COVID-19 Computed tomography patterns in renal replacement therapy patients / Padrões de tomografia computadorizada da COVID-19 em pacientes em terapia renal substitutiva

ABSTRACT Introduction: Lung diseases are common in patients with end stage kidney disease (ESKD), making differential diagnosis with COVID-19 a challenge. This study describes pulmonary chest tomography (CT) findings in hospitalized ESKD patients on renal replacement therapy (RRT) with clinical suspicion of COVID-19. Methods: ESKD individuals referred to emergency department older than 18 years with clinical suspicion of COVID-19 were recruited. Epidemiological baseline clinical information was extracted from electronic health records. Pulmonary CT was classified as typical, indeterminate, atypical or negative. We then compared the CT findings of positive and negative COVID-19 patients. Results: We recruited 109 patients (62.3% COVID-19-positive) between March and December 2020, mean age 60 ± 12.5 years, 43% female. The most common etiology of ESKD was diabetes. Median time on dialysis was 36 months, interquartile range = 12-84. The most common pulmonary lesion on CT was ground glass opacities. Typical CT pattern was more common in COVID-19 patients (40 (61%) vs 0 (0%) in non-COVID-19 patients, p < 0.001). Sensitivity was 60.61% (40/66) and specificity was 100% (40/40). Positive predictive value and negative predictive value were 100% and 62.3%, respectively. Atypical CT pattern was more frequent in COVID-19-negative patients (9 (14%) vs 24 (56%) in COVID-19-positive, p < 0.001), while the indeterminate pattern was similar in both groups (13 (20%) vs 6 (14%), p = 0.606), and negative pattern was more common in COVID-19-negative patients (4 (6%) vs 12 (28%), p = 0.002). Conclusions: In hospitalized ESKD patients on RRT, atypical chest CT pattern cannot adequately rule out the diagnosis of COVID-19.

RESUMO Introdução: Doenças pulmonares são comuns em pacientes com doença renal em estágio terminal (DRET), dificultando o diagnóstico diferencial com COVID-19. Este estudo descreve achados de tomografia computadorizada de tórax (TC) em pacientes com DRET em terapia renal substitutiva (TRS) hospitalizados com suspeita de COVID-19. Métodos: Indivíduos maiores de 18 anos com DRET, encaminhados ao pronto-socorro com suspeita de COVID-19 foram incluídos. Dados clínicos e epidemiológicos foram extraídos de registros eletrônicos de saúde. A TC foi classificada como típica, indeterminada, atípica, negativa. Comparamos achados tomográficos de pacientes com COVID-19 positivos e negativos. Resultados: Recrutamos 109 pacientes (62,3% COVID-19-positivos) entre março e dezembro de 2020, idade média de 60 ± 12,5 anos, 43% mulheres. A etiologia mais comum da DRET foi diabetes. Tempo médio em diálise foi 36 meses, intervalo interquartil = 12-84. A lesão pulmonar mais comum foi opacidades em vidro fosco. O padrão típico de TC foi mais comum em pacientes com COVID-19 (40 (61%) vs. 0 (0%) em pacientes sem COVID-19, p < 0,001). Sensibilidade 60,61% (40/66), especificidade 100% (40/40). Valores preditivos positivos e negativos foram 100% e 62,3%, respectivamente. Padrão atípico de TC foi mais frequente em pacientes COVID-19-negativos (9 (14%) vs. 24 (56%) em COVID-19-positivos, p < 0,001), enquanto padrão indeterminado foi semelhante em ambos os grupos (13 (20%) vs. 6 (14%), p = 0,606), e padrão negativo foi mais comum em pacientes COVID-19-negativos (4 (6%) vs. 12 (28%), p = 0,002). Conclusões: Em pacientes com DRET em TRS hospitalizados, um padrão atípico de TC de tórax não pode excluir adequadamente o diagnóstico de COVID-19.

Acute kidney injury: the experience of a tertiary center of Pediatric Nephrology / Insuficiência renal aguda: experiência de um centro terciário de Nefrologia Pediátrica

ABSTRACT Introduction: Acute kidney injury (AKI) is an abrupt deterioration of kidney function. The incidence of pediatric AKI is increasing worldwide, both in critically and non-critically ill settings. We aimed to characterize the presentation, etiology, evolution, and outcome of AKI in pediatric patients admitted to a tertiary care center. Methods: We performed a retrospective observational single-center study of patients aged 29 days to 17 years and 365 days admitted to our Pediatric Nephrology Unit from January 2012 to December 2021, with the diagnosis of AKI. AKI severity was categorized according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The outcomes considered were death or sequelae (proteinuria, hypertension, or changes in renal function at 3 to 6 months follow-up assessments). Results: Forty-six patients with a median age of 13.0 (3.5-15.5) years were included. About half of the patients (n = 24, 52.2%) had an identifiable risk factor for the development of AKI. Thirteen patients (28.3%) were anuric, and all of those were categorized as AKI KDIGO stage 3 (p < 0.001). Almost one quarter (n = 10, 21.7%) of patients required renal replacement therapy. Approximately 60% of patients (n = 26) had at least one sequelae, with proteinuria being the most common (n = 15, 38.5%; median (P25-75) urinary protein-to-creatinine ratio 0.30 (0.27-0.44) mg/mg), followed by reduced glomerular filtration rate (GFR) (n = 11, 27.5%; median (P25-75) GFR 75 (62-83) mL/min/1.73 m2). Conclusions: Pediatric AKI is associated with substantial morbidity, with potential for proteinuria development and renal function impairment and a relevant impact on long-term prognosis.

RESUMO Introdução: Insuficiência renal aguda (IRA) é uma deterioração abrupta da função renal. A incidência de IRA pediátrica está aumentando em todo o mundo, em ambientes críticos e não críticos. Nosso objetivo foi caracterizar apresentação, etiologia, evolução e desfechos da IRA em pacientes pediátricos internados em um centro de atendimento terciário. Métodos: Realizamos estudo retrospectivo observacional de centro único de pacientes com idade entre 29 dias a 17 anos e 365 dias internados em nossa Unidade de Nefrologia Pediátrica, de janeiro de 2012 a dezembro de 2021, com diagnóstico de IRA. A gravidade da IRA foi categorizada de acordo com os critérios do Kidney Disease Improving Global Outcomes (KDIGO). Os desfechos considerados foram óbito ou sequelas (proteinúria, hipertensão ou alterações na função renal em avaliações de acompanhamento de 3 a 6 meses). Resultados: Incluímos 46 pacientes com idade mediana de 13,0 (3,5-15,5) anos. Cerca de metade (n = 24; 52,2%) apresentou um fator de risco identificável para o desenvolvimento de IRA. Treze pacientes (28,3%) eram anúricos; todos foram classificados como IRA KDIGO 3 (p < 0,001). Quase um quarto (n = 10; 21,7%) dos pacientes necessitaram de terapia renal substitutiva. Aproximadamente 60% (n = 26) apresentou pelo menos uma sequela, sendo proteinúria a mais comum (n = 15; 38,5%; mediana (P25-75) da relação proteína/creatinina urinária 0,30 (0,27-0,44) mg/mg), seguida de taxa de filtração glomerular (TFG) reduzida (n = 11; 27,5%; mediana (P25-75) da TFG 75 (62-83) mL/min/1,73 m2). Conclusões: A IRA pediátrica está associada à morbidade substancial, com potencial para desenvolvimento de proteinúria e comprometimento da função renal e impacto relevante no prognóstico de longo prazo.

Acute kidney injury in nonagenarians: clinical characteristics and mortality / Injúria renal aguda em nonagenários: características clínicas e mortalidade

Abstract Introduction: Nonagenarians constitute a rising percentage of inpatients, with acute kidney injury (AKI) being frequent in this population. Thus, it is important to analyze the clinical characteristics of this demographic and their impact on mortality. Methods: Retrospective study of nonagenarian patients with AKI at a tertiary hospital between 2013 and 2022. Only the latest hospital admission was considered, and patients with incomplete data were excluded. A logistic regression analysis was conducted to define risk factors for mortality. A p-value < 0.05 was considered statistically significant. Results: A total of 150 patients were included, with a median age of 93.0 years (91.2-95.0), and males accounting for 42.7% of the sample. Sepsis was the most common cause of AKI (53.3%), followed by dehydration/hypovolemia (17.7%), and heart failure (17.7%). ICU admission occurred in 39.3% of patients, mechanical ventilation in 14.7%, vasopressors use in 22.7% and renal replacement therapy (RRT) in 6.7%. Death occurred in 56.7% of patients. Dehydration/hypovolemia as an etiology of AKI was associated with a lower risk of mortality (OR 0.18; 95% CI 0.04-0.77, p = 0.020). KDIGO stage 3 (OR 3.15; 95% CI 1.17-8.47, p = 0.023), ICU admission (OR 12.27; 95% CI 3.03-49.74, p < 0.001), and oliguria (OR 5.77; 95% CI 1.98-16.85, p = 0.001) were associated with mortality. Conclusion: AKI nonagenarians had a high mortality rate, with AKI KDIGO stage 3, oliguria, and ICU admission being associated with death.

Resumo Introdução: Nonagenários constituem um percentual de pacientes internados em ascensão, sendo a injúria renal aguda (IRA) frequente nesses pacientes. Sendo assim, é importante analisar as características clínicas dessa população e seu impacto na mortalidade. Métodos: Estudo retrospectivo de pacientes nonagenários com IRA entre 2013 e 2022 em um hospital terciário. Apenas o último internamento foi considerado e pacientes com dados incompletos foram excluídos. Uma análise por regressão logística foi realizada para definir fatores de risco para mortalidade. Um valor de p < 0,05 foi considerado significativo. Resultados: Foram incluídos 150 pacientes com mediana de idade 93,0 anos (91,2-95,0) e sexo masculino em 42,7%. Sepse foi a causa mais comum de IRA (53,3%), seguida de desidratação/hipovolemia (17,7%) e insuficiência cardíaca (17,7%). Admissão na UTI ocorreu em 39,3% dos pacientes, ventilação mecânica em 14,7%, uso de vasopressores em 22,7% e realização de terapia renal substitutiva (TRS) em 6,7%. Óbito ocorreu em 56,7% dos pacientes. Desidratação/hipovolemia como etiologia da IRA foi associado a menor risco de mortalidade (OR 0,18; IC 95% 0,04-0,77, p = 0,020). Estágio KDIGO 3 (OR 3,15; IC 95% 1,17-8,47, p = 0,023), admissão na UTI (OR 12,27; IC 95% 3,03-49,74, p < 0,001) e oligúria (OR 5,77; IC 95% 1,98-16,85, p = 0,001) foram associados à mortalidade. Conclusão: Nonagenários com IRA apresentaram alta mortalidade e IRA KDIGO 3, oligúria e admissão na UTI foram associadas ao óbito.

Bone aluminum accumulation in the current era / Acúmulo de alumínio no tecido ósseo na era atual

In the last few years, evidence from the Brazilian Registry of Bone Biopsy (REBRABO) has pointed out a high incidence of aluminum (Al) accumulation in the bones of patients with CKD under dialysis. This surprising finding does not appear to be merely a passive metal accumulation, as prospective data from REBRABO suggest that the presence of Al in bone may be independently associated with major adverse cardiovascular events. This information contrasts with the perception of epidemiologic control of this condition around the world. In this opinion paper, we discussed why the diagnosis of Al accumulation in bone is not reported in other parts of the world. We also discuss a range of possibilities to understand why bone Al accumulation still occurs, not as a classical syndrome with systemic signs of intoxication, as occurred it has in the past.

Nos últimos anos, evidências do Registro Brasileiro de Biópsia óssea (REBRABO) apontaram uma alta incidência de intoxicação por alumínio (Al) no tecido ósseo de pacientes com DRC em diálise. Essa surpreendente informação parece representar não apenas um acúmulo passivo deste metal, visto que dados prospectivos do REBRABO sugerem que a presença de Al no tecido ósseo pode estar independentemente relacionada a eventos cardiovasculares adversos maiores. Essas informações contrastam com a percepção mundial do controle epidemiológico dessa condição. Neste artigo de opinião, discutimos por que o diagnóstico de acúmulo ósseo de Al não é relatado em outras partes do mundo, e também discutimos uma gama de possibilidades para entender por que nós acreditamos que o acúmulo de Al no tecido ósseo ainda ocorre, não como se apresentava no passado, ou seja, como uma síndrome com sinais e sintomas sistêmicos de intoxicação.

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.

Analysis of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as inflammatory biomarkers in chronic kidney disease: impact of parathyroidectomy / Análise das relações neutrófilo/linfócito e plaqueta/linfócito como marcadores inflamatórios na doença renal crônica: impacto da paratireoidectomia

Abstract Introduction: Secondary hyperparathyroidism (SHPT) is one of the causes for inflammation in CKD. We assessed the impact of parathyroidectomy (PTX) on neutrophil-to-lymphocyte (N/L) and platelet-to-lymphocyte (P/L) ratios in SHPT patients. Methods: A total of 118 patients [hemodialysis (HD, n = 81), and transplant recipients (TX, n = 37)] undergoing PTX between 2015 and 2021 were analyzed. Results: There was a significant reduction in calcium and PTH levels in both groups, in addition to an increase in vitamin D. In the HD group, PTX did not alter N/L and P/L ratios. In the TX group, there was a reduction in N/L and P/L ratios followed by a significant increase in total lymphocyte count. Conclusion: N/L and P/L ratios are not reliable biomarkers of inflammation in SHPT patients undergoing PTX. Uremia, which induces a state of chronic inflammation in dialysis patients, and the use of immunosuppression in kidney transplant recipients are some of the confounding factors that prevent the use of this tool in clinical practice.

Resumo Introdução: O hiperparatireoidismo secundário (HPTS) é uma das causas de inflamação na DRC. Avaliamos o impacto da paratireoidectomia (PTX) nas relações neutrófilo/linfócito (N/L) e plaqueta/linfócito (P/L) em pacientes com HPTS. Métodos: Foram analisados 118 pacientes [hemodiálise (HD, n = 81) e transplantados (TX, n = 37)] submetidos à PTX entre 2015 e 2021. Resultados: Houve redução significativa de cálcio e PTH nos dois grupos, além de elevação de vitamina D. No grupo HD, a PTX não mudou as relações N/L e P/L. Já no grupo TX, houve redução nas relações N/L e P/L acompanhadas de elevação significativa do número de linfócitos totais. Conclusão: As relações N/L e P/L não são marcadores fidedignos de inflamação em pacientes com HPTS submetidos à PTX. A uremia, que induz um estado de inflamação crônica em pacientes dialíticos, e o uso de imunossupressão em pacientes transplantados renais são alguns dos fatores de confusão que impedem o uso dessa ferramenta na prática clínica.

Transitioning to peritoneal dialysis: it does not matter where you come from / Transição para diálise peritoneal: não importa de onde

Introduction: Patients with end-stage renal disease (ESRD) frequently change renal replacement (RRT) therapy modality due to medical or social reasons. We aimed to evaluate the outcomes of patients under peritoneal dialysis (PD) according to the preceding RRT modality. Methods: We conducted a retrospective observational single-center study in prevalent PD patients from January 1, 2010, to December 31, 2017, who were followed for 60 months or until they dropped out of PD. Patients were divided into three groups according to the preceding RRT: prior hemodialysis (HD), failed kidney transplant (KT), and PD-first. Results: Among 152 patients, 115 were PD-first, 22 transitioned from HD, and 15 from a failing KT. There was a tendency for ultrafiltration failure to occur more in patients transitioning from HD (27.3% vs. 9.6% vs. 6.7%, p = 0.07). Residual renal function was better preserved in the group with no prior RRT (p < 0.001). A tendency towards a higher annual rate of peritonitis was observed in the prior KT group (0.70 peritonitis/year per patient vs. 0.10 vs. 0.21, p = 0.065). Thirteen patients (8.6%) had a major cardiovascular event, 5 of those had been transferred from a failing KT (p = 0.004). There were no differences between PD-first, prior KT, and prior HD in terms of death and technique survival (p = 0.195 and p = 0.917, respectively) and PD efficacy was adequate in all groups. Conclusions: PD is a suitable option for ESRD patients regardless of the previous RRT and should be offered to patients according to their clinical and social status and preferences.

Introdução: Pacientes com doença renal em estágio terminal (DRET) frequentemente mudam de modalidade de terapia renal substitutiva (TRS) por razões médicas ou sociais. Nosso objetivo foi avaliar desfechos de pacientes em diálise peritoneal (DP) segundo a modalidade anterior de TRS. Métodos: Realizamos estudo retrospectivo observacional unicêntrico, em pacientes prevalentes em DP, de 1º de janeiro de 2010 a 31 de dezembro de 2017, acompanhados por 60 meses ou até saírem de DP. Pacientes foram divididos em três grupos de acordo com a TRS anterior: hemodiálise prévia (HD), transplante renal malsucedido (TR) e DP como primeira opção (PD-first). Resultados: Entre 152 pacientes, 115 eram PD-first, 22 transitaram da HD e 15 de TR malsucedido. Houve tendência à maior ocorrência de falência de ultrafiltração em pacientes em transição da HD (27,3% vs. 9,6% vs. 6,7%; p = 0,07). A função renal residual foi melhor preservada no grupo sem TRS prévia (p < 0,001). Observou-se tendência à maior taxa anual de peritonite no grupo TR prévio (0,70 peritonite/ano por paciente vs. 0,10 vs. 0,21; p = 0,065). Treze pacientes (8,6%) tiveram um evento cardiovascular maior, cinco dos quais haviam sido transferidos de um TR malsucedido (p = 0,004). Não houve diferenças entre PD-first, TR prévio e HD prévia em termos de óbito e sobrevida da técnica (p = 0,195 e p = 0,917, respectivamente) e a eficácia da DP foi adequada em todos os grupos. Conclusões: A DP é uma opção adequada para pacientes com DRET, independentemente da TRS anterior, e deve ser oferecida aos pacientes de acordo com seu status clínico e social e suas preferências.

Caracterización de la situación problémica en un estudio psicosocial con pacientes con enfermedad renal crónica

Introducción: La enfermedad renal crónica es un problema de salud a nivel mundial, su manifestación más grave, la insuficiencia renal crónica, incide en el contexto cubano y determina el crecimiento de pacientes en hemodiálisis. El objetivo del texto es valorar los principales resultados del diagnóstico y caracterización de la situación problémica en un estudio de carácter psicosocial con pacientes con Insuficiencia Renal Crónica en la sala de Hemodiálisis del municipio Florida, de la provincia de Camagüey. Método: Es una investigación-acción participativa de corte experimental, que se desarrolla entre enero 2023 y diciembre del 2024 la cual constituye salida del proyecto de investigación Sistema de acciones psicosociales para el perfeccionamiento de la atención integral a los pacientes con enfermedades no transmisibles. El universo está constituido por 56 pacientes y la muestra por 22, que reciben tratamiento depurador y conservador, 22 familiares y 12 profesionales del servicio. El instrumento de investigación por excelencia fue la encuesta a participantes. Resultados: La edad de los pacientes no es definitiva de un grupo etario; predominan los hombres; se constata un elevado por ciento de pacientes con poca tolerancia a la adherencia al tratamiento e insuficiente desarrollo de las habilidades psicosociales y declaran la necesidad de poseer conocimientos para lograr estados de salud que conlleven a la sobrevida. Discusión: No existe coincidencia con lo constatado en la determinación de los grupos etarios de prevalencia para la enfermedad, pero los especialistas insisten en que la enfermedad no es privativa de un período de vida específico; reconocen la importancia del conocimiento de los factores de riesgo por el paciente para la prevención, promoción y educación en salud y resaltan la necesidad de la comunicación y la empatía entre el personal de salud y el paciente, para lograr resultados y estados emocionales favorables ante la enfermedad y el tratamiento.

Introduction: Chronic kidney disease is a global health problem. Its most serious manifestation, chronic kidney failure, affects the Cuban context and determines the growth of patients on hemodialysis. The objective of the text is to evaluate the main results of the diagnosis and characterization of the problematic situation in a psychosocial study with patients with Chronic Renal Failure in the Hemodialysis room of the Florida municipality, of the county of Camagüey. Method: It is an experimental participatory action research, which takes place between January 2023 and December 2024, which constitutes the output of the research project System of psychosocial actions for the improvement of comprehensive care for patients with non-communicable diseases. The universe is made up of 56 patients and the sample is made up of 22, who receive purifying and conservative treatment, 22 family members and 12 service professionals. The research instrument par excellence was the participant survey. Results: The age of the patients is not definitive of an age group; men predominate; A high percentage of patients are found to have low tolerance for adherence to treatment and insufficient development of psychosocial skills and declare the need to possess knowledge to achieve health states that lead to survival. Discussion: There is no coincidence with what was found in the determination of the prevalence age groups for the disease, but specialists insist that the disease is not exclusive to a specific period of life; recognize the importance of the patient's knowledge of risk factors for prevention, promotion and health education and highlight the need for communication and empathy between health personnel and the patient, to achieve favorable results and emotional states in the face of the disease and treatment.

Comprehensive analysis of MAPK genes in the prognosis, immune characteristics, and drug treatment of renal clear cell carcinoma using bioinformatic analysis and Mendelian randomization.

Mitogen-activated protein kinase (MAPK) signalling is vitally important in tumour development and progression. This study is the first to comprehensively analyse the role of MAPK-family genes in the progression, prognosis, immune-cell infiltration, methylation, and potential therapeutic value drug candidates in ccRCC. We identified a novel prognostic panel of six MAPK-signature genes (MAP3K12, MAP3K1, MAP3K5, MAPK1, MAPK8, MAPK9), and introduced a robust MAPK-signature risk model for predicting ccRCC prognosis. Model construction, evaluation, and external validation using datasets from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database demonstrated its stability, as well as high sensitivity and specificity. Enrichment analysis suggested the participation of immune-mediated mechanism in MAPK dysregulation in ccRCC. Immune-infiltration analysis confirmed the relationship and revealed that the MAPK-signature risk model might stratify immunotherapy response in ccRCC, which was verified in drug sensitivity analysis and validated in external ccRCC immunotherapy dataset (GSE67501). Potential therapeutic drug predictions for key MAPKs using DSigDB, Network Analyst, CTD, and DGIdb were subsequently verified by molecular docking with AutoDock Vina and PyMol. Mendelian randomization further demonstrated the possibilities of the MAPK-signature genes as targets for therapeutic drugs in ccRCC. Methylation analysis using UALCAN and MethSurv revealed the participation of epigenetic modifications in dysregulation and survival difference of MAPK pathway in ccRCC. Among the key MAPKs, MAP3K12 exhibited the highest significance, indicating its independent prognostic value as single gene in ccRCC. Knockout and overexpression validation experiments in vitro and in vivo found that MAP3K12 acted as a promoter of tumour progression in RCC, suggesting a pivotal role for MAP3K12 in the proliferation, migration, and invasion of RCC cells. Our findings proposed the potential of MAPK-signature genes as biomarkers for prognosis and therapy response, as well as targets for therapeutic drugs in ccRCC.

[Patient-derived renal pelvic carcinoma organoids: establishment and sensitivity to chemotherapeutic drugs].

Renal pelvic carcinoma is a common upper urothelial cancer. The lack of an ideal in vitro model seriously hinders the research progress in the treatment for this disease. This study established a pipeline for the culture of renal pelvic carcinoma organoids based on the tumor tissue samples derived from the patients and tested the organoids to chemotherapeutic drugs. The results of immunohistochemistry and fluorescence experiments confirmed that the renal pelvic carcinoma organoids obtained from culture presented obvious nuclear heteromorphism, which was consistent with the tissue samples from renal pelvic carcinoma patients. The tumor marker molecule CD44 and the cell proliferation marker molecule Ki67 were positive in the organoids, indicating that the organoids were enriched with tumor stem cells and had strong proliferative ability. The renal pelvic carcinoma organoids were highly sensitive to pirarubicin, which had obvious killing effects. In brief, this study successfully established an in vitro model of renal pelvic cancer organoids and tested the sensitivity of the model to chemotherapeutic drugs. The results provide a new laboratory model for the individualized diagnosis and treatment of epithelial carcinomas represented by renal pelvic carcinoma.

Risk factors of death or chronic renal replacement therapy requirements in patients with thrombotic microangiopathies without ADAMTS-13 deficiency.

Thrombotic microangiopathy (TMA), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and multisystem organ dysfunction, is a life-threatening disease. Patients with TMA who do not exhibit a severe ADAMTS-13 deficiency (defined as a disintegrin-like and metalloprotease with thrombospondin type 1 motif no. 13 activity ≥10%: TMA-13n) continue to experience elevated mortality rates. This study explores the prognostic indicators for augmented mortality risk or necessitating chronic renal replacement therapy (composite outcome: CO) in TMA-13n patients. We included 42 TMA-13n patients from January 2008 to May 2018. Median age of 41 years and 60% were female. At presentation, 62% required dialysis, and 57% warranted intensive care unit admission. CO was observed in 45% of patients, including a 9-patient mortality subset. Multivariate logistic regression revealed three independent prognostic factors for CO: early administration of eculizumab (median time from hospitalization to eculizumab initiation: 5 days, range 0-19 days; odds ratio [OR], 0.14; 95% confidence interval [CI], 0.02-0.94), presence of neuroradiological lesions (OR, 6.67; 95% CI, 1.12-39.80), and a PLASMIC score ≤4 (OR, 7.39; 95% CI, 1.18-46.11). In conclusion, TMA-13n patients exhibit a heightened risk of CO in the presence of low PLASMIC scores and neuroradiological lesions, while early eculizumab therapy was the only protective factor.

A case of renal limited myeloperoxidase anti-neutrophil cytoplasmic antibody-positive vasculitis treated with maintenance avacopan monotherapy.

A 76-year-old woman was admitted with progressive renal function decline. A kidney biopsy was performed because of myeloperoxidase anti-neutrophil cytoplasmic antibody (ANCA; 333 IU/mL), proteinuria (1.21 g/d), and urinary erythrocyte sediment (10-19/high-power field). Renal-limited ANCA-positive vasculitis with pauci-immune necrotizing crescentic glomerulonephritis (ANCA-associated vasculitis, AAV) was diagnosed. Glucocorticoid therapy was started, and the patient responded well. About 1 year later, avacopan treatment was started and glucocorticoid therapy was discontinued. Avacopan did not normalize ANCA levels and did not make urinary findings negative. However, further progression of renal function decline is prevented. Factors attributed to the development of AAV in this case were investigated; AAV developed after the second dose of the COVID-19 vaccine and ANCA levels re-elevated after the fifth dose. This suggests that the COVID-19 vaccine may have contributed to the development of AAV in this elderly patient. Avacopan monotherapy has been shown to be effective as maintenance therapy to control the progression of renal failure although not sufficient for complete remission of AAV.

Safety and graft outcome of right retroperitoneal laparoscopic donor nephrectomy for living donor kidney transplantation: A comparison with left retroperitoneal laparoscopic donor nephrectomy.

INTRODUCTION: The left kidney is often preferred for living donor kidney transplantation because of its anatomical advantages. However, the right kidney may be procured due to donor conditions. Few studies have assessed the safety and graft outcome of right retroperitoneal laparoscopic donor nephrectomy (RDN). This study aimed to compare the outcomes between right and left RDN with respect to donor outcome and the graft function of recipients. METHODS: This retrospective study included 230 consecutive living donor kidney transplants performed at our institution between May 2019 and March 2023. We reviewed the outcomes of kidney transplant in the right and left kidneys after RDN. RESULTS: A total of 230 living donor kidney transplants were performed, with 32 donors receiving right RDN (right RDN group) and 198 donors receiving left RDN (left RDN group). The renal veins and ureters were significantly shorter in the right RDN group than in the left RDN group (both p < .001). Donor operation and warm ischemia time were significantly longer in the right RDN group than in the left RDN group (p = .012 and p < .001, respectively). None of the groups exhibited any cases of delayed graft function owing to donor-related reasons. Perioperative changes in the estimated glomerular filtration rate of recipients and death-censored graft survival were not significantly different between the two groups. CONCLUSIONS: In RDN, the outcomes of right donor nephrectomy were comparable to those of left donor nephrectomy in terms of donor safety and recipient renal function.

Following a strict renal protection protocol in cloacal malformations: A descriptive analysis.

BACKGROUND: In children with cloacal malformations, renal dysfunction is a constant concern, with reported incidence as high as 50%. Multiple factors exist that may impair renal function. Our institution follows a strict renal protection protocol in this population. Incidence of renal dysfunction in these patients is unknown. OBJECTIVE: We aimed to evaluate incidence of renal dysfunction while implementing this protocol in a cohort of children with cloacal malformation. STUDY DESIGN: We reviewed a prospectively collected database of children with cloacal malformations managed at a single institution since implementation of a renal protection protocol. This involves regular laboratory evaluation, appropriate selection of total urogenital mobilization or urogenital separation, proactive imaging in patients with signs of impending renal dysfunction or urinary retention, and early catheterization teaching and implementation if necessary. Glomerular filtration rate (GFR) was calculated with the Schwartz formula and CKD grades assigned per standard definitions. Renal dysfunction was defined as CKD grade 3b or higher, need for renal replacement therapy (RRT) or transplantation. Descriptive statistics were computed. RESULTS: A total of 105 children were managed under this protocol with a median follow-up of 4.2 years [IQR: 2.0-5.9]. Six children (5.7%) had renal dysfunction at most recent follow-up; of these children, only three (2.9%) progressed from normal renal function at initial evaluation to renal dysfunction (Table). No child with normal presenting renal function thus far has progressed to require dialysis or transplantation. DISCUSSION: Previous literature estimated rates of renal dysfunction in cloaca patients as high as 50%; in contrast, we demonstrate a rate of progression to renal dysfunction of 2.9% in girls following a strict renal protection protocol. Most children who developed renal dysfunction had dysfunctional kidneys on presentation. This suggests that preservation of renal function may be possible in early childhood with a strict, multi-disciplinary renal protection protocol. CONCLUSION: In our cohort of patients with cloacal malformations following a strict renal protection protocol, incidence of progressive renal dysfunction is low at 2.9%. Most who go on to renal dysfunction present with impaired renal function.

Investigations of Laser-Assisted Renal Denervation for Treatment of Resistant Hypertension.

BACKGROUND AND OBJECTIVES: Renal denervation (RDN) is an emerging surgical treatment for resistant hypertension. However, the current RDN using radiofrequency can cause undesirable thermal damage to the medial and luminal layers due to direct contact between the arterial lumen and energy source. The aim of this study is to evaluate the feasibility of the new laser-assisted RDN by exploring the potential treatment conditions. METHODS: For ex vivo testing, six different treatment conditions (10 and 20 W applied for delivery of 300, 450, and 600 J) were tested on the porcine liver and renal artery (RA) by using a continuous wave 1064 nm laser wavelength. The ablated area in the liver tissue was measured to estimate the extent of the coagulated area. Histological evaluation was performed on the treated RA tissues to confirm the extent of thermal nerve damage. RESULTS: The ablated depth, length, and area in the liver tissue increased with laser power and total energy. According to the histological results, 20 W groups yielded more significant damage to the RA nerves than 10 W groups at the total energy of 300 J (0.0 ± 0.0 mm for 10 W vs. 2.9 ± 1.0 mm for 20 W), 450 J (1.9 ± 0.6 mm for 10 W vs. 6.8 ± 1.5 mm for 20 W), and 600 J (2.9 ± 0.4 mm for 10 W vs. 7.3 ± 0.8 mm for 20 W). The treated RA exhibited insignificant medial injury in depth (medial thinning ≤ 25%), and no difference in the medial thinning was found among the six groups (p = 0.4). CONCLUSION: The current study demonstrated that the 1064 nm laser at 20 W with delivery of 450 J could effectively damage the RA nerves with no or minimal injury to the surrounding tissue. The proposed laser-assisted RDN may enhance physiological effects with insignificant complications in in vivo situations. Further in vivo studies will be conducted to validate the current findings by evaluating the extent of blood pressure reduction and norepinephrine changes after the laser-assisted RDN on a large animal model.

Anxiety and sleep quality in patients receiving maintenance hemodialysis: multiple mediating roles of hope and family function.

The objective of this cross-sectional study was to examine the extent of sleep quality among individuals undergoing maintenance hemodialysis (MHD) and to scrutinize whether hope and family function serve as mediators in the association between anxiety and sleep quality in this cohort. A convenience sampling method was used to recruit 227 patients receiving maintenance hemodialysis from two tertiary hospitals in Wuhan. Participants completed several self-report questionnaires, including the Sociodemographic questionnaire, Hospital Anxiety and Depression Scale, Athens Insomnia Scale, Herth Hope Index, and Family APGAR Index. As per the findings of the chain mediation analysis, it was observed that the sleep quality scores were directly predicted by anxiety. Moreover, anxiety positively predicted sleep quality scores through hope and family function as mediators. The observed types of mediation were partial mediation. The total indirect effect value was 0.354, indicating the mediating effect of hope and family function, while the total effect value was 0.481, representing the overall effect of anxiety on sleep quality. The total effect size was 73.60% (0.354/0.481), indicating that the mediation accounted for a significant portion of the relationship. This study established the chain mediating effect of hope and family function between anxiety and sleep quality in patients receiving maintenance hemodialysis. The findings highlight the importance of addressing anxiety and promoting hope and family function to improve sleep quality in this population. The findings suggest that healthcare professionals should be attentive to the anxiety levels of these patients and implement targeted interventions to help alleviate anxiety, enhance hope, and improve family functioning, with the ultimate goal of improving sleep quality in this population.

Immune landscape of renal cell carcinoma with metastasis to the pancreas.

INTRODUCTION: Clear cell Renal Cell Carcinoma (ccRCC) has a poor prognosis once metastatic. However, certain metastatic sites have been reported to have a different impact on the patient prognosis. For example, patients with pancreatic metastases have a much more favorable prognosis than those with metastases to other organs. The biological basis for this observation remains poorly understood. The aim of this study was to characterize the immune landscape of pancreatic metastases and the corresponding primary tumors in order to identify possible immunological features that correlate with disease biology. PATIENTS AND METHODS: A detailed assessment of immune cell populations was performed using a total of 1,700 microscopic images from ccRCCs from 11 patients, their corresponding pancreatic metastases and ccRCCs from 10 patients without pancreatic metastases. Tumor specimens were stained for CD45, CD8, CD163 and FOXP3 and the densities of the respective immune cells were assessed semiquantitatively in the intratumoral and extratumoral compartment. Multispectral imaging was performed in selected tumors. RESULTS: We found that pancreatic metastases show the lowest intratumoral infiltration with CD8+ cytotoxic T lymphocytes of all tumor specimens analyzed. The frequency of CD8+ lymphocytes was on 1.9 fold lower in pancreatic metastases (median density 8.3 cells per field of view [FOV] = 1.23 mm2) when compared to the corresponding primary tumor (15.6 cells per FOV, P = 0.0002) and more than 3-fold lower when compared to ccRCCs without pancreatic metastases (27.2 cells per FOV, P = 0.0012). There was also a significantly reduced intratumoral infiltration with immunosuppressive FOXP3+ lymphocytes in pancreatic metastases (2.6 cells per FOV, P = 0.009) and corresponding primary tumors (2 cells per FOV, P = 0.028) when compared to ccRCCs without pancreatic metastases (5.6 cells per FOV). CONCLUSIONS: In this proof-of-concept study, we show that pancreatic metastases of ccRCC present with unique immunological features including a low intratumoral density of CD8+ and FOXP3+ lymphocytes. The low counts of CD8+ and FOXP3+ lymphocytes may reflect less aggressive features of ccRCC with pancreatic metastasis that may result in a more favorable patient prognosis.

Molecular docking aided machine learning for the identification of potential VEGFR inhibitors against renal cell carcinoma.

Renal cell carcinoma is a highly vascular tumor associated with vascular endothelial growth factor (VEGF) expression. The Vascular Endothelial Growth Factor -2 (VEGF-2) and its receptor was identified as a potential anti-cancer target, and it plays a crucial role in physiology as well as pathology. Inhibition of angiogenesis via blocking the signaling pathway is considered an attractive target. In the present study, 150 FDA-approved drugs have been screened using the concept of drug repurposing against VEGFR-2 by employing the molecular docking, molecular dynamics, grouping data with Machine Learning algorithms, and density functional theory (DFT) approaches. The identified compounds such as Pazopanib, Atogepant, Drosperinone, Revefenacin and Zanubrutinib shown the binding energy - 7.0 to - 9.5 kcal/mol against VEGF receptor in the molecular docking studies and have been observed as stable in the molecular dynamic simulations performed for the period of 500 ns. The MM/GBSA analysis shows that the value ranging from - 44.816 to - 82.582 kcal/mol. Harnessing the machine learning approaches revealed that clustering with K = 10 exhibits the relevance through high binding energy and satisfactory logP values, setting them apart from compounds in distinct clusters. Therefore, the identified compounds are found to be potential to inhibit the VEGFR-2 and the present study will be a benchmark to validate the compounds experimentally.

Renal and patient outcomes of emergency hemodialysis in elderly individuals: a retrospective cohort study.

PURPOSE: The aging population, commonly defined as individuals aged 65 and above, faces an increased risk of kidney-related diseases. This study investigates emergency dialysis in the elderly population, focusing on indications, clinical and laboratory findings, renal status, and mortality rates. METHODS: The data of 442 elderly patients (≥ 65 years old) who underwent emergency dialysis at a tertiary university hospital were retrospectively examined. Demographics, comorbidities, emergency dialysis indications, clinical presentation, method, complications, pre/post-dialysis status, and follow-up were assessed. RESULTS: 74.9% of the patients had a history of chronic kidney disease (CKD). Emergency dialysis was mainly initiated due to hypervolemia (43.7%) and uremic symptoms (29.2%). Hypotension was the most common dialysis-related complication (34.4%). The mortality rate was 34.6%; among the survivors, 15.2% achieved complete renal recovery, while 32.5% and 52.3% developed dialysis-independent and -dependent CKD, respectively. In multivariate analysis, blood urea, serum sodium, mean arterial pressure, dyspnea, tachypnea, and tachycardia on admission were found to be associated with mortality. CONCLUSION: Our study provides insights into emergency dialysis challenges in the elderly population, emphasizing the need for personalized interventions and further research to improve care and outcomes in this growing demographic.

Renal anemia: from relative insufficiency of EPO to imbalance of erythropoiesis and eryptosis.

Chronic kidney disease has emerged as a major health issue both in China and worldwide. Renal anemia frequently occurs in patients with chronic kidney disease, and its severity and incidence rate increase as the disease progresses. Over the last 30 years, the administration of exogenous EPO and EPO stimulants has been employed to alleviate renal anemia, suggesting that a relative deficiency in EPO may be a primary cause. However, this approach has overshadowed other contributing factors, particularly eryptosis, which results from the reduced lifespan of red blood cells. Numerous studies reveal that there are nephrogenic and extrarenal EPO secretion indicating that an absolute deficiency of EPO is not always present in patients. Therefore, this paper speculates that renal anemia may arise when EPO-driven erythropoiesis fails to adequately compensate for aggravating eryptosis. Other factors including iron metabolism disorder, uremic toxin accumulation, inflammatory state, oxidative stress, and secondary hyperparathyroidism affect EPO reactivity bone marrow hematopoiesis and eryptosis, leading to an imbalance between red blood cell production and destruction, and cause anemia ultimately. More further studies on the pathogenesis and treatment of renal anemia would be expected to provide evidence to support our opinion.