Dietary Phosphorus, Its Sources, and Mortality in Adults on Haemodialysis: The DIET-HD Study.

Dietary phosphorus restrictions are usually recommended for people on haemodialysis, although its impact on patient-relevant outcomes is uncertain. We aimed to evaluate the association between total phosphorus intake and its sources with mortality in haemodialysis. Phosphorus intake was ascertained within the DIET-HD study in 8110 adults on haemodialysis. Adjusted Cox regression analyses were conducted to evaluate the association between the total and source-specific phosphorus (plant-, animal-, or processed and other sources) with mortality. During a median 3.8 years of follow-up, there were 2953 deaths, 1160 cardiovascular-related. The median phosphorus intake was 1388 mg/day. Every standard deviation (SD) (896 mg/day) increase in total phosphorus was associated with higher all-cause mortality [hazard ratio (HR), 1.16; 95% confidence intervals (CI), 1.06-1.26] and cardiovascular mortality (HR, 1.18; 95% CI, 1.03-1.36). Every SD (17%) increase in the proportion of phosphorus from plant sources was associated with lower all-cause mortality (HR, 0.95; 95% CI, 0.90-0.99). Every SD (9%) increase in the proportion of phosphorus from the processed and other sources was associated with higher all-cause mortality (HR, 1.06; 95% CI, 1.02-1.10). A higher total phosphorus intake was associated with increased all-cause and cardiovascular death. This association is driven largely by the phosphorus intake from processed food. Plant based phosphorus was associated with lower all-cause mortality.

Effects of omega-3 polyunsaturated fatty acid intake in patients with chronic kidney disease: Systematic review and meta-analysis of randomized controlled trials.

BACKGROUND & AIMS: Dietary and supplemental long chain omega-3 polyunsaturated fatty acids (n-3 PUFA) have shown vascular benefits for the general population, but effects among people with chronic kidney disease (CKD) are largely uncertain. We aimed to evaluate the effects of n-3 PUFA intake among patients with CKD. METHODS: We searched MEDLINE, Embase, and CENTRAL through January 12, 2018. Eligible studies were randomized controlled trials evaluating n-3 PUFA intake (supplementation or dietary) compared with placebo, standard care, or other treatment, on cardiovascular and all-cause mortality, end stage kidney disease (ESKD), acute transplant rejection, and allograft loss. Risks of bias and evidence certainty were assessed using Cochrane and Grading of Recommendations Assessment, Development and Evaluation processes. RESULTS: Sixty trials (4129 participants) were eligible, all of supplementation, with a median follow-up of 6 months. Low to very low certainty evidence suggested that n-3 PUFA supplementation reduced cardiovascular death for participants on hemodialysis (39 events; relative risk (RR) 0.45, 95% confidence interval (CI) 0.23-0.89), prevented ESKD (29 events; RR 0.30, CI 0.09-0.98) in participants with CKD not receiving renal replacement therapy, and made little or no difference in all-cause mortality (215 events; RR 1.05, CI 0.84-1.33), acute transplant rejection (188 events; RR 0.98, CI 0.80-1.21) or allograft loss (39 events; RR 0.98, CI 0.54-1.81]). Risk of bleeding (44 events; RR 1.40, CI 0.78-2.49) and gastrointestinal side-effects (103 events; RR 1.14, CI 0.79-1.67) were uncertain. CONCLUSIONS: n-3 PUFA supplementation may reduce cardiovascular mortality in patients on hemodialysis but it is uncertain whether supplementation prevents mortality or ESKD in patients with CKD.

Dietary n-3 polyunsaturated fatty acid intake and all-cause and cardiovascular mortality in adults on hemodialysis: The DIET-HD multinational cohort study.

BACKGROUND & AIMS: Patients on hemodialysis suffer from high risk of premature death, which is largely attributed to cardiovascular disease, but interventions targeting traditional cardiovascular risk factors have made little or no difference. Long chain n-3 polyunsaturated fatty acids (n-3 PUFA) are putative candidates to reduce cardiovascular disease. Diets rich in n-3 PUFA are recommended in the general population, although their role in the hemodialysis setting is uncertain. We evaluated the association between the dietary intake of n-3 PUFA and mortality for hemodialysis patients. METHODS: The DIET-HD study is a prospective cohort study (January 2014-June 2017) in 9757 adults treated with hemodialysis in Europe and South America. Dietary n-3 PUFA intake was measured at baseline using the GA2LEN Food Frequency Questionnaire. Adjusted Cox regression analyses clustered by country were conducted to evaluate the association of dietary n-3 PUFA intake with cardiovascular and all-cause mortality. RESULTS: During a median follow up of 2.7 years (18,666 person-years), 2087 deaths were recorded, including 829 attributable to cardiovascular causes. One third of the study participants consumed sufficient (at least 1.75 g/week) n-3 PUFA recommended for primary cardiovascular prevention, and less than 10% recommended for secondary prevention (7-14 g/week). Compared to patients with the lowest tertile of dietary n-3 PUFA intake (<0.37 g/week), the adjusted hazard ratios (95% confidence interval) for cardiovascular mortality for patients in the middle (0.37 to <1.8 g/week) and highest (≥1.8 g/week) tertiles of n-3 PUFA were 0.82 (0.69-0.98) and 1.03 (0.84-1.26), respectively. Corresponding adjusted hazard ratios for all-cause mortality were 0.96 (0.86-1.08) and 1.00 (0.88-1.13), respectively. CONCLUSIONS: Dietary n-3 PUFA intake was not associated with cardiovascular or all-cause mortality in patients on hemodialysis. As dietary n-3 PUFA intake was low, the possibility that n-3 PUFA supplementation might mitigate cardiovascular risk has not been excluded.

Association Between High-Sensitivity Cardiac Troponin I and Cardiac Events in Elderly Women.

BACKGROUND: Elderly women are at high risk of coronary heart disease (CHD) and heart failure. High-sensitivity assays allow detection of cardiac troponin I (hsTnI) well below diagnostic cutoffs for acute coronary syndrome. We investigated the association between these levels with future cardiac events in community-based ambulant white women aged over 70 years initially recruited for a 5-year randomized, controlled trial of calcium supplements. METHODS AND RESULTS: This was a prospective study of 1081 elderly women without clinical CHD at baseline (1998) or hsTnI above the diagnostic cutoffs for acute coronary syndrome with 14.5-year follow-up hospitalization and mortality (events). Two hundred forty-three (22%) women had CHD events, 163 (15%) myocardial infarction or CHD death (hard CHD), and 109 (10%) heart failure. In 99.6% of available serum samples, hsTnI was above the level of detection (median, 4.5 ng/L; interquartile range, 3.6-5.8). After adjusting for Framingham risk factors, each SD natural log-transformed hsTnI increase was associated with an increased hazard for CHD (hazard ratio, 1.34; 95% CI, 1.18-1.53; P<0.001) hard CHD (hazard ratio, 1.51; 95% CI, 1.29-1.76; P<0.001), and heart failure (hazard ratio, 1.65; 95% CI, 1.36-1.99; P<0.001). Step-wise increases in relative hazards were observed with increasing quartiles of hsTnI (P for trend, <0.001), whereas the addition of hsTnI to conventional risk factors modestly improved discrimination indices: Harrell's c-statistic, net reclassification, and integrated discrimination (P<0.05). CONCLUSIONS: Cardiac troponin I is independently associated with future cardiac events in elderly women without apparent clinical manifestations. The addition of cardiac troponin I to conventional risk factors may modestly improve risk prediction in this setting.

Association of dietary nitrate with atherosclerotic vascular disease mortality: a prospective cohort study of older adult women.

Background: Nitrate-rich vegetables lower blood pressure and improve endothelial function in humans. It is not known, however, whether increased consumption of nitrate-rich vegetables translates to a lower risk of atherosclerotic vascular disease (ASVD) mortality.Objective: The objective was to investigate the association of nitrate intake from vegetables with ASVD mortality.Design: A total of 1226 Australian women aged 70-85 y without prevalent ASVD and/or diabetes were recruited in 1998 and were studied for 15 y. We assessed demographic and ASVD risk factors at baseline (1998), and we used a validated food-frequency questionnaire to evaluate dietary intake. Nitrate intake from vegetables was calculated by use of a newly developed comprehensive database. The primary outcome was any death attributed to ASVD ascertained by using linked data that were provided via the Western Australian Data Linkage system. We used Cox proportional hazards modeling to examine the association between nitrate intake and ASVD mortality before and after adjustment for lifestyle and cardiovascular disease risk factors.Results: During a follow-up period of 15,947 person-years, 238 of 1226 (19.4%) women died of ASVD-related causes. The mean ± SD vegetable nitrate intake was 67.0 ± 29.2 mg/d. Each SD higher vegetable nitrate intake was associated with a lower risk of ASVD mortality in both unadjusted [HR: 0.80 (95% CI: 0.70, 0.92), P = 0.002] and multivariable-adjusted [HR: 0.79 (95% CI: 0.68, 0.93), P = 0.004] analyses. This relation was attenuated after further adjustment for diet quality [HR: 0.85 (95% CI: 0.72, 1.01), P = 0.072]. Higher vegetable nitrate intake (per SD) also was associated with a lower risk of all-cause mortality [multivariable-adjusted HR: 0.87 (95% CI: 0.78, 0.97), P = 0.011].Conclusions: Nitrate intake from vegetables was inversely associated with ASVD mortality independent of lifestyle and cardiovascular disease risk factors in this population of older adult women without prevalent ASVD or diabetes. These results support the concept that nitrate-rich vegetables may reduce the risk of age-related ASVD mortality. This trial was registered at www.anzctr.org.au as ACTRN12617000640303.

Total volume and composition of fluid intake and mortality in older women: a cohort study.

OBJECTIVES: The health benefits of 'drinking at least 8 glasses of water a day" in healthy individuals are largely unproven. We aimed to examine the relationship between total fluid and the sources of fluid consumption, risk of rapid renal decline, cardiovascular disease (CVD) mortality and all-cause mortality in elderly women. DESIGN, SETTING AND PARTICIPANTS: We conducted a longitudinal analysis of a population-based cohort study of 1055 women aged ≥70 years residing in Australia. MAIN OUTCOME MEASURES: The associations between total daily fluid intake (defined as total volume of beverage excluding alcohol and milk) and the types of fluid (water, black tea, coffee, milk and other fluids) measured as cups per day and rapid renal decline, CVD and all-cause mortality were assessed using adjusted logistic and Cox regression analyses. RESULTS: Over a follow-up period of 10 years, 70 (6.6%) experienced rapid renal decline and 362 (34.4%) died, of which 142 (13.5%) deaths were attributed to CVD. The median (IQR) intake of total fluid was 10.4 (8.5-12.5) cups per day, with water (median (IQR) 4 (2-6) cups per day) and black tea (median (IQR) 3 (1-4) cups per day) being the most frequent type of fluid consumed. Every cup per day higher intake of black tea was associated with adjusted HRs of 0.90 (95% CI 0.81 to 0.99) and 0.92 (95% CI 0.86 to 0.98) for CVD mortality and all-cause mortality, respectively. There were no associations between black tea intake and rapid renal decline, or between the quantity or type of other fluids, including water intake, and any clinical outcomes. CONCLUSIONS: Habitual higher intake of black tea may potentially improve long-term health outcomes, independent of treating traditional CVD risk factors, but validation of our study findings is essential.

How is health economics relevant to transplant clinicians?

Decision making is complex and difficult in clinical practice. Clinicians are often faced with a large range of possible alternative decision options, each with their own consequences and trade-offs. Health economics methods enable informed decision making on how best to allocate limited resources that could lead to most health gains. Economic evaluation in particular is highly relevant in transplantation medicine. Transplantation is an expensive intervention, but it improves the quality of life and survival of people with chronic diseases. The balance between health care resource use and the optimal health gains is useful not only to decision-makers, but also to consumers, clinicians, and researchers. This article is an overview of the concepts of economic evaluation in the setting of transplantation and highlights the applicability of these concepts in clinical transplantation.

Quality of life of young adults and adolescents with chronic kidney disease.

OBJECTIVE: To elicit utility-based quality of life (QOL) in adolescents and young adults with chronic kidney disease (CKD). STUDY DESIGN: A cross-sectional study was conducted among patients aged 12-25 years with CKD stage 3-5 and 5D from 6 centers in Australia. QOL was measured using a visual analogue scale, and 3 utility-based QOL measures: Health Utilities Index Mark 2 and 3 (HUI2/3), Kidney Disease Quality of Life, incorporating the short form (SF)-12 transformed to SF-6D, and time trade-off (TTO). Multiple linear regression was used to define predictors for TTO QOL weights, SF-6D, and visual analogue scale scores. RESULTS: On a utility scale, with extremes of 0 (death) to 1 (full health), the 27 participants had a mean TTO QOL weight of 0.59 (SD = 0.40), HUI2 of 0.73 (SD = 0.28), HUI3 of 0.74 (SD = 0.26), and SF-6D of 0.70 (SD = 0.14). QOL weights were consistently low across the 4 utility-based instruments with widest variability in TTO responses. Mean QOL weights were higher among predialysis participants. The HUI2 indicated variability in the domain of emotion. From the Kidney Disease Quality of Life measures, decrements were observed in all QOL domains though dialysis patients reported a significantly higher burden attributed to kidney disease. CONCLUSIONS: Adolescent and young adults with CKD report low QOL values. Their utility-based QOL scores imply they are willing to trade considerable life expectancy for perfect health. Holistic care to improve QOL and minimize disease burden are imperative for optimizing health outcomes in young people with CKD, particularly those on dialysis.

The perspectives of adults living with peritoneal dialysis: thematic synthesis of qualitative studies.

BACKGROUND: Most patients with end-stage renal disease require dialysis to survive because they are unable to access kidney transplantation. Peritoneal dialysis (PD) is recommended by some clinical practice guidelines as the dialysis treatment of choice for adults without significant comorbid conditions or those with residual kidney function. This study aims to synthesize published qualitative studies of patients' experiences, beliefs, and attitudes about PD. METHODS: We conducted a systematic review and thematic synthesis of qualitative studies of adult perspectives of living with PD. Databases (MEDLINE, Embase, PsycINFO, and CINAHL), theses, and reference lists were searched to November 2011. RESULTS: 39 studies involving 387 participants were included. We identified 7 themes: resilience and confidence (determination and overcoming vicissitudes), support structures (strong family relationship, peer support, professional dedication, social abandonment, and desire for holistic care), overwhelming responsibility (disruptive intrusion, family burden, and onerous treatment regimen), control (gaining bodily awareness, achieving independence and self-efficacy, and information seeking), freedom (flexibility and autonomy, retaining social functioning, and ability to travel), sick identity (damage to self-esteem and invisible suffering), and disablement (physical incapacitation and social loss and devaluation). CONCLUSIONS: PD can offer patients a sense of control, independence, self-efficacy, and freedom. However, holistic and multidisciplinary care is needed to mitigate the risks of impaired self-esteem, physical incapacitation, reduced social functioning, and poor sense of self-worth. Strategies that aim to strengthen social support and promote resilience and confidence in patients are integral to achieving positive adjustment, improved psychosocial outcomes, and treatment satisfaction.

An economic evaluation of intravenous versus oral iron supplementation in people on haemodialysis.

BACKGROUND: Iron supplementation can be administered either intravenously or orally in patients with chronic kidney disease (CKD) and iron deficiency anaemia, but practice varies widely. The aim of this study was to estimate the health care costs and benefits of parenteral iron compared with oral iron in haemodialysis patients receiving erythropoiesis-stimulating agents (ESAs). METHODS: Using broad health care funder perspective, a probabilistic Markov model was constructed to compare the cost-effectiveness and cost-utility of parenteral iron therapy versus oral iron for the management of haemodialysis patients with relative iron deficiency. A series of one-way, multi-way and probabilistic sensitivity analyses were conducted to assess the robustness of the model structure and the extent in which the model's assumptions were sensitive to the uncertainties within the input variables. RESULTS: Compared with oral iron, the incremental cost-effectiveness ratios (ICERs) for parenteral iron were $74,760 per life year saved and $34,660 per quality-adjusted life year (QALY) gained. A series of one-way sensitivity analyses show that the ICER is most sensitive to the probability of achieving haemoglobin (Hb) targets using supplemental iron with a consequential decrease in the standard ESA doses and the relative increased risk in all-cause mortality associated with low Hb levels (Hb < 9.0 g/dL). If the willingness-to-pay threshold was set at $50,000/QALY, the proportions of simulations that showed parenteral iron was cost-effective compared with oral iron were over 90%. CONCLUSIONS: Assuming that there is an overall increased mortality risk associated with very low Hb level (<9.0 g/dL), using parenteral iron to achieve an Hb target between 9.5 and 12 g/L is cost-effective compared with oral iron therapy among haemodialysis patients with relative iron deficiency.

Adolescent views on transition in diabetes and nephrology.

UNLABELLED: Managing the transition of adolescents from paediatric to adult care is complex and remains an important challenge. This aim of this study was to synthesize studies on perspective on transition to adult care among young people with diabetes or chronic kidney disease. We conducted a systematic review of surveys and qualitative studies that explored adolescent perspectives on transition to adult care in diabetes and chronic kidney disease. Searches were conducted to week 4, June 2010. For quantitative questionnaires, all items were mapped into a domain schema. Thematic synthesis of the qualitative findings was performed. Fourteen studies involving 854 respondents were included. The majority of participants felt somewhat prepared but had reservations about transfer. Five major themes were identified: (1) preparedness (timing of transfer, access to providers, parental involvement), (2) overwhelmed by an impersonal environment in adult service (sterile and unwelcoming, navigating new processes, feeling displaced), (3) independence (developing self-esteem and an adult identity, taking responsibility and ownership), (4) valuing familiarity (building trust, peer support) and (5) service and information needs (leniency, lack of access, efficiency, information needs). CONCLUSION: Holistic and adolescent focussed transition programs are needed which address adolescent needs by providing adequate access to health services, encouraging independence and ownership of health management, promoting trust in providers, giving comprehensive information about what to expect and how to navigate adult services and facilitating interaction with younger patients.