scholarly journals Long-term safety and efficacy of sodium zirconium cyclosilicate for hyperkalaemia in patients with mild/moderate versus severe/end-stage chronic kidney disease: comparative results from an open-label, Phase 3 study

2020 ◽  
Vol 36 (1) ◽  
pp. 137-150 ◽  
Author(s):  
Simon D Roger ◽  
Philip T Lavin ◽  
Edgar V Lerma ◽  
Peter A McCullough ◽  
Javed Butler ◽  
...  

Abstract Background Sodium zirconium cyclosilicate (SZC; formerly ZS-9) is a selective potassium (K+) binder for the treatment of adults with hyperkalaemia. This post hoc analysis of an open-label, single-arm trial (NCT02163499) compared SZC efficacy and safety >12 months among outpatients with hyperkalaemia and Stages 4 and 5 chronic kidney disease (CKD) versus those with Stages 1–3 CKD. Methods Adults with serum K+ ≥5.1 mmol/L (measured by point-of-care i-STAT device) received SZC 10 g three times daily for 24–72 h until normokalaemia (i-STAT K+ 3.5–5.0 mmol/L) was achieved [correction phase (CP)], followed by once daily SZC 5 g for ≤12 months [maintenance phase (MP)]. Here, patients were stratified by baseline estimated glomerular filtration rate (eGFR <30 or ≥30 mL/min/1.73 m2). Study endpoints included percent achieving normokalaemia during CP and MP, mean serum K+ and bicarbonate during MP, and adverse events (AEs). Results Of 751 patients enrolled, 289 (39%), 453 (60%) and 9 (1%) had baseline eGFR values of <30, ≥30 mL/min/1.73 m2 or missing, respectively. During the CP, 82% of patients achieved normokalaemia in both eGFR subgroups within 24 h, and 100 and 95% with baseline eGFR <30 and ≥30 mL/min/1.73 m2, respectively, within 72 h. Corresponding proportions with normokalaemia during the MP were 82 and 90% at Day 365, respectively. Mean serum K+ reduction from baseline during the CP was sustained throughout the MP and serum bicarbonate increased. AEs during the MP were more common in the eGFR <30 ≥30 mL/min/1.73 m2 subgroup. Conclusions SZC corrects hyperkalaemia and maintains normokalaemia among outpatients regardless of the CKD stage.

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1205
Author(s):  
Yoshitaka Isaka

Multi-factors, such as anorexia, activation of renin-angiotensin system, inflammation, and metabolic acidosis, contribute to malnutrition in chronic kidney disease (CKD) patients. Most of these factors, contributing to the progression of malnutrition, worsen as CKD progresses. Protein restriction, used as a treatment for CKD, can reduce the risk of CKD progression, but may worsen the sarcopenia, a syndrome characterized by a progressive and systemic loss of muscle mass and strength. The concomitant rate of sarcopenia is higher in CKD patients than in the general population. Sarcopenia is also associated with mortality risk in CKD patients. Thus, it is important to determine whether protein restriction should be continued or loosened in CKD patients with sarcopenia. We may prioritize protein restriction in CKD patients with a high risk of end-stage kidney disease (ESKD), classified to stage G4 to G5, but may loosen protein restriction in ESKD-low risk CKD stage G3 patients with proteinuria <0.5 g/day, and rate of eGFR decline <3.0 mL/min/1.73 m2/year. However, the effect of increasing protein intake alone without exercise therapy may be limited in CKD patients with sarcopenia. The combination of exercise therapy and increased protein intake is effective in improving muscle mass and strength in CKD patients with sarcopenia. In the case of loosening protein restriction, it is safe to avoid protein intake of more than 1.5 g/kgBW/day. In CKD patients with high risk in ESKD, 0.8 g/kgBW/day may be a critical point of protein intake.


2011 ◽  
Vol 51 (4) ◽  
pp. 192 ◽  
Author(s):  
Eka Laksmi Hidayati ◽  
Partini Pudjiati Trihono

Background Chronic kidney disease (CKD) in children is a potentially fatal disease if left untreated. Early detection and treatment are important to slow progression to end-stage renal disease requiring dialysis.Objective We aimed to find characteristics of CKD patients at admission and evaluate factors associated with end-stage CKD (stage 5).Methods Our cross-sectional study was based on medical records of CKD patients aged less than 18 years in Cipto Mangunkusumo Hospital, Jakarta, from January 2007 to December 2009. Diagnosis and stages of CKD were based on the Kidney Disease Outcomes Quality Initiative (K/DOQI) criteria. Data on disease etiology, symptoms, nutritional status and laboratory tests were collected. Bivariate and multivariate analyses were performed to examine the association between end-stage CKD and its possible risk factors.Results Of the 142 cases eligible for analysis, 55% were boys. Subjects’ median age was 73.5 months (interquartile range of 23.5-122.5 months). Edema and recurrent fever were the two most frequent symptoms of CKD if diagnosed at stages 2-4, while breathlessness was the most frequent symptom of CKD if diagnosed at stage 5. The most common etiologies were glomerulonephritis (49.3%) and anomalies of the kidney and urinary tract (32.4%). Of our CKD subjects, 21.8% were in stage 5. Independent predictors of stage 5 CKD at presentation were hypertension (OR 3.88; 95% CI 1.17 to 12.87; P=0.026), urea level > 60 mg/dL (OR 39.11; 95%CI 4.86 to 314.74; P<0.001) and non-glomerulonephritis as the etiology (OR 6.51; 95%CI 2.12 to 19.92; P<0.001).Conclusion Glomerular disease was the most common cause of CKD in our study. Stage 5 CKD was present in 21.8% of subjects at admission and could be predicted by the presence of hypertension, high serum urea level, and non-glomerular disease as the etiology.


2020 ◽  
Vol 9 (11) ◽  
pp. 3702
Author(s):  
Saraschandra Vallabhajosyula ◽  
Lina Ya’Qoub ◽  
Vinayak Kumar ◽  
Dhiran Verghese ◽  
Anna V. Subramaniam ◽  
...  

Background: There are limited data on acute myocardial infarction with cardiogenic shock (AMI-CS) stratified by chronic kidney disease (CKD) stages. Objective: To assess clinical outcomes in AMI-CS stratified by CKD stages. Methods: A retrospective cohort of AMI-CS during 2005–2016 from the National Inpatient Sample was categorized as no CKD, CKD stage-III (CKD-III), CKD stage-IV (CKD-IV) and end-stage renal disease (ESRD). CKD-I/II were excluded. Outcomes included in-hospital mortality, use of coronary angiography, percutaneous coronary intervention (PCI) and mechanical circulatory support (MCS). We also evaluated acute kidney injury (AKI) and acute hemodialysis in non-ESRD admissions. Results: Of 372,412 AMI-CS admissions, CKD-III, CKD-IV and ESRD comprised 20,380 (5.5%), 7367 (2.0%) and 18,109 (4.9%), respectively. Admissions with CKD were, on average, older, of the White race, bearing Medicare insurance, of a lower socioeconomic stratum, with higher comorbidities, and higher rates of acute organ failure. Compared to the cohort without CKD, CKD-III, CKD-IV and ESRD had lower use of coronary angiography (72.7%, 67.1%, 56.9%, 61.1%), PCI (53.7%, 43.8%, 38.4%, 37.6%) and MCS (47.9%, 38.3%, 33.3%, 34.2%), respectively (all p < 0.001). AKI and acute hemodialysis use increased with increase in CKD stage (no CKD–38.5%, 2.6%; CKD-III–79.1%, 6.5%; CKD-IV–84.3%, 12.3%; p < 0.001). ESRD (adjusted odds ratio [OR] 1.25 [95% confidence interval {CI} 1.21–1.31]; p < 0.001), but not CKD-III (OR 0.72 [95% CI 0.69–0.75); p < 0.001) or CKD-IV (OR 0.82 [95 CI 0.77–0.87] was predictive of in-hospital mortality. Conclusions: CKD/ESRD is associated with lower use of evidence-based therapies. ESRD was an independent predictor of higher in-hospital mortality in AMI-CS.


2020 ◽  
Vol 7 ◽  
pp. 205435812097071
Author(s):  
Melissa Nataatmadja ◽  
Angela W. S. Fung ◽  
Beryl Jacobson ◽  
Jack Ferera ◽  
Eva Bernstein ◽  
...  

Background: The StatSensor is a point-of-care device which measures creatinine in capillary whole blood. Previous studies reported an underestimation of the creatinine measurements at high creatinine concentrations and were performed in the prestandardization era for creatinine. Objective: This accuracy-based study evaluates the use of this device in kidney-transplanted patients and those with chronic kidney disease (CKD). Design: Cross-sectional diagnostic accuracy study. Setting: Nephrology outpatient clinic in an urban tertiary center. Participants: Adults with CKD or a functioning kidney transplant. Measurements: Duplicate StatSensor creatinine measurements were performed on capillary whole blood samples collected by direct fingerstick and SAFE-T-FILL collection device. Results were compared with simultaneous venous blood sampling for serum and plasma creatinine measured by an enzymatic method on the Roche Integra 400 mainframe analyzer with traceability to the ID-GC-MS (isotope dilution gas chromatography mass spectrometry) reference method. Methods: Deming regression, Pearson correlation coefficient, and Bland-Altman analysis were used to assess accuracy and comparability between capillary whole blood measured by StatSensor and plasma creatinine measured by routine analyzer with traceability to the reference method. Estimated glomerular filtration (eGFR) rates were calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and concordance with Kidney Disease Improving Global Outcomes (KDIGO) CKD stage classification was evaluated. Results: There were 60 participants (mean age = 61.9 ± 15.0 years, 55% men, 33% transplant, mean plasma creatinine = 137 ± 59 µmol/L). Bland-Altman analysis indicated a positive mean bias of 12.7 µmol/L between StatSensor fingerstick creatinine measurement and plasma creatinine. Comparison of eGFR (CKD-EPI) calculated from the StatSensor fingerstick creatinine versus plasma creatinine showed misclassification across all KDIGO CKD stages. Postanalytical correction of the bias did not improve misclassifications. The use of mean of duplicate StatSensor creatinine results did not improve performance compared with the use of singlet results. Limitations: Single center, limited participant numbers. Conclusions: The results of our study suggest that the limiting characteristics of the StatSensor device are not only bias, but also imprecision. The level of imprecision observed may influence clinical decision-making and limit the usefulness of StatSensor as a CKD screening tool. If choosing to utilize it for either screening for or monitoring CKD, it is essential that clinicians understand the limitations of point-of-care devices and apply this knowledge to test interpretation.


2019 ◽  
Vol 35 (18) ◽  
pp. 3441-3452 ◽  
Author(s):  
Jing Ma ◽  
Alla Karnovsky ◽  
Farsad Afshinnia ◽  
Janis Wigginton ◽  
Daniel J Rader ◽  
...  

Abstract Motivation Functional enrichment testing methods can reduce data comprising hundreds of altered biomolecules to smaller sets of altered biological ‘concepts’ that help generate testable hypotheses. This study leveraged differential network enrichment analysis methodology to identify and validate lipid subnetworks that potentially differentiate chronic kidney disease (CKD) by severity or progression. Results We built a partial correlation interaction network, identified highly connected network components, applied network-based gene-set analysis to identify differentially enriched subnetworks, and compared the subnetworks in patients with early-stage versus late-stage CKD. We identified two subnetworks ‘triacylglycerols’ and ‘cardiolipins-phosphatidylethanolamines (CL-PE)’ characterized by lower connectivity, and a higher abundance of longer polyunsaturated triacylglycerols in patients with severe CKD (stage ≥4) from the Clinical Phenotyping Resource and Biobank Core. These finding were replicated in an independent cohort, the Chronic Renal Insufficiency Cohort. Using an innovative method for elucidating biological alterations in lipid networks, we demonstrated alterations in triacylglycerols and cardiolipins-phosphatidylethanolamines that precede the clinical outcome of end-stage kidney disease by several years. Availability and implementation A complete list of NetGSA results in HTML format can be found at http://metscape.ncibi.org/netgsa/12345-022118/cric_cprobe/022118/results_cric_cprobe/main.html. The DNEA is freely available at https://github.com/wiggie/DNEA. Java wrapper leveraging the cytoscape.js framework is available at http://js.cytoscape.org. Supplementary information Supplementary data are available at Bioinformatics online.


Author(s):  
Susanne Stolpe ◽  
Bernd Kowall ◽  
Christian Scholz ◽  
Andreas Stang ◽  
Cornelia Blume

Chronic kidney disease (CKD) is associated with an increased risk for cardiovascular events, hospitalizations, end stage renal disease and mortality. Main risk factors for CKD are diabetes, hypertension, and older age. Although CKD prevalence is about 10%, awareness for CKD is generally low in patients and physicians, hindering early diagnosis and treatment. We analyzed baseline data of 3305 participants with CKD Stages 1–4 from German cohorts and registries collected in 2010. Prevalence of CKD unawareness and prevalence ratios (PR) (each with 95%-confidence intervals) were estimated in categories of age, sex, CKD stages, BMI, hypertension, diabetes and other relevant comorbidities. We used a log-binomial regression model to estimate the PR for CKD unawareness for females compared to males adjusting for CKD stage and CKD risk factors. CKD unawareness was high, reaching 71% (68–73%) in CKD 3a, 49% (45–54%) in CKD 3b and still 30% (24–36%) in CKD4. Prevalence of hypertension, diabetes or cardiovascular comorbidities was not associated with lower CKD unawareness. Independent of CKD stage and other risk factors unawareness was higher in female patients (PR = 1.06 (1.01; 1.10)). Even in patients with CKD related comorbidities, CKD unawareness was high. Female sex was strongly associated with CKD unawareness. Guideline oriented treatment of patients at higher risk for CKD could increase CKD awareness. Patient–physician communication about CKD might be amendable.


Author(s):  
Paul Kolm ◽  
Zugui Zhang ◽  
James Bowen ◽  
Rubeen Israni ◽  
William S Weintraub ◽  
...  

Background: Obesity and chronic kidney disease (CKD) are well known risk factors for cardiovascular (CV) events. Studies have shown that in patients with end-stage renal disease, the rate of CV events decreases as body mass index (BMI) increases. These studies, however, used only one measurement of BMI to predict CV events. The objective of this study was to assess whether rates of CV events changed according to variations in BMI and glomerular filtration rate (GFR) over time. Methods: A retrospective cohort of patients followed in outpatient practices from 1995 to 2010 was evaluated. Adult patients with at least 2 records of serum creatinine were included. The practices’ electronic health records (EHRs) were linked to the hospital EHR to assess CV events. GFR (mL/min/1.73m 2 ) was calculated using the Modification of Diet in Renal Disease equation and stratified according to the Kidney Disease Outcomes Quality Initiative guidelines as Normal (≥ 60), CKD stage 3 (30-59) and stage 4-5 (< 30) at each patient’s encounter. Outcomes were identified using ICD9 codes for myocardial infarction, congestive heart failure, coronary heart disease, dysrhythmia, stroke and peripheral vascular disease. The data spanned up to 10 years from a patient’s index to last visit. CV events were modeled as a function of age, gender, race, BMI and CKD status by negative binomial regression for count data. The model included interactions of age, gender, race, BMI and CKD. Results: Over the 10-year period, there were a total of 1,024,891 observations from 39,605 patients with 8,901 CV events. There was a significant age by gender by race by BMI interaction as well as a significant CKD main effect (p < 0.01). Increasing age, being male, black, overweight and having CKD, were associated with higher event rates. However, this association between BMI and event rates was not present for black females over 70, thus the 4-way sex by race by age by BMI interaction (Figure). Conclusion: These results support the hypothesis that overweight / obesity is not protective of CV events in CKD patients.


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