Effects of microplastics on the kidneys: a narrative review.

Microplastics (MPs) and nanoplastics are small synthetic organic polymer particles (<5 mm and <1 µm, respectively) that originate directly from plastic compounds or result from the degradation of plastic. These particles are a global concern because they are widely distributed in water, air, food, and soil, and recent scientific evidence has linked MPs to negative biological effects. Although these particles are difficult to detect in humans, MPs have been identified in different biological fluids and tissues, such as the placenta, lung, intestines, liver, blood, urine, and kidneys. Human exposure to MPs can occur by ingestion, inhalation, or dermal contact, potentially causing metabolic alterations. Data from experimental and clinical studies have revealed that the ability of MPs to promote inflammation, oxidative stress, and organ dysfunction and negatively affect clinical outcomes is associated with their accumulation in body fluids and tissues. Although evidence of the putative action of MPs in the human kidney is still scarce, there is growing interest in studying MPs in this organ. In addition, chronic kidney disease requires investigation because this condition is potentially prone to MP accumulation. The purpose of the present article is (i) to review the general aspects of MP generation, available analytic methods for identification, and the main known biological toxic effects; and (ii) to describe and critically analyze key experimental and clinical studies that support a role of MPs in kidney disease.

Point-of-Care Electrochemical Immunosensor Applied against Nosocomial Infection: Staphylococcus aureus Detection in Human Hand Skin.

Staphylococcus aureus is an important pathogen that causes nosocomial infections, resulting in unacceptable morbidity and mortality rates. In this work, we proposed the construction of a nanostructured ZnO-based electrochemical immunosensor for qualitative and semiquantitative detection of S. aureus using simple methods for growing zinc oxide nanorods (ZnO NRs) on a sensor board and immobilizing the anti-S. aureus antibody on ZnO NRs through cystamine and glutaraldehyde. The immunosensor detected S. aureus in the 103-107 colony-forming unit (CFU) mL-1 range and showed a limit of detection (LoD) around 0.792 × 103 CFU mL-1. Beyond a satisfactory LoD, the developed immunosensor presented other advantages, such as high versatility for point-of-care assays and a suitable selective factor that admits the detection of the S. aureus concentration range in human hand skin after washing. Moreover, the immunosensor showed the potential to be an excellent device to control nosocomial infection by detecting the presence of S. aureus in human hand skin.

Cardiovascular complications in chronic kidney disease: a review from the European Renal and Cardiovascular Medicine Working Group of the European Renal Association.

Chronic kidney disease (CKD) is classified into five stages with kidney failure being the most severe stage (stage G5). CKD conveys a high risk for coronary artery disease, heart failure, arrhythmias, and sudden cardiac death. Cardiovascular complications are the most common causes of death in patients with kidney failure (stage G5) who are maintained on regular dialysis treatment. Because of the high death rate attributable to cardiovascular (CV) disease, most patients with progressive CKD die before reaching kidney failure. Classical risk factors implicated in CV disease are involved in the early stages of CKD. In intermediate and late stages, non-traditional risk factors, including iso-osmotic and non-osmotic sodium retention, volume expansion, anaemia, inflammation, malnutrition, sympathetic overactivity, mineral bone disorders, accumulation of a class of endogenous compounds called 'uremic toxins', and a variety of hormonal disorders are the main factors that accelerate the progression of CV disease in these patients. Arterial disease in CKD patients is characterized by an almost unique propensity to calcification and vascular stiffness. Left ventricular hypertrophy, a major risk factor for heart failure, occurs early in CKD and reaches a prevalence of 70-80% in patients with kidney failure. Recent clinical trials have shown the potential benefits of hypoxia-inducible factor prolyl hydroxylase inhibitors, especially as an oral agent in CKD patients. Likewise, the value of proactively administered intravenous iron for safely treating anaemia in dialysis patients has been shown. Sodium/glucose cotransporter-2 inhibitors are now fully emerged as a class of drugs that substantially reduces the risk for CV complications in patients who are already being treated with adequate doses of inhibitors of the renin-angiotensin system. Concerted efforts are being made by major scientific societies to advance basic and clinical research on CV disease in patients with CKD, a research area that remains insufficiently explored.

Advanced Glycation End Products and Bone Metabolism in Patients with Chronic Kidney Disease.

Advanced glycation end products (AGEs) accumulation may be involved in the progression of CKD-bone disorders. We sought to determine the relationship between AGEs measured in the blood, skin, and bone with histomorphometry parameters, bone protein, gene expression, and serum biomarkers of bone metabolism in patients with CKD stages 3 to 5D patients. Serum levels of AGEs were estimated by pentosidine, glycated hemoglobin (A1c), and N-carboxymethyl lysine (CML). The accumulation of AGEs in the skin was estimated from skin autofluorescence (SAF). Bone AGEs accumulation and multiligand receptor for AGEs (RAGEs) expression were evaluated by immunohistochemistry; bone samples were used to evaluate protein and gene expression and histomorphometric analysis. Data are from 86 patients (age: 51 ± 13 years; 60 [70%] on dialysis). Median serum levels of pentosidine, CML, A1c, and SAF were 71.6 pmol/mL, 15.2 ng/mL, 5.4%, and 3.05 arbitrary units, respectively. AGEs covered 3.92% of trabecular bone and 5.42% of the cortical bone surface, whereas RAGEs were expressed in 0.7% and 0.83% of trabecular and cortical bone surfaces, respectively. AGEs accumulation in bone was inversely related to serum receptor activator of NF-κB ligand/parathyroid hormone (PTH) ratio (R = -0.25; p = 0.03), and RAGE expression was negatively related to serum tartrate-resistant acid phosphatase-5b/PTH (R = -0.31; p = 0.01). Patients with higher AGEs accumulation presented decreased bone protein expression (sclerostin [1.96 (0.11-40.3) vs. 89.3 (2.88-401) ng/mg; p = 0.004]; Dickkopf-related protein 1 [0.064 (0.03-0.46) vs. 1.36 (0.39-5.87) ng/mg; p = 0.0001]; FGF-23 [1.07 (0.4-32.6) vs. 44.1 (6-162) ng/mg; p = 0.01]; and osteoprotegerin [0.16 (0.08-2.4) vs. 6.5 (1.1-23.7) ng/mg; p = 0.001]), upregulation of the p53 gene, and downregulation of Dickkopf-1 gene expression. Patients with high serum A1c levels presented greater cortical porosity and Mlt and reduced osteoblast surface/bone surface, eroded surface/bone surface, osteoclast surface/bone surface, mineral apposition rate, and adjusted area. Cortical thickness was negatively correlated with serum A1c (R = -0.28; p = 0.02) and pentosidine levels (R = -0.27; p = 0.02). AGEs accumulation in the bone of CKD patients was related to decreased bone protein expression, gene expression changes, and increased skeletal resistance to PTH; A1c and pentosidine levels were related to decreased cortical thickness; and A1c levels were related to increased cortical porosity and Mlt. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

When is the best moment to assess the ankle brachial index: pre- or post-hemodialysis?

BACKGROUND: Cardiovascular disease is an important cause of death in patients on dialysis. Peripheral arterial disease (PAD) is a prognostic factor for cardiovascular disease. The ankle brachial index (ABI) is a noninvasive method used for the diagnosis of PAD. The difference between ABI pre- and post-dialysis had not yet been formally tested, and it was the main objective of this study. METHODS: The ABI was assessed using an automated oscillometric device in incident patients on hemodialysis. All blood pressure readings were taken in triplicate pre- and post-dialysis in three consecutive dialysis sessions (times 1, 2, and 3). RESULTS: One hundred and twenty-three patients (85 men) aged 53 ± 19 years were enrolled. We found no difference in ABI pre- and post-dialysis on the right or left side, and there was no difference in times 1, 2, and 3. In patients with a history of PAD, the ABI pre- versus post-dialysis were of borderline significance on the right side (p = 0.088). CONCLUSION: ABI measured pre- and post-dialysis presented low variability. The ABI in patients with a history of PAD should be evaluated with caution. The applicability of the current method in predicting mortality among patients on hemodialysis therefore needs further investigation.

Vitamin K role in mineral and bone disorder of chronic kidney disease.

Vitamin K is a key cofactor for the activation of proteins involved in blood coagulation, apoptosis, bone mineralization regulation, and vessel health. Scientific evidence shows an important role of activated osteocalcin and matrix-Gla protein in bone and vessels, markedly affected along the course of chronic kidney disease (CKD). In fact, CKD corresponds to an unique condition of vitamin K deficiency caused by dietary restriction, intestinal dysfunction, and impaired vitamin K recycling. Clinical data suggest that vitamin K status can be modulated and this prompts us to speculate whether patients with CKD might benefit from vitamin K supplementation. However, as important as whether the improvement in vitamin K status would be able to result in better bone quality, less vascular calcification, and lower mortality rates, several issues need to be clarified. These include better standardized methods for measuring vitamin K levels, and definition of the optimal concentration range for supplementation in different subgroups. Here, we review the literature data concerning the impact of vitamin K deficiency and supplementation on CKD-associated mineral and bone disorders (CKD-MBD). We present and discuss the available evidence from basic science and clinical studies, and highlight perspectives for further research.

Parathyroidectomy in patients with chronic kidney disease: Impacts of different techniques on the biochemical and clinical evolution of secondary hyperparathyroidism.

BACKGROUND: Parathyroidectomy (PTx) decreases the mortality rate of refractory secondary hyperparathyroidism (rSHP) due to chronic kidney disease. A consensus regarding which techniques of PTx are associated with better outcomes is not available. The aims of this study are to evaluate the clinical and laboratory evolution of 49 hemodialysis patients with rSHP who underwent PTx using different techniques. METHODS: Patients underwent subtotal PTx (sub-PTx) or total PTx with autotransplantation (AT) of 45 (PTx-AT45) or 90 parathyroid fragments (PTx-AT90) and were followed for 12 months. We analyzed the expression of proliferating cell nuclear antigen (PCNA), calcium-sensing receptor (CasR), vitamin D receptor (VDR), fibroblast growth factor receptor-1 (FGFR1), sodium-dependent phosphate cotransporter-1 (PIT1), and Klotho in parathyroid glands. RESULTS: Baseline median serum intact parathyroid hormone (iPTH) levels were 1,466 (1,087-2,125) pg/mL; vascular calcification scores correlated with serum iPTH (r = 0.529; P = .002) and serum phosphate levels (r = 0.389; P = .028); and Klotho expression was negatively correlated with serum phosphate levels (r = -0.4; P = .01). After 12 months, serum iPTH and alkaline phosphatase levels were significantly controlled in all groups, as was bone pain. The proportions of patients with serum iPTH levels within the ranges recommended by Kidney Disease: Improving Global Outcomes were similar among the treatment groups. During the hungry bone disease (HBS), patients received 3,786 g (1,412-7,580) of elemental calcium, and a trend toward a positive correlation between the cumulative calcium load at the end of follow up and VC score post-PTx was noted (r = 0.390; P = .06). Two cases evolved to clinically uncontrolled hyperparathyroidism in the sub-PTx group. The expression patterns of PCNA, VDR, CasR, PIT1, FGFR1, and Klotho in parathyroid glands did not correlate with serum systemic iPTH levels or the duration of HBS. CONCLUSIONS: All 3 operative techniques were effective at controlling rSHP, both in clinical and laboratory terms. Neither the quantity nor quality of parathyroid fragments influenced serum systemic iPTH and AT-iPTH levels. The cumulative calcium load appeared to correlate with the VC score and may have affected its progression. The effects of phosphate restriction on Klotho expression in human parathyroid glands and the subsequent decrease in FGF23 resistance must be addressed in further studies.

Uremic serum inhibits in vitro expression of chemokine SDF-1: impact of uremic toxicity on endothelial injury.

INTRODUCTION: Endothelial dysfunction is important in the pathogenesis of cardiovascular disease (CVD) related to chronic kidney disease (CKD). Stromal cell-derived factor-1 (SDF-1) is a chemokine which mobilizes endothelial progenitor cells (EPC) and together with interleukin-8 (IL-8) may be used as markers of tissue injury and repair. OBJECTIVE: This study investigated in vivo and in vitro the effect of uremic media on SDF-1 and IL-8 expression. METHODS: Systemic inflammation was assessed by C-reactive protein (CRP) and interleukin-6 (IL-6). IL-8 and SDF-1 were measured as markers of endothelial dysfunction and tissue repair, respectively, by ELISA. In vitro studies were performed on human umbilical vein endothelial cells (HUVEC) exposed to healthy or uremic media. RESULTS: The study included 26 hemodialysis (HD) patients (17 ± 3 months on dialysis, 52 ± 2 years, 38% men and 11% diabetic). Serum concentrations of CRP, IL-6, SDF-1 and IL-8 were 4.9 ± 4.8 mg/ml, 6.7 ± 8.1 pg/ml, 2625.9 ± 1288.6 pg/ml and 128.2 ± 206.2 pg/ml, respectively. There was a positive correlation between CRP and IL-6 (ρ = 0.57, p < 0.005) and between SDF-1 and IL-8 (ρ = 0.45, p < 0.05). In vitro results showed that after 6 hours treatment, SDF-1 expression by HUVEC treated with uremic media is lower compared to cells treated with healthy media (p < 0.05). After 12 hours of treatment there was an increase in IL-8 when HUVECs were exposed to uremic media (p < 0.005). CONCLUSION: We suggest that SDF-1 and IL-8 in HD patients can be used to measure the extent of damage and subsequent vascular activation in uremia.

The quest for a better understanding of chronic kidney disease complications: an update on uremic toxins.

Chronic kidney disease is characterized by a progressive reduction of glomerular filtration rate and/or the appearance of proteinuria, and subsequently the progressive retention of organic waste compounds called uremic toxins (UT). Over the last decades, a large number of such compounds have been identified and their effects on organs and tissues, especially the cardiovascular system, has been demonstrated. In this review, we present the current classification of UT, as proposed by the EUTox Group, and the effects of some of the probably most important UTs, such as phosphate, FGF-23, PTH, AGEs, indoxyl sulfate and para-cresyl sulfate. We provide an overview on therapeutic approaches aimed to increase their extracorporeal removal via convective and/or adsorptive strategies and to lower their intestinal production/ absorption via dietetic and pharmacological interventions. The recognition that multiple toxins contribute to the uremia supports the need for new therapeutic targets, with a potentially positive impact on CKD progression and survival.

The chronic kidney disease outcomes and practice patterns study Brazil (CKDopps-Brazil): design, data and methodology.

INTRODUCTION: The chronic kidney disease outcomes and practice patterns study (CKDopps) is an international observational, prospective, cohort study involving patients with chronic kidney disease (CKD) stages 3-5 [estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2, with a major focus upon care during the advanced CKD period (eGFR < 30 ml/min/1.73 m2)]. During a 1-year enrollment period, each one of the 22 selected clinics will enroll up to 60 advanced CKD patients (eGFR < 30 ml/min/1.73 m2 and not dialysis-dependent) and 20 earlier stage CKD patients (eGFR between 30-59 ml/min/1.73 m2). EXCLUSION CRITERIA: age < 18 years old, patients on chronic dialysis or prior kidney transplant. The study timeline include up to one year for enrollment of patients at each clinic starting in the end of 2013, followed by up to 2-3 years of patient follow-up with collection of detailed longitudinal patient-level data, annual clinic practice-level surveys, and patient surveys. Analyses will apply regression models to evaluate the contribution of patient-level and clinic practice-level factors to study outcomes, and utilize instrumental variable-type techniques when appropriate. CONCLUSION: Launching in 2013, CKDopps Brazil will study advanced CKD care in a random selection of nephrology clinics across Brazil to gain understanding of variation in care across the country, and as part of a multinational study to identify optimal treatment practices to slow kidney disease progression and improve outcomes during the transition period to end-stage kidney disease.

Brazilian Registry of Bone Biopsy (REBRABO): design, data elements and methodology.

INTRODUCTION: Mineral bone disorder (MBD) is a common condition in chronic kidney disease (CKD) patients and causes significant morbidity and mortality. Data involving prevalence of alterations in bone histological patterns, impact of different treatments and its repercussion in outcomes, such as bone fractures, hospitalization, cardiovascular disease and mortality, are scarce. Data bank registry can be a valuable tool to understand epidemiological aspects of MBD CKD. The Brazilian Registry of Bone Biopsy (REBRABO) will be a national registry, coordinating by the Brazilian Society of Nephrology - Committee of MBD-CKD. OBJECTIVE: To describe REBRABO's design, elements of data and methodology. METHODS: Will be an online national observational and multicentric data registry divided in two phases (retrospective, 1st phase) and prospective (2nd phase), including information from bone tissue histomorphometric analysis and demographics, clinical and laboratorial data from CKD-MBD patients. RESULTS: The REBRABO's first phase will explore data on demographics, clinical, laboratorial and bone histomorphometric analysis data from January/1986 to December/2013. The first RESULTS are expected in early 2015. CONCLUSION: Studies in the field of CKD-MBD are needed, particularly those analyzing its prevalence, associations between demographic, clinical, histological parameters, and major outcomes. The REBRABO will be a unique retrospective and prospective research platform including bone biopsy data in CKD-MBD patients.

Vascular calcification in chronic kidney disease: a review.

Vascular calcification (VC), an independent and strong predictor of cardiovascular risk, is often found in CKD patients. The degree of VC is providing incremental prognostic value over traditional risk markers. There is interest in improving our understanding of mechanisms, establishing diagnostic methods and effective prevention and treatment modalities. The abnormal mineral metabolism of CKD is known to facilitate the progression of VC, in concert with altered activities of VC inhibitors. Possible measures to prevent VC include the control of serum calcium and phosphate as well as other factors involved in its progression, including vitamin D sterols, parathyroid hormone, fibroblast growth factor-23, klotho, and VC inhibitors. In addition, we discuss new possible therapeutic approaches to halt VC or reverse its progression. The principal aim of this review is to provide an updated overview of VC in patients with CKD, with particular focus on pathophysiology, diagnosis, prevention and treatment.

The clinical impact of plasma leptin levels in a cohort of chronic kidney disease patients.

BACKGROUND: Recent research has clarified the relationship between adipokines, metabolic syndrome (MS) and cardiovascular disease (CVD). The results of animal and clinical studies have revealed a positive relationship between leptin and vascular smooth muscle cell counts and calcification, arterial rigidity, carotid thickness and the incidence of CVD. However, despite leptin fulfilling the definition of a uremic toxin, its exact role in chronic kidney disease (CKD) has yet to be determined. METHODS: One hundred and forty-two CKD patients (stages 2-5D) participated in this study, and were followed for a minimum of 20 months at Amiens University Medical Center. RESULTS: Leptin was negatively correlated with the glomerular filtration rate (GFR), total adiponectin (TAdip) and high-molecular weight adiponectin and positively correlated with age, waist circumference, body mass index (BMI), aortic calcification score (ACS), C-reactive protein (CRP), triglycerides, insulin and parathormone (PTH). Leptin and insulin were significantly correlated with the MS score. The BMI, insulin, MS score and PTH were independent predictors of leptin levels (P = 0.002, 0.016, 0.028 and 0.017, respectively). Leptin, insulin and TAdip were independent predictors of the presence of MS (P = 0.05, 0.04 and 0.04). However, leptin levels were not significantly predictive of the clinical outcomes. CONCLUSIONS: Our study was the first to demonstrate a significant, independent link between leptin and MS (but not clinical outcomes) and PTH in patients at different CKD stages. Future studies will have to assess the involvement of leptin in MS and clinical outcomes in CKD, and the potential modulation of leptin by PTH.

[French-Brazilian school of nephrology]. / L'école Franco-Brésilienne de néphrologie.

The recent history of French and Brazilian medicine goes back to the first decades of the xixth century. As regards nephrology, the first links were established starting in the 1950s of the xxth century. Over the past 60 years, the scientific production of the Franco-Brazilian school of nephrology totalized more than a thousand scientific papers and created a new generation of more than two hundred disciples, formed in Brazil by nephrologists who had completed their studies in France. In this article, we would like to memorize the successive exchanges between French and Brazilian physicians, mainly in the field of nephrology.