSCORE, history of atrial fibrillation/atrial flutter, pulmonary disease, previous stroke, CRP, creatinine, hsTNT and NT-proBNP). The cohort was stratified into 5 quintiles according to this propensity score and the survival time after TAVR was compared within each subgroup. RESULTS: Patients in quintile 5 (n = 93) had the highest likelihood for RI. They were characterized by higher creatinine, lower eGFR, higher NYHA class, higher NT-proBNP, being mostly female and having shorter overall survival time. Within quintile 5, patients without RI had significantly shorter survival compared to patients with RI (p = 0.002, HR = 0.32, 95% CI = [0.15-0.69]). There was no survival time difference between patients with and without RI in the whole cohort (p = 0.12) and in quintiles 1 to 4 (all p > 0.16). Analyses of specific subgroups showed that among patients with NYHA class IV, those with RI also had a significant survival time benefit (p < 0.001, HR = 0.15; 95%-CI = [0.05-0.44]) compared to patients without RI. CONCLUSIONS: We here describe a propensity score-derived specific subgroup of patients in which RI after TAVR correlated with a significant survival benefit.

Association Between Adaptive Servo-Ventilation Therapy and Renal Function.

Cardio-renal syndrome is a challenging clinical entity to manage, and is often associated with increased morbidity and mortality. We hypothesized that adaptive servo-ventilation (ASV), non-invasive positive pressure ventilation that ameliorates systemic/pulmonary congestion, may improve renal function in patients with symptomatic heart failure complicated by the cardio-renal syndrome. Patients with symptomatic congestive heart failure who underwent ASV therapy for over 1 month were included in this retrospective study. The trajectory of the estimated glomerular filtration ratio (eGFR) between the pre-1 month period and the post-one-month period (on ASV) were compared. A total of 81 patients (median 65 years old, 65 men) were included. eGFR decreased during the pre-1 month period from 52.7 (41.7, 64.6) down to 49.9 (37.3, 63.5) mL/minute/1.73 m2 (P < 0.001) whereas we observed an increase following one-month of ASV therapy up to 53.4 (38.6, 68.6) mL/minute/1.73 m2 (P = 0.022). A reduction in furosemide equivalent dose following the initiation of ASV therapy was independently associated with increases in eGFR with an adjusted odds ratio of 13.72 (95% confidence interval 3.40-55.3, P < 0.001). In conclusion, short-term ASV therapy was associated with the preservation of renal function, particularly when the dose of loop diuretics was concomitantly reduced.

Impact of Cardio-Renal-Metabolic Comorbidities on Cardiovascular Outcomes and Mortality in Type 2 Diabetes Mellitus.

BACKGROUND: We evaluated the incremental contribution of chronic kidney disease (CKD) to the risk of major adverse cardiovascular (CV) events (MACE), heart failure (HF), and all-cause mortality (ACM) in type 2 diabetes mellitus (T2DM) patients and its importance relative to the presence of other cardio-renal-metabolic (CaReMe) comorbidities. METHODS: Patients (≥40 years) were identified at the time of T2DM diagnosis from US (Humedica/Optum) and UK (Clinical Practice Research Datalink) databases. Patients were monitored post-diagnosis for modified MACE (myocardial infarction, stroke, ACM), HF, and ACM. Adjusted hazard ratios were obtained using Cox proportional-hazards regression to evaluate the relative risk of modified MACE, HF, and ACM due to CKD. Patients were stratified by the presence or absence of atherosclerotic CV disease (ASCVD) and age. RESULTS: Between 2011 and 2015, of 227,224 patients identified with incident T2DM, 40,063 (17.64%) had CKD. Regardless of prior ASCVD, CKD was associated with higher risk of modified MACE, HF, and ACM; this excess hazard was more pronounced in older patients with prior ASCVD. In time-to-event analyses in the overall cohort, patients with T2DM + CKD or T2DM + CKD + hypertension + hyperlipidemia had increased risks for modified MACE, HF, and ACM versus patients with T2DM and no CaReMe comorbidities. Patients with CKD had higher risks for and shorter times to modified MACE, HF, and ACM than those without CKD. CONCLUSION: In T2DM patients, CKD presence was associated with higher risk of modified MACE, HF, and ACM. This may have risk-stratification implications for T2DM patients based on background CKD and highlights the potential importance of novel renoprotective strategies.

Intra-abdominal pressure and its relationship with markers of congestion in patients admitted for acute decompensated heart failure.

Systemic congestion is one of the mechanisms involved in acute decompensated heart failure (ADHF). Increased intra-abdominal pressure (IAP), elicited by abdominal congestion, has been related to acute kidney injury and prognosis. Nonetheless, the link between diuretic response, surrogate markers of congestion and renal function remains poorly understood. We measured IAP in 43 patients from a non-interventional, exploratory, prospective, single center study carried out in patients admitted for ADHF. IAP was measured with a calibrated electronic manometer through a catheter inserted in the bladder. Normal IAP was defined as < 12 mmHg. At baseline, median IAP was 15 mmHg, with a reduction over the next 72 h to a median of 12 mmHg. A higher IAP at admission was associated with higher baseline blood urea (83 mg/dL [62-138] vs. 50 mg/dL [35-65]; p = 0.007) and creatinine (1.30 mg/dL vs. 0.95 mg/dL; p = 0.027), and with poorer diuretic response 72 h after admission, either measured by diuresis (14.4 mL/mg vs. 21.6 mL/mg; [p = 0.005]) or natriuresis (1.2 mEqNa/mg vs. 2.0 mEqNa/mg; [p = 0.008]). A higher incidence for 1-year all-cause mortality (45.0% vs. 16.7%; log-rank test = 0.041) was observed among those patients with IAP > 12 mmHg at 72 h. In patients with ADHF, higher IAP at admission is associated with poorer baseline renal function and impaired diuretic response. The persistence of IAP at 72 h above 12 mmHg associates to longer length of hospital stay and higher 1-year all-cause mortality.

Heart-kidney interactions: mechanistic insights from animal models.

Pathological changes in the heart or kidney can instigate the release of a cascade of cardiorenal mediators that promote injury in the other organ. Combined dysfunction of heart and kidney is referred to as cardiorenal syndrome (CRS) and has gained considerable attention. CRS has been classified into five distinct entities, each with different major pathophysiological changes. Despite the magnitude of the public health problem of CRS, the underlying mechanisms are incompletely understood, and effective intervention is unavailable. Animal models have allowed us to discover pathogenic molecular changes to clarify the pathophysiological mechanisms responsible for heart-kidney interactions and to enable more accurate risk stratification and effective intervention. Here, this article focuses on the use of currently available animal models to elucidate mechanistic insights in the clinical cardiorenal phenotype arising from primary cardiac injury, primary renal disease with special emphasis of chronic kidney disease-specific risk factors, and simultaneous cardiorenal/renocardiac dysfunction. The development of novel animal models that recapitulate more closely the cardiorenal phenotype in a clinical scenario and discover the molecular basis of this condition will be of great benefit.

Continuation of Chronic Heart Failure Therapies During Heart Failure Hospitalization - a Review.

Randomized controlled trials have demonstrated the benefits of guideline-directed medical therapy in the outpatient setting for treatment of chronic heart failure. However, the benefits of continuation (or discontinuation) of major chronic heart failure therapies when treating acute heart failure during hospitalization are less clear. Real and anticipated worsening renal function, hyperkalemia and hypotension are the three major reasons for discontinuation of renin-angiotensin-aldosterone system inhibitors during hospitalization, and a failure to resume renin-angiotensin-aldosterone system inhibitors before discharge could worsen cardiovascular outcomes. Available data, mostly observational, shows that continuation or initiation of renin-angiotensin-aldosterone system inhibitors appears efficacious, safe, and well tolerated in majority of acute heart failure patients during hospitalization. Worsening renal function portends poor prognosis only if associated with congestion in acute heart failure, and clinicians should not de-escalate diuretic therapy routinely for worsening renal function.

Use of Levosimendan in Intensive Care Unit Settings: An Opinion Paper.

Levosimendan is an inodilator that promotes cardiac contractility primarily through calcium sensitization of cardiac troponin C and vasodilatation via opening of adenosine triphosphate-sensitive potassium (KATP) channels in vascular smooth muscle cells; the drug also exerts organ-protective effects through a similar effect on mitochondrial KATP channels. This pharmacological profile identifies levosimendan as a drug that may have applications in a wide range of critical illness situations encountered in intensive care unit medicine: hemodynamic support in cardiogenic or septic shock; weaning from mechanical ventilation or from extracorporeal membrane oxygenation; and in the context of cardiorenal syndrome. This review, authored by experts from 9 European countries (Austria, Belgium, Czech republic, Finland, France, Germany, Italy, Sweden, and Switzerland), examines the clinical and experimental data for levosimendan in these situations and concludes that, in most instances, the evidence is encouraging, which is not the case with other cardioactive and vasoactive drugs routinely used in the intensive care unit. The size of the available studies is, however, limited and the data are in need of verification in larger controlled trials. Some proposals are offered for the aims and designs of these additional studies.

Prognostic Significance of Serum Indoxyl Sulfate and Albumin for Patients with Cardiovascular Disease.

The progression of renal dysfunction reduces serum albumin and deteriorates the binding capacity of protein-bound uremic toxins. We evaluated the prognostic implications of serum indoxyl sulfate (IS) and albumin levels in patients with cardiovascular disease.We prospectively enrolled 351 consecutive patients undergoing percutaneous revascularization for coronary artery disease or peripheral artery disease. The primary endpoint was all-cause mortality. Patients were assigned to four groups according to the median levels of serum IS (0.1 mg/dL) and albumin (3.9 g/dL).During the median follow-up time of 575 days, 16 patients died. The IS level was significantly higher in nonsurvivors (0.33 versus 0.85 mg/dL, P < 0.05). On the Kaplan-Meier curve, the high IS/low albumin group presented the highest mortality rate (log-rank test, P < 0.01). Cox proportional hazard analysis revealed that high IS/low albumin (hazard ratio (HR): 5.33; 95% confidence interval (CI): 1.71-16.5; P < 0.01), diastolic pressure (HR: 0.94; 95% CI: 0.91-0.98; P < 0.01), prior stroke (HR: 4.54; 95% CI: 1.33-15.4; P = 0.01), and left ventricular ejection fraction (LVEF) (HR: 0.92; 95% CI: 0.88-0.96; P < 0.001) were associated with increased mortality. Furthermore, the combination of IS and albumin levels significantly conferred an additive value to LVEF for predicting mortality (C-statistic: 0.69 versus 0.80; P < 0.001; net reclassification improvement: 0.83; P < 0.001; integrated discrimination improvement: 0.02; P = 0.02).A lower albumin level adds potentiating effects on IS as a prognostic factor for cardiovascular disease.

Malnutrition is prevalent in patients with cardiorenal syndrome and negatively influences clinical outcome.

Cardiorenal syndrome (CRS) describes the concurrent failure of cardiac and renal function, each influencing the other. Malnutrition and cachexia frequently develop in patients with heart failure or kidney failure. However, no information is currently available on the prevalence of malnutrition in CRS patients. We studied CRS patients admitted to an internal medicine ward during a 5-month period and evaluated their clinical characteristics and nutritional status. Malnutrition risk was assessed by using the validated screening tool NRS-2002 whilst body composition was assessed by bioimpedance analysis and muscle function was measured by handgrip (HG) strength. Cardiac mass was also recorded. Length of stay, hospital readmission and 6-month mortality were registered. During the study period, 22 CRS patients were studied. Twenty patients were diagnosed with either CRS type 1 or CRS type 5. In CRS patients, fat-free mass showed a trend toward representing a protective factor for 6-month mortality (OR=0.904; p=0.06). Also, fat-free mass correlated with HG strength and cardiac ejection fraction. Malnutrition risk was diagnosed in 45% of the patients, whereas 8 patients met the definition of cachexia. Even without statistical significance, CRS patients with malnutrition had lower BMI (Body Mass Index) (p=0.038) and fat-free mass (p= n.s.). However, CRS malnutrition was associated to higher 6-month mortality (p= 0.05), and appears to negatively influence the outcome in CRS (OR= 9; p= 0.06). Our results show that malnutrition is prevalent in CRS patients and influences the clinical outcome. The assessment of nutritional status, and particularly body composition, should be implemented in daily practice of patients with CRS.

Visions in a Crystal Ball: The Future of Peritoneal Dialysis.

BACKGROUND: Peritoneal dialysis (PD) is one of the corner stones of renal replacement therapy and should be strongly considered if preemptive kidney transplantation is not available. SUMMARY: There are several initiatives that may help the growth in the use of PD around the world. First, PD is an underused and valuable option in patients with heart failure and the chronic cardiorenal syndrome, especially in those with frequent hospitalizations despite optimal medical therapy. To identify these patients, an interdisciplinary approach of nephrologists and cardiologists is needed. These patients and other CKD patients with significant residual kidney function may do well with a regimen employing fewer than the usual number of bag exchanges, referred to as "incremental" dialysis. Second, acute kidney injury (AKI) is a worldwide burden with high morbidity and mortality, especially in low income countries. To reach the goal of zero preventable deaths caused by AKI by 2025 endorsed by the International Society of Nephrology, PD is the therapy of choice for treatment in this setting. Third, although dextrose has served well as the osmotic agent in PD solutions, there has been a continuous search for alternative agents. Hyperbranched polyglycerol might be such an osmole. Finally, to obviate the need for production and delivery of bags of PD solution, the development of home-generated dialysate is of interest. Key Message: The future of PD lies not only in accruing experience from the past decades, but also in staying open to other uses.

Revascularization of atherosclerotic renal artery stenosis for chronic heart failure versus acute pulmonary oedema.

AIM: The aim of the study is to determine whether the apparent benefit of revascularization of renal artery stenosis for 'flash' pulmonary oedema extends to heart failure patients without a history of prior acute pulmonary oedema. METHODS: A prospective study of patients with renal artery stenosis and heart failure at a single centre between 1 January 1995 and 31 December 2010. Patients were divided into those with and without previous acute pulmonary oedema/decompensation. Survival analysis compared revascularization versus medical therapy in each group using Cox regression adjusted for age, estimated glomerular filtration rate, blood pressure and co-morbidities. RESULTS: There were 152 patients: 59% male, 36% diabetic, age 70 ± 9 years, estimated glomerular filtration rate 29 ± 17 mL/min per 1.73 m2 ; 52 had experienced previous acute pulmonary oedema (34%), whereas 100 had no previous acute pulmonary oedema (66%). The revascularization rate was 31% in both groups. For heart failure without previous acute pulmonary oedema, the hazard ratio for death after revascularization compared with medical therapy was 0.76 (0.58-0.99, P = 0.04). In heart failure with previous acute pulmonary enema, the hazard ratio was 0.73 (0.44-1.21, P = 0.22). For those without previous acute pulmonary oedema, the hazard ratio for heart failure hospitalization after revascularization compared with medical therapy was 1.00 (0.17-6.05, P = 1.00). In those with previous acute pulmonary oedema, it was 0.51 (0.08-3.30, P = 0.48). CONCLUSION: The benefit of revascularization in heart failure may extend beyond the current indication of acute pulmonary oedema. However, findings derive from an observational study.

The prognostic value of regadenoson SPECT myocardial perfusion imaging in patients with end-stage renal disease.

BACKGROUND: The prognostic value of regadenoson SPECT myocardial perfusion imaging (MPI) has not been specifically studied in patients with end-stage renal disease (ESRD). METHODS AND RESULTS: We prospectively followed ESRD patients enrolled in the ASSUAGE and ASSUAGE-CKD trials in which they received regadenoson-stress 99mTc-tetrofosmin SPECT-MPI. Images were semiquantitatively analyzed by an investigator blinded to clinical and outcome data. Patients were followed for cardiac death, myocardial infarction (MI), and coronary revascularization (CR). Revascularizations occurring >90 days post-MPI were considered "late" events. Survival analysis was performed using Cox regression models, adjusting for age, gender, diabetes, dyslipidemia, smoking, and known coronary artery disease. We analyzed 303 patients (mean age 54 years; 64% men), who were followed for 35 ± 10 months. Adjusting for clinical covariates, abnormal regadenoson-stress MPI (SSS ≥ 4) was associated with increased risk of the composite of cardiac death or MI (23.9% vs 14.4%; HR 1.88; CI 1.04-3.41; P = .037) and the composite of cardiac death, MI, or late CR (27.3% vs 16.7%; HR 1.80; CI 1.03-3.14; P = .039). Adjusting for clinical covariates, regadenoson-induced myocardial ischemia (SDS ≥ 2) was associated with increased rate of the composite endpoint of cardiac death, MI, or CR (33.3% vs 16.9%; HR 1.97; CI 1.19-3.27; P = .008). CONCLUSION: Regadenoson-stress SPECT-MPI provides a significant prognostic value in patients with ESRD. ESRD patients with normal SPECT-MPI have relatively high adverse event rates.

Prognostic impact of SPECT-MPI after renal transplantation.

BACKGROUND: While renal transplantation is increasingly performed for end-stage renal disease, there is a paucity of data on cardiac screening and prognostication post-transplant. We determined the prognostic value of SPECT-MPI in a cohort who underwent renal transplantation. METHODS: Among 4933 renal transplant recipients identified from the Canadian Organ Replacement Register, we examined outcomes of patients who underwent SPECT-MPI in Ontario, Canada. We determined morbidity and mortality using hospitalization and vital statistics registries, according to SPECT-MPI findings. RESULTS: We studied 282 renal transplant recipients (median age 46 years [25th, 75th percentile 37, 58]) with detailed SPECT-MPI results available, followed for a median of 5.7 (3.3, 7.7) years. Among those undergoing SPECT-MPI (66% pharmacologic stress), 41% had an abnormal summed stress score (SSS > 0) and 31% demonstrated abnormal summed difference score (SDS > 0). Rates of cardiovascular death were 0.4 per 100 person-years among those with normal stress perfusion (SSS = 0) and 0.4 per 100 person-years with SDS = 0. After adjusting for age, sex, prior myocardial infarction (MI), and cardiac risk factors, an SSS ≥ 4 conferred increased risk of cardiovascular death or cardiovascular hospitalization with adjusted hazard ratios of 2.52 (95% CI 1.41, 4.52, P = .002) for SSS 4-6 and 2.61 (95% CI 1.52, 4.49, P < .001) for SSS ≥ 7. SDS was a significant predictor of cardiovascular death or hospitalization, with adjusted hazard ratios of 2.96 (95% CI 1.72, 5.09, P < .001) for SDS 4-6 and 3.26 (95% CI 1.64, 6.50, P < .001) for SDS ≥ 7. CONCLUSION: Among renal transplant recipients, SPECT-MPI predicted risk of cardiovascular death and cardiovascular hospitalization events.

Acute kidney injury increases the risk of end-stage renal disease after cardiac surgery in an Asian population: a prospective cohort study.

BACKGROUND: Acute kidney injury (AKI) after cardiac surgery is associated with increased morbidity and mortality. The long-term association between AKI and end-stage renal disease (ESRD) in an Asian population is unknown. Given the high prevalence of diabetes and a younger age of presentation for cardiac surgery, it is important to track this progression of kidney disease. Therefore, we studied the long-term risk of ESRD and mortality in our Asian patients who developed AKI after cardiac surgery. METHODS: With ethics approval, we prospectively recruited 3008 patients who underwent cardiac surgery in Singapore between 2008 and 2012, and followed them up till 2014. ESRD and mortality information were obtained from the Singapore Renal Registry and Singapore Registry of Births and Deaths respectively. AKI was defined using the Acute Kidney Injury Network (AKIN) criteria, and ESRD was defined as stage 5 chronic kidney disease requiring renal replacement therapy. The Cox proportional hazards regression model was used to analyze associations between AKI and the primary outcome of ESRD and the secondary outcome of death. RESULTS: The AKI incidence was 29.1%. During a mean follow-up of 4.4 ± 2.8 years, 0.9% developed ESRD. The hazard ratio (HR) for developing ESRD was 4.7 (95% C.I. = 1.736-12.603, p = 0.002) for AKIN stage 1 patients, and 5.8 (95% C.I. = 1.769-18.732, p = 0.004) for AKIN stage 2 and 3 patients; while the HR for mortality was 1.7 (95% C.I. = 1.165-2.571, p = 0.007) for AKIN stage 1 patients, and 2.5 (95% C.I. = 1.438-4.229, p < 0.001) for AKIN stage 2 and 3 patients. CONCLUSIONS: AKI is associated with ESRD and mortality after cardiac surgery in our Asian population. The trajectory from AKI to ESRD is rapid within 5 years of cardiac surgery. A concerted periodic follow-up assessment is advocated for AKI patients post-cardiac surgery.

Relationship between history of coronary heart disease at dialysis initiation and onset of events associated with heart disease: a propensity-matched analysis of a prospective cohort study.

BACKGROUND: Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease (CVD) events, and a number of reports have shown a relationship between CKD and CVD in pre-dialysis or maintenance dialysis patients. However, few studies have reported serial observations during dialysis initiation and maintenance. Therefore, we examined whether the incidence of heart disease events differed between CKD patients with and without a history of coronary heart disease (CHD) at dialysis initiation. METHODS: The subjects were patients in the 17 centers participating in the Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis (AICOPP) from October 2011 to September 2013. We excluded nine patients whose outcomes were unknown, as determined by a survey conducted at the end of March 2015. Thus, we enrolled 1,515 subjects into the study. We classified patients into 2 groups according to the history of CHD (i.e., a CHD group and a non-CHD group). Propensity scores (PS) represented the probability of being assigned to a group with or without a history of CHD. Onset of heart disease events and associated mortality and all-cause mortality were compared in PS-matched patients by using the log-rank test for Kaplan-Meier curves. Factors contributing to heart disease events were examined using stepwise multivariate Cox proportional hazards analysis. RESULTS: There were 254 patients in each group after PS-matching. During observation, heart disease events occurred in 85 patients (33.5%) in the CHD group and 48 (18.9%) patients in the non-CHD group. The incidence was significantly higher in the CHD group (p < 0.0001). The CHD group was associated with higher incidence of heart disease events (vs. the non-CHD group, hazard ratio = 1.750, 95% confidence interval = 1.160-2.639). In addition, comorbidities such as diabetes mellitus, low body mass index, and low serum high-density lipoprotein cholesterol were associated with higher incidence of events. CONCLUSION: History of CHD at dialysis initiation was associated with a higher incidence of heart disease events and mortality and all-cause mortality. TRIAL REGISTRATION: UMIN 000007096 . Registered 18 January 2012.

Risk Factors and Prognosis of Cardiorenal Syndrome Type 1 in Elderly Chinese Patients: A Retrospective Observational Cohort Study.

BACKGROUND/AIMS: Cardiorenal syndrome type 1 (CRS1) is a syndrome characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). The aims of this study were to investigate the risk factors and the prognosis of CRS1 in elderly patients. METHODS: A total of 312 elderly patients (≥60 years old) with acute heart failure (AHF) were studied. They were assigned as CRS1 (suffered from in-hospital AKI) or NCRS1 (without AKI) group. Clinical and laboratory data were recorded. Univariate and multivariate analysis were performed to clarify the risk factors for occurrence and mortality of CRS1 in this cohort. RESULTS: Incidence of CRS1 was 52.56%. Basic estimated glomerular filtration (eGFR <60 ml/(min.1.73m2) and use of diuretics were associated with the higher risk of CRS1 in elderly patients (OR=2.239, P=0.025; OR=2.555, P=0.001; respectively). Whereas higher concentration of serum albumin was protective factor for them (OR=0.907, P=0.007). The in-hospital mortality of CRS1 was 23.2%. Dialysis, use of beta blockers or diuretics were associated with all-cause death of CRS1 patients (OR=10.407, P<0.001; OR=0.312, P=0.011; OR=0.345, P=0.040; respectively). The in-hospital mortality of AHF patients was 13.1%. Higher Charlson comorbidity index, occurrence of CRS1 and dialysis were risk factors for in-hospital mortality of AHF patients (OR=4.723, P=0.041; OR=6.096, P=0.008; OR=18.743, P<0.001; respectively). CONCLUSIONS: Incidence of CRS1 in elderly patients is relatively high and associated with poor outcome. Reduced basic eGFR, lower serum albumin and use of diuretics are risk factors for the occurrence of CRS1 in elderly patients, while use of diuretics, beta blockers and dialysis during hospitalization are predictors of in-hospital mortality in patients with CRS1. These results above suggest that more suitable treatments for the elderly with CRS1 might be needed.

Intradialytic Hypoxemia in Chronic Hemodialysis Patients.

When kidney failure occurs, patients are at risk for fluid overload states, which can cause pulmonary edema, pleural effusions, and upper airway obstruction. Kidney disease is also associated with impaired respiratory function, as in central sleep apnea or chronic obstructive pulmonary disease. Hence, respiratory and renal diseases are frequently coexisting. Hypoxemia is the terminal pathway of a multitude of respiratory pathologies. The measurement of oxygen saturation (SO2) is a basic and commonly used tool in clinical practice. Both arterial oxygen saturation (SaO2) and central venous oxygen saturation (ScvO2) can be easily obtained in hemodialysis (HD) patients, SaO2 from an arteriovenous access and ScvO2 from a central catheter. Here, we give a brief overview of the anatomy and physiology of the respiratory system, and the different technologies that are currently available to measure oxygen status in dialysis patients. We then focus on literature regarding intradialytic SaO2 and ScvO2. Lastly, we present clinical vignettes of intradialytic drops in SaO2 and ScvO2 in association with different symptoms and clinical scenarios with an emphasis on the pathophysiology of these cases. Given the fact that in the general population hypoxemia is associated with adverse outcomes, including increased mortality, cardiac arrhythmias and cardiovascular events, we posit that intradialytic SO2 may serve as a potential marker to identify HD patients at increased risk for morbidity and mortality.

N-acteyl-ß-D-glucosaminidase and kidney injury molecule-1: New predictors for long-term progression of chronic kidney disease in patients with heart failure.

AIM: Patients with chronic heart failure (CHF) are often characterized by the cardiorenal syndrome (CRS). The aim of the present study was to assess whether novel markers of kidney injury are able to predict progression of chronic kidney disease (CKD) in patients with CHF. METHODS: New renal biomarkers, N-acteyl-ß-D-glucosaminidase (NAG), kidney injury molecule-1 (KIM-1) and Neutrophil Gelatinase-Associated Lipocalin (NGAL), were assessed from urine samples of 149 patients with chronic heart failure. During a 5-year-follow-up, renal function was assessed by creatinine and estimated glomerular filtration rate (eGFR CKD EPI) and was available for 138 patients. Further, data regarding all-cause mortality was obtained. RESULTS: Twenty-six patients (18.8%) developed a progression of CKD during the follow-up period, as defined by decline in eGFR category accompanied by a ≥25% drop in eGFR form baseline. No difference regarding age, sex, body mass index, hypertension, diabetes or EF was present between patients with and without CKD progression (each P = n.s.). At baseline, creatinine concentrations and eGFR were significantly different between both groups (sCr: 1.50 ± 0.67 vs 1.04 ± 0.37, P = < 0.001; eGFR: 47.8 ± 12.3 vs. 77.3 ± 23.5 mL/min per 1.73m(2) , each P < 0.001). In a Kaplan-Meier-analysis, KIM-1 and NAG were significant predictors for CKD progression (both P < 0.05). In Cox regression analysis, NAG > median (OR 3.25,P = 0.013), initial eGFR (OR 0.94, P < 0.001) and diuretic use (OR 3.92, P = 0.001) were independent predictors of CKD progression. Further, KIM-1 and NAG were also independent predictors of a combined endpoint of CKD progression and all-cause mortality by Cox regression analysis (each P < 0.05). The combination of both markers showed additive value regarding both endpoints. NGAL showed no association with CKD progression. CONCLUSIONS: During long-term follow-up chronic heart failure patients with CKD show a relevant disease progression. The current study emphasizes a strong association of the tubular biomarkers NAG and KIM-1 with CKD progression in chronic heart failure and suggests their usefulness as cardiorenal markers.

Post-procedural hemodiafiltration in acute coronary syndrome patients with associated renal and cardiac dysfunction undergoing urgent and emergency coronary angiography.

OBJECTIVES: We investigated the use of a 3-hr treatment with hemodiafiltration, initiated soon after emergency or urgent coronary angiography in acute coronary syndrome (ACS) patients with associated severe renal and cardiac dysfunction. BACKGROUND: Patients with ACS and severe combined renal and cardiac dysfunction have a particularly high mortality risk. In them, the ideal strategy to both optimize treatment of coronary disease and minimize renal injury risk is currently unknown. METHODS: This was an interventional study. ACS patients (STEMI and NSTEMI) with associated severe renal (eGFR ≤30 ml/min/1.73 m(2) ) and cardiac (LVEF ≤40%) dysfunction, admitted at La Spezia Hospital <24 hr from symptoms onset, underwent a prophylactic 3-hr hemodiafiltration treatment, which was started soon after urgent or emergency coronary procedure. Controls were patients matched for age, gender, Mehran's risk score, and kind of ACS, admitted at the Centro Cardiologico Monzino Milan. In-hospital and 1-year outcomes were evaluated. RESULTS: Sixty patients (30% STEMI), 30 hemodiafiltration-treated patients and 30 controls, with similar baseline characteristics, were included. In-hospital and cumulative 1-year mortality rates were significantly lower in hemodiafiltration-treated patients than in controls (3% vs. 23%; P = 0.05, and 10% vs. 53%; P < 0.001, respectively). Moreover, they had a lower incidence of severe AKI (10% vs. 40%; P = 0.015) and lower need for rescue renal replacement therapy during hospitalization (7% vs. 27%; P = 0.04). CONCLUSIONS: Our pilot study suggests that, in ACS patients with severe renal and cardiac insufficiency, treatment with an aggressive prophylactic hemodiafiltration session after urgent or emergency coronary angiography seems to be associated with a relevant improvement in survival.