Severe Chronic Kidney Disease Patients Research Articles

Comparison of the prognosis between complete and incomplete revascularization among moderate to severe chronic kidney disease patients with acute coronary syndrome

Abstract Background Complete revascularization (CR) in acute coronary syndrome patients with multivessel disease (MVD) is recommended in current clinical practice guidelines. However, the benefit of CR in moderate to severe chronic kidney disease (CKD) patients remains controversial. We aimed to compare the clinical outcomes between complete and incomplete revascularization among moderate to severe CKD patients who presented with ACS. Methods Of 1,924 ACS patients who underwent percutaneous coronary intervention (PCI) in our center, 127 patients were CKD. CR was defined as residual SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score ≤ 3. The primary outcome was the patient oriented clinical outcome (POCO) at 1 year, including all-cause death, any myocardial infarction, any revascularization, and heart failure requiring hospitalization. Results The mean age of the patients was 73.89±9.07 years. The median estimated glomerular filtration rate (eGFR) was 32.56±10.68 ml per minute per 1.73 m2. The rate of POCO at 1 year was significantly lower in the CR group (16.3% vs 39.3%; HR 0.36; 95%CI, 0.16-0.81; p=0.014). The primary outcome was mainly driven by 1-year all-cause death which was significantly lower in the CR group (14.0% vs 39.3%; HR 0.32; 95%CI 0.13-0.76; p=0.017). The rate of initiation of renal replacement therapy was comparable (4.7% vs 2.4%; p=0.55). Conclusion CR with a target SYNTAX score ≤ 3 improved 1-year prognosis of POCO and all-cause death in ACS patients with moderate to severe CKD without increasing the rates of renal replacement therapy.1-year POCOPrespecified Subgroup Analysis of POCO

Application value of real-time shear wave elastography for quantitative evaluation of chronic kidney disease in pediatric patients.

To evaluate the effectiveness of real-time shear wave elastography (SWE) in quantitative evaluation of chronic kidney disease (CKD) in pediatric patients. SWE was conducted on 58 pediatric patients with CKD (CKD group) and 70 healthy volunteers (Control group). Computer-assisted quantitative analysis was utilized to determine the percentage of interstitial fibrosis (IF) in images from the CKD group, categorizing them into mild, moderate, and severe groups according to IF% values. The differences in Young's modulus (YM) and estimated Glomerular Filtration Rate (eGFR) between the renal cortex and medulla in these groups were compared. Additionally, the relationships between YM and IF% as well as YM and eGFR, were analyzed. The YM values in right lower pole cortex and medulla of the CKD group were significantly higher than those in the control group (all P < 0.05). Significant differences were observed in eGFR among mild, moderate, and severe CKD patients (F = 40.882). YM demonstrated a correlation with eGFR in both the renal cortex and medulla (r = -0.329, P = 0.012; r = 0.417, P = 0.001). YM values increased with the severity of renal interstitial fibrosis in a pronounced trend across groups (F = 109.962, F = 72.950, all P < 0.001). Additionally, YM correlated with IF% in both the renal cortex and medulla (r = 0.362, P = 0.006; r = 0.483, P < 0.001). The optimal cut-off value of renal cortex YM for distinguishing between CKD and control group was 4.05 kPa. SWE enables quantitative assessment of kidney YM values, revealing significantly higher values in children with CKD compared to healthy individuals. YM is correlated with the severity of renal interstitial fibrosis, thereby establishing SWE as a valuable non-invasive tool for quantitative evaluation of pediatric CKD.

Ticagrelor versus Clopidogrel in diabetes patients afflicted with acute coronary syndrome stratified by renal function

Abstract Background Ticagrelor has been recommended in place of clopidogrel as part of dual antiplatelet therapy (DAPT) in diabetic patients with acute coronary syndrome (ACS). Chronic kidney disease (CKD) patients also have a worse prognosis in the setting of ACS, but the safety and efficacy data for the use of P2Y12 inhibitors in moderate to severe CKD patients (eGFR &amp;lt;60 mL/min/1.73m2) are insufficient. Purpose There has been limited data on the outcome of prescribing ticagrelor compared to clopidogrel in ACS-DM patients with chronic kidney disease (CKD). Methods This prospective, nationwide, multi-center, observational study, the Acute Coronary Syndrome-Diabetes Mellitus Registry (ACS-DM Registry) was compiled from consecutive patients between October 1, 2013 and September 30, 2016. The primary end point was repeated revascularisation and the composite outcome was CV death, repeat revascularisation and CV-related readmission, was stratified by renal function stages. The Cox proportional hazards models and propensity score models were applied to six-months, one-year, and two-year post ACS, respectively. Results There were 539 patients with moderate to severe CKD or on dialysis identified from ACS-DM Registry. There were 451 patients eligible for inclusion criteria of which 116 patients were taking ticagrelor and 335 patients were taking clopidogrel. At our two-year follow-up, the unadjusted incidence of primary end point resulted higher in Ticagrelor group (HR 2.09, 95% CI 1.37-3.18, p = 0.001). After adjustment, ticagrelor also had poor primary end point event and composite outcome as compared to clopidogrel (HR 2.24, 95% CI 1.36-3.68, p = 0.002; HR 1.63, 95% CI 1.06-2.48, p = 0.024, respectively). In regards to the repeated revascularisation issue, the clopidogrel was preferable within the eGFR strata (CKD stage III: HR 2.53, 95% CI 1.32-4.84, CKD stage IV: 1.06 (0.09-12.51), CKD stage V: 1.91 (0.80-4.59), P for interaction=0.684). Conclusions Cardiovascular benefits associated with ticagrelor may not be as significant as in the landmark trial. Our results show that patients taking ticagrelor was associated with increased CV events as compared to clopidogrel in ACS-DM patients with stage III-V CKD.propensity score matchingForest plots

Incorporating Uremic Solute-mediated Inhibition of OAT1/3 Improves PBPK Prediction of Tenofovir Renal and Systemic Disposition in Patients with Severe Kidney Disease.

Dose modification of renally secreted drugs in patients with chronic kidney disease (CKD) has relied on serum creatinine concentration as a biomarker to estimate glomerular filtration (GFR) under the assumption that filtration and secretion decline in parallel. A discrepancy between actual renal clearance and predicted renal clearance based on GFR alone is observed in severe CKD patients with tenofovir, a compound secreted by renal OAT1/3. Uremic solutes that inhibit OAT1/3 may play a role in this divergence. To examine the impact of transporter inhibition by uremic solutes on tenofovir renal clearance, we determined the inhibitory potential of uremic solutes hippuric acid, indoxyl sulfate, and p-cresol sulfate. The inhibition parameters (IC50) were incorporated into a previously validated mechanistic kidney model; simulated renal clearance and plasma PK profile were compared to data from clinical studies. Without the incorporation of uremic solute inhibition, the PBPK model failed to capture the observed data with an absolute average fold error (AAFE) > 2. However, when the inhibition of renal uptake transporters and uptake transporters in the slow distribution tissues were included, the AAFE value was within the pre-defined twofold model acceptance criterion, demonstrating successful model extrapolation to CKD patients. A PBPK model that incorporates inhibition by uremic solutes has potential to better predict renal clearance and systemic disposition of secreted drugs in patients with CKD. Ongoing research is warranted to determine if the model can be expanded to include other OAT1/3 substrate drugs and to evaluate how these findings can be translated to clinical guidance for drug selection and dose optimization in patients with CKD.

Understanding Statin-Roxadustat Drug-Drug-Disease Interaction Using Physiologically Based Pharmacokinetic Modeling.

A different drug-drug interaction (DDI) scenario may exist in patients with chronic kidney disease (CKD) compared with healthy volunteers (HV), depending on the interplay between drug-drug and disease (drug-drug-disease interaction, DDDI). Physiologically based pharmacokinetic (PBPK) modelling, in lieu of a clinical trial, is a promising tool for evaluating these complex DDDIs in patients. However, the prediction confidence of PBPK modelling in severe CKD population is still low when non-renal pathways are involved. More mechanistic virtual disease population and robust validation cases are needed. To this end, we aimed to: 1) understand the implications of severe CKD on statins (atorvastatin, simvastatin, and rosuvastatin) PK and DDI; and 2) predict untested clinical scenarios of statin-roxadustat DDI risks in patients to guide suitable dose regimens. A novel virtual severe CKD population was developed incorporating the disease effect on both renal and non-renal pathways. Drug and disease PBPK models underwent a four-way validation. The verified PBPK models successfully predicted the altered PK in patients for substrates and inhibitors and recovered the observed statin-rifampicin DDIs in patients and the statin-roxadustat DDIs in HV within 1.25- and 2-fold error. Further sensitivity analysis revealed that the severe CKD disease effect on statins PK is mainly mediated by hepatic BCRP for rosuvastatin and OATP1B1/3 for atorvastatin. The magnitude of statin-roxadustat DDI in severe CKD patients was predicted to be similar to that in HV. PBPK-guided suitable dose regimens were identified to minimize the risk of side effects or therapeutic failure of statins when co-administered with roxadustat.

Association of malnutrition with all-cause and cardiovascular mortality in patients with mild to severe chronic kidney disease undergoing coronary angiography: a large multicenter longitudinal study.

Evidence on the prognostic impact of malnutrition was focused on patients with advanced kidney disease. The relationships between malnutrition and all-cause and cardiovascular mortality in patients with different severity of chronic kidney disease (CKD) have not been adequately addressed. We aimed to reveal the prevalence of malnutrition and its prognostic value in patients with different severity of CKD undergoing coronary angiography (CAG). This was a multicenter, longitudinal, and retrospective cohort study of 12,652 patients with non-dialysis dependent CKD (defined as estimated glomerular filtration rate [eGFR] < 60mL/min/1.73m2) undergoing CAG from five tertiary hospitals between January 2007 and December 2020. The controlling nutritional status (CONUT) score was applied to assess nutritional status. Cox regression models and competing risk Fine and Gray models were used to examine the relationships between malnutrition, all-cause and cardiovascular mortality. Further stratified analysis was performed according to baseline CKD severity (mild, moderate and severe, defined by eGFR < 30, 30-44 and 45-59ml/min/1.73 m2). During a median follow-up of 5.5years (interquartile range: 3.2 to 8.6years), 3801 patients (30.0%) died, and 2150 (17.0%) definitely died of cardiovascular disease. After controlling for confounders, patients had higher all-cause mortality (mild, moderate, and severe vs. absent: HR 1.27, 95 CI % [1.17-1.39]; HR 1.54, 95 CI % [1.39-1.71]; HR 2.22, 95 CI % [1.78-2.77], respectively; P for trend < 0.001) and cardiovascular mortality (mild, moderate and severe vs. absent: HR 1.35, 95 CI % [1.21-1.52]; HR 1.67, 95 CI % [1.45-1.92]; HR 2.10, 95 CI % [1.55-2.85], respectively; P for trend < 0.001) with the severity of malnutrition. In further stratified analysis, a similar prognostic impact of malnutrition was observed in patients with mild to moderate CKD, while mild malnutrition did not seem to have a consistent effect on severe CKD patients. Malnutrition is common among patients with mild to severe CKD undergoing CAG and is strongly associated with increased risk of all-cause and cardiovascular mortality. Malnutrition seems to have a modestly stronger impact on mortality in patients with mild to moderate CKD. This study was registered at Clinicaltrials.gov as NCT05050877.

Efficacy of Salivary Creatinine and Urea and their Association with Serum Creatinine and Urea Levels in Severe Chronic Kidney Disease Patients

Efficacy of Salivary Creatinine and Urea and their Association with Serum Creatinine and Urea Levels in Severe Chronic Kidney Disease Patients

Risk factors for neurocognitive impairment and the relation with structural brain abnormality in children and young adults with severe chronic kidney disease

BackgroundSevere chronic kidney disease (CKD) in children and young adults has shown to be associated with abnormal brain development, which may contribute to neurocognitive impairments. We aimed to investigate risk factors for neurocognitive impairment and investigate the relation with structural brain abnormalities in young severe CKD patients.MethodsThis cross-sectional study includes 28 patients with severe CKD (eGFR < 30), aged 8–30 years (median 18.5 years), on different treatment modalities (pre-dialysis [n = 8], dialysis [n = 8], transplanted [n = 12]). We assessed neurocognitive functioning using a comprehensive test battery and brain structure by magnetic resonance imaging metrics of brain volume and white matter integrity (fractional anisotropy [FA] and mean diffusivity [MD] measured with diffusion tensor imaging). Multivariate regression and mediation analyses were performed between clinical CKD parameters, brain structure, and neurocognitive outcome.ResultsA combination of risk factors (e.g., longer time since kidney transplantation, longer dialysis duration and late CKD onset) was significantly associated with lower intelligence and/or worse processing speed and working memory. Lower FA in a cluster of white matter tracts was associated with lower intelligence and mediated the relation between clinical risk factors and lower intelligence.ConclusionsYoung severe CKD patients with a prolonged duration of kidney replacement therapy, either dialysis or transplantation are at particular risk for impairments in intelligence, processing speed, and working memory. Disrupted white matter integrity may importantly contribute to these neurocognitive impairments. Prospective, longitudinal studies are needed to elucidate the mechanisms involved in CKD and treatment that affect white matter integrity and neurocognitive outcome in young patients.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

Is It Safe to Do Percutaneous Coronary Intervention in Moderate to Severe Chronic Kidney Disease Patients? A Prospective Cohort Study.

Contrast-induced acute kidney injury (CI-AKI) is a common and potentially serious complication of percutaneous coronary intervention (PCI) procedures, as it induces acute kidney injury (AKI), especially in previously diagnosed chronic kidney disease (CKD) patients, particularly in those who also have diabetes. Adequate hydration and using a minimal volume of contrast media are the recommended measures to decrease CI-AKI in CKD patients. A combination of sodium bicarbonate and N-acetylcysteine (NAC) may be a superior strategy for preventing CI-AKI. This study is aimed to evaluate the safety of PCI in moderate to severe CKD patients. This was a prospective, single-center study, from 2019 to 2021. We included all chronic kidney disease who undergo PCI procedures. The kidney level was measured on admission and 24 hours after the PCI procedure. The patients received 75 meq/500 mL of sodium bicarbonate one to six hours before procedures, oral acetylcysteine 600 mg bid for three days, and rehydration with 1000 ml of normal saline infusion for eight hours in patients without congestive heart failure. SPSS Version 23.0 (IBM SPSS Statistics for Windows, Version 23.0., IBM Corp., Armonk, NY) was used to input and process the data. This study included 118 subjects, with baseline characteristics of age 58.77 ± 9.08 years, 80.5% male, 47.5% diabetic, 50% hypertension, and 59.5% congestive heart failure. From the coronary angiogram, we found most of our subjects (57.6%) had three-vessel disease, 28.8% had two-vessel disease, and 15.6% had one-vessel disease. About 67.8% of subjects used <50 ml of low molecular contrast. The baseline creatinine level was 2.46 ± 1.04 mg/dL and the estimated glomerular filtration rate (eGFR) was 30 ± 12.65 mL/min. There were 19 (16.1%) patients with stage 3A CKD, 45 (38.1%) stage 3B, 41 (34.7%) stage 4, and 41 (34.7%) stage 5. The kidney function test after 24 hours of contrast admission showed a creatinine level of 2.37 ± 1.20 mg/dL (P<0.05) and the eGFR of 34.74 ± 16.10 mL/min. There was no significant difference in creatinine levels between stage 3A and stage 5 CKD. There was a significant reduction in creatinine in stage 3B CKD, from 1.917 ± 0.22 to 1.71 ± 0.37 mg/dL (P = 0.001); and stage 4 CKD, from 2.77 ± 0.55 to 2.72 ± 0.94 mg/dL (P = 0.013). CKD is a risk factor for developing CI-AKI after PCI, which is a marker of poor long-term outcomes. The development of CI-AKI is a strong predictor of post-PCI bleeding, which aggravates hemodynamic instability. The combination of NAC and NaHCO3 exerts a better antioxidative effect, which reduces the harmful short-term and long-term consequences of contrast media. Previous studies revealed the use of low-to-zero contrast media was safer in CKD patients who had undergone PCI. By applying these measures, our study showed a good outcome of PCI with no worsening renal function in CKD patients. With good prophylaxis measures, such as using minimal volume contrast media, adequate rehydration, and the combination of sodium bicarbonate and acetylcysteine, it is safe to do PCI in moderate to severe CKD patients.

MO456: Renal and Major Clinical Outcomes After Nephrectomy in Patients With Pre-Existing Chronic Kidney Disease (ON-CKD Study)

Abstract BACKGROUND AND AIMS Partial nephrectomy (PN) has progressively replaced radical nephrectomy (RN) whenever feasible for renal tumors. However, its effects on renal outcomes are less known in patients with pre-existing chronic kidney disease (CKD) or with solitary kidney (SK). We aimed to assess renal and major clinical outcomes after PN or RN in patients with moderate to severe CKD or SK. METHOD We included all surgical procedures conducted between 2013 and 2018 in the Hospices Civils de Lyon, in patients with last pre-operative estimated glomerular filtration rate (eGFR) &amp;lt;60mL/min/1.73m², or with SK. Exclusion criteria were eGFR &amp;lt; 15mL/min/1.73m² or dialysis, RN on SK, ablative therapy. Demographic, tumors and surgeries characteristics were collected, as well as eGFR 1 month and 1 year after surgery. Main outcome was a composite criterion including CKD progression or major cardio-vascular events or death, assessed 1 year after surgery. Predictors of the main outcome were determined using multivariate analyses. RESULTS We included 173 procedures (67 RN and 79 PN on CKD patients, 27 PN on SK patients). Patients undergoing RN were older, had bigger tumors and higher T stages on TNM classification. Preoperative estimated glomerular filtration rate (eGFR) and CKD stages were not different between the groups. One year after surgery, PN was associated with less occurrence of the main composite outcome compared to RN (42.9% versus 70.7%, P &amp;lt; 0.01). On multivariate analysis, independent risk factors for the main outcome were postoperative AKI (no AKI as reference; AKI stage 1 odds ratio (OR) = 8.68, 95% confidence interval (CI) 3.23–23.33; AKI stage 2 OR = 23.50, 95% CI 2.33–236.51; AKI stage 3 OR = 28.87, 95% CI 4.77–167.61) and bigger tumor size (OR = 1.21/cm, 95% CI 1.02–1.45), while preoperative eGFR was not (Table 1). Compared to pre-operative values, eGFR significantly decreased both after RN or PN 1 month after surgery (eGFR loss -12mL/min 1.73m² after RN P &amp;lt; 0.001, −3mL/min/1.73m² after PN, P &amp;lt; 0.05) and this decrease remained stable 1 year after surgery (eGFR loss -11mL/min/1.73m² after RN, P &amp;lt; 0.001, −3mL/min/1.73m² after PN, P &amp;lt; 0.05), but renal function was better preserved after PN than after RN at 1 month (P &amp;lt; 0.05) or 1 year (P &amp;lt; 0.01) (Figure 1). CONCLUSION In moderate to severe CKD patients, PN was associated with less risk of CKD progression or major cardio-vascular event or death 1 year after surgery, compared to RN. Postoperative AKI was the major determinant of clinical and renal outcomes.

PBPK Simulation-Based Evaluation of Ganciclovir Crystalluria Risk Factors: Effect of Renal Impairment, Old Age, and Low Fluid Intake

Dosing guidance is often lacking for chronic kidney disease (CKD) due to exclusion of such patients from pivotal clinical trials. Physiologically based pharmacokinetic (PBPK) modelling supports model-informed dosing when clinical data are lacking, but application of these approaches to patients with impaired renal function is not yet at full maturity. In the current study, a ganciclovir PBPK model was developed for patients with normal renal function and extended to CKD population. CKD-related changes in tubular secretion were explored in the mechanistic kidney model and implemented either as proportional or non-proportional decline relative to GFR. Crystalluria risk was evaluated in different clinical settings (old age, severe CKD and low fluid intake) by simulating ganciclovir medullary collecting duct (MCD) concentrations. The ganciclovir PBPK model captured observed changes in systemic pharmacokinetic endpoints in mild-to-severe CKD; these trends were evident irrespective of assumed pathophysiological mechanism of altered active tubular secretion in the model. Minimal difference in simulated ganciclovir MCD concentrations was noted between young adult and geriatric populations with normal renal function and urine flow (1 mL/min), with lower concentrations predicted for severe CKD patients. High crystalluria risk was identified at reduced urine flow (0.1 mL/min) as simulated ganciclovir MCD concentrations exceeded its solubility (2.6–6 mg/mL), irrespective of underlying renal function. The analysis highlighted the importance of appropriate distribution of virtual subjects’ systems data in CKD populations. The ganciclovir PBPK model illustrates the ability of this translational tool to explore individual and combined effects of age, urine flow, and renal impairment on local drug renal exposure.Graphical

Current aspects of stable ischemic heart disease. ISСHEMIA study: breakthrough or constant optimism in approaches to treatment. Myocardial ischemia in non-obstructive coronary arteries (INOCA)

Approaches to stable coronary artery disease (CАD) treatment have been subject to debate for a long time. One of the first and fundamental studies in stable coronary artery disease patients treatment is the COURAGE study, which showed the advantage of rational drug therapy in comparison with percutaneous intervention in such patients. However, CAD high prevalence with medical and social significance cause the need for future development of relationship between conservative and invasive approaches in the problem of this disease treatment. It was particularly the focus of recently completed multicentre ISCHEMIA trail. The aim of review is to analyze the available data on the management of stable coronary artery disease patients based on the ISCHEMIA study data. Results. In the largest multicenter randomized clinical trial ISCHEMIA, the primary outcome (cardiovascular death, myocardial infarction, cardiac arrest with effective resuscitation, hospitalization due to heart failure) rate was 13.3% in the routine invasive strategy group and 15.5% in the conservative strategy group (p = 0.34). The main secondary outcome rate also does not differ between groups significantly. Quality of life in the non-invasive group was higher only in those patients who had angina at baseline. Study subanalysis demonstrated that left coronary artery borderline stenosis accompanied by a poor prognosis, and an invasive strategy improves angina symptoms. Also, low density lipoprotein cholesterol target values achievement predictors were determined. In addition, women, participated in ISCHEMIA study had more frequent angina episodes, regardless less extensive coronary artery damage, and less severe ischemia manifestations than men. Among stable CAD accompanied moderate to severe ischemia and severe chronic kidney disease patients, no evidence initial invasive strategy, compared initial conservative strategy, in relation of death or non-fatal myocardial infarction risk reduction was found. Conclusion: ISCHEMIA trial data demonstrated necessity more carefully stable coronary artery disease patients selection for invasive treatment, taking into account angina pectoris severity and modern antianginal therapy possibilities.

Исследование ISCHEMIA. Взаимоотношение консервативного и интервенционного подходов к лечению стабильной ишемической болезни сердца. Ишемия миокарда при необструктивном поражении коронарных артерий (INOCA)

Introduction. Approaches to the stable coronary heart disease (CHD) treatment have been the subject to debate a long time. One of the fi rst and fundamental studies in the treatment of stable coronary heart disease patients is the COURAGE trial, which showed the advantage of rational drug therapy in comparison with percutaneous intervention in such patients. However, the CHD high prevalence with medical and social signifi cance necessitate the future consideration of the relationship between medical, that is conservative, and invasive approaches in treatment of this disease. It was particularly the focus of the recently completed multicentre ISCHEMIA trial. Another urgent problem of modern cardiology is myocardial ischemia in non-obstructive (&lt;50% luminal occlusion) coronary arteries (INOCA) identifi ed in approximately 70% of patients who underwent coronary angiography. Aim of the research. Analysis of the available data on the management of stable CHD patients based on the ISCHEMIA trial data and review of publications on the INOCA problem. Results. In the ISCHEMIA trial, the occurrence rate of the primary outcome (cardiovascular death, myocardial infarction (MI), resuscitated cardiac arrest, hospitalization for chronic heart failure) was 13.3% in the routine invasive strategy group and 15.5% in the conservative strategy group (p = 0.34). The occurrence rate of the main secondary outcomes also did not differ between the groups signifi cantly. Quality of life in the invasive group was higher only in patients who had angina at baseline. The study subanalysis demonstrated that borderline left coronary artery stenosis is associated with a poor prognosis, and an invasive strategy relieves the angina symptoms. Women who participated in the ISCHEMIA trial had a higher incidence of angina attacks, despite less extensive coronary arteries (CA) lesions and less severe ischemia manifestations than men. Among patients with stable CHD accompanied with moderate to severe ischemia and severe chronic kidney disease patients, no evidence for the benefi t of the initial invasive strategy in reducing the risk of death or nonfatal myocardial infarction compared to the conservative strategy was found. As for ischemia in non-obstructive coronary arteries (INOCA), it is diagnosed in at least one in five patients who have undergone coronary angiography. This requires the search for new diagnostic methods, verifi cation of risk factors, causes, and optimal treatment approaches. Conclusion. The ISCHEMIA trial data demonstrated the necessity for a more careful selection of patients with stable CHD for invasive treatment, taking into account the angina pectoris severity and modern antianginal therapy possibilities. Management of patients with myocardial ischemia accompanied by non-obstructive CA lesions should be carried out on the basis of the EAPCI Expert Consensus Document on Ischaemia with INOCA (2020) which discusses the genesis of angina, as well as the diagnosis and treatment of this condition.

Impact of chronic kidney disease on mid-term prognosis of stable angina patients with high-dose or low-dose pitavastatin treatment: REAL-CAD sub-study

Abstract Background We previously demonstrated that high-dose (4 mg/day) compared with low-dose (1 mg/day) pitavastatin therapy significantly reduced cardiovascular events in Japanese patients with stable coronary artery disease in the Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study. However, little is known about whether the advantage of high-dose statins over low-dose statins is consistent among non-, mild, and moderate to severe chronic kidney disease (CKD) patients. Purpose The aim of this study was to clarify the effect of high-dose statins on cardiovascular events in Japanese patients with or without CKD. Methods The REAL-CAD study is a prospective, multicenter, randomized, open-label, blinded endpoint, physician-initiated superiority trial. In this sub-analysis of REAL-CAD study, patients were categorized into three groups according to estimated glomerular filtration rate (eGFR). Patients on hemodialysis were excluded in this study. The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction (MI), non-fatal ischemic stroke, or unstable angina requiring emergency hospitalization. A secondary composite endpoint was defined as a composite of the primary endpoint event or clinically-indicated coronary revascularization excluding target-lesion revascularization. Results The total population of the REAL-CAD study was 12,413 patients. After exclusion of patients lacking eGFR data, the numbers of patients categorized into non-CKD (eGFR ≥60 mL/min/1.73m2), mild CKD (eGFR; 45–60), and moderate to severe CKD (eGFR &amp;lt;45) were 7,778 (64%), 3,176 (26%), and 1,164 (10%), respectively. The median follow-up period was 3.9 years. The baseline characteristics and medications were well balanced between the two groups in each CKD group. While high-dose compared to low-dose pitavastatin significantly reduced the primary endpoint in non-CKD patients, the effect was not observed in mild CKD and moderate to severe CKD patients (Figure 1). High-dose compared with low-dose pitavastatin did not significantly reduce the secondary composite endpoint in both mild and moderate to severe CKD patients as well. High-dose pitavastatin significantly reduced the risks of MI and any coronary revascularization in non-CKD patients, however, the effects were diminished in mild CKD and moderate to severe CKD patients. There was no significant difference between high-dose and low-dose pitavastatin treatment in the risk of all-cause death, cardiovascular death, ischemic stroke, or unstable angina requiring emergency hospitalization in patients with or without CKD. Conclusion Although high-dose pitavastatin therapy significantly reduced cardiovascular events in non-CKD patients with stable angina compared to low-dose pitavastatin, such beneficial effects had diminished in Japanese patients with mild or moderate to severe CKD patients. Figure 1. Kaplan-Meier Curves for Endpoints Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Clinical Research of Lifestyle-Related Disease of the Public Health Research Foundation

Asymptomatic hypertension-mediated organ damage in patients with or without moderate to severe chronic kidney disease

Abstract Introduction Moderate or severe chronic kidney disease (CKD) is regarded as high or very high risk factor in the Systematic COronary Risk Evaluation (SCORE) system, as stated in the ESC guidelines on arterial hypertension. Assessment of cardiovascular (CV) risk should be completed evaluating hypertension-mediated organ damage (HMOD). Purpose The aim of our study was to find out differences in HMOD in patients with or without moderate to severe chronic kidney disease (CKD). Methods We enrolled 80 consecutive non-diabetic hypertensive patients, divided into two groups according to the presence of impaired renal function, evaluated by estimated glomerular filtration rate (eGFR): moderate to severe CKD group (n=26 patients, eGFR &amp;lt;60 mL/min/1.73 m2) and mild CKD - normal renal function group (n=54 patients, eGFR ≥60 mL/min/1.73 m2). A transthoracic echocardiogram was performed to evaluate cardiac HMOD. Small and large vessel damage was assessed by means of non-mydriatic digital fundus oculi examination in order to detect arteriolar narrowing using arteriolar-venular ratio (AVr), applanation tonometry to measure carotid-femoral pulse wave velocity (cfPWV) and carotid ultrasound to quantify intima-media tickness (IMT). Results Moderate to severe CKD patients appeared to be older (mean age 75.54±8.06 vs 63.38±9.62, p=0.001) and showed lower level of total and LDL cholesterol. Both groups showed abnormal values of cfPWV, but these were significantly higher in the presence of moderate to severe CKD (14.12±7.93 m/s vs 10.94±5.81 m/s, p=0.03). Abnormal AVr values were found in patients with higher grade of CKD, with statistically significant differences in the two groups (0.75±0.015 vs 0.81±0.06, p=0.00001). Carotid IMT resulted to be at the upper limit of normality in both groups (0.95±0.15 vs 0.90±0.18, p=0.35). With regard to echocardiography evaluation, left ventricular mass index (LVMi: 105.04±0.4 vs 96.35±1.7, p=0.06) and relative wall thickness (RWT: 0.43±0.02 vs 0.42±0.05, p=0.41) did not differ significantly in the two groups, with a mild trend for LVMi. Both groups showed abnormal diastolic dysfunction on average, but no differences emerged in the presence of more severe renal impairment (deceleration time 281.74±0.37 vs 256.30±0.54, p=0.08; E/A 0.86±0.03 vs 0.95±0.25, p=0.20; E/e' 7.89±2.93 vs 7.60±2.46, p=0.66). Conclusions Our study showed significant differences in HMOD in presence of moderate to severe renal impairment. Moderate to severe CKD seemed to be associated to vascular damage (hypertensive retinopathy and arterial stiffness), while no significant differences in echocardiographic markers of cardiac remodeling were found, suggesting that systemic vascular damage is more closely linked to CKD than cardiac damage. Therefore, the use of fundus oculi examination and PWV should always be considered to properly assess the target organ damage in hypertensive patients with CKD. Funding Acknowledgement Type of funding source: None

Optimal treatment of chronic kidney disease with uncertainty in obtaining a transplantable kidney: an MDP based approach

Chronic kidney disease (CKD) is one of the most serious and prevalent health issues all over the world. The evolution of CKD can last for many years until the death of patients, and the method of treatment mainly includes medication, dialysis, and transplantation with the evolution of the disease. It has been validated by many empirical studies that for severe CKD patients, the optimal treatment is transplantation if a suitable kidney is available, otherwise the patients should initiate dialysis at a suitable time. It has also been validated that the initiation time of dialysis significantly impacts not only the direct treatment results, but also the success of a future possible kidney transplantation. Motivated by this consideration, we investigate the decision-making problem of the optimal treatment approach to maximize the patient’s total reward including pre-transplant reward and post-transplant reward (if applicable), considering the possibility of having a suitable kidney transplantation in the future. A Markov decision process model is established in which the status of the process is described by the patient health status. We present some structural properties of the decision-making problem, which are used to choose the optimal treatment approach in different health status of patients. We collect the clinical data in the simulation experiments to obtain the fitted curves of the evolution process of different CKD patients, and compare the simulation results with the actual clinical data to demonstrate the advantage of our model.

New oral spherical carbon adsorbent effectively reduces serum indoxyl sulfate levels in moderate to advanced chronic kidney disease patients: a multicenter, prospective, open-label study

BackgroundElevated levels of serum indoxyl sulfate (IS) have been linked to cardiovascular complications in patients with chronic kidney disease (CKD). Oral sorbent therapy using spherical carbons selectively attenuates IS accumulation in CKD patients. This study aimed to investigate whether oral administration of a new oral spherical carbon adsorbent (OSCA), reduces serum IS levels in moderate to severe CKD patients.MethodsThis prospective, multicenter, open-label study enrolled patients with CKD stages 3–5. Patients were prescribed OSCA for 8 weeks (6 g daily in 3 doses) in addition to standard management. Serum IS levels were measured at baseline and 4 and 8 weeks of treatment with OSCA.ResultsA total of 118 patients were enrolled and 87 eligible patients completed 8 weeks of study. The mean age of the study subjects was 62.8 ± 13.7 years, and 80.5% were male. Baseline levels of serum IS were negatively correlated with estimated glomerular filtration rate (eGFR) (r = − 0.406, P < 0.001) and increased with increasing CKD stages (stage 3, 0.21 ± 0.21 mg/dL; stage 4, 0.54 ± 0.52 mg/dL; stage 5, 1.15 ± 054 mg/dL; P for trend = 0.001). The patients showed significant reduction in serum total IS levels as early as 4 weeks after OSCA treatment (22.5 ± 13.9% reduction from baseline, P < 0.001) and up to 8 weeks (31.9 ± 33.7% reduction from baseline, P < 0.001). This reduction effect was noted regardless of age, kidney function, or diabetes. No severe adverse effects were reported. Gastrointestinal symptoms were the most commonly reported adverse effects. In total, 21 patients withdrew from the study, with dyspepsia due to heavy pill burden as the most common reason. The medication compliance rate was 84.7 ± 21.2% (min 9%, max 101%) for 8 weeks among those who completed the study.ConclusionsOSCA effectively reduced serum IS levels in moderate to severe CKD patients. Gastrointestinal symptoms were the most commonly reported complications, but no treatment-related severe adverse effects were reported.Trial registrationClinical Research Information Service (KCT0001875. 14 December 2015.)

Major adverse cardiovascular events in patients undergoing percutaneous coronary intervention or coronary artery bypass graft with underlying chronic kidney disease

To assess early and late outcome in severe chronic kidney disease patients undergoing revascularisation. The retrospective ambi-directional cohort study was conducted at Tabba Heart Institute, Karachi, and comprised data from May, 2012, to July,2016, related to severe chronic kidney disease patients with creatinine clearance <30ml/min or end-stage renal disease on haemodialysis who had undergone coronary artery bypass graft / percutaneous coronary intervention. Early outcome was in-hospital major adverse cardiac event, like mortality, stroke and new haemodialysis. Late outcome was major adverse cardiac event, like mortality, stroke, re infarction and re-revascularisation. Data was analysed using Stata 12.1. Of the 228 patients with mean age of 64.2±10.8 years, 109(47.8%) with a maen age of 65.4±11.6 had undergone percutaneous coronary intervention, and 119(52.2%) with a mean age of 64.2±10.8 years had undergone coronary artery bypass graft. Overall mortality was 36(15.8%) patients; 15(13.7%) percutaneous coronary intervention, 21(17.6%)coronary artery bypass graft (p>0.05). Predictors of in-hospital adverse events were coronary artery bypass graft and cardiogenic shock (p<0.05). Follow-up was available in 181(94.3%) patients with a mean duration of 22.0±13.9 months. Heart failure and post-procedure stroke were independent predictors of late outcome (p<0.05). Among patients with severe chronic kidney disease or end stage renal disease undergoing revascularisation, percutaneous coronary intervention PCI was performed in patients with less complex anatomy or as emergency for acute ST-elevation myocardial infarction. Coronary artery bypass graft patients had higher early mortality, but improved late survival.

Prognostic Value of Incomplete Revascularization after Percutaneous Coronary Intervention Following Acute Coronary Syndrome: Focus on CKD Patients.

Background: Residual coronary artery disease (CAD) has been associated with worsened prognosis in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS). The residual SYNTAX Score (rSS) aims to assess residual CAD after PCI. The association between kidney function and rSS has not been investigated in ACS patients. In this study, we sought to determine whether chronic kidney disease (CKD) patients exhibit more incomplete revascularization following stage revascularization procedures by PCI. We evaluated the impact of incomplete revascularization on the occurrence of major cardiovascular events (MACE) at one-year follow-up. Methods: A total of 831 ACS patients undergoing PCI were divided into 3 subgroups according to their estimated Glomerular Filtration Rate (eGFR): 695 with eGFR ≥ 60 mL/min/1.73 m², 108 with eGFR 60–30 mL/min/1.73 m², 28 with eGFR < 30 mL/min/1.73 m². Initial SYNTAX score (SS) and rSS were calculated for all patients. Incomplete revascularization was defined by rSS > 8. The primary endpoint was the occurrence of MACE (all-cause mortality, myocardial infarction (MI), repeated revascularization except from planned revascularization, stroke and definite or probable recurrent stent thrombosis) one year after the index procedure. Results: Severe CKD patients had significantly higher MACE (12.0% vs. 25.9% vs. 35.7%; p < 0.001), all-cause mortality, cardiovascular mortality and heart failure events. Patients with rSS > 8 had higher MACE, all-cause and cardiovascular mortality. CKD was an independent predictive factor of rSS > 8 (HR: 1.65, 95% CI: 1.01 to 2.71; p = 0.048). Multivariate analysis identified rSS > 8, but not CKD, as an independent predictor of cardiac death and MACE. Conclusion: In ACS, CKD is predictive of incomplete revascularization, which stands out as a strong predictor of adverse cardiovascular outcomes including cardiac death and MACE.

Assessment of phagocytic activity of polymorphonuclear leukocytes in hospitalized patients with Stages 4 and 5 chronic kidney disease

Background: Infections are the main reason for hospitalization and the second common cause of death in chronic kidney disease (CKD) patients. Infections develop primarily as a consequence of deranged innate immunity. In this study, we assessed the efficiency of phagocytic function of polymorphonuclear (PMN) leukocytes in severe CKD patients. Aims and Objectives: The aims of the study were (i) to assess the phagocytic index and lytic index of PMN leukocytes (PMNLs) in Stages 4 and 5 CKD patients. (ii) To compare the above indices with healthy age and sex-matched controls. Materials and Methods: The study was carried out in 60 adults in the age group of 18–60 years of which 30 were CKD patients in Stages 4 and 5 taking conservative treatment (not on dialysis) and other 30 were age and sex-matched controls. After screening for inclusion and exclusion criteria, 5 ml of venous blood was collected and taken immediately for evaluation. Phagocytic index which is the number of neutrophils positive for ingested microbes per 100 neutrophils and lytic index which is the total number of microbes per 100 cells were calculated. These are indices of neutrophil functioning. Results: Statistically significant decrease in both phagocytic index and lytic index were found in Stages 4 and 5 CKD patients as compared to controls. Conclusion: In the present study, we were able to establish that phagocytic capacity of PMNLs is adversely affected in severe CKD patients. This gains importance in the light of immune dysfunction being considered as a major cause of premature deaths resulting from infections in severe CKD.