What is the value of multidisciplinary care for chronic kidney disease?

In a Persepctive, Richard Fluck and Maarten Taal discuss the potential value of implementing multidisciplinary care programs for chronic kidney disease

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 paper 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 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

Chronic kidney disease in primary care: outcomes after five years in a prospective cohort study

Background Chronic kidney disease (CKD) is commonly managed in primary care, but most guidelines have a secondary care perspective emphasizing the risk of end-stage kidney disease (ESKD) and need for renal replacement therapy. In this prospective cohort study, we sought to study in detail the natural history of CKD in primary care to better inform the appropriate emphasis for future guidance. Methods and Findings In this study, 1,741 people with CKD stage 3 were individually recruited from 32 primary care practices in Derbyshire, United Kingdom. Study visits were undertaken at baseline, year 1, and year 5. Binomial logistic regression and Cox proportional hazards models were used to model progression, CKD remission, and all-cause mortality. We used Kidney Disease: Improving Global Outcomes (KDIGO) criteria to define CKD progression and defined CKD remission as the absence of diagnostic criteria (estimated glomerular filtration rate [eGFR] >60 ml/min/1.73 m2 and urine albumin-to-creatinine ratio [uACR] <3 mg/mmol) at any study visit. Participants were predominantly elderly (mean ± standard deviation (SD) age 72.9 ± 9.0 y), with relatively mild reduction in GFR (mean ± SD eGFR 53.5 ± 11.8 mL/min/1,73 m2) and a low prevalence of albuminuria (16.9%). After 5 y, 247 participants (14.2%) had died, most of cardiovascular causes. Only 4 (0.2%) developed ESKD, but 308 (17.7%) evidenced CKD progression by KDIGO criteria. Stable CKD was observed in 593 participants (34.1%), and 336 (19.3%) met the criteria for remission. Remission at baseline and year 1 was associated with a high likelihood of remission at year 5 (odds ratio [OR] = 23.6, 95% CI 16.5–33.9 relative to participants with no remission at baseline and year 1 study visits). Multivariable analyses confirmed eGFR and albuminuria as key risk factors for predicting adverse as well as positive outcomes. Limitations of this study include reliance on GFR estimated using the Modification of Diet in Renal Disease study (MDRD) equation for recruitment (but not subsequent analysis) and a study population that was predominantly elderly and white, implying that the results may not be directly applicable to younger populations of more diverse ethnicity. Conclusions Management of CKD in primary care should focus principally on identifying the minority of people at high risk of adverse outcomes, to allow intervention to slow CKD progression and reduce cardiovascular events. Efforts should also be made to identify and reassure the majority who are at low risk of progression to ESKD. Consideration should be given to adopting an age-calibrated definition of CKD to avoid labelling a large group of people with age-related decline in GFR and low associated risk as having CKD

Associations of fibroblast growth factor 23, vitamin D and parathyroid hormone with 5-year outcomes in a prospective primary care cohort of people with chronic kidney disease stage 3

Objectives Vitamin D deficiency, elevated fibroblast growth factor 23 (FGF23) and elevated parathyroid hormone (PTH) have each been associated with increased mortality in people with chronic kidney disease (CKD). Previous studies have focused on the effects of FGF23 in relatively advanced CKD. This study aims to assess whether FGF23 is similarly a risk factor in people with early CKD, and how this risk compares to that associated with vitamin D deficiency or elevated PTH. Design Prospective cohort study. Setting Thirty-two primary care practices. Participants One thousand six hundred and sixty-four people who met Kidney Disease: Improving Global Outcomes (KDIGO) definitions for CKD stage 3 (two measurements of estimated glomerular filtration rate (eGFR) between 30 and 60 mL/min/1.73 m2 at least 90 days apart) prior to study recruitment. Outcome measures All-cause mortality over the period of study follow-up and progression of CKD defined as a 25% fall in eGFR and a drop in GFR category, or an increase in albuminuria category. Results Two hundred and eighty-nine participants died during the follow-up period. Vitamin D deficiency (HR 1.62, 95% CI 1.01 to 2.58) and elevated PTH (HR 1.42, 95% CI 1.09 to 1.84) were independently associated with all-cause mortality. FGF23 was associated with all-cause mortality in univariable but not multivariable analysis. Fully adjusted multivariable models of CKD progression showed no association with FGF23, vitamin D status or PTH. Conclusions In this cohort of predominantly older people with CKD stage 3 and low risk of progression, vitamin D deficiency and elevated PTH were independent risk factors for all-cause mortality but elevated FGF23 was not. While FGF23 may have a role as a risk marker in high-risk populations managed in secondary care, our data suggest that it may not be as important in CKD stage 3, managed in primary care

What is acceptance, and how could it affect health outcomes for people receiving renal dialysis?

Renal dialysis is a life-saving treatment for end-stage renal disease (ESRD) but is burdensome, invasive and expensive. Patients’ experiences of dialysis and the outcomes of their treatment could potentially be improved by focusing on ‘acceptance’. However, the concept of acceptance has been used in different ways. This article examines ways that acceptance has been conceptualised in research on chronic illness generally and ESRD specifically, and makes proposals for research to understand better what acceptance means for people with ESRD. The aim is to assist the development of acceptance-related measures and interventions to support people with ESRD.N/

Sodium-glucose linked transporter-2 inhibitor renal outcome modification in type 2 diabetes : Evidence from studies in patients with high or low renal risk

Abstract Data from three completed cardiovascular outcome trials (CVOTs), EMPA-REG OUTCOME, CANVAS Program and DECLARE-TIMI 58, add to the evidence supporting the potential renoprotective effects of sodium-glucose linked transporter-2 (SGLT2) inhibitors in patients with type-2 diabetes (T2D). Despite recommendations in recent guidelines, it is difficult to support a view that definitive evidence for renoprotection exists from these SGLT2 inhibitor CVOT results. To date, the only dedicated trial to report definitive data on the renal impact of SGLT2 inhibition is CREDENCE. Notably, the total number of patient relevant renal endpoint events (dialysis, transplant or renal death) observed in CREDENCE was significantly higher than the total for all three CVOTs collectively (183 events/4,401 patients vs. 69 events/34,322 patients, respectively), which demonstrates the increased statistical power of CREDENCE for these renal endpoints. Treatment with canagliflozin was associated with a 30% relative risk reduction (RRR) in the primary composite endpoint of end-stage kidney disease, doubling of serum creatinine, or death from renal or cardiovascular causes and a 34% RRR for the renal-specific elements of this primary endpoint (PPeer reviewe

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

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