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Current Diabetes Reviews 2020The prevalence of type 2 diabetes (DM) in children is disturbingly increasing in parallel with the increasing childhood obesity. Better knowledge regarding the...
BACKGROUND
The prevalence of type 2 diabetes (DM) in children is disturbingly increasing in parallel with the increasing childhood obesity. Better knowledge regarding the pathophysiology of type 2 DM in children is paramount to devise an effective management plan.
OBJECTIVE
Discuss the pathophysiology of type 2 DM in children and adolescents.
METHODS AND RESULTS
This is a comprehensive review of the literature on this topic. Type 2 DM in childhood is viewed as a continuum of insulin resistance (IR) which is determined by an underlying genetic predisposition, intrauterine environment, excessive food consumption, continued rapid weight gain, and poor lifestyle. Besides IR, this is compounded by multiple metabolic defects including β-cell dysfunction and inadequate insulin secretion, α-cell dysfunction, hyperglucagonemia and increased hepatic glucose production, lipotoxicity, inflammation, deficiencies in incretin production and action, and increased renal glucose reabsorption. The confluence of genetic and environmental factors underscores the complexity in disease progression.
CONCLUSION
A consistent single risk factor for type 2 DM is obesity and related IR and therefore it is essential to curtail the progression of obesity. It is important to investigate the role of stringent dietary and nutritional approaches, medications that enhance β-cell function and insulin sensitivity.
Topics: Adolescent; Child; Diabetes Mellitus, Type 2; Humans; Insulin Resistance; Pediatric Obesity; Risk Factors
PubMed: 29879890
DOI: 10.2174/1573399814666180608074510 -
Health and Quality of Life Outcomes Jun 2020End-stage renal disease (ESRD) leads to renal replacement therapy and certainly has an impact on patients' health-related quality of life (HRQoL). This study aimed to... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
End-stage renal disease (ESRD) leads to renal replacement therapy and certainly has an impact on patients' health-related quality of life (HRQoL). This study aimed to review and compare the HRQoL between peritoneal dialysis (PD) and hemodialysis (HD) patients using the 36-Item Short Form Health Survey (SF-36), EuroQoL-5-dimension (EQ-5D) and the Kidney Disease Quality of Life Instrument (KDQOL).
METHODOLOGY
Systematic review was conducted by identify relevant studies through MEDLINE and SCOPUS up to April 2017. Studies were eligible with following criteria: studied in ESRD patients, compare any pair of renal replacement modalities, and reported HRQoL. The unstandardized mean differences (USMD) of HRQoL among modalities were calculated and pooled using a random-effect models if heterogeneity was present, otherwise a fixed-effect model was applied.
RESULTS
A total of twenty-one studies were included with 29,000 participants. Of them, mean age and percent male were 48.1 years and 45.1, respectively. The pooled USMD (95% CI) of SF-36 between PD and HD (base) were 1.86 (0.47, 3.24) and 0.42 (- 1.99, 2.82) for mental component and physical component summary scores, respectively. For EQ-5D, the pooled USMD of utility and visual analogue scale (VAS) score were 0.02 (- 0.06, 0.10) and 3.56 (1.73, 5.39), respectively. The pooled USMD of KDQOL were 9.67 (5.67, 13.68), 6.71 (- 5.92, 19.32) 6.30 (- 0.41, 12.18), 2.35 (- 4.35, 9.04), 2.10 (0.07, 4.13), and 1.21 (- 2.98, 5.40) for burden of kidney disease, work status, effects of kidney disease, quality of social interaction, symptoms, and cognitive function.
CONCLUSION
Patients with chronic kidney disease (CKD) stage 5 or ESRD treated with PD had better generic HRQoL measured by SF-36 and EQ-5D than HD patients. In addition, PD had higher specific HRQoL by KDQOL than HD patients in subdomain of physical functioning, role limitations due to emotional problems, effects and burden of kidney disease.
Topics: Adult; Aged; Disease Progression; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Quality of Life; Renal Dialysis; Surveys and Questionnaires
PubMed: 32552800
DOI: 10.1186/s12955-020-01449-2 -
Nefrologia 2020Physical exercise may offer multiple benefits to patients with chronic kidney disease (CKD). However, it was not traditionally recommended because of the possibility of... (Meta-Analysis)
Meta-Analysis
Physical exercise may offer multiple benefits to patients with chronic kidney disease (CKD). However, it was not traditionally recommended because of the possibility of impairing renal function and increasing proteinuria. The objective of this study is to review the clinical trials on physical exercise in patients with CKD and describe its effect on the progression of kidney disease and other factors associated. Randomized clinical trials (RCT) comparing an intervention that included an exercise component with a control group without physical exercise in non-dialysis patients with CKD from 2007 to 2018 in English and Spanish were included. PubMed, Scopus, Embase, Ovid (Medline) and PEDro databases were used for the search. Effects of physical exercise were summarized by the standardized mean difference (SMD). No differences were found in glomerular filtration rate or proteinuria between the intervention group and the control group: SMD -0.3 (P=.81); SMD 26.6 (P=.82). Positive effects were obtained on peak oxygen consumption: SMD 2.5 (P<.001), functional capacity: SMD 56.6 (P<.001), upper limb strength: SMD 6.8 (P<.001) and hemoglobin: SMD 0.3 (P=.003). An improvement on the quality of life was also evident using the KDQOL-36 survey: SMD 3.56 (P=.02) and the SF-36 survey: SMD 6.66 (P=.02). In conclusion, the practice of low-intensity physical exercise routinely has no negative impact on renal function. On the contrary, it improves aerobic and functional capacity, impacting positively on the quality of life.
Topics: Cardiovascular System; Combined Modality Therapy; Exercise; Exercise Therapy; Female; Glomerular Filtration Rate; Humans; Kidney; Male; Oxygen Consumption; Proteinuria; Quality of Life; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Renal Replacement Therapy; Treatment Outcome
PubMed: 32305232
DOI: 10.1016/j.nefro.2020.01.002 -
Journal of Cachexia, Sarcopenia and... Oct 2022Quantification and monitoring of lean body mass is an important component of nutrition assessment to determine nutrition status and muscle loss. The negative impact of... (Review)
Review
Quantification and monitoring of lean body mass is an important component of nutrition assessment to determine nutrition status and muscle loss. The negative impact of reduced muscle mass and muscle function is increasingly evident across acute and chronic disease states but is particularly pronounced in patients with cancer. Ultrasound is emerging as a promising tool to directly measure skeletal muscle mass and quality. Unlike other ionizing imaging techniques, ultrasound can be used repeatedly at the bedside and may compliment nutritional risk assessment. This review aims to describe the current use of skeletal muscle ultrasound (SMUS) to measure muscle mass and quality in patients with acute and chronic clinical conditions and its ability to predict functional capacity, severity of malnutrition, hospital admission, and survival. Databases were searched from their inception to August 2021 for full-text articles in English. Relevant articles were included if SMUS was investigated in acute or chronic clinical contexts and correlated with a defined clinical outcome measure. Data were synthesized for narrative review due to heterogeneity between studies. This review analysed 37 studies (3100 patients), which met the inclusion criteria. Most studies (n = 22) were conducted in critical care. The clinical outcomes investigated included functional status at discharge (intensive care unit-acquired weakness), nutritional status, and length of stay. SMUS was also utilized in chronic conditions such as chronic obstructive pulmonary disease, chronic heart failure, and chronic renal failure to predict hospital readmission and disease severity. Only two studies investigated the use of SMUS in patients with cancer. Of the 37 studies, 28 (76%) found that SMUS (cross-sectional area, muscle thickness, and echointensity) showed significant associations with functional capacity, length of stay, readmission, and survival. There was significant heterogeneity in terms of ultrasound technique and outcome measurement across the included studies. This review highlights that SMUS continues to gain momentum as a potential tool for skeletal muscle assessment and predicting clinically important outcomes. Further work is required to standardize the technique in nutritionally vulnerable patients, such as those with cancer, before SMUS can be widely adopted as a bedside prognostic tool.
Topics: Critical Care; Humans; Intensive Care Units; Malnutrition; Muscle, Skeletal; Muscular Diseases; Nutritional Status
PubMed: 35851996
DOI: 10.1002/jcsm.13041 -
Frontiers in Pharmacology 2021We aim to perform a systematic review and meta-analysis examining randomized controlled trials assessing the efficacy and safety of sacubitril/valsartan in patients on... (Review)
Review
We aim to perform a systematic review and meta-analysis examining randomized controlled trials assessing the efficacy and safety of sacubitril/valsartan in patients on renal outcomes, in comparison with the renin-angiotensin-aldosterone system inhibitor (RAASi). Eligible studies were retrieved on MEDLINE, EMBASE, and Cochrane until September 2021. The primary outcome was the incidence of renal impairment, which was defined as the composite of increases in serum creatinine by >0.3 mg/dl and/or a reduction in eGFR ≥25%, development of ESRD, or renal death. We pooled relative risks (RRs) with 95% confidence intervals (CIs) or the mean difference with 95% CIs for the variables. Our search yielded 10 randomized controlled trials with a total of 18,362 patients. Compared with RAASi treatment, patients treated with sacubitril/valsartan had lower incidence of composite renal impairment (10 studies, 18,362 patients, RR 0.84; 95% CI 0.72-0.96, = 0.01; = 22%), ESRD development (3 studies, 13,609 patients, RR 0.53; 95% CI 0.30-0.96, = 0.03; = 0%), drug discontinuation due to renal events (4 studies, 9,995 patients, RR 0.58; 95% CI 0.40-0.83, = 0.003; = 47%), severe hyperkalemia (6 studies, 16,653 patients, RR 0.80; 95% CI 0.68-0.93, = 0.01; = 25%) and a slower eGFR decline (4 studies, 13,608 patients, WMD 0.56; 95% CI 0.36-0.76, < 0.00001; = 65%). Subgroup analysis demonstrated that sacubitril/valsartan was associated with a lower incidence of renal impairment in patients with heart failure and preserved ejection fraction (HFpEF), but not in those with heart failure and reduced ejection fraction (HFrEF). The superior renal function preservation of sacubitril/valsartan treatment was not associated with different baseline eGFR levels and follow-up duration. There was a smaller increase in the change in the urine albumin-to-creatinine ratio (UACR) (3 studies, 9,114 patients, SMD 0.06; 95% CI 0.02-0.10, = 0.003; = 14%) with sacubitril/valsartan treatment. However, patients with heart failure appeared to have increased microalbuminuria, not patients without HF ( = 0.80 for interaction). Sacubitril/valsartan was associated with a lower incidence of composite renal impairment especially in patients with HFpEF, but higher microalbuminuria in patients with heart failure (both HFrEF and HFpEF) compared with RAASi. The lower incidence of severe hyperkalemia and drug discontinuation due to renal events in patients with sacubitril/valsartan treatment demonstrated its superior safety compared with RAASi.
PubMed: 34867310
DOI: 10.3389/fphar.2021.604017 -
Journal of Advanced Research Dec 2023Crush syndrome (CS) is a kind of traumatic and ischemic injury that seriously threatens life after prolonged compression. It is characterized by systemic inflammatory... (Review)
Review
BACKGROUND
Crush syndrome (CS) is a kind of traumatic and ischemic injury that seriously threatens life after prolonged compression. It is characterized by systemic inflammatory reaction, myoglobinuria, hyperkalemia and acute kidney injury (AKI). Especially AKI, it is the leading cause of death from CS. There are various cell death forms in AKI, among which ferroptosis is a typical form of cell death. However, the role of ferroptosis has not been fully revealed in CS-AKI.
AIM OF REVIEW
This review aimed to summarize the evidence of ferroptosis in CS-AKI and its related molecular mechanism, discuss the therapeutic significance of ferroptosis in CS-AKI, and open up new ideas for the treatment of CS-AKI.
KEY SCIENTIFIC CONCEPTS OF REVIEW
One of the main pathological manifestations of CS-AKI is renal tubular epithelial cell dysfunction and cell death, which has been attributed to massive deposition of myoglobin. Large amounts of myoglobin released from damaged muscle deposited in the renal tubules, impeding the normal renal tubules function and directly damaging the tubules with oxidative stress and elevated iron levels. Lipid peroxidation damage and iron overload are the distinguishing features of ferroptosis. Moreover, high levels of pro-inflammatory cytokines and damage-associated molecule pattern molecules (HMGB1, double-strand DNA, and macrophage extracellular trap) in renal tissue have been shown to promote ferroptosis. However, how ferroptosis occurs in CS-AKI and whether it can be a therapeutic target remains unclear. In our current work, we systematically reviewed the occurrence and underlying mechanism of ferroptosis in CS-AKI.
Topics: Humans; Acute Kidney Injury; Cell Death; Crush Syndrome; Ferroptosis; Myoglobin
PubMed: 36702249
DOI: 10.1016/j.jare.2023.01.016 -
Frontiers in Immunology 2022Chronic kidney disease (CKD) is a major public-health problem that increases the risk of end-stage kidney disease (ESKD), cardiovascular diseases, and other... (Review)
Review
INTRODUCTION
Chronic kidney disease (CKD) is a major public-health problem that increases the risk of end-stage kidney disease (ESKD), cardiovascular diseases, and other complications. Kidney transplantation is a renal-replacement therapy that offers better survival compared to dialysis. Antibody-mediated rejection (ABMR) is a significant complication following kidney transplantation: it contributes to both short- and long-term injury. The standard-of-care (SOC) therapy combines plasmapheresis and Intravenous Immunoglobulins (IVIg) with or without steroids, with or without rituximab: however, despite this combined treatment, ABMR remains the main cause of graft loss. IL-6 is a key cytokine: it regulates inflammation, and the development, maturation, and activation of T cells, B cells, and plasma cells. Tocilizumab (TCZ) is the main humanized monoclonal aimed at IL-6R and appears to be a safe and possible strategy to manage ABMR in sensitized recipients. We conducted a literature review to assess the place of the anti-IL-6R monoclonal antibody TCZ within ABMR protocols.
MATERIALS AND METHODS
We systematically reviewed the PubMed literature and reviewed six studies that included 117 patients and collected data on the utilization of TCZ to treat ABMR.
RESULTS
Most studies report a significant reduction in levels of Donor Specific Antibodies (DSAs) and reduced inflammation and microvascular lesions (as found in biopsies). Stabilization of the renal function was observed. Adverse events were light to moderate, and mortality was not linked with TCZ treatment. The main side effect noted was infection, but infections did not occur more frequently in patients receiving TCZ as compared to those receiving SOC therapy.
CONCLUSION
TCZ may be an alternative to SOC for ABMR kidney-transplant patients, either as a first-line treatment or after failure of SOC. Further randomized and controlled studies are needed to support these results.
Topics: Antibodies, Monoclonal, Humanized; Female; Graft Rejection; Graft Survival; HLA Antigens; Humans; Inflammation; Isoantibodies; Kidney Transplantation; Male
PubMed: 35493469
DOI: 10.3389/fimmu.2022.839380 -
International Journal of Molecular... Sep 2020Chronic kidney disease (CKD) is associated with the development of mineral bone disorder (MBD), osteoporosis, and fragility fractures. Among CKD patients, adynamic bone...
Chronic kidney disease (CKD) is associated with the development of mineral bone disorder (MBD), osteoporosis, and fragility fractures. Among CKD patients, adynamic bone disease or low bone turnover is the most common type of renal osteodystrophy. The consequences of CKD-MBD include increased fracture risk, greater morbidity, and mortality. Thus, the goal is to prevent the occurrences of fractures by means of alleviating CKD-induced MBD and treating subsequent osteoporosis. Changes in mineral and humoral metabolism as well as bone structure develop early in the course of CKD. CKD-MBD includes abnormalities of calcium, phosphorus, PTH, and/or vitamin D; abnormalities in bone turnover, mineralization, volume, linear growth, or strength; and/or vascular or other soft tissue calcification. In patients with CKD-MBD, using either DXA or FRAX to screen fracture risk should be considered. Biomarkers such as bALP and iPTH may assist to assess bone turnover. Before initiating an antiresorptive or anabolic agent to treat osteoporosis in CKD patients, lifestyle modifications, such as exercise, calcium, and vitamin D supplementation, smoking cessation, and avoidance of excessive alcohol intake are important. Managing hyperphosphatemia and SHPT are also crucial. Understanding the complex pathogenesis of CKD-MBD is crucial in improving one's short- and long-term outcomes. Treatment strategies for CKD-associated osteoporosis should be patient-centered to determine the type of renal osteodystrophy. This review focuses on the mechanism, evaluation and management of patients with CKD-MBD. However, further studies are needed to explore more details regarding the underlying pathophysiology and to assess the safety and efficacy of agents for treating CKD-MBD.
Topics: Biomarkers; Bone and Bones; Calcium; Calcium, Dietary; Chronic Kidney Disease-Mineral and Bone Disorder; Fractures, Bone; Humans; Kidney Diseases; Osteoporosis; Phosphorus; Renal Dialysis; Renal Insufficiency, Chronic; Vitamin D
PubMed: 32961953
DOI: 10.3390/ijms21186846 -
International Journal of Surgery... Mar 2022Robot-assisted kidney transplantation (RAKT) has emerged as an alternative for kidney transplant recipients with the potential benefits of minimally invasive surgery.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Robot-assisted kidney transplantation (RAKT) has emerged as an alternative for kidney transplant recipients with the potential benefits of minimally invasive surgery. The aim of this systematic review and meta-analysis is to compare the clinical outcomes of RAKT with open kidney transplantation (OKT).
METHODS
MEDLINE, Embase, Web of Science and Cochrane databases were systematically searched. Baseline characteristics, intraoperative and postoperative outcomes were collected, as well as long-term renal function and data on graft and patient survival.
RESULTS
Eleven studies were included, which compared 482 RAKT procedures with 1316 OKT procedures. RAKT was associated with lower a risk of surgical site infection (Risk ratio (RR) = 0.15, p < 0.001), symptomatic lymphocele (RR = 0.20, p = 0.03), less postoperative pain (Mean difference (MD) = -1.38 points, p < 0.001), smaller incision length (MD = -8.51 cm, p < 0.001), and shorter length of hospital stay (MD = -1.69 days, p = 0.03) compared with OKT. No difference was found in renal function, graft, and patient survival.
CONCLUSIONS
RAKT is a safe and feasible alternative to OKT with less surgical complications without compromising renal function, graft and patient survival.
Topics: Humans; Kidney Transplantation; Operative Time; Robotic Surgical Procedures; Robotics; Treatment Outcome
PubMed: 35183735
DOI: 10.1016/j.ijsu.2022.106264 -
The Cochrane Database of Systematic... Nov 2022Acute kidney injury (AKI) is a common condition among patients in intensive care units (ICUs) and is associated with high numbers of deaths. Kidney replacement therapy... (Review)
Review
BACKGROUND
Acute kidney injury (AKI) is a common condition among patients in intensive care units (ICUs) and is associated with high numbers of deaths. Kidney replacement therapy (KRT) is a blood purification technique used to treat the most severe forms of AKI. The optimal time to initiate KRT so as to improve clinical outcomes remains uncertain. This is an update of a review first published in 2018. This review complements another Cochrane review by the same authors: Intensity of continuous renal replacement therapy for acute kidney injury.
OBJECTIVES
To assess the effects of different timing (early and standard) of KRT initiation on death and recovery of kidney function in critically ill patients with AKI.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant's Specialised Register to 4 August 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Register, ClinicalTrials and LILACS to 1 August 2022.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs). We included all patients with AKI in the ICU regardless of age, comparing early versus standard KRT initiation. For safety and cost outcomes, we planned to include cohort studies and non-RCTs.
DATA COLLECTION AND ANALYSIS
Data were extracted independently by two authors. The random-effects model was used, and results were reported as risk ratios(RR) for dichotomous outcomes and mean difference(MD) for continuous outcomes, with 95% confidence intervals (CI).
MAIN RESULTS
We included 12 studies enrolling 4880 participants. Overall, most domains were assessed as being at low or unclear risk of bias. Compared to standard treatment, early KRT initiation may have little to no difference on the risk of death at day 30 (12 studies, 4826 participants: RR 0.97,95% CI 0.87 to 1.09; I²= 29%; low certainty evidence), and death after 30 days (7 studies, 4534 participants: RR 0.99, 95% CI 0.92 to 1.07; I² = 6%; moderate certainty evidence). Early KRT initiation may make little or no difference to the risk of death or non-recovery of kidney function at 90 days (6 studies, 4011 participants: RR 0.91, 95% CI 0.74 to 1.11; I² = 66%; low certainty evidence); CIs included both benefits and harms. Low certainty evidence showed early KRT initiation may make little or no difference to the number of patients who were free from KRT (10 studies, 4717 participants: RR 1.07, 95% CI 0.94 to1.22; I² = 55%) and recovery of kidney function among survivors who were free from KRT after day 30 (10 studies, 2510 participants: RR 1.02, 95% CI 0.97 to 1.07; I² = 69%) compared to standard treatment. High certainty evidence showed early KRT initiation increased the risk of hypophosphataemia (1 study, 2927 participants: RR 1.80, 95% CI 1.33 to 2.44), hypotension (5 studies, 3864 participants: RR 1.54, 95% CI 1.29 to 1.85; I² = 0%), cardiac-rhythm disorder (6 studies, 4483 participants: RR 1.35, 95% CI 1.04 to 1.75; I² = 16%), and infection (5 studies, 4252 participants: RR 1.33, 95% CI 1.00 to 1.77; I² = 0%); however, it is uncertain whether early KRT initiation increases or reduces the number of patients who experienced any adverse events (5 studies, 3983 participants: RR 1.23, 95% CI 0.90 to 1.68; I² = 91%; very low certainty evidence). Moderate certainty evidence showed early KRT initiation probably reduces the number of days in hospital (7 studies, 4589 participants: MD-2.45 days, 95% CI -4.75 to -0.14; I² = 10%) and length of stay in ICU (5 studies, 4240 participants: MD -1.01 days, 95% CI -1.60 to -0.42; I² = 0%).
AUTHORS' CONCLUSIONS
Based on mainly low to moderate certainty of the evidence, early KRT has no beneficial effect on death and may increase the recovery of kidney function. Earlier KRT probably reduces the length of ICU and hospital stay but increases the risk of adverse events. Further adequate-powered RCTs using robust and validated tools that complement clinical judgement are needed to define the optimal time of KRT in critical patients with AKI in order to improve their outcomes. The surgical AKI population should be considered in future research.
Topics: Humans; Renal Replacement Therapy; Acute Kidney Injury; Kidney; Length of Stay; Critical Illness
PubMed: 36416787
DOI: 10.1002/14651858.CD010612.pub3