Abstract
Living a healthy lifestyle is one of the safest and most cost-effective ways to improve one’s quality of life and prevent and/or manage chronic disease. As such, current CKD management guidelines recommend that patients adhere to a healthy diet, perform ≥150 minutes per week of physical activity, manage their body weight, abstain from tobacco use, and limit alcohol. However, there are limited studies that investigate the relationship between these lifestyle factors and the progression of CKD among people with established CKD. In this narrative review, we examine the reported frequencies of health lifestyle behavior engagement among individuals with non–dialysis-dependent CKD and the existing literature that examines the influences of diet, physical activity, weight management, alcohol consumption, and tobacco use on the progression of CKD, as measured by decline in GFR, incident ESKD, or elevated proteinuria or albuminuria in individuals with CKD. Many of the available studies are limited by length of follow-up and small sample sizes, and meta-analyses were limited because the studies were sparse and had heterogeneous classifications of behaviors and/or referent groups and of CKD progression. Further research should be done to determine optimal methods to assess behaviors to better understand the levels at which healthy lifestyle behaviors are needed to slow CKD progression, to investigate the effect of combining multiple lifestyle behaviors on important clinical outcomes in CKD, and to develop effective techniques for behavior change. Despite the lack of evidence of efficacy from large trials on the ability of lifestyle behaviors to slow CKD progression, maintaining a healthy lifestyle remains a cornerstone of CKD management given the undisputed benefits of healthy lifestyle behaviors on cardiovascular health, BP control, and survival.
Introduction
CKD is an epidemic, affecting more than one in ten American adults (1). Patients with CKD have a high burden of risk factors for cardiovascular disease (CVD) and experience high rates of CVD events. Maintaining a healthy lifestyle offers a crosscutting approach to reduce the risk of CVD. Lifestyle behaviors are similarly recommended across relevant guidelines, including the Kidney Disease Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guideline for the Evaluation and Management of CKD, the KDIGO 2020 Guidelines for Diabetes Management in CKD, and the American College of Cardiology/American Heart Association guidelines on the primary prevention of CVD (Table 1) (2,3). In the CKD population, lifestyle behaviors, such as diet, physical activity, weight management, alcohol consumption, and tobacco use, have mainly been studied in relation to reducing CVD events and mortality risk (4⇓–6), and less is known about limiting CKD progression. The purpose of this narrative review is to describe the current evidence of how select lifestyle behaviors relate to CKD progression, defined as progressive decline in GFR, development of ESKD, or increase in proteinuria or albuminuria among people with established CKD without kidney failure requiring transplant or dialysis. Using PubMed, we selected observational studies, randomized controlled trials (RCTs), systematic reviews, and meta-analyses that focused on the relationship of lifestyle behaviors and CKD progression. The search terms included the following: CKD progression, end-stage renal disease, ESRD, end-stage kidney disease, ESKD, glomerular filtration rate decline, GFR decline, lifestyle factors, diet, dietary pattern, dietary acid load, potential renal acid load, sodium, potassium, protein, phosphorous, smoking, smoking cessation, marijuana, alcohol, physical activity, exercise, obesity, body mass index, and BMI. We did not include studies that investigated the effect of multiple lifestyle behaviors and, therefore, this review does not cover how lifestyle behaviors in combination relate to CKD progression. As a narrative review, we were not inclusive of all published studies assessing the relationship between lifestyle behaviors and CKD progression, which limits our ability to assess all published results, but we have focused on including high-quality studies and limiting inclusion of studies that reported very similar results.
Lifestyle behavior recommendations across clinical practice guidelines
Lifestyle Behavior Prevalence in CKD
The majority of people with CKD do not adhere to several of the recommended levels of lifestyle behaviors (Figure 1). Two thirds of adults with CKD in the United States do not meet the recommended physical activity levels and are sedentary (7,8). More than three quarters of people with CKD are overweight/obese (9,10). Nearly a half to three quarters of people with CKD do not consume a healthy diet, depending on the definition of the recommended diet (4,6,9). Nonsmoking ranged between 71%–92% from CKD cohorts in Europe, North America, and Japan (11), and, among individuals with CKD in the United States, reports of nonsmoking is similar to that of the general population (approximately 86%) (4,6,9,12,13). Nearly all individuals with CKD (93%) meet alcohol recommendations (6).
Diet and CKD
The role of diet in progression of kidney disease has been of great interest for many decades. There are several guideline recommendations for diet and CKD (Table 2), and numerous studies examining the relationship of dietary components and patterns with clinical outcomes in CKD (Tables 3 and 4). By far, the most studied dietary intervention has been protein restriction. and ). The Brenner hyperfiltration theory posits that dietary protein restriction reduces progressive glomerular injury by reducing glomerular hyperfiltration (14). Although protein restriction has been shown to be effective in animal models, the data are mixed in human trials. A 2018 meta-analysis of low protein diets in adults with nondiabetic CKD reported that a low protein intake (0.5–0.6 g/kg per day) versus normal protein intake (≥0.8 g/kg per day) had no effect on risk of ESKD. A very low protein intake (0.3–0.4 g/kg per day) probably reduced the risk of ESKD (relative risk [RR], 0.65; 95% confidence interval [95% CI], 0.49 to 0.85) versus a low or normal protein intake, although there were limited data on adverse effects and no data on quality of life (15) (Figure 2) . As such, the Kidney Disease Outcomes Quality Initiative (KDOQI) 2020 nutrition guidelines recommend, under close clinical supervision, protein restriction with or without keto acid analogues to reduce risk of ESKD/death due to high quality evidence (Table 2). In patients with diabetic CKD, benefits are even less certain (16), with the KDIGO diabetes guideline reporting inconclusive evidence of protein restriction on change in eGFR, ESKD, or other health outcomes (17). The type of protein source may matter because animal-based protein seems to induce higher glomerular hyperfiltration than vegetable-based proteins (18), and a vegetarian diet with equivalent nutrients was shown to result in lower levels of serum phosphate, urine phosphate excretion, and fibroblast growth factor-23 levels (19). Studies in animals have shown that excessive phosphate intake can cause renal parenchymal calcification and proximal tubular injury (20). However, scarce evidence exists that current levels of phosphate intake in humans play a significant role in CKD progression, or that reduction of phosphate intake reduces kidney injury (21⇓–23).
Diet recommendations for individuals with CKD
Summary of RCTs of meta-analyses and select large, randomized studies examining diet and CKD progression with at least 100 participants and 12 months of follow-up
Summary of selected observational studies examining diet and CKD progression
Among nondiabetics with CKD, low protein intake had no effect on risk of ESKD and very low protein intake probably reduced risk of ESKD. Reprinted from ref. 15, with permission. IV, inverse variance; M–H, Mantel–Haenszel; MDRD, Modification of Diet in Renal Disease; VLP, very low protein.
Dietary patterns may be a better way to capture the relationship between diet and chronic disease than studies examining individual nutrients. In addition, dietary patterns may make it easier to provide nutritional advice to patients by focusing on a combination of healthful food groups, rather than focusing on restricting specific nutrients. A systematic review and meta-analysis found that healthy dietary patterns were associated with 27% reduced mortality (n=7 studies; 13,930 participants) but not ESKD (RR, 1.04; 95% CI, 0.68 to 1.40; n=3 studies; 10,071 participants) (24). A study using data from the National Health and Nutrition Examination Survey (NHANES; 1988–1994) found that a low Dietary Approaches to Stop Hypertension (DASH) dietary score was associated with ESKD (quintile 1 relative hazard, 1.7; 95% CI, 1.1 to 2.7; quintile 2 relative hazard, 2.2; 95% CI, 1.1 to 4.1) (25). Hu et al. (26) examined the relationship between dietary intake and risk of CKD progression in the Chronic Renal Insufficiency Cohort (CRIC) Study. Compared with participants with the lowest tertile of adherence, the participants in the most adherent tertile of the Alternative Healthy Eating Index-2010 (AHEI-2010), alternate Mediterranean diet (aMed), and DASH diet were associated with lower risk of CKD progression (17% for AHEI-2010, 25% for aMed, 17% for DASH).
Observational studies examining associations between specific foods and risk of ESKD have often found conflicting findings and can be challenging to interpret given the different methods of estimating intake and differing approaches to adjustment. In the Singapore Chinese Health Study, red meat intake was associated with ESKD (highest quartile versus lowest quartile, hazard ratio, 1.40; 95% CI, 1.15 to 1.71), whereas the consumption of poultry, fish, eggs, or dairy products was not associated with ESKD (27). In the CRIC Study, the benefits observed with the aMed study were largely driven by vegetable and nut intake, whereas no association was seen with red/processed meat intake (26). In the NHANES study, the association between DASH dietary score and risk of ESKD appeared to be mediated, in part, by dietary potassium and magnesium, and, to a lesser extent, to dietary acid load (25).
High net endogenous acid production has been theorized to contribute to kidney disease progression by causing net acid retention, which is associated with increased kidney levels of endothelin-1, and markers of kidney and bone injury (28). The most acid-producing foods tend to be sulfur-rich foods, such as hard/processed cheeses, egg yolks, meat, poultry, and fish, because sulfur is oxidized to inorganic sulfate (29). By contrast, fruits and vegetables are rich in citrate and malate, which undergo combustion internally to produce bicarbonate.
Wesson et al. (30) have shown that metabolic acidosis could lead to inflammation and fibrosis. Observational studies have shown an association between dietary acid load and risk of ESKD in NHANES (25), and eGFR decline in the African American Study of Kidney Disease and Hypertension (31). However, these studies used estimates of acid load or net acid excretion. In a recent analysis of the CRIC Study, net acid excretion was measured as the sum of urine ammonium and titratable acidity in 24-hour urine samples of a 980-participant subcohort (32). Surprisingly, higher net acid excretion was associated with decreased risk of a composite outcome of ESKD or 50% eGFR decline in patients with diabetes, whereas no association was found in those without diabetes (Table 4). Reasons for this discrepancy are unclear, but the authors hypothesized there may be diet-independent changes in acid production in diabetes (32). Regardless, interventions reducing net endogenous acid production appear to be beneficial for slowing CKD progression. A systematic review of interventions that treat metabolic acidosis (oral alkali therapy or dietary acid reduction) in stage 3–5 CKD found evidence of low-to-moderate certainty that treatment of metabolic acidosis with oral alkali therapy or dietary acid reduction may slow the rate of eGFR decline or reduce the risk of ESKD (33) (Figure 3) . In a small RCT of 108 patients with stage 3 CKD and bicarbonate levels of 22–24 mmol/L, randomization to alkali therapy, whether delivered as sodium bicarbonate or by providing fruits and vegetables, slowed cystatin C–based eGFR decline over 3 years (34). The KDOQI 2020 nutrition guidelines suggest, based on limited evidence, that increasing intake of fruits and vegetables can reduce net endogenous acid production to slow CKD progression (Table 2).
Among studies of people with stage 3–5 CKD, there was low-to-moderate evidence that treatment of metabolic acidosis with oral alkali therapy or dietary acid reduction slowed the rate of eGFR decline or reduced the risk of ESKD. Reprinted from ref. 33, with permission. IV, inverse variance.
Limited data exist on sodium and potassium intake and CKD progression. Capturing dietary sodium and potassium intake is challenging because collecting multiple-day, 24-hour urine collections or diet records can be burdensome and food frequency questionnaires can be limited if questions are not applicable to local dietary practices; both food frequency questionnaires and 24-hour diet recalls are limited by recall bias. Multiple 24-hour urine collections are the gold standard for estimating sodium intake (35), although there have not been validation studies of 24-hour urine sodium and potassium versus measured dietary intake specifically in patients with CKD. RCTs comparing different levels of sodium intake suggest that sodium reduction lowers albuminuria (36,37), and observational studies (CRIC Study, KoreaN Cohort Study for Outcomes in Patients with Chronic Kidney Disease [KNOW-CKD]) have reported an association between high 24-hour urine sodium and increased risk of CKD progression (Table 4). Data on potassium are mixed, with high 24-hour urine potassium excretion being associated with CKD progression in CRIC, whereas low 24-hour urine potassium excretion was associated with CKD progression in KNOW-CKD (38,39). Unfortunately, there are not yet any long-term RCT data to determine whether modulating either sodium or potassium intake affects CKD progression. A multicenter, double-blind, placebo-controlled RCT testing the effects of 40 mEq of potassium (delivered as potassium chloride or potassium citrate) versus placebo on eGFR decline in patients with hypertension and stage 3b/4 CKD is currently underway (https://clinicaltrials.gov/ct2/show/NCT03253172) (40).
Specific types of CKD may have particular benefits to dietary modification. For example, although an RCT of coaching to increase water intake in patients with stage 3 CKD and albuminuria over 1 year reported no significant effect on kidney function decline (41), there may be benefits in patients with adult autosomal dominant polycystic kidney disease (ADPKD) (42). Increased antidiuretic hormone (arginine vasopressin) stimulates cell proliferation through the vasopressin V2 receptor, resulting in increased intracellular cAMP. Interestingly, high water intake decreases urinary vasopressin, whereas high sodium intake stimulates urinary vasopressin (43). A recent study found that every 1 g/d of sodium was associated with increased eGFR decline (−0.11 ml/min per 1.73 m2 per gram of salt), whereas protein intake was not associated with CKD progression in patients with ADPKD. The association between sodium intake and CKD progression was substantially mediated by plasma copeptin, supporting the possible role of sodium increasing vasopressin and resulting in CKD progression (42). Further randomized trials are needed to determine whether sodium restriction or increased fluid intake can slow progression in ADPKD.
Physical Activity and CKD
There is little controversy regarding the beneficial effects of physical activity on overall health and, thus, the Physical Activity Guidelines for Americans recommends adults should move more and sit less throughout the day and participate in any amount of moderate-to-vigorous physical activity to gain some health benefits. For substantial health benefits, adults should do at least 150 minutes of moderate-intensity activity per week or 75 minutes of vigorous-intensity activity per week. Adults should also do strengthening activities of moderate or greater intensity on ≥2 days a week because these activities provide additional health benefits (44). The term exercise is typically applied to moderate or vigorous physical activities (44).
Depending on how physical activity is defined (see Box 1), many adults with CKD have self-reported sedentary behavior and most do not reach recommended levels of physical activity (4,5,8,9, 45). Reduced physical activity is associated with increased mortality (5) and more CVD events (6), but less is known about its relationship to CKD progression, with much of the research stemming from single-center observational studies and very few clinical trials (Table 5) (46). Robinson-Cohen, et al. (45) described the relationship between self-reported leisure-time physical activity and kidney function decline in 256 outpatients with stage 3–4 CKD (mean age, 61 years). Nearly a quarter of the patients reported no leisure-time activity at all, and they had a greater decline in eGFR per year compared with those who met the guideline-recommended levels of physical activity. Further, each 60 minute–greater duration of leisure-time physical activity was associated with a 0.5% per year slower decline in eGFR, but leisure-time activity was not associated with incident ESKD (45). Leisure-time physical activity was also not associated with rapid kidney function decline (>3 ml/min per year) among 558 older adults with an eGFR of <60 ml/min per 1.73 m2 (47). Walking and participation in physical activity more than one time per week in older adults (mean age, >70 years) has been reported to be associated with reduced risk of incident ESKD (48), but, in a younger cohort of people with CKD, recommended physical activity, compared with inactivity, was not associated with a composite CKD progression outcome (50% decline in eGFR from baseline or incident ESKD) (4). Together, these findings suggest that greater leisure-time physical activity may slow the rate of kidney function decline, and that any physical activity may be beneficial for lowering the risk of ESKD, particularly among older adults. However, due to the observational design and heterogeneous definitions for CKD progression, these studies cannot establish causality, and it is possible that physical activity is a marker of overall morbidity and could be confounded by survival bias or competing risk of CVD events in younger individuals. More data are needed to further assess the relationship of physical activity and, particularly the minimum amount needed to slow CKD progression.
Summary of select epidemiologic studies of the association between physical activity and CKD progression among individuals with established CKD
Physical Activity Intensity and Classifications of Activity
Intensity: Effort required to perform an activity. Aerobic intensity is typically expressed as rate of energy expenditure using kilocalories per minute or metabolic equivalent of task (MET). One MET is equivalent to sitting at rest.
Sedentary: Activity ≤1.5 METs while sitting, reclining or lying down.
Light intensity: Nonsedentary activities while awake, 1.6 to <3.0 METs (e.g., walking at leisurely pace).
Moderate intensity: Activities 3 to <6 METs (e.g., walking briskly, swimming).
Vigorous intensity: Activities ≥6 METs (e.g., walking very fast, running).
Inactive: No moderate- or vigorous-intensity physical activity beyond daily life activities per week.
Insufficiently active: One to <150 min/wk of moderate-intensity physical activity or 1 to <75 min/wk of vigorous-intensity activity per week, or equivalent combination.
Active: Moderate-intensity activity for ≥150 min/week, or equivalent combination of moderate and vigorous (meets guidelines at this level).
Directly assessing the effects of physical activity on CKD progression in patients with established CKD requires RCTs of physical activity or exercise training programs. Two recent meta-analyses investigated the effect of RCTs testing physical activity and exercise interventions on CKD progression among people with CKD, and both meta-analyses found that the interventions were not associated with reduced CKD progression, in terms of no difference in eGFR (Figure 4) (49,50), serum creatinine (49), or proteinuria (50) between intervention and control groups. However, RCTs included in these meta-analyses consisted of small sample sizes, were of short duration, and did not have adequate observation time to evaluate the effect of risk of disease progression. In addition, serum creatinine correlates with muscle mass, which poses a challenge in interpreting small increases in creatinine during an exercise trial due to increased physical activity and increased muscle metabolism, leading to an underestimation of eGFR and, therefore, kidney function.
A meta-analysis of physical activity and exercise interventions tested in randomized controlled trials among people with CKD found there was no difference in eGFR among intervention and control groups. Reprinted from ref. 49, with permission.
Weight Management and CKD
In clinical practice, weight management is typically assessed with body mass index (BMI), determined by body weight and height (in kilograms per meter squared). The World Health Organization considers a BMI of between 18.5 and 25 kg/m2 as normal weight, a BMI between 25 and 30 kg/m2 as overweight, and a BMI of >30 kg/m2 as obese. The prevalence of obesity continues to increase worldwide, and a consistent, graded relationship between obesity and incident CKD has been demonstrated (11,51,52). A recent UK Biobank study using Mendelian randomization suggests that the obesity-CKD relationship is causal and mostly mediated by diabetes and elevated BP (53). However, the relationship between obesity and CKD progression is less clear in patients with established CKD (Table 6).
Summary of select epidemiologic studies of the association of BMI and CKD progression among individuals with established CKD
In a large cohort of 453,946 US veterans with an eGFR of <60 ml/min per 1.73 m2, a BMI corresponding to overweight/mild obesity (25–35 kg/m2) had the lowest risk for CKD progression, and a BMI <25 kg/m2 was consistently associated with worsening of kidney function (10). However, the generalizability of this study’s findings may be limited because the cohort was older (>70 years), and most participants were men. Individual-level meta-analyses were conducted by the CKD Prognosis Consortium in 5.5 million adults in 39 general population cohorts and 91,607 adults in 18 CKD cohorts (11). In models stratified by baseline eGFR, hazard ratios for risk of eGFR decline for a BMI of 35 kg/m2 versus a reference BMI of 25 kg/m2 were 1.88 (95% CI, 1.69 to 2.08) for those with an eGFR of 30–59 ml/min per 1.73 m2 were 1.78 (95% CI, 1.36 to 2.34) and 1.88 (95% CI, 1.61 to 2.18) for those with an eGFR of <30 ml/min per 1.73 m2 (Figure 5). Adjustment for potential mediators (e.g., hypertension, diabetes, albuminuria) attenuated results. Meta-analysis of participants in the CKD cohorts found smaller effect sizes, with sensitivity analysis excluding the first 3 years of follow-up suggesting some role of reverse causation (Figure 5, Table 6). Risks associated with obesity may vary by type of kidney disease. An elevated BMI among individuals with IgA nephropathy and ADPKD has been noted as a risk factor for CKD progression (54,55), whereas no association between elevated BMI and risk of CKD progression was noted in a cohort of patients with biopsy sample–proven glomerulonephritides (56).
Individual-level meta-analyses found the risk of eGFR decline was higher among those with BMI 35 kg/m2, particularly with eGFR <60 ml/min per 1.73 m2. Meta-analyzed hazard ratios and 95% CIs are related to body mass index, modeled by linear splines with knots at body mass indices of 20, 25, 30, and 35 kg/m2 (reference is body mass index of 25 kg/m2 in each category). Reprinted from ref. 11, with permission.
CKD management guidelines recommend weight reduction for adults with CKD and obesity. However, intentional weight loss among these individuals has shown mixed results, and largely depends on the type of weight-loss intervention (e.g., diet, exercise, surgery, medications). The current evidence of the effects of weight loss on the progression of CKD is mainly on the basis of observational reports and a few small randomized trials of low-to-moderate quality. Bariatric surgery has most consistently suggested a beneficial effect of weight loss on kidney function (57), with a recent RCT of patients with type 2 diabetes and albuminuria demonstrating greater resolution of albuminuria in those undergoing Roux-en-Y gastric bypass versus best medical treatment (82% versus 48% remission) (58). At this time, there are no convincing data to support a specific diet for weight loss to slow CKD progression (59). Additionally, some controversy exists in more advanced CKD (i.e., eGFR of <30 ml/min per 1.73 m2) because malnutrition and muscle wasting are potential concerns and observational studies have found an association between weight loss and risk of death in patients with ESKD (60⇓–62). However, much of this weight loss is unintentional, and recent studies have found that bariatric surgery is associated with reduced risk of death in patients with CKD and ESKD (63,64). It is beyond the scope of this review to describe in detail each of the weight-loss strategies and CKD progression; others have provided in-depth reviews of weight-loss strategies that have been used in CKD studies (65,66).
Tobacco Use and CKD
Tobacco use is the leading preventable cause of death and disability in the United States and is a major contributor to CVD (67), which is more common among those with CKD than those without kidney disease. Smoking is associated with increased risk of progression of CKD in some, but not all, studies, and the beneficial effects of smoking cessation on delaying CKD progression is unclear (Table 7) (68,69). Current cigarette smokers, compared with nonsmokers, have been found to have greater eGFR decline per year among those with early-stage CKD and type 2 diabetes (70), or biopsy sample–proven glomerular disease (71), but smoking has not been associated with rapid eGFR decline (>1 ml/min per 1.73 m2 per year) among those with stage 3 CKD and ADPKD (72). In terms of incident ESKD, smoking was observed to have a higher risk in a study of 1722 people with CKD stage 3 (73), but, among larger cohorts (N=3093 and N=6245) of people with similar levels of kidney function (9,13), smoking was not found to be associated with ESKD.
Summary of select epidemiologic studies of the association of smoking and CKD progression among people with established CKD
Former and/or current smoking has been associated with increased risk of a composite outcome of incident ESKD and 50% decline in eGFR in some, but not all, studies—depending on how the smoking exposure was modeled (Table 7). This is exemplified in two studies, using the same data from 3939 adults with an eGFR of 20–70 ml/min per 1.73 m2 in the CRIC Study, that observed current smoking did and did not have an increased risk of CKD progression when modeled from baseline exposure or as cumulative average exposure, respectively (4,74). The inconsistencies of smoking and CKD progression risk may be attributed to the observational nature of most of the smoking research in CKD, including the study design and population, such as differences in age (which could introduce survival bias), proportion with diabetes, and length of follow-up time to observe the outcome of interest.
There appears to be a dose-response relationship of greater smoking exposure and CKD progression in that higher smoking pack-years were associated with increased CKD progression. In a cohort of 1951 middle-aged adults with predominantly CKD stage 3 (Mean eGFR: 53 ml/min per 1.73 m2) from the KNOW-CKD Study, ≥15 pack-year smokers and ≥30 pack-year smokers, compared with never smokers, were each associated with increased risk of CKD progression over 3 years of follow-up (75).
The benefits of smoking cessation on CKD progression have not been well studied but appear to be promising. Several studies have shown that the risk for CKD progression of former smokers was lower than that of current smokers (76,77), and there was a graded decrease in risk as time since smoking cessation increased (78). There has been one clinical trial of 108 smokers and 108 nonsmokers with stage 2 CKD and proteinuria without diabetes treated with angiotensin-converting enzyme inhibitor therapy where the current smokers underwent a smoking-cessation intervention program. After 5 years of follow-up, eGFR was higher in nonsmokers and quitters than in continued smokers (79). The use of electronic cigarettes as a means to quit cigarette smoking is not currently supported because the data on the use of electronic cigarettes in those with kidney disease are sparse.
Alcohol Use and CKD
In the general population, alcohol use is associated with poorer health overall, but moderate drinking appears to be protective for some CVD events (80⇓⇓⇓–84). It is proposed that alcohol consumption has cardioprotective effects on insulin sensitivity, thrombotic activity, and inflammation (85). However, among people with established CKD, no or moderate alcohol intake, compared with excessive intake, has been associated with increased risk of major coronary events (6). Similarly, the epidemiologic literature on alcohol and kidney function, which has focused on both the development and progression of kidney disease, has reported mixed observations, largely due to very few studies specifically investigating the relationship of alcohol consumption and the effect on disease progression among individuals with established CKD (Table 8). According to these studies, only binge alcohol drinking was associated with increased risk of CKD progression, and other levels of drinking (i.e., any, occasional, or moderate) were not associated with CKD progression. In the general population, reducing alcohol consumption among those who drink heavily has been demonstrated in RCTs to lower BP, but there are insufficient data on the risks or benefits of these interventions on BP in CKD populations, which precluded specific recommendations in the most recent KDIGO 2021 Guidelines for Blood Pressure and CKD (86).
Summary of select epidemiologic studies of the association of alcohol use and CKD progression among people with established CKD
Future Research Directions
Published KDOQI and KDIGO clinical practice guidelines that address lifestyle behaviors for the management of CKD in adults have identified research directions to address gaps in the evidence for delaying CKD progression (17,86,87). We summarize some of these recommendations here, including establishing the best methods to assess dietary intake and to support dietary change, such as nutritional education and dietary modification through shared decision making, behavior-modification techniques, and motivational interviewing. More research is needed to understand the role and potential benefits of using technology to assess dietary intake and to support behavior change. Clinical trials are needed to evaluate different strategies for sodium reduction, including identifying the amount of dietary sodium intake that is associated with improved outcomes among people with CKD. Further studies should compare the benefits of various intensity levels and types of physical activity, including the incorporation of resistance training in those with CKD. This research could also identify individual factors for patients with CKD that have the greatest benefit in terms of clinical outcomes, including BP control, that could inform personalized physical-activity recommendations. In terms of weight-management research, future efforts could determine the relationship of weight loss and renoprotection and compare the effect of various weight-loss strategies on clinical outcomes in CKD. Additional lifestyle behavior research should include the effect of behaviors in combination on CKD progression and other important clinical and patient-reported outcomes.
Lifestyle Behaviors in Practice
Despite lack of evidence of efficacy from large trials, maintaining a healthy lifestyle remains a cornerstone of CKD management because healthy lifestyle behaviors are largely modifiable and have been shown to improve cardiovascular health and BP control and are thought to indirectly or directly affect CKD progression (Figure 6). It is reasonable that all adults with CKD receive counseling on the benefits of a healthy lifestyle, including diet, physical activity, smoking cessation, weight management, and moderation of alcohol intake, and it is equally important to address suboptimal lifestyle behavior adherence during routine clinic visits despite competing issues. Health-care providers can refer patients with CKD to medical nutrition therapy–trained dieticians who specialize in behavioral change plans that include exercise, nutrition, and stress control, and this service is covered by most health insurance plans (88). Lifestyle recommendations are of relevance in all countries, with limited to no public health costs, and have the potential to make far-reaching public health gains. The importance of lifestyle behaviors in CKD is underscored in the international CKD management guidelines with the following statement: “for the practicing clinician, ideally working with a team of health-care professionals, it is important to institute general lifestyle modifications practices in people with CKD so that they may gain the benefit of these in addition to more kidney-specific strategies” (89).
Healthy lifestyle behaviors indirectly and/or directly influence cardiovascular health and CKD progression. Gray dashed arrows indicate a harmful effect, and a solid black line reflects a beneficial effect.
Disclosures
A.R. Chang reports having other interests in/relationships with National Kidney Foundation (grant support for NKF Patient Network); having consultancy agreements with Novartis (as consultant); receiving research funding from Novo Nordisk (investigator-sponsored study); receiving honoraria from Reata; and serving as a scientific advisor for, or member of, Reata and Relypsa. S.J. Schrauben reports receiving honoraria from Cowen and Company, LLC. The remaining author has nothing to disclose.
Funding
This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases grants K23 DK 118198-01A1 (to S.J. Schrauben) and K23 DK106515 (to A.R. Chang).
Acknowledgments
The funders had no role in the study design, data collection, analysis and interpretation of data, in the writing of report, or in the decision to submit the article for publication.
Author Contributions
B.J. Apple, A.R. Chang, and S.J. Schrauben reviewed and edited the manuscript and were responsible for data curation; A.R. Chang and S.J. Schrauben were responsible for funding acquisition; A.R. Chang and S.J. Schrauben conceptualized the study and were responsible for formal analysis, investigation, and methodology; and S.J. Schrauben wrote the original draft.
- Received May 7, 2021.
- Accepted January 7, 2022.
- Copyright © 2022 by the American Society of Nephrology
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