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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.

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Rationale and Objective: The NKF-ASN Task Force recommends accurate kidney function estimation avoiding biases through racial adjustments. We explored the use of multiple kidney function biomarkers and hence estimated glomerular filtration rate (eGFR) equations to improve kidney function calculations in an ethnically diverse patient population. Study design: Prospective community cohort study. Setting and Participants: rural New Mexico clinic with patients > 18 yo. Methods: Markers of kidney function, IDMS-Creatinine (SCr), chemiluminescence Beta-2 Microglobulin (B2M), Nephelometry-calibrated ELISA Cystatin C (CysC), inflammation, glucose tolerance, demographics, BUN/UACR from the baseline visit of the COMPASS cohort, were analyzed by Kernel-based Virtual Machine learning methods. Results: Among 205 participants, the mean age was 50.1, 62% were female, 54.1% Hispanic American and 30.2% Native American. Average kidney function biomarkers were: SCr 0.9 mg/dl, B2M 1.8 mg/L, and CysC 0.7 mg/dl. The highest agreement was observed between SCr and B2M-based eGFR equations [mean difference in eGFRs: (4.48 ml/min/1.73m2], and the lowest agreement between B2M and CysC-based eGFR equations (-24.75 ml/min/1.73m2). There was no pattern of association between the differences in eGFR measures and gender. In the continuous analyses, the absolute eGFR value (p<2 x 10-16) and serum albumin (p =6.4 x 10-5) predicted the difference between B2M- and SCr-based e-GFR. The absolute eGFR value (p<2 x 10-16) and age (p =7.6 x 10-5) predicted the difference between CysC- and SCr-based e-GFR. Limitations: Relatively small sample size, elevated inflammatory state in majority of study participants and no inulin excretion rate measurements. Conclusion: B2M should be strongly considered as a kidney function biomarker fulfilling the criteria for the NKF-ASN. B2M's eGFR equation does not need adjustment for gender or race and showed the highest agreement with SCr-based eGFR equations.

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Background: Periodontitis is a chronic infectious disease, characterized by an exacerbated inflammatory response and a progressive loss of the supporting tissues of the teeth. Porphyromonas gingivalis is a key etiologic agent in periodontitis. Cystatin C is an antimicrobial salivary peptide that inhibits the growth of P. gingivalis. This study aimed to evaluate the antimicrobial activity of this peptide and its effect on cytokine production, nitric oxide (NO) release, reactive oxygen species (ROS) production, and programmed cell death in human macrophages infected with P. gingivalis. Methods: Monocyte-derived macrophages generated from peripheral blood were infected with P. gingivalis (MOI 1:10) and stimulated with cystatin C (2.75 µg/ml) for 24 h. The intracellular localization of P. gingivalis and cystatin C was determined by immunofluorescence and transmission electron microscopy (TEM). The intracellular antimicrobial activity of cystatin C in macrophages was assessed by counting Colony Forming Units (CFU). ELISA assay was performed to assess inflammatory (TNFα, IL-1ß) and anti-inflammatory (IL-10) cytokines. The production of nitrites and ROS was analyzed by Griess reaction and incubation with 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA), respectively. Programmed cell death was assessed with the TUNEL assay, Annexin-V, and caspase activity was also determined. Results: Our results showed that cystatin C inhibits the extracellular growth of P. gingivalis. In addition, this peptide is internalized in the infected macrophage, decreases the intracellular bacterial load, and reduces the production of inflammatory cytokines and NO. Interestingly, peptide treatment increased ROS production and substantially decreased bacterial-induced macrophage apoptosis. Conclusions: Cystatin C has antimicrobial and immuno-regulatory activity in macrophages infected with P. gingivalis. These findings highlight the importance of understanding the properties of cystatin C for its possible therapeutic use against oral infections such as periodontitis.

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ABSTRACT Introduction: Kidney problems may be due to low birth weight alone or may occur in association with other conditions. The objective this study was to evaluate the association between maternal and birth characteristics, anthropometric measurements, and kidney function deficit in low birth weight infants. Methods: Cross-sectional study with children who were born weighing < 2500 grams and were under outpatient follow-up. Maternal factors investigated were prenatal care and presence of hypertension, diabetes, and infection during pregnancy. The children's variables were sex, gestational age, birth weight, Apgar score, use of nephrotoxic medications, age, body weight at the time of evaluation, height, and serum creatinine and cystatin C dosages. The glomerular filtration rate (GFR) was estimated with the combined Zapittelli equation. Multivariate logistic regression model was used for identification of associated factors, with renal function deficit (GFR < 60 mL/min/1.73 m2) as the dependent variable. Results: Of the 154 children evaluated, 34.42% had kidney function deficit. Most of them had a gestational age > 32 weeks (56.6%), a mean birth weight of 1439.7 grams, and mean estimated GFR of 46.9 ± 9.3 mL/min/1.73 m2. There was a significant association of GFR < 60 mL/min/1.73 m2 with children's current weight and use of nephrotoxic drugs. Discussion: Children born with low birth weight had a high prevalence of kidney function deficit and current normal weight was a protective factor while the use of nephrotoxic drugs during perinatal period increased the chance of kidney deficit. These findings reinforce the need to evaluate the kidney function in these children, especially those who use nephrotoxic drugs.

RESUMO Introdução: Problemas renais podem ser devido apenas ao baixo peso ao nascer ou podem ocorrer em associação com outras condições. O objetivo deste estudo foi avaliar a associação entre características maternas e de nascimento, medidas antropométricas e déficit da função renal em bebês de baixo peso ao nascer. Métodos: Estudo transversal com crianças que nasceram com peso < 2500 gramas e estavam sob acompanhamento ambulatorial. Os fatores maternos investigados foram cuidados pré-natal e presença de hipertensão, diabetes e infecção durante a gravidez. As variáveis das crianças foram sexo, idade gestacional, peso ao nascer, índice Apgar, uso de medicamentos nefrotóxicos, idade, peso corporal no momento da avaliação, altura e dosagens séricas de creatinina e cistatina C. A taxa de filtração glomerular (TFG) foi estimada com a equação combinada de Zapittelli. Utilizou-se um modelo de regressão logística multivariada para identificação de fatores associados, com déficit da função renal (TFG < 60 mL/min/1,73 m2) como variável dependente. Resultados: Das 154 crianças avaliadas, 34,42% apresentaram déficit da função renal. A maioria tinha idade gestacional > 32 semanas (56,6%), peso médio ao nascer de 1439,7 gramas, e TFG média estimada de 46,9 ± 9,3 mL/min/1,73 m2. Houve uma associação significativa da TFG < 60 mL/min/1,73 m2 com o peso atual das crianças e o uso de medicamentos nefrotóxicos. Discussão: Crianças nascidas com baixo peso apresentaram alta prevalência de déficit da função renal e o peso atual normal foi um fator de proteção, enquanto o uso de medicamentos nefrotóxicos durante o período perinatal aumentou a chance de déficit renal. Estes achados reforçam a necessidade de avaliar a função renal destas crianças, especialmente aquelas que usam medicamentos nefrotóxicos.

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SUMMARY OBJECTIVE: The objective of this study was to identify the best method to replace cystatin C in the evaluation of glomerular filtration in the elderly. METHODS: Individuals over 60 years of age from a primary care center were studied. Blood was collected to determine creatinine and cystatin C and 24-h urine. Three methods were compared to determine glomerular filtration: Creatinine clearance, Cocroft-Gault, modification of diet in renal disease, and Collaboration Epidemiology of Chronic Kidney Disease based on creatinine, considering as a reference the determination of glomerular filtration using the cystatin-based Chronic Kidney Disease Epidemiology Collaboration equation. The statistical methods used were linear regression, Bland-Altman curve, and receiver operating characteristic. RESULTS: A total of 180 elderly people were evaluated, but 14 patients were lost from the sample, resulting in a total of 166 patients. The average age of patients was 66.9±6.1 years, and 69.8% were females. Regarding the number of patients eligible for the study, there were 12 black, 108 brown, and 46 white, 42.77% hypertensive, and 38.3% diabetic. Glomerular filtration was less than 60 mL/min in 22.28% of patients. Regarding the evaluation of the different equations, the correlation coefficient was lower for creatinine clearance and progressively higher for Cocroft-Gault, modification of diet in renal disease, and Collaboration Epidemiology of Chronic Kidney Disease based on creatinine. The Bland-Altman diagram and the receiver operating characteristic curve showed similar performance to the correlation coefficient for the different equations evaluated. CONCLUSION: Collaboration Epidemiology of Chronic Kidney Disease based on creatinine presented the best performance. Creatinine debug had the worst performance, which reinforces the idea that 24-h urine collection is unnecessary in these patients.

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Abstract Background and objective: With the widespread use of allogeneic hematopoietic stem cell transplantation (allo-HSCT), long-term complications have come to the fore. The aim of this study was to determine the prevalence and risk factors of chronic kidney disease (CKD) developing in the long term in patients who underwent allo-HSCT in childhood and also to investigate the superiority of eGFR formulas. Methods: The present study evaluated CKD in patients who underwent allo-HSCT. We analyzed the 94 children who received allo-HSCT at the Ege University in İzmir between August and November, 2019. The patients were evaluated at 2 years after transplantation. CKD was defined as a glomerular filtration rate (GFR) <90 mL/min/1.73 m2 using eGFR equations based on serum creatinine (SCr), cystatin C (CysC), and SCr plus CysC. Results: In our study, 9 (9.4%), according to Bedside Schwartz, 59 (76.6%), according to CKiD-eGFR-CysC, and 20 (26%) patients, according to CKiD-eGFR-SCr-CysC equations were identified with CKD. In cases identifies as CKD according to CysC, early development of acute kidney injury (AKI), post-transplant cytomegalovirus (CMV) reactivation and being >120 months during transplantation were found to be associated with the development of CKD. Conclusion: We may be delayed in detecting CKD by calculating SCr-based formulas in allo-HSCT cases, which is a patient group where early diagnosis and treatment of CKD is very important.

Resumo Antecedentes e objetivo: Com o uso generalizado do transplante alogênico de células-tronco hematopoiéticas (TCTH-alo), as complicações a longo prazo tornaram-se evidentes. O objetivo deste estudo foi determinar a prevalência e os fatores de risco do desenvolvimento de doença renal crônica (DRC) a longo prazo em pacientes submetidos a TCTH-alo na infância, e também investigar a superioridade das fórmulas de TFGe. Métodos: O presente estudo avaliou a DRC em pacientes que foram submetidos ao TCTH-alo. Analisamos as 94 crianças que receberam TCTH-alo na Universidade Ege em İzmir entre Agosto e Novembro de 2019. Os pacientes foram avaliados aos 2 anos após o transplante. A DRC foi definida como uma taxa de filtração glomerular (TFG) <90 mL/min/1,73 m2 usando equações de TFGe baseadas em creatinina sérica (CrS), cistatina C (CisC), e CrS mais CisC. Resultados: Em nosso estudo, 9 pacientes (9,4%), de acordo com a equação de Schwartz (à beira do leito), 59 (76,6%), de acordo com a equação DRC-TFGe-CisC, e 20 (26%) pacientes, de acordo com a equação DRC-TFGe-CrS-CisC, foram classificados com DRC. Quando a TFG é avaliada pela CisC, verificamos que o desenvolvimento precoce de lesão renal aguda (LRA), a reativação do citomegalovírus (CMV) pós-transplante e ter >120 meses durante o transplante foram associados ao desenvolvimento de DRC. Conclusão: Pode haver atraso na detecção da DRC quando usamos fórmulas baseadas em CrS em casos de TCTH-alo, que é um grupo de pacientes onde o diagnóstico e tratamento precoces da DRC são muito importantes.

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SUMMARY OBJECTIVE: Endometriosis is a common chronic inflammatory disease associated with infertility and pelvic pain. Diagnosis is based on the appearance of endometriotic lesions at the time of surgery. Our study aimed to determine whether cystatin C can be used as a predictor of endometriosis and to investigate its potential role in doing so. METHODS: The study included 45 patients with endometriosis between the ages of 18 and 40 years whose pathology results were compatible with endometriosis and were operated on, and a control group of 45 healthy women. These two groups were compared in terms of serum cystatin C levels, demographic-clinical characteristics, operation results, and other laboratory values. RESULTS: The cystatin C and hs-CRP levels of the endometriosis patients were found to be significantly higher than the control subjects (p<0.005). Whether the endometriosis disease could be detected for serum cystatin C levels was determined by the receiver operating characteristic analysis and the most appropriate positive cutoff value for cystatin C was found to be 5.14 ng/mL (86.7% sensitivity and 77.8% specificity). In the linear regression analysis, it was observed that the probability of endometriosis increased 2.5 times when cystatin C levels increased above the threshold value of 5.14 ng/mL (OR: 2.5; 95%CI 2.24-2.76). CONCLUSION: Our study shows that the serum cystatin C levels can be used as a guide for diagnosis in patients with advanced endometriosis. However, more research is needed to prove its reliability and accuracy in order to put it into practice.

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This research investigated the predictive value of combined detection of brain natriuretic peptide (BNP) and cystatin C (Cys C) in heart failure after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI). Sixty-five AMI patients complicated by heart failure (HF) after PCI and 79 non-heart failure (non-HF) patients were involved in this research. The levels of Cys C and BNP were measured. Risk factors for heart failure in AMI patients after PCI were analyzed by multivariate logistic regression analysis. Efficacy of BNP and Cys C on predicting heart failure were analyzed by receiver operating characteristic (ROC) curve. Cys C and BNP levels were significantly higher in the HF group than in the non-HF group. BNP and Cys C levels were the independent influencing factors causing heart failure within one year after PCI. The area under the predicted curve (AUC) of Cys C, BNP, and combined Cys C and BNP were 0.763, 0.829, and 0.893, respectively. The combined detection of Cys C and BNP was highly valuable in predicting heart failure in AMI patients after PCI, which can be regarded as the serum markers for diagnosis and treatment of heart failure.

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El conocimiento y actualización sobre la Cistatina C como marcador de daño renal precoz es en extremo necesario para los profesionales de la salud con vistas a mejorar el diagnóstico temprano de enfermedad renal. Las autoras realizaron una revisión bibliográfica actualizada a través de varios estudios científicos, lo que permitió poder informar que aun cuando para la evaluación de la función renal uno de los marcadores sanguíneos convencionales más utilizados es la creatinina, el estudio sanguíneo de Cistatina C no está sometido a diferentes fuentes de variabilidad biológica, ni a factores dependientes del paciente, por lo que sería idóneo tenerlo en cuenta como marcador de función renal precoz.

Knowledge and updating on Cystatin C as a marker of early kidney damage is extremely necessary for health professionals with a view to improving early diagnosis of kidney disease. The authors carried out an updated bibliographical review through various scientific studies, which allowed us to inform that even when for the evaluation of renal function one of the most widely used conventional blood markers is creatinine, the Cystatin C blood study is not subjected to different sources of biological variability, nor to factors dependent on the patient, so it would be ideal to take it into account as a marker of early renal function.

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Introducción: La estimación del filtrado glomerular a partir de la concentración sérica de creatinina en pacientes con drepanocitosis, es anormal cuando hay un deterioro extenso de la función renal. Objetivos: Evaluar la estimación del filtrado glomerular con el uso de creatinina, de cistatina C y de ambas determinaciones, en adultos con drepanocitosis. Métodos: Estudio observacional, descriptivo de corte transversal. Se incluyeron 44 adultos con drepanocitosis en quienes se estimó el filtrado glomerular, con el uso de creatinina, de cistatina C y de ambas, según las fórmulas de CDK-EPI. Resultados: Se encontraron discrepancias en el filtrado glomerular estimado por creatinina, por cistatina C y por ambas (medias: 112,2 ± 28,4; 55,7 ± 23,1 y 75,1 ± 24,7 mL/min/ 1,73 m2; respectivamente). Los porcentajes más elevados de pacientes con hiperfiltración por creatinina corresponden al genotipo SS y todos los que tiene enfermedad renal crónica en estadio 4 (filtrado estimado por cistatina C y mediante la combinación de ambos marcadores), tienen este tipo de hemoglobinopatía. La hiperfiltración fue más común en los más jóvenes y la disminución del filtrado en los mayores de 40 años. Conclusiones: La estimación del filtrado glomerular muestra diferencias entre los tres métodos estudiados. Con el uso de creatinina está sobrestimado y una elevada proporción de pacientes son clasificados como con hiperfiltración. El uso de la cistatina C o la combinación de ambas determinaciones, pudieran ofrecer una estimación más exacta del filtrado glomerular en pacientes con drepanocitosis(AU)

Introduction: The estimation of the glomerular filtration rate from the serum concentration of creatinine in patients with sickle cell disease is abnormal when there is an extensive deterioration of renal function. Objective: To estimate the glomerular filtration rate with the use of creatinine, cystatin C and both determinations, in adults with sickle cell disease. Determine if there are differences between these methods. Methods: Observational, descriptive cross-sectional study. Forty-four adults with sickle cell disease were included in whom the glomerular filtration rate was estimated using creatinine, cystatin C and both, according to the CDK-EPI formulas. Results: Discrepancies were found in the glomerular filtration rate estimated by creatinine, by cystatin C and by both (means: 112.2 ± 28.4; 55.7 ± 23.1 and 75.1 ± 24.7 mL/min/1.73 m2; respectively). The highest percentages of patients with creatinine hyperfiltration correspond to the SS genotype and all those with stage 4 chronic kidney disease (estimated filtration by cystatin C and by the combination of both markers), have this type of hemoglobinopathy. Hyperfiltration was more common in the youngest and decreased filtration in those older than 40 years. Conclusions: The estimation of the glomerular filtration rate shows differences between the three methods studied. With the use of creatinine, it is overestimated and a high proportion of patients are classified as having hyperfiltration. The use of cystatin C or the combination of both determinations could offer a more accurate estimate of glomerular filtration rate in patients with sickle cell disease(AU)

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