Non-immunosuppressive treatment for IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerular disease, with approximately 20% to 40% of patients progressing to kidney failure within 25 years. Non-immunosuppressive treatment has become a mainstay in the management of IgAN by improving blood pressure (BP) management, decreasing proteinuria, and avoiding the risks of long-term immunosuppressive management. Due to the slowly progressive nature of the disease, clinical trials are often underpowered, and conflicting information about management with non-immunosuppressive treatment is common. This is an update of a Cochrane review, first published in 2011. OBJECTIVES: To assess the benefits and harms of non-immunosuppressive treatment for treating IgAN in adults and children. We aimed to examine all non-immunosuppressive therapies (e.g. anticoagulants, antihypertensives, dietary restriction and supplementation, tonsillectomy, and herbal medicines) in the management of IgAN. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to December 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs of non-immunosuppressive agents in adults and children with biopsy-proven IgAN were included. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed search results, extracted data and assessed study quality. Results were expressed as mean differences (MD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CI) using random-effects meta-analysis. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: This review includes 80 studies (4856 participants), of which 24 new studies (2018 participants) were included in this review update. The risk of bias within the included studies was mostly high or unclear for many of the assessed methodological domains, with poor reporting of important key clinical trial methods in most studies. Antihypertensive therapies were the most examined non-immunosuppressive therapy (37 studies, 1799 participants). Compared to placebo or no treatment, renin-angiotensin system (RAS) inhibition probably decreases proteinuria (3 studies, 199 participants: MD - 0.71 g/24 h, 95% CI -1.04 to -0.39; moderate certainty evidence) but may result in little or no difference to kidney failure or doubling of serum creatinine (SCr), or complete remission of proteinuria (low certainty evidence). Death, remission of haematuria, relapse of proteinuria or > 50% increase in SCr were not reported. Compared to symptomatic treatment, RAS inhibition (3 studies, 168 participants) probably decreases proteinuria (MD -1.16 g/24 h, 95% CI -1.52 to -0.81) and SCr (MD -9.37 µmol/L, 95% CI -71.95 to -6.80) and probably increases creatinine clearance (2 studies, 127 participants: MD 23.26 mL/min, 95% CI 10.40 to 36.12) (all moderate certainty evidence); however, the risk of kidney failure is uncertain (1 study, 34 participants: RR 0.20, 95% CI 0.01 to 3.88; very low certainty evidence). Death, remission of proteinuria or haematuria, or relapse of proteinuria were not reported. The risk of adverse events may be no different with RAS inhibition compared to either placebo or symptomatic treatment (low certainty evidence). In low certainty evidence, tonsillectomy in people with IgAN in addition to standard care may increase remission of proteinuria compared to standard care alone (2 studies, 143 participants: RR 1.90, 95% CI 1.45 to 2.47) and remission of microscopic haematuria (2 studies, 143 participants: RR 1.93, 95% CI 1.47 to 2.53) and may decrease relapse of proteinuria (1 study, 73 participants: RR 0.70, 95% CI 0.57 to 0.85) and relapse of haematuria (1 study, 72 participants: RR 0.70, 95% CI 0.51 to 0.98). Death, kidney failure and a > 50% increase in SCr were not reported. These trials have only been conducted in Japanese people with IgAN, and the findings' generalisability is unclear. Anticoagulant therapy, fish oil, and traditional Chinese medicines exhibited small benefits to kidney function in patients with IgAN when compared to placebo or no treatment. However, compared to standard care, the kidney function benefits are no longer evident. Antimalarial therapy compared to placebo in one study reported an increase in a > 50% reduction of proteinuria (53 participants: RR 3.13 g/24 h, 95% CI 1.17 to 8.36; low certainty evidence). Although, there was uncertainty regarding adverse events from this study due to very few events. AUTHORS' CONCLUSIONS: Available RCTs focused on a diverse range of interventions. They were few, small, and of insufficient duration to determine potential long-term benefits on important kidney and cardiovascular outcomes and harms of treatment. Antihypertensive agents appear to be the most beneficial non-immunosuppressive intervention for IgAN. The antihypertensives examined were predominantly angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. The benefits of RAS inhibition appear to outweigh the harms in patients with IgAN. The certainty of the evidence of RCTs demonstrating a benefit of tonsillectomy to patients with Japanese patients with IgAN was low. In addition, these findings are inconsistent across observational studies in people with IgAN of other ethnicities; hence, tonsillectomy is not widely recommended, given the potential harm of therapy. The RCT evidence is insufficiently robust to demonstrate efficacy for the other non-immunosuppressive treatments evaluated here.

Cranberries for treating urinary tract infections.

BACKGROUND: Cranberries (particularly in the form of cranberry juice) have been used widely for several decades for the prevention and treatment of urinary tract infections (UTIs). The aim of this review is to assess the effectiveness of cranberries in treating such infections. OBJECTIVES: To assess the effectiveness of cranberries for the treatment of UTIs. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 1 August 2023 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 Registry Portal (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs) or quasi-RCTs of cranberry juice or cranberry products for the treatment of UTIs. Studies of men, women or children were to be included. DATA COLLECTION AND ANALYSIS: Titles and abstracts of studies that were potentially relevant to the review were screened and studies that were clearly ineligible were discarded. Further information was sought from the authors where papers contained insufficient information to make a decision about eligibility. MAIN RESULTS: No studies were found that fulfilled all of our inclusion criteria. Seven studies were excluded because they were the wrong study design, mixed interventions or did not report any relevant outcomes. One study is ongoing; however, its current status is unknown. AUTHORS' CONCLUSIONS: After a thorough search, no RCTs which assessed the effectiveness of cranberry juice for the treatment of UTIs were found. Therefore, at the present time, there is no good quality evidence to suggest that it is effective for the treatment of UTIs. Well-designed parallel-group, double-blind studies comparing cranberry juice and other cranberry products versus placebo to assess the effectiveness of cranberry juice in treating UTIs are needed. Outcomes should include a reduction in symptoms, sterilisation of the urine, side effects and adherence to therapy. The dosage (amount and concentration) and duration of therapy should also be assessed. Consumers and clinicians will welcome the evidence from these studies.

Cranberries for preventing urinary tract infections.

BACKGROUND: Cranberries contain proanthocyanidins (PACs), which inhibit the adherence of p-fimbriated Escherichia coli to the urothelial cells lining the bladder. Cranberry products have been used widely for several decades to prevent urinary tract infections (UTIs). This is the fifth update of a review first published in 1998 and updated in 2003, 2004, 2008, and 2012. OBJECTIVES: To assess the effectiveness of cranberry products in preventing UTIs in susceptible populations. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register up to 13 March 2023 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 Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs) or quasi-RCTs of cranberry products compared with placebo, no specific treatment or other intervention (antibiotics, probiotics) for the prevention of UTIs were included. DATA COLLECTION AND ANALYSIS: At least two authors independently assessed and extracted data. Information was collected on methods, participants, interventions and outcomes (incidence of symptomatic UTIs, positive culture results, side effects, adherence to therapy). Risk ratios (RR) with 95% confidence intervals (CI) were calculated where appropriate. Study quality was assessed using the Cochrane risk of bias assessment tool. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: For this update, 26 new studies were added, bringing the total number of included studies to 50 (8857 randomised participants). The risk of bias for sequence generation and allocation concealment was low for 29 and 28 studies, respectively. Thirty-six studies were at low risk of performance bias, and 23 studies were at low risk of detection bias. Twenty-seven, 41, and 17 studies were at low risk of attrition bias, reporting bias and other bias, respectively. Forty-five studies compared cranberry products with placebo, water or no specific treatment in six different groups of participants. Twenty-six of these 45 studies could be meta-analysed for the outcome of symptomatic, culture-verified UTIs. In moderate certainty evidence, cranberry products reduced the risk of UTIs (6211 participants: RR 0.70, 95% CI 0.58 to 0.84; I² = 69%). When studies were divided into groups according to the treatment indication, cranberry products probably reduced the risk of symptomatic, culture-verified UTIs in women with recurrent UTIs (8 studies, 1555 participants: RR 0.74, 95% CI 0.55 to 0.99; I² = 54%), in children (5 studies, 504 participants: RR 0.46, 95% CI 0.32 to 0.68; I² = 21%) and in people with a susceptibility to UTIs due to an intervention (6 studies, 1434 participants: RR 0.47, 95% CI 0.37 to 0.61; I² = 0%). However, there may be little or no benefit in elderly institutionalised men and women (3 studies, 1489 participants: RR 0.93, 95% CI 0.67 to 1.30; I² = 9%; moderate certainty evidence), pregnant women (3 studies, 765 participants: RR 1.06, 95% CI 0.75 to 1.50; I² = 3%; moderate certainty evidence), or adults with neuromuscular bladder dysfunction with incomplete bladder emptying (3 studies, 464 participants: RR 0.97, 95% CI 0.78 to 1.19; I² = 0%; low certainty evidence). Other comparisons were cranberry products with probiotics (three studies) or antibiotics (six studies), cranberry tablets with cranberry liquid (one study), and different doses of PACs (two studies). Compared to antibiotics, cranberry products may make little or no difference to the risk of symptomatic, culture-verified UTIs (2 studies, 385 participants: RR 1.03, 95% CI 0.80 to 1.33; I² = 0%) or the risk of clinical symptoms without culture (2 studies, 336 participants: RR 1.30, 95% CI 0.79 to 2.14; I² = 68%). Compared to probiotics, cranberry products may reduce the risk of symptomatic, culture-verified UTIs (3 studies, 215 participants: RR 0.39, 95% CI 0.27 to 0.56; I = 0%). It is unclear whether efficacy differs between cranberry juice and tablets or between different doses of PACs, as the certainty of the evidence was very low. The number of participants with gastrointestinal side effects probably does not differ between those taking cranberry products and those receiving a placebo or no specific treatment (10 studies, 2166 participants: RR 1.33, 95% CI 1.00 to 1.77; I² = 0%; moderate certainty evidence). There was no clear relationship between compliance with therapy and the risk for repeat UTIs. No difference in the risk for UTIs could be demonstrated between low, moderate and high doses of PACs. AUTHORS' CONCLUSIONS: This update adds a further 26 studies, taking the total number of studies to 50 with 8857 participants. These data support the use of cranberry products to reduce the risk of symptomatic, culture-verified UTIs in women with recurrent UTIs, in children, and in people susceptible to UTIs following interventions. The evidence currently available does not support its use in the elderly, patients with bladder emptying problems, or pregnant women.

Interventions for fatigue in people with kidney failure requiring dialysis.

BACKGROUND: Fatigue is a common and debilitating symptom in people receiving dialysis that is associated with an increased risk of death, cardiovascular disease and depression. Fatigue can also impair quality of life (QoL) and the ability to participate in daily activities. Fatigue has been established by patients, caregivers and health professionals as a core outcome for haemodialysis (HD). OBJECTIVES: We aimed to evaluate the effects of pharmacological and non-pharmacological interventions on fatigue in people with kidney failure receiving dialysis, including HD and peritoneal dialysis (PD), including any setting and frequency of the dialysis treatment. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 18 October 2022 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 Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Studies evaluating pharmacological and non-pharmacological interventions affecting levels of fatigue or fatigue-related outcomes in people receiving dialysis were included. Studies were eligible if fatigue or fatigue-related outcomes were reported as a primary or secondary outcome. Any mode, frequency, prescription, and duration of therapy were considered. DATA COLLECTION AND ANALYSIS: Three authors independently extracted data and assessed the risk of bias. Treatment estimates were summarised using random effects meta-analysis and expressed as a risk ratio (RR) or mean difference (MD), with a corresponding 95% confidence interval (CI) or standardised MD (SMD) if different scales were used. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Ninety-four studies involving 8191 randomised participants were eligible. Pharmacological and non-pharmacological interventions were compared either to placebo or control, or to another pharmacological or non-pharmacological intervention. In the majority of domains, risks of bias in the included studies were unclear or high. In low certainty evidence, when compared to control, exercise may improve fatigue (4 studies, 217 participants (Iowa Fatigue Scale, Modified Fatigue Impact Scale, Piper Fatigue Scale (PFS), or Haemodialysis-Related Fatigue scale score): SMD -1.18, 95% CI -2.04 to -0.31; I2 = 87%) in HD. In low certainty evidence, when compared to placebo or standard care, aromatherapy may improve fatigue (7 studies, 542 participants (Fatigue Severity Scale (FSS), Rhoten Fatigue Scale (RFS), PFS or Brief Fatigue Inventory score): SMD -1.23, 95% CI -1.96 to -0.50; I2 = 93%) in HD. In low certainty evidence, when compared to no intervention, massage may improve fatigue (7 studies, 657 participants (FSS, RFS, PFS or Visual Analogue Scale (VAS) score): SMD -1.06, 95% CI -1.47, -0.65; I2 = 81%) and increase energy (2 studies, 152 participants (VAS score): MD 4.87, 95% CI 1.69 to 8.06, I2 = 59%) in HD. In low certainty evidence, when compared to placebo or control, acupressure may reduce fatigue (6 studies, 459 participants (PFS score, revised PFS, or Fatigue Index): SMD -0.64, 95% CI -1.03 to -0.25; I2 = 75%) in HD. A wide range of heterogenous interventions and fatigue-related outcomes were reported for exercise, aromatherapy, massage and acupressure, preventing our capability to pool and analyse the data. Due to the paucity of studies, the effects of pharmacological and other non-pharmacological interventions on fatigue or fatigue-related outcomes, including non-physiological neutral amino acid, relaxation with or without music therapy, meditation, exercise with nandrolone, nutritional supplementation, cognitive-behavioural therapy, ESAs, frequent HD sections, home blood pressure monitoring, blood flow rate reduction, serotonin reuptake inhibitor, beta-blockers, anabolic steroids, glucose-enriched dialysate, or light therapy, were very uncertain. The effects of pharmacological and non-pharmacological treatments on death, cardiovascular diseases, vascular access, QoL, depression, anxiety, hypertension or diabetes were sparse. No studies assessed tiredness, exhaustion or asthenia. Adverse events were rarely and inconsistently reported. AUTHORS' CONCLUSIONS: Exercise, aromatherapy, massage and acupressure may improve fatigue compared to placebo, standard care or no intervention. Pharmacological and other non-pharmacological interventions had uncertain effects on fatigue or fatigue-related outcomes in people receiving dialysis. Future adequately powered, high-quality studies are likely to change the estimated effects of interventions for fatigue and fatigue-related outcomes in people receiving dialysis.

Cranberries for preventing urinary tract infections.

BACKGROUND: Cranberries contain proanthocyanidins (PACs), which inhibit the adherence of p-fimbriated Escherichia coli to the urothelial cells lining the bladder. Cranberry products have been used widely for several decades to prevent urinary tract infections (UTIs). This is the fifth update of a review first published in 1998 and updated in 2003, 2004, 2008, and 2012. OBJECTIVES: To assess the effectiveness of cranberry products in preventing UTIs in susceptible populations. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register up to 13 March 2023 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 Search Portal (ICTRP) and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs) or quasi-RCTs of cranberry products compared with placebo, no specific treatment or other intervention (antibiotics, probiotics) for the prevention of UTIs were included. DATA COLLECTION AND ANALYSIS: Two authors independently assessed and extracted data. Information was collected on methods, participants, interventions and outcomes (incidence of symptomatic UTIs, positive culture results, side effects, adherence to therapy). Risk ratios (RR) with 95% confidence intervals (CI) were calculated where appropriate. Study quality was assessed using the Cochrane risk of bias assessment tool. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: For this update 26 new studies were added, bringing the total number of included studies to 50 (8857 randomised participants). The risk of bias for sequence generation and allocation concealment was low for 29 and 28 studies, respectively. Thirty-six studies were at low risk of performance bias, and 23 studies were at low risk of detection bias. Twenty-seven, 41, and 17 studies were at low risk of attrition bias, reporting bias and other bias, respectively. Forty-five studies compared cranberry products with placebo or no specific treatment in six different groups of participants. Twenty-six of these 45 studies could be meta-analysed for the outcome of symptomatic, culture-verified UTIs. In moderate certainty evidence, cranberry products reduced the risk of UTIs (6211 participants: RR 0.70, 95% CI 0.58 to 0.84; I² = 69%). When studies were divided into groups according to the treatment indication, cranberry products probably reduced the risk of symptomatic, culture-verified UTIs in women with recurrent UTIs (8 studies, 1555 participants: RR 0.74, 95% CI 0.55 to 0.99; I² = 54%), in children (5 studies, 504 participants: RR 0.46, 95% CI 0.32 to 0.68; I² = 21%) and in people with a susceptibility to UTIs due to an intervention (6 studies, 1434 participants: RR 0.47, 95% CI 0.37 to 0.61; I² = 0%). However, in low certainty evidence, there may be little or no benefit in elderly institutionalised men and women (3 studies, 1489 participants: RR 0.93, 95% CI 0.67 to 1.30; I² = 9%), pregnant women (3 studies, 765 participants: RR 1.06, 95% CI 0.75 to 1.50; I² = 3%), or adults with neuromuscular bladder dysfunction with incomplete bladder emptying (3 studies, 464 participants: RR 0.97, 95% CI 0.78 to 1.19; I² = 0%). Other comparisons were cranberry products with probiotics (three studies) or antibiotics (six studies), cranberry tablets with cranberry liquid (one study), and different doses of PACs (two studies). Compared to antibiotics, cranberry products may make little or no difference to the risk of symptomatic, culture-verified UTIs (2 studies, 385 participants: RR 1.03, 95% CI 0.80 to 1.33; I² = 0%) or the risk of clinical symptoms without culture (2 studies, 336 participants: RR 1.30, 95% CI 0.79 to 2.14; I² = 68%). Compared to probiotics, cranberry products may reduce the risk of symptomatic, culture-verified UTIs (3 studies, 215 participants: RR 0.39, 95% CI 0.27 to 0.56; I = 0%). It is unclear whether efficacy differs between cranberry juice and tablets or between different doses of PACs as the certainty of the evidence was very low. The number of participants with gastrointestinal side effects probably does not differ between those taking cranberry products and those receiving placebo or no specific treatment (10 studies, 2166 participants: RR 1.33, 95% CI 1.00 to 1.77; I² = 0%; moderate certainty evidence). There was no clear relationship between compliance with therapy and the risk for repeat UTIs. No difference in the risk for UTIs could be demonstrated between low, moderate and high doses of PACs. AUTHORS' CONCLUSIONS: This update adds a further 26 studies taking the total number of studies to 50 with 8857 participants. These data support the use of cranberry products to reduce the risk of symptomatic, culture-verified UTIs in women with recurrent UTIs, in children, and in people susceptible to UTIs following interventions. The evidence currently available does not support its use in the elderly, patients with bladder emptying problems, or pregnant women.

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.

Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease.

BACKGROUND: Anaemia occurs in chronic kidney disease (CKD) and is more prevalent with lower levels of kidney function. Anaemia in CKD is associated with death related to cardiovascular (CV) disease and infection. Established treatments include erythropoiesis-stimulating agents (ESAs), iron supplementation and blood transfusions. Oral hypoxia-inducible factors (HIF) stabilisers are now available to manage anaemia in people with CKD. OBJECTIVES: We aimed to assess the benefits and potential harms of HIF stabilisers for the management of anaemia in people with CKD. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 22 November 2021 through contact with the Information Specialist using search terms relevant to our review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: Randomised and quasi-randomised studies evaluating hypoxia-inducible factors stabilisers compared to placebo, standard care, ESAs or iron supplementation in people with CKD were included. DATA COLLECTION AND ANALYSIS: Five authors independently extracted data and assessed the risk of bias. Treatment estimates were summarised using random effects pair-wise meta-analysis and expressed as a relative risk (RR) or mean difference (MD), with a corresponding 95% confidence interval (CI). Evidence certainty was assessed using GRADE. MAIN RESULTS: We included 51 studies randomising 30,994 adults. These studies compared HIF stabilisers to either placebo or an ESA. Compared to placebo, HIF stabiliser therapy had uncertain effects on CV death (10 studies, 1114 participants): RR 3.68, 95% CI 0.19 to 70.21; very low certainty evidence), and nonfatal myocardial infarction (MI) (3 studies, 822 participants): RR 1.29, 95% CI 0.31 to 5.36; I² = 0%; very low certainty evidence), probably decreases the proportion of patients requiring blood transfusion (8 studies, 4329 participants): RR 0.51, 95% CI 0.44 to 0.60; I² = 0%; moderate certainty evidence), and increases the proportion of patients reaching the target haemoglobin (Hb) (10 studies, 5102 participants): RR 8.36, 95% CI 6.42 to 10.89; I² = 37%; moderate certainty evidence). Compared to ESAs, HIF stabiliser therapy may make little or no difference to CV death (17 studies, 10,340 participants): RR 1.05, 95% CI 0.88 to 1.26; I² = 0%; low certainty evidence), nonfatal MI (7 studies, 7765 participants): RR 0.91, 95% CI 0.76 to 1.10; I² = 0%; low certainty evidence), and nonfatal stroke (5 studies, 7285 participants): RR 1.06, 95% CI 0.71 to 1.56; I² = 8%; low certainty evidence), and had uncertain effects on fatigue (2 studies, 3471 participants): RR 0.80, 95% CI 0.56 to 1.16; I² = 0%; very low certainty evidence). HIF stabiliser therapy probably decreased the proportion of patients requiring blood transfusion (11 studies, 10,786 participants): RR 0.87, 95% CI 0.76 to 1.00; I² = 25%; moderate certainty evidence), but may make little or no difference on the proportion of patients reaching the target Hb (14 studies, 4601 participants): RR 1.00, 95% CI 0.93 to 1.07; I² = 70%; low certainty evidence), compared to ESA. The effect of HIF stabilisers on hospitalisation for heart failure, peripheral arterial events, loss of unassisted dialysis vascular access patency, access intervention, cancer, infection, pulmonary hypertension and diabetic nephropathy was uncertain. None of the included studies reported life participation. Adverse events were rarely and inconsistently reported. AUTHORS' CONCLUSIONS: HIF stabiliser management of anaemia had uncertain effects on CV death, fatigue, death (any cause), CV outcomes, and kidney failure compared to placebo or ESAs. Compared to placebo or ESAs, HIF stabiliser management of anaemia probably decreased the proportion of patients requiring blood transfusions, and probably increased the proportion of patients reaching the target Hb when compared to placebo.

Stakeholder perspectives on the implementation and impact of Indigenous health interventions: A systematic review of qualitative studies.

BACKGROUND: Evaluations of health interventions for Indigenous peoples rarely report outcomes that reflect participant and community perspectives of their experiences. Inclusion of such data may provide a fuller picture of the impact of health programmes and improve the usefulness of evaluation assessments. AIM: To describe stakeholder perspectives and experiences of the implementation and impact of Indigenous health programmes. METHODS: We conducted a systematic review of qualitative studies evaluating complex health interventions designed for Indigenous communities in high-income countries. We searched 6 electronic databases (through to January 2020): MEDLINE, PreMEDLINE, Embase, PsycINFO, EconLit and CINAHL and hand-searched reference lists of relevant articles. RESULTS: From 28 studies involving 677 stakeholders (mostly clinical staff and participants), six main themes were identified: enabling engagement, regaining control of health, improving social health and belonging, preserving community and culture, cultivating hope for a better life, and threats to long-term programme viability. CONCLUSION: The prominence of social, emotional and spiritual well-being as important aspects of the health journey for participants in this review highlights the need to reframe evaluations of health programmes implemented in Indigenous communities away from assessments that focus on commonly used biomedical measures. Evaluators, in consultation with the community, should consistently assess the capacity of health professionals to meet community needs and expectations throughout the life of the programme. Evaluations that include qualitative data on participant and community-level outcomes can improve decision-makers' understanding of the impact that health programmes have on communities. PATIENT OR PUBLIC CONTRIBUTION: This paper is a review of evaluation studies and did not involve patients or the public.

Executive summary of the KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease.

The Kidney Disease: Improving Global Outcomes (KDIGO) 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease for patients not receiving dialysis represents an update to the KDIGO 2012 guideline on this topic. Development of this guideline update followed a rigorous process of evidence review and appraisal. Guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence. The strength of recommendations is based on the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) approach. The scope includes topics covered in the original guideline, such as optimal blood pressure targets, lifestyle interventions, antihypertensive medications, and specific management in kidney transplant recipients and children. Some aspects of general and cardiovascular health, such as lipid and smoking management, are excluded. This guideline also introduces a chapter dedicated to proper blood pressure measurement since all large randomized trials targeting blood pressure with pivotal outcomes used standardized preparation and measurement protocols adhered to by patients and clinicians. Based on previous and new evidence, in particular the Systolic Blood Pressure Intervention Trial (SPRINT) results, we propose a systolic blood pressure target of less than 120 mm Hg using standardized office reading for most people with chronic kidney disease (CKD) not receiving dialysis, the exception being children and kidney transplant recipients. The goal of this guideline is to provide clinicians and patients a useful resource with actionable recommendations supplemented with practice points. The burden of the recommendations on patients and resources, public policy implications, and limitations of the evidence are taken into consideration. Lastly, knowledge gaps and recommendations for future research are provided.

Parents' and carers' views on factors contributing to the health and wellbeing of urban Aboriginal children.

OBJECTIVE: To identify and describe caregiver perspectives on factors important for the health and wellbeing of urban Aboriginal children. METHODS: Caregivers of Aboriginal children participating in the Study of Environment on Aboriginal Resilience and Child Health (SEARCH) were asked to describe the single most important factor that would help their children to be healthy and well. Responses were analysed using thematic and content analysis. RESULTS: Of the 626 carers in SEARCH, 425 (68%) provided a response. We identified 13 factors related to: loving family relationships, culturally competent healthcare, food security, active living, community services, education, social and emotional connectedness, safety, breaking cycles of disadvantage, housing availability and affordability, positive Aboriginal role models, strong culture, and carer wellbeing. CONCLUSIONS: Aligning with holistic concepts of health, caregivers believe that a broad range of child, family and environmental-level factors are needed to ensure the health and wellbeing of Aboriginal children. Implications for public health: This study highlights the importance of providing public health initiatives that enable equal access to the social determinants of health for carers of Aboriginal children. Affordable and adequate housing, food security, culturally appropriate healthcare, and family and community connectedness remain critical areas for targeted initiatives.

A Coaching Program to Improve Dietary Intake of Patients with CKD: ENTICE-CKD.

BACKGROUND AND OBJECTIVES: The dietary self-management of CKD is challenging. Telehealth interventions may provide an effective delivery method to facilitate sustained dietary change. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This pilot, randomized, controlled trial evaluated secondary and exploratory outcomes after a dietitian-led telehealth coaching intervention to improve diet quality in people with stage 3-4 CKD. The intervention group received phone calls every 2 weeks for 3 months (with concurrent, tailored text messages for 3 months), followed by 3 months of tailored text messages without telephone coaching, to encourage a diet consistent with CKD guidelines. The control group received usual care for 3 months, followed by nontailored, educational text messages for 3 months. RESULTS: Eighty participants (64% male), aged 62±12 years, were randomized to the intervention or control group. Telehealth coaching was safe, with no adverse events or changes to serum biochemistry at any time point. At 3 months, the telehealth intervention, compared with the control, had no detectable effect on overall diet quality on the Alternative Health Eating Index (3.2 points, 95% confidence interval, -1.3 to 7.7), nor at 6 months (0.5 points, 95% confidence interval, -4.6 to 5.5). There was no change in clinic BP at any time point in any group. There were significant improvements in several exploratory diet and clinical outcomes, including core food group consumption, vegetable servings, fiber intake, and body weight. CONCLUSIONS: Telehealth coaching was safe, but appeared to have no effect on the Alternative Healthy Eating Index or clinic BP. There were clinically significant changes in several exploratory diet and clinical outcomes, which require further investigation. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Evaluation of Individualized Telehealth Intensive Coaching to Promote Healthy Eating and Lifestyle in CKD (ENTICE-CKD), ACTRN12616001212448.

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.

Parenteral versus oral iron therapy for adults and children with chronic kidney disease.

BACKGROUND: The anaemia seen in chronic kidney disease (CKD) may be exacerbated by iron deficiency. Iron can be provided through different routes, with advantages and drawbacks of each route. It remains unclear whether the potential harms and additional costs of intravenous (IV) compared with oral iron are justified. This is an update of a review first published in 2012. OBJECTIVES: To determine the benefits and harms of IV iron supplementation compared with oral iron for anaemia in adults and children with CKD, including participants on dialysis, with kidney transplants and CKD not requiring dialysis. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 7 December 2018 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 in which IV and oral routes of iron administration were compared in adults and children with CKD. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study eligibility, risk of bias, and extracted data. Results were reported as risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes. For continuous outcomes the mean difference (MD) was used or standardised mean difference (SMD) if different scales had been used. Statistical analyses were performed using the random-effects model. Subgroup analysis and univariate meta-regression were performed to investigate between study differences. The certainty of the evidence was assessed using GRADE. MAIN RESULTS: We included 39 studies (3852 participants), 11 of which were added in this update. A low risk of bias was attributed to 20 (51%) studies for sequence generation, 14 (36%) studies for allocation concealment, 22 (56%) studies for attrition bias and 20 (51%) for selective outcome reporting. All studies were at a high risk of performance bias. However, all studies were considered at low risk of detection bias because the primary outcome in all studies was laboratory-based and unlikely to be influenced by lack of blinding.There is insufficient evidence to suggest that IV iron compared with oral iron makes any difference to death (all causes) (11 studies, 1952 participants: RR 1.12, 95% CI 0.64, 1.94) (absolute effect: 33 participants per 1000 with IV iron versus 31 per 1000 with oral iron), the number of participants needing to start dialysis (4 studies, 743 participants: RR 0.81, 95% CI 0.41, 1.61) or the number needing blood transfusions (5 studies, 774 participants: RR 0.86, 95% CI 0.55, 1.34) (absolute effect: 87 per 1,000 with IV iron versus 101 per 1,000 with oral iron). These analyses were assessed as having low certainty evidence. It is uncertain whether IV iron compared with oral iron reduces cardiovascular death because the certainty of this evidence was very low (3 studies, 206 participants: RR 1.71, 95% CI 0.41 to 7.18). Quality of life was reported in five studies with four reporting no difference between treatment groups and one reporting improvement in participants treated with IV iron.IV iron compared with oral iron may increase the numbers of participants, who experience allergic reactions or hypotension (15 studies, 2607 participants: RR 3.56, 95% CI 1.88 to 6.74) (absolute harm: 24 per 1000 with IV iron versus 7 per 1000) but may reduce the number of participants with all gastrointestinal adverse effects (14 studies, 1986 participants: RR 0.47, 95% CI 0.33 to 0.66) (absolute benefit: 150 per 1000 with IV iron versus 319 per 1000). These analyses were assessed as having low certainty evidence.IV iron compared with oral iron may increase the number of participants who achieve target haemoglobin (13 studies, 2206 participants: RR 1.71, 95% CI 1.43 to 2.04) (absolute benefit: 542 participants per 1,000 with IV iron versus 317 per 1000 with oral iron), increased haemoglobin (31 studies, 3373 participants: MD 0.72 g/dL, 95% CI 0.39 to 1.05); ferritin (33 studies, 3389 participants: MD 224.84 µg/L, 95% CI 165.85 to 283.83) and transferrin saturation (27 studies, 3089 participants: MD 7.69%, 95% CI 5.10 to 10.28), and may reduce the dose required of erythropoietin-stimulating agents (ESAs) (11 studies, 522 participants: SMD -0.72, 95% CI -1.12 to -0.31) while making little or no difference to glomerular filtration rate (8 studies, 1052 participants: 0.83 mL/min, 95% CI -0.79 to 2.44). All analyses were assessed as having low certainty evidence. There were moderate to high degrees of heterogeneity in these analyses but in meta-regression, definite reasons for this could not be determined. AUTHORS' CONCLUSIONS: The included studies provide low certainty evidence that IV iron compared with oral iron increases haemoglobin, ferritin and transferrin levels in CKD participants, increases the number of participants who achieve target haemoglobin and reduces ESA requirements. However, there is insufficient evidence to determine whether IV iron compared with oral iron influences death (all causes), cardiovascular death and quality of life though most studies reported only short periods of follow-up. Adverse effects were reported in only 50% of included studies. We therefore suggest that further studies that focus on patient-centred outcomes with longer follow-up periods are needed to determine if the use of IV iron is justified on the basis of reductions in ESA dose and cost, improvements in patient quality of life, and with few serious adverse effects.

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.

Research priorities for childhood chronic conditions: a workshop report.

BACKGROUND: Chronic conditions are the leading cause of mortality, morbidity and disability in children. However, children and caregivers are rarely involved in identifying research priorities, which may limit the value of research in supporting patient-centred practice and policy. OBJECTIVE: To identify priorities of patients, caregivers and health professionals for research in childhood chronic conditions and describe the reason for their choices. SETTING: An Australian paediatric hospital and health consumer organisations. METHODS: Recruited participants (n=73) included patients aged 8 to 14 years with a chronic condition (n=3), parents/caregivers of children aged 0 to 18 years with a chronic condition (n=19), representatives from consumer organisations (n=13) and health professionals including clinicians, researches (n=38) identified and discussed research priorities. Transcripts were thematically analysed. RESULTS: Seventy-eight research questions were identified. Five themes underpinned participants' priorities: maintaining a sense of normality (enabling participation in school, supporting social functioning, promoting understanding and acceptance), empowering self-management and partnership in care (overcoming communication barriers, gaining knowledge and skills, motivation for treatment adherence, making informed decisions, access and understanding of complementary and alternative therapies),strengthening ability to cope (learning to have a positive outlook, preparing for home care management, transitioning to adult services), broadening focus to family (supporting sibling well-being, parental resilience and financial loss, alleviating caregiver burden), and improving quality and scope of health and social care (readdressing variability and inequities, preventing disease complications and treatment side effects, identifying risk factors, improving long-term outcomes, harnessing technology, integrating multidisciplinary services). CONCLUSION: Research priorities identified by children, caregivers and health professionals emphasise a focus on life participation, psychosocial well-being, impact on family and quality of care. These priorities may be used by funding and policy organisations in establishing a paediatric research agenda.

Urinary tract infections in febrile children: Changing spectra of pathogenic bacteria and antibiotic susceptibilities?

AIM: To compare the spectra of pathogens causing febrile urinary tract infections (UTI) in children, treatment and antimicrobial susceptibility between 2004-2006 and 2007-2009. METHODS: UTI were identified from a cohort study of febrile children younger than 5 years presenting to a large tertiary children's hospital's emergency department with febrile illnesses. We compared pathogenic profiles, antibiotic choices and susceptibilities between 2004-2006 and 2007-2009 and tested for differences using χ2 and Fisher's exact tests. Antibiotic choice was compared with national therapeutic guideline recommendations for UTI in children (oral cotrimoxazole, cephalexin or amoxycillin-clavulanate or intravenous gentamicin plus ampicillin). RESULTS: There were 539 (2.71%) confirmed UTI from 19 889 febrile illnesses in 2004-2006 and 654 (2.99%) confirmed UTI from 21 846 febrile illnesses in 2007-2009. There was no difference in the frequency of the isolated pathogens by period: Escherichia coli (69.2 vs. 69.7%, P = 0.85), Proteus mirabilis (7.9 vs. 7.2%, P = 0.66) and Klebsiella species (6.2 vs. 4.7%, P = 0.25). National therapeutic guideline recommendations were followed in 277 of 539 (51.4%) versus 318 of 654 (48.6%) (P = 0.34). Oral antibiotics were given in 20.6 versus 18.9%. There was no difference in extended spectrum beta lactamase (1.5 vs. 1.7%, P = 0.82) or other antibiotic susceptibilities (e.g. E. coli: cotrimoxazole = 75.9 vs. 75.2%, P = 0.8). CONCLUSIONS: Overall, approximately 3% of febrile illnesses were due to UTI, but we found no change in the spectrum of pathogens or antibiotic susceptibility patterns, including extended-spectrum beta-lactamase, with time. In both time periods, treatment followed therapeutic guidelines approximately half the time, and most pathogens were susceptible to oral antibiotics, but they were infrequently used.

General practitioners' perspectives on the prevention of cardiovascular disease: systematic review and thematic synthesis of qualitative studies.

OBJECTIVE: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality globally, and prevention of CVD is a public health priority. This paper aims to describe the perspectives of general practitioners (GPs) on the prevention of CVD across different contexts. DESIGN: Systematic review and thematic synthesis of qualitative studies using the Enhancing Transparency of Reporting the Synthesis of Qualitative research (ENTREQ) framework. DATA SOURCES: MEDLINE, Embase, PsycINFO and CINAHL from database inception to April 2018. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included qualitative studies on the perspectives of GPs on CVD prevention. DATA EXTRACTION AND SYNTHESIS: We used HyperRESEARCH to code the primary papers and identified themes. RESULTS: We selected 34 studies involving 1223 participants across nine countries. We identified six themes: defining own primary role (duty to prescribe medication, refraining from risking patients' lives, mediating between patients and specialists, delegating responsibility to patients, providing holistic care); trusting external expertise (depending on credible evidence and opinion, entrusting care to other health professionals, integrating into patient context); motivating behavioural change for prevention (highlighting tangible improvements, negotiating patient acceptance, enabling autonomy and empowerment, harnessing the power of fear, disappointment with futility of advice); recognising and accepting patient capacities (ascertaining patient's drive for lifestyle change, conceding to ingrained habits, prioritising urgent comorbidities, tailoring to patient environment and literacy); avoiding overmedicalisation (averting long-term dependence on medications, preventing a false sense of security, minimising stress of sickness) and minimising economic burdens (avoiding unjustified costs to patients, delivering practice within budget, alleviating healthcare expenses). CONCLUSIONS: GPs sought to empower patients to prevent CVD, but consideration of patients' individual factors was challenging. Community-based strategies for assessing CVD risk involving other health professionals, and decision aids that address the individuality of the patient's health and environment, may support GPs in their decisions regarding CVD prevention.

Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD).

BACKGROUND: Phosphate binders are used to reduce positive phosphate balance and to lower serum phosphate levels for people with chronic kidney disease (CKD) with the aim to prevent progression of chronic kidney disease-mineral and bone disorder (CKD-MBD). This is an update of a review first published in 2011. OBJECTIVES: The aim of this review was to assess the benefits and harms of phosphate binders for people with CKD with particular reference to relevant biochemical end-points, musculoskeletal and cardiovascular morbidity, hospitalisation, and death. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 12 July 2018 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) or quasi-RCTs of adults with CKD of any GFR category comparing a phosphate binder to another phosphate binder, placebo or usual care to lower serum phosphate. Outcomes included all-cause and cardiovascular death, myocardial infarction, stroke, adverse events, vascular calcification and bone fracture, and surrogates for such outcomes including serum phosphate, parathyroid hormone (PTH), and FGF23. 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 were expressed as risk ratios (RR) for dichotomous outcomes together with 95% confidence intervals (CI) or mean differences (MD) or standardised MD (SMD) for continuous outcomes. MAIN RESULTS: We included 104 studies involving 13,744 adults. Sixty-nine new studies were added to this 2018 update.Most placebo or usual care controlled studies were among participants with CKD G2 to G5 not requiring dialysis (15/25 studies involving 1467 participants) while most head to head studies involved participants with CKD G5D treated with dialysis (74/81 studies involving 10,364 participants). Overall, seven studies compared sevelamer with placebo or usual care (667 participants), seven compared lanthanum to placebo or usual care (515 participants), three compared iron to placebo or usual care (422 participants), and four compared calcium to placebo or usual care (278 participants). Thirty studies compared sevelamer to calcium (5424 participants), and fourteen studies compared lanthanum to calcium (1690 participants). No study compared iron-based binders to calcium. The remaining studies evaluated comparisons between sevelamer (hydrochloride or carbonate), sevelamer plus calcium, lanthanum, iron (ferric citrate, sucroferric oxyhydroxide, stabilised polynuclear iron(III)-oxyhydroxide), calcium (acetate, ketoglutarate, carbonate), bixalomer, colestilan, magnesium (carbonate), magnesium plus calcium, aluminium hydroxide, sucralfate, the inhibitor of phosphate absorption nicotinamide, placebo, or usual care without binder. In 82 studies, treatment was evaluated among adults with CKD G5D treated with haemodialysis or peritoneal dialysis, while in 22 studies, treatment was evaluated among participants with CKD G2 to G5. The duration of study follow-up ranged from 8 weeks to 36 months (median 3.7 months). The sample size ranged from 8 to 2103 participants (median 69). The mean age ranged between 42.6 and 68.9 years.Random sequence generation and allocation concealment were low risk in 25 and 15 studies, respectively. Twenty-seven studies reported low risk methods for blinding of participants, investigators, and outcome assessors. Thirty-one studies were at low risk of attrition bias and 69 studies were at low risk of selective reporting bias.In CKD G2 to G5, compared with placebo or usual care, sevelamer, lanthanum, iron and calcium-based phosphate binders had uncertain or inestimable effects on death (all causes), cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification. Sevelamer may lead to constipation (RR 6.92, CI 2.24 to 21.4; low certainty) and lanthanum (RR 2.98, CI 1.21 to 7.30, moderate certainty) and iron-based binders (RR 2.66, CI 1.15 to 6.12, moderate certainty) probably increased constipation compared with placebo or usual care. Lanthanum may result in vomiting (RR 3.72, CI 1.36 to 10.18, low certainty). Iron-based binders probably result in diarrhoea (RR 2.81, CI 1.18 to 6.68, high certainty), while the risks of other adverse events for all binders were uncertain.In CKD G5D sevelamer may lead to lower death (all causes) (RR 0.53, CI 0.30 to 0.91, low certainty) and induce less hypercalcaemia (RR 0.30, CI 0.20 to 0.43, low certainty) when compared with calcium-based binders, and has uncertain or inestimable effects on cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification. The finding of lower death with sevelamer compared with calcium was present when the analysis was restricted to studies at low risk of bias (RR 0.50, CI 0.32 to 0.77). In absolute terms, sevelamer may lower risk of death (all causes) from 210 per 1000 to 105 per 1000 over a follow-up of up to 36 months, compared to calcium-based binders. Compared with calcium-based binders, lanthanum had uncertain effects with respect to all-cause or cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification and probably had reduced risks of treatment-related hypercalcaemia (RR 0.16, CI 0.06 to 0.43, low certainty). There were no head-to-head studies of iron-based binders compared with calcium. The paucity of placebo-controlled studies in CKD G5D has led to uncertainty about the effects of phosphate binders on patient-important outcomes compared with placebo.It is uncertain whether the effects of binders on clinically-relevant outcomes were different for patients who were and were not treated with dialysis in subgroup analyses. AUTHORS' CONCLUSIONS: In studies of adults with CKD G5D treated with dialysis, sevelamer may lower death (all causes) compared to calcium-based binders and incur less treatment-related hypercalcaemia, while we found no clinically important benefits of any phosphate binder on cardiovascular death, myocardial infarction, stroke, fracture or coronary artery calcification. The effects of binders on patient-important outcomes compared to placebo are uncertain. In patients with CKD G2 to G5, the effects of sevelamer, lanthanum, and iron-based phosphate binders on cardiovascular, vascular calcification, and bone outcomes compared to placebo or usual care, are also uncertain and they may incur constipation, while iron-based binders may lead to diarrhoea.

Children's experiences of congenital heart disease: a systematic review of qualitative studies.

We aimed to describe the experiences of children and adolescents with congenital heart disease (CHD). Electronic databases were searched until August 2016. Qualitative studies of children's perspectives on CHD were included. Data was extracted using thematic synthesis. From 44 studies from 12 countries involving 995 children, we identified 6 themes: disrupting normality (denying the diagnosis, oscillating between sickness and health, destabilizing the family dynamic), powerlessness in deteriorating health (preoccupation with impending mortality, vulnerability to catastrophic complications, exhaustion from medical testing), enduring medical ordeals (traumatized by invasive procedures, disappointed by treatment failure, displaced by transition, valuing empathy and continuity in care, overcoming uncertainty with information), warring with the body (losing stamina, distressing inability to participate in sport, distorted body image, testing the limits), hampering potential and goals (feeling disabled, unfair judgment and exclusion, difficulties with academic achievement, limiting attainment and maintenance of life milestones), and establishing one's own pace (demarcating disease from life, determination to survive, taking limitations in their stride, embracing the positives, finding personal enrichment, relying on social or spiritual support). CONCLUSION: Children with CHD feel vulnerable and burdened by debilitating physical symptoms, unpredictable complications, and discrimination. Clinicians may support patients by sharing recognition of these profound psychosocial consequences. What is Known: • CHD is associated with difficulties in learning and attention, school absenteeism, decreased endurance, poor body image, and peer socialization • What is lesser known is how young patients cope with the symptoms, prognostic uncertainty, and treatment burden What is New: • We found that children are challenged by lifestyle restrictions, fear of invasive procedures, impaired body image, discrimination, and uncertainty about the future. Feelings of disempowerment are intensified by the unpredictability of disease progression • Thus, strategies to improve outcomes include improved patient education on disease and lifestyle management and partnership with school teachers and counselors for unique psychosocial support.