Angiopoietin as a Novel Prognostic Marker in Kidney Disease.

INTRODUCTION: Renal injury is among the leading causes of morbidity and mortality; however, there are no reliable indicators for determining the likelihood of developing chronic kidney disease (CKD), CKD progression, or AKI events. Vascular growth factors called angiopoietins have a role in endothelial function, vascular remodeling, tissue stabilization, and inflammation and have been implicated as prognostic and predictive markers in AKI. METHODS: Although the exact mechanism of the relationship between kidney injury and angiopoietins is unknown, this review demonstrates that AKI patients have higher angiopoietin-2 levels and that higher angiopoietin-1 to angiopoietin-2 ratio may potentially be linked with a reduced risk of the CKD progression. RESULTS: This review therefore emphasizes the importance of angiopoietin-2 and proposes that it could be an important predictor of AKI in clinical settings. CONCLUSION: There is a need for further large-scale randomized clinical trials in order to have a better understanding of the significance of angiopoietin-2 and for the determination of its potential clinical implications.

A potential approach toward the management of sepsis: The extracorporeal cytokine hemadsorption therapy.

Infectious diseases are among the most common cause of morbidity and mortality among hospitalized patients while systemic inflammatory response syndrome is primarily attributed to the imbalance between pro-inflammatory and anti-inflammatory cytokines. Despite the improvements in the antibiotherapy alternatives and diagnostic modalities, the morbidity and mortality rates of sepsis and septic shock are relatively high among patients admitted to the intensive care units. Extracorporeal cytokine hemadsorption therapies are therapeutic approaches for such patient group with promising early results that especially have grown during COVID-19 pandemic. In this narrative review, our aim is to evaluate the current pre-clinical and clinical knowledge regarding the use of cytokine filtration systems among patients with septic shock.

Shared decision making in patients with kidney failure.

'Elderly' is most commonly defined as an individual aged 65 years or older. However, this definition fails to account for the differences in genetics, lifestyle and overall health that contribute to significant heterogeneity among the elderly beyond chronological age. As the world population continues to age, the prevalence of chronic diseases, including chronic kidney disease (CKD), is increasing and CKD frequently progresses to kidney failure. Moreover, frailty represents a multidimensional clinical entity highly prevalent in this population, which needs to be adequately assessed to inform and support medical decisions. Selecting the optimal treatment pathway for the elderly and frail kidney failure population, be it hemodialysis, peritoneal dialysis, or conservative kidney management is complex, because of the presence of comorbidities associated with low survival rates and impaired quality of life. Management of these patients should involve a multidisciplinary approach including doctors from various specialties, nurses, psychologists, dieticians, and physiotherapists. Studies are mostly retrospective and observational, lacking adjustment for confounders or address selection and indication biases, making it difficult to use these data to guide treatment decisions. Throughout this review we discuss the difficulty of making a one-size-fits-all recommendation for the clinical needs of older patients with kidney failure. We advocate that a research agenda for optimization of the critical issues we present in this review be implemented. We recommend prospective studies that address these issues, and systematic reviews incorporating the complementary evidence of both observational and interventional studies. Furthermore, we strongly support a shared decision making process matching evidence with patient preferences to ensure that individualized choices are made regarding dialysis vs. conservative kidney management, dialysis modality, and optimal vascular access.

Tirzepatide and potential use for metabolically healthy obesity.

Metabolically healthy obesity or metabolically healthy overweight (MHO) is best described as being absent of any major metabolic disorder or cardiovascular diseases such as type 2 diabetes mellitus, dyslipidemia, hypertension, and atherosclerotic cardiovascular disease despite being obese or overweight. Nevertheless, MHO is being recognized as an important risk factor for the development of cardiovascular, cerebrovascular, and peripheral artery disease. In addition, these patients are at a high risk of conversion to the metabolically unhealthy phenotype. Tirzepatide is a newly developed glucose-lowering agent which acts on the glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors. It has been shown to result in several highly beneficial outcomes including weight loss and a significant improvement in important metabolic parameters such as HbA1c, fasting serum glucose, and triglyceride/lipoprotein levels. These findings suggest that tirzepatide could potentially be beneficial to metabolically healthy obese or metabolically healthy overweight patients in reducing their risk of adverse cardiovascular outcomes and conversion to the metabolically unhealthy phenotype. In this review, we aim to discuss the potential benefits of using the novel anti-diabetic tirzepatide in the management of MHO to prevent the development of cardiovascular events and to decrease the likelihood of conversion to the unhealthy phenotype. We initially describe the clinical outcomes of MHO as well as the association of MHO with developing future cardiovascular events. We then delineate the currently available evidence behind the clinical effects of tirzepatide. We finally discuss the potential advantages of using tirzepatide in the management of MHO.

A review on renal autologous cell transplantation: an investigational approach towards chronic kidney disease.

Chronic kidney disease is among the most common causes of mortality and morbidity in adult population with limited therapeutic approaches including various medications and kidney replacement therapies. Kidney transplantation is the gold standard therapeutic alternative for the management of chronic kidney disease; nonetheless, important drawbacks include the lack of adequate living or deceased donors, high rates of pre- and post-operative complications including surgical complications, infectious complications and medication-induced adverse effects. With the latest preclinical and in vitro studies demonstrating the potentiality of kidney cells obtained from diseased kidneys to convert into fully functional kidney cells lead to a novel therapeutic alternative referred as autologous selected renal cell transplantation. Even though the clinical studies investigating the efficiency and adverse effects of autologous selected renal cell transplantation are limited, it is no doubt promising. The need for future large-scale studies on chronic kidney disease patients from a diversity of etiologies is clear for the better establishment of the therapeutic potential of autologous selected renal cell transplantation. In this narrative review, our aim is to evaluate the role of renal autologous stem cell therapy in the management of chronic kidney disease.

Novel strategies in nephrology: what to expect from the future?

Chronic kidney disease (CKD) will become the fifth global case of death by 2040. Its largest impact is on premature mortality but the number of persons with kidney failure requiring renal replacement therapy (RRT) is also increasing dramatically. Current RRT is suboptimal due to the shortage of kidney donors and dismal outcomes associated with both hemodialysis and peritoneal dialysis. Kidney care needs a revolution. In this review, we provide an update on emerging knowledge and technologies that will allow an earlier diagnosis of CKD, addressing the current so-called blind spot (e.g. imaging and biomarkers), and improve renal replacement therapies (wearable artificial kidneys, xenotransplantation, stem cell-derived therapies, bioengineered and bio-artificial kidneys).

The pathophysiology and management of vascular calcification in chronic kidney disease patients.

INTRODUCTION: Vascular calcification (VC) which is the pathological mineral deposition in the vascular system, predominantly at the intimal and medial layer of the vessel wall, is an important comorbidity in patients with chronic kidney disease (CKD) leading to significant morbidity and mortality while necessitating appropriate treatment. Our review aims to provide an in-depth analysis of the current understanding of VC. AREAS COVERED: In this review, we first discuss the pathophysiology of VC in CKD patients, then we explain the methods to predict and assess VC. Afterwards, we provide the currently available as well as the potential therapeutic approaches of VC. We finally discuss our understanding regarding the current situation surrounding VC in our expert opinion section. EXPERT OPINION: Predicting, assessing and treating VC is crucial and the future advances in the field of research surrounding VC will potentially occur in one or more of these three areas of clinical management. There is a current lack of evidence and consensus regarding specific therapeutic options for alleviating VC and this situation may not necessitate VC to be determined, detected, and documented before the available options are implemented. Regardless, the prediction and assessment of VC is still important and requires further improvement together with the developments in therapeutic alternatives. The future has the potential to bring better research which would guide and improve the management of this patient group. A more specialized approach consisting of targeted therapies and more tailored management plans for patients with CKD and VC is on the horizon.

Responses to Hypoxia: How Fructose Metabolism and Hypoxia-Inducible Factor-1a Pathways Converge in Health and Disease.

PURPOSE OF REVIEW: Oxygen is critical for the high output of energy (adenosine triphosphate) generated by oxidative phosphorylation in the mitochondria, and when oxygen delivery is impaired due to systemic hypoxia, impaired or reduced delivery of red blood cells, or from local ischemia, survival processes are activated. RECENT FINDINGS: One major mechanism is the activation of hypoxia-inducible factors (HIFs) that act to reduce oxygen needs by blocking mitochondrial function and stimulating glucose uptake and glycolysis while also stimulating red blood cell production and local angiogenesis. Recently, endogenous fructose production with uric acid generation has also been shown to occur in hypoxic and ischemic tissues where it also appears to drive the same functions, and indeed, there is evidence that many of hypoxia-inducible factors effects may be mediated by the stimulation of fructose production and metabolism. Unfortunately, while being acutely protective, these same systems in overdrive lead to chronic inflammation and disease and may also be involved in the development of metabolic syndrome and related disease. The benefit of SGLT2 inhibitors may act in part by reducing the delivery of glucose with the stimulation of fructose formation, thereby allowing a conversion from the glycolytic metabolism to one involving mitochondrial metabolism. The use of hypoxia-inducible factor stabilizers is expected to aid the treatment of anemia but, in the long-term, could potentially lead to worsening cardiovascular and metabolic outcomes. We suggest more studies are needed on the use of these agents.

Thyroid hormone Beta receptor agonists for treatment of kidney disease: A promising agent?

BACKGROUND: Chronic kidney disease is a common disorder affecting a significant portion of the adult population with high mortality and morbidity. Obesity and hyperlipidemia are prevalent in chronic kidney disease, and they may trigger fat accumulation in renal parenchyma and eventually fatty kidney. Chronic kidney disease and fatty kidney are also strongly associated with nonalcoholic fatty liver disease. Because they both lead to detrimental effects on organ function, they both need to be treated effectively to improve the outcome. AIM: In this narrative review, we have hypothesized that thyroid hormone beta receptor agonists, a novel drug group, may potentially be beneficial in the management of chronic kidney disease due to its promising outcomes among patients with nonalcoholic fatty liver disease, a condition sharing multiple common underlying pathophysiological mechanisms. RESULTS AND CONCLUSION: Thyroid hormone beta receptors are abundantly expressed in liver and kidney tissues, while both nonalcoholic fatty liver disease and chronic kidney disease share various similar pathophysiological mechanisms and triggers. Therefore, thyroid hormone beta receptor agonists may become a promising tool in the management of patients with chronic kidney disease.

Visit-to-visit blood pressure variability and risk of dementia in chronic kidney disease patients: why are blood pressure changes so important in cognitive functions?

Chronic kidney disease (CKD) is associated with cognitive functional impairment or dementia in addition to cardiovascular diseases. Aging of the population and the increasing prevalence of CKD in elderly patients are making dementia more prevalent. Blood pressure (BP) variability is an important risk factor for dementia. Although ample data link high BP variability with the risk of dementia in the general population, data on CKD patients are scarce. An observational cohort study conducted by Park et al., including 103 139 patients, demonstrated a strong association between higher visit-to-visit BP variability and increased risk of dementia in CKD patients. Both higher systolic and diastolic BP variabilities were associated with any type of dementia, including Alzheimer's and vascular dementia. Physicians must be aware of BP variability when evaluating CKD patients with hypertension.

The role of body mass index on IgA nephropathy prognosis: a systematic review and meta-analysis.

BACKGROUND: Recent studies show that obese patients have worse outcomes in IgA nephropathy as compared to normal weight patients. MATERIALS AND METHODS: We performed a systematic review and meta-analysis of prospective, retrospective, randomized and nonrandomized studies, which studied the impact of obesity or high body mass index (BMI) on different parameters of IgA nephropathy prognosis and outcome. We searched through PubMed, Ovid/Medline, Web of Science, and the Cochrane Central Register of Controlled Trials (Wiley). RESULTS: We included 16 studies in our final analysis with a total of 4258 patients. Overall, there was a significantly lower estimated glomerular filtration rate (eGFR) in IgA nephropathy patients with BMI in the overweight/obese range than in those with normal BMI (mean difference 6.01, 95% CI 2.78-9.24 ml/min/1.73 m2, P < 0.001), but no significant difference in serum creatinine or proteinuria levels. No studies measured GFR. There were contradictory results regarding the relationship between BMI and blood pressure, histological parameters or outcomes in patients with IgA nephropathy. CONCLUSIONS: Higher BMI in IgA nephropathy patients might be associated with lower kidney function, but this should be confirmed by measuring GFR. Evidence regarding other kidney damage parameters and outcomes is inconclusive.

Future of kidney imaging: Functional magnetic resonance imaging and kidney disease progression.

INTRODUCTION: Chronic kidney disease (CKD) which is a common cause of death has an increasing trend, but there is no established approach for predicting CKD progression yet. Functional magnetic resonance imaging (fMRI) studies such as blood oxygenation level-dependent MRI (BOLD-MRI), diffusion-weighted MRI (DWI-MRI), diffusion-tensor MRI (DTI-MRI) and arterial spin labelling MRI (ASL-MRI) are rising methods for the assessment of kidney functions in native and transplanted kidneys as well as the estimation of CKD progression. METHODS: Systematic literature review was performed through the Embase (Elsevier), Cochrane Central Register of Controlled Trials (Wiley), PubMed/Medline and Web of Science databases, and studies investigating the role of fMRI methods assessing kidney functions in native and transplanted kidneys, as well as the value of fMRI methods to predict CKD progression, were included. Working mechanisms, advantages and limitations of the fMRI modalities were reviewed, and three studies investigating the role of fMRI studies in kidney functions were analysed. RESULTS AND CONCLUSION: BOLD-MRI signal was found to be inversely correlated with annual eGFR change, and DWI/ADC (apparent diffusion coefficient map) values were shown to be correlated with annual eGFR decline. fMRI methods which are currently used for other systems can be utilized to provide more detailed information about kidney functions, and doctors should be ready to interpret kidney MRIs.

Structural, biochemical, and functional properties of the Rap1-Interacting Adaptor Molecule (RIAM).

Leukocytes, the leading players of immune system, are involved in innate and adaptive immune responses. Leukocyte adhesion to endothelial cells during transmigration or to antigen presenting cells during T cell activation, requires integrin activation through a process termed inside-out integrin signaling. In hematopoietic cells, Rap1 and its downstream effector RIAM (Rap1-interacting adaptor molecule) form a cornerstone for inside-out integrin activation. The Rap1/RIAM pathway is involved in signal integration for activation, actin remodeling and cytoskeletal reorganization in T cells, as well as in myeloid cell differentiation and function. RIAM is instrumental for phagocytosis, a process requiring particle recognition, cytoskeletal remodeling and membrane protrusion for engulfment and digestion. In the present review, we discuss the structural and molecular properties of RIAM and the recent discoveries regarding the functional role of the Rap1/RIAM module in hematopoietic cells.

The Use of Treatment Response Assessment Maps in Discriminating Between Radiation Effect and Persistent Tumoral Lesion in Metastatic Brain Tumors Treated with Gamma Knife Radiosurgery.

BACKGROUND: Traditional imaging modalities are not useful in the follow-up of irradiated metastatic brain tumors, because radiation can change imaging characteristics. We aimed to assess the ability of treatment response assessment maps (TRAMs) calculated from delayed-contrast magnetic resonance imaging (MRI) in differentiation between radiation effect and persistent tumoral tissue. METHODS: TRAMs were calculated by subtracting three-dimensional T1 MRIs acquired 5 minutes after contrast injection from the images acquired 60-105 minutes later. Red areas were regarded as radiation effect and blue areas as persistent tumoral lesion. Thirty-seven patients with 130 metastatic brain tumors who were treated with Gamma Knife radiosurgery and who underwent TRAMs perfusion-weighted MRI were enrolled in this retrospective study. RESULTS: The median age was 58 years and the most common primary diagnosis was lung cancer (n = 21). The median follow-up period of patients was 12 months. The overall local control rate was 100% at 1 year and 98.9% at 2 years. The median progression-free survival was 12 months. The mean overall survival was 27.3 months. The radiologic and clinical follow-up showed a clinicoradiologic diagnosis of a persistent tumoral lesion in 3 tumors (2.3%) and radiation effect in 127 tumors (97.7%). There was a fair agreement between clinicoradiologic diagnosis and TRAMs analysis (κ = 0.380). The sensitivity and positive predictive value of TRAMs in diagnosing radiation effect were 96.06% and 99.2%, respectively. TRAMs showed comparable results to perfusion-weighted MRI, with a diagnostic odds ratio of 27.4 versus 20.7, respectively. CONCLUSIONS: The presented results show the ability of TRAMs in differentiating radiation effect and persistent tumoral lesions.