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Journal of the American Society of... Sep 2019Surrogate end points are needed to assess whether treatments are effective in the early stages of CKD. GFR decline leads to kidney failure, but regulators have not... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Surrogate end points are needed to assess whether treatments are effective in the early stages of CKD. GFR decline leads to kidney failure, but regulators have not approved using differences in the change in GFR from the beginning to the end of a randomized, controlled trial as an end point in CKD because it is not clear whether small changes in the GFR slope will translate to clinical benefits.
METHODS
To assess the use of GFR slope as a surrogate end point for CKD progression, we performed a meta-analysis of 47 RCTs that tested 12 interventions in 60,620 subjects. We estimated treatment effects on GFR slope (mean difference in GFR slope between the randomized groups), for the total slope starting at baseline, chronic slope starting at 3 months after randomization, and on the clinical end point (doubling of serum creatinine, GFR<15 ml/min per 1.73 m, or ESKD) for each study. We used Bayesian mixed-effects analyses to describe the association of treatment effects on GFR slope with the clinical end point and to test how well the GFR slope predicts a treatment's effect on the clinical end point.
RESULTS
Across all studies, the treatment effect on 3-year total GFR slope (median =0.97; 95% Bayesian credible interval [BCI], 0.78 to 1.00) and on the chronic slope ( 0.96; 95% BCI, 0.63 to 1.00) accurately predicted treatment effects on the clinical end point. With a sufficient sample size, a treatment effect of 0.75 ml/min per 1.73 m/yr or greater on total slope over 3 years or chronic slope predicts a clinical benefit on CKD progress with at least 96% probability.
CONCLUSIONS
With large enough sample sizes, GFR slope may be a viable surrogate for clinical end points in CKD RCTs.
Topics: Bayes Theorem; Biomarkers; Creatinine; Disease Progression; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Predictive Value of Tests; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic
PubMed: 31292197
DOI: 10.1681/ASN.2019010007 -
International Journal of Molecular... May 2021The kidneys play a vital role in the basic physiological functions of the body [...].
The kidneys play a vital role in the basic physiological functions of the body [...].
Topics: Acute Kidney Injury; Animals; Disease Models, Animal; Humans; Inflammation; Kidney Diseases; Regeneration; Renal Insufficiency, Chronic; Reperfusion Injury
PubMed: 34070441
DOI: 10.3390/ijms22115589 -
Cells Nov 2022Acute kidney injury (AKI) is a major clinical problem associated with increased morbidity and mortality. Despite intensive research, the clinical outcome remains poor,... (Review)
Review
Acute kidney injury (AKI) is a major clinical problem associated with increased morbidity and mortality. Despite intensive research, the clinical outcome remains poor, and apart from supportive therapy, no other specific therapy exists. Furthermore, acute kidney injury increases the risk of developing chronic kidney disease (CKD) and end-stage renal disease. Acute tubular injury accounts for the most common intrinsic cause of AKI. The main site of injury is the proximal tubule due to its high workload and energy demand. Upon injury, an intratubular subpopulation of proximal epithelial cells proliferates and restores the tubular integrity. Nevertheless, despite its strong regenerative capacity, the kidney does not always achieve its former integrity and function and incomplete recovery leads to persistent and progressive CKD. Clinical and experimental data demonstrate sexual differences in renal anatomy, physiology, and susceptibility to renal diseases including but not limited to ischemia-reperfusion injury. Some data suggest the protective role of female sex hormones, whereas others highlight the detrimental effect of male hormones in renal ischemia-reperfusion injury. Although the important role of sex hormones is evident, the exact underlying mechanisms remain to be elucidated. This review focuses on collecting the current knowledge about sexual dimorphism in renal injury and opportunities for therapeutic manipulation, with a focus on resident renal progenitor stem cells as potential novel therapeutic strategies.
Topics: Male; Female; Humans; Acute Kidney Injury; Kidney; Renal Insufficiency, Chronic; Reperfusion Injury; Gonadal Steroid Hormones
PubMed: 36497080
DOI: 10.3390/cells11233820 -
CMAJ : Canadian Medical Association... Jul 2023
Review
Topics: Humans; Aged; Kidney Failure, Chronic; Renal Insufficiency, Chronic
PubMed: 37460121
DOI: 10.1503/cmaj.221427-f -
Seminars in Pediatric Surgery Dec 2021Pediatric hemodialysis access is a demanding field. Procedures are infrequent, technically challenging, and associated with high complication and failure rates. Each...
Pediatric hemodialysis access is a demanding field. Procedures are infrequent, technically challenging, and associated with high complication and failure rates. Each procedure affects subsequent access and transplants sites. The choice is made easier and outcomes improved when access decisions are made by a multidisciplinary, pediatric, hemodialysis access team. This manuscript reviews the current literature and offers technical suggestions to improve outcomes.
Topics: Child; Humans; Renal Dialysis; Renal Insufficiency
PubMed: 34930591
DOI: 10.1016/j.sempedsurg.2021.151121 -
Peritoneal Dialysis International :... May 2020
Topics: Creatinine; Glomerular Filtration Rate; Goals; Humans; Patient Selection; Peritoneal Dialysis; Renal Insufficiency
PubMed: 32063219
DOI: 10.1177/0896860819895364 -
International Journal of Molecular... Dec 2023This review examines the impact of childhood obesity on the kidney from an epidemiological, pathogenetic, clinical, and pathological perspective, with the aim of... (Review)
Review
This review examines the impact of childhood obesity on the kidney from an epidemiological, pathogenetic, clinical, and pathological perspective, with the aim of providing pediatricians and nephrologists with the most current data on this topic. The prevalence of childhood obesity and chronic kidney disease (CKD) is steadily increasing worldwide, reaching epidemic proportions. While the impact of obesity in children with CKD is less pronounced than in adults, recent studies suggest a similar trend in the child population. This is likely due to the significant association between obesity and the two leading causes of end-stage renal disease (ESRD): diabetes mellitus (DM) and hypertension. Obesity is a complex, systemic disease that reflects interactions between environmental and genetic factors. A key mechanism of kidney damage is related to metabolic syndrome and insulin resistance. Therefore, we can speculate about an adipose tissue-kidney axis in which neurohormonal and immunological mechanisms exacerbate complications resulting from obesity. Adipose tissue, now recognized as an endocrine organ, secretes cytokines called adipokines that may induce adaptive or maladaptive responses in renal cells, leading to kidney fibrosis. The impact of obesity on kidney transplant-related outcomes for both donors and recipients is also significant, making stringent preventive measures critical in the pre- and post-transplant phases. The challenge lies in identifying renal involvement as early as possible, as it is often completely asymptomatic and not detectable through common markers of kidney function. Ongoing research into innovative technologies, such as proteomics and metabolomics, aims to identify new biomarkers and is constantly evolving. Many aspects of pediatric disease progression in the population of children with obesity still require clarification. However, the latest scientific evidence in the field of nephrology offers glimpses into various new perspectives, such as genetic factors, comorbidities, and novel biomarkers. Investigating these aspects early could potentially improve the prognosis of these young patients through new diagnostic and therapeutic strategies. Hence, the aim of this review is to provide a comprehensive exploration of the pathogenetic mechanisms and prevalent pathological patterns of kidney damage observed in children with obesity.
Topics: Adult; Humans; Child; Pediatric Obesity; Kidney; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Biomarkers
PubMed: 38139229
DOI: 10.3390/ijms242417400 -
Iranian Journal of Kidney Diseases Mar 2022Zinc is the second most abundant essential trace element in the human body with important regulatory functions in cellular and subcellular levels in several tissues.... (Review)
Review
Zinc is the second most abundant essential trace element in the human body with important regulatory functions in cellular and subcellular levels in several tissues. Zinc deficiency is associated with the development and progression of chronic kidney disease (CKD) and its complications. With the progression of CKD to end-stage kidney disease (ESKD) and initiation of dialysis, zinc is further removed from the body, potentiating the zinc deficiency. Dietary intake plays a major role in zinc-deficiency-related risks and progression of CKD. By taking into account the evidence from clinical studies depicting the mutual correlations between zinc and CKD, and the plausibility based on animal studies, it can be deduced that zinc deficiency has a causative role in CKD and its progression. This review highlights the role of zinc deficiency in kidney disease and the possible indication for supplementation of zinc at various stages of CKD. DOI: 10.52547/ijkd.6702.
Topics: Animals; Female; Humans; Kidney Failure, Chronic; Male; Renal Dialysis; Renal Insufficiency, Chronic; Zinc
PubMed: 35489076
DOI: No ID Found -
Toxins Mar 2020Cardiac remodeling occurs frequently in chronic kidney disease patients and affects quality of life and survival. Current treatment options are highly inadequate. As... (Review)
Review
Cardiac remodeling occurs frequently in chronic kidney disease patients and affects quality of life and survival. Current treatment options are highly inadequate. As kidney function declines, numerous metabolic pathways are disturbed. Kidney and heart functions are highly connected by organ crosstalk. Among others, altered volume and pressure status, ischemia, accelerated atherosclerosis and arteriosclerosis, disturbed mineral metabolism, renal anemia, activation of the renin-angiotensin system, uremic toxins, oxidative stress and upregulation of cytokines stress the sensitive interplay between different cardiac cell types. The fatal consequences are left-ventricular hypertrophy, fibrosis and capillary rarefaction, which lead to systolic and/or diastolic left-ventricular failure. Furthermore, fibrosis triggers electric instability and sudden cardiac death. This review focuses on established and potential pathophysiological cardiorenal crosstalk mechanisms that drive uremia-induced senescence and disease progression, including potential known targets and animal models that might help us to better understand the disease and to identify novel therapeutics.
Topics: Animals; Cardio-Renal Syndrome; Disease Models, Animal; Humans; Renal Insufficiency, Chronic; Ventricular Remodeling
PubMed: 32150864
DOI: 10.3390/toxins12030161 -
Clinical Journal of the American... May 2021
Topics: Exercise; Humans; Renal Insufficiency, Chronic; Sedentary Behavior
PubMed: 33888537
DOI: 10.2215/CJN.03460321