Echocardiographic global longitudinal strain (GLS) is increasingly recognised as a more effective technique than conventional ejection fraction (EF) in detecting subtle changes in left ventricular ...(LV) function. This study investigated the prognostic value of GLS over EF in patients with advanced Chronic Kidney Disease (CKD).
The study included 183 patients (57% male, 63% on dialysis) with CKD stage 4, 5 and 5Dialysis (D). 112 (61%) of patients died in a follow up of 7.8 ± 4.4 years and 41% of deaths were due to cardiovascular (CV) disease. GLS was calculated using 2-dimensional speckle tracking and EF was measured using Simpson's biplane method. Cox proportional hazard models were used to assess the association of measures of LV function and all- cause and CV mortality.
The mean GLS at baseline was -13.6 ± 4.3% and EF was 45 ± 11%. GLS was a significant predictor of all-cause Hazard Ratio (HR) 1.09 95%; Confidence Interval (CI) 1.02-1.16; p = 0.01 and CV mortality (HR 1.16 95%; CI 1.04-1.30; p = 0.008) following adjustment for relevant clinical variables including LV mass index (LVMI) and EF. GLS also had greater predictive power for both all- cause and CV mortality compared to EF. Impaired GLS (>-16%) was associated with a 5.6-fold increased unadjusted risk of CV mortality in patients with preserved EF.
In this cohort of patients with advanced CKD, GLS is a more sensitive predictor of overall and CV mortality compared to EF. Studies of larger populations in CKD are required to confirm that GLS provides additive prognostic value in patients with preserved EF.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The prognostic significance of dialysis-dependent end-stage kidney disease on postoperative mortality is unclear. This study aims to estimate the odds of postoperative mortality in patients receiving ...chronic dialysis undergoing elective surgery compared to patients with normal kidney function, and to examine the influence of comorbidities on the excess mortality risk. A systematic search of studies published up to January 2020 was conducted using MEDLINE, EMBASE and CENTRAL databases. Eligible studies reported postoperative 30-day or in-hospital mortality in chronic dialysis patients compared to patients with normal kidney function undergoing elective surgery. Two investigators independently reviewed all abstracts and performed risk of bias assessments using the Newcastle-Ottawa Scale. Quality of evidence was summarised in accordance with GRADE methodology (grading of recommendations, assessment, development and evaluation). Relative mortality risk estimates were obtained using random effects meta-analysis. Heterogeneity was explored using meta-regression. (PROSPERO CRD42017076565) Forty-nine studies involving 41, 822 chronic dialysis and 10, 476, 321 non-dialysis patients undergoing elective surgery were included. Patients on chronic dialysis had a greatly increased postoperative mortality odds compared to patients with normal kidney function. The excess risk ranged from OR 10.8 (95%CI 7.3-15.9) following orthopaedic surgery to OR 4.0 (95%CI 3.2-4.9) after vascular surgery. Adjustment for age and comorbidity attenuated the excess odds but remained higher for patients on chronic dialysis, irrespective of surgical discipline. Meta-regression analysis demonstrated an inverse linear relationship between excess mortality risk and study-level mean age (slope -0.06; P = 0.001) and diabetes prevalence (slope -0.02; p = 0.001).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There is a paucity of quality evidence regarding the effects of sodium restriction in patients with CKD, particularly in patients with pre-end stage CKD, where controlling modifiable risk factors may ...be especially important for delaying CKD progression and cardiovascular events. We conducted a double-blind placebo-controlled randomized crossover trial assessing the effects of high versus low sodium intake on ambulatory BP, 24-hour protein and albumin excretion, fluid status (body composition monitor), renin and aldosterone levels, and arterial stiffness (pulse wave velocity and augmentation index) in 20 adult patients with hypertensive stage 3-4 CKD as phase 1 of the LowSALT CKD study. Overall, salt restriction resulted in statistically significant and clinically important reductions in BP (mean reduction of systolic/diastolic BP, 10/4 mm Hg; 95% confidence interval, 5 to 15 /1 to 6 mm Hg), extracellular fluid volume, albuminuria, and proteinuria in patients with moderate-to-severe CKD. The magnitude of change was more pronounced than the magnitude reported in patients without CKD, suggesting that patients with CKD are particularly salt sensitive. Although studies with longer intervention times and larger sample sizes are needed to confirm these benefits, this study indicates that sodium restriction should be emphasized in the management of patients with CKD as a means to reduce cardiovascular risk and risk for CKD progression.
Background There is a resurgence of interest in home hemodialysis (HD), especially frequent or extended forms involving unconventionally frequent (>3 times/wk) and/or long (>6 hours) treatments. This ...resurgence is driven by cost containment and experience suggesting lower mortality risk compared with facility HD and peritoneal dialysis (PD). Study Design We performed an observational cohort study using the Australia and New Zealand Dialysis and Transplant Registry, using marginal structural modeling to adjust for time-varying medical comorbidity as both a source of selection bias and an intermediary variable on the causal pathway to death. Setting & Participants All adult patients starting renal replacement therapy in Australia and New Zealand since March 31, 1996, followed up to December 31, 2007. Predictor The main predictor was dialysis modality (conventional facility HD, conventional home HD, frequent/extended facility HD, frequent/extended home HD, and PD). We adjusted for the confounding effects of patient demographics and comorbid conditions. Outcome Patient mortality. Results We analyzed 26,016 patients with 856,007 patient-months of follow-up. Relative to conventional facility HD, adjusted mortality HRs were 0.51 (95% CI, 0.44-0.59) for conventional home HD, 1.16 (95% CI, 0.94-1.44) for frequent/extended facility HD, 0.53 (95% CI, 0.41-0.68) for frequent/extended home HD, and 1.10 (95% CI, 1.06-1.16) for PD. The apparent benefit of home HD on mortality risk was less for patients who were nonwhite, non-Asian, and older. Limitations Potential for residual confounding from the limited collection of comorbid conditions (no collection of cognitive or motor impairment, depression, left ventricular volume or structure, or blood pressure/fluid volume status) and lack of socioeconomic, medication, and biochemical data in analyses. Conclusions Our study supports a survival advantage of home HD without a difference between conventional and frequent/extended modalities. Suitably designed clinical trials of frequent/extended HD are needed to determine the presence and extent of mortality benefit with this modality.
Patient training has widely been considered to be one of the most critical factors for achieving optimal peritoneal dialysis clinical outcomes, including avoidance of peritonitis. However, research ...in this important area has been remarkably scant to date. This article will critically review the clinical evidence underpinning PD patient training and will specifically focus on four key areas: who should provide training and how, when and where should it be performed to obtain the best results. Evidence gaps and future research directions will also be discussed.
A new class of dialysis membrane, the mid cut-off (MCO) dialyzer, has been developed to improve the clearance of uremic toxins in hemodialysis (HD). The a tRial Evaluating Mid cut-Off Value membrane ...clearance of Albumin and Light chains in HemoDialysis patients (REMOVAL-HD) study aimed to determine if regular use of MCO dialyzer was safe and specifically did not result in a significant loss of albumin.
This investigator initiated, crossover, longitudinal, device study was conducted across 9 centers in Australia and New Zealand (n = 89). Participants had a 4-week wash-in with high-flux HD, followed by 24-week intervention with MCO HD and a subsequent 4-week wash-out with high-flux HD. The primary outcome was change in serum albumin between weeks 4 and 28. Secondary outcomes included trends in serum albumin, changes in kappa- and lambda-free light chains (FLC), 6-min walk test (6MWT), malnutrition inflammation score (MIS), restless legs score and quality of life.
Participants had a mean age of 66 ± 14 years, 62% were men, 45% were anuric, and 51% had -diabetes. There was no reduction in serum albumin following treatment with MCO HD (mean reduction -0.7 g/L, 95% CI -1.5 to 0.1). A sustained, unexplained reduction in serum albumin (>25%) was not observed in any participant. A reduction in FLC was observed 2 weeks into MCO HD (lambda-FLC: Δ -9.1 mg/L, 95% CI -14.4 to -3.7; kappa-FLC: Δ -5.7 mg/L, 95% CI -9.8 to -1.6) and was sustained for the rest of the study intervention. Both FLC increased after the cessation of MCO use. There was no improvement in restless legs symptoms, quality of life, 6MWT or MIS scores.
Regular HD using the MCO dialyzer did not result in a significant fall in serum albumin. There were no effects on quality of life, functional status or nutrition.
Australian New Zealand Clinical Trials Registry Number (ANZCTRN) 12616000804482.
Non-randomized studies suggest an association between serum uric acid levels and progression of chronic kidney disease (CKD). The aim of this systematic review is to summarize evidence from ...randomized controlled trials (RCTs) concerning the benefits and risks of uric acid-lowering therapy on renal outcomes.
Medline, Excerpta Medical Database and Cochrane Central Register of Controlled Trials were searched with English language restriction for RCTs comparing the effect of uric acid-lowering therapy with placebo/no treatment on renal outcomes. Treatment effects were summarized using random-effects meta-analysis.
Eight trials (476 participants) evaluating allopurinol treatment were eligible for inclusion. There was substantial heterogeneity in baseline kidney function, cause of CKD and duration of follow-up across these studies. In five trials, there was no significant difference in change in glomerular filtration rate from baseline between the allopurinol and control arms mean difference (MD) 3.1 mL/min/1.73 m2, 95% confidence intervals (CI) -0.9, 7.1; heterogeneity χ2=1.9, I2=0%, P=0.75. In three trials, allopurinol treatment abrogated increases in serum creatinine from baseline (MD -0.4 mg/dL, 95% CI -0.8, -0.0 mg/dL; heterogeneity χ2=3, I2=34%, P=0.22). Allopurinol had no effect on proteinuria and blood pressure. Data for effects of allopurinol therapy on progression to end-stage kidney disease and death were scant. Allopurinol had uncertain effects on the risks of adverse events.
Uric acid-lowering therapy with allopurinol may retard the progression of CKD. However, adequately powered randomized trials are required to evaluate the benefits and risks of uric acid-lowering therapy in CKD.
Hyperphosphatemia is associated with increased fibroblast growth factor 23 (FGF23), arterial calcification, and cardiovascular mortality. Effects of phosphate-lowering medication on vascular ...calcification and arterial stiffness in CKD remain uncertain.
To assess the effects of non-calcium-based phosphate binders on intermediate cardiovascular markers, we conducted a multicenter, double-blind trial, randomizing 278 participants with stage 3b or 4 CKD and serum phosphate >1.00 mmol/L (3.10 mg/dl) to 500 mg lanthanum carbonate or matched placebo thrice daily for 96 weeks. We analyzed the primary outcome, carotid-femoral pulse wave velocity, using a linear mixed effects model for repeated measures. Secondary outcomes included abdominal aortic calcification and serum and urine markers of mineral metabolism.
A total of 138 participants received lanthanum and 140 received placebo (mean age 63.1 years; 69% male, 64% White). Mean eGFR was 26.6 ml/min per 1.73 m
; 45% of participants had diabetes and 32% had cardiovascular disease. Mean serum phosphate was 1.25 mmol/L (3.87 mg/dl), mean pulse wave velocity was 10.8 m/s, and 81.3% had abdominal aortic calcification at baseline. At 96 weeks, pulse wave velocity did not differ significantly between groups, nor did abdominal aortic calcification, serum phosphate, parathyroid hormone, FGF23, and 24-hour urinary phosphate. Serious adverse events occurred in 63 (46%) participants prescribed lanthanum and 66 (47%) prescribed placebo. Although recruitment to target was not achieved, additional analysis suggested this was unlikely to have significantly affected the principle findings.
In patients with stage 3b/4 CKD, treatment with lanthanum over 96 weeks did not affect arterial stiffness or aortic calcification compared with placebo. These findings do not support the role of intestinal phosphate binders to reduce cardiovascular risk in patients with CKD who have normophosphatemia.
Australian Clinical Trials Registry, ACTRN12610000650099.
We determined weights for a multi-criteria tool for assessing the relative merits of clinical-trial research proposals, and investigated whether the weights vary across relevant stakeholder groups. A ...cross-sectional, adaptive discrete choice experiment using 1000minds online software was administered to consumers, researchers and funders affiliated with the Australian Clinical Trials Alliance (ACTA). We identified weights for four criteria-Appropriateness, Significance, Relevance, Feasibility-and their levels, representing their relative importance, so that research proposals can be scored between 0% (nil or very low merit) and 100% (very high merit). From 220 complete survey responses, the most important criterion was Appropriateness (adjusted for differences between stakeholder groups, mean weight 28.9%) and the least important was Feasibility (adjusted mean weight 19.5%). Consumers tended to weight Relevance more highly (2.7% points difference) and Feasibility less highly (3.1% points difference) than researchers. The research or grant writing experience of researchers or consumers was not associated with the weights. A multi-criteria tool for evaluating research proposals that reflects stakeholders' preferences was created. The tool can be used to assess the relative merits of clinical trial research proposals and rank them, to help identify the best proposals for funding.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Diabetes is the commonest cause of chronic kidney disease (CKD). Both conditions commonly co‐exist. Glucometabolic changes and concurrent dialysis in diabetes and CKD make glucose‐lowering ...challenging, increasing the risk of hypoglycaemia. Glucose‐lowering agents have been mainly studied in people with near‐normal kidney function. It is important to characterise existing knowledge of glucose‐lowering agents in CKD to guide treatment.
Objectives
To examine the efficacy and safety of insulin and other pharmacological interventions for lowering glucose levels in people with diabetes and CKD.
Search methods
We searched the Cochrane Kidney and Transplant Register of Studies up to 12 February 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
All randomised controlled trials (RCTs) and quasi‐RCTs looking at head‐to‐head comparisons of active regimens of glucose‐lowering therapy or active regimen compared with placebo/standard care in people with diabetes and CKD (estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2) were eligible.
Data collection and analysis
Four authors independently assessed study eligibility, risk of bias, and quality of data and performed data extraction. Continuous outcomes were expressed as post‐treatment mean differences (MD). Adverse events were expressed as post‐treatment absolute risk differences (RD). Dichotomous clinical outcomes were presented as risk ratios (RR) with 95% confidence intervals (CI).
Main results
Forty‐four studies (128 records, 13,036 participants) were included. Nine studies compared sodium glucose co‐transporter‐2 (SGLT2) inhibitors to placebo; 13 studies compared dipeptidyl peptidase‐4 (DPP‐4) inhibitors to placebo; 2 studies compared glucagon‐like peptide‐1 (GLP‐1) agonists to placebo; 8 studies compared glitazones to no glitazone treatment; 1 study compared glinide to no glinide treatment; and 4 studies compared different types, doses or modes of administration of insulin. In addition, 2 studies compared sitagliptin to glipizide; and 1 study compared each of sitagliptin to insulin, glitazars to pioglitazone, vildagliptin to sitagliptin, linagliptin to voglibose, and albiglutide to sitagliptin. Most studies had a high risk of bias due to funding and attrition bias, and an unclear risk of detection bias.
Compared to placebo, SGLT2 inhibitors probably reduce HbA1c (7 studies, 1092 participants: MD ‐0.29%, ‐0.38 to ‐0.19 (‐3.2 mmol/mol, ‐4.2 to ‐2.2); I2 = 0%), fasting blood glucose (FBG) (5 studies, 855 participants: MD ‐0.48 mmol/L, ‐0.78 to ‐0.19; I2 = 0%), systolic blood pressure (BP) (7 studies, 1198 participants: MD ‐4.68 mmHg, ‐6.69 to ‐2.68; I2 = 40%), diastolic BP (6 studies, 1142 participants: MD ‐1.72 mmHg, ‐2.77 to ‐0.66; I2 = 0%), heart failure (3 studies, 2519 participants: RR 0.59, 0.41 to 0.87; I2 = 0%), and hyperkalaemia (4 studies, 2788 participants: RR 0.58, 0.42 to 0.81; I2 = 0%); but probably increase genital infections (7 studies, 3086 participants: RR 2.50, 1.52 to 4.11; I2 = 0%), and creatinine (4 studies, 848 participants: MD 3.82 μmol/L, 1.45 to 6.19; I2 = 16%) (all effects of moderate certainty evidence). SGLT2 inhibitors may reduce weight (5 studies, 1029 participants: MD ‐1.41 kg, ‐1.8 to ‐1.02; I2 = 28%) and albuminuria (MD ‐8.14 mg/mmol creatinine, ‐14.51 to ‐1.77; I2 = 11%; low certainty evidence). SGLT2 inhibitors may have little or no effect on the risk of cardiovascular death, hypoglycaemia, acute kidney injury (AKI), and urinary tract infection (low certainty evidence). It is uncertain whether SGLT2 inhibitors have any effect on death, end‐stage kidney disease (ESKD), hypovolaemia, fractures, diabetic ketoacidosis, or discontinuation due to adverse effects (very low certainty evidence).
Compared to placebo, DPP‐4 inhibitors may reduce HbA1c (7 studies, 867 participants: MD ‐0.62%, ‐0.85 to ‐0.39 (‐6.8 mmol/mol, ‐9.3 to ‐4.3); I2 = 59%) but may have little or no effect on FBG (low certainty evidence). DPP‐4 inhibitors probably have little or no effect on cardiovascular death (2 studies, 5897 participants: RR 0.93, 0.77 to 1.11; I2 = 0%) and weight (2 studies, 210 participants: MD 0.16 kg, ‐0.58 to 0.90; I2 = 29%; moderate certainty evidence). Compared to placebo, DPP‐4 inhibitors may have little or no effect on heart failure, upper respiratory tract infections, and liver impairment (low certainty evidence). Compared to placebo, it is uncertain whether DPP‐4 inhibitors have any effect on eGFR, hypoglycaemia, pancreatitis, pancreatic cancer, or discontinuation due to adverse effects (very low certainty evidence).
Compared to placebo, GLP‐1 agonists probably reduce HbA1c (7 studies, 867 participants: MD ‐0.53%, ‐1.01 to ‐0.06 (‐5.8 mmol/mol, ‐11.0 to ‐0.7); I2 = 41%; moderate certainty evidence) and may reduce weight (low certainty evidence). GLP‐1 agonists may have little or no effect on eGFR, hypoglycaemia, or discontinuation due to adverse effects (low certainty evidence). It is uncertain whether GLP‐1 agonists reduce FBG, increase gastrointestinal symptoms, or affect the risk of pancreatitis (very low certainty evidence).
Compared to placebo, it is uncertain whether glitazones have any effect on HbA1c, FBG, death, weight, and risk of hypoglycaemia (very low certainty evidence).
Compared to glipizide, sitagliptin probably reduces hypoglycaemia (2 studies, 551 participants: RR 0.40, 0.23 to 0.69; I2 = 0%; moderate certainty evidence). Compared to glipizide, sitagliptin may have had little or no effect on HbA1c, FBG, weight, and eGFR (low certainty evidence). Compared to glipizide, it is uncertain if sitagliptin has any effect on death or discontinuation due to adverse effects (very low certainty).
For types, dosages or modes of administration of insulin and other head‐to‐head comparisons only individual studies were available so no conclusions could be made.
Authors' conclusions
Evidence concerning the efficacy and safety of glucose‐lowering agents in diabetes and CKD is limited. SGLT2 inhibitors and GLP‐1 agonists are probably efficacious for glucose‐lowering and DPP‐4 inhibitors may be efficacious for glucose‐lowering. Additionally, SGLT2 inhibitors probably reduce BP, heart failure, and hyperkalaemia but increase genital infections, and slightly increase creatinine. The safety profile for GLP‐1 agonists is uncertain. No further conclusions could be made for the other classes of glucose‐lowering agents including insulin. More high quality studies are required to help guide therapeutic choice for glucose‐lowering in diabetes and CKD.
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