The Dietary Inflammatory Index

The pathophysiologic process involved in the progression of CKD is characterized by low-grade chronic inflammation.1 Diet may be a key factor in regulating this chronic inflammation and could potentially influence kidney function. Anti-inflammatory nutrients, including n−3 polyunsaturated fatty acids, fiber, and vitamins, have been associated with a slower decline in kidney function, whereas proinflammatory nutrients, such as saturated fatty acids and sugar, have been linked to worsening kidney function. Indeed, previous studies have reported that a Western-style diet, which consists mainly of calorie-dense foods high in saturated fats, refined grains, processed foods, red meat, and sodium, is associated with an increased risk of microalbuminuria and accelerated kidney function decline.2 On the contrary, healthy dietary patterns (e.g., Dietary Approaches to Stop Hypertension, Mediterranean, and plant-based diets) that emphasize a high intake of whole grains, fruits, vegetables, nuts, lean protein, and polyunsaturated fatty acids are associated with lower risk of CKD progression.3,4 The Dietary Inflammatory Index (DII) was designed to assess the inflammatory properties of a diet based on the proinflammatory and anti-inflammatory potential of its various components.5 The DII has been widely used to investigate the role of diet-induced inflammation in chronic diseases, such as CKD. Mazidi et al. were the first to provide evidence that those with a higher DII score were more likely to have lower kidney function in the National Health and Nutrition Examination Survey participants (N=21,649; mean age 55 years).6 Compared with the lowest quartile of DII, the highest quartile was associated with 29% higher odds (95% confidence interval, 1.03 to 1.62; P trend < 0.001) of experiencing an eGFR of <60 ml/min per 1.73 m2. In this issue of Kidney360, Johns et al. present observational data from 17,334 postmenopausal women obtained from the Women's Health Initiative, a large-scale, long-term study that aimed to examine the effects of various interventions on the health of postmenopausal women from the early 1990s to 2005, with extended follow-up until the present.7 The authors included women without CKD (defined by eGFR ≥60 ml/min per 1.73 m2 at baseline) and evaluated whether the DII score was associated with incident kidney failure (based on the International Classification of Diseases [ICD]-9 or ICD-10 codes for stage 5 CKD, ESKD, or kidney transplant). The median follow-up time was 11.2 years, and there were 1852 events of kidney failure. Women in the top quartile of the DII score had an 18% higher risk (95% confidence interval, 1.03 to 1.37) of incident kidney failure compared with those in the lowest quartile in the fully adjusted model. Similar findings, but with a reduced hazard ratio, were observed in the sensitivity analyses, either when restricting outcomes to ICD-9/10 codes for ESKD or considering death as a competing risk. The authors deserve recognition for undertaking the largest prospective cohort analysis to date examining the association of diet-induced inflammation using the DII score with the risk of incident kidney failure, with a long follow-up period. Importantly, their focus on postmenopausal women, who are a population at high-risk for adverse kidney outcomes, yet understudied, adds significant value to the field. However, there are also limitations, some of which the authors highlight in their discussion. Incident kidney failure was defined by ICD codes, which are less robust than adjudicated end points because of limited sensitivity. In the Women's Health Initiative dataset, individuals with available creatinine measurements included a disproportionately large number of racial and ethnic minorities, a group already at high CKD risk, which limits the applicability of the findings to other racial and ethnic backgrounds. The findings are also not generalizable to premenopausal women and men. The underlying mechanisms through which diet influences CKD progression are not fully understood, but diet-induced chronic inflammation may be a potential contributing factor. Figure 1 presents a schematic of the potential mechanisms by which diet may be associated with CKD progression. A Western-style diet that is calorie-dense and high in saturated fats and sugars can lead to postprandial hyperlipidemia and hyperglycemia, resulting in postprandial inflammation (i.e., an acute inflammatory response after consuming a meal). Although this acute inflammatory response is a normal physiologic defense mechanism, a prolonged and recurring response from abnormal postprandial metabolic fluctuation may lead to persistent, low-grade, systemic inflammation.8 In addition, an accumulative high-sugar diet induces a hyperglycemic state that promotes the formation of advanced glycosylation end-products. These advanced glycosylation end-products activate inflammatory pathways and can lead to insulin resistance, exacerbating inflammation. Moreover, excessive intake of dietary sodium can alter the structure and function of small renal arteries through abnormal leukocyte-endothelial cell interactions, proinflammatory cytokine secretion, and vascular endothelial dysfunction, further inducing systemic inflammation.9 Finally, given that gut dysbiosis has been increasingly recognized as a potential contributor to CKD progression and that diet is the primary driver of gut microbiota composition,10 the effect of the gut on diet-induced inflammation and its role in the progression of CKD warrants further attention.Figure 1: Potential mechanism by which diet may be associated with the progression of CKD. Designed with resources from flaticon.com. AGEs, advanced glycosylation end-products; DASH, Dietary Approaches to Stop Hypertension; PUFAs, polyunsaturated fatty acids.Chronic low-grade inflammation is now recognized as a hallmark of CKD and substantially contributes to the development of CKD.1 Kidneys are especially susceptible to inflammation as they receive 25% of the entire blood volume but lack anti-inflammatory defenses present in other highly vascularized organs. Chronic low-grade inflammation induces numerous intrarenal microvascular changes that contribute to renal damage. Circulating proinflammatory cytokines activate intrarenal microvessels, particularly endothelial cells and leukocytes, further amplifying inflammation and oxidative stress within the kidney. These processes alter cell-surface adhesion molecules, deteriorate the glycocalyx layer, impair endothelial barrier function, activate the coagulation system, and disrupt vasoreactivity. Moreover, the renal tubules harbor numerous inflammatory cytokines and fibrosis mediators that respond to renal injury, but dysregulation of these mediators accelerates CKD progression. The proximal tubule also requires substantial energy, making it vulnerable to ischemia with chronic low-grade inflammation. Taken together, a proinflammatory diet (or Western-style diet) can trigger the inflammatory factors that promote a persistent low-grade inflammatory state in the body, leading to accelerated renal damage and eventually the progression of CKD. The authors proposed focusing on healthy dietary patterns for improving kidney health. Understanding whether this finding extends to premenopausal women and men, as well as to a population composed entirely of patients with CKD, will be crucial to determine the generalizability of the results. In addition, it will be important to ascertain whether the DII score correlates with circulating inflammatory markers and if these markers mediate the association between diet and CKD progression. Future research, including well-conduced randomized controlled trials, will be necessary to determine whether an anti-inflammatory diet (or healthy dietary patterns) can indeed protect against CKD progression. It should be noted, however, that diet modification interventions are often challenging for the participants to maintain. Evaluating outcomes such as kidney function changes or CKD progression in clinical trials can also be challenging due to the lengthy duration needed for progression. Furthermore, investigating how these dietary patterns interact with other factors, such as gut microbiome, genetics, or comorbidities, could provide a more comprehensive understanding of their effects on CKD progression. In conclusion, although promoting healthy dietary patterns may offer a promising strategy for kidney health, further research is needed to establish causality, assess generalizability, and elucidate underlying mechanisms. Overcoming the challenges of dietary adherence and long-term outcome evaluation will be essential for advancing evidence-based dietary interventions in nephrology.