Lamivudine-based two-drug regimens with dolutegravir or protease inhibitor: Virological suppression in spite of previous therapy failure or renal dysfunction

Abstract Background Two-Drug Regimens (2DR) have proven effective in clinical trials but real-world data, especially in resource-limited settings, is limited. Objectives To evaluate viral suppression of lamivudine-based 2DR, with dolutegravir or ritonavir-boosted protease inhibitor (lopinavir/r, atazanavir/r or darunavir/r), among all cases regardless of selection criteria. Patients and methods A retrospective study, conducted in an HIV clinic in the metropolitan area of São Paulo, Brazil. Per-protocol failure was defined as viremia above 200 copies/mL at outcome. Intention-To-Treat-Exposed (ITT-E) failure was considered for those who initiated 2DR but subsequently had either (i) Delay over 30 days in Antiretroviral Treatment (ART) dispensation, (ii) ART changed or (iii) Viremia > 200 copies/mL in the last observation using 2DR. Results Out of 278 patients initiating 2DR, 99.6% had viremia below 200 copies/mL at last observation, 97.8% below 50 copies/mL. Lamivudine resistance, either documented (M184V) or presumed (viremia > 200 copies/mL over a month using 3TC) was present in 11% of cases that showed lower suppression rates (97%), but with no significant hazard ratio to fail per ITT-E (1.24, p= 0.78). Decreased kidney function, present in 18 cases, showed of 4.69 hazard ratio (p= 0.02) per ITT-E for failure (3/18). As per protocol analysis, three failures occurred, none with renal dysfunction. Conclusions The 2DR is feasible, with robust suppression rates, even when 3TC resistance or renal dysfunction is present, and close monitoring of these cases may guarantee long-term suppression.

USUAL VALUES OF GLOMERULAR FILTRATION RATE BY THE CG, MDRD AND CKD-EPI METHODS IN A SENEGALESE ADULT POPULATION

The estimation of the glomerular ?ltration rate (GFR), whose formulas are usually based on serum creatinine, is a fundamental data in clinical nephrology. The concept of “reference” or usual values adopted by health professionals is essential because of the paucity of research on the usual values of GFR in black Africa. The Modi?cation of Diet in Renal disease (MDRD) and Chronik Kidney disease-Epidemiology collaboration (CKDEpi) equations were determined in non-African populations. Usual values speci?c to the black African population by the evaluation of the formulas of Cockroft and Gault (CG), MDRD and CKD-Epi must be rigorous and are the subject of this study. The GFR was determined using the CG, MDRD and CKD-Epi formulas in a sample of 233 presumed healthy Senegalese adults (118 men, 115 women). SPSS and Excel 2016 software were used for statistical analysis. A value of P<0.05 was considered statistically signi?cant. The determination of the GFR by the Cockcroft method overestimates the CKD values by 10.24 (9.82 - 14.53) with p=0.001 and that of the MDRD by 7.47 (5.91 - 9.03) the CKD values with p=0.001. For a GFR measurement uncertainty of +/- 10%, the CG and CKD formulas cannot be superimposed with a low correlation coef?cient r = 0.52 and a coef?cient of determination R² = 0.28; whereas those of MDRD and CKD-Epi are on the other hand superimposable with r = 0.79 and R² = 0.63. Thus, the CKD-Epi formula should be preferred for determining the usual value of GFR in a healthy person.

Screening de enfermedad renal crónica en pacientes diabéticos de larga evolución de la UMF (unidad de medicina familiar) 222

Contexto: la nefropatía diabética es la primera causa de enfermedad renal crónica en el mundo, sin embargo, no existe información de la prevalencia de Enfermedad Renal Crónica (ERC) en estadios tempranos en México. Una tarea fundamental del primer nivel de atención es la detección oportuna de enfermedades y la ERC en pacientes diabéticos es subdiagnosticada en estadios tempranos al ser asintomática. Objetivo: determinar la frecuencia y la estadificación de ERC en pacientes con diabetes mellitus tipo 2 de larga evolución en una unidad de primer nivel de atención, en el estado de México. Metodología: estudio transversal descriptivo. Se incluyeron 263 pacientes calculados por fórmula de población finita y selección aleatoria simple. Se incluyeron pacientes con diabetes tipo 2, ≥ 5 años de evolución, sin encontrarse en terapia sustitutiva de la función renal que cumplieran los criterios de inclusión. Las variables de estudio: características sociodemográficas y la estimación de la tasa de filtración glomerular por la ecuación CKD-EPI fueron descritas en frecuencias y porcentajes para variables categóricas y las variables continuas se reportaron medias y de desviación estándar, la diferencia entre grupos fue establecida por medio de prueba de Chi cuadrado o prueba exacta de Fisher y distribución t de student, de acuerdo con el tipo de variable. Un valor de p ˂ 0,05 fue considerado estadísticamente significativo. Resultados: la clasificación Kdigo presenta seis estadios y los resultados con respecto al grado de filtrado glomerular fueron: estadio 1 con 39,5 % (IC 95 %, 34,2-45,6), estadio 2 con 38,8 % (IC 95 %, 32,7-44,5), estadio 3a con 8 % (IC 95 %, 4,9-11,4), estadio 3b con 5,7 % (IC 95 %, 3,4-8,7), estadio 4 con 6,8 % (IC 95 %, 3,8-9,9) y el estadio 5 con 1,1 % (IC 95 % 0,0-2,7). El promedio de edad fue 69,26 ±11,01 en el grupo con ERC, en la segmentación por género estuvo: masculino en el grupo con ERC con 59,6 % y femenino con 40,3 %. Con respecto a comorbilidades, hipertensión arterial y tratamiento al analizarlas en grupos con ausencia de ERC y presencia de ERC fueron estadísticamente significativas, lo mismo en los resultados de laboratorio. Conclusiones: la prevalencia de sospecha de ERC en nuestra población es de 21 %, al menos 1 de cada 5 pacientes diabéticos con ≥ 5 años de evolución padecen una disminución del FG, sin embargo, no podemos considerarla ERC hasta que se valore la presencia de daño renal y corroborarlo a los tres meses.

Background: Diabetic nephropathy is the main cause of chronic kidney disease (CKD), however, there are no data available about the prevalence of chronic kidney disease in the early stages in Mexico. A key role in first level attention consists in performing timely screenings for diseases such as CKD. In most cases CKD is underdiagnosed in early stages, because it is asymptomatic. Purpose: To determine the frequency of CKD in long-standing diabetes type 2 Methods: This was a cross-sectional descriptive study. We included 263 patients with diabetes type 2 with at least 5 years of evolution, not undergoing renal function replacement therapy. The variables of this study were: sociodemographic characteristics and estimation of the glomerular filtration rate through the CKD-EPI equation. Categorical variables were summarized as frequencies and percentages. For continuous variables, mean and standard deviation were reported. The significance of differences between groups was assessed by Student's t-test or square chi or Fisher's exact test, and p-value ≤ 0.05 was considered statistically significant. Results: the KDIGO classification has 5 stages. The results regarding the degree of glomerular filtration: stage 1 with 39.5% (95% CI, 34.2-45.6) , stage 2 with 38.8% ( 95% CI, 32.77-44.5),stage 3a with 8% ( 95% CI, 4.9-11.4), stage 3b with 5.7% (95% CI, 3.4-8.7), grade 4 with 6.8% (95% CI, 3.8-9.9) and stage 5 with 1.1% (95% CI 0.0-2.7). The average age was 69.26 ± 11.01 in the group with CKD. Male gender predominated in the group CKD with 34 (59.6%) and 23 (40.3%), for female. Regarding comorbidities, hypertension arterial and treatment when analyzed for either absence or presence of CKD were statistically significant. The same findings can be obtained in laboratory results. Conclusion: The prevalence of suspected CKD in our population is 21%, at least 1 in 5 diabetic patients with ≥5 years of evolution suffer a decrease in GFR; however, we cannot consider it to be CKD until the presence of kidney damage is assessed and confirmed at 3 months.

Estimación de la tasa de filtración glomerular: concordancia de la ecuación del European Kidney Function Consortium de 2020 con CKD-EPI y FAS en adultos jóvenes

Contexto: la TFG es un indicador de la función renal y se estima por ecuaciones TFGe, la mayoría son aplicables en un rango etario, aunque se producen discrepancias en los valores al cambiar de fórmula por cruzar un límite de edad. Así, la ecuación CKD-EPI sobreestima la TFG en adultos jóvenes, mientras que la ecuación FAS la sobreestima para creatininemias bajas. Para minimizar sus limitaciones, el European Kidney Function Consortium propuso la ecuación EKFC combinando características de diseño de FAS y CKD-EPI. Objetivo: evaluar el comportamiento de las ecuaciones EKFC vs. CKD-EPI y FAS en jóvenes, las diferencias en TFGe y la concordancia en asignación a categorías de TFG. Metodología: estudio analítico aprobado por el Comité Asesor de Ética y Seguridad de la Investigación de la Facultad de Bioquímica y Ciencias Biológicas de la UNL, con una muestra de 157 estudiantes voluntarios, de entre 18 y 37 años. Para la medición de la creatininemia se utilizó el método Jaffé cinético trazable a Isotopic Dilution Mass Spectroscopy, con el programa estadístico MedCalc. Resultados: EKFC: TFGe menores que CKD-EPI y FAS, total y por sexo. Media de las diferencias (mL/min/1,73 m2): (CKD-EPI - EKFC) totales = 10,42; 18-20 años = 11,91; 21-30 años = 11,10; 31-37 años = 8,96 / (FAS-EKFC) totales = 2,79; FAS ≤ 110 mL/min/1,73 m2 y mayor: 1,1 y 9,0 respectivamente. Asignación a categorías G: kappa menores EKFC vs. CKD-EPI que vs. FAS. Recategorización: 13,4 % en G1 por CKD-EPI categorizados G2 por EKFC; 0,6 % respecto a FAS en igual sentido. Asignación a categorías ≥ 75mL/min/1,73 m2 o menor: buena concordancia. Conclusiones: en la muestra, EKFC cumple los objetivos de su diseño. La sobreestimación de TFGe por CKD-EPI en adultos jóvenes disminuyó, más fuertemente hacia los 18 años, y corrigió la de FAS para creatininemias bajas. Es importante desarrollar estimadores de TFG basados en creatininemia que cubran todo el rango de edades y estados de función renal.

Introduction: GFR is a kidney function indicator. The estimation of the GFR (eGFR) is carried out by equations. Most of them are applicable with in an age range. Discrepancies between the values are found when crossing a limit of age. CKD-EPI overestimates GFR in young adults; FAS overestimates it for low creatininemias. To minimize these limitations, the European Kidney Function Consortium proposed the EKFC equation that combines design features of FAS and CKD-EPI. Objective: The performance of EKFC vs. CKD-EPI and FAS in young people was evaluated: differences in eGFR and agreement in the allocation to GFR categories were found. Methods: Analytical study approved by the Ethics Committee. Sample: 157 volunteer students, 18-37 years old. Creatininemia: kinetic Jaffé method traceable to Isotopic Dilution Mass Spectroscopy. Program: MedCalc. Results: EKFC: eGFR lower than CKD-EPI and FAS, total and by sex. Means of the differences (mL/min/1.73m2): total (CKD-EPI - EKFC) = 10.42; 18-20 years = 11.91; 21-30 years = 11.10; 31-37 years = 8.96 // (FAS-EKFC) total = 2.79; FAS≤ 110 mL/min/1.73m2 and higher: 1.1 and 9.0 respectively. Allocation to G categories: lower kappa EKFC vs. CKD-EPI than vs. FAS. Recategorization: 13.4% in G1 by CKD-EPI categorized G2 by EKFC; 0.6% compared to FAS, in the same sense. Allocation to categories ≥75mL/min/1.73 m2 or less: good agreement. Conclusions: In the sample, EKFC meets the objectives of its design. The overestimation of eGFR by CKD-EPI in young adults decreased, even more around 18 years of age, and corrected that of FAS for low creatininemias. It is important to develop GFR estimators based on creatininemia that cover the entire range of ages and renal function status.

Correlación entre las ecuaciones para la estimación del filtrado glomerular (MDRD, CKD-EPI,) y la depuración de creatinina en orina de 24 horas en pacientes oncológicos / Correlation between the equations for the estimation of the filtering glomerular (MDRD, CKD-EPI,) and creatinine clearance in 24-hour urine in cancer patients

Demostrar la correlación entre las ecuaciones MDRD, CKD-EPI con la depuración de creatinina de 24 horas en pacientes oncológicos. Estudio transversal realizado en el Instituto Oncológico Nacional Dr Juan Tanca Marengo durante el periodo de tiempo comprendido entre el mes de agosto 2019 a agosto de 2020. Al evaluar las distintas variable MDRD obtuvo un valor promedio de 44,81 ml/min/m2 con un intervalo de 41,07 ­ 48,55 ml/min/m2 , la variable CKD-EPI el valor promedio fue 43,59 + 18,09 ml/min/m2 con un intervalo de 40,01 ­ 47,18 ml/min/m2 , para el estándar de referencia depuración de creatinina de 24 horas el promedio fue de 54ml/min/m2 Al evaluar la relación entre los dos estimadores de TFG se encontró que ambos presentan una fiabilidad regular presentando una correlación intraclase de 0,43 (p<0,05) entre los estimadores CKD-EPI y MDRD en relación con la TFG de creatinina de 24horas. Cuando se evaluó pacientes con tumores sólidos y hematológicos, se encontró una mayor correlación intraclase con la escala MDRD-4 0,60 (0,25 ­ 0,82) < 0,05 en tumores hematológicos en comparación con CKD-EPI. En la población general, CKD-EPI es la fórmula recomendada, y se está recomendado con mayor frecuencia en pacientes oncológicos. Nuestro estudio demostró que la ecuación MDRD es la fórmula que mejor se correlaciona con la depuración de creatinina de 24 horas, siendo mejor en el grupo de tumores hematológicos, pero no existe diferencia estadísticamente significativa entre las dos ecuaciones.

To demonstrate the correlation between the MDRD, CKD-EPI equations with the 24-hour creatinine clearance in cancer patients. Cross-sectional study carried out at the National Oncological Institute Dr Juan Tanca Marengo during the period of time between the month of August 2019 to August 2020. When evaluating the different MDRD variables, an average value of 44.81 ml / min / m2 was obtained with an interval of 41.07 ­ 48.55 ml / min / m2, the CKD-EPI variable the average value was 43.59 + 18 , 09 ml / min / m2 with an interval of 40.01 ­ 47.18 ml / min / m2, for the reference standard creatinine clearance of 24 hours the average was 54 ml / min / m2 When evaluating the relationship between the two estimators of GFR, it was found that both present a regular reliability, presenting an intraclass correlation of 0.43 (p <0.05) between the CKD-EPI and MDRD estimators in relation to the 24-hour creatinine GFR. When patients with solid and hematological tumors were evaluated, a higher intraclass correlation was found with the MDRD-4 scale 0.60 (0.25 ­ 0.82) <0.05 in hematological tumors compared to CKD-EPI. In the general population, CKD-EPI is the recommended formulation, and it is more frequently recommended in cancer patients. Our study showed that the MDRD equation is the formula that best correlates with 24-hour creatinine clearance, being better in the group of hematological tumors, but there is no statistically significant difference between the two equations.

A comparative study of different methods of estimating glomerular filtration rate in a subset of Filipinos with normal renal function

@#Kidney function is commonly quantified using the glomerular filtration rate (GFR). However, the gold standard of measuring GFR, inulin clearance, is not practical for daily clinical use. This study compares different methods of GFR estimation based on serum creatinine, plasma levels of 99mTc-diethylenetriaminepentaacetic acid (DTPA), and camera acquisition of 99mTc-DTPA uptake. Seventy-five Filipino adults between ages 20 and 35 presumed to have normal kidneys were recruited. Each subject underwent gamma camera scintigraphy using the Gates and Inoue protocols after receiving a dose of 99mTc-DTPA. Blood samples were subsequently extracted at 1 hour and 3 hours after tracer injection, and GFRs were calculated based on single- and double-plasma sampling methods (SPSM and DPSM, respectively). Serum creatinine was also measured to derive GFR using the CKD-EPI, MDRD, and CockroftGault equations. Each method was correlated with a reference standard (DPSM) based on accuracy, linear regression, bias, and precision. SPSM tends to overestimate GFR unlike the other methods evaluated, but otherwise shows the most favorable diagnostic performance among the six methods when correlated with DPSM. The Inoue method appears modestly better than the routinely utilized Gates protocol, though both methods exhibit lack of precision. The CKD-EPI formula shows similar, if not slightly superior, diagnostic properties to the MDRD and Cockroft-Gault equations, thus confirming its validity for use in this Filipino population subset. Further studies are needed, particularly involving SPSM and CKD-EPI, to determine the applicability of our findings in Filipinos with varying degrees of kidney function. It is hoped that modifications to these methods can be made that are tailor-fit to derive more accurate and population-specific GFR values.

Consecuencias de la selección inadecuada de la ecuación de estimación de la tasa de filtración glomerular / Consequences of inadequate selection of estimated glomerular filtration rate equation / Consequências da seleção inadequada da equação de estimação da taxa de filtração glomerular

El objetivo del trabajo consistió en evaluar, en una muestra de estudiantes, las consecuencias sobre la Tasa de Filtración Glomerular estimada (TFGe) por MDRD-4, MDRD-4 IDMS y CKD-EPI producidas por la selección inadecuada de las fórmulas según la trazabilidad de la creatininemia utilizada y valorar el efecto sobre la categorización por estadio G de TFG al utilizar valores numéricos de MDRD-4 y MDRD-4 IDMS≥60 mL/min/1,73 m². Se realizó un estudio descriptivo, analítico, de corte transversal con 100 alumnos de bioquímica, que participaron voluntariamente. Se determinó la creatininemia por métodos Jaffé cinéticos, valores trazables y no trazables al Isotopic Dilution Mass Spectroscopy (IDMS). La TFGe se calculó por las fórmulas MDRD-4, MDRD-4 IDMS y CKD-EPI introduciendo en cada fórmula valores de creatinina trazables y no trazables a IDMS. Los estudiantes se clasificaron por categoría G según los resultados. El mal empleo de las ecuaciones respecto a la trazabilidad de la creatininemia según fueron diseñadas cambió sensiblemente los valores de TFGe (p<0,05) y la proporción de jóvenes por estadio G respecto a lo hallado con el empleo adecuado (MDRD-4. G1: 67,4% vs. 53,7%; G2: 32,6% vs. 45,3%; G3a: 0,0% vs. 1,0%. MDRD-4 IDMS. G1: 37,9% vs. 59,0%; G2: 56,8% vs. 40,0%; G3a: 5,3% vs. 1,0%. CKD-EPI. G1: 70,5% vs. 85,3%; G2: 29,5% vs. 14,7%). El uso de valores numéricos para TFGe por MDRD-4 y MDRD-4 IDMS≥60 mL/min/1,73 m² infraestimó lo obtenido con CKD-EPI, que puede informarse numéricamente en ese rango. Ambas situaciones conllevan errores que afectan la categorización funcional renal de pacientes y la prevalencia en estudios epidemiológicos.

The objective of this work was to evaluate the consequences on the estimated Glomerular Filtration Rate (eGFR) by MDRD-4, MDRD-4 IDMS and CKD-EPI produced by the inadequate equation selection according to the creatinine traceability in a sample of biochemistry students and to assess the effect on G categorization if numerical values of the MDRD-4 and MDRD-4 IDMS equations≥60 mL/ min/1.73 m² were used. A descriptive, analytical, cross-sectional study was performed between 2014- 2016, 100 volunteer students of biochemistry were studied. Creatininemia was determined by kinetic Jaffé methods, traceable and non-traceable to Isotopic Dilution Mass Spectroscopy (IDMS). The eGFR was estimated by the MDRD-4, MDRD-4 IDMS and CKD-EPI formula, by feeding each formula with traceable and non traceable creatinine values to IDMS. Students were classified by category G according to the results obtained. Inappropriate equation use regarding the traceability of the creatinine for which they were designed significantly changed eGFR values (p<0.05) and the proportion of young people per G stage compared to what was found with adequate use (MDRD-4. G1: 67.4% vs. 53.7%; G2: 32.6% vs. 45.3%; G3a: 0.0% vs. 1.0%. MDRD-4 IDMS. G1: 37.9% vs. 59.0%; G2: 56.8% vs. 40.0%; G3a: 5.3% vs. 1.0%. CKD-EPI. G1: 70.5% vs. 85.3%; G2: 29.5% vs. 14.7%). The use of numerical values for eGFR by MDRD-4 and MDRD-4 IDMS≥60mL/min/1.73 m² underestimated what was obtained with CKD-EPI, which can be reported numerically in that range. Both situations involve errors that affect patient renal functional categorization and prevalence in epidemiological studies.

Este trabalho teve como objetivo avaliar as consequências sobre a Taxa de Filtração Glomerular estimada (TFGe) por MDRD-4, MDRD-4 IDMS e CKD-EPI produzidas pela seleção inadequada das fórmulas, segundo a rastreabilidade da creatininemia utilizada e o efeito sobre a categorização por estágio G de TFG ao utilizar valores numéricos de MDRD-4 e MDRD-4 IDMS≥60 mL/min/1,73 m². Este é um estudo descritivo, analítico e de corte transversal com 100 alunos de bioquímica, que participaram em forma voluntária. Foi determinada a creatininemia através do métodos Jaffé cinéticos, valores rastreáveis e não rastreáveis ao Isotopic Dilution Mass Spectroscopy (IDMS). A TFGe foi estimada pela fórmula MDRD-4, MDRD-4 IDMS e CKD-EPI introduzindo em cada fórmula valores de creatinina rastreáveis e não rastreáveis a IDMS. Os estudantes foram classificados por categoria G conforme os resultados. Uso indevido das equações a respeito da rastreabilidade da creatinina conforme foram desenhadas, mudou sensivelmente os valores de TFGe (p<0,05) e a proporção de jovens por estágio G em relação ao encontrado com o uso adequado adecuado (MDRD-4. G1: 67,4% vs. 53,7%; G2: 32,6% vs. 45,3%; G3a: 0,0% vs. 1,0%. MDRD-4 IDMS. G1: 37,9% vs. 59,0%; G2: 56,8% vs. 40,0%; G3a: 5,3% vs. 1,0%. CKD-EPI. G1: 70,5% vs. 85,3%; G2: 29,5% vs. 14,7%). Utilizar valores numéricos para TFGe por MDRD-4 e MDRD-4 IDMS≥60mL/min/1,73 m² infraestimou o obtido com CKD-EPI, que pode informar-se numericamente nesse intervalo. Ambas as situações conduzem a erros que afetam a categorização funcional renal de pacientes e a prevalência em estudos epidemiológicos.

Evaluación de la función renal con la fórmula CKD-EPI y factores de riesgo que predisponen a su disminución en adultos mayores de 60 años / Kidney function evaluation with CKD-EPI equation and risk factors that prevent its decrease in elderly people

Objetivo: estimar la filtración glomerular mediante la ecuación CKD-EPI a partir de la concentración de creatinina sérica en pacientes mayores de 60 años de edad con el fin de estadificarlos, además de identificar los factores de riesgo que conllevan a la progresión de su disminución diferenciándolos por edad y sexo. Método: se realizó un estudio descriptivo de carácter transversal, en pacientes mayores de 60 años que acuden al Hospital Municipal Andrés Cuschieri de Colcapirhua durante los meses de enero a junio del 2016 con una muestra de 408 pacientes de los cuales se realizó la revisión de la historia clínica, y estimación de la filtración glomerular a partir de la fórmula CKD-EPI, con la posterior clasificación e identificación de los factores de riesgo. Resultados: entre los más sobresalientes son que el sexo femenino presenta menor filtrado glomerular, la edad no fue un factor predisponente en este grupo, los factores de riesgo asociados a su disminución fueron la hipertensión arterial, diabetes mellitus y un IMC alterado. Conclusiones: el uso y conocimiento de la ecuación CKD-EPI es un instrumento de pesquisaje oportuno y de estadiaje; sin embargo, la identificación y corrección de los factores de riesgo son importantes para prevenir la progresión de la enfermedad.

Objective: to estimate the glomerular filtration rate using the CKD-EPI equation, based on the serum creatinine concentration in patients over 60 years of age, in order to staging them, as well as to identify the risk factors that lead to the progression of their decrease by differentiating them by age and sex. Method: a cross-sectional descriptive study was performed in patients older than 60 years of age who attended the Hospital Municipal Andrés Cuschieri from Colcapirhua during the months of January to June 2016 with a sample of 408 patients from whom it was realized the review of the clinical history, and estimation of glomerular filtration from the CKD-EPI formula, with subsequent classification and identification of risk factors. Results: among the most outstanding are that the female sex has less glomerular filtration, age was not a predisposing factor in this group, the risk factors associated with its decrease were hypertension, diabetes mellitus and a modified BMI. Conclusions: the use and knowledge of the CKD-EPI equation is an instrument of timely screening and staging; however, the identification and correction of risk factors are important in preventing the progression of the disease.

A comparative study on the applicability of three CKD-EPI equations for estimation of glomerular filtration rate in Chinese patients with diabetic nephropathy / 中华肾脏病杂志

Objective To evaluate whether three chronic kidney disease epidemiology collaboration (CKD-EPI) equations (CKD-EPI2009Scr,CKD-EPI2012SCysC and CKD-EPI2012Scr-SCysC) are applicable in the prediction of glomerular filtration rate (GFR) in Chinese patients with diabetic nephropathy (DN).Methods One hundred and eight patients with DN who were hospitalized in the First Affiliated Hospital of Guangzhou Medical University with GFR being measured by dynamic renal imaging with 99mTc-DTPA from June 2012 to April 2014 were enrolled in this study.GFR measured by dynamic renal imaging with 99mTe-DTPA was used as the reference value (rGFR).GFR was estimated by the CKD-EPI2009Scr equation,the CKD-EPI2012SCySC equation,and the CKD-EPI2012Scr-SCysC equation (labeled as eGFR1,eGFR2,eGFR3).The correlation,30％ accuracy,staging consistency,deviation and diagnostic accuracy were compared among the three CKD-EPI equations.Results The rGFR in 108 DN patients was (61.78±26.51) ml· min-1· (1.73 m2)-1.The correlation between three eGFRs and rGFR was significant (all P ＜ 0.01),the correlation coefficients were 0.738,0.708,0.782.The 30％ accuracy were 74.07％,52.78％,67.59％,The 30％ accuracy of eGFR1 and eGFR3 were higher than eGFR2 (all P ＜ 0.05),but there was no significant difference between eGFR3 and eGFR1 (x2=0.874,P=0.436).The staging consistency was not ideal,Kappa values were 0.391,0.180 and 0.422.For the deviations between three eGFRs and rGFR,there was no significant difference between eGFR3 and rGFR (P ＞ 0.05),eGFR1 underestimated rGFR,eGFR2 overestimated rGFR (all P ＜ 0.01).The results of the Bland-Altman chart showed that consistencies between three eGFRs and rGFR were poor,the degree of deviation of eGFR3 was the smallest.The area under the ROC curve (AUC) of three eGFRs was 0.878,0.883 and 0.915.The AUC,sensitivity,specificity,overall compliance rate and Youden index of eGFR3 were the highest.Conclusions The eGFRs predicted by the three CKD-EPI equations showed good relevance,accuracy and diagnostic accuracy with the rGFR,but poor in consistencies.Comparatively,CKD-EPI2012Scr-SCysC may be better than others,but its consistency limits exceeds the acceptable limits.Therefore,the applicability of using the three CKD-EPI equations to predict the GFR in Chinese DN patients requires a larger sample and multiple verifications as well as further improvement.

Comparing Results of Five Glomerular Filtration Rate-Estimating Equations in the Korean General Population: MDRD Study, Revised Lund-Malmö, and Three CKD-EPI Equations

BACKGROUND: Estimated glomerular filtration rate (eGFR) is a widely used index of kidney function. Recently, new formulas such as the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations or the Lund-Malmö equation were introduced for assessing eGFR. We compared them with the Modification of Diet in Renal Disease (MDRD) Study equation in the Korean adult population. METHODS: The study population comprised 1,482 individuals (median age 51 [42-59] yr, 48.9% males) who received annual physical check-ups during the year 2014. Serum creatinine (Cr) and cystatin C (CysC) were measured. We conducted a retrospective analysis using five GFR estimating equations (MDRD Study, revised Lund-Malmö, and Cr and/or CysC-based CKD-EPI equations). Reduced GFR was defined as eGFR <60 mL/min/1.73 m2. RESULTS: For the GFR category distribution, large discrepancies were observed depending on the equation used; category G1 (≥90 mL/min/1.73 m2) ranged from 7.4-81.8%. Compared with the MDRD Study equation, the other four equations overestimated GFR, and CysC-based equations showed a greater difference (-31.3 for CKD-EPI(CysC) and -20.5 for CKD-EPI(Cr-CysC)). CysC-based equations decreased the prevalence of reduced GFR by one third (9.4% in the MDRD Study and 2.4% in CKD-EPI(CysC)). CONCLUSIONS: Our data shows that there are remarkable differences in eGFR assessment in the Korean population depending on the equation used, especially in normal or mildly decreased categories. Further prospective studies are necessary in various clinical settings.

Comparação das equações MDRD e CKD-EPI na estimativa da taxa de filtração glomerular em pacientes diabéticos e hipertensos não diagnosticados com doença renal crônica atendidos em ambulatório de um hospital universitário / Comparing the equation MDRD & CKD-EPI in the estimate of glomerular filtration rate in diabetic and hypertensive patients not diagnosed with chronic kidney disease served in a outpatient university hospital

A demonstração clínica da função renal é primordial para a prática médica. A taxa de filtração glomerular (TFG) é uma medição direta da função renal e é reduzida antes do início dos sintomas deinsuficiência renal. Determinar essa taxa é crucial para o diagnóstico e estadiamento da doença renal crônica (DRC) e para a avaliação da resposta aotratamento. A TFG pode ser estimada utilizando-se equações matemáticas empíricas baseadas na dosagem de creatinina sérica, como a MDRD e CKD-EPI. Seu uso tem sido incentivado como um meio simples, rápido e viável da avaliação da função renal. O objetivo deste estudo foi comparar a eTFG gerada pelas equações MDRD e CKD-EPI em indivíduos não diagnosticados com DRC. Foram selecionados noventa pacientes atendidos no Ambulatório do Hospital Universitário do Oeste do Paraná (HUOP). Entre os pacientesselecionados para o estudo, a e TFG média obtida, utilizando-se as fórmulas CKD-EPI e MDRD, foi de 91ml/min/1,73 m2 (DP±28) e 93 ml/min/1,73 m2 (DP±41). A taxa global de pacientes com eTFG <60 ml/min/1,73 m2 , utilizando-se o cálculo do CKD-EPI, foi de 14%e, com o MDRD, foi de 17%. Foi possível concluir que a TFG de pacientes ambulatoriais apresentando ou não comorbidades pré-existentes pode ser estimada tanto pela equação CKD-EPI quanto pelo estudo MDRD...

Application of MDRD and CKD-EPI equations in patients with peripheral arterial diseases / 中华肾脏病杂志

Objective To compare the performance of newly developed Chronic Kidney Disease Epideniology Collaboration (CKD-EPI) equation and Modification of Diet in Renal Disease (MDRD) equation in patients with peripheral arterial diseases (PAD).Methods A total of 841 patients with PAD were enrolled in this retrospective cohort study.Estimated glomerular filtration rate (eGFR), calculated by MDRD and CKD-EPI equation respectively, was analyzed by Spearman correlation analysis, Bland-Altman method and Kappa test for the evaluation of correlation and consistency.Net reclassification improvement (NRI) was adopted to compare the death risk assessment between these two equations.Results Although the eGFR was 4.33 ml· min-1 · (1.73 m2)-1 higher with MDRD equation than with CKD-EPI equation, there were still significant correlation and fine consistency between eGFRMDRD and eGFRCKD-EPI (Kappa: 0.749, r=0.991, P＜0.05).The CKD-EPI equation re-classified 9 (1.1％) patients upward to higher eGFR category and 143 (17.0％) patients downward to lower eGFR category.Besides, the performance of risk assessment for all-cause death was better with CKD-EPI equation than with MDRD equation (NRI=0.059, P ＜ 0.05), which was not the case for cardiovascular death (NRI=0.022, P ＞ 0.05).Conclusions There is no solid evidence suggesting that CKD-EPI equation performs better than MDRD equation.

Assessment of Renal Function and Predictive Performances of GFR Estimating Equations among Nigerian Diabetic Patients.

Aims: To assess the renal functions in Nigerian diabetic patients and to examine the predictive performances of Glomerular Filtration Rate (GFR) estimating equations. Study Design: A case-control study. Place and Duration of Study: Department of Physiology and University College Hospital, University of Ibadan, Ibadan, Nigeria. May-August, 2009. Methodology: One hundred and nine volunteers comprising 58 diabetic patients receiving treatments and 51 healthy individuals. Measured GFR (mGFR) was by creatinine clearance and the equations includes Cockcroft and Gault, CG; Modification of Diet in Renal Disease, MDRD study equation; Chronic Kidney Disease and Epidemiological study group, CKD-EPI and Mayo Clinic Quadratic, Q equation. Ethnicity factor was administered as appropriate. Performances were determined by mean bias, precision and accuracy. Results: mGFR was significantly (P=.05) reduced among the diabetic when compared with the non-diabetic though within the recommended range for normal renal function. Among the diabetics, CG equation has the least bias when compared with the mGFR but overestimated the GFR by 2.42ml/min/1.73m2 while Q has the highest bias. When the bias of other equations where compared with that of CG, the CKD/EPI formula significantly underestimated the GFR (P=.05) and the Q significantly overestimated GFR (P=.05). The highest precision was by CG and the least was found in the CKD/EPI though not significantly. The highest accuracy in this group was by CKD/EPI. In the nondiabetics, the least bias was recorded in the MDRD when compared with the mGFR while the highest was recorded in the CKD/EPI, the bias when compared with that of CG, the CKD significantly underestimated GFR by up to 7.54ml/min/1.73m2 (P=.001). Precision was highest in the Q though, not significant while its accuracy was significantly lower (P=.05) when compared with the CG. Adjustment for the ethnicity factor significantly overestimated GFR in our two study groups. Conclusion: Creatinine-based predictive equations are useful in estimating renal functions but the CG as well as the MDRD equations are more superior in their predictive ability among Nigerians and the use of the ethnicity factor is not recommended in Nigerian African as there is overestimation when used with the relevant equations.

Enfermedad renal crónica determinada mediante la creatinina sérica / Chronic kidney disease as measured by serum creatinine

La enfermedad renal crónica se relaciona con un mayor riesgo de enfermedad renal crónica terminal, de enfermedades cardiovasculares y de muerte, por lo que se requiere sudiagnóstico desde las primeras etapas de la enfermedad. Para ello, se disponen de un gran número de ecuaciones para estimar la tasa de filtración glomerular basadas en la concentración de creatinina sérica. Si bien la creatinina no es el analito ideal para estimar la filtración glomerular, ésta continuará empleándose hasta que haya una amplia disponibilidad en el medio de otros marcadores, como la cistatina C, por lo que el laboratorio clínico debe velar por la calidad analíticade los resultados y por lo tanto, debe determinar la creatinina a través de un método estandarizado frente a los procedimientos de medida de referencia. El objetivo de este módulo es revisar ladetección de la enfermedad renal crónica desde sus etapas iniciales, a partir de la creatinina sérica y de la estimación de la tasa de filtración glomerular.

Chronic kidney disease is associated with an increased risk of end-stage renal disease,cardiovascular diseases and death; hence, it is necessary to make a diagnosis in the early phasesof the disease. Many equations for estimating glomerular filtration rates are available for thispurpose, and are based on serum creatinine concentration. Although creatinine is not the idealanalyte to gauge glomerular filtration rate, it will be used until there is extensive availability of othermarkers, such as cystatin C. On these grounds, clinical laboratories must offer results with highstandards of quality control, and accordingly, they must measure serum creatinine with suitablemethods, previously standardized by reference measurement procedures. The aim of this moduleis to assess early diagnosis of chronic kidney disease through serum creatinine quantification andglomerular filtration rate estimation.

Comparative performance of the equations for estimating GFR in type 2 diabetic patients / 中华内分泌代谢杂志

Serum creatinine was determined by enzymatic method.99mTc-GFR was measured by 99mTc-DTPA dynamic renal imaging and considered as GFR marker in 210 males and 180 females with type 2 diabetes,eGFR was calculated by Cockcroft-Gault formula,MDRD equation7,abbreviated MDRD equation,modified MDRD equation for Chinese (c-7GFR4 and c-aGFR4),and CKD-EPI equation.They were analyzed by correlation,regression,Bland-Altman analysis and receiver operating characteristic (ROC) curve analysis.The correlation coefficients for Cockcroft-Gault formula,MDRD equation7,abbreviated MDRD equation,c-7GFR4,c-aGFR4,and CKD-EPI equation were 0.79,0.76,0.77,0.76,0.76,0.81 respectively.And the differences were-14.99,-18.85,-23.79,-25.85,-32.07,and-7.16,respectively.The area under ROC curves were 0.91,0.88,0.89,0.88,0.90,and 0.92,respeetively.Kappa values were 0.67、0.52、0.39、0.49、0.46、0.54respectively.The CKD-EPI equation seams to be the most accurate measurement among the six methods when the serum creatinine was determined by enzymatic method in Chinese type 2 diabetic patients.

Comparación entre las ecuaciones CKD-EPI y MDRD para la estimación del filtrado glomerular en pacientes con enfermedad renal crónica / Comparison between CKD-EPI and MDRD-equations to estimate glomerular filtration rate in chronic kidney disease patients

La ecuación MDRD para la estimación del índice de filtrado glomerular (IFG), es la estrategia más utilizada para evaluar pacientes con enfermedad renal crónica (ERC). Sin embargo, puede subestimar el IFG con el riesgo de asignar al paciente a estadios más avanzados de ERC. La nueva ecuación CKD-EPI, mejoraría la exactitud y precisión de las estimaciones. Sus autores sugieren que reemplace a la anterior. No habiendo comparaciones de estas ecuaciones aplicadas en un gran número de pacientes en nuestro país, nuestro objetivo fue realizarla en una amplia cohorte de pacientes. Se evaluó la concordancia de asignación en estadios de ERC entre ambas ecuaciones, tomando como referencia los datos surgidos de MDRD. Se calculó la media de las diferencias de los IFG obtenidos empleando ambas ecuaciones y se aplicó el análisis estadístico de Bland-Altman. Se estudió una cohorte de 9 319 pacientes con una media de creatinina sérica de 1.60 ± 1.03 mg/dl, 67% de sexo femenino y edad media 58 ± 20 años. En el grupo total, CKD-EPI presentó una media de IFG 0.61 ml/min/1.73 m² mayor que MDRD (p: NS). En los estadios 2 y 3A las medias del IFG fueron respectivamente 6.95 ± 4.76 y 3.21 ± 3.31, y la concordancia de 81 y 74%. El porcentaje de pacientes con un IFG menor de 60 ml/min/1.73 m², se redujo de 76.3% (MDRD) a 70.1% (CKD-EPI). Por lo tanto, la nueva ecuación CKD-EPI disminuye el número de pacientes con IFG debajo de 60 ml/min/1.73 m² y asigna estadios de IFG más elevado a un número mayor de pacientes.

The MDRD equation to estimate glomerular filtration rate (GFR) is the most widely used strategy to assess chronic kidney disease. Nonetheless, for the individual patient the true GFR can be underestimated with the risk of diagnosing a more elevated CKD stage. This novel CKD-EPI equation would improve accuracy and precision of estimations, and several authors recommend this new equation replace the former. In our country there is only a limited registration of these comparisons performed on a large number of patients. Therefore, our aim was to develop a comparison in a wide cohort of patients. The concordance between both equations to assign the GFR stages was determined by using the MDRD formula as a reference. The mean difference of GFR obtained with both equations as well as the Bland-Altman analysis were calculated. A cohort of 9 319 individuals, of whom 67% were females, aged 58 ± 20 years, with serum creatinine values of 1.6 ± 1.03 mg/dl, was studied. In the whole group, CKD-EPI displayed an average GFR 0.61 ml/min/1.73 m² larger than MDRD (p: NS). For CKD stages 2 and 3A the mean estimated GFR difference was 6.95 ± 4.76 and 3.21 ± 3.31, while the concordance was 81 and 74% respectively. The percentage of patients with GFR < 60 ml/min/1.73 m², decreased from 76.3% with the former equation to 70.1% with the latter. The novel equation CKD-EPI reduces the number of patients with GFR values lower than 60 ml/min/1.73 m² and consequently assigns a higher GFR stage to a considerable quantity of individuals.

Recomendações atuais para a detecção da nefropatia diabética / Guidelines for the detection of diabetic nephropathy

A nefropatia diabética (ND) é uma complicação crônica grave do diabetes melito (DM); é a principal causa de insuficiência renal terminal. A ND é classificada em 3 estágios conforme a excreção urinária de albumina (EUA): normoalbuminúria (EUA <17 mg/l), microalbuminúria (EUA 17-174 mg/l) e macroalbuminúria (>174 mg/l). Da fase de microalbuminúria pode ocorrer regressão para normoalbuminúria (30% casos) ou progressão para a macroalbuminúria, quando ocorre maior risco de evolução para a doença renal crônica (DRC) terminal. O diagnóstico da ND é realizado através da medida da albumina na urina e pela avaliação da taxa de filtração glomerular (TFG). Recomenda-se a medida da albumina em amostra isolada de urina (primeira da manhã ou amostra casual), podendo-se medir o índice albumina-creatinina ou a concentração de albumina. Valores elevados de albuminúria devem ser confirmados em pelo menos 2 de 3 coletas de urina, em um intervalo de 3 a 6 meses. Na impossibilidade da medida da albuminúria, a medida de proteínas totais (proteinúria @430 mg/l em amostra ou >500 mg/24 h), pode ser utilizada para diagnóstico de fases mais avançadas de ND. Em pacientes com DM tipo 2 o rastreamento deve iniciar ao diagnóstico de DM, e nos pacientes com DM tipo 1 deve ser após os 10 anos de idade; logo após o início da puberdade; ou quando a duração do DM for >5 anos. Se negativo repetir anualmente; e, se positivo, recomenda-se a monitoração mais frequente da albumina urinária. A estimativa da TFG é realizada através de fórmulas que empregam a creatinina sérica, ajustadas para idade, gênero e etnia. São recomendadas as equações do estudo Modification of Diet in Renal Disease (MDRD) e Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). Deve ser levado em conta que, em pacientes com DM, essas equações tendem a subestimar a TFG. A ND deve ser identificada o mais precocemente possível e para isto tanto os profissionais de saúde como os pacientes com DM devem ser conscientizados.

Diabetic nephropathy (DN) is an important chronic complication of diabetes mellitus (DM) and is the leading cause of end-staage renal disease. DN is classified into stages according to the urinary albumin excretion (UAE): normoalbuminuria (UAE <17 mg/l), microalbuminuria (UAE 17-174 mg/l), and macroalbuminuria (UAE >174 mg/l. From microalbuminuria there might be regression to normoalbuminuria (30% cases) or progression to macroalbuminuria, in which case there is higher risk of progression to advanced chronic kidney disease (CKD). DN has a high cardiovascular morbidity and mortality rate that is possibly more significant than the progression to terminal CKD. DN diagnosis is established by the measurement of albumin in the urine and assessment of glomerular filtration rate (GFR). The measurement of albumin in an isolated urine sample (first morning urine or random sample) is recommended, with the possibility of measuring albumin-creatinine ratio or albumin concentration. High levels of albuminuria should be confirmed by at least 2 out of 3 urine samples within a time interval of 3 to 6 months. If albuminuria cannot be measured, total protein level (proteinuria @ 430 mg/l in a sample or > 500 mg/24 h) can be used to diagnose advanced stages of DN. In patients with type 2 DM, screening should start upon diagnosis of DM, and in patients with type 1 DM, it should be started after the patient turns 10 years old; soon after the onset of puberty; or when the duration of DM is >5 years. In case of negative results, screening should be repeated annually and, if the result is positive, more frequent monitoring of urinary albumin is recommended. GFR estimation is calculated using formulas that employ serum creatinine adjusted for age, gender, and ethnicity. Modification of Diet in Renal Disease (MDRD) study and CKD-EPI (Chronic Kidney Disease - Epidemiology Collaboration) equations are the recommended. In patients with DM, this equation shows a tendency to underestimate GFR.