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PloS One 2020Diabetes is a global epidemic, and the high cost of annually and quantitatively measuring urine albumin excretion using the turbidimetric immunoassay is challenging. We... (Meta-Analysis)
Meta-Analysis
Can a semi-quantitative method replace the current quantitative method for the annual screening of microalbuminuria in patients with diabetes? Diagnostic accuracy and cost-saving analysis considering the potential health burden.
OBJECTIVES
Diabetes is a global epidemic, and the high cost of annually and quantitatively measuring urine albumin excretion using the turbidimetric immunoassay is challenging. We aimed to determine whether a semi-quantitative urinary albumin-creatinine ratio test could be used as a screening tool for microalbuminuria in diabetic patients.
METHODS
We assessed the diagnostic accuracy of the semi-quantitative method. The costs of false results in the semi-quantitative method were calculated based on the annual probability of disease progression analyzed through a systematic literature review and meta-analysis. The pooled long-term cost-saving effect of the semi-quantitative method compared with the quantitative test was assessed using a Markov model simulating a long-term clinical setting. Diagnostic accuracy and the cost-saving effect were also validated in an independent external cohort.
RESULTS
Compared with the quantitative test, the semi-quantitative method had sensitivities of 93.5% and 81.3% and specificities of 61.4% and 63.1% in the overall sample of diabetic patients (n = 1,881) and in diabetic patients with eGFR ≥60 ml/min/1.73 m2 and a negative dipstick test (n = 1,110), respectively. After adjusting for direct and indirect medical costs, including the risk of disease progression, which was adjusted by the meta-analyzed hazard ratio for clinical outcomes, it was determined that using the semi-quantitative method could save 439.4 USD per person for 10 years. Even after adjusting the result to the external validation cohort, 339.6 USD could be saved for one diabetic patient for 10 years.
CONCLUSIONS
The semi-quantitative method could be an appropriate screening tool for albuminuria in diabetic patients. Moreover, it can minimize the testing time and inconvenience and significantly reduce national health costs.
Topics: Albuminuria; Cohort Studies; Cost Savings; Diabetes Mellitus; Diabetic Nephropathies; Humans; Mass Screening; Reproducibility of Results; Republic of Korea; Urinalysis
PubMed: 31961894
DOI: 10.1371/journal.pone.0227694 -
Nutrition Research (New York, N.Y.) Dec 2019No conclusive information is available about the association between the Dietary Approaches to Stop Hypertension (DASH)-style diet and chronic kidney disease (CKD).... (Meta-Analysis)
Meta-Analysis
Adherence to the dietary approaches to stop hypertension-style diet is inversely associated with chronic kidney disease: a systematic review and meta-analysis of prospective cohort studies.
No conclusive information is available about the association between the Dietary Approaches to Stop Hypertension (DASH)-style diet and chronic kidney disease (CKD). Hence, we aimed to summarize the findings of prospective cohort studies on the relationship between adherence to the DASH-style diet and risk of CKD. A systematic search was done using relevant keywords in the online databases for relevant publications up through July 2018. In total, we included 6 studies in the current systematic review and meta-analysis, with a total sample size of 568 156 individuals and 9249 cases of CKD. Combining 6 effect sizes from 6 studies revealed a significant inverse association between adherence to the DASH diet and risk of CKD (Combined effect size: 0.72, 95% CI: 0.61-0.85, P < .001). In addition, adherence to a DASH-style diet was inversely associated with a risk of rapid decline in estimated glomerular filtration rate (eGFR) (Combined effect size: 0.74, 95% CI: 0.54-0.99, P = .04) and microalbuminuria (Combined effect size: 0.61, 95% CI: 0.43-0.88, P = .009), but not with low eGFR. Adherence to the DASH-style diet, as a healthy dietary pattern, might be beneficial for the prevention of CKD.
Topics: Cohort Studies; Dietary Approaches To Stop Hypertension; Humans; Patient Compliance; Prospective Studies; Renal Insufficiency, Chronic
PubMed: 31740009
DOI: 10.1016/j.nutres.2019.10.007 -
Scientific Reports Sep 2019This study was conducted to investigate the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on individual renal outcomes in patients with type 2 diabetes.... (Meta-Analysis)
Meta-Analysis
Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Renal Outcomes in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
This study was conducted to investigate the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on individual renal outcomes in patients with type 2 diabetes. We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception to September 2017 to identify randomized controlled trials comparing SGLT2 inhibitors with placebo or antidiabetic drugs and reporting any renal outcomes in patients with type 2 diabetes. Additionally, we identified 4 articles which were published after the predefined period to include relevant data. A meta-analysis was performed to calculate weighted mean differences (WMDs) and relative risks (RRs) with 95% confidence intervals (CIs) for each renal outcome. We included 48 studies involving 58,165 patients in the analysis. SGLT2 inhibitors significantly lowered urine albumin-to-creatinine ratio (UACR) (WMD, -14.64 mg/g; 95% CI, -25.15 to -4.12; P = 0.006) compared with controls. The UACR-lowering effects of SGLT2 inhibitors were greater with a higher baseline UACR. Overall changes in estimated glomerular filtration rate (eGFR) were comparable between two groups (WMD, 0.19 mL/min/1.73 m; 95% CI, -0.44 to 0.82; P = 0.552). However, SGLT2 inhibitors significantly slowed eGFR decline in patients with a higher baseline eGFR and a longer duration of treatment. Compared with controls, SGLT2 inhibitors significantly reduced the risk of microalbuminuria (RR, 0.69; 95% CI, 0.49 to 0.97; P = 0.032), macroalbuminuria (RR, 0.49; 95% CI, 0.33 to 0.73; P < 0.001), and worsening nephropathy (RR, 0.73; 95% CI, 0.58 to 0.93; P = 0.012). In addition, the risk of end-stage renal disease was significantly lower in SGLT2 inhibitors than in controls (RR, 0.70; 95% CI, 0.57 to 0.87; P = 0.001). In conclusion, SGLT2 inhibitors had beneficial renal effects by lowering the risk of albuminuria development or progression and reducing the risk of end-stage renal disease compared with placebo or other antidiabetic drugs.
Topics: Diabetes Mellitus, Type 2; Diabetic Nephropathies; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 31506585
DOI: 10.1038/s41598-019-49525-y -
Journal of Hypertension Jan 2020In experimental animal models, exogenous aldosterone excess has been linked to the progression of renal disease. However, the evidence of an increased risk of renal... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
In experimental animal models, exogenous aldosterone excess has been linked to the progression of renal disease. However, the evidence of an increased risk of renal damage in patients affected by primary aldosteronism remains controversial. We aimed at evaluating the association between primary aldosteronism and renal damage through a meta-analysis.
METHODS
We performed a quantitative review of studies evaluating parameters of renal function in patients affected by primary aldosteronism compared with hypertensive patients without primary aldosteronism and in patients affected by primary aldosteronism before and after treatment. We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from January 1960 up to April 2019.
RESULTS
Forty-six studies including 6056 patients with primary aldosteronism and 9733 patients affected by arterial hypertension without primary aldosteronism were included. After 8.5 years from hypertension diagnosis, patients with primary aldosteronism had an increased estimated glomerular filtration rate (eGFR) compared with hypertensive patients without primary aldosteronism [by 3.37 ml/min IQR (0.82-5.93)] and a more severe albuminuria [standard mean difference 0.55 (0.19-0.91)], resulting into an association with microalbuminuria [odds ratio (OR) 2.09 (1.40; 3.12)] and proteinuria [OR 2.68 (1.89;3.79)]. Following primary aldosteronism treatment, after a median follow-up of 12 months, a reduction in eGFR was observed [by -10.69 ml/min (-13.23; -8.16)], consistent in both medically and surgically treated patients. Similarly, a reduction in albumin excretion and an increase in serum creatinine were observed after treatment.
CONCLUSION
Patients affected by primary aldosteronism, compared with patients affected by arterial hypertension without primary aldosteronism, display a more pronounced target organ damage, which can be mitigated by the specific treatment.
Topics: Creatinine; Glomerular Filtration Rate; Humans; Hyperaldosteronism; Hypertension; Kidney Diseases
PubMed: 31385870
DOI: 10.1097/HJH.0000000000002216 -
Archives of Endocrinology and Metabolism Jul 2019Chronic kidney disease (CKD) risk is inconsistent in the normal-weight, overweight, and obese individuals due to the heterogeneity of metabolic status. This... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Chronic kidney disease (CKD) risk is inconsistent in the normal-weight, overweight, and obese individuals due to the heterogeneity of metabolic status. This meta-analysis aimed to examine the combined effects of body mass index (BMI) and metabolic status on CKD risk.
MATERIALS AND METHODS
The MEDLINE, EMBASE, and Web of Knowledge databases were systematically searched up to March 2019 to identify all eligible studies investigating the CKD risk (defined as GFR < 60 mL/min per 1.73 m2 and/or microalbuminuria or proteinuria) associated with the body size phenotypes which are known as metabolically unhealthy normal-weight (MUNW), metabolically healthy overweight (MHOW), metabolically unhealthy overweight, metabolically healthy obese (MHO) and metabolically unhealthy obese (MUHO). The classification of subjects in included studies as metabolically unhealthy was based on the presence of three components of metabolic syndrome. BMI categorization was based on the criteria of included studies. The risk estimates and 95% confidence intervals (CIs) were extracted and pooled using random effects analysis.
RESULTS
A total of 9 prospective cohort studies with 128773 participants and 4797 incident cases were included in the meta-analysis. Compared with healthy normal-weight individuals as reference, MUNW and MHO subjects showed an increased risk for CKD events with a pooled RR of 1.58 (95% CI = 1.28-1.96) in MUNW and 1.55 (95% CI = 1.34-1.79) in MHO persons. Also, MHOW was at increased risk for CKD (RR = 1.34, 95% CI = 1.20-1.51). MUHO individuals were at the highest risk for the development of CKD (RR = 2.13, 95% CI = 1.66-2.72).
CONCLUSIONS
Individuals with metabolic abnormality, although at normal-weight, have an increased risk for CKD. Healthy overweight and obese individuals had higher risk; refuting the notion that metabolically healthy overweight and obese phenotypes are benign conditions.
Topics: Body Mass Index; Body Weight; Humans; Metabolic Syndrome; Observational Studies as Topic; Phenotype; Renal Insufficiency, Chronic; Risk
PubMed: 31365625
DOI: 10.20945/2359-3997000000149 -
Hypertension Research : Official... Apr 2019The efficacy and safety of renin-angiotensin system inhibitors (RAS-I) in hypertensive adults with non-diabetic chronic kidney disease (CKD) differ depending on the... (Meta-Analysis)
Meta-Analysis
The efficacy and safety of renin-angiotensin system inhibitors (RAS-I) in hypertensive adults with non-diabetic chronic kidney disease (CKD) differ depending on the presence or the absence of proteinuria. To estimate the effects of RAS-I in this population, we performed a systematic review and meta-analysis of randomized controlled trials where treatment with angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers were compared with placebo or active controls in adults with non-diabetic CKD. The treatment effects were separately reviewed in patients with and without proteinuria. Based on a search of Medline and the Cochrane Library up to September 2017, we identified 42 eligible trials (28, proteinuria-positive group; 6, proteinuria-negative group; 2, mixed-proteinuria group; and 6, proteinuria data-unavailable group). RAS-I reduced renal failure events in comparison to placebo or active agents in the proteinuria-positive group (relative risk [RR] 0.63, 95% confidence interval [CI] 0.52-0.75), but showed no significant effects on renal failure risk in the proteinuria-negative group (RR 0.64, 95% CI 0.18-2.30) although it reduced microalbuminuria. For cardiovascular events, RAS-I was not associated with a significantly reduced risk in both the proteinuria-positive and proteinuria-negative group (RR 0.77 and 1.06, 95% CI 0.51-1.16 and 0.85-1.32, respectively). In the mixed-proteinuria group and proteinuria data-unavailable group, RAS-I showed no significant effects on renal and cardiovascular events. Among adverse events, hyperkalemia increased with RAS-I administration in the proteinuria-positive group (RR 2.01, 95% CI 1.07-3.77). Our analysis showed the renoprotective effects of RAS-I treatment in patients with non-diabetic CKD having proteinuria, supporting its use as the first-line antihypertensive therapy in this population.
Topics: Adult; Angiotensin II Type 2 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Humans; Hypertension; Proteinuria; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Renin-Angiotensin System
PubMed: 30948820
DOI: 10.1038/s41440-018-0116-3 -
Endocrinology and Metabolism (Seoul,... Mar 2019To investigate the effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on renal outcomes in patients with type 2 diabetes. (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
To investigate the effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on renal outcomes in patients with type 2 diabetes.
METHODS
MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched to identify randomized controlled trials (RCTs) of DPP-4 inhibitors from inception to September 2017. We selected eligible RCTs comparing DPP-4 inhibitors with placebo or other antidiabetic agents and reporting at least one renal outcome. A meta-analysis was conducted to calculate standardized mean differences, weighted mean differences (WMDs), relative risks (RRs), and 95% confidence intervals (CIs) for each renal outcome.
RESULTS
We included 23 RCTs with 19 publications involving 41,359 patients. Overall changes in urine albumin-to-creatinine ratio were comparable between DPP-4 inhibitors and controls (=0.150). However, DPP-4 inhibitors were associated with significantly lower risk of incident microalbuminuria (RR, 0.89; 95% CI, 0.80 to 0.98; =0.022) and macroalbuminuria (RR, 0.77; 95% CI, 0.61 to 0.97; =0.027), as well as higher rates of regression of albuminuria (RR, 1.22; 95% CI, 1.10 to 1.35; <0.001) compared with controls. Although DPP-4 inhibitors were associated with small but significantly lower estimated glomerular filtration rate (WMD, -1.11 mL/min/1.73 m²; 95% CI, -1.78 to -0.44; =0.001), there was no difference in the risk of end-stage renal disease between two groups (RR, 0.93; 95% CI, 0.76 to 1.14; =0.475).
CONCLUSION
DPP-4 inhibitors had beneficial renal effects mainly by reducing the risk of development or progression of albuminuria compared with placebo or other antidiabetic agents.
Topics: Aged; Albumins; Albuminuria; Diabetes Complications; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dipeptidyl-Peptidase IV Inhibitors; Glomerular Filtration Rate; Humans; Hypoglycemic Agents; Kidney; Kidney Failure, Chronic; Middle Aged; Placebos; Randomized Controlled Trials as Topic
PubMed: 30912341
DOI: 10.3803/EnM.2019.34.1.80 -
Diabetes/metabolism Research and Reviews Jul 2019Diabetic kidney disease is one of the most serious microvascular complications and among the leading causes of end stage renal disease. Persistently increasing...
Diabetic kidney disease is one of the most serious microvascular complications and among the leading causes of end stage renal disease. Persistently increasing albuminuria has been considered to be the central hallmark of nephropathy. However, albuminuria can indicate kidney damage for clinicians; it is not a specific biomarker for prediction of diabetic kidney disease prior to the onset of this devastating complication, and in fact all individuals with microalbuminuria do not progress to overt nephropathy. Controlled glycemia is unable to prevent nephropathy in all diabetic individuals indicating the role of other factors in progression of diabetic kidney disease. There are numerous cellular and molecular defects persisting prior to appearance of clinical symptoms. So, there is an urgent need to look for easy, novel, and accurate way to detect diabetic kidney disease prior to its beginning or at the infancy stage so that its progression can be slowed or arrested. It is now accepted that initiation and progression of diabetic kidney disease are a result of complex interactions between genetic and environmental factors. Environmental signals can alter the intracellular pathways by chromatin modifiers and regulate gene expression patterns leading to diabetes and its complications. In the present review, we have discussed a possible link between aberrant DNA methylation and altered gene expression in diabetic kidney disease. Drugs targeting to reverse epigenetic alteration can retard or stop the development of this devastating disease, just by breaking the chain of events occurring prior to the development of this microvascular complication in patients with diabetes.
Topics: Animals; Biomarkers; Blood Glucose; Diabetic Nephropathies; Diagnostic Techniques, Endocrine; Epigenesis, Genetic; Humans; Prognosis
PubMed: 30892801
DOI: 10.1002/dmrr.3155 -
Current Diabetes Reviews 2020This study was conducted to discuss the clinical value of published Diabetic Retinopathy Progression determinants.
OBJECTIVE
This study was conducted to discuss the clinical value of published Diabetic Retinopathy Progression determinants.
METHODS
The data for systematic review was collected from the published studies through PubMed and Medline. These studies discussed the clinical predictors of Diabetic Retinopathy (DR) progression. The common keywords used were diabetic Retinopathy, diabetes mellitus, systolic blood pressure, hemoglobin, and albuminuria.
RESULTS
Diabetic Retinopathy is one of the common causes of irreversible visual impairment among adults. Poor glycemic control, systemic hypertension, diabetes duration, dyslipidemia, and microalbuminuria are the major risk factors for the development and progression of diabetic retinopathy. Recently, increased aortic stiffness has been identified as a prognostic marker of diabetic retinopathy and peripheral neuropathy.
CONCLUSION
Certain groups of diabetic individuals are at higher risk to have progressive diabetic retinopathy and eventually visual impairment. Clinical determinants and predictors are considered as prognostic markers and could help physicians to develop an effective risk-based screening program for this condition.
Topics: Diabetic Retinopathy; Disease Progression; Humans; Prognosis; Risk Factors; Vascular Stiffness
PubMed: 30767747
DOI: 10.2174/1573399815666190215120435 -
American Journal of Cardiovascular... Jun 2019Current guidelines recommend renin-angiotensin-aldosterone system (RAAS) inhibitors in the treatment of diabetic kidney disease (DKD). However, evidence suggests that... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Current guidelines recommend renin-angiotensin-aldosterone system (RAAS) inhibitors in the treatment of diabetic kidney disease (DKD). However, evidence suggests that the combined use of RAAS blockers may be associated with increased rates of adverse events.
OBJECTIVES
Our objective was to examine the efficacy and safety of dual blockade of the RAAS in patients with DKD.
METHODS
This was a systematic review and meta-analysis of randomized controlled trials (RCTs) published between January 1990 and January 2018 sourced via the PubMed, EMBASE, and Cochrane Library databases. RCTs were included if they investigated the efficacy and safety of dual blockade therapy compared with monotherapy in patients with DKD. Random effects models were used in meta-analysis to account for heterogeneities in effect sizes across the reviewed studies. Analyses were stratified by blood pressure and albuminuria. We further conducted subgroup analyses by considering various combinations of RAAS inhibitors.
RESULTS
Based on 42 RCTs with 14,576 patients, dual RAAS blockade therapy was associated with significant decreases in blood pressure, albuminuria, and proteinuria. However, dual therapy was not superior to monotherapy in terms of reductions in all-cause mortality, cardiovascular mortality, or progression to end-stage renal disease (ESRD). Significant increases in serum potassium and rates of hyperkalemia and hypotension were more common in patients treated with dual therapy. However, glomerular filtration rates (GFR) did not decrease significantly with dual therapy. In subgroup analysis, an angiotensin-converting enzyme inhibitor (ACEI) plus an angiotensin-receptor blocker (ARB) or a direct renin inhibitor (DRI) plus an ACEI/ARB did not significantly increase the risk of hyperkalemia, hypotension, and adverse events, and the risk of hypotension increased significantly within the normotensive subgroup but not within the hypertensive subgroup. The risk of hyperkalemia increased significantly in patients with DKD with macroalbuminuria but not in those with microalbuminuria.
CONCLUSION
Dual inhibition therapy is superior to monotherapy for blood pressure control and urine protein reduction, though such superiority does not translate into improvements in longer-term outcomes, such as reduced progression to ESRD, all-cause mortality, and cardiovascular mortality. An ACEI plus an ARB or a DRI plus an ACEI/ARB may be a safe and effective therapy for patients with DKD, and combination therapy may be suitable for patients with DKD and hypertension and microalbuminuria.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Diabetic Nephropathies; Disease Progression; Drug Therapy, Combination; Humans; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Renin; Renin-Angiotensin System
PubMed: 30737754
DOI: 10.1007/s40256-018-00321-5