Evolution Of Chronic Kidney Disease Research Articles

Discrimination of myocardial function changes: Evolution of chronic kidney disease or hemodialysis effect?

Discrimination of myocardial function changes: Evolution of chronic kidney disease or hemodialysis effect?

SA45 Natural Evolution of Chronic Kidney Disease in Diabetic Patients: Costs and Consequences in Portuguese Reality

SA45 Natural Evolution of Chronic Kidney Disease in Diabetic Patients: Costs and Consequences in Portuguese Reality

SGLT2 Inhibitors and Diabetic Kidney Disease: Targeting Multiple and Interrelated Signaling Pathways for Renal Protection.

Almost 20-40% of all patients suffering from diabetes mellitus experience chronic kidney disease, which is related to higher mortality (cardiovascular and all-cause). The implication of several pathophysiological mechanisms (hemodynamic, tubular, metabolic and inflammatory) in the pathogenesis of diabetic kidney disease generates an urgent need to develop multitarget therapeutic strategies to face its development and progression. SGLT2 inhibitors are undoubtedly a practice-changing drug class for individuals who experience type 2 diabetes and diabetic kidney disease. In vitro studies, exploratory research, sub-analyses of large randomized controlled trials, and investigation of several biomarkers have demonstrated that SGLT2 inhibitors achieved multiple beneficial activities, targeting several renal cellular and molecular pathways independent of their antihyperglycemic activity. These mainly include the reduction in intraglomerular pressure through the restoration of TGF, impacts on the renin-angiotensin-aldosterone system, improvement of renal hypoxia, adaptive metabolic alterations in substrate use/energy expenditure, improvement of mitochondrial dysfunction, and reduction of inflammation, oxidative stress and fibrosis. This manuscript thoroughly investigates the possible mechanisms that underlie their salutary renal effects in patients with diabetes, focusing on several pathways involved and the interplay between them. It also explores their upcoming role in ameliorating the evolution of chronic kidney disease in patients with diabetes.

The Role of Urinary NGAL in the Management of Primary Vesicoureteral Reflux in Children.

Vesicoureteral reflux (VUR) is the most frequent congenital urinary tract malformation and an important risk factor for urinary tract infections (UTIs). Up to 50% of children with VUR may develop reflux nephropathy (RN), and the diagnosis and monitoring of renal scars are invasive and costly procedures, so it is paramount to find a non-invasive and accurate method to predict the risk of renal damage. Neutrophil gelatinase-associated lipocalin (NGAL) has already proven to be a good predictive biomarker in acute kidney injuries, but there are few studies that have investigated the role of NGAL in primary VUR in children. Our aim is to review the predictive value of urine NGAL (uNGAL) as a non-invasive biomarker of RN in children with primary VUR, as well as its ability to predict the evolution of chronic kidney disease (CKD). Based on our analysis of the available original studies, uNGAL can be an accurate and reliable biomarker of RN and its progression to CKD. Some studies suggested a good correlation between VUR severity and uNGAL levels, but other studies found no significant correlation. The relationship between VUR severity and uNGAL levels is likely complex and influenced by factors such as UTIs, the timing of the urine sample collection, and the age and overall health of the patient.

Proteomic landscape of the extracellular matrix in the fibrotic kidney

The extracellular matrix (ECM) is a complex three-dimensional network of proteins surrounding cells, forming a niche that controls cell adhesion, proliferation, migration and differentiation. The ECM network provides an architectural scaffold for surrounding cells and undergoes dynamic changes in composition and contents during the evolution of chronic kidney disease (CKD). Here, we unveiled the proteomic landscape of the ECM by delineating proteome-wide and ECM-specific alterations in normal and fibrotic kidneys. Decellularized kidney tissue scaffolds were made and subjected to proteomic profiling by liquid chromatography with tandem mass spectrometry. A total of 172 differentially expressed proteins were identified in these scaffolds from mice with CKD. Through bioinformatics analysis and experimental validation, we identified a core set of nine signature proteins, which could play a role in establishing an oxidatively stressed, profibrotic, proinflammatory and antiangiogenetic microenvironment. Among these nine proteins, glutathione peroxidase 3 (GPX3) was the only protein with downregulated expression during CKD. Knockdown of GPX3 invivo augmented ECM expression and aggravated kidney fibrotic lesions after obstructive injury. Transcriptomic profiling revealed that GPX3 depletion resulted in an altered expression of the genes enriched in hypoxia pathway. Knockdown of GPX3 induced NADPH oxidase 2 expression, promoted kidney generation of reactive oxygen species and activated p38 mitogen-activated protein kinase. Conversely, overexpression of exogenous GPX3 alleviated kidney fibrosis, inhibited NADPH oxidase 2 and p38 mitogen-activated protein kinase. These findings suggest that oxidative stress is a pivotal element of the fibrogenic microenvironment. Thus, our studies represent a comprehensive proteomic characterization of the ECM in the fibrotic kidney and provide novel insights into molecular composition of the fibrogenic microenvironment.

Late discovery of pregnancy in an advanced age dialytic patient: case report

Pregnancy in dialysis women still has a low prevalence due to possible complications resulting from the evolution of chronic kidney disease. However, recent outcomes have shown an advance in the continuity of pregnancy increasing the chances of renal dialysis patients completing the gestational process. Among the care for a pregnant woman on dialysis, strict control of the urea value, monitoring of anemia, blood pressure levels, balanced nutrition, metabolic control, and electrolyte changes are the main determinants of preventing complications in this disease. Monitoring fetal growth, when pregnancy is known, is necessary. When pregnancies arise from patients undergoing renal replacement therapy, the obstacles are greater for the mother as well as for the fetus, making it essential to bring the nephrological team closer to the obstetrician and pediatrician. This report addresses the experience of a multidisciplinary team directed to a woman of advanced age and undergoing dialysis, reporting the discovery of a late pregnancy of 29 weeks and the unfolding of its evolution given the peculiarity of this morbid condition.

GSTM1 Copy Number and Kidney Disease in People With HIV

GSTM1 Copy Number and Kidney Disease in People With HIV

A systematic review and meta-analysis of the association between uric acid levels and chronic kidney disease

The function of uric acid (UA) in the genesis and evolution of chronic kidney disease (CKD) has motivated numerous studies, but the results remain inconclusive. We sought to conduct a systematic review and meta-analysis of cohort studies aiming to analyze the association of UA levels with the incidence and progression of CKD. Pubmed/Medline, Lilacs/Bireme and Web of Science were searched to identify eligible studies, following the PRISMA protocol. Data were presented for CKD incidence and progression separately. For the meta-analysis, studies with data stratified by subgroups according to serum UA levels were selected. The inverse variance-weighted random effects model was used to generate a combined effect estimate. Meta-regressions were performed to identify the causes of heterogeneity. The Newcastle–Ottawa Scale was used to assess the risk of bias. The publication bias was tested by funnel plot and Egger’s test. Eighteen CKD incidence studies (n = 398,663) and six CKD progression studies (n = 13,575) were included. An inverse relationship was observed between UA levels and protection from CKD incidence and progression. Lower UA levels were protective for the risk of CKD incidence (RR 0.65 [95% CI 0.56–0.75]) and progression (RR 0.55 [95% CI 0.44–0.68]). UA seems to be implicated both in the genesis of CKD and its evolution.

MIF rs755622 and IL6 rs1800795 Are Implied in Genetic Susceptibility to End-Stage Renal Disease (ESRD).

Chronic kidney disease (CKD) is characterized by an increased risk of kidney failure and end-stage renal disease (ESRD). Aging and comorbidities as cardiovascular diseases, metabolic disorders, infectious diseases, or tumors, might increase the risk of dialysis. In addition, genetic susceptibility factors might modulate kidney damage evolution. We have analyzed, in a group of ESRD patients and matched controls, a set of SNPs of genes (Klotho rs577912, rs564481, rs9536314; FGF23 rs7955866; IGF1 rs35767; TNFA rs1800629; IL6 rs1800795; MIF rs755622, rs1007888) chosen in relation to their possible involvement with renal disease and concomitant pathologies. Analysis of the raw data did indicate that IL6 rs180795 and MIF rs755622 SNPs might be markers of genetic susceptibility to ESRD. In particular, the C positive genotypes of MIF rs755622, (dominant model) seem to be an independent risk factor for ESDR patients (data adjusted for age, gender, and associated pathologies). Stratifying results according to age MIF rs755622 C positive genotype frequencies are increased in both the two age classes considered (<59 and ≥59-year-old subjects). Analyses of data according to gender allowed us to observe that ESRD women shoved a significantly reduced frequency of genotypes bearing IL6 rs180795 C allele. In addition, MIF rs755622 might interact with diabetes or hypercholesterolemia in increasing susceptibility to ESRD. In conclusion, our data indicate that some polymorphisms involved in the regulation of both renal function and inflammatory response can influence the evolution of chronic kidney disease and suggest that the modulation of the activities of these and other genes should also be considered as therapeutic targets on to intervene with innovative therapies.

Technology legitimacy and the legitimacy of technology: The case of chronic kidney disease therapies

In this paper we explore how the institutional environment in which technologies are embedded serves to select certain technological options while marginalizing others. To do this, we trace the activities occurring among and between sponsors and the legitimacy assemblage – that is, the distributed set of actors, materials and methodologies that collectively confer legitimacy to a technology. Specifically, we employ an analytic narrative of the evolution of chronic kidney disease (CKD) treatment modalities to demonstrate how dialysis has become an accepted form of treatment while an effective preventative and complementary treatment, dietary protein restriction (DPR), has been marginalized. Our account highlights the emergence of a legitimacy assemblage that establishes the boundaries of what constitutes an appropriate technology, the bandwagon process by which technologies accrue legitimacy, and how actors subsequently engage in legitimacy capture that can contribute to technology stagnation in a domain. In highlighting these legitimacy dynamics, we provide new insights to the literature on technology selection, develop an expanded elaboration of technology legitimacy, and also offer insights for the medical and healthcare policy domains.

POS-446 SPECIFIC FEATURES AND OUTCOME OF NEPHROCALCINOSIS IN CHILDREN: ABOUT A SERIES OF 30 CASES

Nephrocalcinosis is a rare pediatric renal disease resulting in calcifications of the kidney tissue. It comes from various causes, especially genetic mutations. Management is based on symptomatic measures and treatment of the underlying condition. The aim of this study (from January 2010 to June 2020) is to underly the specific features of nephrocalcinosis in our pediatric population. For this, we gathered retrospective data of 30 children diagnosed with nephrocalcinosis. The mean age at diagnosis was of 3,5 years. One-third of our patients had first-degree consanguineous parents, while two-thirds of them were males. Similar cases in siblings and family members were absent. The majority of children presented with polyuria, polydipsia, and dehydration at diagnosis. Also, half of them had simultaneous urologic calculus. In five cases, nephrocalcinosis was discovered on routine abdominal ultrasound while the children were asymptomatic. The sonographic classification was in favor of stage III nephrocalcinosis in 23 cases. The underlying disease was represented mostly by tubulopathies in 40% of cases. Distal tubular acidosis was predominant. Nephrocalcinosis secondary to recurrent urinary tract infections was seen in 10% of our children. While, prematurity, primary hyperoxaluria, and familial hypercalciuria were rare (both seen in 10% of children). One child developed chronic kidney disease stage II after a follow up of seven years. Meanwhile, management was successful in stopping the evolution of the disease in all the remaining cases. It consisted on hyperhydration in all cases, alkalinization of urine in the case of acidosis, along with the specific treatment of the underlying disease. Early management of nephrocalcinosis in children can prevent the evolution of chronic kidney disease. Systematic screening should be implemented in high-risk children, especially those with tubulopathies. The high frequency of consanguineous marriages in our population suggests a genetic predisposition that needs to be proven by further studies.

Chronic Nephropathies in the Internal Medicine Department of the Sylvanus Olympio University Hospital

Introduction: The chronic nephropathies constitute a real global public health concern due to the constant increase in the prevalence estimated between 10% and 15%. In Sub-Saharan Africa, this prevalence has been estimated at 13.9%. This study will allow knowing the epidemiological, clinical, paraclinical and etiological aspects of chronic kidney disease in the internal medicine department of CHU-SO Lomé. Method: This was a cross-sectional, retrospective and descriptive study. It concerned all the patients suffering from a chronic kidney disease, hospitalized between the 1st of January 2014 and the 31st of December 2018, for a duration of 5 years. Results: During our study, 330 cases of chronic nephropathy were identified. The prevalence of chronic kidney disease was 8.3% of admissions. The mean age of the patients was 46.3 years with extremes of 19 and 86 years and a sex ratio of 1.32. A low socio-economic level of patients was observed in 63.9% with an urban origin in 69.7%. The main risk factors for renal impairment were hypertension (55.2%), diabetes mellitus (29.1%), obesity (20.6%), use of nephrotoxic products (19.4%), HIV infection (17%) and smoking (16.1%). The causes were dominated by nephroangiosclerosis (33.3%), followed by diabetic nephropathy (25.5%) and HIV-associated nephropathy (17%). Chronic renal failure was present in 95.8% of cases and was end stage in 69.7% of cases. Anemia was the main complication during the evolution of chronic kidney disease (98.2%). Mortality was 57.3% during hospitalization. Conclusion: Chronic kidney disease is a fairly common reason for hospitalization in the internal medicine department. Emphasis should therefore be placed on preventive measures for hypertension, diabetes and HIV.

Determinant factors for the evolution of chronic kidney disease: historical cohort in a public network nephrology ambulatory

Determinant factors for the evolution of chronic kidney disease: historical cohort in a public network nephrology ambulatory

Technology Legitimacy and the Legitimacy of Technology: The Case of Kidney Disease Treatments

In this paper we explore how the institutional environment in which technologies are embedded serves to select certain technologies and marginalize others. Specifically, we trace the dynamics occurring within the legitimacy ecosystem – that is, the distributed set of actors who employ different evaluation and endorsement methods to collectively confer legitimacy to a technology. We employ a historical narrative of the evolution of chronic kidney disease (CKD) treatment modalities to demonstrate how two of these (dialysis and transplantation) have become accepted forms of treatment while another (dietary protein restriction) has been institutionally locked out. In doing so, we highlight how legitimacy ecosystems are historically conditioned to select “science based” technologies. Our analysis also indicates that the role for institutional entrepreneurship activity is often circumscribed. Finally, we elaborate on the unintended impacts that such legitimation processes have on the evolution of a technological field. Our findings contribute to the technological change literature as well as the growing discourse on technology legitimacy, besides offering important implications to the medical practice and healthcare policy domains.

P0261NARRATIVE NEPHROLOGY: A BIO-PSYCHO-SOCIAL APPROACH WITH CDK PATIENTS

Abstract Background and Aims Poor medication adherence in CKD patients can reach up to 80%. Non-adherence is associated with high mortality and morbidity and it is a negative criterion for the inclusion in the transplant waiting list. Poor adherence increases also the costs for health care in terms of diagnostic procedures, dialysis in emergency, etc. Therefore, to increase patients’ adherence to medical treatments is one of the priority of clinical nephrology. According to the WHO adherence behaviors are associated to several factors (e.g. organization of health services, doctor-patient relationship, patients’ psychosocial factors). The most efficacy interventions descried in the literature to increase patients’ adherence to treatments are conducted by a multi-professional team and with the active participation of patients. In the last years, narrative evidenced-based medicine has been proved as a useful methodology in the care of chronic patients also in promoting adherence to treatments. Aim of this clinical project is to obtain the best control of the evolution of chronic kidney disease through a multidisciplinary approach of narrative medicine. Method Within the pre-dialysis service of the Division of Nephrology and Dialysis Firenze 2, it has been integrated the clinical care for CKD patients with a protocol based on a narrative medicine approach (Fig.1). The clinical protocol is composed by the following procedures: Results This project begun around 2 months ago. In this period 15 patients were met, collecting stories by 12 of them (80%). Most of the stories were rich of contents and useful from a medical point of view. None patients refuse the medical consultation at the presence of psychologist, and 5 of them asked for psychotherapy sessions. In line with the literature, 30% of patients presented symptoms of depression. Due to logistic reasons we are going to start the pharmacy counseling intervention at the end of January. All patients were grateful to have been included in this protocol. In the following months we will be able to assess the impact of this protocol in terms of medical outcome. Conclusion To promote an active role of patients in taking care of themselves and follow medical prescriptions, it has been implemented a clinical protocol based on narrative medicine approach in which the biological, psychological and social needs of patients are considered and discussed with them. The empirical results obtained in these first months indicate a positive response from patients in terms of wish to write the experience with the disease and to receive the medical visit with the nephrologist at the presence of a psychologist.

Sacubitril/valsartan in chronic kidney disease, the nephrologist point of view

IntroductionSacubitril/valsartan reduces cardiovascular morbidity and mortality in patients with systolic dysfunction (SD). The aim of the present study was to assess the evolution of chronic kidney disease (CKD) patients after initiating sacubitril/valsartan. MethodsWe included 66 consecutive CKD patients with SD followed up in outpatient care. Patients had to meet the inclusion criteria of having a New York Heart Association class II to IV, receiving maximum tolerated doses of optimal medical therapy and CKD stages 1–4. At baseline, comorbidities and epidemiological data were collected and low doses of sacubitril/valsartan were initiated. At month 1 and 3, doses of sacubitril/valsartan were increased up to the maximum doses if tolerated. In each visit, renal function and cardiac biomarkers were recorded. All the data were analyzed at the end of follow up (6 months). ResultsOf the 66 patients, 42 (63 %) were men, with a mean age of 73±15 years. Mean creatinine at baseline was 1.42±0.5mg/dl (glomerular filtration rate (GFR) estimated by CKD-EPI was 50±19ml/min/1.73m2) and mean left ventricular ejection fraction (LVEF) was 31±9 %. At the end of follow up, LVEF improved from 31±9%–39±15 % (p<0.001). After one month of treatment, renal function improved up to 53±21ml/min/1.73m2, p=0.005. For the remaining follow-up time, GFR remained stable (mean at end of follow-up 51±18ml/min/1.73m2). Seven patients (10.6 %) withdrew from treatment. ConclusionIn our experience, sacubitril/Valsartan is safe in CKD, offering stability in CKD progression after 6 months.

Experiencia clínica con sacubitrilo/valsartán en pacientes con insuficiencia renal: la visión del nefrólogo

Background and objectivesSacubitril/valsartan reduces cardiovascular morbidity and mortality in patients with systolic dysfunction. The aim of the present study was to assess the evolution of chronic kidney disease (CKD) patients after initiating sacubitril/valsartan. Material and methodsWe included 66 consecutive CKD patients with systolic dysfunction followed up in outpatient care. Patients had to meet the inclusion criteria of having a New York Heart Association class ii to iv, receiving maximum tolerated doses of optimal medical therapy and CKD stages 1 to 4. At baseline, comorbidities and epidemiological data were collected and low doses of sacubitril/valsartan were initiated. At month 1 and 3, doses of sacubitril/valsartan were increased up to the maximum doses if tolerated. In each visit, renal function and cardiac biomarkers were recorded. All the data were analyzed at the end of follow up (6 months). ResultsOf the 66 patients, 42 (63%) were men, with a mean age of 73±15 years. Mean creatinine at baseline was 1.42±0.5 mg/dL (glomerular filtration rate estimated by CKD-EPI was 50±19 mL/min/1.73 m2) and mean left ventricular ejection fraction (LVEF) was 31±9%. At the end of follow up, LVEF improved from 31±9% to 39±15% (P <0.001). After one month of treatment, renal function improved up to 53±21 mL/min/1.73 m2, P=0.005. For the remaining follow-up time, glomerular filtration rate remained stable (mean at end of follow-up 51±18 mL/min/1.73 m2). Seven patients (10.6%) withdrew from treatment. ConclusionIn our experience, sacubitril/valsartan is safe in CKD, offering stability in CKD progression after 6 months.

Evolution of chronic kidney disease after surgical aortic valve replacement or transcatheter aortic valve implantation

Immediate improvement in kidney function has been reported after surgical aortic valve replacement or transcatheter aortic valve implantation. Long-term data, however, are not available. To assess the evolution of kidney function in chronic kidney disease stage 3b-5, 1 year after surgical aortic valve replacement or transcatheter aortic valve implantation. All patients with chronic kidney disease stage 3b-5 undergoing surgical aortic valve replacement or transcatheter aortic valve implantation for aortic stenosis in a single centre were included. Kidney function was assessed 1 year postprocedure. Improvement or deterioration in estimated glomerular filtration rate was defined by an increase or decrease of 5mL/min/1.73 m2, respectively. Overall, 127 procedures were analysed (54 surgical aortic valve replacements and 73 transcatheter aortic valve implantations). Kidney function improved in 51% of patients at 1 year (45% of the surgical aortic valve replacement group versus 57% of the transcatheter aortic valve implantation group; P=0.21), and deteriorated in only 14% of patients at 1 year (18% of the surgical aortic valve replacement group versus 10% of the transcatheter aortic valve implantation group; P=0.22). Almost a quarter of patients (23%) had an improvement in estimated glomerular filtration rate of>15mL/min/1.73 m2, and this was consistent at later follow-up. Few patients went onto chronic dialysis at 1 year (three after surgical aortic valve replacement and one after transcatheter aortic valve implantation). Acute kidney injury was an independent prognostic factor for long-term deterioration in kidney function (odds ratio 2.1, 95% confidence interval 1.4-3.6; P=0.006). Aortic valve replacement, whether by surgical aortic valve replacement or transcatheter aortic valve implantation, improved estimated glomerular filtration rate at 1 year in more than half of patients with chronic kidney disease stage 3b-5.

Cell cycle arrest and the evolution of chronic kidney disease from acute kidney injury.

For several decades, acute kidney injury (AKI) was generally considered a reversible process leading to complete kidney recovery if the individual survived the acute illness. Recent evidence from epidemiologic studies and animal models, however, have highlighted that AKI can lead to the development of fibrosis and facilitate the progression of chronic renal failure. When kidney injury is mild and baseline function is normal, the repair process can be adaptive with few long-term consequences. When the injury is more severe, repeated, or to a kidney with underlying disease, the repair can be maladaptive and epithelial cell cycle arrest may play an important role in the development of fibrosis. Indeed, during the maladaptive repair after a renal insult, many tubular cells that are undergoing cell division spend a prolonged period in the G2/M phase of the cell cycle. These tubular cells recruit intracellular pathways leading to the synthesis and the secretion of profibrotic factors, which then act in a paracrine fashion on interstitial pericytes/fibroblasts to accelerate proliferation of these cells and production of interstitial matrix. Thus, the tubule cells assume a senescent secretory phenotype. Characteristic features of these cells may represent new biomarkers of fibrosis progression and the G2/M-arrested cells may represent a new therapeutic target to prevent, delay or arrest progression of chronic kidney disease. Here, we summarize recent advances in our understanding of the biology of the cell cycle and how cell cycle arrest links AKI to chronic kidney disease.

Obesity and renal disease: not all fat is created equal and not all obesity is harmful to the kidneys.

The prevalence of obesity is increasing worldwide and contributes to many health problems, including kidney disease. Unexpectedly, 10-30% of obese individuals are apparently not at increased risk of metabolic diseases, e.g. type 2 diabetes, cardiovascular disease and risk of renal disease. Their phenotype is labeled 'metabolically healthy obesity'. In the search for mechanisms explaining this unexpected condition, a favourable type of body fat distribution with low insulin resistance and with low subclinical inflammation has been identified. Furthermore, signalling pathways have been found that distinguish between metabolically benign and malignant obesity. In addition, the important roles of fatty acids, adipokines and hepatokines were identified. These factors regulate insulin resistance and subclinical inflammation. Onset and evolution of chronic kidney disease (CKD) are affected by obesity. CKD also increases the risk of insulin resistance and subclinical inflammation, two pathways that play an important role in the pathogenesis of renal malfunction. This brief review summarizes novel insights, specifically how distinct body fat compartments (including perivascular and even renal sinus fat) may have an impact on progression of CKD.