Addressing the Threat to Kidney Health from Modern Diets

CKD prevalence and its associated adverse outcomes continue to increase, driven by progression from early to more advanced stages and by longer survival among affected individuals.1 As a result, people with CKD have greater opportunity to develop complications for which CKD confers excess risk, particularly cardiovascular disease (CVD), as well as disability, while health care costs borne by patients and society rise. CKD typically develops and progresses without symptoms, leaving most individuals unaware of their disease until late stages or until it is detected incidentally. Individual clinicians help reduce the national CKD burden by instituting kidney-protective strategies in identified patients. However, addressing the large number of individuals with undiagnosed CKD or elevated risk will likely require population-based strategies that target modifiable risk factors operating at the societal level. Diet is a well-documented contributor to chronic disease in modern societies, including CKD. It plays a major contributor to the initiation, progression, and adverse outcomes from the two major causes of CKD in modern societies, diabetes, and primary hypertension. This recognition informs guidelines recommending “healthy” diets, including those with high proportions of fruits and vegetables (F&V), as first-line treatment for these most common causes of CKD, usually as adjuncts to pharmacologic therapy. There is, however, an opportunity for more consistent recommendation of these diets by clinicians and for better uptake of these diets by patients when recommended. The latter speaks to challenges faced by patients to adopt these diets, given their lower accessibility compared with that for less healthy diets. Lower accessibility to “healthy” diets is a particular challenge for residents of underresourced communities who are at greater risk for CKD. Epidemiologic data linking higher F&V intake with lower rates of diabetes and hypertension support population-level dietary interventions as a means to reduce CKD incidence and progression. Populations consuming diets high in F&V have lower CKD incidence and slower disease progression.2 Diets eaten by most modern society adults have much lower F&V proportions than recommended by dietary guidelines.3 Interventional studies examining the effects of increasing the dietary proportion of F&V on kidney health of study participants with asymptomatic, early-stage CKD showed no further albuminuria increase and slower rate of decline of eGFR.4 These data support increasing population-level dietary F&V content to reduce the population-level CKD burden. Diets high in F&V have features that can promote kidney health and might mediate these described benefits. Reduced Dietary Acid Production Most modern diets are net acid producing because they contain proportionately more acid-producing, ultra-processed, and animal-sourced foods than base-producing, plant-sourced foods such as F&V. Acid-producing diets in population epidemiologic studies were associated with increased CKD incidence and progression, supporting dietary acid reduction as a public health approach to reduce CKD incidence and progression.5 Dietary acid reduction achieved by adding either base-producing F&V or sodium-based oral mineral alkali as sodium bicarbonate (NaHCO3) slowed progression of early-stage CKD.4 Although both dietary acid reduction strategies yielded comparable protection for albuminuria and eGFR than usual care, F&V yielded showed improvement of CVD risk parameters, including lower BP, than NaHCO3.4 Recognizing that CVD is the major mortality cause in CKD,1 these data support F&V over NaHCO3 as the preferred dietary acid reduction strategy for kidney protection in patients with CKD. Yielding Gut Microbiota Supportive of Kidney Health There is increasing recognition that the gut microbiota profile contributes to kidney health. The low F&V content of most modern diets yields a gut microbiota profile that increases production of substances that cause kidney injury and might contribute to CKD progression.6 As such, diets high in F&V might also improve kidney health by shifting the gut microbiota profile toward one that reduces production of uremic toxins. Fats in many plants are anti-inflammatory, and plant fiber fermentation by gut bacteria can produce anti-inflammatory short-chain fatty acids that can enhance kidney health by this mechanism.7 These data support that diets proportionately high in F&V promote a kidney protective microbiota profile, possibly reducing the risk for incident CKD and for its progression. Reducing Oxidative Stress Oxidative stress occurs when there is an imbalance between production of oxidants that can cause tissue injury and processes that limit or metabolize them. It can occur when uremic toxins described earlier cause mitochondria dysfunction with production of oxygen radicals.8 Oxidative stress can trigger kidney fibrosis and thereby mediate CKD progression.8 The high acid-producing contribution of diets, which are low in F&V, help mediate the systemic oxidative stress associated with these diets.8 Diets high in F&V might therefore promote kidney health by reducing systemic oxidative stress. Reducing Inflammation Inflammation contributes to CKD progression and is now an important clinical target in sustained kidney health. Many dietary plants, most notably F&V, reduce systemic inflammation by various mechanisms, including reduced acid production, and so, the low F&V content of most modern diets contributes to increased systemic inflammation.9 Adding F&V to modern diets reduced systemic inflammation and thereby can be kidney protective as the anti-inflammatory effects can slow CKD progression.8 Together, these data support that individual and population level diets high in F&V might promote kidney health by reducing systemic inflammation. Figure 1 graphically shows how reduced dietary F&V consumption can lead to the systemic changes described that can cause kidney injury and might contribute to progression of CKD, therapy increasing the population-level CKD burden.Figure 1: Graphic representation showing that reduced F&V consumption leads to systemic changes that lead to kidney injury. F&V, fruits and vegetables.Implementing Population-Wide Diets That Promote Kidney Health A typical framework for advancing the discovery of a potential health-improving innovation to its ultimate impact shows its efficacy, effectiveness, and then its implementation and dissemination. Efficacy studies determine the kidney benefits of a specific dietary change.4 Effectiveness studies typically involve larger populations and assess the magnitude of achievable improvement in kidney health at the population level. Regarding implementation, one might ask how the F&V will be provided, including whether it should be provided with instructions as to how to prepare the food in a healthy manner to enhance kidney and cardiovascular health.10 With dissemination, investigators and/or policy makers might ask what guidelines are necessary to ensure fidelity when the F&V intervention is scaled. Once these stages are completed, innovations with commercial potential are often adopted by industry and disseminated broadly. This framework, however, developed largely for drugs and devices, is unlikely to apply to diets high in F&V, which lack clear commercial incentives. Specifically, incentives for commercial food production are largely driven by consumption without focus on health, particularly kidney health. This insight along with the asymptomatic nature of the occurrence and progression of CKD in populations supports that the F&V innovation to support population-wide kidney health will likely require a societal approach executed through policy.