Critically ill patients with COVID-19-associated acute kidney injury treated with kidney replacement therapy: Comparison between the first and second pandemic waves in São Paulo, Brazil.

INTRODUCTION: This study aimed to compare the characteristics and outcomes of critically ill patients with COVID-19-associated acute kidney injury (AKI) who were treated with kidney replacement therapy (KRT) in the first and second waves of the pandemic in the megalopolis of Sao Paulo, Brazil. METHODS: A multicenter retrospective study was conducted in 10 intensive care units (ICUs). Patients aged ≥18 years, and treated with KRT due to COVID-19-associated AKI were included. We compared demographic, laboratory and clinical data, KRT parameters and patient outcomes in the first and second COVID-19 waves. RESULTS: We assessed 656 patients (327 in the first wave and 329 in the second one). Second-wave patients were admitted later (7.1±5.0 vs. 5.6±3.9 days after the onset of symptoms, p<0.001), were younger (61.4±13.7 vs. 63.8±13.6 years, p = 0.023), had a lower frequency of diabetes (37.1% vs. 47.1%, p = 0.009) and obesity (29.5% vs. 40.0%, p = 0.007), had a greater need for vasopressors (93.3% vs. 84.6%, p<0.001) and mechanical ventilation (95.7% vs. 87.8%, p<0.001), and had higher lethality (84.8% vs. 72.7%, p<0.001) than first-wave patients. KRT quality markers were independently associated with a reduction in the OR for death in both pandemic waves. CONCLUSIONS: In the Sao Paulo megalopolis, the lethality of critically ill patients with COVID-19-associated AKI treated with KRT was higher in the second wave of the pandemic, despite these patients being younger and having fewer comorbidities. Potential factors related to this poor outcome were difficulties in health care access, lack of intra-hospital resources, delay vaccination and virus variants.

Prevalence, outcomes and costs of patients with renal dysfunction in the emergency department of a specialized cardiology hospital

INTRODUCTION: Chronic kidney disease and acute kidney injury (AKI) are important complications of heart diseases. In developing countries, epidemiological and cost information on the interaction of these conditions are scarce. OBJECTIVES: To determine the prevalence, costs and outcomes of patients admitted for acute coronary syndrome (ACS) with renal dysfunction and AKI. METHODS: The study was based on a prospective database analysis of patients admitted for ACS to a Brazilian public hospital specialized in cardiology between 7/16/2018 and 12/31/2019. Renal dysfunction was defined as an estimated glomerular filtration rate (eGFR) <60ml/min/1.73m² at hospital admission. Community-acquired and hospital-acquired AKI were defined as a fall and an increase of ≥0.3mg/dl in serum creatinine from baseline, respectively. RESULTS: 1295 of the 1620 patients had a confirmed diagnosis of ACS (median age 64.2 [56.5-70.6] years, 65.4% male, 82.7% had hypertension, 45.5% diabetes and 22.6% renal dysfunction). The imaging diagnosis of ACS was coronary angiography in 84.3% and the treatment was performed by angioplasty, only clinically and by myocardial revascularization in 47.3%, 40.0% and 12.7%, respectively. Hospital- and community-acquired AKI occurred in 43.9% and 2.3% of patients, respectively. Compared with patients admitted with eGFR ≥60ml/min/1.73m², those with eGFR <60 were older (70.6 vs. 62.5 years, p<0.001), had a higher prevalence of hypertension (92.1% vs. 80.0%, p<0.001) and diabetes mellitus (60.6% vs.54.5%, p=0.010), had a higher incidence of AKI (65.0% vs. 51.4%, p <0.001) and higher: median amount reimbursed for hospitalization (1,344 [366-2,103] vs. 1,334 [290-2,018] dollars, p=0.034), median length of stay (5 [3-10] vs. 4 [2-7] days, p<0.001), death within 30 days (4.1% vs. 1.4%, p=0.004) and death within 12 months (9.2% vs. 2.9%, p<0.001). Patients with AKI, compared to those without this condition, were older (65.6 vs.63.3 years, p=0.008), had lower eGFR on admission (78.1 ml/min/1.73m² vs.86.1 ml/min/1.73m², p<0.001) and greater: median amount reimbursed for hospitalization (1,334 [301-1,865] vs. 1,724 [973-2,549] dollars, p<0.001), median length of stay (6 [4-13] vs. 3 [2-5] days, p <0.001) and death within 12 months (4.8% vs. 2.3%, p=0.032). CONCLUSIONS: In patients with ACS at a cardiology referral hospital, renal dysfunction on admission and AKI during hospitalization were frequent and associated with worse clinical and economic outcomes.

Recognition and management of acute kidney injury in children: The ISN 0by25 Global Snapshot study.

BACKGROUND: In low and middle-income countries, reliable data on the epidemiology of childhood acute kidney injury (AKI) is lacking. The Global Snapshot, conducted by the ISN "0by25" AKI initiative, was a world-wide cross-sectional, observational study to evaluate AKI in hospitalized patients. Here we report the pediatric results of this study. PATIENTS AND METHODS: We prospectively collected data on children who met the Kidney Disease Improving Global Outcomes AKI criteria during a 10-week window in late 2014. AKI risk factors, etiological factors, management and outcomes were recorded using standardized forms and protocols. Countries were classified according to their 2014 gross national income (GNI) per person into high-income countries (HIC), upper-middle income countries (UMIC) and low and low-middle income countries (LLMIC). Need for renal replacement therapy, mortality, and renal recovery were assessed 7 days after AKI diagnosis or at hospital discharge, whichever came first. RESULTS: 92 centers from 41 countries collected data on 354 pediatric AKI patients; 53% of the children developed AKI while hospitalized and 47% in the community. The most common etiological factors for AKI differed across GNI categories as well as between patients with community-acquired vs. hospital-acquired AKI. Children from HIC were younger, and larger proportion of AKI in this group were due to post-surgical complications vs. other etiologies when compared to other income categories. In patients with hypotension as the cause of AKI, the adjusted risk of death was almost 10-fold higher compared to patients without hypotension as an etiological factor for AKI development. Mortality was similar within AKI stages in HIC and UMIC. In LLMIC, patients with the highest AKI level of severity had higher mortality than patients in higher income categories. Patients from LLMIC and UMIC had a 57-fold and 11 fold higher adjusted risk of death, respectively, compared to patients from HIC. CONCLUSION: In resource-limited countries, pediatric AKI-associated mortality is disproportionately higher when compared to high-resource areas, especially among patients with more severe AKI.

Glomerular deposition of immune complexes as a first manifestation of malignant melanoma - a case report.

INTRODUCTION: Immune complex (IC) deposition in renal tissue is considered as a possible tumor marker. This raised the hypothesis that some tumor markers might be related to the patient prognosis, with emphasis in the possibility to detect them in tissue sample, not only in blood. We report a patient with membranous glomerulonephritis (MGN) and tumoral IC deposition that were detected previous to the diagnosis of melanoma. CASE REPORT: A 55-year-old male was admitted to our department with symptoms of renal disease; a kidney biopsy was performed and the diagnosis was phase II MGN. A few months later he returned to the hospital with ascites, dyspnea, anorexia, and macular erythematous skin lesions in the body. A new urinalysis showed proteinuria, hematuria, and leukocyturia; the chest X-ray showed a lung nodule; and a brain CT scan revealed a frontal nodular lesion, suggesting metastasis. The brain biopsy suggested the diagnosis of metastatic melanoma and a posterior kidney immunohistochemistry study with S-100 and HMB-45 antibodies showed glomerular and tubular positivity for these markers. CONCLUSIONS: MGN and deposition of tumoral IC as a first manifestation of melanoma has not been previously reported. This case reinforces the importance of a clinical evolution focused on the diagnosis of a hidden cancer in patients with MGN. Oncologists should also be aware of the potential occurrence of glomerular lesion in their patients and that could be important during tumor therapy.

Depressão em idosos portadores de insuficiência renal crônica em tratamento hemodialítico / Depression in the elderly on hemodialysis for chronic renal failure / Depresión en personas ancianas con insuficiencia renal crónica en tratamiento de hemodiálisis

Objetivos: Caracterizar idosos com insuficiência renal crônica submetidos à hemodiálise em um hospital escola e identificar níveis de depressão na população estudada. Métodos: Trata-se de uma pesquisa descritiva - exploratória, de natureza quantitativa utilizando a Geriatric Depression Scale (GDS) e questionário de caracterização populacional, sendo entrevistados 61 pacientes. Na análise dos dados foi utilizado método quantitativo progressivo (porcentagem) e correlação de Spearmann. Resultados: A média de idade foi de 69,97±7,51 anos, 57 por cento eram do sexo masculino, 79 por cento de cor branca, 72 por cento eram casados, sendo 26 por cento analfabetos. A média de respostas depressivas foi 10,43±4,37, o que sugere humor normal-levemente deprimido na população em geral. Conclusão: Houve correlação estatisticamente significativa entre renda mensal familiar e escolaridade (valor p=0, 004) e escore GDS e analfabetismo (p=0,028), mostrando que os analfabetos apresentaram mais respostas depressivas, sugerindo menor capacidade de adaptabilidade/resiliência desses indivíduos à doença e suas implicações.

Objectives: This study aimed to characterize the elderly on hemodialysis for chronic renal failure in a teaching hospital and to describe their levels of depression. Methods: This is a descriptive exploratory study with 61 patients. A socio-demographic questionnaire and the geriatric depression scale (GDS) were used to collect the data. Data analysis consisted of descriptive statistics and Spearman rho correlations. Results: The mean age of patients was 69.97±7.51. The majority was white (79 percent), married (72 percent), and male (57 percent). Approximate a quarter of the patients (26 percent) were illiterate. The mean depression score was 10.43±4.37, suggesting the presence of normal to slightly depressive symptoms. Conclusions: There were statistically significant correlation coefficients between family monthly income and education (p value=0.004) and between depressive symptoms and illiteracy (p=0.028). This last finding indicates that the illiterate patients had more depressive symptoms, suggesting they have less adaptation capacity or resilience to cope with the disease and its implications.

Objetivos: Caracterizar a personas ancianas con insuficiencia renal crónica sometidos a hemodiálisis en un hospital docente e identificar niveles de depresión en la población estudiada. Métodos: Se trata de una investigación descriptiva - exploratoria, de naturaleza cuantitativa en la cual se utilizó la Geriatric Depression Scale (GDS) y el cuestionario de caracterización poblacional, siendo entrevistados 61 pacientes. En el análisis de los datos se utilizó el método cuantitativo progresivo (porcentaje) y la correlación de Spearmann. Resultados: El promedio de edad fue de 69,97±7,51 años, el 57 por ciento era del sexo masculino, el 79 por ciento de raza blanca, el 72 por ciento era casado, siendo el 26 por ciento analfabetos. El promedio de respuestas depresivas fue 10,43±4,37, lo que sugiere humor normal-levemente deprimido en la población en general. Conclusión: Hubo correlación estadísticamente significativa entre el ingreso mensual familiar y la escolaridad (valor p=0, 004) y escore GDS y analfabetismo (p=0,028), mostrando que los analfabetos presentaron más respuestas depresivas, sugiriendo menor capacidad de adaptabilidad/resiliencia de esas personas a la enfermedad y sus implicancias.

FTY720 in combination with cyclosporine--an analysis of skin allograft survival and renal function.

Acute and chronic nephrotoxicity caused by CsA continuous administration impair kidney allograft survival. Several clinical and experimental protocols have shown benefits to the kidney after decreasing CsA dose, withdrawing the drug or delaying its introduction after transplantation. FTY720 is a new compound that has immunosuppressive characteristics and increase allograft survival in animal models without causing the side effects of calcineurin inhibitors (CNIs). FTY720 described mechanism of action that consists to alter the lymphocyte migration pattern without impairment of the immune system response against pathogens. In our mice model, FTY720 administered alone or in combination with CsA during 21 days increased skin allograft survival in a fully mismatched strain combination and did not cause significant changes in renal function. Moreover, renal structure was normal in all groups suggesting that at low doses (10 mg/kg/day) CsA can be associated during short-term period to other immunosuppressive drugs, i.e. FTY720 without affecting the kidney. Combination of immunosuppressive compounds with FTY720 and/or delayed introduction of low cyclosporine dose could prevent graft rejection and avoid nephrotoxicity.

Tacrolimus in combination with FTY720--an analysis of renal and blood parameters.

Calcineurin inhibitors (CNIs) are routinely used in immunosuppressive therapy and both Cyclosporine (CsA) and Tacrolimus (FK506) show similar efficacies to prevent rejection and death within the first year after organ transplantation. However, their use is limited by side effects such as kidney damage, hypertension, onset of diabetes and hyperlipidemia. It is a consensus that compared with CsA, FK506 causes less changes in blood pressures, serum lipids and renal function. Nevertheless, FK506 use is associated with a higher incidence of post-transplant diabetes mellitus (PTDM). FTY720 is a new compound that has shown a protective effect in animal models with respect to rejection in transplantation, ischemia-reperfusion injury, autoimmune diseases and tumor development. FTY720 acts by altering lymphocytes homing from blood to peripheral lymphoid organs. In mice, FTY720 administered in combination with CsA during 21 days has prolonged skin allograft survival without causing significant renal changes. In a model of CsA-induced chronic nephropathy in rats, FTY720 administration prevented renal injury suggesting benefit from using a combination of these drugs. In a canine kidney allograft model, FTY720 in combination with low doses of CsA or FK506 showed an addictive anti-rejection effect without causing critical adverse effects. We therefore, investigated whether 21 days of FTY720 administration in association with FK506 could prevent renal damage and development of diabetes in mice. Mice receiving FK506 alone or FTY720 + FK506 during 21 days showed changes in kidney function and structure besides an increase in blood glucose and lymphopenia. The FTY720 + FK506 combination requires further investigation with an aim toward understanding the mechanisms involved with respect to side effects.