Renal deficit and associated factors in children born with low birth weight / Déficit renal e fatores associados em crianças nascidas com baixo peso

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.

Prognostic Value of Isolated High Serum Cystatin C Levels Without Glomerular Filtration Rate Reduction. / Valor pronóstico de la elevación aislada de los niveles de cistatina C sin reducción del filtrado glomerular.

OBJECTIVES: Cystatin C is increasingly used as a marker of renal function as a complement to serum creatinine and glomerular filtration rate (GFR). We have assessed its efficacy as a predictor of mortality in a group of patients with increased cystatin C but GFR> 60mL/min. DESIGN AND METHODS: We included 608 patients, 65.9% male, 34.6% had diabetes mellitus. The mean age was 58.5±14.5 years and a mean GFR of 64.1±33.5mL/min. Patients were divided into 3 groups: CONTROL (normal cystatin C and GFR> 60mL/min, age 53.3±12.8years, GFR 96.6±22.4mL/min,n=193), INCREASED CYSTATIN (cystatin C>1.03mg/l and GFR>60mL/min, age 58.9±13,1years, GFR 72.2±10.4mL/min, n=40) and CKD (chronic kidney disease, increased cystatin C and GFR <60mL/min, age 61.4±14.8years, GFR 36.0±12.7mL/min, n=160). The relationship with overall mortality was analyzed using the Kaplan-Meier method. RESULTS: Mean cystatin C was 0.75±0.13 versus 1.79±0.54 in CKD group and 1.14±0.14mg/l, p <0.001). In CONTROL group survival was 93.9% at 5y, compared to 78.8% in the ERC group and 82.3% in the INCREASED CYSTATIN group (p <0.001) Five-year survival before renal replacement therapy was also different for the ERC group (73%, p <0.001 Log Rank) but not between the other two groups (CONTROL 99.0%, INCREASED CYSTATIN 94.3% p=0.08). CONCLUSIONS: Increased plasmatic levels of cystatin C in patients with GFR> 60mL/min was a predictor of increased mortality but not of progression to end-stage renal failure. These results confirm the interest of routinely measuring cystatin C.

Long-term kidney outcomes in children after allogeneic hematopoietic stem cell transplantation assessed with estimated glomerular filtration rate equations, creatinine levels, and cystatin C levels / Desfechos renais a longo prazo em crianças após transplante alogênico de células-tronco hematopoiéticas avaliados com equações de taxa de filtração glomerular estimada, níveis de creatinina e níveis de cistatina C

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.

Cistatina C: la necesidad de su conocimiento en la atención preventiva de daño renal / Cystatin c: the need to know it in the preventive care of kidney damage

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.

Estimación del filtrado glomerular por valores séricos de creatinina y cistatina C en adultos con drepanocitosis / Estimation of glomerular filtration rate using serum creatinine and cystatin C in adults with sickle cell anemia

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)

Patients With Atopic Dermatitis Sensitized to Pet Dander Mount IgE and T-Cell Responses to Mammalian Cystatins, Including the Human Self-Protein

Background: Immediate and delayed-type hypersensitivity reactions to pet-borne allergens are common in atopic diseases. In atopic dermatitis (AD), controversy surrounds the contribution to the disease of cross-reactivity to self-proteins. Human cystatin A and the cat allergen Fel d 3 belong to the cystatins, an evolutionary conserved protein family. The objective of the present study was to assess crossreactivity between mammalian cystatins and to analyze T-cell responses to cystatin in AD patients sensitized to pet dander. Methods: cDNA coding for dog cystatin was cloned from dog skin. Sera from 245 patients with IgE-mediated sensitization to cat and dog dander were tested for IgE binding to recombinantly expressed feline, canine, and human cystatin. Of these, 141 were also diagnosed with AD. Results: Cystatin-specific IgE was detected in 36 patients (14.7%), of whom 19 were considerably affected by AD. Within the AD patients, 9 had measurable IgE against all 3 cystatins. Cystatin-sensitized AD patients did not differ from non–cystatin-sensitized patients in terms of disease severity, age, or total IgE levels. T-cell cytokine measurements showed elevated IL-4 levels after stimulation with feline and human cystatin. Conclusion: The humoral response suggests that in addition to Fel d 3, the homologous protein from dog might play a role in allergy. Furthermore, human cystatin appears to be capable of driving a type 2 immune response in sensitized AD patients and may therefore be considered a so-called autoallergen, as proposed for other evolutionary conserved proteins. (AU)

Antecedentes: Las reacciones de hipersensibilidad de tipo inmediato y retardado a los alérgenos que están en las mascotas son comunes en las enfermedades atópicas. En este estudio, en pacientes con dermatitis atopica (DA), se analiza la reactividad cruzada con las autoproteínas y su contribución a la enfermedad. Tanto la cistatina A humana como el alérgeno felino Fel d 3 pertenecen a la familia de las cistatinas, una familia de proteínas conservadas evolutivamente. El objetivo del presente estudio fue evaluar la reactividad cruzada entre las cistatinas de mamíferos y analizar la respuestas de las células T a la cistatina en pacientes con DA sensibilizados a la caspa de las mascotas. Métodos: El ADNc que codifica la cistatina de perro se clonó a partir de piel de perro. Se analizaron sueros de 245 pacientes con sensibilización por IgE a la caspa de gato y perro para determinar la unión de IgE a cistatina felina, canina y humana expresada de forma recombinante, respectivamente. De estos 245 pacientes, 141 fueron diagnosticados de DA. Resultados: Se detectó IgE específica frente a cistatina en el 14,7% (36) de los pacientes, de los cuales 19 padecían DA. Dentro de los pacientes con DA, 9 tenían IgE medible contra las tres cistatinas. Los pacientes con DA sensibilizados frente a cistatina no difirieron de los pacientes no sensibilizados con cistatina en términos de gravedad de la enfermedad, edad o niveles totales de IgE. El análisis de citocinas de células T reveló niveles elevados de IL-4 después de la estimulación con cistatina felina y humana. Conclusión: La respuesta humoral sugiere que, además de Fel d 3, la proteína homóloga de perro también podría desempeñar un papel en la alergia. Además, la cistatina humana parece ser capaz de promover una respuesta inmune de tipo 2 en pacientes con DA sensibilizados y, por lo tanto, puede considerarse un autoalérgeno, como se ha propuesto para otras proteínas conservadas evolutivamente. (AU)

Determinación de cistatina C para evaluación del filtrado glomerular en fases predialíticas de la enfermedad renal crónica / Cystatin C's determination for evaluation of glomerular masking in pre-dialytic phases of the chronic renal disease

RESUMEN Introducción: La enfermedad renal crónica afecta alrededor de la décima parte de la población mundial y los métodos analíticos que más se utilizan para su diagnóstico tienen una baja sensibilidad y precisión. Objetivo: Determinar las concentraciones de cistatina C para la evaluación del filtrado glomerular en fases predialíticas de la enfermedad renal crónica. Métodos: Se realizó un estudio descriptivo, transversal. El universo de estudio estuvo conformado por 102 pacientes con enfermedad renal crónica en estadios del uno al cuatroque se atendieron en consulta externa del servicio de Nefrología.La muestra fueron 81 pacientes que no presentaron factores modificadores del filtrado glomerular, creatinina y cistatina C relacionados con la enfermedad renal crónica. Resultados: Predominaron los pacientes mayores de 61 años. La cistatina C se elevó en más pacientes que la creatinina. La cistatina C se elevó por igual en ambos sexos y la creatinina más en hombres. La media de los resultados se alejó más de la media del valor de referencia en la cistatina C y la creatinina no presentó valores normales en pacientes con insuficiencia renal crónica. Las ecuaciones que utilizan la cistatina C fueron mejor predictoras de daño renal. Conclusiones: La cistatina C fue mejor predictora de daño renal.

ABSTRACT Introduction: The renal chronic disease affects around a tenth part of the worldwide population and the most used analytical methods for its diagnosis have a low sensibility and precision. Objective: To determine cystatin C's concentrations for evaluation of glomerular masking in pre-dialytic phases of the renal chronic disease. Methods: A descriptive, cross-sectional study was carried out.The study universe was made up of 102 patients with chronic kidney disease in stages from one to four who were treated in an outpatient department of the Nephrology service. The samplewas 81 patients who did not present the modifier factors of glomerular masking, creatinine and cystatin C related with the renal chronic disease. Results: The patients older than 61 years predominated. The cystatin C augmented in more patients than the creatinine. The cystatin C augmented equally in both sexes and the creatinine more in men. The average of the results moved away over the average of the value of reference in the cystatin C and the creatinine did not present normal values in patients with renal chronic insufficiency. The equations that they use cystatin C were better forecaster of damage renal. Conclusions: The cystatin C was the best predictor of renal damage.

Prevalencia de Cistatina C elevada en pacientes con sobrepeso y obesidad en el noroeste de México

RESUMEN Introducción: en los últimos años se ha reportado un incremento en la prevalencia de obesidad infantil, siendo este un factor de riesgo para enfermedades crónico-degenerativas como la Enfermedad Renal Crónica; por ende, se requieren de biomarcadores endógenos para detectar las alteraciones en el filtrado glomerular, siendo la Cistatina C uno de ellos. Objetivo: Identificar la frecuencia de Cistatina C elevada en pacientes con sobrepeso y Obesidad del noroeste de México. Material y Métodos: se estudió un grupo de infantes de 6 a 12 años, a los cuales según antropometría se clasificó en normopeso, sobrepeso u obesidad. Se obtuvo la somatometria y los niveles de Cistatina C de cada uno de ellos para el cálculo del filtrado glomerular y clasificar la función renal y se buscó asociación entre estas dos condiciones mediante prueba de chi cuadrado. Resultados: de un grupo de 80 pacientes el 51.3% presentó sobrepeso/obesidad; de estos en el 46.3% se reportaron niveles altos de Cistatina C, de acuerdo con el rango de referencia propuesto por Filler 2003. La media para Tasa de Filtración Glomerular (TFG) en el grupo con sobrepeso/obesidad fue de 103.1 ml/min/1.73 m2, comparada con el grupo normopeso de 121.2 ml/min/1.73 m2. La frecuencia de niveles altos de Cistatina C en población con sobrepeso/obesidad fue de 62.9% comparado con un 26.6% en normopeso. Conclusiones: Los Niños de 6 a 12 años con exceso de peso presentan mayor frecuencia de nivel elevado de Cistatina C.

ABSTRACT Introduction: in recent years an increase has been reported in the prevalence of childhood obesity, which is a risk factor for chronic degenerative diseases such as Chronic Kidney Disease; therefore, endogenous biomarkers are needed to detect alterations in glomerular filtration, Cystatin C being one of them. Objective: To identify the frequency of elevated Cystatin C in overweight and obese patients in northwestern Mexico. Materials and Methods: a group of infants aged 6 to 12 years was studied, who according to anthropometry were classified as normal weight, overweight or obesity. Somatometry and Cystatin C levels were obtained from each of them to calculate glomerular filtration rate and classify renal function, and an association between these two conditions was sought using the chi-square test. Results: of a group of 80 patients, 51.3% were overweight / obese; Of these, 46.3% had high levels of Cystatin C, according to the reference range proposed by Filler 2003. The mean Glomerular Filtration Rate (GFR) in the overweight / obese group was 103.1 ml / min / 1.73 m2, compared to the normal weight group of 121.2 ml / min / 1.73 m2. The frequency of high levels of Cystatin C in the overweight / obese population was 62.9% compared to 26.6% in normal weight. Conclusions: Children from 6 to 12 years of age with excess weight have a higher frequency of high levels of Cystatin C.

Assessment of estimated glomerular filtration rate based on cystatin C in diabetic nephropathy / Avaliação da taxa de filtração glomerular estimada com base na cistatina C em nefropatia diabética

Abstract Introduction: GFR is estimated by using creatinine and cystatin C to determine renal dysfunction. Our aim was to evaluate estimated GFR (eGFR) based on cystatin C in type 2 diabetic patients with diabetic nephropathy (DN). Methods: Study group included 52 controls (46% male, age: 54.5±12.4) and 101 diabetic patients (46.5% male, age: 58.2±11). The diabetics were divided into three subgroups according to 24-hour urine albumin: normal to mildly increased (A1) (n=51), moderately increased (A2) (n=25), severely increased (A3) (n=25) albuminuria. Creatinine clearance (CrCl) was determined. Correlations between CrCl and eGFRs estimated according to the CKD-EPI, MDRD, and Cockcroft-Gault (CG) formulas, and ROC curves were evaluated. Data were analyzed using SPSS 22.0. Results: Only CKD-EPI-cys eGFR was significantly lower in the A1 group than the controls (p=0.021). All GFRs were lower in the A3 group than the control (CKD-EPI-cr, MDRD, CKD-EPI-cys, CKD-EPI-cr-cys: p=0.0001, CG and CrCl: p=0.001) and A1 (for all GFRs p=0.0001) groups. CKD-EPI-cr (p=0.004), MDRD (p=0.01), CG (p=0.037), CKD-EPI-cys (p=0.033), and CKD-EPI-cr-cys (p=0.016) eGFRs in the A2 group were significantly different from the A1 group. All eGFRs showed a moderate correlation with CrCl in the A1group (CKD-EPI-cr and CKD-EPI-cr-cys: r=0.49, p=0.0001, MDRD: r=0.44, p=0.001, CG r=0.48, p=0.0001: CKD-EPI-cys r=0.40, p=0.004). The area under the CKD-EPI-cys ROC curve was the highest and found to be 0.847 (95%CI 0.763-0.931, p=0.0001). Conclusions: Our results showed that the CKD-EPI-cys eGFR can be useful in detecting the early stage of DN and more predictive than the others for prediction of DN.

Resumo Introdução: A TFG é estimada usando creatinina e cistatina C para determinar a disfunção renal. Nosso objetivo foi avaliar a TFG estimada (TFGe) com base na cistatina C em pacientes com diabetes do tipo 2 com nefropatia diabética (ND). Métodos: O grupo de estudo incluiu 52 controles (46% homens, idade: 54,5±12,4) e 101 pacientes diabéticos (46,5% homens, idade: 58,2±11). Os diabéticos foram divididos em três subgrupos de acordo com a albumina na urina de 24 horas: albuminúria normal a levemente aumentada (A1) (n=51), moderadamente aumentada (A2) (n=25) e severamente aumentada (A3) (n=25). Foi determinado o clearance de creatinina (Clcr). As correlações entre Clcr e TFGe calculadas de acordo com as fórmulas CKD-EPI, MDRD, e Cockcroft-Gault (CG), e as curvas ROC foram avaliadas. Os dados foram analisados usando o SPSS 22.0. Resultados: Somente a TFGe CKD-EPI-cis foi significativamente menor no grupo A1 do que nos controles (p=0,021). Todas as TFGs foram mais baixas no grupo A3 do que no grupo controle (CKD-EPI-cr, MDRD, CKD-EPI-cis, CKD-EPI-cr-cis: p=0,0001, CG e Clcr: p=0,001) e no grupo A1 (para todas as TFGs p=0,0001). As TFGes CKD-EPI-cr (p=0,004), MDRD (p=0,01), CG (p=0,037), CKD-EPI-cis (p=0,033), e CKD-EPI-cr-cis (p=0,016) no grupo A2 foram significativamente diferentes do grupo A1. Todas as TFGes mostraram uma correlação moderada com Clcr no grupo A1 (CKD-EPI-cr e CKD-EPI-cr-cis: r=0,49, p=0,0001, MDRD: r=0,44, p=0,001, CG r=0,48, p=0,0001: CKD-EPI-cis r=0,40, p=0,004). A área sob a curva ROC CKD-EPI-cis foi a mais alta e foi considerada 0,847 (95%IC 0,763-0,931, p=0,0001). Conclusões: Nossos resultados mostraram que a TFGe CKD-EPI-cis pode ser útil na detecção do estágio inicial de ND e com maior valor de predição do que as outras para a predição da ND.

Cistatina C como biomarcador Gold estándar para el diagnóstico de problemas renales agudos en caninos / Cystatin C as a gold standard biomarker for the acute kidney disease diagnosis in canines / Cistatina C como um biomarcador padrão de ouro para o diagnóstico de problemas renais agudos em caninos

Resumen Los caninos con lesiones renales tienen afectados distintos procesos tales como filtración, reabsorción y excreción que alteran la homeostasis. La medición de biomarcadores alternativos ha servido para el diagnóstico y pronóstico de daño renal, lo que ha servido para el médico veterinario, no solo por la oportunidad en el diagnóstico temprano sino por ejercicio preventivo. Uno de los marcadores que permite evaluar la tasa de filtración glomerular (TFG) es la concentración sérica de creatinina, ya que esta varía en proporciones inversas, por otro lado, se encuentra la creatinina (Ccr), siendo una buena herramienta para indicar el compromiso de la función glomerular, aunque esta no suele ser tan confiable, por sus altas interferencias al momento de medir. Por esto se ha postulado otros biomarcadores que dan un pronóstico más temprano y que permiten dar un tratamiento oportuno, entre ellos está la cistatina C, que presenta una baja variabilidad interindividual, ya que no genera uniones proteicas, no tiene secreción tubular y no se genera reabsorción tubular si no existe catabolismo de la proteína. El objetivo de esta revisión es presentar a la Cistatina C (CisC) como un biomarcador Gold estándar para el diagnóstico de problemas renales agudos en caninos, puesto que en medicina humana ya se ha establecido que la CisC tiene un mejor valor diagnóstico renal y de determinación de la TFG que la creatinina sérica, además de que tiene una constante producción y visibilidad en la concentración plasmática en situaciones de ausencia de variaciones de la TFG. Para la recolección de la información utilizada en esta revisión, se emplearon diversas fuentes como: PubMed, Scielo, Journal of Small Animal Practice, National Center for Biotechnology Information, en donde fueron seleccionados 50 artículos para realizar esta investigación.

Abstract Canines with kidney lesions are affected by different processes such as filtration, reabsorption and excretion that alter homeostasis. The measurement of alternative biomarkers has served for the diagnosis and prognosis of kidney damage, which has served the veterinarian, not only for the opportunity in early diagnosis but also for preventive exercise. One of the markers that allows evaluating the glomerular filtration rate (GFR) is the serum concentration of creatinine, since it varies in inverse proportions, on the other hand there is creatinine (Ccr), being a good tool to indicate the commitment of glomerular function, although this is not usually so reliable, due to its high interferences at the time of measurement. For this reason, other biomarkers have been postulated that give an earlier prognosis and that allow timely treatment, among them is cystatin C, which has low interindividual variability, since it does not generate protein junctions, does not have tubular secretion, is not generated tubular reabsorption if there is no protein catabolism. The objective of this review is to present Cystatin C (CisC) as a gold standard biomarker for the diagnosis of acute kidney problems in canines, since in human medicine it has already been established that CisC has a better renal diagnostic and determination value. of GFR than serum creatinine. The characteristics that lead this protein to be an excellent renal biomarker is due to the fact that it has a constant production and plasma concentration in situations of absence of GFR variations. To collect the information used in this review, various sources were used such as: PubMed, Scielo, Journal of Small Animal Practice, National Center for Biotechnology Information, where 50 articles were selected to carry out this research.

Resumo Caninos com lesão renal são afetados por diferentes processos como filtração, reabsorção e excreção que alteram a homeostase. A mensuração de biomarcadores alternativos tem servido para o diagnóstico e prognóstico de lesões renais, o que tem servido ao veterinário, não só pela oportunidade no diagnóstico precoce, mas também pelo exercício preventivo. Um dos marcadores que permite avaliar a taxa de filtração glomerular (TFG) é a concentração sérica de creatinina, pois ela varia em proporções inversas, por outro lado existe a creatinina (Ccr), sendo uma boa ferramenta para indicar o comprometimento da função glomerular, embora isso geralmente não seja tão confiável, devido às suas altas interferências no momento da medição. Por esse motivo, têm sido postulados outros biomarcadores que dão um prognóstico mais precoce e que permitem o tratamento oportuno, entre eles está a cistatina C, que tem baixa variabilidade interindividual, pois não gera junções protéicas, não tem secreção tubular, não é gerada tubular reabsorção se não houver catabolismo protéico. O objetivo desta revisão é apresentar a Cistatina C (CisC) como um biomarcador padrão ouro para o diagnóstico de problemas renais agudos em caninos, uma vez que na medicina humana já foi estabelecido que a CisC tem melhor valor para diagnóstico e determinação renal. do que a creatinina sérica. As características que levam essa proteína a ser um excelente biomarcador renal se devem ao fato de ter produção e concentração plasmática constantes em situações de ausência de variações da TFG. Para coletar as informações utilizadas nesta revisão, foram utilizadas várias fontes como: PubMed, Scielo, Journal of Small Animal Practice, National Center for Biotechnology Information, onde 50 artigos foram selecionados para realizar esta pesquisa.

Índice de sarcopenia en pacientes hospitalizados por agudización de la enfermedad pulmonar obstructiva crónica / Sarcopenia index in hospitalized patients with chronic obstructive pulmonary disease exacerbation

Resumen La presencia de sarcopenia (pérdida de masa y función muscular) implica peor pronóstico. Sin embargo, su diagnóstico es complejo y no se realiza en la atención clínica habitual. Se ha propuesto un biomarcador como estimador subrogado de la masa muscular esquelética, el denominado índice de sarcopenia ([creatinina sérica/cistatina C] x100) que se asocia a características pronósticas en diversas enfermedades incluyendo pacientes con enfermedad pulmonar obstructiva crónica (EPOC) estable. El objetivo de nuestro estudio ha sido evaluar de forma prospectiva la potencial información clínica y pronóstica de este biomarcador en agudización de la EPOC. Se trata de un estudio prospectivo, durante un año, de los pacientes consecutivos que ingresan por agudización de su EPOC. Se incluyeron 89 pacientes, 70 varones (79%) y 19 mujeres (21%). Aquellos con valores disminuidos del índice de sarcopenia tenían más disnea y requerían una internación más prolongada. En el análisis de correlación se obtuvo valores con significación estadística del índice con FEV1 (r = 0.23), PaCO (r = -0.30) y bicarbonato (r = -0.31), y con la disnea (r = -0.25) y la duración del ingreso (r =0.30). En los ingresados por agudización de la EPOC el índice de sarcopenia se relacionó con características pronósticas, de modo que los valores inferiores se asociaron a mayor duración de la internación, más disnea y mayor afectación funcional. Al tratarse de un índice asociado a la masa muscular, su determinación podría identificar a pacientes a incluir en un plan terapéutico diferenciado.

Abstract Sarcopenia (loss of muscle mass and function) implies a worse prognosis. However, its diagnosis is complex and is not made in routine clinical care. A biomarker has been proposed as a surrogate estimator of skeletal muscle mass, the so-called sarcopenia index ([serum creatinine/cystatine C] x100) which is associated with prognostic features in various diseases including patients with stable chronic obstructive pulmonary disease (COPD). The aim of our study was to prospectively evaluate the potential clinical and prognostic information of this biomarker in COPD exacerbation. This is a one-year prospective study of consecutive patients admitted for COPD exacerbation. A total of 89 patients, 70 men (79%) and 19 women (21%) were included. Those with lower values of the sarcopenia index had a higher level of dyspnoea and a longer hospitalization. In the correlation analysis, the index had statistically significant values with FEV1 (r = 0.23), PaCO (r = -0.30), bicarbonate (r = -0.31), dyspnoea (r = -0.25) and length of admission (r = -0.30). In patients admitted for COPD exacerbation, the sarcopenia index was related to prognostic characteristics, so that lower values were associated with longer duration of hospital admission, more dyspnoea and greater functional impairment. As this is an index associated with muscle mass, its determination may identify patients who could be the subject of a differentiated therapeutic plan.

Association between severe chronic kidney disease defined by cystatin-c and creatinine and clinical outcomes in an elderly population - an observational study / Associação entre doença renal crônica grave definida por cistatina-c e creatinina e desfechos clínicos em uma população idosa - um estudo observacional

ABSTRACT Introduction: Estimated glomerular filtration rate (eGFR) based on serum cystatin-C (sCys) seems as accurate as when based on serum creatinine (sCr), but sCys seems a better predictor of adverse outcomes. We aimed to study whether sCys could be a reliable tool for the prediction of adverse outcomes in elderly patients with severe chronic kidney disease (CKD). Methods: A group of 348 elderly patients with non-end-stage CKD (stages 1-4, according to eGFR-EPI sCr and/or sCys), referred to our consultation unit during 2016, was retrospectively studied and divided into four exclusive categories: CKD_stage4_neither (eGFR-sCr≥30mL/min; eGFR-sCys≥30mL/min), CKD_stage4_sCr_only (eGFR-sCr<30mL/min), CKD_stage4_sCys_only (eGFR-sCys<30mL/min) and CKD_stage4_combined (eGFRsCr<30mL/min; eGFR-sCys<30mL/min). Baseline characteristics, predictors of death, and clinical events (cardiovascular events and admissions for cardiovascular, acute kidney injury or infectious events) were explored until December 2018. Results: A 77±7.4 year-old cohort, with a modified Charlson Comorbidty Index (mCCI) of 3 (IQR:1-4), was followed-up during 29 (IQR: 26-33) months. There were no significant differences between the characteristics of the stage 4 groups. Survival analysis was stratified by follow-up at 12 months, and in the first year, survival curves of CKD_stage4_sCys_only and CKD_stage4_combined groups were significantly lower than the other groups (p=0.028). Adjusting for age, sex, and mCCI, CKD_stage4_sCys_only, conversely to CKD_stage4_sCr_only, had higher rates of clinical events (p<0.05) than CKD_stage4_neither group. Conclusion: In elderly patients with discordant CKD staging, sCys-based eGFR seems to be a better predictor of adverse outcomes than sCr-based eGFR. Patients with stage 4 CKD defined by sCr alone seem to behave similar to those with less severe CKD.

RESUMO Introdução: A taxa estimada de filtração glomerular (TFGe) com base na cistatina-C sérica (Cis-C) parece ser tão precisa quanto aquela baseada na creatinina sérica (Cr), mas cis-C parece ser um melhor preditor de resultados adversos. Nosso objetivo foi avaliar se a cis-C poderia ser uma ferramenta confiável para a previsão de desfechos adversos em pacientes idosos com doença renal crônica grave (DRC). Métodos: Um grupo de 348 pacientes idosos com DRC em estágio não terminal (estágios 1-4, de acordo com TFGe-EPI Cr e/ou Cis-C), encaminhados para nossa unidade de consulta durante 2016, foi estudado retrospectivamente e dividido em quatro categorias exclusivas: DRC_estágio 4 nenhum (TFGe-Cr≥30mL/min; TFGe -Cis-C≥30mL/min), DRC_estágio 4_Cr apenas (TFGe-Cr <30mL/min), DRC_estágio 4 _Cis-C_apenas (TFGe-Cis-C <30 mL/min), DRC_estágio4_combinado (TFGe-Cis-C <30mL/min. TFGe-Cr <30mL/min). Características basais, preditores de óbito e eventos clínicos (eventos cardiovasculares e internações por doenças cardiovasculares, lesão renal aguda ou eventos infecciosos) foram explorados até dezembro de 2018. Resultados: Uma coorte de 77 ± 7,4 anos, com índice de comorbidade de Charlson modificado (mCCI) de 3 (IQR: 1-4), foi acompanhada durante 29 (IQR: 26-33) meses. Não houve diferenças significativas entre as características dos grupos no estágio 4. A análise de sobrevida foi estratificada pelo acompanhamento aos 12 meses, sendo que no primeiro ano, as curvas de sobrevida dos grupos DRC_estágio4_Cis-C_apenas e DRC_estágio4_ combinado foram significativamente inferiores quando comparadas com os restantes grupos (p = 0,028). Ajustando para idade, sexo e mCCI, DRC_estágio4_Cis-C_apenas, ao contrário do grupo DRC_estágio4_Cr_apenas, teve maiores taxas de eventos clínicos (p <0,05) do que o grupo DRC_estágio4_nenhum. Conclusão: Em pacientes idosos com estadiamento discordante da DRC, a TFGe baseada na Cis-C parece ser um melhor preditor de resultados adversos do que a TFGe baseada na Cr. Pacientes com DRC em estágio 4, definida apenas por Cr, parecem se comportar de forma semelhante àqueles com DRC menos grave.

Melia azedarach L. extract induced the production of phytocystatin in passion fruit leaves / Extrato de Melia azedarach L. induz a produção de uma fitocistatina em folhas de maracujá

Phytocystatins belong to the family of cysteine proteinases inhibitors. These proteinase inhibitors have crucial functions in plant defense against insects and pathogens attack. In the present study Melia azedarach L. extract acts as an elicitor of plant defense responses in passion fruit seedlings inducing the increase of a phytocystatin levels in of these plants. The leaf protein content of the seedlings was extracted 24 hours after treatment with plant extract and analyzed for the induction of proteinase inhibitor activity. The results demonstrated the induction of a ~ 60 kD phytocystatin (Pfcyst) that has in vitro inhibitory effects against papain.  These findings suggest that M. azedarach plant extracts may act as a potential activator of induced resistance against insects and pathogens by upregulating cystatin proteins synthesis in passion fruits plants. Thus, the use of plant extracts as biodefensives could reduce the use of pesticides in economically important agricultural crops.

As fitocistatinas pertencem à familia de inibidores de proteinase cisteínica. Esses inibidores de proteinase têm função crucial na defesa de plantas contra o ataque de insetos e patógenos. No presente estudo, extrato de Melia azedarach L. atuam como um eliciador da resposta de defesa em plântulas de maracujá induzindo o aumento dos níveis de fitocistatinas nessas plantas. O conteúdo proteico foliar dessas plântulas foi extraído 24 horas após o tratamento com o extrato vegetal e analisado quanto a indução da atividade do inibidor de proteinase. Os resultados demonstraram a indução de uma fitocistatina (Pfcyst) de ~60 kDa que possui efeito inibitório in vitro contra a papaína. Essas descobertas sugerem que o extrato da planta M. azedarach pode atuar como um potencial ativador da resistência induzida contra insetos e patógenos por regular positivamente a síntese de proteínas cistatinas em plantas de maracuja. Dessa forma, o uso de extratos vegetais como biodefensivos poderia reduzir o uso de agrotóxicos em culturas agrícolas economicamente importantes.

Intervalo de referencia para la cistatina C en una muestra de población adulta cubana / Reference Interval for Cystatin C in a Sample of Adult Cuban Population

RESUMEN Fundamento: el estudio de la cistatina C ha despertado un interés creciente a medida que se define su utilidad como marcador precoz y sensible de enfermedad renal crónica. La determinación de los rangos de referencia para análisis químicos en el laboratorio clínico constituye requisito imprescindible para implementar un programa de control de calidad adecuado. Objetivo: establecer el intervalo de referencia de la cistatina C en una muestra de la población adulta cubana, en el laboratorio del Hospital Clínico Quirúrgico Hermanos Ameijeiras. Método: estudio descriptivo de corte transversal en 249 donantes de sangre (hombres y mujeres en igual proporción), con edades comprendidas entre 18 y 50 años. Se obtuvieron por método inmunoturbidimétrico los valores séricos de cistatina C y se compararon por sexo y grupo etáreo. Se calculó el intervalo de referencia y se comparó con el propuesto por el fabricante. Resultados: el intervalo de referencia obtenido mostró asociación con el sexo, pero no con el grupo etáreo. Se encontraron diferencias estadísticamente significativas entre el intervalo de referencia sérico de cistatina C en ambos sexos y el propuesto por el fabricante. Conclusiones el intervalo de referencia obtenido en esta investigación para cada sexo fue más alto que lo planteado por el fabricante del reactivo utilizado, ambos límites del intervalo tuvieron valores más elevados, se encontró además diferencia estadísticamente significativa entre ambos. Se evidenció la necesidad de disponer en cada laboratorio clínico, de valores de referencia acordes a cada lugar, según recomiendan las instituciones internacionales.

ABSTRACT Foundation: studying cystatin C has risen interest as it is defined its utility as an early marker and sensitive to chronic renal disease. Determining the range of reference for chemical analysis in clinical laboratories constitutes an essential requirement to implement an adequate quality control program. Objective: to establish the interval of reference of Cystatin C in a sample of adult Cuban population, in the laboratory of the Clinical Surgical Hospital Hermanos Ameijeiras. Method: cross-descriptive study in 249 blood donors (women and men in the same proportion), aged between 18 and 50. By the inmunoturbidimetric method the values of seric cystatin C were obtained and were compared by sex and age group. The interval of reference was calculated and compared with the one proposed by the manufacturer. Results: the interval of reference obtained showed association with sex, but not with the age group. Statistically significant differences were found between the interval of seric reference of cystatin C in both sexes and the one proposed by the manufacturer. Conclusion the need of counting with values of reference according to each place was evidenced, according to the International Federation of Clinical Chemistry and the standards of clinical laboratory.

Cystatin C as a potential biomarker to evaluate migraine / Cistatina C como potencial biomarcador para avaliação de enxaqueca

ABSTRACT Background: Migraine is a multifactorial neurovascular syndrome and closely associated to inflammation. Cystatin C (Cys C) is a neuroendocrine polypeptide which also plays a role in inflammation. Objective: To investigate the levels of Cys C in migraine patients without aura. Methods: A total of 80 participants were included in the study; 40 patients and 40 healthy controls. Serum Cys C levels were investigated by using enzyme-linked immunosorbent assay (ELISA). Statistical analysis were performed using Statistical Package for the Social Sciences (SPSS) version 22.0 (SPSS Inc, IL, USA). Results: Serum Cys C levels were found as 73.88 ng/mL in the patient group and 24.92 ng/mL in the healthy control group, being significantly higher among patients (p=0.000). Serum Cys C levels were significacntly different across age subgroups among patients (p=0.049), but not among controls. However, visual analog scale (VAS) (p=0.707), disease duration time (p=0.725) and body mass index (p=0.136) were not significantly different between the two groups. Conclusion: Our findings demonstrate that high serum Cys C levels are independently associated to migraine without aura. To the best of our knowledge, this is the first study to determine the serum levels of Cys C in patients with migraine. Thus, serum Cys C may be a potential biomarker of migraine.

RESUMO Introdução: A enxaqueca é uma síndrome neurovascular multifatorial e está intimamente associada à inflamação. A cistatina C (Cys C) é um polipeptídeo neuroendócrino que também desempenha papel importante na inflamação. Objetivo: Investigar os níveis de Cys C em pacientes com enxaqueca sem aura. Métodos: Foram incluídos no estudo 80 participantes; 40 pacientes e 40 controles saudáveis. Os níveis séricos de Cys C foram investigados usando o ensaio de imunoabsorção ligado à enzima (enzyme-linked immunosorbent assay - ELISA). A análise estatística foi realizada utilizando o Statistical Package for the Social Sciences (SPSS), versão 22.0 (SPSS Inc, IL, EUA). Resultados: Em nosso estudo, os níveis séricos de Cys C foram encontrados em 73,88 ng/mL no grupo de pacientes e 24,92 no grupo de controle saudável, sendo os níveis significativamente maiores nos pacientes (p=0,000). Os níveis séricos de Cys C foram significativamente diferentes entre faixas etárias no grupo de pacientes (p=0,049). No entanto, a escala visual analógica (EVA) (p=0,707), o tempo de duração da doença (p=0,725) e o índice de massa corporal (p=0,136) não foram significativamente diferentes entre os dois grupos. Conclusão: Nossos achados demonstram que altos níveis séricos de Cys C estão independentemente associados à enxaqueca sem aura. Até onde sabemos, este é o primeiro estudo a determinar os níveis séricos de Cys C em pacientes com enxaqueca e os resultados sugerem que o Cys C sérico pode ser um potencial biomarcador nessa condição clínica.

Correlación de cistatina "C" y creatinina sérica frente al filtrado glomerular en pacientes con nefropatía diabética / Correlation cystatin "C" and serum creatinine regarding to glomerular filtration in patients with diabetic nephropathy

INTRODUCCIÓN. La Nefropatía Diabética es una complicación vascular crónica que ori-gina una serie de alteraciones funcionales y estructurales de manera principal a nivel glomerular. La cistatina C y la creatinina sérica son marcadores de la función renal. OBJE-TIVO. Correlacionar las pruebas de la función renal cistatina C y la creatinina sérica frente al filtrado glomerular en pacientes con Nefropatía Diabética. MATERIALES Y MÉTODOS. Estudio descriptivo, transversal. De una población de 418 se seleccionó una muestra de 124 datos de Historias Clínicas. Se analizaron los datos de resultados de medición de la cistatina C y creatinina sérica frente al filtrado glomerular de pacientes con Nefropatía Diabética en el período de junio a diciembre de 2017. RESULTADOS. Frecuencia de edad de 36 a 93 años, media: 69 años, desviación estándar 10,76; un 56% (69; 124) del sexo femenino y 44% (54; 124) del sexo masculino. La cistatina C vs la creatinina sérica frente al filtrado glomerular presentaron una correlación de 92% (114; 124) y 66% (81; 124) de forma respectiva, se obtuvo una mayor correlación con la cistatina C y una estrecha sig-nificancia bilateral de 0,000. El daño renal más frecuente fue del estadío II en pacientes de 66 a 75 años. CONCLUSIÓN. La cistatina C y la creatinina sérica mostraron una alta correlación con el filtrado glomerular en pacientes con Nefropatía Diabética, la principal fue la cistatina C que detectó cambios precoces en el filtrado.

INTRODUCTION. Diabetic Nephropathy is a chronic vascular complication that causes a series of functional and structural alterations, mainly at the glomerular level. Cystatin C and serum creatinine are markers of kidney function. OBJECTIVE. To correlate the tests of renal function cystatin C and serum creatinine against glomerular filtration in patients with Diabetic Nephropathy. MATERIALS AND METHODS. Descriptive, cross-sectional study. From a population of 418, a sample of 124 data from Medical Records was selected. The data from the measurement results of cystatin C and serum creatinine were analyzed against glomerular filtration of patients with Diabetic Nephropathy in the period from june to december 2017. RESULTS. Frequency of age from 36 to 93 years, means: 69 years, standard deviation 10,76; 56% (69; 124) of the female sex and 44% (54; 124) of the male sex. Cystatin C vs serum creatinine versus glomerular filtration showed a correlation of 92% (114; 124) and 66% (81; 124), respectively, was obtained, a higher correlation was obtained with cystatin C and a close bilateral significance of 0,000. The most frequent kidney damage was stage II in patients aged 66 to 75 years. CONCLUSION. Cystatin C and serum creatinine showed a high correlation with glomerular filtration in patients with Diabetic Nephropathy, the main one being cystatin C, which detected early changes in the filtrate.

[Cystatin C: Biomarker of cardiovascular risk in HIV]. / Cistatina C: Biomarcador de riesgo cardiovascular en VIH.

INTRODUCTION: Patients infected with the human immunodeficiency virus (HIV) have a higher cardiovascular risk (CVR). The development of cardiovascular disease (CVD) in this population involves traditional CVR factors and factors related to the infection itself, such as chronic inflammatory status, immune dysfunction, as well as the antiretroviral therapy received. Cystatin C (CC) has shown to be useful in assessing the presence of CVR factors and CVD established in the general population, the elderly population, and patients with chronic kidney disease. An analysis was performed on this association in an HIV positive population (HIV+). MATERIAL AND METHODS: Analytical, observational, cross-sectional study was conducted, and included collecting information about CVR factors and CVD in HIV+, as well as measuring CC. The patients were divided into 2 groups: Group1=high CC (≥0.95mg/L) and Group2=normal CC (<0.95mg/L). RESULTS: A total of 95 patients were included. Group1=27 (28.4%) and Group2=68 (71.5%). A value of CC≥0.95mg/L was related to the presence of CVD (P=.01). It was also related with and an increase in waist circumference (P=.05), neck circumference (P=.04), systolic blood pressure (P=.04), diastolic blood pressure (P=.01), Framingham score (P=.03), and Framingham score adapted for HIV (P=.01). After performing multivariate analysis with incorporation of variables associated with CVD in the bivariate analysis, only CC≥0.95mg/L continued to be related to CVD. CONCLUSION: CC≥0.95mg/L was independently associated with CVD. This cut-off point was also linked to higher levels of blood pressure, and higher CVR at 10 years using the Framingham Score and Framingham Score adapted for HIV population.

Does Cystatin C have a role as metabolic surrogate in peritoneal dialysis beyond its association with residual renal function? / Teria a Cistatina C um papel como substituto metabólico na diálise peritoneal além de sua associação com a função renal residual?

ABSTRACT Introduction: It has been suggested that cystatin C levels are modified by obesity and inflammation. Furthermore, cystatin C has been associated with cardiovascular events and mortality outcomes. Aim: To study the association of cystatin C with the metabolic profile and cardiovascular disease of peritoneal dialysis patients. Methods: Data collected included clinical, laboratorial, and multifrequency bioimpedance assessment of 52 stable peritoneal dialysis patients. Minimal residual renal function was defined as > 2mL/min/1.73m2. Results: Serum cystatin C was not significantly associated with peritoneal or urinary cystatin C excretion. Negative correlation of cystatin C with normalized protein catabolic rate (rho -0.33, p = 0.02) and a trend towards positive correlation with relative body fat (rho 0.27, p = 0.05) were not independent from residual renal function. Cystatin C was not significantly associated with cardiovascular disease (p = 0.28), nor with glycated hemoglobin (p = 0.19) or c-reactive protein (p = 0.56). In the multivariate model, both age and diabetes were the strongest predictors of cardiovascular disease (odds ratio 1.09, p = 0.029 and odds ratio 29.95, p = 0.016, respectively), while relative body fat was negatively associated with cardiovascular disease (p = 0.038); neither cystatin C (p = 0.096) nor minimal residual renal function (p = 0.756) reached a significant association with cardiovascular disease. Conclusions: In this group of peritoneal dialysis patients, cystatin C did not correlate with the metabolic or inflammatory status, nor cardiovascular disease, after adjustment for residual renal function.

RESUMO Introdução: Tem sido sugerido que os níveis de cistatina C são modificados pela obesidade e inflamação. Além disso, a cistatina C tem sido associada a eventos cardiovasculares e desfechos de mortalidade. Objetivo: Estudar a associação da cistatina C com o perfil metabólico e doença cardiovascular de pacientes em diálise peritoneal. Métodos: Os dados coletados incluíram avaliação clínica, laboratorial e de bioimpedância múltipla de 52 pacientes estáveis em diálise peritoneal. A função renal residual mínima foi definida como > 2mL/min/1,73m2. Resultados: A cistatina C sérica não esteve significativamente associada à excreção peritoneal ou urinária. A correlação negativa da cistatina C com a taxa catabólica protéica normalizada (rho -0,33, p = 0,02) e uma tendência de correlação positiva com a gordura corporal relativa (rho 0,27, p = 0,05) não foram independentes da função renal residual. A cistatina C não se associou significativamente à doença cardiovascular (p = 0,28), nem com hemoglobina glicada (p = 0,19) ou proteína C reativa (p = 0,56). No modelo multivariado, idade e diabetes foram os mais fortes preditores de doença cardiovascular (razões de probabilidade 1,09, p = 0,029 e 29,95, p = 0,016, respectivamente) enquanto a gordura corporal relativa se associou negativamente à doença cardiovascular (p = 0,038). A cistatina C não se associou significativamente com doença cardiovascular (p = 0,096), tampouco a função residual mínima (p = 0,756). Conclusão: Neste grupo de pacientes em diálise peritoneal, a cistatina C não se correlacionou com o estado metabólico ou inflamatório, nem com doença cardiovascular, após ajuste para função renal residual.

Comparison of MDRD and the old CKD-EPI equations with the new CKD-EPI equations in kidney transplant patients when glomerular filtration rate is measured with 51Cr-EDTA. / Comparación de las ecuaciones MDRD y de las antiguas ecuaciones CKD-EPI frente a las nuevas ecuaciones CKD-EPI en pacientes con trasplante renal cuando se emplea 51Cr-EDTA para medir el filtrado glomerular.

BACKGROUND: When estimating the glomerular filtration rate (GFR) in kidney transplant patients, significant differences have been found between MDRD and the 2009 CKD-EPI equations, and reference techniques. OBJECTIVE: To analyse and compare the performance of MDRD and the 2009 and 2012 CKD-EPI equations against 51Cr-EDTA plasma clearance in measuring GFR in 270 kidney transplant patients after one year. RESULTS: The mean measured GFR was 43.0±11.4 (18.2-79.4)ml/min/1.73m2, with creatinine levels of 1.42±0.46 (0.60-4.33)mg/dl and cystatin C levels of 1.45±0.53 (0.42-3.48)mg/l. This correlated moderately with creatinine (r=-0.61, P<.001) and cystatin C (r=-0.52, P<.001). Using linear regression techniques, it was found that creatinine, cystatin C, gender and age only explained 52% of GFR total variance. All equations overestimated GFR, with a mean bias of +11.1ml/min/1.73m2 for MDRD, +16.4ml/min/1.73m2 for 2009-CKD-EPI, +15ml/min/1.73m2 for CKD-EPI with cystatin C, and +14.1ml/min/1.73m2 for 2012-CKD-EPI with creatinine and cystatin C. eGFR by MDRD and the 2009 CKD-EPI equation correlated better with 51Cr-EDTA than CKD-EPI with creatinine and/or cystatin C. The overestimations were negatively correlated with creatinine and cystatin C levels, most significantly for CKD-EPI with creatinine and/or cystatin C when GFR was greater than 60ml/min/1.73m2. CONCLUSIONS: The 2012 CKD-EPI equations with creatinine and/or cystatin C significantly overestimate GFR in stage 1 and 2 chronic kidney disease. The MDRD equations is therefore recommended in these cases. The reference method used to measure GFR seems to heavily influence the bias of the equations.

Avaliação da Cistatina C como marcador de Lesão Glomerular em mulheres portadoras de pré-eclâmpsia / Evaluation of Cystatin C as a marker of Glomerular Injury in women with pre-eclampsia

A função renal alterada é um componente essencial do processo fisiopatológico que está relacionado ao pior prognóstico materno-fetal. Os rins estão entre os órgãos centrais afetados na pré-eclâmpsia, e desempenham um papel significativo na síntese e degradação das substâncias de baixo peso molecular, como creatinina, ureia e cistatina C. A cistatina C vem sendo apontada como uma substância promissora para avaliar a função renal, e alterações da filtração glomerular precocemente. O presente trabalho foi realizado para investigar a cistatina C sérica e urinária como marcador de lesão glomerular em grávidas portadoras de PE, e correlacionar com a dosagem de creatinina e uréia. Trata-se de um estudo transversal com 44 gestantes com diagnóstico da pré-eclâmpsia e 24 normotensas. Os níveis de cistatina C plasmáticos e urinárias apresentam-se elevados e estatisticamente significativos (respectivamente, p=0,001, p=0,012) nas mulheres portadoras de PE quando comparadas com as normotensas. Comparando-se com outros marcadores, a cistatina C sérica demonstrou melhor capacidade de identificar a função renal, com valor percentual de área da curva ROC de 91,7%. Nesse estudo, a cistatina C mostra-se um bom marcador de lesão glomerular em gestantes portadoras de pré eclâmpsia, comparável aos marcadores tradicionais uréia e creatinina. Sua vantagem sobre estes marcadores refere-se a sua menor influência de diversos aspectos biológicos não relacionados a doença gestacional propriamente dita.

Renal function is an essential component of the pathophysiological process that is related to the worst maternal-fetal prognosis. The kidneys are among the major levels of affection in PE, and play a significant role in the turnover of most low molecular weight substances such as creatinine, urea and cystatin C. Cystatin C has been shown to be a promising substance for assessing renal function and glomerular filtration changes earlier. The present study was carried out to investigate serum and urinary cystatin C as marker of glomerular lesion in pregnant women with PE, and correlate with creatinine and urea. It is a cross-sectional study with 44 pregnant women diagnosed with preeclampsia and 24 normotensive women. Plasma and urinary cystatin C levels were elevated and statistically significant (p = 0.001, p = 0.012) in women with PE compared to normotensive women, respectively. Compared with other markers, serum cystatin C demonstrated a better ability to identify renal function, with a percentage of area of the ROC curve of 91.7%. Cystatin C is a good marker of glomerular lesion in pregnant women with preeclampsia, comparable to traditional urea and creatinine markers. Their advantage over these markers is their lower influence of several biological aspects unrelated to gestational disease itself.