A comprehensive description of kidney disease progression after acute kidney injury from a prospective, parallel-group cohort study.

Acute kidney injury (AKI) is associated with adverse long-term outcomes, but many studies are retrospective, focused on specific patient groups or lack adequate comparators. The ARID (AKI Risk in Derby) Study was a five-year prospective parallel-group cohort study to examine this. Hospitalized cohorts with and without exposure to AKI were matched 1:1 for age, baseline kidney function, and diabetes. Estimated glomerular filtration rate (eGFR) and the urinary albumin:creatinine ratio (uACR) were measured at three-months, one-, three- and five-years. Outcomes included kidney disease progression, heart failure episodes and mortality. In 866 matched individuals, kidney disease progression at five years was found to be significantly increased in 30% of the exposed group versus 7% of those non-exposed (adjusted odds ratio 2.49 [95% confidence interval 1.43 to 4.36]). In the AKI group, this was largely characterized by incomplete recovery of kidney function by three months. Further episodes of AKI during follow-up were significantly more common in the exposed group (odds ratio 2.71 [1.94 to 3.77]) 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 three-month eGFR and uACR. In a general hospitalized population, kidney disease progression after five years was common and strongly associated with AKI. Thus, the time course of changes and the attenuation of associations with adverse outcomes after adjustment for three-month eGFR and uACR suggest non-recovery of kidney function is an important assessment in post-AKI care and a potential future target for intervention. STUDY REGISTRATION: ISRCTN25405995.

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 thirty-one peritoneal dialysis patients in this prospective study. Nutritional assessments (Subjective Global Assessment (SGA), anthropometry and 24-h 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 1 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.

Nutritional status assessment: a neglected biomarker in persons with end-stage kidney disease.

PURPOSE OF REVIEW: Malnutrition is a frequent complication and risk factor for adverse outcomes in the dialysis population that is often underrecognized and neglected. This article reviews published literature on the associations between malnutrition, mortality, quality of life and hospitalizations in persons on dialysis in order to raise awareness of the importance of preventing and treating it. RECENT FINDINGS: All methods of nutritional assessment namely serum biochemistry, body composition, dietary intake, handgrip strength and nutritional scoring tools are independently associated with increased mortality in dialysis populations. Malnutrition severely affects physical and mental measures of quality of life and increases the number and length of hospitalizations in persons receiving dialysis, resulting in increased healthcare costs. Worsening of nutritional status is also associated with poor survival and higher rates of hospitalizations in this patient population. SUMMARY: Malnutrition is an unacceptably common complication in dialysis patients that is substantially associated with adverse outcomes and higher hospital costs. Further interventional studies assessing the impact of preventing and treating malnutrition on clinical outcomes are warranted and should be considered a priority.

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

BACKGROUND: Skin 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. METHODS: SAF 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. RESULTS: Median 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. CONCLUSIONS: Although 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.

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. It has been 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, nonrandomized proof-of-principle study. We enrolled 27 patients on HD and one on peritoneal dialysis with malnutrition who received individualized nutritional advice and support over 6 months. SAF was measured at baseline, 3 months, and 6 months. Dietary intake and nutritional status were assessed at baseline and 6 months. Results were compared with a control group of malnourished patients on dialysis (n = 41 HD and 8 peritoneal dialysis) from a previous observational study. RESULTS: The intervention group showed a significant increase in dietary intake, including AGEs, Subjective Global Assessment score, and serum albumin, while SAF levels remained stable for over 6 months (3.8 ± 0.7 arbitrary units [AU] vs. 3.7 ± 0.7 AU; P = .3). Conversely, in the control group, SAF increased significantly during the observation period (3.5 ± 0.9 AU vs. 3.8 ± 1.2 AU; P = .03) during which there was no improvement in nutritional intake and other markers of nutrition, although dietary AGE intake and Subjective Global Assessment score did increase. CONCLUSION: Dietetic support was associated with stable SAF levels in this proof-of-principal study despite an increase in dietary AGE intake, suggesting that interventions to improve nutrition may be important in preventing the rise in SAF observed in malnourished dialysis populations. Further long-term studies are needed to test this hypothesis and evaluate the impact on survival.

Skin autofluorescence: an emerging biomarker in persons with kidney disease.

PURPOSE OF REVIEW: Skin autofluorescence (SAF) is a measure of the accumulation of advanced glycation end-products (AGEs) proposed to act as a marker of 'cumulative metabolic stress'. This article discusses mechanisms of AGE formation and reviews published literature on SAF as a biomarker and risk factor across the spectrum of kidney disease. RECENT FINDINGS: SAF is elevated in adults and children on dialysis. Higher SAF is an independent risk factor for cardiovascular and all-cause mortality in persons receiving haemodialysis and for all-cause mortality in persons performing peritoneal dialysis, though the increase in discrimination when SAF was added to traditional risk factors was modest. In less advanced chronic kidney disease, higher SAF predicts all-cause mortality and progression. SAF is elevated in renal transplant recipients, but to a lesser extent than in dialysis patients. In one study, higher SAF predicted graft loss and mortality. SAF has been reported to be increased in patients with acute kidney injury. SUMMARY: A growing body of evidence attests that SAF, a marker of AGE accumulation, is a risk factor for mortality and kidney function decline in multiple types of kidney disease. Further studies are warranted to evaluate interventions to reduce SAF and the impact on clinical outcomes.

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 METHODS: This was a single center cross-sectional study that included 120 participants on HD dialyzing at least 3 times per week for 3-4 hours. SAF was measured using an Autofluorescence Reader. Dietary AGE, energy, protein and fat intake, handgrip strength (HGS), anthropometric measurements and biochemistry were also assessed. The Subjective Global Assessment was performed to evaluate the 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.

The Effects of Probiotics and Symbiotics on Risk Factors for Hepatic Encephalopathy: A Systematic Review.

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.

Effect of a symbiotic gel (Lactobacillus acidophilus + Bifidobacterium lactis + inulin) on presence and severity of gastrointestinal symptoms in hemodialysis patients.

OBJECTIVE: The study aimed to assess the effect of a symbiotic gel on presence and severity of gastrointestinal symptoms (GIS) in hemodialysis patients. DESIGN: A double-blinded, placebo-controlled, randomized, clinical trial was designed. The study was conducted at 2 public hospitals in Guadalajara, Mexico. SUBJECTS AND INTERVENTION: Twenty-two patients were randomized to the intervention group (nutritional counseling + symbiotic gel) and 20 patients were randomized to the control group (nutritional counseling + placebo), during 2 months of follow-up. MAIN OUTCOME MEASURE: Presence and monthly episodes of GIS were assessed by direct interview and severity by using the self-administered GIS questionnaire. Additionally, biochemical parameters, inflammatory markers, and nutritional status (dietary intake, subjective global assessment, anthropometry, and body composition) were evaluated. RESULTS: After a 2-month treatment, intervention group had a significant reduction in prevalence and monthly episodes of vomit, heartburn, and stomachache, as well as a significant decrease in GIS severity compared with control group. Moreover, intervention group had a greater yet not significant decrease in the prevalence of malnutrition and a trend to reduce their C-reactive protein and tumor necrosis factor α levels compared with control group. No symbiotic-related adverse side effects were shown in these patients. Clinical studies with longer follow-up and sample size are needed to confirm these results. CONCLUSIONS: We concluded that administration of a symbiotic gel is a safe and simple way to improve common GIS in dialysis patients.

Effects of a symbiotic on gut microbiota in Mexican patients with end-stage renal disease.

OBJECTIVES: Gut microbiota provides beneficial effects under physiological conditions, but is able to contribute to inflammatory diseases in susceptible individuals. Thus, we designed this study to test whether additional intake of symbiotic gel affects specific modifications of gut microbiota in patients with end-stage renal disease (ESRD). METHODS: Eighteen patients with ESRD diagnosis with renal replacement therapy (hemodialysis) were included in this study. They were randomly assigned to 2 treatment groups: (1) test group (nutritional counseling + symbiotic) and (2) control group (nutritional counseling + placebo). Clinical history and the evaluation of Gastrointestinal Symptom Rating Scale were performed. Gut microbiota composition was analyzed by real-time polymerase chain reaction from fecal samples. All subjects were followed for 2 months. RESULTS: Bifidobacterial counts were higher in the second samples (mean: 5.5 ± 1.72 log10 cells/g) than in first samples (4.2 ± 0.88 log 10 cells/g) in the patients of the test group (P = .0344). Also, lactobacilli counts had a little decrease in the test group (2.3 ± 0.75 to 2.0 ± 0.88 log 10 cells/g) and the control group (2.2 ± 0.90 to 1.8 ± 1.33 log 10 cells/g), between the first and the second samples. Gastrointestinal symptoms scores (scale 8-40) were reduced in the test group (start 12 [10-14] and end 9 [8-10]) compared with control group (start 11 [8-21] and end 11 [9-15]). CONCLUSIONS: Short-term symbiotic treatment in patients with ESRD can lead to the increase of Bifidobacterium counts, maintaining the intestinal microbial balance.

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.

Factors Associated With Change in Skin Autofluorescence, a Measure of Advanced Glycation End Products, in Persons Receiving Dialysis.

INTRODUCTION: An 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. METHODS: We 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. RESULTS: The 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. CONCLUSION: SAF 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.