Advanced Chronic Kidney Disease Patients Research Articles

Effect of Renamezin upon attenuation of renal function decline in pre-dialysis chronic kidney disease patients: 24-week prospective observational cohort study

Renamezin® is a modified capsule-type oral spherical adsorptive carbon which lowers indoxyl sulfate levels in patients with advanced chronic kidney disease (CKD). This 24-week prospective observational cohort study was performed to evaluate the effect of Renamezin® upon attenuation of renal function decline. A total of 1,149 adult patients with baseline serum creatinine 2.0–5.0 mg/dL were enrolled from 22 tertiary hospital in Korea from April 2016 to September 2018. Among them, a total of 686 patients completed the study and were included in the intention-to-treat analysis. A total of 1,061 patients were included in the safety analysis. The mean age was 63.5 years and male patients were predominant (63.6%). Most of the patients (76.8%) demonstrated high compliance with study drug (6g per day). After 24 week of treatment, serum creatinine was increased from 2.86±0.72 mg/dL to 3.06±1.15 mg/dL (p<0.001), but estimated glomerular filtration rate was not changed significantly during observation period (22.3±6.8 mL/min/1.73m2 to 22.1±9.1 mL/min/1.73m2, p = 0.243). Patients with age over 65 years old and those under good systolic blood pressure control <130 mmHg were most likely to get benefit from Renamezin® treatment to preserve renal function. A total of 98 (9.2%) patients out of 1,061 safety population experienced 134 adverse events, of which gastrointestinal disorders were the most common. There were no serious treatment-related adverse events. Renamezin® can be used safely to attenuate renal function decline in moderately advanced CKD patients.

Proteomic Profiling of Leukocytes Reveals Dysregulation of Adhesion and Integrin Proteins in Chronic Kidney Disease-Related Atherosclerosis.

A progressive loss of functional nephrons defines chronic kidney disease (CKD). Complications related to cardiovascular disease (CVD) are the principal causes of mortality in CKD; however, the acceleration of CVD in CKD remains unresolved. Our study used a complementary proteomic approach to assess mild and advanced CKD patients with different atherosclerosis stages and two groups of patients with different classical CVD progression but without renal dysfunction. We utilized a label-free approach based on LC-MS/MS and functional bioinformatic analyses to profile CKD and CVD leukocyte proteins. We revealed dysregulation of proteins involved in different phases of leukocytes' diapedesis process that is very pronounced in CKD's advanced stage. We also showed an upregulation of apoptosis-related proteins in CKD as compared to CVD. The differential abundance of selected proteins was validated by multiple reaction monitoring, ELISA, Western blotting, and at the mRNA level by ddPCR. An increased rate of apoptosis was then functionally confirmed on the cellular level. Hence, we suggest that the disturbances in leukocyte extravasation proteins may alter cell integrity and trigger cell death, as demonstrated by flow cytometry and microscopy analyses. Our proteomics data set has been deposited to the ProteomeXchange Consortium via the PRIDE repository with the data set identifier PXD018596.

Nutrition in Chronic Kidney Disease-The Role of Proteins and Specific Diets.

Chronic kidney disease (CKD) is a global public health burden, needing comprehensive management for preventing and delaying the progression to advanced CKD. The role of nutritional therapy as a strategy to slow CKD progression and uremia has been recommended for more than a century. Although a consistent body of evidence suggest a benefit of protein restriction therapy, patients’ adherence and compliance have to be considered when prescribing nutritional therapy in advanced CKD patients. Therefore, these prescriptions need to be individualized since some patients may prefer to enjoy their food without restriction, despite knowing the potential importance of dietary therapy in reducing uremic manifestations, maintaining protein-energy status.

Approach to stable angina in patients with advanced chronic kidney disease.

Chronic kidney disease is one of the major risk factors for coronary artery disease. Both end-stage renal disease (ESRD) and advanced chronic kidney disease patients have atypical presentations of coronary artery disease (CAD) due to modifications in cardinal symptoms and clinical presentation. Data on evaluation and management of coronary artery or stable angina is limited in advanced chronic kidney disease (CKD) patients due to a limited number of trials. There are sparse data supporting either percutaneous coronary intervention (PCI) or coronary artery bypass graft in advanced CKD patients. The ISCHEMIA-CKD trial to date is the most extensive prospective randomized study looking at advanced CKD patients study looking at advanced CKD stage 4/5 patients randomized to medical treatment alone vs. invasive strategy for moderate to severe myocardial ischemia. There was no evidence found that an initial invasive strategy compared with conservative strategy with maximal medical management resulted in reduced risk of death or nonfatal myocardial infarction in patients with advanced CKD and coronary artery disease with stable angina. In this review, we will discuss the existing data on assessment and management of stable coronary artery disease/stable angina. And how this extrapolates to the application in advanced CKD patients awaiting kidney transplant.

Fenofibrate Delays the Need for Dialysis and Reduces Cardiovascular Risk Among Patients With Advanced CKD.

Fenofibrate provides limited cardiovascular (CV) benefits in the general population; however, little is known about its benefit among advanced chronic kidney disease (CKD) patients. This study compared outcomes among advanced CKD patients treated with fenofibrate, statins, a combination of both, and none of these. This national cohort study was based on Taiwan's National Health Insurance Research Database. Patients younger than 20 years with advanced CKD were identified and further divided into 4 groups according to treatment. The inverse probability of treatment weighting was used to balance baseline characteristics. Patients received fenofibrate, statins, a combination of fenofibrate and statins, or none of these in the 3 months preceding the advanced CKD date. Main outcome measures included all-cause mortality, CV death, and incidence of permanent dialysis. The fenofibrate and statin groups exhibited a lower risk of CV death (fenofibrate vs nonuser: hazard ratio [HR]: 0.84; 95% CI, 0.75-0.94; statins vs nonuser: HR: 0.94; 95% CI, 0.90-0.97) compared with the nonuser group. The fenofibrate group further exhibited the lowest incidence of permanent dialysis (fenofibrate vs nonuser: subdistribution HR [SHR]: 0.78; 95% CI, 0.77-0.80; statins vs fenofibrate: SHR: 1.27; 95% CI, 1.26-1.29; combination vs fenofibrate: SHR: 1.15; 95% CI, 1.13-1.17). Furthermore, the combined administration of fenofibrate and high-intensity statins exhibited a lower risk of major adverse cardiac and cerebrovascular events. For patients with advanced CKD, continuing fenofibrate may provide a protective effect on CV outcomes equal to that of statins, and it may further delay the need for permanent dialysis. The combination of fenofibrate and high-intensity statins may have additional benefits.

Epicardial fat tissue, coronary arterial calcification and mortality in patients with advanced chronic kidney disease and hemodialysis

Introduction and objectivesEpicardial and mediastinal adipose tissue (EAT, MAT) are linked to metabolic syndrome and coronary artery disease. Patients with chronic kidney disease (CKD) have thicker EAT. We assessed if EAT and MAT could be associated with increased mortality and cardiovascular events in patients with advanced CKD and haemodialysis therapy. MethodsA post-hoc study was performed. We analyzed a prospective series of 104 cases. EAT thickness was quantified by a multislice synchronized computed tomography (MSCT). ResultsThe follow-up period was 112.68 (109.94–115.42) months. The optimal cut-off point of EAT for prediction of total mortality was 11.45 mm (92.86% and 43.75%). EAT thickness was associated with serum albumin levels, serum triglyceride levels, phosphorus and calcium phosphate product. The EAT was greater in haemodialysis patients compared to those with advanced CKD (P < .001). Patients with diabetes mellitus had greater EAT and MAT thickness (P = .018). At the end of follow up, the survival average time of patients with EAT thickness <11.45 mm was 97.48 months vs. 76.65 months for thickness > 11.45 mm (P = .007). ConclusionsA higher EAT and MAT thickness was associated with increased mortality. Furthermore, EAT was associated with lower free survival time to fatal and non-fatal cardiovascular events. The measurement of EAT and MAT by MSCT could be a prognostic tool to predict cardiovascular events and mortality risk in advanced CKD patients.

Association of serum lncRNA H19 expression with inflammatory and oxidative stress markers and routine biochemical parameters in chronic kidney disease.

Chronic kidney disease (CKD) is a disorder that affects millions worldwide, and current treatment options aiming at inhibiting the progression of kidney damage are limited. Long noncoding RNA (lncRNA) H19 is one of the first explored lncRNAs and its deregulation is associated with renal pathologies, such as renal cell injury and nephrotic syndrome. However, there is still no research investigating the connection between serum lncRNA H19 expressions and clinical outcomes in CKD patients. Therefore, we investigated the relation of serum lncRNA H19 expressions with routine biochemical parameters, inflammatory cytokines, oxidative stress and mineralization markers in advanced CKD patients. lncRNA H19 serum levels from 56 CKD patients and 20 healthy controls were analyzed with reverse-transcription quantitative polymerase chain reaction method. Serum tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and osteocalcin (OC) levels were measured with enzyme linked-immunosorbent assay. Total antioxidant status (TAS) and total oxidative status (TOS) levels were evaluated by the routine measurement method. We found that lncRNA H19 expressions were upregulated in patients with CKD compared to the controls. Furthermore, lncRNA H19 relative expression levels showed a negative relationship with glomerular filtration rate (GFR) while it was positively correlated with ferritin, phosphorus, parathyroid hormone, TNF-α, IL-6, OC, TAS and TOS levels. lncRNA H19 expressions were increased in CKD stage 3-5 and HD patients, and elevated lncRNA H19 expressions were associated with decreased glomerular filtration rate, inflammation, and mineralization markers in these patients.

Association of digoxin with mortality in patients with advanced chronic kidney disease: A population-based cohort study.

Digoxin is commonly prescribed for heart failure and atrial fibrillation, but there is limited data on its safety in patients with chronic kidney disease (CKD). We conducted a population-based cohort study using the pre-end stage renal disease (ESRD) care program registry and the National Health Insurance Research Database in Taiwan. Of advanced CKD patient cohort (N = 31,933), we identified the digoxin user group (N = 400) matched with age and sex non-user group (N = 2,220). Multivariable Cox proportional hazards and sub-distribution hazards models were used to evaluate the association between digoxin use and the risk of death, cardiovascular events (acute coronary syndrome, ischemic stroke, or hemorrhagic stroke) and renal outcomes (ESRD, rapid decline in estimated glomerular filtration rate-eGFR, or acute kidney injury). Results showed that all-cause mortality was higher in the digoxin user group than in the non-user group, after adjusting for covariates (adjusted hazard ratio, aHR 1.63; 95% CI 1.23-2.17). The risk for acute coronary syndrome (sub-distribution hazard ratio, sHR 1.18; 95% CI 0.75-1.86), ischemic stroke (sHR 1.42; 95% CI 0.85-2.37), and rapid eGFR decline (sHR 1.00 95% CI 0.78-1.27) was not significantly different between two groups. In conclusion, our study demonstrated that digoxin use was associated with increased mortality, but not cardiovascular events or renal function decline in advanced CKD patients. This finding warns the safety of prescribing digoxin in this population. Future prospective studies are needed to overcome the limitations of cohort study design.

Improving hepatitis B vaccination rates for advanced chronic kidney disease patients: a quality improvement initiative.

IntroductionChronic kidney disease (CKD) patients are vulnerable to hepatitis B, and immunization prior to end stage kidney disease is recommended to optimize seroconversion. Our institution undertook a process improvement approach to increase hepatitis B vaccination in stage 4 and 5 CKD patients.MethodsFour strategies were utilized such as: (1) Electronic health record (EHR)-based CKD registry to identify patients, (2) EHR-based physician/nurse reminders, (3) a co-located nurse appointment for vaccine administration, and (4) information sharing and provider awareness effort. The CKD registry was utilized to identify patients with stage 4 or 5 CKD, with at least two clinic visits in the prior 2 years, who had not received the hepatitis B vaccine or did not have serologic evidence of immunity. Target monthly vaccination rate was set at 75%, based on clinic leadership, nephrologist, and nurse consensus.ResultsA total of 239 patients were included in the study period, from November 2018 to January 2019 (observation period) and from February 2019 to September 2019 (intervention period). Monthly vaccination rate improved from 48% in November 2018 to the target rate of 75% by the end of the intervention (August and September 2019). There was a statistically significant increase from the rate of vaccination at a unique patient level in the first month of the baseline period, compared to the last month of the intervention period (51 vs. 75% p = 0.03).ConclusionsUtilizing a nurse-led approach to hepatitis B vaccination, coupled with EHR-based tools, along with continuous monitoring of performance, helped to improve hepatitis B vaccination among CKD stage 4 and 5 patients.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10157-020-02013-4.

Novel conservative management of chronic kidney disease via dialysis-free interventions.

In advanced chronic kidney disease (CKD) patients with progressive uremia, dialysis has traditionally been the dominant treatment paradigm. However, there is increasing interest in conservative and preservative management of kidney function as alternative patient-centered treatment approaches in this population. The primary objectives of conservative nondialytic management include optimization of quality of life and treating symptoms of end-stage renal disease (ESRD). Dietetic-nutritional therapy can be a cornerstone in the conservative management of CKD by reducing glomerular hyperfiltration, uremic toxin generation, metabolic acidosis, and phosphorus burden. Given the high symptom burden of advanced CKD patients, routine symptom assessment using validated tools should be an integral component of their treatment. As dialysis has variable effects in ameliorating symptoms, palliative care may be needed to manage symptoms such as pain, fatigue/lethargy, anorexia, and anxiety/depression. There are also emerging treatments that utilize intestinal (e.g., diarrhea induction, colonic dialysis, oral sorbents, gut microbiota modulation) and dermatologic pathways (e.g., perspiration reduction) to reduce uremic toxin burden. As dialysis may not confer better survival nor improved patient-centered outcomes in certain patients, conservative management is a viable treatment option in the advanced CKD population.

The Efficacy and Renal Protective Effect of Tolvaptan in Chronic Kidney Disease Patients after Open-Heart Surgery.

Purpose: Unlike loop diuretics, tolvaptan is reported to have a renal protective effect. The purpose of this study was to retrospectively assess the efficacy of tolvaptan administration in chronic kidney disease (CKD) patients following open-heart surgery.Methods: From February 2017 to August 2020, 75 patients with preoperative CKD stages IIIb–V were enrolled in this study and were divided into two groups: the control group (n = 30) and the tolvaptan group (n = 45). All patients routinely received conventional diuretics starting from postoperative day (POD) 1. Tolvaptan at 7.5–15 mg/day was administered if the patients had persistent fluid retention or poor response to conventional diuretics.Results: Tolvaptan administration was initiated at a mean of POD 2.9 ± 2.2, and the mean dosing period was 4.1 ± 3.0 days. The mean time to return to the preoperative body weight in the control and tolvaptan groups was similar. However, estimated glomerular filtration rate (eGFR) was significantly increased at the time when body weight reached the preoperative level and at discharge in the tolvaptan group than in the control group.Conclusion: This study demonstrated the renal protective effect of tolvaptan even in advanced CKD patients after open-heart surgery.

Tejido graso epicárdico, calcificación arterial coronaria y mortalidad en pacientes con enfermedad renal crónica avanzada y hemodiálisis

Introduction and objectivesEpicardial and mediastinal adipose tissue (EAT, MAT) are linked to metabolic syndrome and coronary artery disease. Patients with chronic kidney disease (CKD) have thicker EAT. We assessed if EAT and MAT could be associated with increased mortality and cardiovascular events in patients with advanced CKD and haemodialysis therapy. MethodsA post-hoc study was performed. We analyzed a prospective series of 104 cases. EAT thickness was quantified by a multislice synchronized computed tomography (MSCT). ResultsThe follow-up period was 112.68 (109.94 -115.42) months. The optimal cut-off point of EAT for prediction of total mortality was 11.45mm (92.86% and 43.75%). EAT thickness was associated with serum albumin levels, serum triglyceride levels, phosphorus and calcium phosphate product. The EAT was greater in haemodialysis patients compared to those with advanced CKD (P<.001). Patients with diabetes mellitus had greater EAT and MAT thickness (P=.018). At the end of follow up, the survival average time of patients with EAT thickness <11.45mm was 97.48 months vs. 76.65 months for thickness > 11.45mm (P=.007). ConclusionsA higher EAT and MAT thickness was associated with increased mortality. Furthermore, EAT was associated with lower free survival time to fatal and non-fatal cardiovascular events. The measurement of EAT and MAT by MSCT could be a prognostic tool to predict cardiovascular events and mortality risk in advanced CKD patients.

Advanced Glycation End Products (AGE) and Soluble Forms of AGE Receptor: Emerging Role as Mortality Risk Factors in CKD.

Advanced glycation end-products (AGE) can promote chronic kidney disease (CKD) progression and CKD-related morbidities. The soluble receptor for AGE (sRAGE) is a potential biomarker of inflammation and oxidative stress. Here, we explored the role of AGE, glycated albumin, sRAGE and its different forms, cRAGE and esRAGE, as prognostic factors for mortality in 111 advanced CKD patients. The median follow-up time was 39 months. AGE were quantified by fluorescence, sRAGE and its forms by ELISA. Malnutrition was screened by the Malnutrition Inflammation Score (MIS). The Cox proportional hazards regression model was used to assess the association of variables with all-cause mortality. Mean levels of sRAGE, esRAGE and cRAGE were 2318 ± 1224, 649 ± 454 and 1669 ± 901 pg/mL. The mean value of cRAGE/esRAGE was 2.82 ± 0.96. AGE were 3026 ± 766 AU and MIS 6.0 ± 4.7. eGFR correlated negatively with AGE, sRAGE, esRAGE and cRAGE, but not with cRAGE/esRAGE. Twenty-eight patients died. No difference was observed between diabetic and non-diabetic patients. Starting dialysis was not associated with enhanced risk of death. AGE, esRAGE and cRAGE/esRAGE were independently associated with all-cause mortality. AGE, esRAGE and cRAGE/esRAGE may help to stratify overall mortality risk. Implementing the clinical evaluation of CKD patients by quantifying these biomarkers can help to improve patient outcomes.

Arterial endothelial function, carotid artery intima-media thickness and abdominal aortic calcification in diabetic and nondiabetic CKD stage 4–5 patients not on dialysis

AimsWe aimed to study the effect of diabetes (DM) on endothelial dysfunction assessed by flow-mediated vasodilatation (FMD), carotid intima-media thickness (cIMT) and abdominal aortic calcification score (AAC) in chronic kidney disease (CKD) stage 4–5 patients not on dialysis. MethodsAltogether 199 non-dialysis CKD stage 4–5 patients enrolled in the Chronic Arterial Disease, quality of life and mortality in chronic KIDney injury (CADKID) study with plain lumbar radiograph for the assessment of AAC were included. Data on cIMT and FMD were available for 172 and 161 patients, respectively. ResultsMedian age was 65 (IQR 54–76) years, 88 (44.2%) patients had DM and median eGFR was 12 (IQR 10–14) ml/min/1.73 m2 in the study. FMD [controls: 3.3(2.0–6.7)% vs. DM-patients: 4.3(1.3–6.6)%, p = 0.73] and cIMT [controls: 0.65(0.58–0.87)mm vs. DM-patients: 0.67(0.59–0.81)mm, p = 0.65], were similar between the groups. AAC was higher in patients with DM [controls: 5(1–9) vs. DM-patients: 7(2–13), p = 0.01]. The significant multivariate determinants for AAC were older age (β = 0.22, p < 0.0001), pulse pressure (β = 0.05, p < 0.0001), DM (β = 1.33, p = 0.04) and ProBNP (per µg/l β = 0.18, p = 0.0008). AAC and cIMT were associated with incident cardiovascular death independent of DM. ConclusionsDM is associated with increased AAC but not increased cIMT or attenuated FMD in advanced CKD patients.

The impact of chronic kidney disease on long-term outcomes following semi-urgent and elective percutaneous coronary intervention.

The effects of chronic kidney disease (CKD) on outcomes in patients undergoing semi-urgent and elective percutaneous coronary intervention (PCI) are unclear. This study aims to investigate impact of CKD on long-term outcomes of this population. This was a retrospective cohort study of patients who underwent semi-urgent and elective PCI from 1 January 2014 to 31 December 2015 at a tertiary academic center. They were stratified into five groups - group 1 [estimated glomerular filtration rate (eGFR) ≥90 ml/min/1.73m2], group 2 (eGFR 60-89 ml/min/1.73m2), group 3 (eGFR 30-59 ml/min/1.73 m2), group 4 (eGFR <30 ml/min/1.73m2), and group 5 (dialysis). Demographics, risk factors in relation to endpoints of all-cause mortality, contrast-induced nephropathy (CIN), three-point major adverse cardiac events (MACE) (cardiac death, subsequent myocardial infarction, subsequent stroke), and four-point MACE (including target lesion revascularization) were analyzed. One thousand six hundred nine patients were included. Advanced CKD patients were more likely to be female and older, with higher prevalence of co-morbidities. Compared to group 1, group 4 patients were associated with increased risk of three-point [adjusted hazard ratio (aHR) 1.94, 95% confidence interval (CI): 1.06-3.55; P = 0.031] and four-point MACE (aHR 2.15, 95% CI: 1.21-3.80; P = 0.009). However, higher contrast volume usage [odds ratio (OR) 2.20, 95% CI: 1.04-4.68; P = 0.040) was associated with increased CIN risk but not reduced eGFR (OR 1.62, 95% CI: 0.57-4.65; P = 0.369). Advanced CKD patients undergoing PCI were associated with higher co-morbid burden. Despite adjustments for co-morbidities, these patients had higher mortality and worse cardiovascular outcomes at 3 years following contemporary PCI.

Abstract 16043: Effectiveness and Safety of Switching From Warfarin to Apixaban in Advanced Chronic Kidney Disease Patients With Prevalent Atrial Fibrillation in the United States Between 2012 and 2016

Introduction: Apixaban is the preferred direct acting oral anticoagulant in patients with CKD and has advantages compared with warfarin. Data on effectiveness and safety outcomes after switching from warfarin to apixaban in patients with prevalent AF and CKD are limited. Methods: Individuals with advanced CKD not on dialysis and prevalent AF who receive ≥6 months of continuous warfarin prior to Jan 1, 2012 were identified from the United States Data Renal System (USRDS) database. Individuals were followed from Jan 1, 2012 - Dec 31, 2015 to identify switches from warfarin to apixaban. The primary efficacy outcome was combined all-cause stroke, transient ischemic attack, or systemic thromboembolism. The primary safety outcome was major bleeding. Outcomes were compared between patients switching from apixaban and those continuing warfarin. Individuals were censored at the time of the first event or anticoagulation discontinuation, discontinuous Medicare part D coverage, dialysis, kidney transplant, a 2 nd switch in anti-coagulant, or death. Results: 1762 individuals with advanced CKD not receiving dialysis with non valvular AF or flutter were on warfarin during the 6 months prior to Jan 1, 2012. Of these, 71 (4.0%; 57.8% male, mean age 78.2 years (SD ±6.6), 78.9% white) switched from warfarin to apixaban and 1691 (41.3%; 47.6% male, mean age 80.1 years (SD ±8.7), 87.9% white) continued warfarin from Jan 1, 2012 - Dec 31, 2015. Incidence of all cause stroke or systemic thromboembolism in the apixaban switch and warfarin continuation groups were 1 (1.4%) and 303 (17.8%) respectively. Incidence of major bleeding events in the two groups were 1 (1.4%) and 201 (11.9%). Conclusions: Among advanced CKD patients with AF in the US who switched from warfarin to apixaban the proportion of all cause stroke or systemic thromboembolism and major bleeding events were low. Data is limited by duration of apixaban market authorization and short follow up.

The validity of Dutch health claims data for identifying patients with chronic kidney disease: a hospital-based study in the Netherlands.

BackgroundHealth claims data may be an efficient and easily accessible source to study chronic kidney disease (CKD) prevalence in a nationwide population. Our aim was to study Dutch claims data for their ability to identify CKD patients in different subgroups.MethodsFrom a laboratory database, we selected 24 895 adults with at least one creatinine measurement in 2014 ordered at an outpatient clinic. Of these, 15 805 had ≥2 creatinine measurements at least 3 months apart and could be assessed for the chronicity criterion. We estimated the validity of a claim-based diagnosis of CKD and advanced CKD. The estimated glomerular filtration rate (eGFR)-based definitions for CKD (eGFR < 60 mL/min/1.73 m2) and advanced CKD (eGFR < 30 mL/min/1.73 m2) satisfying and not satisfying the chronicity criterion served as reference group. Analyses were stratified by age and sex.ResultsIn general, sensitivity of claims data was highest in the population with the chronicity criterion as reference group. Sensitivity was higher in advanced CKD patients than in CKD patients {51% [95% confidence interval (CI) 47–56%] versus 27% [95% CI 25–28%]}. Furthermore, sensitivity was higher in young versus elderly patients. In patients with advanced CKD, sensitivity was 72% (95% CI 62–83%) for patients aged 20–59 years and 43% (95% CI 38–49%) in patients ≥75 years. The specificity of CKD and advanced CKD was ≥99%. Positive predictive values ranged from 72% to 99% and negative predictive values ranged from 40% to 100%.ConclusionWhen using health claims data for the estimation of CKD prevalence, it is important to take into account the characteristics of the population at hand. The younger the subjects and the more advanced the stage of CKD the higher the sensitivity of such data. Understanding which patients are selected using health claims data is crucial for a correct interpretation of study results.

Chlortalidone and bumetanide in advanced chronic kidney disease: HEBE-CKD Trial

Abstract Introduction Current treatment for hypertension and volume overload in chronic kidney disease consists of loop diuretics, nevertheless, chronic use leads to adaptive changes at the distal nephron, which in turn decreases their efficacy. The use of thiazide diuretics could be another treatment option in these patients, notwithstanding, there's not enough evidence to justify their use in this population. Purpose To evaluate the efficacy and safety of treatment with bumetanide plus chlorthalidone in in patients with advanced chronic kidney disease. Methods A double-blind randomized controlled trial was conducted at our hospital. Thirty-two patients with hypertension, chronic kidney disease stage IV/V, and chronic loop diuretic use where divided in two groups. The dual treatment group received bumetanide (4 mg QD) plus chlorthalidone (100 mg QD), while the control group was given bumetanide (4 mg QD) plus placebo, both for twenty-eight days. Systemic blood pressure, bioimpedance, and urinary electrolytes were measured at seven and twenty-eight days of treatment. Results There was a significant decrease of systemic blood pressure in the dual treatment group when compared with the control group; systolic blood pressure −26.1±15.3 vs. −10±23.3 mmHg (p=0.028), diastolic blood pressure −13.5±10.7 vs. −3.4±11.9 mmHg (p=0.018), and mean arterial pressure −18.1±8.7 vs. −5.4±14.3 mmHg (p=0.006). There was also a significant decrease of volume overload in the dual treatment group when compared to the control group; total body water −4.36±3.29 vs. +0.075±1.78 litres (p&amp;lt;0.001), extracellular water −2.55±1.1 vs. +0.150±1.2 litres (p&amp;lt;0.001), and extracellular water to total body water ratio −2.92±4.76 vs. −0.24±1.42 (p=0.039). The treatment group increased its fractional excretion of sodium, while the control group demonstrated an increase, though differences were non-significant. As for adverse effects, there was a non-significant increase of urea and creatinine levels in the dual treatment group when compared with controls. Conclusions In advanced chronic kidney disease plus hypertension patients whose treatment with loop diuretics is insufficient, combined use of bumetanide plus chlorthalidone can be useful for systemic blood pressure and volume overload control. Figure 1 Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Hospital General de México

Metformin Use and Risk of All-Cause Mortality and Cardiovascular Events in Patients With Chronic Kidney Disease-A Systematic Review and Meta-Analysis.

BackgroundTo evaluate whether metformin use assuredly alters overall all-cause death in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD).MethodsPubmed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials were systematically searched from inception to Feb. 29, 2020 with no language restriction. All related articles comparing all-cause death of T2DM and CKD patients after metformin use (monotherapy or combination) versus non-metformin treatment were identified. Pooled risk ratios (RR) and 95% confidence intervals (CI) were computed using random-effects models regardless of the heterogeneity quantified by Cochrane χ2 and I2 statistics.ResultsTotally 13 studies (9 cohort studies [CSs], 3 subanalyses or post-hoc analyses of randomized controlled trials [RCTs], and 1 nested case-control article) involving 303,540 patients were included. Metformin-based treatments relative to any other measure displayed significantly lower risks of all-cause mortality (Pooled RRs 0.71, 95%CI 0.61 to 0.84; I2 = 79.0%) and cardiovascular events (Pooled RRs 0.76, 95%CI 0.60 to 0.97; I2 = 87.0%) in CKD patients at stage G1-3, with substantial heterogeneity. Metformin use was not significantly related with these end points in advanced CKD patients.ConclusionsMetformin use is connected with significantly less risks of all-cause mortality and cardiovascular events in patients with T2DM and mild/moderate CKD. However, RCTs with large sample sizes are warranted in the future to assess whether these key benefits extend to later stages of CKD by dose adjustment.

Ramadan fasting among advanced chronic kidney disease patients. Nephrologists' perspectives in Saudi Arabia.

Objectives:To explore nephrologists’ concerns and recommendations in counseling their advanced chronic kidney disease (CKD) patients on Ramadan fasting.Methods:This cross-sectional study was carried out in King Khalid University Hospital, Riyadh, Saudi Arabia between January 2019 and January 2020. An electronic survey was completed by 48 nephrologists practicing in Saudi Arabia. The questionnaire focused on demographics, clinical experience, and factors to consider when advising CKD patients about fasting. Statistical analysis was performed by the Statistical Package for Social Sciences for Windows, version 21 (IBM Corp, Armonk, NY, USA). Statistics include frequency and percentages using multiple response dichotomy analysis and thematic analysis.Results:Most respondents were consultant nephrologists (75%), practicing nephrology for over 10 years (68.8%). The majority of responding nephrologists (85.4%) were concerned about estimated glomerular filtration rate (eGFR), diabetes (68.8%), patient age (64.6%), use of diuretics (62.5%), body fluid volume (60.4%), and blood pressure (60.4%).Conclusion:This research addresses nephrologists’ perspectives about Ramadan fasting for patients with advanced CKD. It highlights factors they consider when advising CKD patients about fasting, which were used to suggest applications in practice. Further studies are needed to comprehend nephrologists’ and CKD patients’ perspectives on fasting.