The role of podocyte injury in the pathogenesis of Fabry disease nephropathy / O papel da injúria podocitária na patogênese da nefropatia da doença de Fabry

Abstract Renal involvement is one of the most severe morbidities of Fabry disease (FD), a multisystemic lysosomal storage disease with an X-linked inheritance pattern. It results from pathogenic variants in the GLA gene (Xq22.2), which encodes the production of alpha-galactosidase A (α-Gal), responsible for glycosphingolipid metabolism. Insufficient activity of this lysosomal enzyme generates deposits of unprocessed intermediate substrates, especially globotriaosylceramide (Gb3) and derivatives, triggering cellular injury and subsequently, multiple organ dysfunction, including chronic nephropathy. Kidney injury in FD is classically attributed to Gb3 deposits in renal cells, with podocytes being the main target of the pathological process, in which structural and functional alterations are established early and severely. This configures a typical hereditary metabolic podocytopathy, whose clinical manifestations are proteinuria and progressive renal failure. Although late clinical outcomes and morphological changes are well established in this nephropathy, the molecular mechanisms that trigger and accelerate podocyte injury have not yet been fully elucidated. Podocytes are highly specialized and differentiated cells that cover the outer surface of glomerular capillaries, playing a crucial role in preserving the structure and function of the glomerular filtration barrier. They are frequent targets of injury in many nephropathies. Furthermore, dysfunction and depletion of glomerular podocytes are essential events implicated in the pathogenesis of chronic kidney disease progression. We will review the biology of podocytes and their crucial role in regulating the glomerular filtration barrier, analyzing the main pathogenic pathways involved in podocyte injury, especially related to FD nephropathy.

Resumo O acometimento renal é uma das mais severas morbidades da doença de Fabry (DF), enfermidade multissistêmica de depósito lisossômico com padrão de herança ligada ao cromossomo X, decorrente de variantes patogênicas do gene GLA (Xq22.2), que codifica a produção de alfa-galactosidase A (α-Gal), responsável pelo metabolismo de glicoesfingolipídeos. A atividade insuficiente dessa enzima lisossômica gera depósitos de substratos intermediários não processados, especialmente do globotriaosilceramida (Gb3) e derivados, desencadeando injúria celular e, posteriormente, disfunção de múltiplos órgãos, incluindo a nefropatia crônica. A lesão renal na DF é classicamente atribuída aos depósitos de Gb3 nas células renais, sendo os podócitos o alvo principal do processo patológico, nos quais as alterações estruturais e funcionais são instaladas de forma precoce e severa, configurando uma podocitopatia metabólica hereditária típica, cujas manifestações clínicas são proteinúria e falência renal progressiva. Embora os desfechos clínicos tardios e as alterações morfológicas estejam bem estabelecidos nessa nefropatia, os mecanismos moleculares que deflagram e aceleram a injúria podocitária ainda não estão completamente elucidados. Podócitos são células altamente especializadas e diferenciadas que revestem a superfície externa dos capilares glomerulares, desempenhando papel essencial na preservação da estrutura e função da barreira de filtração glomerular, sendo alvos frequentes de injúria em muitas nefropatias. A disfunção e depleção dos podócitos glomerulares são, além disso, eventos cruciais implicados na patogênese da progressão da doença renal crônica. Revisaremos a biologia dos podócitos e seu papel na regulação da barreira de filtração glomerular, analisando as principais vias patogênicas envolvidas na lesão podocitária, especialmente relacionadas à nefropatia da DF.

Estimated glomerular filtration rate in clinical practice: Consensus positioning of the Brazilian Society of Nephrology (SBN) and Brazilian Society of Clinical Pathology and Laboratory Medicine (SBPC/ML) / Estimativa da taxa de filtração glomerular na prática clínica: posicionamento consensual da Sociedade Brasileira de Nefrologia (SBN) e Sociedade Brasileira de Patologia Clínica e Medicina Laboratorial (SBPC/ML)

ABSTRACT Chronic kidney disease (CKD) represents one of today's main public health problems. Serum creatinine measurement and estimation of the glomerular filtration rate (GFR) are the main tools for evaluating renal function. There are several equations to estimate GFR, and CKD-EPI equation (Chronic Kidney Disease - Epidemiology) is the most recommended one. There are still some controversies regarding serum creatinine measurement and GFR estimation, since several factors can interfere in this process. An important recent change was the removal of the correction for race from the equations for estimating GFR, which overestimated kidney function, and consequently delayed the implementation of treatments such as dialysis and kidney transplantation. In this consensus document from the Brazilian Societies of Nephrology and Clinical Pathology and Laboratory Medicine, the main concepts related to the assessment of renal function are reviewed, as well as possible existing controversies and recommendations for estimating GFR in clinical practice.

RESUMO A doença renal crônica (DRC) representa um dos principais problemas de saúde pública da atualidade. A dosagem da creatinina sérica e a estimativa da taxa de filtração glomerular (TFG) são as principais ferramentas para avaliação da função renal. Para a estimativa da TFG, existem diversas equações, sendo a mais recomendada a CKD-EPI (Chronic Kidney Disease - Epidemiology). Existem ainda algumas controvérsias com relação à dosagem da creatinina sérica e da estimativa da TFG, uma vez que vários fatores podem interferir nesse processo. Uma importante mudança recente foi a retirada da correção por raça das equações para estimativa da TFG, que superestimavam a função renal, e consequentemente retardavam a implementação de tratamentos como diálise e transplante renal. Neste documento de consenso da Sociedade Brasileira de Nefrologia e Sociedade Brasileira de Patologia Clínica e Medicina Laboratorial são revisados os principais conceitos relacionados à avaliação da função renal, possíveis controvérsias existentes e recomendações para a estimativa da TFG na prática clínica.

Estimated glomerular filtration rate slope and risk of primary and secondary major adverse cardiovascular events and heart failure hospitalization in people with type 2 diabetes: An analysis of the EXSCEL trial.

AIM: The decline in estimated glomerular filtration rate (eGFR), a significant predictor of cardiovascular disease (CVD), occurs heterogeneously in people with diabetes because of various risk factors. We investigated the role of eGFR decline in predicting CVD events in people with type 2 diabetes in both primary and secondary CVD prevention settings. MATERIALS AND METHODS: Bayesian joint modelling of repeated measures of eGFR and time to CVD event was applied to the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial to examine the association between the eGFR slope and the incidence of major adverse CV event/hospitalization for heart failure (MACE/hHF) (non-fatal myocardial infarction, non-fatal stroke, CV death, or hospitalization for heart failure). The analysis was adjusted for age, sex, smoking, systolic blood pressure, baseline eGFR, antihypertensive and lipid-lowering medication, diabetes duration, atrial fibrillation, high-density cholesterol, total cholesterol, HbA1c and treatment allocation (once-weekly exenatide or placebo). RESULTS: Data from 11 101 trial participants with (n = 7942) and without (n = 3159) previous history of CVD were analysed. The mean ± SD eGFR slope per year in participants without and with previous CVD was -0.68 ± 1.67 and -1.03 ± 2.13 mL/min/1.73 m2, respectively. The 5-year MACE/hHF incidences were 7.5% (95% CI 6.2, 8.8) and 20% (95% CI 19, 22), respectively. The 1-SD decrease in the eGFR slope was associated with increased MACE/hHF risks of 48% (HR 1.48, 95% CI 1.12, 1.98, p = 0.007) and 33% (HR 1.33, 95% CI 1.18,1.51, p < 0.001) in participants without and with previous CVD, respectively. CONCLUSIONS: eGFR trajectories over time significantly predict incident MACE/hHF events in people with type 2 diabetes with and without existing CVD, with a higher hazard ratio for MACE/hHF in the latter group.

Adoption of the PREVENT (Predicting Risk of Cardiovascular Disease EVENTs) Risk Algorithm: Potential International Implications.

Background: The PREVENT (Predicting Risk of cardiovascular disease EVENTs risk algorithm was developed to better reflect the impact of metabolic factors on cardiovascular risk. Objectives: The purpose of this study was to compare the relative performance of PREVENT with standard comparator algorithms (Framingham risk score, pooled cohort equation, SCORE2 [Systematic COronary Risk Evaluation2]) for risk stratification emphasizing the implications of weighing chronic kidney disease. Methods: A simulated cohort was created of males and females aged 40 to 75 years with and without other traditional risk factors and either normal estimated glomerular filtration rates (eGFR 90 or 60 ml/min/1.73 m2) or abnormal eGFR (45 or 30 ml/min/1.73 m2). The concordance and reclassification rates were calculated for each category of risk with emphasis on subjects characterized as moderate risk by the standard comparator algorithms. Results: PREVENT demonstrated increased risk with progressive decreases in eGFR. When the standard comparator algorithms identified moderate risk, PREVENT was concordant in 6% to 88% of simulations. In simulations with normal eGFR, PREVENT identified a lower risk in 18% to 88% and a higher risk in 0% to 12% of simulations. Conversely, with abnormal eGFR, PREVENT identified lower risk in 0% to 26% and higher risk in 4% to 94% of simulations. Conclusions: PREVENT substantially reclassifies risk and has the potential to alter prevention practice patterns. The tendency to assign a lower risk compared to standard algorithms when eGFR is normal may diminish implementation of preventive therapy. National health care systems need to monitor whether such changes improve overall public health.

Association between Polycystic Ovarian Syndrome, Impaired Kidney Function and Hyperuricaemia: A Systematic Review and Meta-analysis.

Background: Polycystic ovarian syndrome (PCOS) is a gynaecological problem affecting women within reproductive age, accompanied by several metabolic anomalies, thus leading to alteration in kidney function and hyperuricaemia. Due to the high prevalence of cardiometabolic factors in PCOS, there is a need to anticipate an increased number of kidney impairments amongst these women. Objectives: This review aims to investigate the potential link between PCOS, impaired kidney function, and elevated uric acid levels. By elucidating this association, we hope to provide clinicians with a tool to stratify the risk of kidney disease in women diagnosed with PCOS, based on readily available kidney function parameters. Materials and Methods: The recommendations used for the analysis were outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Subsequently, eligible studies were identified using several databases (MEDLINE, ProQuest and EBSCOhost) between 1996 and 2022, with a total of 13 studies included. Serum uric acid, serum creatinine, as well as estimated glomerular filtration rate (eGFR) were evaluated as the outcome of interest. Quality assessment for cohort, case-control and cross-sectional studies was conducted utilising the Newcastle-Ottawa Scale, while Review Manager 5.4 was utilised for meta-analysis. Results: Uric acid was significantly higher in women with PCOS (mean difference [MD] = 0.70, 95% confidence interval [CI] [0.45-0.95], P < 0.00001). Meanwhile, serum creatinine and eGFR were statistically similar in each group (MD = 0.08, 95% CI [-0.05-0.21], P = 0.22 and MD = 3.54, 95% CI [-4.53-11.61], P = 0.39, respectively). Interpretation: This review showed that PCOS was significantly associated with elevated uric acid. However, no significant difference was found between eGFR and creatinine levels compared to healthy controls. Routine uric acid assessment in PCOS patients is recommended as a simple tool for risk stratification. Limitations: No body mass index (BMI) subgroup analysis was done due to limited BMI reporting in our included studies. Quantitative analysis of all kidney function parameters was also limited by sparse data on urea and albumin. PROSPERO Registration Number: CRD42023410092 (02 April 2023).

Nuclear factor erythroid 2-related factor 2 activation in streptozotocin-induced diabetic rats normalize renal hemodynamics and oxygen consumption.

Background: Diabetic kidney disease is a major contributor to end stage renal disease. A change in kidney oxygen homeostasis leading to decreased tissue oxygen tension is an important factor initiating alterations in kidney function in diabetes. However, the mechanism contributing to changed oxygen homeostasis is still unclear. Hyperglycemia-induced production of reactive oxygen species and an altered response to them have previously been demonstrated. In the present study, chronic treatment with DL-sulforaphane to induce nuclear factor erythroid 2-related factor 2 (Nrf2) expression, a master transcriptional regulator binding to antioxidant response elements inducing increased protection against reactive oxygen species, is studied. Methods: Sprague-Dawley rats were made diabetic using streptozotocin and either left untreated or received daily subcutaneous injections of DL-sulforaphane for 4 weeks. Age-matched non-diabetic rats served as controls. After 4 weeks of treatment, rats were anesthetized using thiobutabarbital, and kidney functions were studied in terms of glomerular filtration rate (GFR), renal blood flow (RBF), sodium transport, kidney oxygen consumption, and kidney oxygen tension. Mitochondria was isolated from kidney cortical tissue and investigated using high-resolution respirometry. Results: GFR was increased in diabetics but not RBF resulting in increased filtration fraction in diabetics. DL-sulforaphane treatment did not affect RBF and GFR in controls but decreased the same parameters in diabetics. Increased GFR resulted in increased sodium transport and oxygen consumption, hence decreased efficiency in diabetics compared to controls. Increased oxygen consumption in diabetics resulted in decreased cortical tissue oxygen tension. DL-sulforaphane treatment decreased oxygen consumption in diabetics, whereas transport efficiency was not significantly affected. DL-sulforaphane treatment increased cortical pO2 in diabetics. Conclusions: DL-sulforaphane treatment affects renal hemodynamics, improving cortical oxygen tension but not mitochondrial efficiency.

Particulate Matter and Incident Chronic Kidney Disease in Japan: The Ibaraki Prefectural Health Study (IPHS).

Introduction: Global health hazards caused by air pollution, such as chronic kidney disease (CKD), have been gaining attention; however, air pollution-associated CKD has not been explored in Japan. Methods: We examined 77,770 men and women with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2 in the Ibaraki Prefecture who participated in annual community-based health checkups from 1993 at 40-75 years old and were followed up through December 2020. The outcome was newly developed kidney dysfunction with eGFR of <60 ml/min/1.73 m2 during follow-up. To assess air pollution, a PM2.5 exposure model was employed to estimate yearly means at 1 × 1-km resolution, converted into means at the municipal level. Hazard modeling was employed to examine PM2.5 concentrations in residential areas as a risk factor for outcomes. Results: Participants were distributed across 23 municipalities in the Ibaraki Prefecture, with PM2.5 concentrations between 16.2 and 33.4 µg/m3 (mean, 22.7 µg/m3) in 1987-1995 as the exposure period. There were 942 newly developed kidney dysfunctions during follow-up. Based on 1987-1995 PM2.5 concentrations as the baseline exposure, the multivariate-adjusted hazard ratio per 10-µg/m3 increase in PM2.5 for newly developed kidney dysfunction was 1.02 (95%CI, 0.80-1.24) in men and 1.19 (95%CI, 0.95-1.44) in women. Conclusions: Elevated PM2.5 did not represent a significant risk factor for incident CKD in a prefecture in Japan.

Investigating the filtration performance and service life of vehicle cabin air filters in China.

To protect occupants in vehicle cabin environments from the health risks of high concentrations of particulate matter (PM), it is important to install vehicle cabin air filter (VCAF) to eliminate PM. In this study, we investigated the filtration performance of 22 VCAFs. Results showed that the minimum average filtration efficiency was 56.1 % for particles with a diameter of 0.1-0.3 µm, a pressure drop of 33.2-250 Pa at air velocity of 2.5 m/s, and the dust-holding capacity ranged from 5.8 to 19.4 g. In addition, as the filter area increased from 0.23 m2 to 0.50 m2, the filtration efficiency for particles with a diameter of 0.1-0.3 µm increased from 56.7 % to 77.5 %, the pressure drop decreased from 96.1 to 62.5 Pa, and the dust holding capacity increased 2.7 times. Furthermore, we compared the service life of VCAF from 31 major Chinese cities and found that the service life varied greatly from maximum of 1730 h for Haikou to minimum of 352 h for Shijiazhuang. Considering occupant health risks, Beijing requires that VCAFs have PM2.5 filtration efficiency at least 88.1 %, and Liaoning requires minimum of 97.5 %. Hence, choosing the appropriate VCAF based on the atmospheric environment of different cities deserves our attention.

Electrothermally-Driven Ultrafast Chemical Modulation of Multifunctional Nanocarbon Aerogels.

Ultrahigh-temperature Joule-heating of carbon nanostructures opens up unique opportunities for property enhancements and expanded applications. This study employs rapid electrical Joule-heating at ultrahigh temperatures (up to 3000 K within 60 s) to induce a transformation in nanocarbon aerogels, resulting in highly graphitic structures. These aerogels function as versatile platforms for synthesizing customizable metal oxide nanoparticles while significantly reducing carbon emissions compared to conventional furnace heating methods. The thermal conductivity of the aerogel, characterized by Umklapp scattering, can be precisely adjusted by tuning the heating temperature. Utilizing the aerogel's superhydrophobic properties enables its practical application in filtration systems for efficiently separating toxic halogenated solvents from water. The hierarchically porous aerogel, featuring a high surface area of 607 m2 g-1, ensures the uniform distribution and spacing of embedded metal oxide nanoparticles, offering considerable advantages for catalytic applications. These findings demonstrate exceptional catalytic performance in oxidative desulfurization, achieving a 98.9% conversion of dibenzothiophene in the model fuel. These results are corroborated by theoretical calculations, surpassing many high-performance catalysts. This work highlights the pragmatic and highly efficient use of nanocarbon structures in nanoparticle synthesis under ultrahigh temperatures, with short heating durations. Its broad implications extend to the fields of electrochemistry, energy storage, and high-temperature sensing.

Effects of Ranolazine and Ivabradine on Pulmonary Microhemodynamics in Experimental Model of Pulmonary Thromboembolism.

We studied changes of pulmonary microhemodynamics when modeling pulmonary artery thromboembolism on perfused isolated rabbit lungs after pretreatment with ranolazine and ivabradine. The increase in pulmonary artery pressure, pulmonary vascular resistance, and pre- and postcapillary resistance was less pronounced than in control animals, but was close to that in case of pulmonary thromboembolism after pretreatment with voltage-gated Na+ channel blockers lidocaine and ropivacaine. The increase of capillary filtration coefficient inversely correlated with values of capillary hydrostatic pressure. Thus, ranolazine and ivabradine exhibit the properties of voltage-gated Na+ channel blockers mainly in smooth muscles of pulmonary arterial vessels and promote the decrease in endothelial permeability.

Innovative techniques for combating a common enemy forever chemicals: A comprehensive approach to mitigating per- and polyfluoroalkyl substances (PFAS) contamination.

The pervasive presence of per and polyfluoroalkyl substances (PFAS), commonly referred to as "forever chemicals," in water systems poses a significant threat to both the environment and public health. PFAS are persistent organic pollutants that are incredibly resistant to degradation and have a tendency to accumulate in the environment, resulting in long-term contamination issues. This comprehensive review delves into the primary impacts of PFAS on both the environment and human health while also delving into advanced techniques aimed at addressing these concerns. The focus is on exploring the efficacy, practicality, and sustainability of these methods. The review outlines several key methods, such as advanced oxidation processes, novel materials adsorption, bioremediation, membrane filtration, and in-situ chemical oxidation, and evaluates their effectiveness in addressing PFAS contamination. By conducting a comparative analysis of these techniques, the study aims to provide a thorough understanding of current PFAS remediation technologies, as well as offer insights into integrated approaches for managing these persistent pollutants effectively. While acknowledging the high efficiency of adsorption and membrane filtration in reducing persistent organic pollutants due to their relatively low cost, versatility, and wide applicability, the review suggests that the integration of these methods could result in an overall enhancement of removal performance. Additionally, the study emphasizes the need for researcher attention in key areas and underscores the necessity of collaboration between researchers, industry, and regulatory authorities to address this complex challenge.

Clinical and pathological significance of Orai1 channel expression in human diabetic nephropathy.

Background: Targeted therapies for diabetic nephropathy (DN) are lacking, partly due to their irreversible nature. The role of Orai1, a store-operated Ca2+ channel, in DN remains debated, with conflicting evidence on its effect on proteinuria in animal models. We aimed to elucidate the functional relevance of Orai1 expression for clinicopathological parameters in patients with DN. Methods: In this study, we included 93 patients diagnosed with DN between 2009 and 2019. Immunohistochemical staining for Orai1 was performed on paraffin-embedded kidney sections. The significance of Orai1 expression in human DN was assessed by examining its correlation with DN's pathological and clinical parameters using Pearson's correlation coefficient and univariate logistic regression. Results: Orai1 was significantly overexpressed in DN patients compared to control. A strong correlation was observed between increased Orai1 expression and higher Renal Pathology Society DN classification, enhanced interstitial fibrosis and tubular atrophy scores. Positive correlations with serum creatinine levels and prognosis of chronic kidney disease (CKD) by glomerular filtration rate (GFR) and albuminuria category were noted but the estimated GFR was inversely related to Orai1 expression. Orai1's association with advanced CKD stages persisted even after adjusting for confounding variables in multivariate logistic regression analysis. Conclusion: Orai1 expression is closely associated with histological and clinical severities of DN, suggesting its potential as a predictive biomarker for disease progression and prognosis. These findings provide new perspectives on therapeutic interventions targeting Orai1 in DN.

Impact of Race-Free Glomerular Filtration Rate Estimations on CKD Prevalence in the US Military Health System: A Retrospective Cohort Study.

Rationale & Objective: The 2021 CKD-EPI removes Black race as a factor in calculating the estimated glomerular filtration rate (eGFR). We assessed its effect on CKD prevalence in the demographically-diverse US Military Health System. Study Design: A retrospective calculation of the eGFR from serum creatinine measured over 2016-2019 using both the 2009 and 2021 CKD-EPI equations. Setting & Population: Multicenter health care network with data from 1,502,607 adults in the complete case analysis and from 1,970,433 adults in an imputed race analysis. Predictors: Serum creatinine, age, sex, and race. Outcome: CKD stages 3-5, defined as the last eGFR persistently < 60 mL/min/1.73m2 for ≥90 days. Analytical Approach: The t test and Kruskal-Wallis test were used for continuous variables and Χ2 for categorical data. Results: The population in the complete case analysis had a median age of 40 years and was 18.8% Black race and 35.4% female. With the 2021 equation, the number of Black adults with CKD stages 3-5 increased by 58.1% from 4,147 to 6,556, a change in the crude prevalence from 1.47% to 2.32%. The number of non-Black adults with CKD stages 3-5 decreased by 30.4% from 27,596 to 19,213, a crude prevalence change from 2.26% to 1.58%. Similar results were seen with race imputation. Cumulatively, among adults with CKD stages 3-5 by at least one equation, 45.8% of Black adults were reclassified to more advanced stages of CKD and 44.0% of non-Black adults were reclassified to less severe stages across eGFR thresholds that could change clinical management. Limitations: Potential underestimation of CKD in individuals with only 1 measurement. Conclusions: Adoption of the 2021 CKD-EPI equation in the Military Health System reclassifies many Black adults into new CKD stages 3-5 or into more advanced CKD stages, with the opposite effect on non-Black adults. This may have an effect on CKD treatment and outcomes in ways that are yet unknown.

Until recently, kidney function level was calculated from equations that adjusted the result if the individual was of Black race. Because this may contribute to racial disparities in kidney disease care, a new equation was developed in 2021 that excludes race as a factor. We assessed the possible effects of this equation using data from adults in the US Military Health System from 2016 to 2019. With the new equation, the number of Black adults classified with kidney disease increased while that of non-Black adults decreased. There were similar trends seen in the more severe levels of kidney disease, which could affect decisions in clinical care. These results emphasize the potential positive and negative outcomes to be monitored with the new equation.

A brief history and future directions of dielectrophoretic filtration: A review.

Dielectrophoresis (DEP) is an electrokinetic effect first studied in the early 20th century. Since then, DEP has gained significant interest in research, owing to its ability to solve particle separation problems in various industries. Dielectrophoretic filtration (DEP filtration) is a separation method using DEP to filter a wide range of microparticles, from bacterial cells to catalytic particles. DEP filtration can selectively separate particles based on size or dielectric properties, recover trapped particles and avoid common problems associated with mechanical filtration based on pore size (e.g. pressure drops and regular filter replacements). This review describes the simple beginnings of DEP filtration and how our understanding and applications for DEP filtration have progressed over time. A brief section of DEP theory as well as a note on the general outlook for DEP filtration in the future is presented. DEP filtration offers an exciting opportunity to selectively separate diverse particle mixtures. To achieve such a feat, technical challenges such as Joule Heating and low throughputs must be addressed.

CYSTATIN C-A Monitoring Perspective of Chronic Kidney Disease in Patients with Diabetes.

Chronic kidney disease (CKD) is a microvascular complication that frequently affects numerous patients diagnosed with diabetes. For the diagnosis of CKD, the guidelines recommend the identification of the urinary albumin/creatinine ratio and the determination of serum creatinine, based on which the estimated rate of glomerular filtration (eGFR) is calculated. Serum creatinine is routinely measured in clinical practice and reported as creatinine-based estimated glomerular filtration rate (eGFRcr). It has enormous importance in numerous clinical decisions, including the detection and management of CKD, the interpretation of symptoms potentially related to this pathology and the determination of drug dosage. The equations based on cystatin C involve smaller differences between race groups compared to GFR estimates based solely on creatinine. The cystatin C-based estimated glomerular filtration rate (eGFRcys) or its combination with creatinine (eGFRcr-cys) are suggested as confirmatory tests in cases where creatinine is known to be less precise or where a more valid GFR estimate is necessary for medical decisions. Serum creatinine is influenced by numerous factors: age, gender, race, muscle mass, high-protein diet, including protein supplements, and the use of medications that decrease tubular creatinine excretion (H2 blockers, trimethoprim, fenofibrate, ritonavir, and other HIV drugs). The low levels of creatinine stemming from a vegetarian diet, limb amputation, and conditions associated with sarcopenia such as cirrhosis, malnutrition, and malignancies may lead to inaccurately lower eGFRcr values. Therefore, determining the GFR based on serum creatinine is not very precise. This review aims to identify a new perspective in monitoring renal function, considering the disadvantages of determining the GFR based exclusively on serum creatinine.

Prevalence and clinical determinants of rapid eGFR decline among patients with newly diagnosed type 2 diabetes.

BACKGROUND: Diabetic kidney disease is the most common cause of end-stage kidney disease (ESKD) in the western world. Rapid estimated glomerular filtration rate (eGFR) decline is an independent predictor of ESKD and death in the general population and in subjects with type 2 diabetes mellitus (T2D). AIM: We investigated in a large sample of subjects with newly diagnosed T2D the prevalence and clinical determinants of fast eGFR decline, taking advantage from the dataset of the Associazione Medici Diabetologi (AMD) Annals initiative. METHODS: The eGFR trajectories were evaluated by applying a linear mixed model for repeated measures (LMMRM) and rapid eGFR decline defined as an eGFR decline greater than 5 mL/min/1.73 m2 per year at 3 years. RESULTS: Among 105,163 (57.7% M) subjects with newly diagnosed T2D, 13,587 (12.9 %) subjects showed a rapid eGFR loss. The independent significant predictors were age, female gender, HbA1c, smoking, high baseline eGFR, albuminuria and retinopathy. CONCLUSION: Our study demonstrates that a significant percentage of newly diagnosed T2D subjects have a rapid eGFR decline. Given the association between dynamic changes in eGFR and the risk of ESKD or death, we suggest to include this variable in the definition of CKD.

Direct antiglobulin test type, red blood cell distribution width, and estimated glomerular filtration rate for early prediction of in-hospital mortality of patients with COVID-19.

Objective: This study aimed to investigate the correlation between COVID-19 and the direct antiglobulin test (DAT) and establish an in-hospital mortality risk predictive model based on the DAT type, which can be used for the early prediction of inpatients with COVID-19. Methods: In this study, 502 patients admitted to our hospital who underwent DAT testing from January 29 to February 8, 2023, were included (252 DAT-positive and 250 DAT-negative). Among them, 241 cases of COVID-19 were screened(171 DAT-positive and 70 DAT-negative), clinical and laboratory indicators were compared between DAT-positive and DAT-negative groups. Univariate and multivariate logistic regression analysis, the Kaplan-Meier survival curve and receiver operating curves were used to explore the relation between the DAT type and in-hospital mortality of patients with COVID-19. Results: The proportion of confirmed COVID-19 cases was higher in the DAT-positive group than in the DAT-negative group (67.9 % vs. 28.0 %, P < 0.05). Patients with COVID-19 in the DAT-positive group had higher age-adjusted Charlson comorbidity index scores, red blood cell distribution width (RDW), lactate dehydrogenase, prothrombin time, D-dimer, creatinine, and high-sensitive cardiac troponin T levels than the negative group (P < 0.05), In contrast, hemoglobin and estimated glomerular filtration rate (eGFR) levels were lower in the DAT-positive group. The DAT-positive group also had a higher red blood cell usage volume and in-hospital mortality rate than the DAT-negative group. The mortality rate of patients with COVID-19 with both IgG and C3d positive was higher than that of the other groups. Multivariate logistic regression analysis showed that RDW and eGFR were associated with mortality in patients with COVID-19. The combined predictive model of DAT type, RDW, and eGFR showed an area under the curve of 0.782, sensitivity of 0.769, and specificity of 0.712 in predicting in-hospital mortality risk in patients with COVID-19. Conclusion: The established predictive model for in-hospital mortality risk of patients with COVID-19 based on DAT type, RDW, and eGFR can provide a basis for timely intervention to reduce the mortality rates of patients with COVID-19. This model is accessible at https://jijijiduola.shinyapps.io/0531// for research purposes.

Prevalence and metabolic risk factors of chronic kidney disease among a Mexican adult population: a cross-sectional study in primary healthcare medical units.

Introduction: The intricate relationship between obesity and chronic kidney disease (CKD) progression underscores a significant public health challenge. Obesity is strongly linked to the onset of several health conditions, including arterial hypertension (AHTN), metabolic syndrome, diabetes, dyslipidemia, and hyperuricemia. Understanding the connection between CKD and obesity is crucial for addressing their complex interplay in public health strategies. Objective: This research aimed to determine the prevalence of CKD in a population with high obesity rates and evaluate the associated metabolic risk factors. Material and Methods: In this cross-sectional study conducted from January 2017 to December 2019 we included 3,901 participants of both sexes aged ≥20 years who were selected from primary healthcare medical units of the Mexican Social Security Institute (IMSS) in Michoacan, Mexico. We measured the participants' weight, height, systolic and diastolic blood pressure, glucose, creatinine, total cholesterol, triglycerides, HDL-c, LDL-c, and uric acid. We estimated the glomerular filtration rate using the Collaborative Chronic Kidney Disease Epidemiology (CKD-EPI) equation. Results: Among the population studied, 50.6% were women and 49.4% were men, with a mean age of 49 years (range: 23-90). The prevalence of CKD was 21.9%. Factors significantly associated with an increased risk of CKD included age ≥60 years (OR = 11.70, 95% CI [9.83-15.93]), overweight (OR = 4.19, 95% CI [2.88-6.11]), obesity (OR = 13.31, 95% CI [11.12-15.93]), abdominal obesity (OR = 9.25, 95% CI [7.13-11.99]), AHTN (OR = 20.63, 95% CI [17.02-25.02]), impaired fasting glucose (IFG) (OR = 2.73, 95% CI [2.31-3.23]), type 2 diabetes (T2D) (OR = 14.30, 95% CI [11.14-18.37]), total cholesterol (TC) ≥200 mg/dL (OR = 6.04, 95% CI [5.11-7.14]), triglycerides (TG) ≥150 mg/dL (OR = 5.63, 95% CI 4.76-6.66), HDL-c <40 mg/dL (OR = 4.458, 95% CI [3.74-5.31]), LDL-c ≥130 mg/dL (OR = 6.06, 95% CI [5.12-7.18]), and serum uric acid levels ≥6 mg/dL in women and ≥7 mg/dL in men (OR = 8.18, 95% CI [6.92-9.68]), (p < 0.0001). These factors independently contribute to the development of CKD. Conclusions: This study underscores the intricate relationship between obesity and CKD, revealing a high prevalence of CKD. Obesity, including overweight, abdominal obesity, AHTN, IFG, T2D, dyslipidemia, and hyperuricemia emerged as significant metabolic risk factors for CKD. Early identification of these risk factors is crucial for effective intervention strategies. Public health policies should integrate both pharmacological and non-pharmacological approaches to address obesity-related conditions and prevent kidney damage directly.