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Current Pharmaceutical Design 2023Chronic kidney disease (CKD) has a clinical characteristic of progressive loss of kidney function and becomes a serious health and social concern. SGLT2i (sodium-glucose... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Chronic kidney disease (CKD) has a clinical characteristic of progressive loss of kidney function and becomes a serious health and social concern. SGLT2i (sodium-glucose cotransporter 2 inhibitors), a class of anti-diabetic medications, are shown to reduce cardiovascular and renal events. This systematic review and meta-analysis aimed to assess whether SGLT2i could become a new treatment strategy for CKD for its renal protection and safety.
METHODS
Based on predetermined criteria, a bibliographical search was performed on May 31, 2022, by searching the following databases: ISI Web of Science, Embase, PubMed, and the Cochrane Library. Statistical analysis was conducted to assess renal protection and safety of SGLT2i by using Cochrane Review Manager Version 5.3.
RESULTS
Thirty randomised controlled trials fulfilled the inclusion criteria and were eligible for this meta-analysis. Our study found that the SGLT2i can sustainably reduce the urine albumin/creatinine ratio (UACR) at different time points and prevent the progression to macroalbuminuria. Before 24 weeks, SGLT2i can decrease the estimated glomerular filtration rate (eGFR) compared to the control group. Interestingly, after 24 weeks, SGLT2i can continuously maintain the increase in eGFR when compared with the control group. Furthermore, SGLT2i can reduce the event rates of incident or worsening nephropathy, a decline in estimated eGFR of ≥ 50%, doubling of serum creatinine level, acute renal failure and renal failure. Interestingly, the renoprotective effects of SGLT2i are independent of its glycemic effects. SGLT2i can reduce the morbidity rate of any related adverse events, any related severe adverse events and SGLT2i have not increased the event rates of urinary tract infection, bone fractures, amputation, and acute pancreatitis when compared with the control group.
CONCLUSION
SGLT2i can protect renal function and are safe drug for CKD. SGLT2i are promising therapeutic agents for CKD patients.
Topics: Humans; Acute Disease; Diabetes Mellitus, Type 2; Kidney; Renal Insufficiency, Chronic; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 37537933
DOI: 10.2174/1381612829666230804103643 -
BMC Nephrology Jul 2023
PubMed: 37495940
DOI: 10.1186/s12882-023-03274-3 -
Pharmacology & Therapeutics Sep 2023We have performed a systematic review of studies reporting on the renal effects of SGLT2 inhibitors in rodent models of diabetes. In 105 studies, SGLT2 inhibitors... (Review)
Review
We have performed a systematic review of studies reporting on the renal effects of SGLT2 inhibitors in rodent models of diabetes. In 105 studies, SGLT2 inhibitors improved not only the glycemic control but also various aspects of renal function in most cases. These nephroprotective effects were similarly reported whether treatment with the SGLT2 inhibitor started concomitant with the onset of diabetes (within 1 week), early after onset (1-4 weeks) or after nephropathy had developed (>4 weeks after onset) with the latter probably having the greatest translational value. They were observed across various animal models of type 1 and type 2 diabetes/obesity (4 and 23 models, respectively), although studies in the type 2 diabetes model of db/db mice more often had negative data than in other models. Among possibly underlying pathophysiological mechanisms of nephroprotection, treatment with SGLT2 inhibitors had beneficial effects on lipid metabolism, blood pressure, glomerulosclerosis as well as renal tubular fibrosis, apoptosis, oxidative stress, and inflammation. These pathomechanisms highly influence atherosclerosis and renal health, which are two major factors that lead to an enhanced mortality in patients with diabetes and/or chronic kidney disease. Interestingly, renal SGLT2 inhibitor effects did not always correlate with those on glucose homeostasis, particularly in a limited number of direct comparative studies with other anti-diabetic treatments, indicating that nephroprotection may at least partly occur by mechanisms other than improving glycemic control. Our analyses did not provide evidence for different nephroprotective efficacy between SGLT2 inhibitors. Importantly, only four of 105 studies reported on female animals, and none provided direct comparative data between sexes. We conclude that more data on female animals and more direct comparative studies with other anti-diabetic compounds and combinations of treatments are needed.
Topics: Animals; Female; Mice; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Kidney; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 37495021
DOI: 10.1016/j.pharmthera.2023.108503 -
Frontiers in Pharmacology 2023Diabetic nephropathy (DN) is the main cause of chronic kidney disease (CKD) and end-stage renal failure (ESRF), and the control of disease progression and adverse...
Diabetic nephropathy (DN) is the main cause of chronic kidney disease (CKD) and end-stage renal failure (ESRF), and the control of disease progression and adverse events during treatment needs to be improved. This study aimed to systematically evaluate the clinical efficacy and safety of Niaoduqing granules (NDQG) in the treatment of diabetic kidney disease (DKD). Randomized controlled trials (RCTs) of NDQG for DKD from Chinese and English databases up to 31 August 2022 were included. The quality of the literature was assessed using the risk of bias tool of the Cochrane Handbook. At a 95% confidence interval (CI), relative risk (RR) and Cohen's d were used for the categorical and continuous variables, respectively, and Stata 16.0 software was used for statistical analysis. A funnel plot and Egger's tests were used to assess publication bias. A total of 4,006 patients were included in 52 RCTs, including 1,987 cases in the control group and 2,019 cases in the treatment group. Compared with conventional treatment (CT), combined NDQG therapy is more effective in improving clinical efficiency [RR = 1.23, 95% confidence interval (1.17, 1.29), < 0.001, = 53.17%], kidney function (urinary albumin excretion rate [SMD = -0.90, 95% CI (-1.14, -0.66), < 0.001, = 78.19%], 24hUTP levels [SMD = -0.81, 95% CI (-1.08, -0.55), < 0.001, = 87.08%], blood urea nitrogen [SMD = -0.54, 95% CI (-0.69, -0.39), < 0.01, = 77.01%], SCr [SMD = -0.68, 95% CI (-0.90, -0.45), < 0.001, = 89.97%], CCr [SMD = 0.76, 95% CI (0.10,1.42), = 0.02, = 95.97%], and Cys-C [SMD = -1.32, 95% CI (-2.25, -0.40), = 0.01, = 93.44%]), the level of glucose metabolism (fasting blood glucose [SMD = -0.18, 95% CI (-0.38, 0.03), = 0.10, = 71.18%] and HbA1c [SMD = -0.42, 95% CI (-0.86, -0.02), = 0.06, = 81.64%]), the level of lipid metabolism (total cholesterol [SMD = -0.70, 95% CI (-1.01, -0.39), < 0.001, = 86.74%] and triglyceride [SMD = -0.61, 95% CI (-0.87,-0.36), < 0.001, = 80.64%]), inflammatory factors (Hs-CRP [SMD = -1.00, 95% CI (-1.54, -0.46), < 0.001, = 86.81%], IL-18 [SMD = -1.25, 95% CI (-1.58, -0.92), < 0.001, = 0], and TNF-α [SMD = -1.28, 95% CI (-1.64, -0.91), < 0.001, = 75.73%]), and indicators of oxidative stress (malondialdehyde [SMD = -0.88, 95% CI (-1.22, -0.54), < 0.001, = 66.01%] and advanced oxidation protein products [SMD = -0.92, 95% CI (-1.85, 0.00), < 0.001, = 90.68%]). In terms of improving uric acid [SMD = -1.59, 95% CI (-3.45, 0.27), = 0.09, = 94.67%], 2hPG [SMD = -0.04, 95% CI (-0.61, 0.53), = 0.89, = 84.33%], HDL-C [SMD = 0.71, 95% CI (0.02, 1.40), = 0.04, = 87.43%], Hb [SMD = 0.11, 95% CI (-0.10, 0.32), = 0.32, = 0.00]), and superoxide dismutase [SMD = 1.32, 95% CI (0.44, 2.20), < 0.001, = 93.48%], the effect is not obvious. Adjuvant treatment with NDQG did not increase the incidence of adverse reactions in the control group [SMD = 0.98, 95% CI (0.71, 1.34), = 0.89, = 1.59%]. Obvious publication bias was detected by funnel plot and Egger's test. Our meta-analysis showed that adjuvant treatment with NDQG has more advantages than conventional treatment alone in the DKD treatment, which could improve clinical efficiency, kidney function, the level of glucose metabolism, the level of lipid metabolism, inflammatory factors, and oxidative stress indicators. At the same time, it also showed that NDQG are relatively safe. However, more high-quality studies are needed to provide more reliable evidence for clinical use. : https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022373726, identifier CRD42022373726.
PubMed: 37475716
DOI: 10.3389/fphar.2023.1180751 -
BMC Endocrine Disorders Jul 2023Hyperuricemia increases morbidity and mortality in type 2 diabetic individuals. It is linked to the expansion of diabetes and cardiovascular diseases indicators, as well... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hyperuricemia increases morbidity and mortality in type 2 diabetic individuals. It is linked to the expansion of diabetes and cardiovascular diseases indicators, as well as being a significant predictor of coronary artery disease. It also leads to a poor prognosis and increment of diabetic complications including diabetic neuropathy, retinopathy, and nephropathy. Therefore, this systematic review and meta-analysis was aimed to determine the pooled prevalence of hyperuricemia among type 2 diabetes mellitus patients in Africa.
METHODS
We conducted a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. To identify relevant articles, we searched electronic databases such as PubMed, Google Scholar, African Journal Online, Science Direct, Embase, ResearchGate, Scopus, and Web of Sciences. The quality of the included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. Statistical analysis was performed using Stata 14.0 software. To evaluate heterogeneity, we utilized Cochran's Q test and I statistics. Publication bias was assessed through the examination of a funnel plot and Egger's test. The pooled prevalence was estimated using a random effect model. Furthermore, sub-group and sensitivity analyses were conducted.
RESULTS
The overall pooled prevalence of hyperuricemia among type 2 diabetic patients in Africa was 27.28% (95% CI: 23.07, 31.49). The prevalence was highest in Central Africa 33.72% (95% CI: 23.49, 43.95), and lowest in North Africa 24.72% (95% CI: 14.38, 35.07). Regarding sex, the pooled prevalence of hyperuricemia among female and male type 2 diabetic patients was 28.02% (95% CI: 22.92, 33.48) and 28.20% (95% CI: 22.92, 33.48), respectively.
CONCLUSION
This systematic review and meta-analysis showed a high prevalence of hyperuricemia among type 2 diabetic patients. So, regular screening and diagnosis of hyperuricemia required for preventing its pathological effects and contribution to chronic complications of diabetes.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO (2022: CRD42022331279).
Topics: Humans; Male; Female; Diabetes Mellitus, Type 2; Prevalence; Hyperuricemia; Africa; Diabetes Complications
PubMed: 37464401
DOI: 10.1186/s12902-023-01408-0 -
Diabetes, Metabolic Syndrome and... 2023Microalbuminuria (MAU) is considered the earliest sign of diabetic nephropathy among diabetes patients. In order to effectively manage diabetic nephropathy and its... (Review)
Review
BACKGROUND
Microalbuminuria (MAU) is considered the earliest sign of diabetic nephropathy among diabetes patients. In order to effectively manage diabetic nephropathy and its consequences early, detection of microalbuminuria as soon as possible, especially for diabetes patients, is critical. Therefore, the present study aimed to determine the pooled prevalence of microalbuminuria among diabetes patients in Africa.
METHODS
Electronic databases such as Google Scholar, PubMed, African Journals Online, Web of Science, Cochrane Library, EMBASE, and ResearchGate were searched for articles and grey literature. The STATA version 14 software was used to conduct the meta-analysis. I and Cochran's Q test were employed to assess the presence of heterogeneity between studies. Due to the presence of heterogeneity, a random effect model was used. The publication bias was assessed using the symmetry of the funnel plot and Egger's test statistics. Moreover, subgroup analysis, trim and fill analysis, and sensitivity analysis were also done.
RESULTS
The overall pooled prevalence of microalbuminuria among diabetes patients in Africa was 37.11% (95% CI 31.27-42.95). Substantial heterogeneity was observed between studies, with I values of 94.7%. Moreover, this meta-analysis showed that the pooled estimate of microalbuminuria among type 1 and type 2 diabetes patients was 35.34% (95% CI: 23.89-46.80, I=94.2), and 40.24% (95% CI: 32.0-48.47, I=94.9) respectively. MAU, on the other hand, was more common in people with diabetes for more than 5 years 38.73% (95% CI: 29.34-48.13) than in people with diabetes for less than 5 years 31.48% (95% CI: 18.73-44.23).
CONCLUSION
This systematic review and meta-analysis found a high prevalence of microalbuminuria among diabetes patients. As a result, early detection of microalbuminuria is critical for preventing and treating microvascular complications such as diabetic nephropathy and the onset of end-stage renal disease.
PubMed: 37457109
DOI: 10.2147/DMSO.S409483 -
Diabetes Therapy : Research, Treatment... Sep 2023Diabetic nephropathy is a common complication among patients with diabetes mellitus, and it has been linked to a higher risk of depression. However, the magnitude of...
INTRODUCTION
Diabetic nephropathy is a common complication among patients with diabetes mellitus, and it has been linked to a higher risk of depression. However, the magnitude of this association remains unclear. This study aimed to systematically review and meta-analyse the risk of depression in patients with diabetic nephropathy compared to diabetes patients without nephropathy.
METHODS
We conducted a systematic literature review, searching multiple databases from January 1964 to March 2023, and included randomized controlled trials, non-randomized controlled trials, and observational studies. We assessed the risk of bias using the Newcastle Ottawa scale for observational studies. The statistical analysis was performed using STATA version 14.2, and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. A total of 60 studies were included.
RESULTS
The pooled OR for the risk of depression among patients with diabetic nephropathy was 1.78 (95% CI 1.56-2.04; I = 83%; n = 56), indicating a significantly higher risk compared to diabetes patients without nephropathy (p < 0.001). Pooling the effect size across these studies showed that the pooled OR was 1.15 (95% CI 1.14-1.16; I = 88%; n = 32). Subgroup analyses based on the type of diabetes and study region revealed no significant differences in the pooled estimates.
CONCLUSION
This study demonstrates that patients with diabetic nephropathy have a significantly higher risk of depression compared to diabetes patients without nephropathy. These findings highlight the importance of assessing and addressing the mental health of patients with diabetic nephropathy as part of their overall healthcare management.
PubMed: 37368150
DOI: 10.1007/s13300-023-01436-y -
Nephrology, Dialysis, Transplantation :... Oct 2023Dual renin-angiotensin-aldosterone system (RAAS) blockade involves dual therapy with a combination of angiotensin-converting enzyme inhibitors (ACEis),... (Meta-Analysis)
Meta-Analysis
The association between dual RAAS inhibition and risk of acute kidney injury and hyperkalemia in patients with diabetic kidney disease: a systematic review and meta-analysis.
BACKGROUND AND OBJECTIVES
Dual renin-angiotensin-aldosterone system (RAAS) blockade involves dual therapy with a combination of angiotensin-converting enzyme inhibitors (ACEis), angiotensin-receptor blockers (ARBs), direct renin inhibitors (DRIs), or mineralocorticoid receptor antagonists (MRAs). It is hypothesized that dual RAAS blockade would result in a more complete inhibition of the RAAS cascade. However, large clinical trials on dual RAAS inhibition have shown increased risk of acute kidney injury (AKI) and hyperkalemia without additional benefit on mortality, cardiovascular events, or chronic kidney disease (CKD) progression compared to RAAS inhibitor monotherapy in patients with diabetic kidney disease (DKD). The development of newer, more selective non-steroidal MRAs as cardiorenal protective therapies has created a new opportunity for dual RAAS inhibition. We conducted a systematic review and meta-analysis of the risks of AKI and hyperkalemia with dual RAAS blockade in patients with DKD.
DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS
This is a systematic review and meta-analysis of the randomized controlled trials (RCT) published from 1 January 2006 to 30 May 2022. The study population included adult patients with DKD receiving dual RAAS blockade. A total of 31 RCTs and 33 048 patients were included in the systematic review. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using random effects.
RESULTS
There were 208 AKI events in 2690 patients on ACEi + ARB versus 170 in 4264 patients with ACEi or ARB monotherapy (pooled RR 1.48, 95% CI: 1.23-1.39). There were 304 hyperkalemia events in 2818 patients on ACEi + ARB versus 208 in 4396 patients with ACEi or ARB monotherapy (pooled RR 1.97, 95% CI: 1.32-2.94). A non-steroidal MRA + ACEi or ARB showed no increase in the risk of AKI (pooled RR 0.97, 95% CI: 0.81-1.16) compared to ACEi or ARB monotherapy but had a 2-fold higher risk of hyperkalemia with 953 events in 7837 patients in dual therapy versus 454 events in 6895 patients in monotherapy (pooled RR 2.05, 95% CI: 1.84-2.28). A steroidal MRA + ACEi or ARB had a 5-fold higher risk of hyperkalemia with 28 events in 245 at risk in dual therapy versus five events in 248 at risk in monotherapy (pooled RR 5.42 95% CI: 2.15-13.67).
CONCLUSION
Dual therapy with RAASi is associated with an increased risk of AKI and hyperkalemia compared to RAASi monotherapy. Conversely, dual therapy with RAAS inhibitors and non-steroidal MRAs have no additional risk of AKI but a similar risk of hyperkalemia, which is lower than dual therapy with RAAS inhibitors and steroidal MRAs.
Topics: Adult; Humans; Renin-Angiotensin System; Diabetic Nephropathies; Hyperkalemia; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Acute Kidney Injury; Diabetes Mellitus
PubMed: 37309038
DOI: 10.1093/ndt/gfad101 -
Journal of Renal Nutrition : the... Sep 2023Diabetes Mellitus is a highly prevalent condition in which Diabetes Mellitus type 2 is the most common. Diabetic Kidney Disease is one of the most relevant complications... (Review)
Review
Diabetes Mellitus is a highly prevalent condition in which Diabetes Mellitus type 2 is the most common. Diabetic Kidney Disease is one of the most relevant complications and affects approximately one-third of patients with Diabetes Mellitus. It is characterized by increased urinary protein excretion and a decrease in glomerular filtration rate, assessed by serum creatinine levels. Recent studies have shown that vitamin D levels are low in these patients. This study aimed to conduct a systematic review of the effects of vitamin D supplementation on proteinuria and creatinine, which are important markers for assessing the severity of kidney disease in patients with Diabetic Kidney Disease. PUBMED, EMBASE, and COCHRANE databases were consulted, Preferred Reporting Items for a Systematic Review and Meta-Analysis guidelines were followed, and the COCHRANE toll for bias assessment was applied. Six papers were quantitative studies and fulfilled the inclusion criteria for this review. The results showed that vitamin D supplementation of 50,000 I.U./week for 8 weeks effectively reduced proteinuria and creatinine in patients with Diabetic Kidney Disease, particularly in patients with Diabetes Mellitus type 2. Vitamin D supplementation is beneficial for patients with Diabetic Kidney Disease by having essential effects on disease-related inflammatory markers, such as the reduction of proteinuria and creatinine. However, more clinical trials must be conducted to evaluate the intervention among more significant numbers of patients.
Topics: Humans; Diabetic Nephropathies; Creatinine; Vitamin D; Diabetes Mellitus, Type 2; Proteinuria; Dietary Supplements
PubMed: 37302723
DOI: 10.1053/j.jrn.2023.05.006 -
BMC Nephrology Jun 2023Changes of serum galectin-3 (Gal-3) is associated with the pathogenesis of diabetic nephropathy (DN). However, current literature indicates that the given results remain... (Meta-Analysis)
Meta-Analysis
AIMS
Changes of serum galectin-3 (Gal-3) is associated with the pathogenesis of diabetic nephropathy (DN). However, current literature indicates that the given results remain debatable and inconsistent. Hence, the aim of this present meta-analysis was to focus on the predictive role of serum Gal-3 in patients with DN.
METHODS
The PubMed, Embase, Cochrane Library and Web of Science databases were systematically searched for studies that reported the relationship between Gal-3 levels and DN risk, from the inception of each database to March, 2023. The literature we selected for inclusion based on inclusion and exclusion criteria. The standard mean difference (SMD) with corresponding 95% confidence intervals (95% CI) were used to investigate the association. When I value exceeding 50%, we will consider it has the presence of a higher level of heterogeneity. A sensitivity analysis and subgroup analysis were performed to seek the potential sources of heterogeneity. The quality assessment was performed using according to the Newcastle-Ottawa Quality Assessment Scale (NOS). The data analysis was conducted using STATA version 13.0 software.
RESULTS
We ultimately enrolled 9 studies enrolling a total of 3137 patients in the final analysis. The SMD of serum Gal-3 was higher in patients with DN group (SMD 1.10 ng/mL [0.63, 1.57]; I: 96.1%). Upon removal of a study in sensitivity analysis, patients with DN had higher serum Gal-3 levels compared to control patients (SMD 1.03 ng/mL [0.52, 1.54], I: 94.4%). Further subgroup analysis was performed based on the region. No matter in Asia, Europe or Africa, the serum Gal-3 level of DN patients is significantly higher than that of the control population (SMD: 0.73; 95% CI: 0.58 to 0.87 for Asian; SMD: 0.79; 95% CI: 0.48 to 1.10 for Europe; SMD: 3.15; 95% CI: 2.73 to 3.56 for Africa).
CONCLUSION
In conclusion, these results suggested that higher serum Gal-3 may increase the risk of DN. More fundamental studies are necessary to clarify the exact physiopathological basis mechanisms of Gal-3 effects. In addition, further research, especially emphasis on the cut-off value should be given, and is best to predict their actual importance as well as the diagnostic accuracy.
Topics: Humans; Galectin 3; Diabetic Nephropathies; Europe; Africa; Diabetes Mellitus
PubMed: 37291488
DOI: 10.1186/s12882-023-03226-x