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Hormone and Metabolic Research =... Aug 2019Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new kind of hypoglycemic drugs that improve glucose homeostasis by inhibiting renal glucose reabsorption. Recent... (Meta-Analysis)
Meta-Analysis
Systematic Review and Meta-Analysis of Randomized Controlled Trials on the Effect of SGLT2 Inhibitor on Blood Leptin and Adiponectin Level in Patients with Type 2 Diabetes.
Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new kind of hypoglycemic drugs that improve glucose homeostasis by inhibiting renal glucose reabsorption. Recent studies have shown that SGLT2 inhibitors can also mediate body metabolism through regulation of adipokines level, but the effects of SGLT2 inhibitors on the concentration of adipokines (leptin and adiponectin) remains controversial. This meta-analysis was set out to evaluate the changes in circulating leptin and adiponectin levels in patients with type 2 diabetes mellitus (T2DM) receiving SGLT2 inhibitors therapy. Ten randomized controlled trials (RCTs), that evaluated the effects of SGLT2 inhibitors on blood leptin and adiponectin levels in patients with type 2 diabetes, were identified by performing a systematic search of Pubmed, Embase, Cochrane, and Web of science databases through July 2018. Data were calculated using a random-effects model and presented as standardized mean difference (SMD) and 95% confidence interval (CI). Compared with placebo, treatment with SGLT2 inhibitors contributed to a decreased circulating leptin levels (SMD -0.29, 95% CI -0.56, -0.03) and an increased circulating adiponectin levels (SMD 0.30, 95% CI 0.22, 0.38). SGLT2 inhibitor treatment was associated with decreased circulating leptin levels and increased circulating adiponectin levels, which might contribute to the beneficial effects of SGLT2 inhibitors on metabolic homeostasis.
Topics: Adiponectin; Biomarkers; Diabetes Mellitus, Type 2; Humans; Leptin; Prognosis; Randomized Controlled Trials as Topic; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 31408894
DOI: 10.1055/a-0958-2441 -
Critical Care (London, England) Oct 2018Metabolic alkalosis is common in patients with respiratory failure and may delay weaning in mechanically ventilated patients. Carbonic anhydrase inhibitors block renal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Metabolic alkalosis is common in patients with respiratory failure and may delay weaning in mechanically ventilated patients. Carbonic anhydrase inhibitors block renal bicarbonate reabsorption, and thus reverse metabolic alkalosis. The objective of this systematic review is to assess the benefits and harms of carbonic anhydrase inhibitor therapy in patients with respiratory failure and metabolic alkalosis.
METHODS
We searched the following electronic sources from inception to August 2017: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and SCOPUS. Randomized clinical trials were included if they assessed at least one of the following outcomes: mortality, duration of hospital stay, duration of mechanical ventilation, adverse events, and blood gas parameters. Teams of two review authors worked in an independent and duplicate manner to select eligible trials, extract data, and assess risk of bias of the included trials. We used meta-analysis to synthesize statistical data and then assessed the certainty of evidence using the GRADE methodology.
RESULTS
Six eligible studies were identified with a total of 564 participants. The synthesized data did not exclude a reduction or an increase in mortality (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.57 to 1.56) or in duration of hospital stay (mean difference (MD) 0.42 days, 95% CI -4.82 to 5.66) with the use of carbonic anhydrase inhibitors. Carbonic anhydrase inhibitor therapy resulted in a decrease in the duration of mechanical ventilation of 27 h (95% CI -50 to -4). Also, it resulted in an increase in PaO (MD 11.37 mmHg, 95% CI 4.18 to 18.56) and a decrease in PaCO (MD -4.98 mmHg, 95% CI -9.66, -0.3), serum bicarbonate (MD -5.03 meq/L, 95% CI -6.52 to -3.54), and pH (MD -0.04, 95% CI -0.07 to -0.01). There was an increased risk of adverse events in the carbonic anhydrase inhibitor group (RR 1.71, 95% CI 0.98 to 2.99). Certainty of evidence was judged to be low for most outcomes.
CONCLUSION
In patients with respiratory failure and metabolic alkalosis, carbonic anhydrase inhibitor therapy may have favorable effects on blood gas parameters. In mechanically ventilated patients, carbonic anhydrase inhibitor therapy may decrease the duration of mechanical ventilation. A major limitation of this finding was that only two trials assessed this clinically important outcome.
Topics: Alkalosis; Carbonic Anhydrase Inhibitors; Humans; Metabolic Diseases; Odds Ratio; Randomized Controlled Trials as Topic; Respiratory Insufficiency; Ventilator Weaning
PubMed: 30371345
DOI: 10.1186/s13054-018-2207-6 -
Amino Acids Jul 2018We recently found that renal carbonic anhydrase (CA) is involved in the reabsorption of inorganic nitrite (NO), an abundant reservoir of nitric oxide (NO) in tissues and... (Meta-Analysis)
Meta-Analysis
Results, meta-analysis and a first evaluation of UR, the urinary nitrate-to-nitrite molar ratio, as a measure of nitrite reabsorption in experimental and clinical settings.
We recently found that renal carbonic anhydrase (CA) is involved in the reabsorption of inorganic nitrite (NO), an abundant reservoir of nitric oxide (NO) in tissues and cells. Impaired NO synthesis in the endothelium and decreased NO bioavailability in the circulation are considered major contributors to the development and progression of renal and cardiovascular diseases in different conditions including diabetes. Isolated human and bovine erythrocytic CAII and CAIV can convert nitrite to nitrous acid (HONO) and its anhydride NO which, in the presence of thiols (RSH), are further converted to S-nitrosothiols (RSNO) and NO. Thus, CA may be responsible both for the homeostasis of nitrite and for its bioactivation to RSNO/NO. We hypothesized that enhanced excretion of nitrite in the urine may contribute to NO-related dysfunctions in the renal and cardiovascular systems, and proposed the urinary nitrate-to-nitrite molar ratio, i.e., UR, as a measure of renal CA-dependent excretion of nitrite. Based on results from clinical and experimental animal studies, here, we report on a first evaluation of UR. We determined UR values in preterm neonates, healthy children, and adults, in children suffering from type 1 diabetes mellitus (T1DM) or Duchenne muscular dystrophy (DMD), in elderly subjects suffering from chronic rheumatic diseases, type 2 diabetes mellitus (T2DM), coronary artery disease (CAD), or peripheral arterial occlusive disease (PAOD). We also determined UR values in healthy young men who ingested isosorbide dinitrate (ISDN), pentaerythrityl tetranitrate (PETN), or inorganic nitrate. In addition, we tested the utility of UR in two animal models, i.e., the LEW.1AR1-iddm rat, an animal model of human T1DM, and the APOE*3-Leiden.CETP mice, a model of human dyslipidemia. Mean UR values were lower in adult patients with rheumatic diseases (187) and in T2DM patients of the DALI study (74) as compared to healthy elderly adults (660) and healthy young men (1500). The intra- and inter-variabilities of UR were of the order of 50% in young and elderly healthy subjects. UR values were lower in black compared to white boys (314 vs. 483, P = 0.007), which is in line with reported lower NO bioavailability in black ethnicity. Mean UR values were lower in DMD (424) compared to healthy (730) children, but they were higher in T1DM children (1192). ISDN (3 × 30 mg) decreased stronger UR compared to PETN (3 × 80 mg) after 1 day (P = 0.046) and after 5 days (P = 0.0016) of oral administration of therapeutically equivalent doses. In healthy young men who ingested NaNO (0.1 mmol/kg/d), UR was higher than in those who ingested the same dose of NaCl (1709 vs. 369). In LEW.1AR1-iddm rats, mean UR values were lower than in healthy rats (198 vs. 308) and comparable to those in APOE*3-Leiden.CETP mice (151).
Topics: Animals; Arterial Occlusive Diseases; Carbonic Anhydrases; Cattle; Coronary Artery Disease; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Kidney; Mice; Muscular Dystrophy, Duchenne; Nitrates; Nitric Oxide; Nitrites; Rats; Rheumatic Diseases
PubMed: 29728915
DOI: 10.1007/s00726-018-2573-z -
Archives of Endocrinology and Metabolism May 2024Burosumab, a monoclonal antibody directed against the fibroblast growth factor 23 (FGF23), has been approved for the treatment of X-linked hypophosphatemia (XLH). We... (Comparative Study)
Comparative Study
Burosumab, a monoclonal antibody directed against the fibroblast growth factor 23 (FGF23), has been approved for the treatment of X-linked hypophosphatemia (XLH). We conducted a systematic review to compare the efficacy and safety of burosumab versus conventional therapy (phosphorus and calcitriol) on XLH treatment. After a comprehensive literature search on MEDLINE/PubMed and Embase, we found nine studies for inclusion in the analysis. Risk of bias was assessed, and a random-effects model was used to determine the effect size. Clinical, biochemical, and radiological parameters of disease severity before and after treatment were analyzed and expressed in standardized mean difference (SMD). Burosumab resulted in normalization of phosphate homeostasis with an increase in renal tubular phosphate reabsorption and significant resolution of skeletal lesions (change in Thacher's total rickets severity score SMD: -1.46, 95% confidence interval [CI]: -1.76 to -1.17, < 0.001, improvement in deformities, and decline in serum alkaline phosphatase levels [SMD: 130.68, 95% CI: 125.26-136.1, < 0.001)]. Conventional therapy led to similar improvements in all these parameters but to a lower degree. In adults, burosumab normalized phosphorus levels (SMD: 1.23, 95% CI: 0.98-1.47, < 0.001) with resultant clinical improvement. Burosumab treatment was well tolerated, with only mild treatment-related adverse effects. The present review indicates a potential role for burosumab in improving rickets, deformities, and growth in children with XLH. Given its superior efficacy and safety profile, burosumab could be an effective therapeutic option in children. We suggest further studies comparing burosumab versus conventional therapy in children and adults with XLH.
Topics: Humans; Familial Hypophosphatemic Rickets; Antibodies, Monoclonal, Humanized; Fibroblast Growth Factor-23; Treatment Outcome; Calcitriol; Antibodies, Monoclonal; Phosphorus
PubMed: 38788147
DOI: 10.20945/2359-4292-2023-0242 -
The Cochrane Database of Systematic... Mar 2019Improvements in diagnostics and treatment for paediatric malignancies resulted in a major increase in survival. However, childhood cancer survivors (CCS) are at risk of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Improvements in diagnostics and treatment for paediatric malignancies resulted in a major increase in survival. However, childhood cancer survivors (CCS) are at risk of developing adverse effects caused by multimodal treatment for their malignancy. Nephrotoxicity is a known side effect of several treatments, including cisplatin, carboplatin, ifosfamide, radiotherapy and nephrectomy, and can cause glomerular filtration rate (GFR) impairment, proteinuria, tubulopathy, and hypertension. Evidence about the long-term effects of these treatments on renal function remains inconclusive. It is important to know the risk of, and risk factors for, early and late adverse renal effects, so that ultimately treatment and screening protocols can be adjusted. This review is an update of a previously published Cochrane Review.
OBJECTIVES
To evaluate existing evidence on the effects of potentially nephrotoxic treatment modalities on the prevalence of renal dysfunction in survivors treated for childhood cancer with a median or mean survival of at least one year after cessation of treatment, where possible in comparison with the general population or CCS treated without potentially nephrotoxic treatment. In addition, to evaluate evidence on associated risk factors, such as follow-up duration, age at time of diagnosis and treatment combinations, as well as the effect of doses.
SEARCH METHODS
On 31 March 2017 we searched the following electronic databases: CENTRAL, MEDLINE and Embase. In addition, we screened reference lists of relevant studies and we searched the congress proceedings of the International Society of Pediatric Oncology (SIOP) and The American Society of Pediatric Hematology/Oncology (ASPHO) from 2010 to 2016/2017.
SELECTION CRITERIA
Except for case reports, case series and studies including fewer than 20 participants, we included studies with all study designs that reported on renal function (one year or longer after cessation of treatment), in CCS treated before the age of 21 years with cisplatin, carboplatin, ifosfamide, radiation involving the kidney region, a nephrectomy, or a combination of two or more of these treatments. When not all treatment modalities were described or the study group of interest was unclear, a study was not eligible for the evaluation of prevalence. We still included it for the assessment of risk factors if it had performed a multivariable analysis.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed study selection, 'Risk of bias' assessment and data extraction using standardised data collection forms. We performed analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions.
MAIN RESULTS
Apart from the remaining 37 studies included from the original review, the search resulted in the inclusion of 24 new studies. In total, we included 61 studies; 46 for prevalence, six for both prevalence and risk factors, and nine not meeting the inclusion criteria, but assessing risk factors. The 52 studies evaluating the prevalence of renal dysfunction included 13,327 participants of interest, of whom at least 4499 underwent renal function testing. The prevalence of adverse renal effects ranged from 0% to 84%. This variation may be due to diversity of included malignancies, received treatments, reported outcome measures, follow-up duration and the methodological quality of available evidence.Seven out of 52 studies, including 244 participants, reported the prevalence of chronic kidney disease, which ranged from 2.4% to 32%.Of these 52 studies, 36 studied a decreased (estimated) GFR, including at least 432 CCS, and found it was present in 0% to 73.7% of participants. One eligible study reported an increased risk of glomerular dysfunction after concomitant treatment with aminoglycosides and vancomycin in CCS receiving total body irradiation (TBI). Four non-eligible studies assessing a total cohort of CCS, found nephrectomy and (high-dose (HD)) ifosfamide as risk factors for decreased GFR. The majority also reported cisplatin as a risk factor. In addition, two non-eligible studies showed an association of a longer follow-up period with glomerular dysfunction.Twenty-two out of 52 studies, including 851 participants, studied proteinuria, which was present in 3.5% to 84% of participants. Risk factors, analysed by three non-eligible studies, included HD cisplatin, (HD) ifosfamide, TBI, and a combination of nephrectomy and abdominal radiotherapy. However, studies were contradictory and incomparable.Eleven out of 52 studies assessed hypophosphataemia or tubular phosphate reabsorption (TPR), or both. Prevalence ranged between 0% and 36.8% for hypophosphataemia in 287 participants, and from 0% to 62.5% for impaired TPR in 246 participants. One non-eligible study investigated risk factors for hypophosphataemia, but could not find any association.Four out of 52 studies, including 128 CCS, assessed the prevalence of hypomagnesaemia, which ranged between 13.2% and 28.6%. Both non-eligible studies investigating risk factors identified cisplatin as a risk factor. Carboplatin, nephrectomy and follow-up time were other reported risk factors.The prevalence of hypertension ranged from 0% to 50% in 2464 participants (30/52 studies). Risk factors reported by one eligible study were older age at screening and abdominal radiotherapy. A non-eligible study also found long follow-up time as risk factor. Three non-eligible studies showed that a higher body mass index increased the risk of hypertension. Treatment-related risk factors were abdominal radiotherapy and TBI, but studies were inconsistent.Because of the profound heterogeneity of the studies, it was not possible to perform meta-analyses. Risk of bias was present in all studies.
AUTHORS' CONCLUSIONS
The prevalence of adverse renal effects after treatment with cisplatin, carboplatin, ifosfamide, radiation therapy involving the kidney region, nephrectomy, or any combination of these, ranged from 0% to 84% depending on the study population, received treatment combination, reported outcome measure, follow-up duration and methodological quality. With currently available evidence, it was not possible to draw solid conclusions regarding the prevalence of, and treatment-related risk factors for, specific adverse renal effects. Future studies should focus on adequate study designs and reporting, including large prospective cohort studies with adequate control groups when possible. In addition, these studies should deploy multivariable risk factor analyses to correct for possible confounding. Next to research concerning known nephrotoxic therapies, exploring nephrotoxicity after new therapeutic agents is advised for future studies. Until more evidence becomes available, CCS should preferably be enrolled into long-term follow-up programmes to monitor their renal function and blood pressure.
Topics: Adult; Antineoplastic Agents; Carboplatin; Child; Cisplatin; Glomerular Filtration Rate; Humans; Hypertension; Hypophosphatemia; Ifosfamide; Magnesium Deficiency; Nephrectomy; Proteinuria; Radiotherapy; Renal Insufficiency, Chronic; Risk Factors; Survivors
PubMed: 30855726
DOI: 10.1002/14651858.CD008944.pub3