A Review of Focal Segmental Glomerulosclerosis Classification With a Focus on Genetic Associations.

Focal segmental glomerulosclerosis (FSGS) defines a distinct histologic pattern observed in kidney tissue that is linked to several distinct underlying causes, all converging on the common factor of podocyte injury. It presents a considerable challenge in terms of classification because of its varied underlying causes and the limited correlation between histopathology and clinical outcomes. Critically, precise nomenclature is key to describe and delineate the pathogenesis, subsequently guiding the selection of suitable and precision therapies. A proposed pathomechanism-based approach has been suggested for FSGS classification. This approach differentiates among primary, secondary, genetic, and undetermined causes, aiming to provide clarity. Genetic FSGS from monogenic mutations can emerge during childhood or adulthood, and it is advisable to conduct genetic testing in cases in which there is a family history of chronic kidney disease, nephrotic syndrome, or resistance to treatment. Genome-wide association studies have identified several genetic risk variants, such as those in apolipoprotein L1 (APOL1), that play a role in the development of FSGS. Currently, no specific treatments have been approved to treat genetic FSGS; however, interventions targeting underlying cofactor deficiencies have shown potential in some cases. Furthermore, encouraging results have emerged from a phase 2 trial investigating inaxaplin, a novel small molecule APOL1 channel inhibitor, in APOL1-associated FSGS.

Dentin remineralization using a stimuli-responsive engineered small molecule GSK3 antagonists-functionalized adhesive.

OBJECTIVES: Tideglusib has shown great performance in terms of dentin regenerative properties. This study aims to evaluate bonding ability, of demineralized dentin infiltrated with polymeric nanoparticles (NPs) doped with tideglusib (TG) (TG-NPs). METHODS: Dentin conditioned surfaces were infiltrated with NPs and TG-NPs. Bonded interfaces were created and stored for 24 h and then submitted to mechanical, chemical and thermal challenging. The resin-dentin interface was evaluated through a doubled dye fluorescent technique and a calcium chelator fluorophore under a confocal laser scanning microscopy, and by field emission scanning electron microscopy. RESULTS: Dentin surfaces treated with TG-NPs and load cycled produced higher bond strength than the rest of the groups. Immersion of dentin specimens treated with undoped-NPs in collagenase solution attained the lowest microtensile bond strength (MTBS) values. Both porosity and nanoleakage decreased when dentin was infiltrated with TG-NPs, that revealed strong signals of xylenol orange stain at both hybrid layer and dentinal tubules. The presence of NPs, in general, inducted the presence of mineralized interfaces after mechanical loading and thermocycling. CONCLUSIONS: Nanoparticles doped with tideglusib promoted the highest dentin bonding efficacy among groups, as they facilitated the maximum bond strength values with creation of mineral deposits at the hybrid layer and dentinal walls. Tideglusib enabled scarce porosity, nanoleakage and advanced sealing among dentin groups. SIGNIFICANCE: Doping hydrophilic polymeric NPs with tideglusib, infiltrated in etched dentin represents a reproducible technique to create reparative dentin at the resin-dentin interface, by inducing therapeutic bioactivity.

COVID-19 outcomes in patients with a history of immune-mediated glomerular diseases.

Introduction: Patients with immune-mediated glomerular diseases are considered at high risk for severe COVID-19 outcomes. However, conclusive evidence for this patient population is scarce. Methods: We created a global registry and retrospectively collected clinical data of patients with COVID-19 and a previously diagnosed immune-mediated glomerular disease to characterize specific risk factors for severe COVID-19 outcomes. Results: Fifty-nine patients with a history of immune-mediated glomerular diseases were diagnosed with COVID-19 between 01.03.2020 and 31.08.2021. Over a mean follow-up period of 24.79 ± 18.89 days, ten patients (16.9%) developed acute kidney injury. Overall, 44.1% of patients were managed in an outpatient setting and therefore considered as having "non-severe" COVID-19, while 55.9% of patients had severe COVID-19 requiring hospitalization including worse outcomes. Comparing both groups, patients with severe COVID-19 were significantly older (53.55 ± 17.91 versus 39.77 ± 14.95 years, p = .003), had lower serum albumin levels at presentation (3.00 ± 0.80 g/dL versus 3.99 ± 0.68 g/dL, p = .016) and had a higher risk of developing acute kidney injury (27% versus 4%, p = .018). Male sex (p <.001) and ongoing intake of corticosteroids at presentation (p = .047) were also significantly associated with severe COVID-19 outcomes, while the overall use of ongoing immunosuppressive agents and glomerular disease remission status showed no significant association with the severity of COVID-19 (p = .430 and p = .326, respectively). Conclusion: Older age, male sex, ongoing intake of corticosteroids and lower serum albumin levels at presentation were identified as risk factors for severe COVID-19 outcomes in patients with a history of various immune-mediated glomerular diseases.

Onconephrology 2022: An Update.

Onconephrology is an upcoming and expanding subspecialty that deals with the intersections between hematology/oncology and nephrology. With the paradigm shift in the understanding of cancer immunobiology and mechanisms of oncotherapeutic drug toxicities, it is important for a nephrologist to have a sound understanding of this field. Over the last 5 years, there have been immense developments in our understanding of kidney-related adverse events from various targeted, immuno- and cellular-based therapies. Pathogenic mechanisms of electrolyte imbalance, hypertension (oncohypertension), and AKI from multiple forms of cancer therapies have been explored. Significant research has also been conducted in the field of transplant onconephrology. In this review, we have tried to assimilate the most recent updates in the last 2 years in this ever-growing and fascinating field.

Anaplastic lymphoma kinase inhibitors and their effect on the kidney.

Lung cancer is the leading cause of cancer-related mortality and approximately 5% of non-small-cell lung cancer (NSCLC) patients are positive for anaplastic lymphoma kinase (ALK) gene rearrangement or fusion with echinoderm microtubule-associated protein-like 4. ALK inhibitors are the mainstay treatment for patients with NSCLC harboring a rearrangement of the ALK gene or the ROS1 oncogenes. With the recent publication of pivotal trials leading to the approval of these compounds in different indications, their toxicity profile warrants an update. Several ALK-1 inhibitors are used in clinical practice, including crizotinib, ceritinib and alectinib. According to the package insert and published literature, treatment with several ALK-1 inhibitors appears to be associated with the development of peripheral edema and rare electrolyte disorders, kidney failure, proteinuria and an increased risk for the development and progression of renal cysts. This review introduces the different types of ALK inhibitors, focusing on their detailed kidney-related side effects in clinical practice.

Hypomagnesemia in Patients With Cancer: The Forgotten Ion.

Magnesium is crucial for various cellular and enzymatic processes, yet it often is overlooked or underappreciated. Hypomagnesemia, a deficiency of magnesium in the blood, is a frequent problem in cancer patients and can lead to severe symptoms and morbidity. In this review, we provide an in-depth analysis of the physiology and regulation of magnesium, and signs and symptoms of hypomagnesemia in cancer patients. We also examine the causes and mechanisms of magnesium imbalances in cancer patients, specifically focusing on cancer-specific therapies that can lead to hypomagnesemia. Finally, we provide updates on the management of hypomagnesemia, including oral and parenteral supplementation, as well as the role of drugs in cases that are resistant to treatment. This review aims to raise awareness among health care providers caring for cancer patients about the significance of monitoring magnesium levels in cancer patients and function as a guide. Future clinical studies should focus on magnesium monitoring, its impact on cancer progression, and its potential for preventing acute kidney injury.

Análisis pre mundial del paso de un marchista de élite en pista electrónica / Análise prémundial do passo de um marchista de elite em pista eletrônica / Pre-world analysis of the step of an elite marchist on an electronic track

Problema: en el mundial, los marchistas participan con el más alto nivel de ejecución técnica y con las mejores condiciones físicas, por lo que el análisis de los pasos de un marchista es clave para la obtención de un resultado óptimo. Objetivo: analizar la técnica del paso de un marchista de elite y el comportamiento de las variables de la marcha atlética, pre competencia al mundial de atletismo. Método: al deportista se le aplicó una prueba en una pista electrónica, evaluando las variables cinemáticas: longitud de paso, frecuencia de pasos, tiempo de vuelo y velocidad. Se utilizó ANOVA para determinar diferencias significativas (p ≤0.05). Resultados: en las tres pruebas realizadas, todas las variables incrementaron significativamente, aunque la diferencia más significativa se encontró entre tiempo de vuelo y frecuencia de pasos p=0.0000001, p<0.05. Conclusión: debido a que el tiempo de vuelo se incrementa rápidamente, se debe cuidar que no influya en la ejecución técnica del marchista para que sea más efectiva y así evitar una amonestación o descalificación.

Problem: In the World Athletics Championships, the racewalkers participate with the highest level of technical execution and with the best physical conditions, so the analysis of the steps of a racewalker is key to obtain an optimal result. Objective: To analyze the technique of an elite racewalker and the behavior of the variables of the athletic racewalking, pre-competition to the World Athletics Championships. Method: A test on an electronic track was given to one athlete, evaluating the kinematic variables: step length, step frequency, flight time, and speed. ANOVA was used to determine significant differences (p ≤0.05). Result: In the three tests carried out, all the variables increased significantly, although the most significant difference was found between flight time and step frequency p = 0.0000001, p <0.05. Conclusion: Since the flight time increases rapidly, it must be careful that this not influence the technical execution of the racewalkers, to be more effective, and thus avoid a warning or disqualification.

Problema: No mundial, os marchistas participam com o maior nível de execução técnica e com as melhores condições físicas, é por isso que a análise dos passos de um marchista é a chave para a obtenção de melhores resultados. Objetivo: analisar a técnica de passo de um marchista de elite e o comportamento das variáveis da marcha atlética, pré-competição rumo ao mundial de atletismo. Método: um teste foi aplicado em uma pista eletrônica de um marchista e se estudaram as seguintes variáveis cinemáticas: o comprimento do passo, a frequência de passos, o tempo de voo e a velocidade. ANOVA foi utilizada para determinar as diferenças significativas (p ≤0.05). Resultados: Em todos os três testes realizados, todas as variáveis aumentaram significativamente, embora a diferença mais significativa foi encontrada entre o tempo de voo e a frequência de passos p = 0.0000001, p <0,05. Conclusão: Porque o tempo de voo aumenta rapidamente, deve ser assegurado que não tenha nenhuma influência sobre a execução técnica do marchista, para que seja mais eficaz e, assim, evitar uma advertência ou desqualificação.