Micronutrients and Renal Outcomes: A Prospective Cohort Study

Background: Micronutrients are essential in maintaining normal human physiology. Data regarding the association between micronutrients and renal outcomes in chronic kidney disease (CKD) are lacking. Methods: This prospective observational cohort study enrolled 261 patients with CKD stages 1–5 and 30 subjects with normal renal function. Baseline serum zinc (Zn), selenium (Se), chromium, manganese, and copper, and laboratory tests were performed at enrolment. The primary endpoint was the presence of end-stage renal disease (ESRD) requiring long-term renal replacement therapy. Results: The median follow-up periods of renal and non-renal survivals were 67.78 and 29.03 months, respectively. Multiple linear regression showed that Zn and Se (β ± SE: 24.298 ± 8.616, p = 0.005; 60.316 ± 21.875, p = 0.006, respectively) levels were positively correlated with renal function. Time to ESRD was significantly longer for those with Zn levels ≥1287.24 ng/g and Se levels ≥189.28 ng/g (both p < 0.001). Cox regression analysis identified a higher Zn level as an independently negative predictor of ESRD after adjusting for renal function (hazard ratio, 0.450, p = 0.019). Conclusion: Serum Se and Zn concentrations are positively associated with renal function and better renal outcomes. A higher Zn concentration could independently predict better renal survival.     

The KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD): A Korean Chronic Kidney Disease Cohort

The KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) was launched in 2011 with the support of the Korea Disease Control and Prevention Agency. The study was designed with the aim of exploring the various clinical features and characteristics of chronic kidney disease (CKD) in Koreans, and elucidating the risk factors for CKD progression and adverse outcomes of CKD. For the cohort study, nephrologists at 9 tertiary university-affiliated hospitals participated in patient recruitment and follow-up. Biostatisticians and epidemiologists also participated in the basic design and structuring of the study. From 2011 until 2016, the KNOW-CKD Phase I recruited 2238 adult patients with CKD from stages G1 to G5, who were not receiving renal replacement therapy. The KNOW-CKD Phase II recruitment was started in 2019, with an enrollment target of 1500 subjects, focused on diabetic nephropathy and hypertensive kidney diseases in patients with reduced kidney function who are presumed to be at a higher risk of adverse outcomes. As of 2021, the KNOW-CKD investigators have published articles in the fields of socioeconomics, quality of life, nutrition, physical activity, renal progression, cardiovascular disease and outcomes, anemia, mineral bone disease, serum and urine biomarkers, and international and inter-ethnic comparisons. The KNOW-CKD researchers will elaborate a prediction model for various outcomes of CKD such as the development of end-stage kidney disease, major adverse cardiovascular events, and death.     

Neighborhood Food Outlet Access and Dietary Intake among Adults with Chronic Kidney Disease: Results from the Chronic Renal Insufficiency Cohort Study

BackgroundHealthy diet is essential in the management of chronic kidney disease (CKD) and preventing related comorbidities. Food outlet access has been studied in the general population; however, the influence of the local food environment on dietary intake among people with CKD has not been evaluated.ObjectivesThis study examined the associations of food outlet density and type of outlets with dietary intake in a multicenter cohort of racially and ethnically diverse patients with CKD.MethodsThe Chronic Renal Insufficiency Cohort Study is a multicenter prospective study of patients with CKD that used a validated food frequency questionnaire to capture dietary intake at the baseline visit. This is a cross-sectional analysis of 2,484 participants recruited in 2003-2006 from seven Chronic Renal Insufficiency Cohort Study centers. Food outlet data were used to construct a count of the number of fast-food restaurants, convenience stores, and grocery stores per 10,000 population for each geocoded census block group. Multivariable linear and logistic regression models were used to evaluate the associations between measures of food outlet availability and dietary factors.ResultsThe proportion of participants living in zero–, low–, and high–food outlet density areas differed by gender, race or ethnicity, and income level. Among male subjects, living in areas with zero or the highest number of outlets was associated with having the highest caloric intakes in multivariable models. Male subjects living in areas with zero outlets consumed the highest levels of sodium and phosphorous. Female subjects living in areas with zero outlets had the lowest average intake of calories, sodium, and phosphorous. Among low-income female subjects, close proximity to more outlets was associated with higher calorie consumption. Among all participants, access to fast-food restaurants was not associated with an unhealthy diet score, and access to grocery stores was not associated with a healthy diet score.ConclusionsAverage caloric and nutrient intakes differed by outlet availability; however, there were no strong associations with type of food outlet. This should be considered when developing food-focused public health policies.     

Dietary Lipids and Dyslipidemia in Chronic Kidney Disease

The progression of chronic kidney disease (CKD) leads to altered lipid metabolism. CKD patients exhibit high blood triglyceride (TG) levels, reduced concentrations and functionality of high-density lipoproteins (HDL), and elevated levels of atherogenic small, dense, low-density lipoproteins (sdLDL). Disorders of lipid metabolism and other metabolic disturbances place CKD patients at high risk for cardiovascular disease (CVD). Extensive evidence supports the cardioprotective effects of unsaturated fatty acids, including their beneficial effect on serum cholesterol and TG levels. Dietary lipids might therefore be especially important in the nutritional management of CKD. We review current dietary recommendations for fat intake by CKD patients and suggest potential nutritional interventions by emphasizing dietary lipids that might improve the blood lipid profile and reduce cardiovascular risk in CKD.     

Nutritional Predictors of Mortality after 10 Years of Follow-Up in Patients with Chronic Kidney Disease at a Multidisciplinary Unit of Advanced Chronic Kidney Disease

Nutritional monitoring in advanced chronic kidney disease (ACKD) units provides personalized care and improves clinical outcomes. This study aimed to identify mortality risk factors in chronic kidney disease (CKD) patients on nutritional follow-up in the multidisciplinary ACKD unit. A retrospective cross-sectional observational study was conducted in 307 CKD patients’ stage 3b, 4–5 followed-up for 10 years. Clinical and nutritional monitoring was performed by malnutrition-inflammation score (MIS), biochemical parameters (s-albumin, s-prealbumin, and serum C-reactive protein (s-CRP), body composition measured by bioelectrical impedance analysis (BIA), anthropometry, and handgrip strength measurements. The sample was classified into non-survivors, survivors, and censored groups. Of the 307 CKD patients, the prevalence of protein-energy wasting (PEW) was 27.0% using MIS > 5 points, s-CRP > 1 mg/dL was 19.20%, and 27.18% died. Survivors had higher significant body cell mass (BCM%) and phase angle (PA). Survival analyses significantly showed that age > 72 years, MIS > 5 points, s-prealbumin ≤ 30 mg/dL, PA ≤ 4°, and gender-adjusted handgrip strength (HGS) were associated with an increased risk of mortality. By univariate and multivariate Cox regression, time on follow-up (HR:0.97), s-prealbumin (HR:0.94), and right handgrip strength (HR:0.96) were independent predictors of mortality risk at 10 years of follow-up in the ACKD unit. Nutritional monitoring in patients with stage 3b, 4–5 CKD helps to identify and treat nutritional risk early and improve adverse mortality prognosis.     

Dietary Phosphorus as a Marker of Mineral Metabolism and Progression of Diabetic Kidney Disease

Phosphorus is an essential nutrient that is critically important in the control of cell and tissue function and body homeostasis. Phosphorus excess may result in severe adverse medical consequences. The most apparent is an impact on cardiovascular (CV) disease, mainly through the ability of phosphate to change the phenotype of vascular smooth muscle cells and its contribution to pathologic vascular, valvular and other soft tissue calcification. Chronic kidney disease (CKD) is the most prevalent chronic disease manifesting with the persistent derangement of phosphate homeostasis. Diabetes and resulting diabetic kidney disease (DKD) remain the leading causes of CKD and end-stage kidney disease (ESRD) worldwide. Mineral and bone disorders of CKD (CKD-MBD), profound derangement of mineral metabolism, develop in the course of the disease and adversely impact on bone health and the CV system. In this review we aimed to discuss the data concerning CKD-MBD in patients with diabetes and to analyze the possible link between hyperphosphatemia, certain biomarkers of CKD-MBD and high dietary phosphate intake on prognosis in patients with diabetes and DKD. We also attempted to clarify if hyperphosphatemia and high phosphorus intake may impact the onset and progression of DKD. Careful analysis of the available literature brings us to the conclusion that, as for today, no clear recommendations based on the firm clinical data can be provided in terms of phosphorus intake aiming to prevent the incidence or progression of diabetic kidney disease.     

Association between Vitamin Intake and Chronic Kidney Disease According to a Variant Located Upstream of the PTGS1 Gene: A Cross-Sectional Analysis of Shika Study

Chronic kidney disease (CKD) patients have been advised to take vitamins; however, the effects have been controversial. The individual differences in developing CKD might involve genetic variants of inflammation, including variant rs883484 located upstream of the prostaglandin-endoperoxide synthase 1 (PTGS1) gene. We aimed to identify whether the 12 dietary vitamin intake interacts with genotypes of the rs883484 on developing CKD. The population-based, cross-sectional study had 684 Japanese participants (≥40 years old). The study used a validated, brief, self-administered diet history questionnaire to estimate the intake of the dietary vitamins. CKD was defined as estimated glomerular filtration < 60 mL/min/1.73 m². The study participants had an average age of 62.1 ± 10.8 years with 15.4% minor homozygotes of rs883484, and 114 subjects had CKD. In the fully adjusted model, the higher intake of vitamins, namely niacin (odds ratio (OR) = 0.74, 95% confidence interval (CI): 0.57–0.96, p = 0.024), α-tocopherol (OR = 0.49, 95% CI: 0.26–0.95, p = 0.034), and vitamin C (OR = 0.97, 95% CI: 0.95–1.00, p = 0.037), was independently associated with lower CKD tendency in the minor homozygotes of rs883484. The results suggested the importance of dietary vitamin intake in the prevention of CKD in middle-aged to older-aged Japanese with minor homozygous of rs883484 gene variant.     

Chronic Kidney Disease

Chronic kidney disease (CKD) is highly prevalent and has major health consequences for patients. Caring for patients with CKD requires knowledge of the food supply, renal pathophysiology, and nutrition‐related medications used to work synergistically with diet to control the signs and symptoms of the disease. The nutrition care process and International Dietetic and Nutrition Terminology allow for systematic, holistic, quality care of patients with this complex, progressive disease. Nutrition interventions must be designed with the individual patients needs in mind while prioritizing factors with the largest negative impact on health outcomes and mortality risk. New areas of nutrition treatment are emerging that involve a greater focus on micronutrient needs, the microbiome, and vegetarian‐style diets. These interventions may improve outcomes by decreasing inflammation, improving energy and protein delivery, and lowering phosphorus, electrolytes, and fluid retention.     

Role and Treatment of Insulin Resistance in Patients with Chronic Kidney Disease: A Review

Patients with chronic kidney disease (CKD) and dialysis have higher mortality than those without, and cardiovascular disease (CVD) is the main cause of death. As CVD is caused by several mechanisms, insulin resistance plays an important role in CVD. This review summarizes the importance and mechanism of insulin resistance in CKD and discusses the current evidence regarding insulin resistance in patients with CKD and dialysis. Insulin resistance has been reported to influence endothelial dysfunction, plaque formation, hypertension, and dyslipidemia. A recent study also reported an association between insulin resistance and cognitive dysfunction, non-alcoholic fatty liver disease, polycystic ovary syndrome, and malignancy. Insulin resistance increases as renal function decrease in patients with CKD and dialysis. Several mechanisms increase insulin resistance in patients with CKD, such as chronic inflammation, oxidative stress, obesity, and mineral bone disorder. There is the possibility that insulin resistance is the potential future target of treatment in patients with CKD.     

Sex Difference in the Associations among Hyperuricemia with New-Onset Chronic Kidney Disease in a Large Taiwanese Population Follow-Up Study

The global prevalence and incidence of chronic kidney disease (CKD) continue to increase. Whether hyperuricemia is an independent risk factor for renal progression and whether there are sex differences in the relationships between serum uric acid (UA) and a decline in renal function are unclear. Therefore, in this longitudinal study, we aimed to explore these relationships in a large cohort of around 27,000 Taiwanese participants in the Taiwan Biobank (TWB), and also to identify serum UA cutoff levels in men and women to predict new-onset CKD. A total of 26,942 participants with a median 4 years of complete follow-up data were enrolled from the TWB. We excluded those with CKD (estimated glomerular filtration rate <60 mL/min/1.73 m²) at baseline (n = 297), and the remaining 26,645 participants (males: 9356; females: 17,289) were analyzed. The participants who developed CKD during follow-up were defined as having incident new-onset CKD, and those with a serum UA level >7 mg/dL in males and >6 mg/dL in females were classified as having hyperuricemia. After multivariable analysis, hyperuricemia (odds ratio [OR], 2.541; 95% confidence interval [CI], 1.970–3.276; p < 0.001) was significantly associated with new-onset CKD. Furthermore, in the male participants (n = 9356), hyperuricemia (OR, 1.989; 95% CI, 1.440–2.747; p < 0.001), and quartile 4 of UA (vs. quartile 1; OR, 2.279; 95% CI, 1.464–3.547; p < 0.001) were significantly associated with new-onset CKD, while in the female participants (n = 17,289), hyperuricemia (OR, 3.813; 95% CI, 2.500–5.815; p < 0.001), quartile 3 of UA (vs. quartile 1; OR, 3.741; 95% CI, 1.250–11.915; p = 0.018), and quartile 4 of UA (vs. quartile 1; OR, 12.114; 95% CI, 14.278–34.305; p < 0.001) were significantly associated with new-onset CKD. There were significant interactions between hyperuricemia and sex (p = 0.024), and quartiles of serum UA and sex (p = 0.010) on new-onset CKD. Hyperuricemia was associated with new-onset CKD in the enrolled participants, and the interactions between hyperuricemia and sex were statistically significant. Hyperuricemia was more strongly associated with new-onset CKD in the women than in the men.     

Association between Dietary Fat Intake and Hyperuricemia in Men with Chronic Kidney Disease

Despite a close relationship between chronic kidney disease (CKD) and uric acid level, few studies have examined the relationship between uric acid level and fat intake by kidney function status. Therefore, we investigated the association between dietary fat intake and hyperuricemia with and without decreased kidney function in males living in Shika Town, Ishikawa Prefecture, Japan. This study included 361 males with a mean age of 60.7 years. Dietary fat and fatty acid intakes were evaluated using the brief-type self-administered diet history questionnaire. Reduced kidney function was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m², while hyperuricemia was defined as a serum uric acid level >7.0 mg/dL. A two-way analysis of covariance showed that saturated fatty acid (p = 0.026), monounsaturated fatty acid (p = 0.014), and polyunsaturated fatty acid (p = 0.022) were significantly lower in the high uric acid group than in the normal uric acid group. In multiple logistic analysis stratified by renal function, lipid intake was negatively associated with hyperuricemia in the low eGFR group. These findings suggest that higher dietary lipid/fatty acid intake may be effective in the prevention and treatment of hyperuricemia in men with CKD.     

Association between Daily Urinary Sodium Excretion,Ratio of Extracellular Water-to-Total Body Water Ratio,and Kidney Outcome in Patients with Chronic Kidney Disease

Whether dietary salt intake affects chronic kidney disease (CKD) progression remains unclear. We conducted a retrospective cohort study to analyze the effects of both daily salt intake (DSI) and volume status on renal outcomes in 197 CKD patients. DSI was estimated by 24-h urinary sodium excretion and volume status was assessed by the ratio of extracellular water (ECW) to total body water (TBW) measured by bioelectrical impedance analysis (BIA). We divided patients into two groups according to DSI (6 g/day) or median ECW/TBW (0.475) and compared renal outcomes of each group. Furthermore, we classified and analyzed four groups according to both DSI and ECW/TBW. The higher DSI group showed a 1.69-fold (95% confidence interval (CI) 1.12–2.57, p = 0.01) excess risk of outcome occurrence compared to the lower group. Among the four groups, compared with Group 1 (low DSI and low ECW/TBW), Group 3 (high DSI and low ECW/TBW) showed a 1.84-fold (95% CI 1.03–3.30, p = 0.04) excess risk of outcome occurrence; however, Group 2 (low DSI and high ECW/TBW) showed no significant difference. High salt intake appears to be associated with poor renal outcome independent of blood pressure (BP), proteinuria, and volume status.     

Dietary Phosphorus to Protein Ratio for the Mexican Population with Chronic Kidney Disease

Objective: Hyperphosphatemia is a major contributor to poor outcomes among cases of chronic kidney disease. Considering that foods with high protein content are major sources of phosphorus, a more suitable dietary phosphorus measure is the phosphorus to protein ratio. However, Mexican phosphorus to protein ratio tables do not exist. This article aims to estimate the phosphorus to protein ratio in foods commonly used by the Mexican population and to establish its usefulness in the selection of foods for patients with chronic kidney disease.

Methods: Six tables with the phosphorus to protein ratio were developed from different data sources concerning Mexican animal food composition.

Results: Egg whites have the best phosphorus to protein ratio. Partially skimmed milk has the lowest ratio among dairy products. Dairy products have high phosphorus to protein ratio variability. Red meat products have a ratio with an average of 9?mg/g. The phosphorus to protein ratio varies considerably for seafood (1.2–38.3?mg/g).

Conclusions: The phosphorus to protein ratio could be a good strategy to choose each food during chronic kidney disease dietary treatment for the Mexican population.     

Association of Nutrition Education and Its Interaction with Lifestyle Factors on Kidney Function Parameters and Cardiovascular Risk Factors among Chronic Kidney Disease Patients in Taiwan

We evaluated the interactive effects of nutrition education (NE) and lifestyle factors on kidney function parameters and cardiovascular risk factors among chronic kidney disease (CKD) patients. This cross-sectional cohort study recruited 2176 CKD stages 3–5 patients aged > 20 years from Integrated Chronic Kidney Disease Care Network, Shuang Ho Hospital, Taiwan between December 2008 and April 2019. The multivariable regression analysis was performed to investigate the interactive effects of NE with lifestyle factors on kidney function parameters and cardiovascular risk factors. Relative excess risk due to interaction (RERI) and attributable proportion (AP) were applied to assess additive interaction. Patients who were smoking or physically inactive but received NE had better estimated glomerular filtration rate (eGFR) (β: 3.83, 95% CI: 1.17–6.49 or β: 3.67, 95% CI: 2.04–5.29) compared to those without NE. Patients with smoking and NE significantly reduced risks for having high glycated hemoglobin A_1c (HbA_1c) by 47%, high low-density lipoprotein cholesterol (LDL-C) by 38%, and high corrected calcium (C-Ca) by 50% compared to those without NE. Moreover, NE and smoking or inactive physical activity exhibited an excess risk of high C-Ca (RERI: 0.47, 95% CI: 0.09–0.85 for smoking or RERI: 0.46, 95% CI: 0.01–0.90 and AP: 0.51, 95% CI: 0.03–0.99 for physical activity). Our study suggests that CKD patients who were enrolled in the NE program had better kidney function. Thus, NE could be associated with slowing kidney function decline and improving cardiovascular risk factors.     

Genetically Predicted Circulating Copper and Risk of Chronic Kidney Disease: A Mendelian Randomization Study

Elevated circulating copper levels have been associated with chronic kidney disease (CKD), kidney damage, and decline in kidney function. Using a two sample Mendelian randomization approach where copper-associated genetic variants were used as instrumental variables, genetically predicted higher circulating copper levels were associated with higher CKD prevalence (odds ratio 1.17; 95% confidence interval 1.04, 1.32; p-value = 0.009). There was suggestive evidence that genetically predicted higher copper was associated with a lower estimated glomerular filtration rate and a more rapid kidney damage decline. In conclusion, we observed that elevated circulating copper levels may be a causal risk factor for CKD.     

Dietary Advanced Glycation End Products and Risk Factors for Chronic Disease: A Systematic Review of Randomised Controlled Trials

Dietary advanced glycation end-products (AGEs) form during heating and processing of food products and are widely prevalent in the modern Western diet. Recent systematic reviews indicate that consumption of dietary AGEs may promote inflammation, oxidative stress and insulin resistance. Experimental evidence indicates that dietary AGEs may also induce renal damage, however, this outcome has not been considered in previous systematic reviews. The purpose of this review was to examine the effect of consumption of a high AGE diet on biomarkers of chronic disease, including chronic kidney disease (CKD), in human randomized controlled trials (RCTs). Six databases (SCOPUS, CINHAL, EMBASE, Medline, Biological abstracts and Web of Science) were searched for randomised controlled dietary trials that compared high AGE intake to low AGE intake in adults with and without obesity, diabetes or CKD. Twelve dietary AGE interventions were identified with a total of 293 participants. A high AGE diet increased circulating tumour necrosis factor-alpha and AGEs in all populations. A high AGE diet increased 8-isoprostanes in healthy adults, and vascular cell adhesion molecule-1 (VCAM-1) in patients with diabetes. Markers of CKD were not widely assessed. The evidence presented indicates that a high AGE diet may contribute to risk factors associated with chronic disease, such as inflammation and oxidative stress, however, due to a lack of high quality randomised trials, more research is required.