scholarly journals Association between hyperkalemia, RAASi non-adherence and outcomes in chronic kidney disease

Author(s):  
Antonio Santoro ◽  
Valentina Perrone ◽  
Elisa Giacomini ◽  
Diego Sangiorgi ◽  
Davide Alessandrini ◽  
...  

Abstract Background Hyperkalemia is relatively frequent in CKD patients treated with renin-angiotensin-aldosterone-system inhibitors (RAASi). Aim The aim of the present study was to estimate the increased risk of cardiovascular events and mortality due to sub-optimal adherence to RAASi in CKD patients with hyperkalemia. Methods An observational retrospective cohort study was conducted, based on administrative and laboratory databases of five Local Health Units. Adult patients discharged from the hospital with a diagnosis of CKD, who were prescribed RAASi between January 2010 and December 2017, were included. We evaluated the appearance of documented episodes of hyperkalemia, RAASi therapy adherence and the effects of these two variables on cardiovascular events, death and dialysis inception for study patients. Results Of the 9241 selected patients, 4451 met all the criteria for study inclusion. Among them, 1071 had at least one documented episode of hyperkalemia, while 3380 did not. After propensity score matching based on several variables we obtained 2 groups of patients. The appearance of hyperkalemia caused treatment discontinuation in 21.8% of patients previously on RAASi therapy, and sub-optimal adherence (proportion of days covered  < 80%) in 33.6% of them. Non-adherence to RAASi therapy among hyperkalemia patients was associated with a higher risk of cardiovascular events (hazard ratio [HR] 1.45, confidence interval [CI] 1.02–2.08; p < 0.05). Moreover, in non-adherent hyperkalemia patients, the risk of death increased by 126% (HR 2.26, CI 1.62–3.15; p < 0.001) compared with adherent patients. Conclusions In a large cohort of CKD patients treated with RAASi, we observed that following hyperkalemia onset, non-adherence to RAASi medication can result in an increased risk of cardiovascular events and death. Graphical abstract

2021 ◽  
Vol 6 (1) ◽  
pp. e000672
Author(s):  
Ryan Pratt ◽  
Mete Erdogan ◽  
Robert Green ◽  
David Clark ◽  
Amanda Vinson ◽  
...  

BackgroundThe risk of death and complications after major trauma in patients with chronic kidney disease (CKD) is higher than in the general population, but whether this association holds true among Canadian trauma patients is unknown.ObjectivesTo characterize patients with CKD/receiving dialysis within a regional major trauma cohort and compare their outcomes with patients without CKD.MethodsAll major traumas requiring hospitalization between 2006 and 2017 were identified from a provincial trauma registry in Nova Scotia, Canada. Trauma patients with stage ≥3 CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2) or receiving dialysis were identified by cross-referencing two regional databases for nephrology clinics and dialysis treatments. The primary outcome was in-hospital mortality; secondary outcomes included hospital/intensive care unit (ICU) length of stay (LOS) and ventilator-days. Cox regression was used to adjust for the effects of patient characteristics on in-hospital mortality.ResultsIn total, 6237 trauma patients were identified, of whom 4997 lived within the regional nephrology catchment area. CKD/dialysis trauma patients (n=101; 28 on dialysis) were older than patients without CKD (n=4896), with higher rates of hypertension, diabetes, and cardiovascular disease, and had increased risk of in-hospital mortality (31% vs 11%, p<0.001). No differences were observed in injury severity, ICU LOS, or ventilator-days. After adjustment for age, sex, and injury severity, the HR for in-hospital mortality was 1.90 (95% CI 1.33 to 2.70) for CKD/dialysis compared with patients without CKD.ConclusionIndependent of injury severity, patients without CKD/dialysis have significantly increased risk of in-hospital mortality after major trauma.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Takeshi Hasegawa ◽  
Hiroki Nihiwaki ◽  
Erika Ota ◽  
William Levack ◽  
Hisashi Noma

Abstract Background and Aims Patients with chronic kidney disease (CKD) undergoing dialysis are at a particularly high risk of cardiovascular mortality and morbidity. This systematic review and meta-analysis aimed to evaluate the benefits and harms of aldosterone antagonists, both non-selective (spironolactone) and selective (eplerenone), in comparison to control (placebo or standard care) in patients with CKD requiring haemodialysis or peritoneal dialysis. Method We searched the Cochrane Kidney and Transplant Register of Studies up to 29 July 2019 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register Search Portal and ClinicalTrials.gov. We included individual and cluster randomised controlled trials (RCTs), cross-over trials, and quasi-RCTs that compared aldosterone antagonists with placebo or standard care in patients with CKD requiring dialysis. We used a random-effects model meta-analysis to perform a quantitative synthesis of the data. We used the I2 statistic to measure heterogeneity among the trials in each analysis. We indicated summary estimates as a risk ratio (RR) for dichotomous outcomes with their 95% confidence interval (CI). We assessed the certainty of the evidence for each of the main outcomes using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. Results We included 16 trials (14 parallel RCTs and two cross-over trials) involving a total of 1,446 patients. Among included studies, 13 trials compared spironolactone to placebo or standard care and one trial compared eplerenone to a placebo. Most studies had an unclear or high risk of bias. Compared to control, aldosterone antagonists reduced the risk of all-cause death for patients with CKD requiring dialysis (9 trials, 1,119 patients: RR 0.45, 95% CI 0.30 to 0.67; moderate certainty of evidence). Aldosterone antagonist also decreased the risk of death due to cardiovascular disease (6 trials, 908 patients: RR 0.37, 95% CI 0.22 to 0.64; moderate certainty of evidence) and cardiovascular and cerebrovascular morbidity (3 trials, 328 patients: RR 0.38, 95% CI 0.18 to 0.76; moderate certainty of evidence). While aldosterone antagonists had an apparent increased risk of gynaecomastia compared with control (4 trials, 768 patients: RR 5.95, 95% CI 1.93 to 18.3; moderate certainty of evidence), the elevated risk of hyperkalaemia due to aldosterone antagonists was uncertain (9 trials, 981 patients: RR 1.41, 95% CI 0.72 to 2.78; low certainty of evidence). Conclusion Based on moderate certainty of the evidence, aldosterone antagonists could reduce the risk of all-cause and cardiovascular death and morbidity due to cardiovascular and cerebrovascular disease but increase the risk of gynaecomastia in patients with CKD requiring dialysis.


2019 ◽  
pp. 78-85
Author(s):  
S. A. Martynov ◽  
M. Sh. Shamkhalova

Hyperphosphatemia in renal pathology is a key factor for developing mineral and bone disorders. It can develop even in the early stages of renal function decline and predict the formation of vascular calcification and an increased risk for developing cardiovascular complications in patients with chronic kidney disease, especially in those, who receive program hemodialysis. The use of calcium-free phosphate-binding agents that are not associated with the risk for developing hypercalcemia can slow the development of vascular calcification, reduce the incidence of adverse cardiovascular events and mortality in patients with chronic kidney disease.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Sol Carriazo ◽  
Maria Dolores Sanchez-Nino ◽  
Maria Vanessa Perez Gomez ◽  
Laura Castañeda-Infante ◽  
Catalina Martin ◽  
...  

Abstract Background and Aims Chronic kidney disease (CKD) is the most common risk factor for lethal COVID19 and the risk factor that most increases the risk of death of COVID19 patients. Additionally, acute kidney injury (AKI) is frequent in COVID19 and AKI increases the risk of death. However, the underlying cellular and molecular mechanisms of such increased risk are unclear. SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs) are required for and/or regulate (in a positive or negative manner) coronary cell entry and/or viral replication. We have now studied changes in the expression of genes encoding for SCARF in the context of acute and chronic kidney disease. Method Data mining of in-house (experimental models of AKI -folic acid nephropathy- and CKD -Unilateral ureteral obstruction- in mice) and publicly available databases (Nephroseq, published single cell transcriptomics studies) of kidney tissue transcriptomics as well as the Protein Atlas database. Results Out of 28 SCARF genes identified by Singh et al (Cell Reports 2020), 26 were represented in the experimental AKI database. Of them 7 (27%) were differentially expressed during AKI (FDR &lt;0.05), 4 of them upregulated and 3 downregulated (Figure 1.A). Additionally, 27 were represented in the experimental CKD database. Of them 17 (63%) were differentially expressed during experimental CKD, 6 of them upregulated and 11 downregulated (Figure 1.B). Two genes were consistently upregulated (Ctsl and Ifitm3) and two consistently downregulated (Tmprss2 and Top3b) in both experimental AKI and CKD (Figure 1.A and B). They encode cathepsin L, interferon induced transmembrane protein 3, transmembrane serine protease 2, DNA topoisomerase III beta, respectively. Single cell transcriptomics databases localized Ctsl expression mainly to podocytes and tubular cells while protein atlas showed clear tubular staining. The main site of Ifitm3 was endothelium in both datasets and it was also localized to leukocytes by single cell transcriptomics. Tmprss2 was mainly localized to tubular cells in both datasets while Top3b was widely expressed in parenchymal renal cells, endothelium and leucocytes in single cell transcriptomics. Increased kidney expression of Ifitm3 and decreased expression of Tmprss2 and Top3b were confirmed in diverse CKD datasets in Nephroseq. Conclusion Both AKI and CKD are associated with differential expression of SCARF genes in kidney tissue, the impact of CKD appearing to be larger. Characterization of these changes and their functional impact in kidney tissue and beyond the kidneys may provide clues to the increased risk of severe or lethal COVID19 in kidney disease patients. Kidney SCARF gene expression


Open Heart ◽  
2019 ◽  
Vol 6 (1) ◽  
pp. e000856 ◽  
Author(s):  
Xiao-jing Chen ◽  
Salim Bary Barywani ◽  
Per-Olof Hansson ◽  
Erik Östgärd Thunström ◽  
Annika Rosengren ◽  
...  

BackgroundResting heart rate (RHR), a known cardiovascular risk factor, changes with age. However, little is known about the association between changes in RHR and the risk of cardiovascular events. The purpose of this study was therefore to assess the impact of RHR at baseline, and the change in RHR over time, on the risk of all-cause death and cardiovascular events.DesignA random population sample of men born in 1943 who were living in Gothenburg, Sweden was prospectively followed for a 21-year period.MethodsParticipants were examined three times: first in 1993 and then re-examined in 2003 and 2014. At each visit, a clinical examination, an ECG and laboratory analyses were performed. Change in RHR between 1993 and 2003 was defined as a decrease if RHR decreased by 5 beats per minute (bpm), an increase if RHR increased by 5 bpm or stable if the RHR change was <4bpm).ResultsParticipants with a baseline RHR of >75 bpm in 1993 had about a twofold higher risk of all-cause death (HR 2.3, CI 1.2 to 4.7, p=0.018), cardiovascular disease (CVD) (HR 1.8, CI 1.1 to 3.0, p=0.014) and coronary heart disease (CHD) (HR 2.2, CI 1.1 to 4.5, p=0.025) compared with those with <55 bpm in 1993. Participants with a stable RHR between 1993 and 2003 had a 44% decreased risk of CVD (HR 0.56, CI 0.35 to 0.87, p=0.011) compared with participants with an increasing RHR. Furthermore, every beat increase in heart rate from 1993 was associated with a 3% higher risk for all-cause death, 1% higher risk for CVD and 2% higher risk for CHD.ConclusionHigh RHR was associated with an increased risk of death and cardiovascular events in men from the general population. Moreover, individuals with an increase in RHR between 50 and 60 years of age had worse outcome.


2019 ◽  
Vol 4 (5) ◽  
pp. e001715 ◽  
Author(s):  
Liana Macpherson ◽  
Morris Ogero ◽  
Samuel Akech ◽  
Jalemba Aluvaala ◽  
David Gathara ◽  
...  

IntroductionThere were almost 1 million deaths in children aged between 5 and 14 years in 2017, and pneumonia accounted for 11%. However, there are no validated guidelines for pneumonia management in older children and data to support their development are limited. We sought to understand risk factors for mortality among children aged 5–14 years hospitalised with pneumonia in district-level health facilities in Kenya.MethodsWe did a retrospective cohort study using data collected from an established clinical information network of 13 hospitals. We reviewed records for children aged 5–14 years admitted with pneumonia between 1 March 2014 and 28 February 2018. Individual clinical signs were examined for association with inpatient mortality using logistic regression. We used existing WHO criteria (intended for under 5s) to define levels of severity and examined their performance in identifying those at increased risk of death.Results1832 children were diagnosed with pneumonia and 145 (7.9%) died. Severe pallor was strongly associated with mortality (adjusted OR (aOR) 8.06, 95% CI 4.72 to 13.75) as were reduced consciousness, mild/moderate pallor, central cyanosis and older age (>9 years) (aOR >2). Comorbidities HIV and severe acute malnutrition were also associated with death (aOR 2.31, 95% CI 1.39 to 3.84 and aOR 1.89, 95% CI 1.12 to 3.21, respectively). The presence of clinical characteristics used by WHO to define severe pneumonia was associated with death in univariate analysis (OR 2.69). However, this combination of clinical characteristics was poor in discriminating those at risk of death (sensitivity: 0.56, specificity: 0.68, and area under the curve: 0.62).ConclusionChildren >5 years have high inpatient pneumonia mortality. These findings also suggest that the WHO criteria for classification of severity for children under 5 years do not appear to be a valid tool for risk assessment in this older age group, indicating the urgent need for evidence-based clinical guidelines for this neglected population.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Daisuke Mori ◽  
Shinjiro Tamai ◽  
Maho Tokuchi ◽  
Natsumi Inoue ◽  
Hideaki Kawai ◽  
...  

Abstract Background and Aims Plasma potassium levels are impacted by decreased kidney function and are known to be associated with increased mortality, adverse cardiovascular events and adverse kidney events. However, the prognostic implication of urinary potassium is unclear. Method We conducted an observational study of 1102 patients with chronic kidney disease (CKD) who were hospitalized between 2010 and 2018. The expected primary outcomes were all-cause mortality, adverse cardiovascular events and CKD progression. CKD progression was defined as a 30% increase in serum creatinine, the initiation of maintenance dialysis or the need for kidney transplantation. The Cox proportional hazards model was used to analyse the association between urinary potassium excretion and adverse clinical outcomes after adjustment for potential confounders. Results At baseline, 66% of the patients were men, with a median age of 72 years (interquartile range or IQR, 64–79 years); 61% of the patients were diabetic, and 54% of them were hypertensive. The median values for estimated glomerular filtration rate (eGFR) was 12 mL/min/1.73m2 (IQR, 8–18), serum potassium 4.5 mmol/L (IQR, 4.1–5.1) and urinary potassium/creatinine ratio (UK/Cr) 27 mmol/gCr (IQR, 20–38). Over a median follow-up period of 2.6 years (IQR 0.2–4.5), the number of all-cause deaths was 87. There were 171 cases of cardiovascular events and 860 cases of CKD progression. After adjusting for the eGFR, serum potassium level, proteinuria, renin–angiotensin system inhibitors, diuretics and other potential confounders, UK/Cr was found to be neither significantly associated with all-cause mortality nor with adverse cardiovascular events. However, a low UK/Cr was associated with an increased risk of CKD progression (adjusted hazard ratio [95% confidence interval] for the first, second and third quartiles, compared with the fourth quartile, were as follows: 2.09 [1.43-3.06], 1.33 [0.96-1.86] and 1.05 [0.75-1.46]) Conclusion A low UK/Cr might be an independent risk factor for poor renal outcome.


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