Despite increasing incidence of CKD, no evidence-based lifestyle recommendations for CKD primary prevention apparently exist.
To evaluate the consistency of evidence associating modifiable lifestyle ...factors and CKD incidence, we searched MEDLINE, Embase, CINAHL, and references from eligible studies from database inception through June 2019. We included cohort studies of adults without CKD at baseline that reported lifestyle exposures (diet, physical activity, alcohol consumption, and tobacco smoking). The primary outcome was incident CKD (eGFR<60 ml/min per 1.73 m
). Secondary outcomes included other CKD surrogate measures (RRT, GFR decline, and albuminuria).
We identified 104 studies of 2,755,719 participants with generally a low risk of bias. Higher dietary potassium intake associated with significantly decreased odds of CKD (odds ratio OR, 0.78; 95% confidence interval 95% CI, 0.65 to 0.94), as did higher vegetable intake (OR, 0.79; 95% CI, 0.70 to 0.90); higher salt intake associated with significantly increased odds of CKD (OR, 1.21; 95% CI, 1.06 to 1.38). Being physically active versus sedentary associated with lower odds of CKD (OR, 0.82; 95% CI, 0.69 to 0.98). Current and former smokers had significantly increased odds of CKD compared with never smokers (OR, 1.18; 95% CI, 1.10 to 1.27). Compared with no consumption, moderate consumption of alcohol associated with reduced risk of CKD (relative risk, 0.86; 95% CI, 0.79 to 0.93). These associations were consistent, but evidence was predominantly of low to very low certainty. Results for secondary outcomes were consistent with the primary finding.
These findings identify modifiable lifestyle factors that consistently predict the incidence of CKD in the community and may inform both public health recommendations and clinical practice.
Traditional dietary recommendations for patients with chronic kidney disease (CKD) focus on the quantity of nutrients consumed. Without appropriate dietary counselling, these restrictions can result ...in a low intake of fruits and vegetables and a lack of diversity in the diet. Plant nutrients and plant-based diets could have beneficial effects in patients with CKD: increased fibre intake shifts the gut microbiota towards reduced production of uraemic toxins; plant fats, particularly olive oil, have anti-atherogenic effects; plant anions might mitigate metabolic acidosis and slow CKD progression; and as plant phosphorus has a lower bioavailability than animal phosphorus, plant-based diets might enable better control of hyperphosphataemia. Current evidence suggests that promoting the adoption of plant-based diets has few risks but potential benefits for the primary prevention of CKD, as well as for delaying progression in patients with CKD G3-5. These diets might also help to manage and prevent some of the symptoms and metabolic complications of CKD. We suggest that restriction of plant foods as a strategy to prevent hyperkalaemia or undernutrition should be individualized to avoid depriving patients with CKD of these potential beneficial effects of plant-based diets. However, research is needed to address knowledge gaps, particularly regarding the relevance and extent of diet-induced hyperkalaemia in patients undergoing dialysis.
Management of the global crisis of the coronavirus disease 2019 pandemic requires detailed appraisal of evidence to support clear, actionable, and consistent public health messaging. The use of cloth ...masks for general public use is being debated, and is in flux. We searched the MEDLINE and EMBASE databases and Google for articles reporting the filtration properties of flat cloth or cloth masks. We reviewed the reference lists of relevant articles to identify further articles and identified articles through social and conventional news media. We found 25 articles. Study of protection for the wearer used healthy volunteers, or used a manikin wearing a mask, with airflow to simulate different breathing rates. Studies of protection of the environment, also known as source control, used convenience samples of healthy volunteers. The design and execution of the studies was generally rigorously described. Many descriptions of cloth lacked the detail required for reproducibility; no study provided all the expected details of material, thread count, weave, and weight. Some of the homemade mask designs were reproducible. Successful masks were made of muslin at 100 threads per inch (TPI) in 3 to 4 layers (4-layer muslin or a muslin-flannel-muslin sandwich), tea towels (also known as dish towels), made using 1 layer (2 layers would be expected to be better), and good-quality cotton T-shirts in 2 layers (with a stitched edge to prevent stretching). In flat-cloth experiments, linen tea towels, 600-TPI cotton in 2 layers, and 600-TPI cotton with 90-TPI flannel performed well but 80-TPI cotton in 2 layers did not. We therefore recommend cotton or flannel at least 100 TPI, at least 2 layers. More layers, 3 or 4, will provide increased filtration but there is a trade-off in that more layers increases the resistance to breathing. Although this is not a systematic review, we included all the articles that we identified in an unbiased way. We did not include gray literature or preprints. A plain language summary of these data and recommendations, as well as information on making, wearing and cleaning cloth masks is available at www.clothmasks.ca.
It is unknown whether stopping renin-angiotensin system (RAS) inhibitor therapy in patients with advanced CKD affects outcomes.
We studied patients referred to nephrologist care, listed on the ...Swedish Renal Registry during 2007-2017, who developed advanced CKD (eGFR<30 ml/min per 1.73 m
) while on RAS inhibitor therapy. Using target trial emulation techniques on the basis of cloning, censoring, and weighting, we compared the risks of stopping within 6 months and remaining off treatment versus continuing RAS inhibitor therapy. These included risks of subsequent 5-year all-cause mortality, major adverse cardiovascular events, and initiation of kidney replacement therapy (KRT).
Of 10,254 prevalent RAS inhibitor users (median age 72 years, 36% female) with new-onset eGFR <30 ml/min per 1.73 m
, 1553 (15%) stopped RAS inhibitor therapy within 6 months. Median eGFR was 23 ml/min per 1.73 m
. Compared with continuing RAS inhibition, stopping this therapy was associated with a higher absolute 5-year risk of death (40.9% versus 54.5%) and major adverse cardiovascular events (47.6% versus 59.5%), but with a lower risk of KRT (36.1% versus 27.9%); these corresponded to absolute risk differences of 13.6 events per 100 patients, 11.9 events per 100 patients, and -8.3 events per 100 patients, respectively. Results were consistent whether patients stopped RAS inhibition at higher or lower eGFR, across prespecified subgroups, after adjustment and stratification for albuminuria and potassium, and when modeling RAS inhibition as a time-dependent exposure using a marginal structural model.
In this nationwide observational study of people with advanced CKD, stopping RAS inhibition was associated with higher absolute risks of mortality and major adverse cardiovascular events, but also with a lower absolute risk of initiating KRT.
AbstractObjectiveTo identify the optimal estimated glomerular filtration rate (eGFR) at which to initiate dialysis in people with advanced chronic kidney disease.DesignNationwide observational cohort ...study.SettingNational Swedish Renal Registry of patients referred to nephrologists.ParticipantsPatients had a baseline eGFR between 10 and 20 mL/min/1.73 m2 and were included between 1 January 2007 and 31 December 2016, with follow-up until 1 June 2017.Main outcome measuresThe 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 m2 in increments of 1 mL/min/1.73 m2. An eGFR between 6 and 7 mL/min/1.73 m2 (eGFR6-7) was taken as the reference.ResultsAmong 10 290 incident patients with advanced chronic kidney disease (median age 73 years; 3739 (36%) women; median eGFR 16.8 mL/min/1.73 m2), 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 eGFR15-16. Compared with dialysis initiation at eGFR6-7, initiation at eGFR15-16 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 (eGFR10-14v eGFR5-7) and the achieved eGFRs in IDEAL (eGFR7-10v eGFR5-7), 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.ConclusionsVery 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.
We congratulate the KDIGO (Kidney Disease: Improving Global Outcomes) work group on their comprehensive work in a broad subject area and agreed with many of the recommendations in their clinical ...practice guideline on the evaluation and management of chronic kidney disease. We concur with the KDIGO definitions and classification of kidney disease and welcome the addition of albuminuria categories at all levels of glomerular filtration rate (GFR), the terminology of G categories rather than stages to describe level of GFR, the division of former stage 3 into new G categories 3a and 3b, and the addition of the underlying diagnosis. We agree with the use of the heat map to illustrate the relative contributions of low GFR and albuminuria to cardiovascular and renal risk, though we thought that the highest risk category was too broad, including as it does people at disparate levels of risk. We add an albuminuria category A4 for nephrotic-range proteinuria and D and T categories for patients on dialysis or with a functioning renal transplant. We recommend target blood pressure of 140/90 mm Hg regardless of diabetes or proteinuria, and against the combination of angiotensin receptor blockers with angiotensin-converting enzyme inhibitors. We recommend against routine protein restriction. We concur on individualization of hemoglobin A1c targets. We do not agree with routine restriction of sodium intake to <2 g/d, instead suggesting reduction of sodium intake in those with high intake (>3.3 g/d). We suggest screening for anemia only when GFR is <30 mL/min/1.73 m2 . We recognize the absence of evidence on appropriate phosphate targets and methods of achieving them and do not agree with suggestions in this area. In drug dosing, we agree with the recommendation of using absolute clearance (ie, milliliters per minute), calculated from the patient’s estimated GFR (which is normalized to 1.73 m2 ) and the patient’s actual anthropomorphic body surface area. We agree with referral to a nephrologist when GFR is <30 mL/min/1.73 m2 (and for many other scenarios), but suggest urine albumin-creatinine ratio > 60 mg/mmol or proteinuria with protein excretion > 1 g/d as the referral threshold for proteinuria.
The reported incidence, prevalence and outcomes of atrial fibrillation (AF) in patients with end-stage renal disease (ESRD) are variable. The risks and benefits of warfarin anticoagulation need to be ...defined as the risk of bleeding in ESRD patients may overwhelm the benefits of embolic stroke prevention. We undertook a systematic literature review to clarify these issues.
A literature search was undertaken using Medline and EMBASE from 1990 to September 2011. Studies that reported incidence, prevalence or selected outcomes in ESRD patients with AF were included. Cross-sectional, cohort and randomized controlled trials with >25 participants were included. The lists of authors and abstracts from the search were reviewed by two investigators to determine the manuscripts for full text review. Data were abstracted to a form designed specifically for this study. The quality of the studies was assessed using the Newcastle-Ottawa scale. Event rates were calculated using a random-effects model.
Twenty-five studies met our inclusion criteria. The prevalence of AF was 11.6% and the overall incidence was 2.7/100 patient-years. The risk of mortality and stroke was increased in ESRD patients with AF at 26.9 and 5.2/100 patient-years versus 13.4 and 1.9/100 patient-years compared with ESRD patients without AF. The majority of studies do not support a protective effect for warfarin in ESRD patients with AF.
The incidence and prevalence of AF in ESRD patients are higher than in the general population and are associated with an increased risk of stroke and mortality. An appropriately designed randomized controlled trial is required to determine whether anticoagulation is an appropriate therapeutic strategy in patients with end-stage renal disease and atrial fibrillation.
Mineralocorticoid receptor (MR) activation is involved in propagating kidney injury, inflammation, and fibrosis and in the progression of chronic kidney disease (CKD). Multiple clinical studies have ...defined the efficacy of MR antagonism in attenuating progressive kidney disease, and the US Food and Drug Administration recently approved the nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone for this indication. In this review, we consider the basic science and clinical applicability of MR antagonism. Because hyperkalemia constitutes a constraint to implementing evidence-based MR blockade, we review MRA-associated hyperkalemia in the context of finerenone and discuss evolving mitigation strategies to enhance the safety and efficacy of this treatment. Although the FIDELIO-DKD and FIGARO-DKD clinical trials focused solely on patients with type 2 diabetes mellitus, we propose that MR activation and the resulting inflammation and fibrosis act as a substantive pathogenetic mediator not only in people with diabetic CKD but also in those with CKD without diabetes. We close by briefly discussing both recently initiated and future clinical trials that focus on extending the attributes of MR antagonism to a wider array of nondiabetic kidney disorders, such as patients with nonalbuminuric CKD.
Patients are often advised to reduce sodium and potassium intake, but supporting evidence is limited. To help provide such evidence we estimated 24h urinary sodium and potassium excretion in 28,879 ...participants at high cardiovascular risk who were followed for a mean of 4.5 years in the ONTARGET and TRANSCEND trials. The primary outcome was eGFR decline of 30% or more or chronic dialysis. Secondary outcomes were eGFR decline of 40% or more or chronic dialysis, doubling of serum creatinine or chronic dialysis, an over 5%/year loss of eGFR, progression of albuminuria, and hyperkalemia. Multinomial logit regression with multivariable fractional polynomials, adjusted for confounders, determined the association between urinary sodium and potassium excretion and renal outcomes, with death as a competing risk. The primary outcome occurred in 2,052 (7.6%) patients. There was no significant association between sodium and any renal outcome (primary outcome odds ratio 0.99; 95% CI 0.89–1.09 for highest median 6.2g/day vs. lowest third median 3.3g/day). Higher potassium was associated with lower odds of all renal outcomes (primary outcome odds ratio 0.74; 95% CI 0.67–0.82 for highest median 2.7g/day vs. lowest third median 1.7g/day, except hyperkalemia nonsignificant. Thus, urinary potassium, but not sodium, excretion predicted clinically important renal outcomes. Our findings do not support routine low sodium and potassium diets for prevention of renal outcomes in people with vascular disease with or without chronic kidney disease.