The effects of probiotics and symbiotics on risk factors for hepatic encephalopathy

Alterations in the levels of intestinal microbiota, endotoxemia, and inflammation are novel areas of interest in the pathogenesis of hepatic encephalopathy (HE). Probiotics and symbiotics are a promising treatment option for HE due to possible beneficial effects in modulating gut microflora and might be better tolerated and more cost-effective than the traditional treatment with lactulose, rifaximin or L-ornithine-L-aspartate. A systematic search of the electronic databases PubMed, ISI Web of Science, EMBASE, and Cochrane Library was conducted for randomized controlled clinical trials in adult patients with cirrhosis, evaluating the effect of probiotics and symbiotics in changes on intestinal microflora, reduction of endotoxemia, inflammation, and ammonia, reversal of minimal hepatic encephalopathy (MHE), prevention of overt hepatic encephalopathy (OHE), and improvement of quality of life. Nineteen trials met the inclusion criteria. Probiotics and symbiotics increased beneficial microflora and decreased pathogenic bacteria and endotoxemia compared with placebo/no treatment, but no effect was observed on inflammation. Probiotics significantly reversed MHE [risk ratio, 1.53; 95% confidence interval (CI): 1.14, 2.05; P=0.005] and reduced OHE development (risk ratio, 0.62; 95% CI: 0.48, 0.80; P=0.0002) compared with placebo/no treatment. Symbiotics significantly decreased ammonia levels compared with placebo (15.24; 95% CI: −26.01, −4.47; P=0.006). Probiotics did not show any additional benefit on reversal of MHE and prevention of OHE development when compared with lactulose, rifaximin, and L-ornithine-L-aspartate. Only 5 trials considered tolerance with minimal side effects reported. Although further research is warranted, probiotics and symbiotics should be considered as an alternative therapy for the treatment and management of HE given the results reported in this systematic review

The association of nutritional factors and skin autofluorescence in persons receiving hemodialysis

Objective: Advanced glycation end-products (AGEs) are uremic toxins that result from hyperglycemia, oxidative stress and systemic inflammation. AGEs are also formed in food during cooking. On the other hand, malnutrition may contribute to AGE formation through its association with oxidative stress and inflammation. AGE accumulation can be measured by skin autofluorescence (SAF) and elevated SAF is independently associated with higher mortality on hemodialysis (HD). We aimed to investigate associations between SAF, dietary AGE intake and markers of malnutrition in persons receiving HD.Design and setting: single center cross-sectional study.Subjects: 120 participants on HD dialyzing at least three times per week for 3-4 hours.Main outcome measures: SAF was measured using an Autofluorescence Reader. Dietary AGE, energy, protein and fat intake, handgrip strength (HGS), anthropometric measurements and biochemistry were also assessed. Subjective Global Assessment was performed to evaluate nutritional status.Results: SAF was higher in malnourished participants and correlated negatively with serum albumin and cholesterol, HGS and energy, protein and fat intake and positively with C reactive protein and chronological age; SAF did not correlate with dietary AGE intake. Multivariable linear regression analysis showed that diabetes, smoking, serum albumin, HGS, protein intake and dialysis vintage were independent predictors of increased SAF.Conclusions: Markers of malnutrition were more important determinants of increased SAF than high dietary AGE intake in this HD population. Nutritional interventions aiming to reduce SAF by correcting malnutrition should therefore be investigated. The observed association between higher SAF and malnutrition may in part explain the previously reported association between higher SAF and mortality on HD

Factors associated with change in skin autofluorescence in persons receiving dialysis

IntroductionAn increase over time in skin autofluorescence (SAF), a measure of accumulation of advanced glycation end products (AGE), predicts higher mortality on hemodialysis (HD). However, evidence is lacking regarding factors that contribute to changes in SAF over time in populations on dialysis. We investigated the rate of change in SAF over 1 year and the factors associated with these changes.MethodsWe enrolled 109 patients on HD and 28 on peritoneal dialysis in a prospective study. SAF was measured at baseline, 3, 6, 9, and 12 months. Rate of change in SAF was calculated using the SLOPE function in Microsoft Excel (Microsoft, Redmond, WA). Participants were then grouped into those with stable SAF or increasing SAF. Dietary AGE intake and nutritional assessments were performed at baseline, 6, and 12 months.ResultsThe mean SAF trend observed was an increase of 0.30 ± 0.63 arbitrary units (AU) per year, but this varied from a decrease of 0.15 ± 0.44 to an increase of 0.76 ± 0.42 AU per year in stable and increasing SAF groups, respectively. Increasing SAF was more common in participants who developed malnutrition during the observation period, whereas those who became well-nourished were more likely to have stable SAF (8 [80%] vs. 14 [42%]; P = 0.02). Development/prevalence of malnutrition over 1 year, HD as first dialysis modality, and current smoking were independent predictors of increasing SAF.ConclusionSAF increases over time in most persons on dialysis. Independent determinants of increasing SAF were development/prevalence of malnutrition, HD as first dialysis modality, and current smoking. Strategies to reduce/prevent the rise in SAF, including prevention/correction of malnutrition, should be investigated in prospective studies

Prospective study of change in skin autofluorescence over time and mortality in people receiving hemodialysis

Introduction: Elevated skin autofluorescence (SAF), a measure of tissue accumulation of advanced glycation end products (AGEs), is a strong predictor of all-cause and cardiovascular mortality in the hemodialysis population. However, prospective studies investigating the association between changes in SAF over time and mortality are scarce. We therefore aimed to investigate the prognostic value of SAF trend for predicting mortality in a hemodialysis population. Methods: We enrolled 120 patients on hemodialysis in a 5-year observational, prospective study. SAF was measured at baseline, 3, 6, 9, 12, and 24 months. Rate of change in SAF (i.e., SAF trend) was calculated using linear regression. Time to event was the number of days from baseline to death, kidney transplantation, or March 31, 2022. Results: Mean age, mean baseline SAF, and median SAF trend were 65 ± 14 years, 3.4 ± 0.9 arbitrary units (AU), and an increase of 0.1 (−0.1 to 0.4) AU/yr, respectively. Median observation time was 42 months, during which 59 participants (49%) died. Univariable analysis identified age, history of smoking, lower serum albumin, higher baseline SAF, and increase in SAF as significant predictors of higher mortality. In multivariable analysis, higher baseline SAF (hazard ratio: 1.45; 95% confidence interval: 1.08–1.94; P = 0.01) and increasing SAF trend (2.37 [1.43–3.93]; P < 0.001) were independent predictors of increased mortality. Conclusion: An increasing SAF trend and higher baseline SAF were independent predictors of all-cause mortality in this hemodialysis population, suggesting that monitoring of SAF may have clinical utility. Strategies to improve outcomes by reducing or preventing the increase in SAF should now be investigated in prospective studies

Skin autofluorescence and malnutrition as predictors of mortality in persons receiving dialysis: a prospective cohort study

BackgroundSkin autofluorescence (SAF), which is a measure of accumulation of advanced glycation end‐products (AGE), and malnutrition are each associated with higher mortality in dialysis populations, although no studies have investigated these potentially related associations together. We simultaneously assessed SAF and malnutrition as risk factors for mortality in persons receiving dialysis.MethodsSAF was measured in 120 haemodialysis and 31 peritoneal dialysis patients using an AGE Reader (DiagnOptics, Groningen, The Netherlands). Dietary AGE, energy, protein and fat intake, handgrip strength, anthropometry, biochemistry and Subjective Global Assessment were also evaluated. Time to event was days from baseline to death, kidney transplantation or 30 September 2018.ResultsMedian observation time was 576 days, during which 33 (21.9%) patients died. Those who died had higher baseline SAF levels [3.8 ± 1.0 versus 3.3 ± 0.8 arbitrary units (AU); P = 0.001] and were more likely to be malnourished (58% versus 31%; P = 0.006). Malnourished persons who died had higher SAF values than those who died but were well‐nourished (4.2 ± 1.1 versus 3.3 ± 0.7 AU; P = 0.007). Survival was significantly better in participants with baseline SAF below the median and in those well‐nourished than those with baseline SAF above the median and in those malnourished, respectively. Multivariable analysis identified SAF [hazards ratio (HR) = 1.44; 95% confidence interval (CI) = 1.05–1.97; P = 0.02], malnutrition (HR = 2.35; 95% CI = 1.16–4.78; P = 0.02) and chronological age (HR = 1.60; 95% CI = 1.10–2.33; P = 0.01) as independent predictors of mortality.ConclusionsAlthough higher SAF and malnutrition are potentially inter‐related, they were both independently associated with increased mortality in this population. Interventions to improve outcomes by reducing SAF through correction of malnutrition or dietary AGE restriction require testing in prospective studies

The association of nutritional factors and skin autofluorescence in persons receiving hemodialysis

Objective: Advanced glycation end-products (AGEs) are uremic toxins that result from hyperglycemia, oxidative stress and systemic inflammation. AGEs are also formed in food during cooking. On the other hand, malnutrition may contribute to AGE formation through its association with oxidative stress and inflammation. AGE accumulation can be measured by skin autofluorescence (SAF) and elevated SAF is independently associated with higher mortality on hemodialysis (HD). We aimed to investigate associations between SAF, dietary AGE intake and markers of malnutrition in persons receiving HD. Design and setting: single center cross-sectional study. Subjects: 120 participants on HD dialyzing at least three times per week for 3-4 hours. Main outcome measures: SAF was measured using an Autofluorescence Reader. Dietary AGE, energy, protein and fat intake, handgrip strength (HGS), anthropometric measurements and biochemistry were also assessed. Subjective Global Assessment was performed to evaluate nutritional status. Results: SAF was higher in malnourished participants and correlated negatively with serum albumin and cholesterol, HGS and energy, protein and fat intake and positively with C reactive protein and chronological age; SAF did not correlate with dietary AGE intake. Multivariable linear regression analysis showed that diabetes, smoking, serum albumin, HGS, protein intake and dialysis vintage were independent predictors of increased SAF. Conclusions: Markers of malnutrition were more important determinants of increased SAF than high dietary AGE intake in this HD population. Nutritional interventions aiming to reduce SAF by correcting malnutrition should therefore be investigated. The observed association between higher SAF and malnutrition may in part explain the previously reported association between higher SAF and mortality on HD

Impact of malnutrition on health-related quality of life in persons receiving dialysis: a prospective study

Health-related quality of life (HRQoL) is severely impaired in persons receiving dialysis. Malnutrition has been associated with some measures of poor HRQoL in cross-sectional analyses in dialysis populations, but no studies have assessed the impact of malnutrition and dietary intake on change in multiple measures of HRQoL over time. We investigated the most important determinants of poor HRQoL and the predictors of change in HRQoL over time using several measures of HRQoL. We enrolled 119 haemodialysis and 31 peritoneal dialysis patients in this prospective study. Nutritional assessments (Subjective Global Assessment [SGA], anthropometry and 24-hour dietary recalls) and HRQoL questionnaires (Short Form-36 [SF-36] mental [MCS] and physical component scores [PCS] and European QoL-5 Dimensions [EQ5D] health state [HSS] and visual analogue scores [VAS]) were performed at baseline, 6 and 12 months. Mean age was 64(14) years. Malnutrition was present in 37% of the population. At baseline, malnutrition assessed by SGA was the only factor independently (and negatively) associated with all four measures of HRQoL. No single factor was independently associated with decrease in all measures of HRQoL over 1 year. However, prevalence/development of malnutrition over one year was an independent predictor of 1-year decrease in EQ5D HSS and 1-year decrease in fat intake independently predicted the 1-year decline in SF-36 MCS and PCS, and EQ5D VAS. These findings strengthen the importance of monitoring for malnutrition and providing nutritional advice to all persons on dialysis. Future studies are needed to evaluate the impact of nutritional interventions on HRQoL and other long-term outcomes

Impact of Dietetic Intervention on Skin Autofluorescence and Nutritional Status in Persons Receiving Dialysis: A Proof of Principle Study

Objective: Advanced glycation end-products (AGEs) are uremic toxins that result from oxidative stress and food consumption. We have previously reported that markers of malnutrition are more important determinants of increased skin autofluorescence (SAF), a measure of AGE accumulation and risk factor for mortality, than high dietary AGE intake in a hemodialysis (HD) population, suggesting that correcting malnutrition may decrease SAF. Design and methods: We investigated this hypothesis in a single center, non-randomized proof of principle study. We enrolled 27 HD and one peritoneal dialysis (PD) patient with malnutrition who received individualized nutritional advice and support over 6 months. SAF was measured at baseline, 3 and 6 months. Dietary intake and nutritional status were assessed at baseline and 6 months. Results were compared with a control group of malnourished dialysis patients (n= 41 HD and 8 PD) from a previous observational study

A comprehensive description of kidney disease progression after Acute Kidney Injury: results of a prospective, parallel group cohort study

Acute kidney injury (AKI) is associated with adverse long-term outcomes, but many studies are retrospective, focussed on specific patient groups or lack adequate comparators. The ARID (AKI Risk in Derby) Study is a 5-year prospective parallel-group cohort study. Hospitalised cohorts with and without exposure to AKI were matched 1:1 for age, baseline renal function and diabetes. Estimated glomerular filtration rate (eGFR) and urinary albumin:creatinine ratio (uACR) were measured at 3-months, 1, 3 and 5-years. Outcomes included kidney disease progression, heart failure episodes and mortality.In 866 matched individuals, kidney disease progression at 5-years occurred in 94 (30%) of the exposed group versus 24 (7%) of those non-exposed (adjusted odds ratio (OR) 2.49 [95%CI 1.43 to 4.36]; P=0.001). In the AKI group, this was largely characterised by incomplete recovery of kidney function by 3-months. Further episodes of AKI during follow-up were more common in the exposed group (OR 2.71 [95% CI 1.94 to 3.77]; P<0.001) and had an additive effect on risk of kidney disease progression. Mortality and heart failure episodes were more frequent in the exposed group, but the association with AKI was no longer significant when models were adjusted for 3-month eGFR and uACR. In a general hospitalised population, kidney disease progression after 5-years was common and strongly associated with AKI. The time-course of changes and the attenuation of associations with adverse outcomes after adjustment for 3-month eGFR and uACR suggest that non-recovery of kidney function is an important assessment in post-AKI care and a potential future target for intervention. Study registration: ISRCTN2540599

The association of nutritional factors and skin autofluorescence in persons receiving hemodialysis

Objective: Advanced glycation end-products (AGEs) are uremic toxins that result from hyperglycemia, oxidative stress and systemic inflammation. AGEs are also formed in food during cooking. On the other hand, malnutrition may contribute to AGE formation through its association with oxidative stress and inflammation. AGE accumulation can be measured by skin autofluorescence (SAF) and elevated SAF is independently associated with higher mortality on hemodialysis (HD). We aimed to investigate associations between SAF, dietary AGE intake and markers of malnutrition in persons receiving HD. Design and setting: single center cross-sectional study. Subjects: 120 participants on HD dialyzing at least three times per week for 3-4 hours. Main outcome measures: SAF was measured using an Autofluorescence Reader. Dietary AGE, energy, protein and fat intake, handgrip strength (HGS), anthropometric measurements and biochemistry were also assessed. Subjective Global Assessment was performed to evaluate nutritional status. Results: SAF was higher in malnourished participants and correlated negatively with serum albumin and cholesterol, HGS and energy, protein and fat intake and positively with C reactive protein and chronological age; SAF did not correlate with dietary AGE intake. Multivariable linear regression analysis showed that diabetes, smoking, serum albumin, HGS, protein intake and dialysis vintage were independent predictors of increased SAF. Conclusions: Markers of malnutrition were more important determinants of increased SAF than high dietary AGE intake in this HD population. Nutritional interventions aiming to reduce SAF by correcting malnutrition should therefore be investigated. The observed association between higher SAF and malnutrition may in part explain the previously reported association between higher SAF and mortality on HD