Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes.

BACKGROUND: Diabetes is associated with high risks of premature chronic kidney disease (CKD), cardiovascular diseases, cardiovascular death and impaired quality of life. People with diabetes are more likely to develop kidney impairment, and approximately one in three adults with diabetes have CKD. People with CKD and diabetes experience a substantially higher risk of cardiovascular outcomes. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors have shown potential effects in preventing kidney and cardiovascular outcomes in people with CKD and diabetes. However, new trials are emerging rapidly, and evidence synthesis is essential to summarising cumulative evidence. OBJECTIVES: This review aimed to assess the benefits and harms of SGLT2 inhibitors for people with CKD and diabetes. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 17 November 2023 using a search strategy designed by an Information Specialist. Studies in the Register are continually identified through regular searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled studies were eligible if they evaluated SGLT2 inhibitors versus placebo, standard care or other glucose-lowering agents in people with CKD and diabetes. CKD includes all stages (from 1 to 5), including dialysis patients. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed the study 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). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The primary review outcomes were all-cause death, 3-point and 4-point major adverse cardiovascular events (MACE), fatal or nonfatal myocardial infarction (MI), fatal or nonfatal stroke, and kidney failure. MAIN RESULTS: Fifty-three studies randomising 65,241 people with CKD and diabetes were included. SGLT2 inhibitors with or without other background treatments were compared to placebo, standard care, sulfonylurea, dipeptidyl peptidase-4 (DPP-4) inhibitors, or insulin. In the majority of domains, the risks of bias in the included studies were low or unclear. No studies evaluated the treatment in children or in people treated with dialysis. No studies compared SGLT2 inhibitors with glucagon-like peptide-1 receptor agonists or tirzepatide. Compared to placebo, SGLT2 inhibitors decreased the risk of all-cause death (20 studies, 44,397 participants: RR 0.85, 95% CI 0.78 to 0.94; I2 = 0%; high certainty) and cardiovascular death (16 studies, 43,792 participants: RR 0.83, 95% CI 0.74 to 0.93; I2 = 29%; high certainty). Compared to placebo, SGLT2 inhibitors probably make little or no difference to the risk of fatal or nonfatal MI (2 studies, 13,726 participants: RR 0.95, 95% CI 0.80 to 1.14; I2 = 24%; moderate certainty), and fatal or nonfatal stroke (2 studies, 13,726 participants: RR 1.07, 95% CI 0.88 to 1.30; I2 = 0%; moderate certainty). Compared to placebo, SGLT2 inhibitors probably decrease 3-point MACE (7 studies, 38,320 participants: RR 0.89, 95% CI 0.81 to 0.98; I2 = 46%; moderate certainty), and 4-point MACE (4 studies, 23,539 participants: RR 0.82, 95% CI 0.70 to 0.96; I2 = 77%; moderate certainty), and decrease hospital admission due to heart failure (6 studies, 28,339 participants: RR 0.70, 95% CI 0.62 to 0.79; I2 = 17%; high certainty). Compared to placebo, SGLT2 inhibitors may decrease creatinine clearance (1 study, 132 participants: MD -2.63 mL/min, 95% CI -5.19 to -0.07; low certainty) and probably decrease the doubling of serum creatinine (2 studies, 12,647 participants: RR 0.70, 95% CI 0.56 to 0.89; I2 = 53%; moderate certainty). SGLT2 inhibitors decrease the risk of kidney failure (6 studies, 11,232 participants: RR 0.70, 95% CI 0.62 to 0.79; I2 = 0%; high certainty), and kidney composite outcomes (generally reported as kidney failure, kidney death with or without ≥ 40% decrease in estimated glomerular filtration rate (eGFR)) (7 studies, 36,380 participants: RR 0.68, 95% CI 0.59 to 0.78; I2 = 25%; high certainty) compared to placebo. Compared to placebo, SGLT2 inhibitors incur less hypoglycaemia (16 studies, 28,322 participants: RR 0.93, 95% CI 0.89 to 0.98; I2 = 0%; high certainty), and hypoglycaemia requiring third-party assistance (14 studies, 26,478 participants: RR 0.75, 95% CI 0.65 to 0.88; I2 = 0%; high certainty), and probably decrease the withdrawal from treatment due to adverse events (15 studies, 16,622 participants: RR 0.94, 95% CI 0.82 to 1.08; I2 = 16%; moderate certainty). The effects of SGLT2 inhibitors on eGFR, amputation and fracture were uncertain. No studies evaluated the effects of treatment on fatigue, life participation, or lactic acidosis. The effects of SGLT2 inhibitors compared to standard care alone, sulfonylurea, DPP-4 inhibitors, or insulin were uncertain. AUTHORS' CONCLUSIONS: SGLT2 inhibitors alone or added to standard care decrease all-cause death, cardiovascular death, and kidney failure and probably decrease major cardiovascular events while incurring less hypoglycaemia compared to placebo in people with CKD and diabetes.

Erythropoiesis-stimulating agents for anaemia in adults with chronic kidney disease: a network meta-analysis.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are commonly used to treat anaemia in people with chronic kidney disease (CKD). However, their use has been associated with cardiovascular events. This is an update of a Cochrane review first published in 2014. OBJECTIVES: To compare the efficacy and safety of ESAs (epoetin alfa, epoetin beta, darbepoetin alfa, methoxy polyethylene glycol-epoetin beta, and biosimilar ESAs against each other, placebo, or no treatment) to treat anaemia in adults with CKD. SEARCH METHODS: In this update, we searched the Cochrane Kidney and Transplant Register of Studies up to 29 April 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 Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) that included a comparison of an ESA (epoetin alfa, epoetin beta, darbepoetin alfa, methoxy polyethylene glycol-epoetin beta, a biosimilar epoetin or a biosimilar darbepoetin alfa) with another ESA, placebo or no treatment in adults with CKD were considered for inclusion. DATA COLLECTION AND ANALYSIS: Two independent authors screened the search results and extracted data. Data synthesis was performed using random-effects pairwise meta-analysis (expressed as odds ratios (OR) and their 95% confidence intervals (CI)) and network meta-analysis. We assessed for heterogeneity and inconsistency within meta-analyses using standard techniques and planned subgroup and meta-regression to explore sources of heterogeneity or inconsistency. We assessed certainty in treatment estimates for the primary outcomes (preventing blood transfusions and death (any cause)) using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Sixty-two new studies (9237 participants) were included in this update, so the review now includes 117 studies with 25,237 participants. Most studies were at high or unclear risk of bias in most methodological domains. Overall, results remain similar in this update compared to our previous review in 2014. For preventing blood transfusion, epoetin alfa (OR 0.28, 95% CI 0.13 to 0.61; low certainty evidence) and epoetin beta (OR 0.19, 95% CI 0.08 to 0.47; low certainty evidence) may be superior to placebo, and darbepoetin alfa was probably superior to placebo (OR 0.27, 95% CI 0.11 to 0.67; moderate certainty evidence). Methoxy polyethylene glycol-epoetin beta (OR 0.33, 95% CI 0.11 to 1.02; very low certainty evidence), a biosimilar epoetin (OR 0.34, 95% CI 0.11 to 1.03; very low certainty evidence) and a biosimilar darbepoetin alfa (OR 0.37, 95% CI 0.07 to 1.91; very low certainty evidence) had uncertain effects on preventing blood transfusion compared to placebo. The comparative effects of ESAs compared with another ESA on preventing blood transfusions were uncertain, in low to very low certainty evidence. Effects on death (any cause) were uncertain for epoetin alfa (OR 0.79, 95% CI 0.51 to 1.22; low certainty evidence), epoetin beta (OR 0.69, 95% CI 0.40 to 1.20; low certainty evidence), methoxy polyethylene glycol-epoetin beta (OR 1.07, 95% CI 0.67 to 1.71; very low certainty evidence), a biosimilar epoetin (OR 0.80, 95% CI 0.47 to 1.36; low certainty evidence) and a biosimilar darbepoetin alfa (OR 1.63, 95% CI 0.51 to 5.23; very low certainty evidence) compared to placebo. There was probably no difference between darbepoetin alfa and placebo on the odds of death (any cause) (OR 0.99, 95% CI 0.81 to 1.21; moderate certainty evidence). The comparative effects of ESAs compared with another ESA on death (any cause) were uncertain in low to very low certainty evidence. Epoetin beta probably increased the odds of hypertension when compared to placebo (OR 2.17, 95% CI 1.17 to 4.00; moderate certainty evidence). Compared to placebo, epoetin alfa (OR 2.10, 95% CI 1.22 to 3.59; very low certainty evidence), darbepoetin alfa (OR 1.88, 95% CI 1.12 to 3.14; low certainty evidence) and methoxy polyethylene glycol-epoetin beta (OR 1.98, 95% CI 1.05 to 3.74; low certainty evidence) may increase the odds of hypertension, but a biosimilar epoetin (OR 1.88, 95% CI 0.96 to 3.67; low certainty evidence) and biosimilar darbepoetin alfa (OR 1.98, 95% CI 0.84 to 4.66; low certainty evidence) had uncertain effects on hypertension. The comparative effects of all ESAs compared with another ESA, placebo or no treatment on cardiovascular death, myocardial infarction, stroke, vascular access thrombosis, kidney failure, and breathlessness were uncertain. Network analysis for fatigue was not possible due to sparse data.  AUTHORS' CONCLUSIONS: The comparative effects of different ESAs on blood transfusions, death (any cause and cardiovascular), major cardiovascular events, myocardial infarction, stroke, vascular access thrombosis, kidney failure, fatigue and breathlessness were uncertain.

ANTECEDENTES: Los fármacos estimulantes de la eritropoyesis (FEE) se suelen utilizar para tratar la anemia en personas con nefropatía crónica. Sin embargo, su uso se ha asociado a eventos cardiovasculares. Esta es una actualización de una revisión Cochrane publicada por primera vez en 2014. OBJETIVOS: Comparar la eficacia y la seguridad de los FEE (epoetina alfa, epoetina beta, darbepoetina alfa o metoxi­polietilenglicol epoetina beta y FEE biosimilares) entre sí, con placebo, o ningún tratamiento, para el tratamiento de la anemia en adultos con nefropatía crónica. MÉTODOS DE BÚSQUEDA: En esta actualización, a través del contacto con el documentalista, y con el uso de términos de búsqueda pertinentes para esta revisión, se realizaron búsquedas en el Registro de estudios del Grupo Cochrane de Riñón y trasplante (Cochrane Kidney and Transplant) hasta el 29 de abril de 2022. Los estudios en el registro se identifican mediante búsquedas en CENTRAL, MEDLINE y EMBASE, en resúmenes de congresos, en el portal de búsqueda de la Plataforma de registros internacionales de ensayos clínicos (ICTRP) y en ClinicalTrials.gov. CRITERIOS DE SELECCIÓN: Se consideraron para la inclusión los ensayos controlados aleatorizados (ECA) que incluían una comparación de un FEE (epoetina alfa, epoetina beta, darbepoetina alfa o metoxi­polietilenglicol epoetina beta, una epoetina biosimilar o una darbepoetina alfa biosimilar) con otro FEE, placebo o ningún tratamiento en adultos con NC. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores independientes examinaron los resultados de la búsqueda y extrajeron los datos. La síntesis de los datos se realizó mediante un metanálisis pareado de efectos aleatorios (expresada como odds ratio [OR] y sus intervalos de confianza [IC] del 95%) y un metanálisis en red. Se evaluó la heterogeneidad y la inconsistencia dentro de los metanálisis con técnicas estándares y se planeó crear subgrupos y una metarregresión para explorar las fuentes de heterogeneidad o la inconsistencia. Se evaluó la certeza en las estimaciones del tratamiento para los desenlaces principales (prevención de transfusiones de sangre y muerte [por cualquier causa]) mediante el método Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTADOS PRINCIPALES: En esta actualización se incluyeron 62 nuevos estudios (9237 participantes), por lo que la revisión incluye ahora 117 estudios con 25 237 participantes. La mayoría de los estudios tuvieron riesgo alto o incierto de sesgo en la mayoría de los dominios metodológicos. En general, los resultados siguen siendo similares en esta actualización en comparación con la revisión anterior de 2014. Para prevenir la transfusión de sangre, la epoetina alfa (OR 0,28; IC del 95%: 0,13 a 0,61; evidencia de certeza baja) y la epoetina beta (OR 0,19; IC del 95%: 0,08 a 0,47; evidencia de certeza baja) podrían ser superiores al placebo, y la darbepoetina alfa fue probablemente superior al placebo (OR 0,27; IC del 95%: 0,11 a 0,67; evidencia de certeza moderada). La metoxi­polietilenglicol epoetina beta (OR 0,33; IC del 95%: 0,11 a 1,02; evidencia de certeza muy baja), una epoetina biosimilar (OR 0,34; IC del 95%: 0,11 a 1,03; evidencia de certeza muy baja) y una darbepoetina alfa biosimilar (OR 0,37; IC del 95%: 0,07 a 1,91; evidencia de certeza muy baja) tuvieron efectos inciertos sobre la prevención de la transfusión de sangre en comparación con el placebo. Los efectos comparativos de los FEE comparados con otro FEE sobre la prevención de las transfusiones de sangre fueron inciertos, en evidencia de certeza baja a muy baja. Los efectos sobre la mortalidad (por cualquier causa) fueron inciertos para la epoetina alfa (OR 0,79; IC del 95%: 0,51 a 1,22; evidencia de certeza baja), la epoetina beta (OR 0,69; IC del 95%: 0,40 a 1,20; evidencia de certeza baja), la metoxi­polietilenglicol epoetina beta (OR 1,07; IC del 95%: 0,67 a 1,71; evidencia de certeza muy baja), una epoetina biosimilar (OR 0,80; IC del 95%: 0,47 a 1,36; evidencia de certeza baja) y una darbepoetina alfa biosimilar (OR 1,63; IC del 95%: 0,51 a 5,23; evidencia de certeza muy baja) en comparación con el placebo. Es probable que no hubiera diferencias entre la darbepoetina alfa y el placebo en las probabilidades de muerte (por cualquier causa) (OR 0,99; IC del 95%: 0,81 a 1,21; evidencia de certeza moderada). Los efectos comparativos de los FEE comparados con otro FEE sobre la mortalidad (por cualquier causa) fueron inciertos en evidencia de certeza baja a muy baja. Es probable que la epoetina beta aumentara el riesgo de hipertensión en comparación con el placebo (OR 2,17; IC del 95%: 1,17 a 4,00; evidencia de certeza moderada). En comparación con el placebo, la epoetina alfa (OR 2,10; IC del 95%: 1,22 a 3,59; evidencia de certeza muy baja), la epoetina beta (OR 1,88; IC del 95%: 1,12 a 3,14; evidencia de certeza baja) y la metoxi­polietilenglicol epoetina beta (OR 1,98; IC del 95%: 1,05 a 3,74; evidencia de certeza baja) podrían aumentar las probabilidades de hipertensión, pero una epoetina biosimilar (OR 1,88; IC del 95%: 0,96 a 3,67; evidencia de certeza baja) y una darbepoetina alfa biosimilar (OR 1,98; IC del 95%: 0,84 a 4,66; evidencia de certeza baja) tuvieron efectos inciertos sobre la hipertensión. Los efectos comparativos de todos los FEE comparados con otro FEE, placebo o ningún tratamiento sobre la mortalidad cardiovascular, el infarto de miocardio, el accidente cerebrovascular, la trombosis de acceso vascular, la insuficiencia renal y la disnea fueron inciertos. El análisis en red para el cansancio no fue posible debido a los pocos datos disponibles. CONCLUSIONES DE LOS AUTORES: Los efectos comparativos de los diferentes FEE sobre las transfusiones de sangre, la mortalidad (por cualquier causa y cardiovascular), los eventos cardiovasculares mayores, el infarto de miocardio, el accidente cerebrovascular, la trombosis de acceso vascular, la insuficiencia renal, el cansancio y la disnea fueron inciertos.

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.

HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis.

BACKGROUND: Cardiovascular disease is the most frequent cause of death in people with early stages of chronic kidney disease (CKD), and the absolute risk of cardiovascular events is similar to people with coronary artery disease. This is an update of a review first published in 2009 and updated in 2014, which included 50 studies (45,285 participants). OBJECTIVES: To evaluate the benefits and harms of statins compared with placebo, no treatment, standard care or another statin in adults with CKD not requiring dialysis. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 4 October 2023. 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. An updated search will be undertaken every three months. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs that compared the effects of statins with placebo, no treatment, standard care, or other statins, on death, cardiovascular events, kidney function, toxicity, and lipid levels in adults with CKD (estimated glomerular filtration rate (eGFR) 90 to 15 mL/min/1.73 m2) were included. DATA COLLECTION AND ANALYSIS: Two or more authors independently extracted data and assessed the study risk of bias. Treatment effects were expressed as mean difference (MD) for continuous outcomes and risk ratios (RR) for dichotomous benefits and harms with 95% confidence intervals (CI). The risk of bias was assessed using the Cochrane risk of bias tool, and the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: We included 63 studies (50,725 randomised participants); of these, 53 studies (42,752 participants) compared statins with placebo or no treatment. The median duration of follow-up was 12 months (range 2 to 64.8 months), the median dosage of statin was equivalent to 20 mg/day of simvastatin, and participants had a median eGFR of 55 mL/min/1.73 m2. Ten studies (7973 participants) compared two different statin regimens. We were able to meta-analyse 43 studies (41,273 participants). Most studies had limited reporting and hence exhibited unclear risk of bias in most domains. Compared with placebo or standard of care, statins prevent major cardiovascular events (14 studies, 36,156 participants: RR 0.72, 95% CI 0.66 to 0.79; I2 = 39%; high certainty evidence), death (13 studies, 34,978 participants: RR 0.83, 95% CI 0.73 to 0.96; I² = 53%; high certainty evidence), cardiovascular death (8 studies, 19,112 participants: RR 0.77, 95% CI 0.69 to 0.87; I² = 0%; high certainty evidence) and myocardial infarction (10 studies, 9475 participants: RR 0.55, 95% CI 0.42 to 0.73; I² = 0%; moderate certainty evidence). There were too few events to determine if statins made a difference in hospitalisation due to heart failure. Statins probably make little or no difference to stroke (7 studies, 9115 participants: RR 0.64, 95% CI 0.37 to 1.08; I² = 39%; moderate certainty evidence) and kidney failure (3 studies, 6704 participants: RR 0.98, 95% CI 0.91 to 1.05; I² = 0%; moderate certainty evidence) in people with CKD not requiring dialysis. Potential harms from statins were limited by a lack of systematic reporting. Statins compared to placebo may have little or no effect on elevated liver enzymes (7 studies, 7991 participants: RR 0.76, 95% CI 0.39 to 1.50; I² = 0%; low certainty evidence), withdrawal due to adverse events (13 studies, 4219 participants: RR 1.16, 95% CI 0.84 to 1.60; I² = 37%; low certainty evidence), and cancer (2 studies, 5581 participants: RR 1.03, 95% CI 0.82 to 1.30; I² = 0%; low certainty evidence). However, few studies reported rhabdomyolysis or elevated creatinine kinase; hence, we are unable to determine the effect due to very low certainty evidence. Statins reduce the risk of death, major cardiovascular events, and myocardial infarction in people with CKD who did not have cardiovascular disease at baseline (primary prevention). There was insufficient data to determine the benefits and harms of the type of statin therapy. AUTHORS' CONCLUSIONS: Statins reduce death and major cardiovascular events by about 20% and probably make no difference to stroke or kidney failure in people with CKD not requiring dialysis. However, due to limited reporting, the effect of statins on elevated creatinine kinase or rhabdomyolysis is unclear. Statins have an important role in the primary prevention of cardiovascular events and death in people who have CKD and do not require dialysis. Editorial note: This is a living systematic review. We will search for new evidence every three months and update the review when we identify relevant new evidence. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.

Antiplatelet agents for chronic kidney disease.

BACKGROUND: Antiplatelet agents are widely used to prevent cardiovascular events. The risks and benefits of antiplatelet agents may be different in people with chronic kidney disease (CKD) for whom occlusive atherosclerotic events are less prevalent, and bleeding hazards might be increased. This is an update of a review first published in 2013. OBJECTIVES: To evaluate the benefits and harms of antiplatelet agents in people with any form of CKD, including those with CKD not receiving renal replacement therapy, patients receiving any form of dialysis, and kidney transplant recipients. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 13 July 2021 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 selected randomised controlled trials of any antiplatelet agents versus placebo or no treatment, or direct head-to-head antiplatelet agent studies in people with CKD. Studies were included if they enrolled participants with CKD, or included people in broader at-risk populations in which data for subgroups with CKD could be disaggregated. DATA COLLECTION AND ANALYSIS: Four authors independently extracted data from primary study reports and any available supplementary information for study population, interventions, outcomes, and risks of bias. Risk ratios (RR) and 95% confidence intervals (CI) were calculated from numbers of events and numbers of participants at risk which were extracted from each included study. The reported RRs were extracted where crude event rates were not provided. Data were pooled using the random-effects model. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: We included 113 studies, enrolling 51,959 participants; 90 studies (40,597 CKD participants) compared an antiplatelet agent with placebo or no treatment, and 29 studies (11,805 CKD participants) directly compared one antiplatelet agent with another. Fifty-six new studies were added to this 2021 update. Seven studies originally excluded from the 2013 review were included, although they had a follow-up lower than two months. Random sequence generation and allocation concealment were at low risk of bias in 16 and 22 studies, respectively. Sixty-four studies reported low-risk methods for blinding of participants and investigators; outcome assessment was blinded in 41 studies. Forty-one studies were at low risk of attrition bias, 50 studies were at low risk of selective reporting bias, and 57 studies were at low risk of other potential sources of bias. Compared to placebo or no treatment, antiplatelet agents probably reduces myocardial infarction (18 studies, 15,289 participants: RR 0.88, 95% CI 0.79 to 0.99, I² = 0%; moderate certainty). Antiplatelet agents has uncertain effects on fatal or nonfatal stroke (12 studies, 10.382 participants: RR 1.01, 95% CI 0.64 to 1.59, I² = 37%; very low certainty) and may have little or no effect on death from any cause (35 studies, 18,241 participants: RR 0.94, 95 % CI 0.84 to 1.06, I² = 14%; low certainty). Antiplatelet therapy probably increases major bleeding in people with CKD and those treated with haemodialysis (HD) (29 studies, 16,194 participants: RR 1.35, 95% CI 1.10 to 1.65, I² = 12%; moderate certainty). In addition, antiplatelet therapy may increase minor bleeding in people with CKD and those treated with HD (21 studies, 13,218 participants: RR 1.55, 95% CI 1.27 to 1.90, I² = 58%; low certainty). Antiplatelet treatment may reduce early dialysis vascular access thrombosis (8 studies, 1525 participants) RR 0.52, 95% CI 0.38 to 0.70; low certainty). Antiplatelet agents may reduce doubling of serum creatinine in CKD (3 studies, 217 participants: RR 0.39, 95% CI 0.17 to 0.86, I² = 8%; low certainty). The treatment effects of antiplatelet agents on stroke, cardiovascular death, kidney failure, kidney transplant graft loss, transplant rejection, creatinine clearance, proteinuria, dialysis access failure, loss of primary unassisted patency, failure to attain suitability for dialysis, need of intervention and cardiovascular hospitalisation were uncertain. Limited data were available for direct head-to-head comparisons of antiplatelet drugs, including prasugrel, ticagrelor, different doses of clopidogrel, abciximab, defibrotide, sarpogrelate and beraprost. AUTHORS' CONCLUSIONS: Antiplatelet agents probably reduced myocardial infarction and increased major bleeding, but do not appear to reduce all-cause and cardiovascular death among people with CKD and those treated with dialysis. The treatment effects of antiplatelet agents compared with each other are uncertain.

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.

Incidence and Outcomes of COVID-19 in People With CKD: A Systematic Review and Meta-analysis.

RATIONALE & OBJECTIVE: Coronavirus disease 2019 (COVID-19) disproportionately affects people with chronic diseases such as chronic kidney disease (CKD). We assessed the incidence and outcomes of COVID-19 in people with CKD. STUDY DESIGN: Systematic review and meta-analysis by searching MEDLINE, EMBASE, and PubMed through February 2021. SETTING & STUDY POPULATIONS: People with CKD with or without COVID-19. SELECTION CRITERIA FOR STUDIES: Cohort and case-control studies. DATA EXTRACTION: Incidences of COVID-19, death, respiratory failure, dyspnea, recovery, intensive care admission, hospital admission, need for supplemental oxygen, hospital discharge, sepsis, short-term dialysis, acute kidney injury, and fatigue. ANALYTICAL APPROACH: Random-effects meta-analysis and evidence certainty adjudicated using an adapted version of GRADE (Grading of Recommendations Assessment, Development and Evaluation). RESULTS: 348 studies (382,407 participants with COVID-19 and CKD; 1,139,979 total participants with CKD) were included. Based on low-certainty evidence, the incidence of COVID-19 was higher in people with CKD treated with dialysis (105 per 10,000 person-weeks; 95% CI, 91-120; 95% prediction interval [PrI], 25-235; 59 studies; 468,233 participants) than in those with CKD not requiring kidney replacement therapy (16 per 10,000 person-weeks; 95% CI, 4-33; 95% PrI, 0-92; 5 studies; 70,683 participants) or in kidney or pancreas/kidney transplant recipients (23 per 10,000 person-weeks; 95% CI, 18-30; 95% PrI, 2-67; 29 studies; 120,281 participants). Based on low-certainty evidence, the incidence of death in people with CKD and COVID-19 was 32 per 1,000 person-weeks (95% CI, 30-35; 95% PrI, 4-81; 229 studies; 70,922 participants), which may be higher than in people with CKD without COVID-19 (incidence rate ratio, 10.26; 95% CI, 6.78-15.53; 95% PrI, 2.62-40.15; 4 studies; 18,347 participants). LIMITATIONS: Analyses were generally based on low-certainty evidence. Few studies reported outcomes in people with CKD without COVID-19 to calculate the excess risk attributable to COVID-19, and potential confounders were not adjusted for in most studies. CONCLUSIONS: The incidence of COVID-19 may be higher in people receiving maintenance dialysis than in those with CKD not requiring kidney replacement therapy or those who are kidney or pancreas/kidney transplant recipients. People with CKD and COVID-19 may have a higher incidence of death than people with CKD without COVID-19.

Dietary Patterns and Mortality in a Multinational Cohort of Adults Receiving Hemodialysis.

RATIONALE & OBJECTIVE: Clinical practice guidelines for dietary intake in hemodialysis focus on individual nutrients. Little is known about associations of dietary patterns with survival. We evaluated the associations of dietary patterns with cardiovascular and all-cause mortality among adults treated by hemodialysis. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 8,110 of 9,757 consecutive adults on hemodialysis (January 2014 to June 2017) treated in a multinational private dialysis network and with analyzable dietary data. EXPOSURES: Data-driven dietary patterns based on the GA2LEN food frequency questionnaire. Participants received a score for each identified pattern, with higher scores indicating closer resemblance of their diet to the identified pattern. Quartiles of standardized pattern scores were used as primary exposures. OUTCOMES: Cardiovascular and all-cause mortality. ANALYTICAL APPROACH: Principal components analysis with varimax rotation to identify common dietary patterns. Adjusted proportional hazards regression analyses with country as a random effect to estimate the associations between dietary pattern scores and mortality. Associations were expressed as adjusted HRs with 95% CIs, using the lowest quartile score as reference. RESULTS: During a median follow-up of 2.7 years (18,666 person-years), there were 2,087 deaths (958 cardiovascular). 2 dietary patterns, "fruit and vegetable" and "Western," were identified. For the fruit and vegetable dietary pattern score, adjusted HRs, in ascending quartiles, were 0.94 (95% CI, 0.76-1.15), 0.83 (95% CI, 0.66-1.06), and 0.91 (95% CI, 0.69-1.21) for cardiovascular mortality and 0.95 (95% CI, 0.83-1.09), 0.84 (95% CI, 0.71-0.99), and 0.87 (95% CI, 0.72-1.05) for all-cause mortality. For the Western dietary pattern score, the corresponding estimates were 1.10 (95% CI, 0.90-1.35), 1.11 (95% CI, 0.87-1.41), and 1.09 (95% CI, 0.80-1.49) for cardiovascular mortality and 1.01 (95% CI, 0.88-1.16), 1.00 (95% CI, 0.85-1.18), and 1.14 (95% CI, 0.93-1.41) for all-cause mortality. LIMITATIONS: Self-reported food frequency questionnaire, data-driven approach. CONCLUSIONS: These findings did not confirm an association between mortality among patients receiving long-term hemodialysis and the extent to which dietary patterns were either high in fruit and vegetables or consistent with a Western diet.

Potassium binders for chronic hyperkalaemia in people with chronic kidney disease.

BACKGROUND: Hyperkalaemia is a common electrolyte abnormality caused by reduced renal potassium excretion in patients with chronic kidney diseases (CKD). Potassium binders, such as sodium polystyrene sulfonate and calcium polystyrene sulfonate, are widely used but may lead to constipation and other adverse gastrointestinal (GI) symptoms, reducing their tolerability. Patiromer and sodium zirconium cyclosilicate are newer ion exchange resins for treatment of hyperkalaemia which may cause fewer GI side-effects. Although more recent studies are focusing on clinically-relevant endpoints such as cardiac complications or death, the evidence on safety is still limited. Given the recent expansion in the available treatment options, it is appropriate to review the evidence of effectiveness and tolerability of all potassium exchange resins among people with CKD, with the aim to provide guidance to consumers, practitioners, and policy-makers. OBJECTIVES: To assess the benefits and harms of potassium binders for treating chronic hyperkalaemia among adults and children with CKD. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 10 March 2020 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: Randomised controlled trials (RCTs) and quasi-randomised controlled studies (quasi-RCTs) evaluating potassium binders for chronic hyperkalaemia administered in adults and children with CKD. DATA COLLECTION AND ANALYSIS: Two authors independently assessed risks of bias and extracted data. Treatment estimates were summarised by random effects meta-analysis and expressed as relative risk (RR) or mean difference (MD), with 95% confidence interval (CI). Evidence certainty was assessed using GRADE processes. MAIN RESULTS: Fifteen studies, randomising 1849 adult participants were eligible for inclusion. Twelve studies involved participants with CKD (stages 1 to 5) not requiring dialysis and three studies were among participants treated with haemodialysis. Potassium binders included calcium polystyrene sulfonate, sodium polystyrene sulfonate, patiromer, and sodium zirconium cyclosilicate. A range of routes, doses, and timing of drug administration were used. Study duration varied from 12 hours to 52 weeks (median 4 weeks). Three were cross-over studies. The mean study age ranged from 53.1 years to 73 years. No studies evaluated treatment in children. Some studies had methodological domains that were at high or unclear risks of bias, leading to low certainty in the results. Studies were not designed to measure treatment effects on cardiac arrhythmias or major GI symptoms. Ten studies (1367 randomised participants) compared a potassium binder to placebo. The certainty of the evidence was low for all outcomes. We categorised treatments in newer agents (patiromer or sodium zirconium cyclosilicate) and older agents (calcium polystyrene sulfonate and sodium polystyrene sulfonate). Patiromer or sodium zirconium cyclosilicate may make little or no difference to death (any cause) (4 studies, 688 participants: RR 0.69, 95% CI 0.11, 4.32; I2 = 0%; low certainty evidence) in CKD. The treatment effect of older potassium binders on death (any cause) was unknown. One cardiovascular death was reported with potassium binder in one study, showing that there was no difference between patiromer or sodium zirconium cyclosilicate and placebo for cardiovascular death in CKD and HD. There was no evidence of a difference between patiromer or sodium zirconium cyclosilicate and placebo for health-related quality of life (HRQoL) at the end of treatment (one study) in CKD or HD. Potassium binders had uncertain effects on nausea (3 studies, 229 participants: RR 2.10, 95% CI 0.65, 6.78; I2 = 0%; low certainty evidence), diarrhoea (5 studies, 720 participants: RR 0.84, 95% CI 0.47, 1.48; I2 = 0%; low certainty evidence), and vomiting (2 studies, 122 participants: RR 1.72, 95% CI 0.35 to 8.51; I2 = 0%; low certainty evidence) in CKD. Potassium binders may lower serum potassium levels (at the end of treatment) (3 studies, 277 participants: MD -0.62 mEq/L, 95% CI -0.97, -0.27; I2 = 92%; low certainty evidence) in CKD and HD. Potassium binders had uncertain effects on constipation (4 studies, 425 participants: RR 1.58, 95% CI 0.71, 3.52; I2 = 0%; low certainty evidence) in CKD. Potassium binders may decrease systolic blood pressure (BP) (2 studies, 369 participants: MD -3.73 mmHg, 95%CI -6.64 to -0.83; I2 = 79%; low certainty evidence) and diastolic BP (one study) at the end of the treatment. No study reported outcome data for cardiac arrhythmias or major GI events. Calcium polystyrene sulfonate may make little or no difference to serum potassium levels at end of treatment, compared to sodium polystyrene sulfonate (2 studies, 117 participants: MD 0.38 mEq/L, 95% CI -0.03 to 0.79; I2 = 42%, low certainty evidence). There was no evidence of a difference in systolic BP (one study), diastolic BP (one study), or constipation (one study) between calcium polystyrene sulfonate and sodium polystyrene sulfonate. There was no difference between high-dose and low-dose patiromer for death (sudden death) (one study), stroke (one study), myocardial infarction (one study), or constipation (one study). The comparative effects whether potassium binders were administered with or without food, laxatives, or sorbitol, were very uncertain with insufficient data to perform meta-analysis. AUTHORS' CONCLUSIONS: Evidence supporting clinical decision-making for different potassium binders to treat chronic hyperkalaemia in adults with CKD is of low certainty; no studies were identified in children. Available studies have not been designed to measure treatment effects on clinical outcomes such as cardiac arrhythmias or major GI symptoms. This review suggests the need for a large, adequately powered study of potassium binders versus placebo that assesses clinical outcomes of relevance to patients, clinicians and policy-makers. This data could be used to assess cost-effectiveness, given the lack of definitive studies and the clinical importance of potassium binders for chronic hyperkalaemia in people with CKD.

Immunosuppressive agents for treating IgA nephropathy.

BACKGROUND: IgA nephropathy is the most common glomerulonephritis world-wide. IgA nephropathy causes end-stage kidney disease (ESKD) in 15% to 20% of affected patients within 10 years and in 30% to 40% of patients within 20 years from the onset of disease. This is an update of a Cochrane review first published in 2003 and updated in 2015. OBJECTIVES: To determine the benefits and harms of immunosuppression strategies for the treatment of IgA nephropathy. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 9 September 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 treatment for IgA nephropathy in adults and children and that compared immunosuppressive agents with placebo, no treatment, or other immunosuppressive or non-immunosuppressive agents. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study risk of bias and extracted data. Estimates of treatment effect were summarised using random effects meta-analysis. Treatment effects were expressed as relative risk (RR) and 95% confidence intervals (95% CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Risks of bias were assessed using the Cochrane tool. Evidence certainty was evaluated using GRADE methodology. MAIN RESULTS: Fifty-eight studies involving 3933 randomised participants were included. Six studies involving children were eligible. Disease characteristics (kidney function and level of proteinuria) were heterogeneous across studies. Studies evaluating steroid therapy generally included patients with protein excretion of 1 g/day or more. Risk of bias within the included studies was generally high or unclear for many of the assessed methodological domains. In patients with IgA nephropathy and proteinuria > 1 g/day, steroid therapy given for generally two to four months with a tapering course probably prevents the progression to ESKD compared to placebo or standard care (8 studies; 741 participants: RR 0.39, 95% CI 0.23 to 0.65; moderate certainty evidence). Steroid therapy may induce complete remission (4 studies, 305 participants: RR 1.76, 95% CI 1.03 to 3.01; low certainty evidence), prevent doubling of serum creatinine (SCr) (7 studies, 404 participants: RR 0.43, 95% CI 0.29 to 0.65; low certainty evidence), and may lower urinary protein excretion (10 studies, 705 participants: MD -0.58 g/24 h, 95% CI -0.84 to -0.33;low certainty evidence). Steroid therapy had uncertain effects on glomerular filtration rate (GFR), death, infection and malignancy. The risk of adverse events with steroid therapy was uncertain due to heterogeneity in the type of steroid treatment used and the rarity of events. Cytotoxic agents (azathioprine (AZA) or cyclophosphamide (CPA) alone or with concomitant steroid therapy had uncertain effects on ESKD (7 studies, 463 participants: RR 0.63, 95% CI 0.33 to 1.20; low certainty evidence), complete remission (5 studies; 381 participants: RR 1.47, 95% CI 0.94 to 2.30; very low certainty evidence), GFR (any measure), and protein excretion. Doubling of serum creatinine was not reported. Mycophenolate mofetil (MMF) had uncertain effects on the progression to ESKD, complete remission, doubling of SCr, GFR, protein excretion, infection, and malignancy. Death was not reported. Calcineurin inhibitors compared with placebo or standard care had uncertain effects on complete remission, SCr, GFR, protein excretion, infection, and malignancy. ESKD and death were not reported. Mizoribine administered with renin-angiotensin system inhibitor treatment had uncertain effects on progression to ESKD, complete remission, GFR, protein excretion, infection, and malignancy. Death and SCr were not reported. Leflunomide followed by a tapering course with oral prednisone compared to prednisone had uncertain effects on the progression to ESKD, complete remission, doubling of SCr, GFR, protein excretion, and infection. Death and malignancy were not reported. Effects of other immunosuppressive regimens (including steroid plus non-immunosuppressive agents or mTOR inhibitors) were inconclusive primarily due to insufficient data from the individual studies in low or very low certainty evidence. The effects of treatments on death, malignancy, reduction in GFR at least of 25% and adverse events were very uncertain. Subgroup analyses to determine the impact of specific patient characteristics such as ethnicity or disease severity on treatment effectiveness were not possible. AUTHORS' CONCLUSIONS: In moderate certainty evidence, corticosteroid therapy probably prevents decline in GFR or doubling of SCr in adults and children with IgA nephropathy and proteinuria. Evidence for treatment effects of immunosuppressive agents on death, infection, and malignancy is generally sparse or low-quality. Steroid therapy has uncertain adverse effects due to a paucity of studies. Available studies are few, small, have high risk of bias and generally do not systematically identify treatment-related harms. Subgroup analyses to identify specific patient characteristics that might predict better response to therapy were not possible due to a lack of studies. There is no evidence that other immunosuppressive agents including CPA, AZA, or MMF improve clinical outcomes in IgA nephropathy.

Interventions for improving sleep quality in people with chronic kidney disease.

BACKGROUND: Sleep disorders are commonly experienced by people with chronic kidney disease (CKD). Several approaches for improving sleep quality are used in clinical practice including relaxation techniques, exercise, acupressure, and medication. OBJECTIVES: To assess the effectiveness and associated adverse events of interventions designed to improve sleep quality among adults and children 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 Register of Studies up to 8 October 2018 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-randomised RCTs of any intervention in which investigators reported effects on sleep quality. Two authors independently screened titles and abstracts of identified records. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias for included studies. The primary outcomes were sleep quality, sleep onset latency, sleep duration, sleep interruption, and sleep efficiency. Risks of bias were assessed using the Cochrane tool. Evidence certainty was assessed using the GRADE approach. We calculated treatment estimates as risk ratios (RR) for dichotomous outcomes or mean difference (MD) or standardised MD (SMD) for continuous outcomes to account for heterogeneity in measures of sleep quality. MAIN RESULTS: Sixty-seven studies involving 3427 participants met the eligibility criteria. Thirty-six studies involving 2239 participants were included in meta-analyses. Follow-up for clinical outcomes ranged between 0.3 and 52.8 weeks (median 5 weeks). Interventions included relaxation techniques, exercise, acupressure, cognitive-behavioural therapy (CBT), educational interventions, benzodiazepine treatment, dopaminergic agonists, telephone support, melatonin, reflexology, light therapy, different forms of peritoneal dialysis, music, aromatherapy, and massage. Incomplete reporting of key methodological details resulted in uncertain risk of bias in many studies.In very low certainty evidence relaxation techniques had uncertain effects on sleep quality and duration, health-related quality of life (HRQoL), depression, anxiety, and fatigue. Studies were not designed to evaluate the effects of relaxation on sleep latency or hospitalisation. Exercise had uncertain effects on sleep quality (SMD -1.10, 95% CI -2.26 to 0.05; I2 = 90%; 5 studies, 165 participants; very low certainty evidence). Exercise probably decreased depression (MD -9.05, 95% CI -13.72 to -4.39; I2 = 0%; 2 studies, 46 participants; moderate certainty evidence) and fatigue (SMD -0.68, 95% CI -1.07 to -0.29; I2 = 0%; 2 studies, 107 participants; moderate certainty evidence). Compared with no acupressure, acupressure had uncertain effects on sleep quality (Pittsburgh Sleep Quality Index (PSQI) scale 0 - 21) (MD -1.27, 95% CI -2.13 to -0.40; I2 = 89%; 6 studies, 367 participants: very low certainty evidence). Acupressure probably slightly improved sleep latency (scale 0 - 3) (MD -0.59, 95% CI -0.92 to -0.27; I2 = 0%; 3 studies, 173 participants; moderate certainty evidence) and sleep time (scale 0 - 3) (MD -0.60, 95% CI -1.12 to -0.09; I2 = 68%; 3 studies, 173 participants; moderate certainty evidence), although effects on sleep disturbance were uncertain as the evidence certainty was very low (scale 0 - 3) (MD -0.49, 95% CI -1.16 to 0.19; I2 = 97%). In moderate certainty evidence, acupressure probably decrease fatigue (MD -1.07, 95% CI -1.67 to -0.48; I2 = 0%; 2 studies, 137 participants). Acupressure had uncertain effects on depression (MD -3.65, 95% CI -7.63 to 0.33; I2 = 27%; 2 studies, 137 participants; very low certainty evidence) while studies were not designed to evaluate the effect of acupressure on HRQoL, anxiety, or hospitalisation. It was uncertain whether acupressure compared with sham acupressure improved sleep quality (PSQI scale 0 to 21) because the certainty of the evidence was very low (MD -2.25, 95% CI -6.33 to 1.82; I2 = 96%; 2 studies, 129 participants), but total sleep time may have been improved (SMD -0.34, 95% CI -0.73 to 0.04; I2 = 0%; 2 studies, 107 participants; low certainty evidence). 2 =2 =There were no studies designed to directly examine and/or correlate efficacy of any interventions aimed at improving sleep that may have been attempted for the spectrum of sleep disordered breathing. No studies reported treatment effects for children. Adverse effects of therapies were very uncertain. AUTHORS' CONCLUSIONS: The evidence base for improving sleep quality and related outcomes for adults and children with CKD is sparse. Relaxation techniques and exercise had uncertain effects on sleep outcomes. Acupressure may improve sleep latency and duration, although these findings are based on few studies. The effects of acupressure were not confirmed in studies in which sham acupressure was used as the control. Given the very low certainly evidence, future research will very likely change the evidence base. Based on the importance of symptom management to patients, caregivers and clinicians, future studies of sleep interventions among people with CKD should be a priority.

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.

The Association of Mediterranean and DASH Diets with Mortality in Adults on Hemodialysis: The DIET-HD Multinational Cohort Study.

Background Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets associate with lower cardiovascular and all-cause mortality in the general population, but the benefits for patients on hemodialysis are uncertain.Methods Mediterranean and DASH diet scores were derived from the GA2LEN Food Frequency Questionnaire within the DIET-HD Study, a multinational cohort study of 9757 adults on hemodialysis. We conducted adjusted Cox regression analyses clustered by country to evaluate the association between diet score tertiles and all-cause and cardiovascular mortality (the lowest tertile was the reference category).Results During the median 2.7-year follow-up, 2087 deaths (829 cardiovascular deaths) occurred. The adjusted hazard ratios (95% confidence intervals) for the middle and highest Mediterranean diet score tertiles were 1.20 (1.01 to 1.41) and 1.14 (0.90 to 1.43), respectively, for cardiovascular mortality and 1.10 (0.99 to 1.22) and 1.01 (0.88 to 1.17), respectively, for all-cause mortality. Corresponding estimates for the same DASH diet score tertiles were 1.01 (0.85 to 1.21) and 1.19 (0.99 to 1.43), respectively, for cardiovascular mortality and 1.03 (0.92 to 1.15) and 1.00 (0.89 to 1.12), respectively, for all-cause mortality. The association between DASH diet score and all-cause death was modified by age (P=0.03); adjusted hazard ratios for the middle and highest DASH diet score tertiles were 1.02 (0.81 to 1.29) and 0.70 (0.53 to 0.94), respectively, for younger patients (≤60 years old) and 1.05 (0.93 to 1.19) and 1.08 (0.95 to 1.23), respectively, for older patients.Conclusions Mediterranean and DASH diets did not associate with cardiovascular or total mortality in hemodialysis.

Continuous erythropoiesis receptor activator (CERA) for the anaemia of chronic kidney disease.

BACKGROUND: Continuous erythropoiesis receptor activator (CERA) is a newer, longer acting ESA which might be preferred to other ESAs (epoetin or darbepoetin) based on its lower frequency of administration. Different dosing requirements and molecular characteristics of CERA compared with other ESAs may lead to different health outcomes (mortality, cardiovascular events, quality of life) in people with anaemia and chronic kidney disease (CKD). OBJECTIVES: To assess benefits and harms of CERA compared with other epoetins (darbepoetin alfa and epoetin alfa or beta) or placebo/no treatment or CERA with differing strategy of administration for anaemia in individuals with CKD. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register to 13 June 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: We included randomised controlled trials (RCTs) of at least three months' duration, comparing CERA with a different ESA (darbepoetin alfa or epoetin alfa or beta) or placebo or standard care or versus CERA with different strategies for administration in people with any stage of CKD. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent investigators. We summarised patient-centred outcomes (all-cause and cardiovascular mortality, major adverse cardiovascular events, red cell blood transfusion, iron therapy, cancer, hypertension, seizures, dialysis vascular access thrombosis, drug injection-related events, hyperkalaemia and health-related quality of life and haemoglobin levels) using random effects meta-analysis. Treatment estimates were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean differences or standardized mean difference with 95% CI for continuous outcomes. MAIN RESULTS: We included 27 studies involving 5410 adults with CKD. Seven studies (1273 participants) involved people not requiring dialysis, 19 studies (4209 participants) involved people treated with dialysis and one study (71 participants) evaluated treatment in recipients of a kidney transplant. Treatment was given for 24 weeks on average. No data were available for children with CKD. Studies were generally at high or unclear risk of bias from allocation concealment and blinding of outcomes. Only two studies masked participants and investigators to treatment allocation. One study compared CERA with placebo, nine studies CERA with epoetin alfa or beta, nine studies CERA with darbepoetin alfa, and two studies compared CERA with epoetin alfa or beta and darbepoetin alfa. Three studies assessed the effects of differing frequencies of CERA administration and five assessed differing CERA doses.There was low certainty evidence that CERA had little or no effects on mortality (RR 1.07, 95% CI 0.73 to 1.57; RR 1.11, 95% CI 0.75 to 1.65), major adverse cardiovascular events (RR 5.09, 95% CI 0.25 to 105.23; RR 5.56, 95% CI 0.99 to 31.30), hypertension (RR 1.01, 95% CI 0.75 to 1.37; RR 1.00, 95% CI 0.79 to 1.28), need for blood transfusion (RR 1.02, 95% CI 0.72 to 1.46; RR 0.94, 95% CI 0.55 to 1.61), or additional iron therapy (RR 1.03, 95% CI 0.91 to 1.15; RR 0.99, 95% CI 0.95 to 1.03) compared to epoetin alfa/beta or darbepoetin alfa respectively. There was insufficient evidence to compare the effect of CERA to placebo on clinical outcomes. Only one low quality study reported that CERA compared to placebo might lead to little or no difference in the risk of major cardiovascular events (RR 2.97, 95% CI 0.31 to 28.18) and hypertension ((RR 0.73, 95% CI 0.35 to 1.52). There was low certainty evidence that different doses (higher versus lower) or frequency (twice versus once monthly) of CERA administration had little or no different effect on all-cause mortality (RR 3.95, 95% CI 0.17 to 91.61; RR 0.97, 95% CI 0.56 to 1.66), hypertension (RR 0.45, 95% CI 0.08 to 2.52; RR 0.85, 95% CI 0.60 to 1.21), and blood cell transfusions (RR 4.16, 95% CI 0.89 to 19.53; RR 0.91, 95% CI 0.51 to 1.62). No studies reported comparative treatment effects of different ESAs on health-related quality of life. AUTHORS' CONCLUSIONS: There is low certainty evidence that CERA has little or no effects on patient-centred outcomes compared with placebo, epoetin alfa or beta or darbepoetin alfa for adults with CKD. The effects of CERA among children who have CKD have not studied in RCTs.

Glucose targets for preventing diabetic kidney disease and its progression.

BACKGROUND: Diabetes is the leading cause of end-stage kidney disease (ESKD) around the world. Blood pressure lowering and glucose control are used to reduce diabetes-associated disability including kidney failure. However there is a lack of an overall evidence summary of the optimal target range for blood glucose control to prevent kidney failure. OBJECTIVES: To evaluate the benefits and harms of intensive (HbA1c < 7% or fasting glucose levels < 120 mg/dL versus standard glycaemic control (HbA1c ≥ 7% or fasting glucose levels ≥ 120 mg/dL for preventing the onset and progression of kidney disease among adults with diabetes. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register up to 31 March 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 evaluating glucose-lowering interventions in which people (aged 14 year or older) with type 1 or 2 diabetes with and without kidney disease were randomly allocated to tight glucose control or less stringent blood glucose targets. DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for eligibility and risks of bias, extracted data and checked the processes for accuracy. Outcomes were mortality, cardiovascular complications, doubling of serum creatinine (SCr), ESKD and proteinuria. Confidence in the evidence was assessing using GRADE. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. MAIN RESULTS: Fourteen studies involving 29,319 people with diabetes were included and 11 studies involving 29,141 people were included in our meta-analyses. Treatment duration was 56.7 months on average (range 6 months to 10 years). Studies included people with a range of kidney function. Incomplete reporting of key methodological details resulted in uncertain risks of bias in many studies. Using GRADE assessment, we had moderate confidence in the effects of glucose lowering strategies on ESKD, all-cause mortality, myocardial infarction, and progressive protein leakage by kidney disease and low or very low confidence in effects of treatment on death related to cardiovascular complications and doubling of serum creatinine (SCr).For the primary outcomes, tight glycaemic control may make little or no difference to doubling of SCr compared with standard control (4 studies, 26,874 participants: RR 0.84, 95% CI 0.64 to 1.11; I2= 73%, low certainty evidence), development of ESKD (4 studies, 23,332 participants: RR 0.62, 95% CI 0.34 to 1.12; I2= 52%; low certainty evidence), all-cause mortality (9 studies, 29,094 participants: RR 0.99, 95% CI 0.86 to 1.13; I2= 50%; moderate certainty evidence), cardiovascular mortality (6 studies, 23,673 participants: RR 1.19, 95% CI 0.73 to 1.92; I2= 85%; low certainty evidence), or sudden death (4 studies, 5913 participants: RR 0.82, 95% CI 0.26 to 2.57; I2= 85%; very low certainty evidence). People who received treatment to achieve tighter glycaemic control probably experienced lower risks of non-fatal myocardial infarction (5 studies, 25,596 participants: RR 0.82, 95% CI 0.67 to 0.99; I2= 46%, moderate certainty evidence), onset of microalbuminuria (4 studies, 19,846 participants: RR 0.82, 95% CI 0.71 to 0.93; I2= 61%, moderate certainty evidence), and progression of microalbuminuria (5 studies, 13,266 participants: RR 0.59, 95% CI 0.38 to 0.93; I2= 75%, moderate certainty evidence). In absolute terms, tight versus standard glucose control treatment in 1,000 adults would lead to between zero and two people avoiding non-fatal myocardial infarction, while seven adults would avoid experiencing new-onset albuminuria and two would avoid worsening albuminuria. AUTHORS' CONCLUSIONS: This review suggests that people who receive intensive glycaemic control for treatment of diabetes had comparable risks of kidney failure, death and major cardiovascular events as people who received less stringent blood glucose control, while experiencing small clinical benefits on the onset and progression of microalbuminuria and myocardial infarction. The adverse effects of glycaemic management are uncertain. Based on absolute treatment effects, the clinical impact of targeting an HbA1c < 7% or blood glucose < 6.6 mmol/L is unclear and the potential harms of this treatment approach are largely unmeasured.

Antidepressants for treating depression in adults with end-stage kidney disease treated with dialysis.

BACKGROUND: Depression affects approximately one-quarter of people treated with dialysis and is considered an important research uncertainty by patients and health professionals. Treatment for depression in dialysis patients may have different benefits and harms compared to the general population due to different clearances of antidepressant medication and the severity of somatic symptoms associated with end-stage kidney disease (ESKD). Guidelines suggest treatment of depression in dialysis patients with pharmacological therapy, preferably a selective serotonin reuptake inhibitor. This is an update of a review first published in 2005. OBJECTIVES: To evaluate the benefit and harms of antidepressants for treating depression in adults with ESKD treated with dialysis. SEARCH METHODS: We searched Cochrane Kidney and Transplant's Specialised Register to 20 January 2016 through contact with the Information Specialist using search terms relevant to this review. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing antidepressant treatment with placebo or no treatment, or compared to another antidepressant medication or psychological intervention in adults with ESKD (estimated glomerular filtration rate < 15 mL/min/1.73 m(2)). DATA COLLECTION AND ANALYSIS: Data were abstracted by two authors independently onto a standard form and subsequently entered into Review Manager. Risk ratios (RR) for dichotomous data and mean differences (MD) for continuous data were calculated with 95% confidence intervals (95% CI). MAIN RESULTS: Four studies in 170 participants compared antidepressant therapy (fluoxetine, sertraline, citalopram or escitalopram) versus placebo or psychological training for 8 to 12 weeks. In generally very low or ungradeable evidence, compared to placebo, antidepressant therapy had no evidence of benefit on quality of life, had uncertain effects on increasing the risk of hypotension (3 studies, 144 participants: RR 1.72, 95% CI 0.75 to 3.92), headache (2 studies 56 participants: RR 2.91, 95% CI 0.73 to 11.57), and sexual dysfunction (2 studies, 101 participants: RR 3.83, 95% CI 0.63 to 23.34), and increased nausea (3 studies, 114 participants: RR 2.67, 95% CI 1.26 to 5.68). There were few or no data for hospitalisation, suicide or all-cause mortality resulting in inconclusive evidence. Antidepressant therapy may reduce depression scores during treatment compared to placebo (1 study, 43 participants: MD -7.50, 95% CI -11.94 to -3.06). Antidepressant therapy was not statistically different from group psychological therapy for effects on depression scores or withdrawal from treatment and a range of other outcomes were not measured. AUTHORS' CONCLUSIONS: Despite the high prevalence of depression in dialysis patients and the relative priority that patients place on effective treatments, evidence for antidepressant medication in the dialysis setting is sparse and data are generally inconclusive. The relative benefits and harms of antidepressant therapy in dialysis patients are poorly known and large randomised studies of antidepressants versus placebo are required.

Calcifediol supplementation in adults on hemodialysis: a randomized controlled trial.

BACKGROUND: Vitamin D deficiency is associated with increased risks of mortality in people with chronic kidney disease. The benefits and harm of vitamin D supplementation on cardiovascular outcomes and mortality are unknown. We aimed to assess the effectiveness of calcifediol in reducing mortality in patients with vitamin D insufficiency on hemodialysis compared to no additional therapy. METHODS: A phase III, multicenter, randomized, open-label trial was conducted including 284 adults with vitamin D insufficiency undergoing hemodialysis who were randomly assigned to receive oral calcifediol or standard care for 24 months. RESULTS: Two hundred eighty-four participants were enrolled (143 assigned to the calcifediol group and 141 to the no additional therapy group). The primary outcome (mortality) occurred in 34 and 31 participants in the calcifediol and control group, respectively [hazard ratio (HR) 1.03; 95% confidence interval (CI) 0.63-1.67]. Calcifediol had no detectable effects on cardiovascular death (HR 1.06; 95% CI 0.41-2.74), non-cardiovascular death (HR 1.13; 95% CI 0.62-2.04), nonfatal myocardial infarction (HR 0.20; 95% CI 0.02-1.67) or nonfatal stroke (HR could not be estimated). The incidence of hypercalcemia and hyperphosphatemia was similar between groups. None of the participants underwent parathyroidectomy. CONCLUSIONS: In adults treated with hemodialysis and who had vitamin D insufficiency, calcifediol supplementation for 24 months had inconclusive effects on mortality and cardiovascular outcomes. TRIAL REGISTRATION NUMBER: NCT01457001.

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.

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.

Fruit and Vegetable Intake and Mortality in Adults undergoing Maintenance Hemodialysis.

BACKGROUND AND OBJECTIVES: Higher fruit and vegetable intake is associated with lower cardiovascular and all-cause mortality in the general population. It is unclear whether this association occurs in patients on hemodialysis, in whom high fruit and vegetable intake is generally discouraged because of a potential risk of hyperkalemia. We aimed to evaluate the association between fruit and vegetable intake and mortality in hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Fruit and vegetable intake was ascertained by the Global Allergy and Asthma European Network food frequency questionnaire within the Dietary Intake, Death and Hospitalization in Adults with ESKD Treated with Hemodialysis study, a multinational cohort study of 9757 adults on hemodialysis, of whom 8078 (83%) had analyzable dietary data. Adjusted Cox regression analyses clustered by country were conducted to evaluate the association between tertiles of fruit and vegetable intake with all-cause, cardiovascular, and noncardiovascular mortality. Estimates were calculated as hazard ratios with 95% confidence intervals (95% CIs). RESULTS: During a median follow up of 2.7 years (18,586 person-years), there were 2082 deaths (954 cardiovascular). The median (interquartile range) number of servings of fruit and vegetables was 8 (4-14) per week; only 4% of the study population consumed at least four servings per day as recommended in the general population. Compared with the lowest tertile of servings per week (0-5.5, median 2), the adjusted hazard ratios for the middle (5.6-10, median 8) and highest (>10, median 17) tertiles were 0.90 (95% CI, 0.81 to 1.00) and 0.80 (95% CI, 0.71 to 0.91) for all-cause mortality, 0.88 (95% CI, 0.76 to 1.02) and 0.77 (95% CI, 0.66 to 0.91) for noncardiovascular mortality and 0.95 (95% CI, 0.81 to 1.11) and 0.84 (95% CI, 0.70 to 1.00) for cardiovascular mortality, respectively. CONCLUSIONS: Fruit and vegetable intake in the hemodialysis population is low and a higher consumption is associated with lower all-cause and noncardiovascular death.