Smoking, Smoking Cessation, and Progression of Chronic Kidney Disease: Results From KNOW-CKD Study

Author(s):  
Sangmi Lee ◽  
Shinchan Kang ◽  
Young Su Joo ◽  
Changhyun Lee ◽  
Ki Heon Nam ◽  
...  

Abstract Introduction In patients with chronic kidney disease (CKD), studies investigating the association between smoking and deterioration of kidney function are scarce. Aims and Methods We analyzed data for 1,951 patients with an estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73 m2 enrolled in the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD) from 2011 to 2016. Patients were categorized by smoking load. Primary outcome was a composite of a ≥50% reduction in eGFR, initiation of dialysis, or kidney transplantation. Results There were 967 never-smokers and 369, 276, and 339 smokers who smoked <15, 15 to 29, ≥30 pack-years, respectively. During a mean follow-up of 3.0 years, the incidence rates (95% confidence interval [CI]) of the primary outcome were 54.3 (46.4–63.5), 46.9 (35.9–61.4), 69.2 (52.9–90.6), and 76.3 (60.7–96.0) events per 1,000 person-yr in never-, <15, 15 to 29, and ≥30 pack-year smokers. In cause-specific hazard model after adjustment of confounding factors, smokers were associated with 1.09 (0.73–1.63), 1.48 (1.00–2.18), and 1.94 (1.35–2.77) fold increased risk (95% CI) of primary outcome in <15, 15–29, and ≥30 pack-year smokers compared with never-smokers. The association of longer smoking duration with higher risk of CKD progression was evident particularly in patients with eGFR < 45 mL/min/1.73 m2 and proteinuria ≥ 1.0 g/g. In contrast, the risk of adverse kidney outcome decreased with longer smoking-free periods among former-smokers. Conclusions These findings suggest potentially harmful effects of the degree of exposure to smoking on the progression of CKD. Implications Among patients with CKD, there has been lack of studies on the association between smoking and CKD progression and studies to date have yielded conflicting results. In this prospective cohort study involving Korean CKD patients, smoking was associated with significantly higher risk of worsening kidney function. Furthermore, the risk of adverse kidney outcome was incrementally higher as smoking pack-years were higher. As the duration of smoking cessation increased, the hazard ratios for adverse kidney outcome were attenuated, suggesting that quitting smoking may be a modifiable factor to delay CKD progression.

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Mark Behan ◽  
Leonard Browne ◽  
Stack Austin

Abstract Background and Aims Lithium is implicated as a causative factor in the development and progression of chronic kidney disease (CKD). Few studies have assessed the independent impact of plasma levels and duration of lithium therapy on CKD progression. We examined the influence of lithium on CKD progression in the Irish health system. Method We utilised data from the Irish Kidney Disease Surveillance System (IKDSS) to explore associations of lithium levels and duration of exposure with kidney function in a regional cohort. A retrospective cohort study was conducted between 1999 to 2014 from the Midwest Region. All adult patients with lithium levels were identified and followed longitudinally. Kidney function was assessed at baseline and longitudinally using serum creatinine and estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI. Patients with < 2 lithium values, missing data on creatinine were excluded. The index date was the date of the first lithium blood test. Toxicity from lithium was defined as levels >1.2mmol/L as per NICE guidelines while duration of treatment was calculated based on patient –years of exposure as determined by positive blood lithium levels. Relationships between baseline kidney function, lithium levels, duration of exposure and each patients most recent eGFR value on follow up were assessed using multiple linear regression Results We identified 1,978 patients exposed to lithium from 1999-2014, mean age was 47.4 (15.6), 45.1% were men, eGFR [median (IQR)] at baseline was 84.4 (32.1) ml/min1.73m and the median duration of exposure was 3.0 years (IQR=4 years). Frequency of lithium testing increased from 1.77 in 1999 to 2.66 in 2014. In multiple linear regression, the final eGFR on follow-up was significantly lower in older patients (-0.48 ml/min/1.73m per year increase in age), P<0.001; in patients with elevated baseline lithium levels (-2.18 ml/min1.73m lower per unit increase), P<0.05, with long duration of exposure (-1.42 ml/min/1.73m lower for each year on lithium), P<0.001, and for patients with low GFR at baseline (P<0.001). Together these variables explained 58% of the variation in the final model. Conclusion Both the magnitude of and the duration of lithium exposure are both independently associated with CKD progression among lithium users in the Irish health system. Higher baseline lithium values had a more deleterious impact on kidney function. Continued efforts should be expended in minimising the risks of lithium induced nephrotoxicity through switching to alternatives and dose reduction when over possible. Funding This study is funded by the Health Research Board and the Midwest Research and Education Foundation (MKid).


Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1517
Author(s):  
Juyeon Lee ◽  
Kook-Hwan Oh ◽  
Sue-Kyung Park

We investigated the association between dietary micronutrient intakes and the risk of chronic kidney disease (CKD) in the Ansan-Ansung study of the Korean Genome and Epidemiologic Study (KoGES), a population-based prospective cohort study. Of 9079 cohort participants with a baseline estimate glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 and a urine albumin to creatinine ratio (UACR) <300 mg/g and who were not diagnosed with CKD, we ascertained 1392 new CKD cases over 12 year follow-up periods. The risk of CKD according to dietary micronutrient intakes was presented using hazard ratios (HRs) and 95% confidence intervals (95% CIs) in a full multivariable Cox proportional hazard models, adjusted for multiple micronutrients and important clinico-epidemiological risk factors. Low dietary intakes of phosphorus (<400 mg/day), vitamin B2 (<0.7 mg/day) and high dietary intake of vitamin B6 (≥1.6 mg/day) and C (≥100 mg/day) were associated with an increased risk of CKD stage 3B and over, compared with the intake at recommended levels (HR = 6.78 [95%CI = 2.18–21.11]; HR = 2.90 [95%CI = 1.01–8.33]; HR = 2.71 [95%CI = 1.26–5.81]; HR = 1.83 [95%CI = 1.00–3.33], respectively). In the restricted population, excluding new CKD cases defined within 2 years, an additional association with low folate levels (<100 µg/day) in higher risk of CKD stage 3B and over was observed (HR = 6.72 [95%CI = 1.40–32.16]). None of the micronutrients showed a significant association with the risk of developing CKD stage 3A. Adequate intake of micronutrients may lower the risk of CKD stage 3B and over, suggesting that dietary guidelines are needed in the general population to prevent CKD.


Author(s):  
Young Su Joo ◽  
Hyung Woo Kim ◽  
Ki Heon Nam ◽  
Jee Young Lee ◽  
Tae Ik Chang ◽  
...  

Studies on the longitudinal temporal trend of blood pressure (BP) and its impact on kidney function are scarce. Here, we evaluated the association of dynamic changes in systolic blood pressure (SBP) over time with adverse kidney outcomes. We analyzed 1837 participants from the KNOW-CKD (Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease). The main exposure was 3 distinct SBP trajectories determined by the latent class mixed model (decreasing, stable, and increasing) using 3 SBP measurements at 0, 6, and 12 months. The primary outcome was CKD progression, defined as a composite of halving estimated glomerular filtration rate from baseline value or onset of end-stage kidney disease. SBP declined from 144 to 120 mm Hg in the decreasing SBP trajectory group and rose from 114 to 136 mm Hg in the increasing trajectory group within 1 year. During 6576 person-years of follow-up (median, 3.7 years), the composite outcome occurred in 521 (28.4%) participants. There were fewer primary outcome events in the decreasing (30.6%) and stable (26.5%) SBP trajectory groups than in the increasing trajectory group (33.0%). In the multivariable-adjusted cause-specific hazards model, increasing SBP trajectory was associated with a 1.28-fold higher risk for adverse kidney outcome compared with stable SBP trajectory. However, the risk for the primary outcome did not differ between the decreasing and stable SBP trajectory groups. In this longitudinal CKD cohort study, compared with stable SBP trajectory, increasing SBP trajectory was associated with higher risk for adverse kidney outcome, whereas decreasing SBP trajectory showed similar risk.


2020 ◽  
Author(s):  
Luciana Saraiva da Silva ◽  
Tiago Ricardo Moreira ◽  
Rodrigo Gomes da Silva ◽  
Rosângela Minardi Mitre Cotta

Abstract Background Recent studies suggest that the progression of chronic kidney disease (CKD) is not linear, but we do not have clear evidence on this issue, especially in hypertensive patients. We sought to evaluate the progression of CKD and associated factors over four years in a cohort of hypertensive patients. Methods We conducted a prospective cohort study during the years 2012 and 2016, with hypertensive patients diagnosed with CKD (n = 113). The progression of CKD was assessed through the evolution of the glomerular filtration rate (GFR) and the change in the stage of CKD between 2012 and 2016. Sociodemographic, economic, lifestyle, clinical, anthropometric, and biochemical variables were evaluated. The strength of the association between CKD progression and explanatory variables was assessed by odds ratio (OR) and their respective 95% confidence intervals using univariate and multivariate logistic regression. Results Regarding progression, 78.1% of the CKD patients did not progress over four years. When assessing the CKD trajectory (2012–2016) through the evolution of GFR, there was a mean reduction of 1.3 mL/min/1.73m² in four years. In the group that progressed, there was a reduction of 13 mL/min/1.73m², while in the group that did not progress, there was an increase of 2 mL/min/1.73m². In the multivariate analyses, age (p = 0.047), diabetes mellitus (DM) (p = 0.042), and urea (p = 0.050) were independently associated with CKD progression. Conclusions The findings of the present study showed a non-linear progression of CKD over the four years, contrary to what is traditionally expected. Age, DM and urea were independently associated with CKD progression.


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.


Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Changwei Li ◽  
Michael Francis ◽  
Adrianna Westbrook ◽  
Ruiyuan Zhang ◽  
Ye Shen ◽  
...  

Introduction: Most genetic variants for chronic kidney disease (CKD) have been identified in non-coding regions, with functional roles that are difficult to interpret. Hypothesis: A whole exome sequencing study focusing on coding variants will reveal novel mechanisms of kidney function and CKD. Methods: We performed whole exome sequencing analyses of cystatin C among 29,789 UK Biobank (UKB) participants with further confirmation among 4,297 white and 607 African American participants of the Health and Retirement Study (HRS). Conditional analyses for loci achieving exome-wide significance ( P <3.5х10 -7 ) were conducted in UKB using both the exome (n=29,789) and imputed GWAS data (n=295,122). Genomic findings were tested for relevance to baseline estimated glomerular filtration rate (eGFR) and stringently adjudicated CKD progression events among participants of the Chronic Renal Insufficiency Cohort (CRIC) by race and smoking status, using a base model and a full model ( Table ). Results: We identified a common missense variant, CST9 rs2983640, in a previously reported locus ( CST3 intron rs13038305), of which the minor G allele was associated with lower serum cystatin C level (UKB: beta=-0.03 mg/L, P =7.64х10 -92 ; HRS whites: beta=-0.05 mg/L, P =4.71х10 -6 ; HRS African Americans: beta=-0.03 mg/L, P =0.64; and multi-ethnic meta-analysis beta=-0.03 mg/L, P =2.46х10 -91 ). After controlling for the CST3 variant, the G allele was associated with higher cystatin C level (UKB exome: beta=0.003 mg/L, P =0.04; UKB GWAS: beta=0.003 mg/L, P =1.47х10 -10 ). Similar associations were identified in white CRIC participants (direct effect: beta=-0.05 mg/L, P =0.005; conditional effect: beta=0.004 mg/L, P =0.86). The CST9 rs2983640 G allele was associated with lower baseline eGFR (base model beta=-0.33 ml/min/1.73 m 2 , P =1.98х10 -6 ) and higher hazard of developing CKD progression independent of the reported CST3 variant ( Table ). Conclusions: We identified a novel missense variant influencing cystatin C level and CKD progression.


BMJ Open ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. e019661 ◽  
Author(s):  
Yu-Feng Wei ◽  
Jung-Yueh Chen ◽  
Ho-Shen Lee ◽  
Jiun-Ting Wu ◽  
Chi-Kuei Hsu ◽  
...  

ObjectiveOur population-based research aimed to clarify the association between chronic kidney disease (CKD) and mortality risk in patients with lung cancer.DesignRetrospective cohort studySettingNational health insurance research database in TaiwanParticipantsAll (n=1 37 077) Taiwanese residents who were diagnosed with lung cancer between 1997 and 2012 were identified. Eligible patients with baseline CKD (n=2269) were matched with controls (1:4, n=9076) without renal disease according to age, sex and the index day of lung cancer diagnosis.MethodsThe cumulative incidence of death was calculated by the Kaplan-Meier method, and the risk determinants were explored by the Cox proportional hazards model.ResultsMortality occurred in 1866 (82.24%) and 7135 (78.61%) patients with and without CKD, respectively (P=0.0001). The cumulative incidences of mortality in patients with and without chronic renal disease were 72.8% vs 61.6% at 1 year, 82.0% vs 76.6% at 2 years and 88.9% vs 87.2% at 5 years, respectively. After adjusting for multiple confounding factors including age and comorbidities, Cox regression analysis revealed that CKD was associated with an increased risk of mortality (adjusted HR 1.38; 95% CI 1.29 to 1.47). Stratified analysis further showed that the association was consistent across patient subgroups.ConclusionComorbidity associated with CKD is a risk factor for mortality in patients with lung cancer.


Author(s):  
Cynthia J Janmaat ◽  
Merel van Diepen ◽  
Yvette Meuleman ◽  
Nicholas C Chesnaye ◽  
Christiane Drechsler ◽  
...  

Abstract Background Initiation of renal replacement therapy often results from a combination of kidney function deterioration and symptoms related to chronic kidney disease (CKD) progression. We investigated the association between kidney function decline and symptom development in patients with advanced CKD. Methods In the European Quality study on treatment in advanced CKD (EQUAL study), a European prospective cohort study, patients with advanced CKD aged ≥65 years and a kidney function that dropped &lt;20 mL/min/1.73 m2 were followed for 1 year. Linear mixed-effects models were used to assess the association between kidney function decline and symptom development. The sum score for symptom number ranged from 0 to 33 and for overall symptom severity from 0 to 165, using the Dialysis Symptom Index. Results At least one kidney function estimate with symptom number or overall symptom severity was available for 1109 and 1019 patients, respectively. The mean (95% confidence interval) annual kidney function decline was 1.70 (1.32; 2.08) mL/min/1.73 m2. The mean overall increase in symptom number and severity was 0.73 (0.28; 1.19) and 2.93 (1.34; 4.52) per year, respectively. A cross-sectional association between the level of kidney function and symptoms was lacking. Furthermore, kidney function at cohort entry was not associated with symptom development. However, each mL/min/1.73 m2 of annual kidney function decline was associated with an extra annual increase of 0.23 (0.07; 0.39) in the number of symptoms and 0.87 (0.35; 1.40) in overall symptom severity. Conclusions A faster kidney function decline was associated with a steeper increase in both symptom number and severity. Considering the modest association, our results seem to suggest that repeated thorough assessment of symptom development during outpatient clinic visits, in addition to the monitoring of kidney function decline, is important for clinical decision-making.


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