Psychosocial interventions for preventing and treating depression in dialysis patients

Background: People with end-stage kidney disease (ESKD) treated with dialysis are frequently affected by major depression. Dialysis patients have prioritised depression as a critically important clinical outcome in nephrology trials. Psychological and social support are potential treatments for depression, although a Cochrane review in 2005 identified zero eligible studies. This is an update of the Cochrane review first published in 2005. Objectives: To assess the effect of using psychosocial interventions versus usual care or a second psychosocial intervention for preventing and treating depression in patients with ESKD treated with dialysis. Search methods: We searched Cochrane Kidney and Transplant's Register of Studies up to 21 June 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Selection criteria: We included randomised controlled trials (RCTs) and quasi-RCTs of psychosocial interventions for prevention and treatment of depression among adults treated with long-term dialysis. We assessed effects of interventions on changes in mental state (depression, anxiety, cognition), suicide, health-related quality of life (HRQoL), withdrawal from dialysis treatment, withdrawal from intervention, death (any cause), hospitalisation and adverse events. Data collection and analysis: Two authors independently selected studies for inclusion and extracted study data. We applied the Cochrane 'Risk of Bias' tool and used the GRADE process to assess evidence certainty. We estimated treatment effects using random-effects meta-analysis. Results for continuous outcomes were expressed as a mean difference (MD) or as a standardised mean difference (SMD) when investigators used different scales. Dichotomous outcomes were expressed as risk ratios. All estimates were reported together with 95% confidence intervals (CI). Main results: We included 33 studies enrolling 2056 participants. Twenty-six new studies were added to this 2019 update. Seven studies originally excluded from the 2005 review were included as they met the updated review eligibility criteria, which have been expanded to include RCTs in which participants did not meet criteria for depression as an inclusion criterion. Psychosocial interventions included acupressure, cognitive-behavioural therapy, counselling, education, exercise, meditation, motivational interviewing, relaxation techniques, social activity, spiritual practices, support groups, telephone support, visualisation, and voice-recording of a psychological intervention. The duration of study follow-up ranged between three weeks and one year. Studies included between nine and 235 participants. The mean study age ranged between 36.1 and 73.9 years. Random sequence generation and allocation concealment were at low risk of bias in eight and one studies respectively. One study reported low risk methods for blinding of participants and investigators, and outcome assessment was blinded in seven studies. Twelve studies were at low risk of attrition bias, eight studies were at low risk of selective reporting bias, and 21 studies were at low risk of other potential sources of bias. Cognitive behavioural therapy probably improves depressive symptoms measured using the Beck Depression Inventory (4 studies, 230 participants: MD -6.10, 95% CI -8.63 to -3.57), based on moderate certainty evidence. Cognitive behavioural therapy compared to usual care probably improves HRQoL measured either with the Kidney Disease Quality of Life Instrument Short Form or the Quality of Life Scale, with a 0.5 standardised mean difference representing a moderate effect size (4 studies, 230 participants: SMD 0.51, 95% CI 0.19 to 0.83), based on moderate certainty evidence. Cognitive behavioural therapy may reduce major depression symptoms (one study) and anxiety, and increase self-efficacy (one study). Cognitive behavioural therapy studies did not report hospitalisation. We found low-certainty evidence that counselling may slightly reduce depressive symptoms measured with the Beck Depression Inventory (3 studies, 99 participants: MD -3.84, 95% CI -6.14 to -1.53) compared to usual care. Counselling reported no difference in HRQoL (one study). Counselling studies did not measure risk of major depression, suicide, or hospitalisation. Exercise may reduce or prevent major depression (3 studies, 108 participants: RR 0.47, 95% CI 0.27 to 0.81), depression of any severity (3 studies, 108 participants: RR 0.69, 95% CI 0.54 to 0.87) and improve HRQoL measured with Quality of Life Index score (2 studies, 64 participants: MD 3.06, 95% CI 2.29 to 3.83) compared to usual care with low certainty. With moderate certainty, exercise probably improves depression symptoms measured with the Beck Depression Inventory (3 studies, 108 participants: MD -7.61, 95% CI -9.59 to -5.63). Exercise may reduce anxiety (one study). No exercise studies measured suicide risk or withdrawal from dialysis. We found moderate-certainty evidence that relaxation techniques probably reduce depressive symptoms measured with the Beck Depression Inventory (2 studies, 122 participants: MD -5.77, 95% CI -8.76 to -2.78). Relaxation techniques reported no difference in HRQoL (one study). Relaxation studies did not measure risk of major depression or suicide. Spiritual practices have uncertain effects on depressive symptoms measured either with the Beck Depression Inventory or the Brief Symptom Inventory (2 studies, 116 participants: SMD -1.00, 95% CI -3.52 to 1.53; very low certainty evidence). No differences between spiritual practices and usual care were reported on anxiety (one study), and HRQoL (one study). No study of spiritual practices evaluated effects on suicide risk, withdrawal from dialysis or hospitalisation. There were few or no data on acupressure, telephone support, meditation and adverse events related to psychosocial interventions. Authors' conclusions: Cognitive behavioural therapy, exercise or relaxation techniques probably reduce depressive symptoms (moderate-certainty evidence) for adults with ESKD treated with dialysis. Cognitive behavioural therapy probably increases health-related quality of life. Evidence for spiritual practices, acupressure, telephone support, and meditation is of low certainty. Similarly, evidence for effects of psychosocial interventions on suicide risk, major depression, hospitalisation, withdrawal from dialysis, and adverse events is of low or very low certainty

Dietary intake in adults on hemodialysis compared with guideline recommendations

Background: Clinical practice guidelines of dietary management are designed to promote a balanced diet and maintain health in patients undergoing haemodialysis but they may not reflect patients’ preferences. We aimed to investigate the consistency between the dietary intake of patients on maintenance haemodialysis and guideline recommendations. Methods: Cross-sectional analysis of the DIET-HD study, which included 6,906 adults undergoing haemodialysis in 10 European countries. Dietary intake was determined using the Global Allergy and Asthma European Network (GA2LEN) Food Frequency Questionnaire (FFQ), and compared with the European Best Practice Guidelines. Consistency with guidelines was defined as achieving the minimum daily recommended intake for energy (≥ 30 kcal/kg) and protein (≥ 1.1 g/kg), and not exceeding the maximum recommended daily intake for phosphate (≤ 1000 mg), potassium (≤ 2730 mg), sodium (≤ 2300 mg) and calcium (≤ 800 mg). Results: Overall, patients’ dietary intakes of phosphate and potassium were infrequently consistent with guidelines (consistent in 25% and 25% of patients, respectively). Almost half of the patients reported that energy (45%) and calcium intake (53%) was consistent with the guidelines, while the recommended intake of sodium and protein was consistent in 85% and 67% of patients, respectively. Results were similar across all participating countries. Intake was consistent with all six guideline recommendations in only 1% of patients. Conclusion: Patients on maintenance haemodialysis usually have a dietary intake which is inconsistent with current recommendations, especially for phosphate and potassium

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

Transparency, trust and minimizing burden to increase recruitment and retentio in trials: A systematic review

Objective: To describe patient perspectives on recruitment and retention in clinical trials. Study Design and Setting: Systematic review of qualitative studies that reported the perspective of adult patients with any health condition who accepted or declined to participate in clinical trials. Results: Sixty-three articles involving 1681 adult patients were included. Six themes were identified. Four themes reflected barriers: ambiguity of context and benefit – patients were unaware of the research question and felt pressured in making decisions; lacking awareness of opportunities – some believed health professionals obscured trials opportunities, or felt confused because of language barriers; wary of added burden – patients were without capacity because of sickness or competing priorities; and skepticism, fear and mistrust – patients feared loss of privacy, were suspicious of doctor's motivation, afraid of being a guinea pig, and disengaged from not knowing outcomes. Two themes captured facilitators: building confidence – patients hoped for better treatment, were supported from family members and trusted medical staff; and social gains and belonging to the community – altruism, a sense of belonging and peer encouragement motivated participation in trials. Conclusion: Improving the visibility and transparency of trials, supporting informed decision making, minimizing burden, and ensuring confidence and trust may improve patient participation in trials

PERIODONTITIS AND EARLY MORTALITY IN ADULTS WITH KIDNEY FAILURE TREATED WITH HEMODIALYSIS: A MULTINATIONAL OBSERVATIONAL STUDY

Introduction and Aims: Periodontitis is associated with cardiovascular mortality in the general population and adults with chronic diseases, however prognostic data for periodontitis in the setting of kidney failure are sparse. The aim of the study was to evaluate whether periodontitis was prognostic for all-cause and cardiovascular-related death in adults with kidney failure. Methods: ORALD is a multinational cohort study in adults with kidney failure treated with haemodialysis in Europe (France, Hungary, Italy, Poland, Portugal and Spain) and Argentina. Periodontitis was measured at baseline according to the World Health Organization Community Periodontal Index. The outcomes were all-cause and cardiovascular mortality. Analyses were conducted using a fixed-effect Cox proportional hazards analysis and additionally using a random effects model fitted using shared frailty to account for clustering within countries. Results: Periodontitis was evaluable in 3338 dentate participants of which 1355 (40.6%) had moderate to severe periodontitis. During 6150 person-years of follow-up, 650 deaths occurred of which 325 were cardiovascular. In multivariable analyses, moderate to severe periodontitis was associated with a lower hazard of all-cause (HR 0.76, 95% confidence interval 0.64 to 0.90) and cardiovascular (0.69, 0.54 to 0.87) mortality. There was evidence of decreasing mortality risks with more severe periodontal disease (P≤0.001 for trend). However, when analyses accounted for clustering of participants within countries, the associations between periodontitis and all-cause (0.92, 0.75 to 1.11) and cardiovascular (0.83, 0.63 to 1.09) mortality were not significant. Similar results were observed in analyses restricted to participants with 12 or more teeth and when competing risks for cardiovascular death were considered. Conclusions: Unlike in the general population, there is limited evidence that periodontitis is independently associated with increased all-cause or cardiovascular mortality in adults with kidney failure

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

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Effects of the dose of erythropoiesis stimulating agents on cardiovascular events, quality of life, and health-related costs in hemodialysis patients: the clinical evaluation of the dose of erythropoietins (C.E. DOSE) trial protocol

<p>Abstract</p> <p>Background</p> <p>Anemia is a risk factor for death, adverse cardiovascular outcomes and poor quality of life in patients with chronic kidney disease (CKD). Erythropoietin Stimulating Agents (ESA) are commonly used to increase hemoglobin levels in this population. In observational studies, higher hemoglobin levels (around 11-13 g/dL) are associated with improved survival and quality of life compared to hemoglobin levels around 9-10 g/dL. A systematic review of randomized trials found that targeting higher hemoglobin levels with ESA causes an increased risk of adverse vascular outcomes. It is possible, but has never been formally tested in a randomized trial, that ESA dose rather than targeted hemoglobin concentration itself mediates the increased risk of adverse vascular outcomes. The Clinical Evaluation of the DOSe of Erythropoietins (C.E. DOSE) trial will assess the benefits and harms of a high versus a low fixed ESA dose for the management of anemia in patients with end stage kidney disease.</p> <p>Methods/Design</p> <p>This is a randomized, prospective open label blinded end-point (PROBE) trial due to enrol 2204 hemodialysis patients in Italy. Patients will be randomized 1:1 to 4000 IU/week versus 18000 IU/week of intravenous epoietin alfa or beta, or any other ESA in equivalent doses. The dose will be adjusted only if hemoglobin levels fall outside the 9.5-12.5 g/dL range. The primary outcome will be a composite of all-cause mortality, non fatal stroke, non fatal myocardial infarction and hospitalization for cardiovascular causes. Quality of life and costs will also be assessed.</p> <p>Discussion</p> <p>The C.E.DOSE study will help inform the optimal therapeutic strategy for the management of anemia of hemodialysis patients, improving clinical outcomes, quality of life and costs, by ascertaining the potential benefits and harms of different fixed ESA doses.</p> <p>Trial registration</p> <p>Clinicaltrials.gov NCT00827021</p

Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: Systematic review and network meta-analysis of randomised controlled trials

Objective To evaluate sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at varying cardiovascular and renal risk. Design Network meta-analysis. Data sources Medline, Embase, and Cochrane CENTRAL up to 11 August 2020. Eligibility criteria for selecting studies Randomised controlled trials comparing SGLT-2 inhibitors or GLP-1 receptor agonists with placebo, standard care, or other glucose lowering treatment in adults with type 2 diabetes with follow up of 24 weeks or longer. Studies were screened independently by two reviewers for eligibility, extracted data, and assessed risk of bias. Main outcome measures Frequentist random effects network meta-analysis was carried out and GRADE (grading of recommendations assessment, development, and evaluation) used to assess evidence certainty. Results included estimated absolute effects of treatment per 1000 patients treated for five years for patients at very low risk (no cardiovascular risk factors), low risk (three or more cardiovascular risk factors), moderate risk (cardiovascular disease), high risk (chronic kidney disease), and very high risk (cardiovascular disease and kidney disease). A guideline panel provided oversight of the systematic review. Results 764 trials including 421 346 patients proved eligible. All results refer to the addition of SGLT-2 inhibitors and GLP-1 receptor agonists to existing diabetes treatment. Both classes of drugs lowered all cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and kidney failure (high certainty evidence). Notable differences were found between the two agents: SGLT-2 inhibitors reduced mortality and admission to hospital for heart failure more than GLP-1 receptor agonists, and GLP-1 receptor agonists reduced non-fatal stroke more than SGLT-2 inhibitors (which appeared to have no effect). SGLT-2 inhibitors caused genital infection (high certainty), whereas GLP-1 receptor agonists might cause severe gastrointestinal events (low certainty). Low certainty evidence suggested that SGLT-2 inhibitors and GLP-1 receptor agonists might lower body weight. Little or no evidence was found for the effect of SGLT-2 inhibitors or GLP-1 receptor agonists on limb amputation, blindness, eye disease, neuropathic pain, or health related quality of life. The absolute benefits of these drugs vary substantially across patients from low to very high risk of cardiovascular and renal outcomes (eg, SGLT-2 inhibitors resulted in 5 to 48 fewer deaths in 1000 patients over five years; see interactive decision support tool (https://magicevidence.org/match-it/200820dist/#!/) for all outcomes. Conclusions In patients with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists reduced cardiovascular and renal outcomes, with notable differences in benefits and harms. Absolute benefits are determined by individual risk profiles of patients, with clear implications for clinical practice, as reflected in the BMJ Rapid Recommendations directly informed by this systematic review. Systematic review registration PROSPERO CRD42019153180