scholarly journals Timing of dialysis initiation to reduce mortality and cardiovascular events in advanced chronic kidney disease: nationwide cohort study

BMJ ◽  
2021 ◽  
pp. e066306
Author(s):  
Edouard L Fu ◽  
Marie Evans ◽  
Juan-Jesus Carrero ◽  
Hein Putter ◽  
Catherine M Clase ◽  
...  

Abstract Objective To identify the optimal estimated glomerular filtration rate (eGFR) at which to initiate dialysis in people with advanced chronic kidney disease. Design Nationwide observational cohort study. Setting National Swedish Renal Registry of patients referred to nephrologists. Participants Patients had a baseline eGFR between 10 and 20 mL/min/1.73 m 2 and were included between 1 January 2007 and 31 December 2016, with follow-up until 1 June 2017. Main outcome measures The strict design criteria of a clinical trial were mimicked by using the cloning, censoring, and weighting method to eliminate immortal time bias, lead time bias, and survivor bias. A dynamic marginal structural model was used to estimate adjusted hazard ratios and absolute risks for five year all cause mortality and major adverse cardiovascular events (composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) for 15 dialysis initiation strategies with eGFR values between 4 and 19 mL/min/1.73 m 2 in increments of 1 mL/min/1.73 m 2 . An eGFR between 6 and 7 mL/min/1.73 m 2 (eGFR 6-7 ) was taken as the reference. Results Among 10 290 incident patients with advanced chronic kidney disease (median age 73 years; 3739 (36%) women; median eGFR 16.8 mL/min/1.73 m 2 ), 3822 started dialysis, 4160 died, and 2446 had a major adverse cardiovascular event. A parabolic relation was observed for mortality, with the lowest risk for eGFR 15-16 . Compared with dialysis initiation at eGFR 6-7 , initiation at eGFR 15-16 was associated with a 5.1% (95% confidence interval 2.5% to 6.9%) lower absolute five year mortality risk and 2.9% (0.2% to 5.5%) lower risk of a major adverse cardiovascular event, corresponding to hazard ratios of 0.89 (95% confidence interval 0.87 to 0.92) and 0.94 (0.91 to 0.98), respectively. This 5.1% absolute risk difference corresponded to a mean postponement of death of 1.6 months over five years of follow-up. However, dialysis would need to be started four years earlier. When emulating the intended strategies of the Initiating Dialysis Early and Late (IDEAL) trial (eGFR 10-14 v eGFR 5-7 ) and the achieved eGFRs in IDEAL (eGFR 7-10 v eGFR 5-7 ), hazard ratios for all cause mortality were 0.96 (0.94 to 0.99) and 0.97 (0.94 to 1.00), respectively, which are congruent with the findings of the randomised IDEAL trial. Conclusions Very early initiation of dialysis was associated with a modest reduction in mortality and cardiovascular events. For most patients, such a reduction may not outweigh the burden of a substantially longer period spent on dialysis.

2015 ◽  
Vol 42 (5) ◽  
pp. 361-368 ◽  
Author(s):  
Anna J. Jovanovich ◽  
Michel B. Chonchol ◽  
Atousa Sobhi ◽  
Jessica B. Kendrick ◽  
Alfred K. Cheung ◽  
...  

Background: Evidence suggests that the renin-angiotensin-aldosterone system (RAAS) interacts with the vitamin D-fibroblast growth factor 23-Klotho axis. We investigated whether circulating mineral metabolism markers modify outcomes in response to RAAS inhibition in subjects with advanced chronic kidney disease (CKD). Methods: In this retrospective cohort study, we analyzed the association of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) use with all-cause mortality and dialysis initiation among 1,753 subjects (1,099 CKD, estimated glomerular filtration rate 18 ± 6 ml/min/1.73 m2 and 654 end-stage renal disease [ESRD]) from the Homocysteine in Kidney and End Stage Renal Disease (HOST) study. A propensity score analysis accounted for indication bias and Cox regression models adjusted for mineral metabolism markers. Results: Mean follow-up was 3.2 years; 714 (41%) subjects died and 615 (56%) initiated dialysis. In adjusted analyses, all subjects treated with ACEI/ARB had a significantly lower hazard of death (hazards ratio (HR) 0.81, 95% CI 0.70-0.95, p = 0.007). Those with CKD not on dialysis and treated with ACEI/ARB trended toward a lower hazard of dialysis initiation (HR 0.86, 95% CI 0.73-1.01, p = 0.06). The association with mortality did not differ by level of mineral metabolism marker (p for interaction >0.16); however, the relationship with dialysis initiation differed according to the median serum phosphorus level (p for interaction <0.001). Conclusions: RAAS inhibition was associated with decreased all-cause mortality independent of disordered mineral metabolism among mostly male HOST subjects with advanced CKD and ESRD. However, among those with CKD not requiring dialysis, the renoprotection associated with RAAS inhibition was attenuated by higher serum phosphorus levels. Further studies are needed to confirm this association.


2021 ◽  
pp. 1-9
Author(s):  
Ankur A. Dashputre ◽  
Keiichi Sumida ◽  
Fridtjof Thomas ◽  
Justin Gatwood ◽  
Oguz Akbilgic ◽  
...  

<b><i>Introduction:</i></b> Hypo- and hyperkalemia are associated with a higher risk of ischemic stroke. However, this association has not been examined in an advanced chronic kidney disease (CKD) population. <b><i>Methods:</i></b> From among 102,477 US veterans transitioning to dialysis between 2007 and 2015, 21,357 patients with 2 pre-dialysis outpatient estimated glomerular filtration rates &#x3c;30 mL/min/1.73 m<sup>2</sup> 90–365 days apart and at least 1 potassium (K) each in the baseline and follow-up period were identified. We separately examined the association of both baseline time-averaged K (chronic exposure) and time-updated K (acute exposure) treated as categorized (hypokalemia [K &#x3c;3.5 mEq/L] and hyperkalemia [K &#x3e;5.5 mEq/L] vs. referent [3.5–5.5 mEq/L]) and continuous exposure with time to the first ischemic stroke event prior to dialysis initiation using multivariable-adjusted Cox regression models. <b><i>Results:</i></b> A total of 2,638 (12.4%) ischemic stroke events (crude event rate 41.9 per 1,000 patient years; 95% confidence interval [CI] 40.4–43.6) over a median (Q<sub>1</sub>–Q<sub>3</sub>) follow-up time of 2.56 (1.59–3.89) years were observed. The baseline time-averaged K category of hypokalemia (adjusted hazard ratio [aHR], 95% CI: 1.35, 1.01–1.81) was marginally associated with a significantly higher risk of ischemic stroke. However, time-updated hyperkalemia was associated with a significantly lower risk of ischemic stroke (aHR, 95% CI: 0.82, 0.68–0.98). The exposure-outcome relationship remained consistent when using continuous K levels for both the exposures. <b><i>Discussion/Conclusion:</i></b> In patients with advanced CKD, hypokalemia (chronic exposure) was associated with a higher risk of ischemic stroke, whereas hyperkalemia (acute exposure) was associated with a lower risk of ischemic stroke. Further studies in this population are needed to explore the mechanisms underlying these associations.


Scientifica ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Umberto Barbero ◽  
Fabrizio D’Ascenzo ◽  
Freek Nijhoff ◽  
Claudio Moretti ◽  
Giuseppe Biondi-Zoccai ◽  
...  

Background. A large number of clinical and laboratory markers have been appraised to predict prognosis in patients with stable angina, but uncertainty remains regarding which variables are the best predictors of prognosis. Therefore, we performed a meta-analysis of studies in patients with stable angina to assess which variables predict prognosis.Methods. MEDLINE and PubMed were searched for eligible studies published up to 2015, reporting multivariate predictors of major adverse cardiac events (MACE, a composite endpoint of death, myocardial infarction, and revascularization) in patients with stable angina. Study features, patient characteristics, and prevalence and predictors of such events were abstracted and pooled with random-effect methods (95% CIs). Major adverse cardiovascular event (MACE) was the primary endpoint.Results. 42 studies (104,559 patients) were included. After a median follow-up of 57 months, cardiovascular events occurred in 7.8% of patients with MI in 6.2% of patients and need for repeat revascularization (both surgical and percutaneous) in 19.5% of patients. Male sex, reduced EF, diabetes, prior MI, and high C-reactive protein were the most powerful predictors of cardiovascular events.Conclusions. We show that simple and low-cost clinical features may help clinicians in identifying the most appropriate diagnostic and therapeutic approaches within the broad range of outpatients presenting with stable coronary artery disease.


Hypertension ◽  
2015 ◽  
Vol 65 (1) ◽  
pp. 93-100 ◽  
Author(s):  
Nisha Bansal ◽  
Charles E. McCulloch ◽  
Mahboob Rahman ◽  
John W. Kusek ◽  
Amanda H. Anderson ◽  
...  

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3381
Author(s):  
Sang Heon Suh ◽  
Tae Ryom Oh ◽  
Hong Sang Choi ◽  
Chang Seong Kim ◽  
Eun Hui Bae ◽  
...  

To investigate the association of body weight variability (BWV) with adverse cardiovascular (CV) outcomes in patient with pre-dialysis chronic kidney disease (CKD), a total of 1867 participants with pre-dialysis CKD from Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) were analyzed. BWV was defined as the average absolute difference between successive values. The primary outcome was a composite of non-fatal CV events and all-cause mortality. Secondary outcomes were fatal and non-fatal CV events and all-cause mortality. High BWV was associated with increased risk of the composite outcome (adjusted hazard ratio (HR) 1.745, 95% confidence interval (CI) 1.065 to 2.847) as well as fatal and non-fatal CV events (adjusted HR 1.845, 95% CI 1.136 to 2.996) and all-cause mortality (adjusted HR 1.861, 95% CI 1.101 to 3.145). High BWV was associated with increased risk of fatal and non-fatal CV events, even in subjects without significant body weight gain or loss during follow-up periods (adjusted HR 2.755, 95% CI 1.114 to 6.813). In conclusion, high BWV is associated with adverse CV outcomes in patients with pre-dialysis CKD.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Edouard L Fu ◽  
Catherine M Clase ◽  
Marie Evans ◽  
Bengt Lindholm ◽  
Joris Rotmans ◽  
...  

Abstract Background and Aims There is a lack of data that could help to guide the choice of antihypertensive agents in patients with advanced chronic kidney disease (CKD). We evaluated whether initiating treatment with a renin-angiotensin system inhibitor (RASi) is superior to calcium channel blockers (CCB) in preventing mortality, major adverse cardiovascular events (MACE) or kidney replacement therapy (KRT) in patients with advanced CKD. Method Observational study from the Swedish Renal Register, 2007-2017. We identified all nephrologist-referred patients in Sweden who initiated RASi or CCB treatment and had non-dialysis dependent advanced CKD (eGFR &lt;30 ml/min/1.73m2). The associations between RASi vs CCB initiation, mortality, MACE and KRT were assessed by Cox regression. Analyses were adjusted with propensity score weighting for a wide range of confounders, including demographics, blood pressure, laboratory measures, comorbidities and medications. As a positive control we evaluated new use of the same drugs in patients with CKD G3 (N = 2608; eGFR between 30-60 ml/min/1.73m2). Furthermore subgroup, as-treated and competing risk analyses were performed. Results The propensity-score weighted cohort included 2479 RASi and 2327 CCB initiators who were well-matched for baseline confounders (all standardized differences &lt;0.1). Median follow-up was 4.1 years, with a maximum follow-up of over 10 years. Compared to CCB, initiation of RASi was associated with a similar risk of mortality (adjusted HR 0.94; 95% CI 0.85-1.03) and MACE (0.99; 0.87-1.13), but with a lower risk of KRT (0.87; 0.78-0.98). Results were consistent across subgroups, in as-treated analyses and after accounting for the competing risk of death. In the control cohort of patients with CKD G3, initiation of RASi (versus CCB) was associated with lower KRT risk (adjusted HR 0.67; 0.47-0.96), and similar risk of mortality (0.91; 0.76-1.08) and MACE (1.06; 0.82-1.35). Conclusion Compared with CCB, initiation of RASi in patients with advanced CKD was associated with a lower risk of KRT, but no different risk of mortality or MACE.


Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2192
Author(s):  
Hsun Yang ◽  
Shiun-Yang Juang ◽  
Kuan-Fu Liao ◽  
Yi-Hsin Chen

Background: We hypothesized that the nutrient loss and chronic inflammation status may stimulate progression in advanced chronic kidney disease. Therefore, we aimed to generate a study to state the influence of combined nutritional and anti-inflammatory interventions. Methods: The registry from the National Health Insurance Research Database in Taiwan was searched for 20–90 years individuals who had certified end-stage renal disease. From January 2005 through December 2010, the diagnosis code ICD-9 585 (chronic kidney disease, CKD) plus erythropoiesis-stimulating agent (ESA) use was defined as entering advanced chronic kidney disease. The ESA starting date was defined as the first index date, whereas the initiation day of maintenance dialysis was defined as the second index date. The duration between the index dates was analyzed in different medical treatments. Results: There were 10,954 patients analyzed. The combination therapy resulted in the longest duration (n = 2184, median 145 days, p < 0.001) before the dialysis initiation compared with folic acid (n = 5073, median 111 days), pentoxifylline (n = 1119, median 102 days, p = 0.654), and no drug group (control, n = 2578, median 89 days, p < 0.001). Lacking eGFR data and the retrospective nature are important limitations. Conclusions: In patients with advanced CKD on the ESA treatment, the combination of folic acid and pentoxifylline was associated with delayed initiation of hemodialysis.


BMJ ◽  
2019 ◽  
pp. l1516 ◽  
Author(s):  
Jonas H Kristensen ◽  
Saima Basit ◽  
Jan Wohlfahrt ◽  
Mette Brimnes Damholt ◽  
Heather A Boyd

ABSTRACTObjectiveTo investigate associations between pre-eclampsia and later risk of kidney disease.DesignNationwide register based cohort study.SettingDenmark.PopulationAll women with at least one pregnancy lasting at least 20 weeks between 1978 and 2015.Main outcome measureHazard ratios comparing rates of kidney disease between women with and without a history of pre-eclampsia, stratified by gestational age at delivery and estimated using Cox regression.ResultsThe cohort consisted of 1 072 330 women followed for 19 994 470 person years (average 18.6 years/woman). Compared with women with no previous pre-eclampsia, those with a history of pre-eclampsia were more likely to develop chronic renal conditions: hazard ratio 3.93 (95% confidence interval 2.90 to 5.33, for early preterm pre-eclampsia (delivery <34 weeks); 2.81 (2.13 to 3.71) for late preterm pre-eclampsia (delivery 34-36 weeks); 2.27 (2.02 to 2.55) for term pre-eclampsia (delivery ≥37 weeks). In particular, strong associations were observed for chronic kidney disease, hypertensive kidney disease, and glomerular/proteinuric disease. Adjustment for cardiovascular disease and hypertension only partially attenuated the observed associations. Stratifying the analyses on time since pregnancy showed that associations between pre-eclampsia and chronic kidney disease and glomerular/proteinuric disease were much stronger within five years of the latest pregnancy (hazard ratio 6.11 (3.84 to 9.72) and 4.77 (3.88 to 5.86), respectively) than five years or longer after the latest pregnancy (2.06 (1.69 to 2.50) and 1.50 (1.19 to 1.88). By contrast, associations between pre-eclampsia and acute renal conditions were modest.Conclusions Pre-eclampsia, particularly early preterm pre-eclampsia, was strongly associated with several chronic renal disorders later in life. More research is needed to determine which women are most likely to develop kidney disease after pre-eclampsia, what mechanisms underlie the association, and what clinical follow-up and interventions (and in what timeframe post-pregnancy) would be most appropriate and effective.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ali S. Omrani ◽  
Muna A. Almaslamani ◽  
Joanne Daghfal ◽  
Rand A. Alattar ◽  
Mohamed Elgara ◽  
...  

Abstract Background There are limited data on Coronavirus Disease 2019 (COVID-19) outcomes at a national level, and none after 60 days of follow up. The aim of this study was to describe national, 60-day all-cause mortality associated with COVID-19, and to identify risk factors associated with admission to an intensive care unit (ICU). Methods This was a retrospective cohort study including the first consecutive 5000 patients with COVID-19 in Qatar who completed 60 days of follow up by June 17, 2020. The primary outcome was all-cause mortality at 60 days after COVID-19 diagnosis. In addition, we explored risk factors for admission to ICU. Results Included patients were diagnosed with COVID-19 between February 28 and April 17, 2020. The majority (4436, 88.7%) were males and the median age was 35 years [interquartile range (IQR) 28–43]. By 60 days after COVID-19 diagnosis, 14 patients (0.28%) had died, 10 (0.2%) were still in hospital, and two (0.04%) were still in ICU. Fatal COVID-19 cases had a median age of 59.5 years (IQR 55.8–68), and were mostly males (13, 92.9%). All included pregnant women (26, 0.5%), children (131, 2.6%), and healthcare workers (135, 2.7%) were alive and not hospitalized at the end of follow up. A total of 1424 patients (28.5%) required hospitalization, out of which 108 (7.6%) were admitted to ICU. Most frequent co-morbidities in hospitalized adults were diabetes (23.2%), and hypertension (20.7%). Multivariable logistic regression showed that older age [adjusted odds ratio (aOR) 1.041, 95% confidence interval (CI) 1.022–1.061 per year increase; P < 0.001], male sex (aOR 4.375, 95% CI 1.964–9.744; P < 0.001), diabetes (aOR 1.698, 95% CI 1.050–2.746; P 0.031), chronic kidney disease (aOR 3.590, 95% CI 1.596–8.079, P 0.002), and higher BMI (aOR 1.067, 95% CI 1.027–1.108 per unit increase; P 0.001), were all independently associated with increased risk of ICU admission. Conclusions In a relatively younger national cohort with a low co-morbidity burden, COVID-19 was associated with low all-cause mortality. Independent risk factors for ICU admission included older age, male sex, higher BMI, and co-existing diabetes or chronic kidney disease.


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