Nutrition and dietary intake and their association with mortality and hospitalization in adults with chronic kidney disease treated with hemodialysis

Adults receiving hemodialysis still experience high mortality rates. Several interventions that address the typical cardiovascular risk factors which are almost universally present in people with ESKD have been introduced. These interventions unfortunately do not significantly improve health outcomes in such populations. Nutrition and dietary patterns are potential factors influencing health in other health settings but poorly explored in the setting of ESKD. The aim of this body of work was to evaluate the association between exposure to different nutrients and dietary patterns and the risk of mortality (all-cause and cause-specific) and hospital admissions (any, and cause-specific) in adults with chronic kidney disease and specifically those with or end stage kidney disease receiving hemodialysis for renal replacement therapy. This project focused on understanding the impact of diet and nutrient intake, on CKD and ESKD through a comprehensive and systematic series of literature reviews and the design and conduct of the first large scale multinational primary cohort study to explore the association between nutrition (dietary intake) and clinical adverse events in the setting of hemodialysis

Dietary patterns for adults with chronic kidney disease

This is the protocol for a review and there is no abstract. The objectives are as follows: This review will evaluate the benefits and harms of dietary patterns among adults with CKD (any stage including people with end-stage kidney disease (ESKD) treated with dialysis, transplantation or supportive care)

the validity of drug effects on proteinuria albuminuria serum creatinine and estimated gfr as surrogate end points for eskd a systematic review

Rationale & Objective Proteinuria, albuminuria, and serum creatinine level are widely used as surrogate end point measures of end-stage kidney disease (ESKD). We evaluated the correlation between antihypertensive drug effects on surrogate renal end points and ESKD. Study Design Systematic review. Setting & Participants Randomized controlled trials of blood pressure–lowering therapy. Selection Criteria for Studies Trials of pharmacological blood pressure–lowering strategies reporting drug effects on albuminuria, proteinuria, or serum creatinine level and ESKD through March 26, 2018. Analytical Approach Bayesian bivariate meta-analysis to calculate correlations between drug effects on surrogate end points and drug effects on ESKD. Risks of bias were adjudicated using the Cochrane tool. Results 22 randomized controlled trials involving 69,642 participants were eligible. Risks of bias in the included trials were frequently unclear due to incomplete reporting. Relative risk for ESKD was statistically significant in 1 of 29 (3.4%) treatment comparisons. There appeared to be little or no correlation between antihypertensive drug effects on serum creatinine level, albuminuria, proteinuria, and the corresponding effects on ESKD. All correlations had wide 95% credible intervals that included the null effect. Limitations Low power due to infrequent outcomes of ESKD and incomplete data reporting in primary trials. Conclusions The association between antihypertensive drug effects on doubling of serum creatinine level and albuminuria or proteinuria with ESKD in treatment trials is not sufficiently certain to enable the confident use of these markers to guide clinical or regulatory decision making

Dietary interventions for adults with chronic kidney disease

Background: Dietary changes are routinely recommended in people with chronic kidney disease (CKD) on the basis of randomised evidence in the general population and non-randomised studies in CKD that suggest certain healthy eating patterns may prevent cardiovascular events and lower mortality. People who have kidney disease have prioritised dietary modifications as an important treatment uncertainty. Objectives: This review evaluated the benefits and harms of dietary interventions among adults with CKD including people with end-stage kidney disease (ESKD) treated with dialysis or kidney transplantation. Search methods: We searched the Cochrane Kidney and Transplant Specialised Register (up to 31 January 2017) through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Selection criteria: Randomised controlled trials (RCTs) or quasi-randomised RCTs of dietary interventions versus other dietary interventions, lifestyle advice, or standard care assessing mortality, cardiovascular events, health-related quality of life, and biochemical, anthropomorphic, and nutritional outcomes among people with CKD. Data collection and analysis: Two authors independently screened studies for inclusion and extracted data. Results were summarised as risk ratios (RR) for dichotomous outcomes or mean differences (MD) or standardised MD (SMD) for continuous outcomes, with 95% confidence intervals (CI) or in descriptive format when meta-analysis was not possible. Confidence in the evidence was assessed using GRADE. Main results: We included 17 studies involving 1639 people with CKD. Three studies enrolled 341 people treated with dialysis, four studies enrolled 168 kidney transplant recipients, and 10 studies enrolled 1130 people with CKD stages 1 to 5. Eleven studies (900 people) evaluated dietary counselling with or without lifestyle advice and six evaluated dietary patterns (739 people), including one study (191 people) of a carbohydrate-restricted low-iron, polyphenol enriched diet, two studies (181 people) of increased fruit and vegetable intake, two studies (355 people) of a Mediterranean diet and one study (12 people) of a high protein/low carbohydrate diet. Risks of bias in the included studies were generally high or unclear, lowering confidence in the results. Participants were followed up for a median of 12 months (range 1 to 46.8 months). Studies were not designed to examine all-cause mortality or cardiovascular events. In very-low quality evidence, dietary interventions had uncertain effects on all-cause mortality or ESKD. In absolute terms, dietary interventions may prevent one person in every 3000 treated for one year avoiding ESKD, although the certainty in this effect was very low. Across all 17 studies, outcome data for cardiovascular events were sparse. Dietary interventions in low quality evidence were associated with a higher health-related quality of life (2 studies, 119 people: MD in SF-36 score 11.46, 95% CI 7.73 to 15.18; I = 0%). Adverse events were generally not reported. Dietary interventions lowered systolic blood pressure (3 studies, 167 people: MD -9.26 mm Hg, 95% CI -13.48 to -5.04; I = 80%) and diastolic blood pressure (2 studies, 95 people: MD -8.95, 95% CI -10.69 to -7.21; I = 0%) compared to a control diet. Dietary interventions were associated with a higher estimated glomerular filtration rate (eGFR) (5 studies, 219 people: SMD 1.08; 95% CI 0.26 to 1.97; I = 88%) and serum albumin levels (6 studies, 541 people: MD 0.16 g/dL, 95% CI 0.07 to 0.24; I = 26%). A Mediterranean diet lowered serum LDL cholesterol levels (1 study, 40 people: MD -1.00 mmol/L, 95% CI -1.56 to -0.44). Authors' conclusions: Dietary interventions have uncertain effects on mortality, cardiovascular events and ESKD among people with CKD as these outcomes were rarely measured or reported. Dietary interventions may increase health-related quality of life, eGFR, and serum albumin, and lower blood pressure and serum cholesterol levels. Based on stakeholder prioritisation of dietary research in the setting of CKD and preliminary evidence of beneficial effects on risks factors for clinical outcomes, large-scale pragmatic RCTs to test the effects of dietary interventions on patient outcomes are required

Association of Drug Effects on Serum Parathyroid Hormone, Phosphorus, and Calcium Levels With Mortality in CKD: A Meta-analysis

Background Serum parathyroid hormone (PTH), phosphorus, and calcium levels are surrogate outcomes that are central to the evaluation of drug treatments in chronic kidney disease (CKD). This systematic review evaluates the evidence for the correlation between drug effects on biochemical (PTH, phosphorus, and calcium) and all-cause and cardiovascular mortality end points in adults with CKD. Study Design Systematic review and meta-analysis. Setting & Population Adults with CKD. Selection Criteria for Studies Randomized trials reporting drug effects on biochemical and mortality end points. Intervention Drug interventions with effects on serum PTH, phosphorus, and calcium levels, including vitamin D compounds, phosphate binders, cinacalcet, bisphosphonates, and calcitonin. Outcomes Correlation between drug effects on biochemical and all-cause and cardiovascular mortality. Results 28 studies (6,999 participants) reported both biochemical and mortality outcomes and were eligible for analysis. Associations between drug effects on surrogate biochemical end points and corresponding effects on mortality were weak and imprecise. All correlation coefficients were less than 0.70, and 95% credible intervals were generally wide and overlapped with zero, consistent with the possibility of no association. The exception was an inverse correlation between drug effects on serum PTH levels and all-cause mortality, which was nominally significant (−0.64; 95% credible interval, −0.85 to −0.15), but the strength of this association was very imprecise. Risk of bias within available trials was generally high, further reducing confidence in the summary correlations. Findings were robust to adjustment for age, baseline serum PTH level, allocation concealment, CKD stage, and drug class. Limitations Low power in analyses and combining evidence from many different drug comparisons with incomplete data across studies. Conclusions Drug effects on serum PTH, phosphorus, and calcium levels are weakly and imprecisely correlated with all-cause and cardiovascular death in the setting of CKD. Risks of mortality (patient-level outcome) cannot be inferred from treatment-induced changes in biochemical outcomes in people with CKD. Similarly, existing data do not exclude a mortality benefit with treatment. Trials need to address patient-centered outcomes to evaluate drug effectiveness in this setting

KDIGO 2020 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease.

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Comparative effi cacy and safety of blood pressure-lowering agents in adults with diabetes and kidney disease: a network meta-analysis

Summary Background The comparative effi cacy and safety of pharmacological agents to lower blood pressure in adults with diabetes and kidney disease remains controversial. We aimed to investigate the benefi ts and harms of blood pressurelowering drugs in this population of patients

Prevention of contrast-induced acute kidney injury in patients undergoing cardiovascular procedures : a systematic review and network meta-analysis

BACKGROUND: Interventional diagnostic and therapeutic procedures requiring intravascular iodinated contrast steadily increase patient exposure to the risks of contrast-induced acute kidney injury (CIAKI), which is associated with death, nonfatal cardiovascular events, and prolonged hospitalization. The aim of this study was to investigate the efficacy of pharmacological and non-pharmacological treatments for CIAKI prevention in patients undergoing cardiovascular invasive procedures with iodinated contrast.METHODS AND FINDINGS: MEDLINE, Google Scholar, EMBASE and Cochrane databases as well as abstracts and presentations from major cardiovascular and nephrology meetings were searched, up to 22 April 2016. Eligible studies were randomized trials comparing strategies to prevent CIAKI (alone or in combination) when added to saline versus each other, saline, placebo, or no treatment in patients undergoing cardiovascular invasive procedures with administration of iodinated contrast. Two reviewers independently extracted trial-level data including number of patients, duration of follow-up, and outcomes. Eighteen strategies aimed at CIAKI prevention were identified. The primary outcome was the occurrence of CIAKI. Secondary outcomes were mortality, myocardial infarction, dialysis and heart failure. The data were pooled using network meta-analysis. Treatment estimates were calculated as odds ratios (ORs) with 95% credible intervals (CrI). 147 RCTs involving 33,463 patients were eligible. Saline plus N-acetylcysteine (OR 0.72, 95%CrI 0.57-0.88), ascorbic acid (0.59, 0.34-0.95), sodium bicarbonate plus N-acetylcysteine (0.59, 0.36-0.89), probucol (0.42, 0.15-0.91), methylxanthines (0.39, 0.20-0.66), statin (0.36, 0.21-0.59), device-guided matched hydration (0.35, 0.12-0.79), prostaglandins (0.26, 0.08-0.62) and trimetazidine (0.26, 0.09-0.59) were associated with lower odds of CIAKI compared to saline. Methylxanthines (0.12, 0.01-0.94) or left ventricular end-diastolic pressure-guided hydration (0.09, 0.01-0.59) were associated with lower mortality compared to saline.CONCLUSIONS: Currently recommended treatment with saline as the only measure to prevent CIAKI during cardiovascular procedures may not represent the optimal strategy. Vasodilators, when added to saline, may significantly reduce the odds of CIAKI following cardiovascular procedures

Dental Health and Mortality in People With End-Stage Kidney Disease Treated With Hemodialysis: A Multinational Cohort Study

Background Dental disease is more extensive in adults with chronic kidney disease, but whether dental health and behaviors are associated with survival in the setting of hemodialysis is unknown. Study Design Prospective multinational cohort. Setting & Participants 4,205 adults treated with long-term hemodialysis, 2010 to 2012 (Oral Diseases in Hemodialysis [ORAL-D] Study). Predictors Dental health as assessed by a standardized dental examination using World Health Organization guidelines and personal oral care, including edentulousness; decayed, missing, and filled teeth index; teeth brushing and flossing; and dental health consultation. Outcomes All-cause and cardiovascular mortality at 12 months after dental assessment. Measurements Multivariable-adjusted Cox proportional hazards regression models fitted with shared frailty to account for clustering of mortality risk within countries. Results During a mean follow-up of 22.1 months, 942 deaths occurred, including 477 cardiovascular deaths. Edentulousness (adjusted HR, 1.29; 95% CI, 1.10-1.51) and decayed, missing, or filled teeth score ≥ 14 (adjusted HR, 1.70; 95% CI, 1.33-2.17) were associated with early all-cause mortality, while dental flossing, using mouthwash, brushing teeth daily, spending at least 2 minutes on oral hygiene daily, changing a toothbrush at least every 3 months, and visiting a dentist within the past 6 months (adjusted HRs of 0.52 [95% CI, 0.32-0.85], 0.79 [95% CI, 0.64-0.97], 0.76 [95% CI, 0.58-0.99], 0.84 [95% CI, 0.71-0.99], 0.79 [95% CI, 0.65-0.95], and 0.79 [95% CI, 0.65-0.96], respectively) were associated with better survival. Results for cardiovascular mortality were similar. Limitations Convenience sample of clinics. Conclusions In adults treated with hemodialysis, poorer dental health was associated with early death, whereas preventive dental health practices were associated with longer survival

Comparative effectiveness of calcimimetic agents for secondary hyperparathyroidism in adults: a systematic review and network meta-analysis

Rationale & Objective: Comparative benefits and harms of calcimimetic agents used for the treatment of secondary hyperparathyroidism have not been well characterized. We sought to compare the effectiveness of 3 calcimimetic agents using published data. Study Design: Systematic review of randomized controlled trials and network meta-analysis. Setting & Study Population: Adults with chronic kidney disease enrolled in a clinical trial of a calcimetic agent. Search Strategy & Sources: MEDLINE, EMBASE, CENTRAL (from February 7, 2013, to November 21, 2019), and a published meta-analysis. Data Extraction: Two reviewers independently extracted the study data, assessed risk of bias, and rated evidence certainty using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. Analytical Approach: Frequentist network meta-analysis was conducted. The primary review outcomes were achievement of a target reduction in serum parathyroid hormone (PTH) levels and hypocalcemia. Additional outcomes were nausea, vomiting, serious adverse events, all-cause mortality, cardiovascular mortality, heart failure, and fracture. Results: 36 trials (11,247 participants) were included. All except 4 trials involved dialysis patients. Median follow-up was 26 weeks (range, 1 week to 21.2 months). Compared with placebo, calcimimetic agents had higher odds of achieving target PTH levels with high or moderate certainty. Etelcalcetide had the highest odds of achieving a PTH target compared with evocalcet (OR, 4.93; 95% CI, 1.33-18.2) and cinacalcet (OR, 2.78; 95% CI, 1.19-6.67). Etelcalcetide appeared to cause more hypocalcemia than cinacalcet and evocalcet. Cinacalcet and to a lesser extent etelcalcetide appeared to cause more nausea than placebo. Differences in risk for mortality, cardiovascular end points, or fractures across calcimimetic agents could not be discerned with sufficient certainty. Limitations: Lack of longer-term data; heterogeneous end point definitions. Conclusions: Evidence of the benefits of calcimimetic therapy is limited to short-term assessment of a putative surrogate outcome (serum PTH). Although etelcalcetide was associated with the largest reduction in PTH levels, side-effect profiles differed across the 3 calcimimetic agents, making it not possible to identify 1 preferred agent