Incremento de peso en pacientes con fibrosis quística: ¿es siempre beneficioso?

Introduction: The primary objective of this study was to find out the prevalence of overweight and obese status, as well as their association to pulmonary function, total cholesterol and vitamin D in patients with cystic fibrosis (CF). Materials and methods: This is a multicenter descriptive and cross-sectional study. Twelve Spanish hospitals participated. 451 patients with CF were included. Adults were classified according to body mass index (BMI) and children were classified according to BMI percentiles (WHO tables). Pearson’s correlation, Anova, Student’s t-test and multiple linear regression were conducted. Results: Mean age was 12.3 (range 4-57) years old, 51% were male and 18% had pancreatic sufficiency. Participants were classified in five nutritional status categories: 12% were malnourished; 57%, at nutritional risk; 24%, normally nourished; 6%, overweight; and 1%, obese. Pulmonary function in overweight or obese patients (91 ± 19%) was better than in malnourished patients (77 ± 24%) (p = 0.017). However, no difference was observed between those at nutritional risk (86 ± 19%) or normally nourished (90 ± 22%) groups. Overweight and obese patients had higher levels of total cholesterol (p = 0.0049), a greater proportion of hypercholesterolemia (p = 0.001), as well as lower levels of 25 OH vitamin D (p = 0.058). Conclusions: Prevalence of overweight and obese was 6 and 1%. Excess weight status does not offer any benefit in pulmonary function in comparison to normally nourished patientsIntroducción y objetivos: conocer la prevalencia de sobrepeso y obesidad, así como su asociación con la función pulmonar, el colesterol total y la vitamina D en pacientes con fi brosis quística (FQ). Material y métodos: estudio multicéntrico descriptivo y transversal. Participaron 12 hospitales españoles. Fueron incluidos 451 pacientes con FQ, clasifi cados según el índice de masa corporal (IMC) en adultos y el IMC percentilado (tablas OMS) en niños. Análisis estadístico: C.Pearson, Anova, t de Student y regresión lineal múltiple. Resultados: la mediana de edad fue 12,3 (rango 4-57) años. Un 51% eran varones y el 18%, sufi cientes pancreáticos (SP). El 12% estaba desnutrido; el 57%, en riesgo nutricional; el 24%, normonutrido; el 6% presentaba sobrepeso; y un 1%, obesidad. La función pulmonar en los pacientes con sobrepeso (91 ± 19%) era mejor que en los desnutridos (77 ± 24%) (p = 0,017), sin embargo, no se observaron diferencias con respecto a los que estaban en riesgo nutricional (86 ± 19%) o normonutridos (90 ± 22%). Los pacientes con sobrepeso tenían más elevado el colesterol total (p = 0,0049), mayor proporción de hipercolesterolemia (p = 0,001), así como niveles más bajos de 25 OH vitamina D (p = 0,058). Conclusiones: la prevalencia de sobrepeso y obesidad fue del 6 y el 1%. El sobrepeso y la obesidad no ofrecen benefi cio sobre la función pulmonar en comparación con los normonutrido

Vitamin d and chronic lung colonization in pediatric and young adults cystic fibrosis patients

Introducción y objetivos: conocer la situación en la que se encuentran los pacientes con fibrosis quística en relación con sus niveles de vitamina D y su asociación con las colonizaciones pulmonares crónicas. Material y métodos: estudio multicéntrico transversal. Participaron 12 hospitales nacionales. De noviembre a abril del 2012 al 2014 se incluyeron 377 pacientes con fibrosis quística. Se consideraron insuficientes niveles de vitamina D < 30 ng/ml. Presentar al menos dos cultivos positivos en el último año fue considerado un criterio de colonización crónica. Resultados: los pacientes tenían una mediana de edad de 8,9 años (2 meses—20 años). Un 65% presentaban niveles insuficientes de vitamina D. Se observó una correlación inversa entre edad y niveles de vitamina D (r = -0,20 p < 0,001). Los diagnosticados por cribado eran más jóvenes y tenían niveles de vitamina D más altos. Los niveles de vitamina D presentaron una correlación inversa con el número de colonizaciones pulmonares (r = -0,16 p = 0,0015). Ajustando por edad, función pancreática y diagnóstico mediante cribado, la colonización por S. Aureus en menores de seis años y por Pseudomonas sp. en los mayores de esa edad, incrementaban el riesgo de presentar niveles insuficientes de vitamina D: OR 3,17 (IC95% 1,32-7,61) (p=0,010) y OR 3,77 (IC95% 1,37- 10,37)(p = 0,010), respectivamente. Conclusiones: a pesar de una suplementación adecuada, más de la mitad de nuestros pacientes no alcanzan niveles óptimos de vitamina D. La colonización crónica por Pseudomonas sp. en escolares y adolescentes y por S. Aureus en lactantes y preescolares se asocia de forma independiente con la deficiencia de vitamina D.Introduction and objectives: evaluate vitamin D status and its association with chronic lung colonisation in Cystic Fibrosis patients. Material and methods: descriptive cross-sectional multicenter study. From November 2012 to April 2014, at 12 national hospitals, 377 patients with Cystic Fibrosis were included. Vitamin D levels < 30 ng/ml were classified as insufficient. Chronic colonisation was considered if they had at least two positive cultures in the past year. Results: the median age was 8.9 years (2 months to 20 years). 65% had insufficient levels of vitamin D. There was an inverse correlation between age and vitamin D levels (r = -0.20 p < 0.001). Those diagnosed by screening, were younger and had higher levels of vitamin D. There was an inverse correlation between the number of colonisations and vitamin D levels (r = -0.16 p = 0.0015). Adjusting for age, pancreatic status and diagnosis by screening, colonization by S. aureus in <6 years and Pseudomonas sp. in > 6 years, increased the risk of insufficient levels of vitamin D: OR 3.17 (95% CI 1.32 to 7.61) (p = 0.010) and OR 3.77 (95% CI 1.37 to 10 , 37) (p = 0.010), respectively. Conclusions: despite adequate supplementation, more than half of our patients did not achieve optimal levels of vitamin D. Regardless of age, diagnosis by screening or pancreatic status, chronic colonization by Pseudomonas sp. in children and adolescents and S. Aureus in infants and preschoolars increases the risk of developing vitamin D deficiency in these patients.S

Longitudinal change in proteinuria and kidney outcomes in C3 glomerulopathy

11 p.-4 fig.-4 tab.Introduction: The association between a change in proteinuria over time and its impact in kidney prognosis has not been analyzed in C3 glomerulopathy. This study aims to investigate the association between the longitudinal change in proteinuria and the risk of kidney failure.Methods: Retrospective, multicenter observational cohort study in 35 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases (GLOSEN). Patients diagnosed with C3 glomerulopathy between 1995 and 2020 were enrolled. A joint modeling of linear mixed-effects models was applied to assess the underlying trajectory of a repeatedly measured proteinuria, and a Cox model to evaluate the association of this trajectory with the risk of kidney failure.Results: The study group consisted of 85 patients, 70 C3 glomerulonephritis and 15 dense deposit disease, with a median age of 26 years (range 13-41). During a median follow-up of 42 months, 25 patients reached kidney failure. The longitudinal change in proteinuria showed a strong association with the risk of this outcome, with a doubling of proteinuria levels resulting in a 2.5-fold increase of the risk. A second model showed that a ≥ 50% proteinuria reduction over time was significantly associated with a lower risk of kidney failure (HR: 0.79; 95% CI : 0.56-0.97; p < 0.001). This association was also found when the ≥50% proteinuria reduction was observed within the first 6 and 12 months of follow-up.Conclusion: The longitudinal change in proteinuria is strongly associated with the risk of kidney failure. The change in proteinuria over time can provide clinicians a dynamic prediction of kidney outcomes.This study was supported by the Instituto de Salud Carlos III/Fondo Europeo de Desarrollo Regional (ISCIII/FEDER) grant PI16/01685 and PI19/1624, and Red de Investigación Renal (RedInRen) (RD12/0021/0029) (to M.P.), the Autonomous Region of Madrid (S2017/BMD-3673) (to M.P.); E.G.d.J. was supported by the Spanish ‘Ministerio de Ciencia, Innovación y Universidades’ (RYC-2013-13395 and RTI2018-095955-B-100); S.R.d.C. was supported by Ministerio de Economía y Competitividad/FEDER grant SAF2015-66287R and Autonomous Region of Madrid grant S2017/BMD3673.Peer reviewe

Development and validation of a nomogram to predict kidney survival at baseline in patients with C3 glomerulopathy

10 p.-4 fig.-2 tab. 1 graph. abst.Background: C3 glomerulopathy is a rare and heterogeneous complement-driven disease. It is often challenging to accurately predict in clinical practice the individual kidney prognosis at baseline. We herein sought to develop and validate a prognostic nomogram to predict long-term kidney survival.Methods: We conducted a retrospective, multicenter observational cohort study in 35 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases. The dataset was randomly divided into a training group (n = 87) and a validation group (n = 28). The least absolute shrinkage and selection operator (LASSO) regression was used to screen the main predictors of kidney outcome and to build the nomogram. The accuracy of the nomogram was assessed by discrimination and risk calibration in the training and validation sets.Results: The study group comprised 115 patients, of whom 46 (40%) reached kidney failure in a median follow-up of 49 months (range 24–112). No significant differences were observed in baseline estimated glomerular filtration rate (eGFR), proteinuria or total chronicity score of kidney biopsies, between patients in the training versus those in the validation set. The selected variables by LASSO were eGFR, proteinuria and total chronicity score. Based on a Cox model, a nomogram was developed for the prediction of kidney survival at 1, 2, 5 and 10 years from diagnosis. The C-index of the nomogram was 0.860 (95% confidence interval 0.834–0.887) and calibration plots showed optimal agreement between predicted and observed outcomes.Conclusions: We constructed and validated a practical nomogram with good discrimination and calibration to predict the risk of kidney failure in C3 glomerulopathy patients at 1, 2, 5 and 10 years.Work on this study was supported by the Instituto de Salud Carlos III / Fondo Europeo de Desarrollo Regional (ISCIII/FEDER; grants PI16/01685 and PI19/1624) and Red de Investigación Renal (RD12/0021/0029; to M.P.) and the Autonomous Region of Madrid (S2017/BMD-3673; to M.P.). S.R.d.C. is supported by the Ministerio de Economia y Competitividad (grant PID2019-104912RB-I00) and the Autonomous Region of Madrid (grant S2017/BMD-3673).Peer reviewe

Clinical Profiles and Patterns of Kidney Disease Progression in C3 Glomerulopathy

C3 glomerulopathy is a rare kidney disease, which makes it difficult to collect large cohorts of patients to better understand its variability. The aims of this study were to describe the clinical profiles and patterns of progression of kidney disease. This was a retrospective, observational cohort study. Patients diagnosed with C3 glomerulopathy between 1995 and 2020 were enrolled. Study population was divided into clinical profiles by combining the following predictors: eGFR under/above 30 ml/min per 1.73 m 2, proteinuria under/above 3.5 g/d, and histologic chronicity score under/above 4. The change in eGFR and proteinuria over time was evaluated in a subgroup with consecutive measurements of eGFR and proteinuria. One hundred and fifteen patients with a median age of 30 years (interquartile range 19-50) were included. Patients were divided into eight clinical profiles. Kidney survival was significantly higher in patients with a chronicity score <4 and proteinuria <3.5 g/d, both in those presenting with an eGFR under/above 30 ml/min per 1.73 m 2. The median eGFR slope of patients who reached kidney failure was −6.5 ml/min per 1.73 m 2 per year (interquartile range −1.6 to −17). Patients who showed a reduction in proteinuria over time did not reach kidney failure. On the basis of the rate of eGFR decline, patients were classified as faster eGFR decline (≥5 ml/min per 1.73 m 2 per year), slower (<5 ml/min per 1.73 m 2 per year), and those without decline. A faster eGFR decline was associated with higher probability of kidney failure. Kidney survival is significantly higher in patients with a chronicity score <4 and proteinuria <3.5 g/d regardless of baseline eGFR, and a faster rate of decline in eGFR is associated with higher probability of kidney failure

Longitudinal change in proteinuria and kidney outcomes in C3 glomerulopathy

11 p.-4 fig.-4 tab.Introduction: The association between a change in proteinuria over time and its impact in kidney prognosis has not been analyzed in C3 glomerulopathy. This study aims to investigate the association between the longitudinal change in proteinuria and the risk of kidney failure.Methods: Retrospective, multicenter observational cohort study in 35 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases (GLOSEN). Patients diagnosed with C3 glomerulopathy between 1995 and 2020 were enrolled. A joint modeling of linear mixed-effects models was applied to assess the underlying trajectory of a repeatedly measured proteinuria, and a Cox model to evaluate the association of this trajectory with the risk of kidney failure.Results: The study group consisted of 85 patients, 70 C3 glomerulonephritis and 15 dense deposit disease, with a median age of 26 years (range 13-41). During a median follow-up of 42 months, 25 patients reached kidney failure. The longitudinal change in proteinuria showed a strong association with the risk of this outcome, with a doubling of proteinuria levels resulting in a 2.5-fold increase of the risk. A second model showed that a ≥ 50% proteinuria reduction over time was significantly associated with a lower risk of kidney failure (HR: 0.79; 95% CI : 0.56-0.97; p < 0.001). This association was also found when the ≥50% proteinuria reduction was observed within the first 6 and 12 months of follow-up.Conclusion: The longitudinal change in proteinuria is strongly associated with the risk of kidney failure. The change in proteinuria over time can provide clinicians a dynamic prediction of kidney outcomes.This study was supported by the Instituto de Salud Carlos III/Fondo Europeo de Desarrollo Regional (ISCIII/FEDER) grant PI16/01685 and PI19/1624, and Red de Investigación Renal (RedInRen) (RD12/0021/0029) (to M.P.), the Autonomous Region of Madrid (S2017/BMD-3673) (to M.P.); E.G.d.J. was supported by the Spanish ‘Ministerio de Ciencia, Innovación y Universidades’ (RYC-2013-13395 and RTI2018-095955-B-100); S.R.d.C. was supported by Ministerio de Economía y Competitividad/FEDER grant SAF2015-66287R and Autonomous Region of Madrid grant S2017/BMD3673.Peer reviewe

Mycophenolate Mofetil in C3 Glomerulopathy and Pathogenic Drivers of the Disease

12 p.-4 fig.-4 tab.BACKGROUND AND OBJECTIVES: C3 glomerulopathy is a complement-mediated disease arising from abnormalities in complement genes and/or antibodies against complement components. Previous studies showed that treatment with corticosteroids plus mycophenolate mofetil (MMF) was associated with improved outcomes, although the genetic profile of these patients was not systematically analyzed. This study aims to analyze the main determinants of disease progression and response to this therapeutic regimen.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective, multicenter, observational cohort study in 35 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases. Patients diagnosed with C3 glomerulopathy (n=81) or dense deposit disease (n=16) between January 1995 and March 2018 were enrolled. Multivariable and propensity score matching analyses were used to evaluate the association of clinical and genetic factors with response to treatment with corticosteroids and MMF as measured by proportion of patients with disease remission and kidney survival (status free of kidney failure).RESULTS: The study group comprised 97 patients (84% C3 glomerulopathy, 16% dense deposit disease). Forty-two patients were treated with corticosteroids plus MMF, and this treatment was associated with a higher rate of remission and lower probability of kidney failure (79% and 14%, respectively) compared with patients treated with other immunosuppressives (24% and 59%, respectively), or ecluzimab (33% and 67%, respectively), or conservative management (18% and 65%, respectively). The therapeutic superiority of corticosteroids plus MMF was observed both in patients with complement abnormalities and with autoantibodies. However, patients with pathogenic variants in complement genes only achieved partial remission, whereas complete remissions were common among patients with autoantibody-mediated forms. The main determinant of no remission was baseline proteinuria. Relapses occurred after treatment discontinuation in 33% of the patients who had achieved remission with corticosteroids plus MMF, and a longer treatment length of MMF was associated with a lower risk of relapse.CONCLUSIONS: The beneficial response to corticosteroids plus MMF treatment in C3 glomerulopathy appears independent of the pathogenic drivers analyzed in this study.Work in this study was supported by the Instituto de Salud CarlosIII/ Fondo Europeo de Desarrollo Regional (ISCIII/FEDER) grant PI16/01685 and Red de Investigación Renal (RedInRen) (RD12/0021/0029) (to M. Praga), and the Autonomous Region of Madrid (S2017/BMD-3673) (to S. Rodríguez de Córdoba and M. Praga).E. Goicoechea de Jorge is supported by the Spanish “Ministerio de Ciencia, Innovación y Universidades” (RYC-2013-13395 and RTI2018-095955-B-100). S. Rodríguez de Córdoba is supported by Ministerio de Economía y Competitividad/FEDER grant SAF2015-66287R and Autonomous Region of Madrid grant S2017/BMD3673.Peer reviewe

Mycophenolate Mofetil in C3 glomerulopathy and pathogenic drivers of the disease

12 p.-4 fig.-4 tab.BACKGROUND AND OBJECTIVES: C3 glomerulopathy is a complement-mediated disease arising from abnormalities in complement genes and/or antibodies against complement components. Previous studies showed that treatment with corticosteroids plus mycophenolate mofetil (MMF) was associated with improved outcomes, although the genetic profile of these patients was not systematically analyzed. This study aims to analyze the main determinants of disease progression and response to this therapeutic regimen.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective, multicenter, observational cohort study in 35 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases. Patients diagnosed with C3 glomerulopathy (n=81) or dense deposit disease (n=16) between January 1995 and March 2018 were enrolled. Multivariable and propensity score matching analyses were used to evaluate the association of clinical and genetic factors with response to treatment with corticosteroids and MMF as measured by proportion of patients with disease remission and kidney survival (status free of kidney failure).RESULTS: The study group comprised 97 patients (84% C3 glomerulopathy, 16% dense deposit disease). Forty-two patients were treated with corticosteroids plus MMF, and this treatment was associated with a higher rate of remission and lower probability of kidney failure (79% and 14%, respectively) compared with patients treated with other immunosuppressives (24% and 59%, respectively), or ecluzimab (33% and 67%, respectively), or conservative management (18% and 65%, respectively). The therapeutic superiority of corticosteroids plus MMF was observed both in patients with complement abnormalities and with autoantibodies. However, patients with pathogenic variants in complement genes only achieved partial remission, whereas complete remissions were common among patients with autoantibody-mediated forms. The main determinant of no remission was baseline proteinuria. Relapses occurred after treatment discontinuation in 33% of the patients who had achieved remission with corticosteroids plus MMF, and a longer treatment length of MMF was associated with a lower risk of relapse.CONCLUSIONS: The beneficial response to corticosteroids plus MMF treatment in C3 glomerulopathy appears independent of the pathogenic drivers analyzed in this study.Work in this study was supported by the Instituto de Salud CarlosIII/ Fondo Europeo de Desarrollo Regional (ISCIII/FEDER) grant PI16/01685 and Red de Investigación Renal (RedInRen) (RD12/0021/0029) (to M. Praga), and the Autonomous Region of Madrid (S2017/BMD-3673) (to S. Rodríguez de Córdoba and M. Praga).E. Goicoechea de Jorge is supported by the Spanish “Ministerio de Ciencia, Innovación y Universidades” (RYC-2013-13395 and RTI2018-095955-B-100). S. Rodríguez de Córdoba is supported by Ministerio de Economía y Competitividad/FEDER grant SAF2015-66287R and Autonomous Region of Madrid grant S2017/BMD3673.Peer reviewe