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Cerebrovascular Diseases (Basel,... 2010Gross albuminuria is associated with increased stroke risk, but it is unclear whether stroke incidence varies by level of albuminuria. We meta-analyzed prospective... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Gross albuminuria is associated with increased stroke risk, but it is unclear whether stroke incidence varies by level of albuminuria. We meta-analyzed prospective cohort studies to investigate the impact of various albuminuria levels and continuous urinary albumin excretion (UAE) change on stroke risk.
METHODS
Systematic search for studies reporting quantitative estimates of the multivariate-adjusted relative risk (RR) and 95% CI for stroke risk associated with microalbuminuria (UAE 30-300 mg/day or nearest equivalent interval) and macroalbuminuria (UAE >300 mg/day) and studies that analyzed the relation of stroke with UAE continuously. Estimates were combined using a random-effect model.
RESULTS
We identified seven studies comprising 46,638 participants with 1,479 stroke events. Incident stroke risk was greater for macroalbuminuria (RR 2.65, 95% CI 2.25-3.14) than microalbuminuria (RR 1.58, 95% CI 1.39-1.80), a difference that was significant (p for heterogeneity < 0.001, I(2) = 96%). In addition, risk of stroke increased proportionally with rising UAE (p < 0.001), even for UAE within normal range (beginning from levels as low as 2-4 mg/g).
CONCLUSIONS
Higher albuminuria level confers greater stroke risk. These findings provide additional weight to evidence that albuminuria is strongly linked to stroke risk, and suggest that persons with elevated UAE levels may especially benefit from more intensive vascular risk reduction.
Topics: Aged; Albuminuria; Cohort Studies; Humans; Middle Aged; Multivariate Analysis; Prospective Studies; Risk Factors; Severity of Illness Index; Stroke
PubMed: 20733300
DOI: 10.1159/000317069 -
Diabetes Care Aug 2010To synthesize the cost-effectiveness (CE) of interventions to prevent and control diabetes, its complications, and comorbidities. (Review)
Review
OBJECTIVE
To synthesize the cost-effectiveness (CE) of interventions to prevent and control diabetes, its complications, and comorbidities.
RESEARCH DESIGN AND METHODS
We conducted a systematic review of literature on the CE of diabetes interventions recommended by the American Diabetes Association (ADA) and published between January 1985 and May 2008. We categorized the strength of evidence about the CE of an intervention as strong, supportive, or uncertain. CEs were classified as cost saving (more health benefit at a lower cost), very cost-effective (
$100,000 per LYG or QALY). The CE classification of an intervention was reported separately by country setting (U.S. or other developed countries) if CE varied by where the intervention was implemented. Costs were measured in 2007 U.S. dollars. RESULTS
Fifty-six studies from 20 countries met the inclusion criteria. A large majority of the ADA recommended interventions are cost-effective. We found strong evidence to classify the following interventions as cost saving or very cost-effective: (I) Cost saving- 1) ACE inhibitor (ACEI) therapy for intensive hypertension control compared with standard hypertension control; 2) ACEI or angiotensin receptor blocker (ARB) therapy to prevent end-stage renal disease (ESRD) compared with no ACEI or ARB treatment; 3) early irbesartan therapy (at the microalbuminuria stage) to prevent ESRD compared with later treatment (at the macroalbuminuria stage); 4) comprehensive foot care to prevent ulcers compared with usual care; 5) multi-component interventions for diabetic risk factor control and early detection of complications compared with conventional insulin therapy for persons with type 1 diabetes; and 6) multi-component interventions for diabetic risk factor control and early detection of complications compared with standard glycemic control for persons with type 2 diabetes. (II) Very cost-effective- 1) intensive lifestyle interventions to prevent type 2 diabetes among persons with impaired glucose tolerance compared with standard lifestyle recommendations; 2) universal opportunistic screening for undiagnosed type 2 diabetes in African Americans between 45 and 54 years old; 3) intensive glycemic control as implemented in the UK Prospective Diabetes Study in persons with newly diagnosed type 2 diabetes compared with conventional glycemic control; 4) statin therapy for secondary prevention of cardiovascular disease compared with no statin therapy; 5) counseling and treatment for smoking cessation compared with no counseling and treatment; 6) annual screening for diabetic retinopathy and ensuing treatment in persons with type 1 diabetes compared with no screening; 7) annual screening for diabetic retinopathy and ensuing treatment in persons with type 2 diabetes compared with no screening; and 8) immediate vitrectomy to treat diabetic retinopathy compared with deferred vitrectomy.
CONCLUSIONS
Many interventions intended to prevent/control diabetes are cost saving or very cost-effective and supported by strong evidence. Policy makers should consider giving these interventions a higher priority.
Topics: Cost-Benefit Analysis; Diabetes Mellitus; Humans; Quality-Adjusted Life Years
PubMed: 20668156
DOI: 10.2337/dc10-0843 -
BMJ Clinical Evidence Jul 2010Up to one third of people with type 1 or 2 diabetes will develop microalbuminuria or macroalbuminuria after 20 years. (Review)
Review
INTRODUCTION
Up to one third of people with type 1 or 2 diabetes will develop microalbuminuria or macroalbuminuria after 20 years.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in people with type 1 diabetes and early nephropathy? What are the effects of treatments in people with type 1 diabetes and late nephropathy? What are the effects of treatments in people with type 2 diabetes and early nephropathy? What are the effects of treatments in people with type 2 diabetes and late nephropathy? We searched: Medline, Embase, The Cochrane Library, and other important databases up to November 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 19 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, glycaemic control, protein restriction, and tight control of blood pressure.
Topics: Albuminuria; Angiotensin-Converting Enzyme Inhibitors; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Humans
PubMed: 21418671
DOI: No ID Found -
Clinical Journal of the American... Oct 2009Obesity is an independent risk factor for development and progression of chronic kidney disease (CKD). We conducted a systematic review to assess the benefits of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
Obesity is an independent risk factor for development and progression of chronic kidney disease (CKD). We conducted a systematic review to assess the benefits of intentional weight loss in patients with non-dialysis-dependent CKD and glomerular hyperfiltration.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
We searched MEDLINE, SCOPUS, and conference proceedings for randomized, controlled trials and observational studies that examined various surgical and nonsurgical interventions (diet, exercise, and/or antiobesity agents) in adult patients with CKD. Results were summarized using random-effects model.
RESULTS
Thirteen studies were included. In patients with CKD, body mass index (BMI) decreased significantly (weighted mean difference [WMD] -3.67 kg/m(2); 95% confidence interval [CI] -6.56 to -0.78) at the end of the study period with nonsurgical interventions. This was associated with a significant decrease in proteinuria (WMD -1.31 g/24 h; 95% CI -2.11 to -0.51) and systolic BP with no further decrease in GFR during a mean follow-up of 7.4 mo. In morbidly obese individuals (BMI >40 kg/m(2)) with glomerular hyperfiltration (GFR >125 ml/min), surgical interventions decreased BMI, which resulted in a decrease in GFR (WMD -25.56 ml/min; 95% CI -36.23 to -14.89), albuminuria, and systolic BP.
CONCLUSIONS
In smaller, short-duration studies in patients with CKD, nonsurgical weight loss interventions reduce proteinuria and BP and seem to prevent further decline in renal function. In morbidly obese individuals with glomerular hyperfiltration, surgical interventions normalize GFR and reduce BP and microalbuminuria. Larger, long-term studies to analyze renal outcomes such as development of ESRD are needed.
Topics: Blood Glucose; Body Mass Index; Chronic Disease; Creatinine; Glomerular Filtration Rate; Humans; Kidney Diseases; Obesity; Proteinuria; Systole; Weight Loss
PubMed: 19808241
DOI: 10.2215/CJN.02250409 -
BMJ Clinical Evidence Jan 2009Up to a third of people with type 1 or 2 diabetes will develop microalbuminuria or macroalbuminuria after 20 years. (Review)
Review
INTRODUCTION
Up to a third of people with type 1 or 2 diabetes will develop microalbuminuria or macroalbuminuria after 20 years.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in people with type 1 diabetes and early nephropathy? What are the effects of treatments in people with type 1 diabetes and late nephropathy? What are the effects of treatments in people with type 2 diabetes and early nephropathy? What are the effects of treatments in people with type 2 diabetes and late nephropathy? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2008 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 15 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, captopril, glycaemic control, protein restriction, and tight control of blood pressure.
Topics: Albuminuria; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Humans
PubMed: 19445773
DOI: No ID Found -
Diabetologia Apr 2009Glomerular hyperfiltration is a well-established phenomenon occurring early in some patients with type 1 diabetes. However, there is no consistent answer regarding... (Meta-Analysis)
Meta-Analysis
AIMS/HYPOTHESIS
Glomerular hyperfiltration is a well-established phenomenon occurring early in some patients with type 1 diabetes. However, there is no consistent answer regarding whether hyperfiltration predicts later development of nephropathy. We performed a systematic review and meta-analysis of observational studies that compared the risk of developing diabetic nephropathy in patients with and without glomerular hyperfiltration and also explored the impact of baseline GFR.
METHODS
A systematic review and meta-analysis was carried out. Cohort studies in type 1 diabetic participants were included if they contained data on the development of incipient or overt nephropathy with baseline measurement of GFR and presence or absence of hyperfiltration.
RESULTS
We included ten cohort studies following 780 patients. After a study median follow-up of 11.2 years, 130 patients had developed nephropathy. Using a random effects model, the pooled odds of progression to a minimum of microalbuminuria in patients with hyperfiltration was 2.71 (95% CI 1.20-6.11) times that of patients with normofiltration. There was moderate heterogeneity (heterogeneity test p = 0.05, measure of degree of inconsistency = 48%) and some evidence of funnel plot asymmetry, possibly due to publication bias. The pooled weighted mean difference in baseline GFR was 13.8 ml min(-1) 1.73 m(-2) (95% CI 5.0-22.7) greater in the group progressing to nephropathy than in those not progressing (heterogeneity test p < 0.01).
CONCLUSIONS/INTERPRETATION
In published studies, individuals with glomerular hyperfiltration were at increased risk of progression to diabetic nephropathy using study level data. Further larger studies are required to explore this relationship and the role of potential confounding variables.
Topics: Adolescent; Adult; Age of Onset; Albuminuria; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Disease Progression; Follow-Up Studies; Glomerular Filtration Rate; Hemodynamics; Humans; Kidney Glomerulus; Patient Selection; Risk Factors; Young Adult
PubMed: 19198800
DOI: 10.1007/s00125-009-1268-0 -
PLoS Medicine Oct 2008Markers of kidney dysfunction such as proteinuria or albuminuria have been reported to be associated with coronary heart disease, but the consistency and strength of any... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Markers of kidney dysfunction such as proteinuria or albuminuria have been reported to be associated with coronary heart disease, but the consistency and strength of any such relationship has not been clearly defined. This lack of clarity has led to great uncertainty as to how proteinuria should be treated in the assessment and management of cardiovascular risk. We therefore undertook a systematic review of published cohort studies aiming to provide a reliable estimate of the strength of association between proteinuria and coronary heart disease.
METHODS AND FINDINGS
A meta-analysis of cohort studies was conducted to obtain a summary estimate of the association between measures of proteinuria and coronary risk. MEDLINE and EMBASE were searched for studies reporting an age- or multivariate-adjusted estimate and standard error of the association between proteinuria and coronary heart disease. Studies were excluded if the majority of the study population had known glomerular disease or were the recipients of renal transplants. Two independent researchers extracted the estimates of association between proteinuria (total urinary protein >300 mg/d), microalbuminuria (urinary albumin 30-300 mg/d), macroalbuminuria (urinary albumin >300 mg/d), and risk of coronary disease from individual studies. These estimates were combined using a random-effects model. Sensitivity analyses were conducted to examine possible sources of heterogeneity in effect size. A total of 26 cohort studies were identified involving 169,949 individuals and 7,117 coronary events (27% fatal). The presence of proteinuria was associated with an approximate 50% increase in coronary risk (risk ratio 1.47, 95% confidence interval [CI] 1.23-1.74) after adjustment for known risk factors. For albuminuria, there was evidence of a dose-response relationship: individuals with microalbuminuria were at 50% greater risk of coronary heart disease (risk ratio 1.47, 95% CI 1.30-1.66) than those without; in those with macroalbuminuria the risk was more than doubled (risk ratio 2.17, 1.87-2.52). Sensitivity analysis indicated no important differences in prespecified subgroups.
CONCLUSION
These data confirm a strong and continuous association between proteinuria and subsequent risk of coronary heart disease, and suggest that proteinuria should be incorporated into the assessment of an individual's cardiovascular risk.
Topics: Cardiovascular Diseases; Humans; Proteinuria; Risk Factors
PubMed: 18942886
DOI: 10.1371/journal.pmed.0050207 -
Health Technology Assessment... Aug 2005To determine whether microalbuminuria is an independent prognostic factor for the development of diabetic complications and whether improved glycaemic or blood pressure... (Review)
Review
OBJECTIVES
To determine whether microalbuminuria is an independent prognostic factor for the development of diabetic complications and whether improved glycaemic or blood pressure control has a greater influence on the development of diabetic complications in those with microalbuminuria than in those with normoalbuminuria.
DATA SOURCES
Electronic databases up until January 2002.
REVIEW METHODS
A protocol for peer review by an external expert panel was prepared that included selection criteria for data extraction and required two independent reviewers to undertake article selection and review. Completeness was assessed using hand-searching of major journals. Random effects meta-analysis was used to obtain combined estimates of relative risk (RR). Funnel plots, trim and fill methods and meta-regression were used to assess publication bias and sources of heterogeneity.
RESULTS
In patients with type 1 or type 2 DM and microalbuminuria there is a RR of all-cause mortality of 1.8 [95% confidence interval (CI) 1.5 to 2.1] and 1.9 (95% CI 1.7 to 2.1) respectively. Similar RRs were found for other mortality end-points, with age of cohort being inversely related to the RR in type 2 DM. In patients with type 1 DM, there is evidence that microalbuminuria or raised albumin excretion rate has only weak, if any, independent prognostic significance for the incidence of retinopathy and no evidence that it predicts progression of retinopathy, although strong evidence exists for the independent prognostic significance of microalbuminuria or raised albumin excretion rate for the development of proliferative retinopathy (crude RR of 4.1, 95% CI 1.8 to 9.4). For type 2 DM, there is no evidence of any independent prognostic significance for the incidence of retinopathy and little, if any, prognostic relationship between microalbuminuria and the progression of retinopathy or development of proliferative retinopathy. In patients with type 1 DM and microalbuminuria there is an RR of developing end-stage renal disease (ESRD) of 4.8 (95% CI 3.0 to 7.5) and a higher RR (7.5, 95% CI 5.4 to 10.5) of developing clinical proteinuria, with a significantly greater fall in glomerular filtration rate (GFR) in patients with microalbuminuria. In patients with type 2 DM, similar RRs were observed: 3.6 (95% CI 1.6 to 8.4) for developing ESRD and 7.5 (95% CI 5.2 to 10.9) for developing clinical proteinuria, with a significantly greater decline in GFR in the microalbuminuria group of 1.7 (95% CI 0.1 to 3.2) ml per minute per year compared with those who were normoalbuminuric. In adults with type 1 or type 2 DM and microalbuminuria at baseline, the numbers progressing to clinical proteinuria (19% and 24%, respectively) and those regressing to normoalbuminuria (26% and 18%, respectively) did not differ significantly. In children with type 1 DM, regression (44%) was significantly more frequent than progression (15%). In patients with type 1 or type 2 DM and microalbuminuria, there is scarce evidence as to whether improved glycaemic control has any effect on the incidence of cardiovascular disease (CVD), the incidence or progression of retinopathy, or the development of renal complications. However, among patients not stratified by albuminuria, improved glycaemic control benefits retinal and renal complications and may benefit CVD. In the effects of angiotensin-converting enzyme (ACE) inhibitors on GFR in normotensive microalbuminuric patients with type 1 DM, there was no evidence of a consistent treatment effect. There is strong evidence from 11 trials in normotensive type 1 patients with microalbuminuria of a beneficial effect of ACE inhibitor treatment on the risk of developing clinical proteinuria and on the risk of regression to normoalbuminuria. Patients with type 2 DM and microalbuminuria, whether hypertensive or not, may obtain additional cardiovascular benefit from an ACE inhibitor and there may be a beneficial effect on the development of retinopathy in normotensive patients irrespective of albuminuria. There is limited evidence that treatment of hypertensive microalbuminuric type 2 diabetic patients with blockers of the renin--angiotensin system is associated with preserved GFR, but also evidence of no differences in GFR in comparisons with other antihypertensive agents. The data on GFR in normotensive cohorts are inconclusive. In normotensive type 2 patients with microalbuminuria there is evidence from three trials (all enalapril) of a reduction in risk of developing clinical proteinuria; in hypertensive patients there is evidence from one placebo-controlled trial (irbesartan) of a reduction in this risk. Intensive compared with moderate blood pressure control did not affect the rate of progression of microalbuminuria to clinical proteinuria in the one available study. There is inconclusive evidence from four trials of any difference in the proportions of hypertensive patients progressing from microalbuminuria to clinical proteinuria when ACE inhibitors are compared with other antihypertensive agents, and in one trial regression was two-fold higher with lisinopril than with nifedipine.
CONCLUSIONS
The most pronounced benefits of glycaemic control identified in this review are on retinal and renal complications in both normoalbuminuric and microalbuminuric patients considered together, with little or no evidence of any greater benefit in those with microalbuminuria. Hence, microalbuminuric status may be a false boundary when considering the benefits of glycaemic control. Classification of a person as normoalbuminuric must not serve to suggest that they will derive less benefit from optimal glycaemic control than a person who is microalbuminuric. All hypertensive patients benefit from blood pressure lowering and there is little evidence of additional benefit in those with microalbuminuria. Antihypertensive therapy with an ACE inhibitor in normotensive patients with microalbuminuria is beneficial. Monitoring microalbuminuria does not have a proven role in modulating antihypertensive therapy while the patient remains hypertensive. Recommendations for microalbuminuria research include: determining rate and predictors of development and factors involved in regression; carrying out economic evaluations of different screening strategies; investigating the effects of screening on patients; standardising screening tests to enable use of common reference ranges; evaluating the effects of lipid-lowering therapy; and using to modulate antihypertensive therapy.
Topics: Age Factors; Albuminuria; Antihypertensive Agents; Blood Glucose; Blood Pressure; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Kidney Failure, Chronic
PubMed: 16095545
DOI: 10.3310/hta9300 -
BMJ (Clinical Research Ed.) Oct 2004To evaluate the effects of angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists (AIIRAs) on renal outcomes and all cause mortality in... (Review)
Review
OBJECTIVE
To evaluate the effects of angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists (AIIRAs) on renal outcomes and all cause mortality in patients with diabetic nephropathy.
DATA SOURCES
Medline, Embase, the Cochrane controlled trials register, conference proceedings, and contact with investigators.
STUDY SELECTION
Trials comparing ACE inhibitors or AIIRAs with placebo or with each other in patients with diabetic nephropathy.
DATA EXTRACTION
Mortality, renal outcomes (end stage renal disease, doubling of serum creatinine concentration, prevention of progression of microalbuminuria to macroalbuminuria, remission of microalbuminuria), and quality of trials.
DATA SYNTHESIS
36 of 43 identified trials compared ACE inhibitors with placebo (4008 patients), four compared AIIRAs with placebo (3331 patients), and three compared ACE inhibitors with AIIRAs (206 patients). We obtained unpublished data for 11 trials. ACE inhibitors significantly reduced all cause mortality (relative risk 0.79, 95% confidence interval 0.63 to 0.99) compared with placebo but AIIRAs did not (0.99, 0.85 to 1.17), although baseline mortality was similar in the trials. Both agents had similar effects on renal outcomes. Reliable estimates of the unconfounded relative effects of ACE inhibitors compared with AIIRAs could not be obtained owing to small sample sizes.
CONCLUSION
Although the survival benefits of ACE inhibitors for patients with diabetic nephropathy are known, the relative effects of ACE inhibitors and AIIRAs on survival are unknown owing to the lack of adequate head to head trials.
Topics: Angiotensin II Type 2 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Humans; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 15459003
DOI: 10.1136/bmj.38237.585000.7C