Search

14 p.-4 fig.-3 tab., Background 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., Methods 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 m2, 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., Results 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, Conclusions Kidney survival is significantly higher in patients with a chronicity score, Work in 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 MP), the Autonomous Region of Madrid (S2017/BMD-3673) (to MP). SRdeC is supported by Ministerio de Economia y Competitividad grant PID2019-104912RB-I00 y Autonomous Region of Madrid grant S2017/BMD-3673.

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.

Background and Aims Metformin is the antidiabetic of choice in patients with type 2 diabetes mellitus. Experimental studies and clinical observations have shown that metformin could have a beneficial effect on the progression of kidney disease through the activation of cAMP due to its anti-inflammatory, antifibrotic, and anti-oxidative action. The objective was to compare the progression of CKD in diabetic patients with or without metformin as antidiabetic in their treatment and the prevalence of cardiovascular events in both groups. Method Unicentric retrospective observational analysis. Inclusion criteria: outpatients seen in nephrology consultation during the year of 2012 with diabetes mellitus and stage 3 CKD. Renal, cardiovascular outcomes and mortality were analyzed between patients treated with / without metformin. Median follow-up of 76.5 months (41-84). Renal end-point: estimated glomerular filtration rate drop (MDRD-4) by 50% and / or start of dialysis program. Cardiovascular end-point: ischemic heart disease, stroke, arterial revascularization and / or amputation. Cardiovascular or any cause mortality. Results 148 patients (96M, 52W) with a mean age of 75±9 years and an eGFR of 40±9 ml / min / 1.73 m2 were included. In relation to hypoglycemic therapy: 45 received metformin, 61 insulin and 31 DPP4i. 80% received treatment with RAAS blockers. After the follow-up, the progression of the renal disease was greater in patients who did not receive metformin: eGFR fall of -7.0±16 vs -0.15±16 ml / min in those treated with metformin (p = 0.019). 25 patients in the group without metformin suffered a renal event vs. 5 in the metformin group (logRank: 4.186, p = 0.045). In the Cox analysis, metformin treatment decreases the progression of kidney disease in a model adjusted for baseline renal function and treatment with RAASB (HR 0.368, p = 0.043), losing its predictive power in a proteinuria-adjusted model. During the follow-up, 45 patients died (20 metformin, 25 non-metformin) and 45 patients suffered a cardiovascular event (15 metformin, 30 non-metformin), with no differences between the two groups. Conclusion Metformin treatment in patients with stage 3 CKD could slow the progression of CKD, this effect should be demonstrated in randomized studies with larger sample size.

Background and Aims Since the introduction of direct-acting antivirals (DAAs), few data have been published about kidney outcome in hepatitis C virus related mixed cryoglobulinaemia (HCV-MC) patients treated with combined DAAs and rituximab. We aimed to asses if combined treatment with DAAs and rituximab in patients with HCV-MC improves kidney survival and immunological response. Method Observational, multicentre, cohort study of 100 patients with HCV-MC from 14 Spanish centres treated with DAAs. Patients were followed up for a median duration of 138 months (11.5 years). Long-term kidney survival and immunological response were evaluated based on immunosuppressive treatment received. Kidney event was defined as duplication of creatinine level or 50% decrease in glomerular filtration rate, dependence on renal replacement therapy or non-reduction of proteinuria by 50% compared to baseline. Immunological response was defined as the decrease in cryocrit ≤1%. Results Sustained virological response was attained in 98 (98%) patients. 49 patients were treated with immunosuppressive treatment associated with DAAs, 26 with rituximab and the rest (23) with steroids and/or cyclophosphamide. Patients receiving immunosuppressive treatment had higher basal cryocrit (6.3±4.5 vs 3.8±3.9%, p=0.011), lower glomerular filtration rate (55±27 vs 68±25 ml/min/1.73 m2) and more haematuria (p=0.001). The 26 patients treated with rituximab had more severe disease: higher viral load (p=0.001), cryocrit (p=0.011), proteinuria (p=0.004), microhaematuria (p=0.012) and hypertension (p=0.012) and lower glomerular filtration rate (p=0.001). 15 patients had a kidney event at the end of follow-up. Predictive variables of kidney events were lower age (HR 0.94, 95%CI 0.89-0.99; P= 0.038) and lower glomerular filtrate rate (HR 0.97, 95%CI 0.94-0.99; p=0.026), in a model adjusted to proteinuria and microhaematuria. Immunosuppressive treatment with or without rituximab did not change kidney survival. Regarding the immunological response, only 19 patients had a cryocrit >1% at the end of follow-up. There were no differences in age, viral load, proteinuria and basal glomerular filtration rate between these patients with no immunological response and those who had a sustained immunological response over time. The only differences between these two groups were a higher basal cryocrit and a minor C4 levels. Immunosuppressive treatment with or without rituximab did not changed the immunological response. Conclusion Patients with more severe HCV-MC are those receiving immunosuppressive treatment. However, immunosuppressive treatment does not change kidney survival nor immunological response of these patients in the long term.

Introducción: El acetato cálcico/carbonato magnésico (MgCO3) es un quelante de fósforo con ventajas en cuanto a coste, seguridad y tolerancia, con similar eficacia a la de otros fármacos. El objetivo del estudio es evaluar los efectos sobre el metabolismo fosfocálcico al sustituir hidróxido de aluminio [Al(OH3)] por MgCO3 en una cohorte de pacientes en hemodiálisis. Material y métodos: Se incluyen 21 pacientes con fósforo < 5 mg/dl, con Al(OH3) como único quelante. La conversión a MgCO3 se realizó sin variar el número de comprimidos. Se registraron características clínico-demográficas, tratamiento para hiperparatiroidismo secundario y parámetros analíticos antes de la conversión, y mensualmente durante cuatro meses. Resultados: La fosforemia disminuyó de 4,52 ± 0,99 a 4,02 ± 1,07 mg/dl (p = 0,027), con una reducción del producto calcio-fósforo de 40,20 ± 10,44 a 35,16 ± 11,06 mg²/dl² (p = 0,037). No encontramos variaciones significativas en los niveles de calcio, hormona paratiroidea o 25-OH-vitamina D3. El número prescrito de comprimidos diarios se redujo de 3,33 ± 2,29 a 2,15 ± 2,21 (p = 0,020). Los tratamientos concomitantes no variaron. Observamos un aumento significativo inicial de la magnesemia de 2,21 ± 0,24 a 2,43 ± 0,39 mg/dl (p = 0,001), que posteriormente se mantuvo estable. Encontramos una disminución del aluminio sérico de 14,91 ± 8,55 a 8,47 ± 3,98 µg/l (p = 0,004), con niveles en rango recomendado en todos los pacientes. Conclusiones: El MgCO3 permite un buen control del fósforo sérico en pacientes en hemodiálisis previamente bien controlados con Al(OH)3, con menos comprimidos diarios. Se produce un ligero aumento en el magnesio sérico, sin significado clínico a corto plazo. Desconocemos los efectos de este aumento a más largo plazo. Introduction: Calcium acetate/magnesium carbonate (MgCO3) is a phosphorus binder with advantages in terms of cost, safety and tolerance and it has a similar efficacy to other drugs. The objective of the study is to assess the effects of replacing aluminium hydroxide [Al(OH3)] with MgCO3 on phosphorus and calcium metabolism in a cohort of haemodialysis patients. Materials and methods: We included 21 patients with phosphorus

Antecedentes: El síndrome metabólico (SM) es un factor de riesgo cardiovascular y de mortalidad en la población general y en pacientes con enfermedad renal crónica. Sin embargo, apenas se ha estudiado en pacientes en hemodiálisis (HD). Objetivos: El objetivo del estudio es analizar el efecto del SM sobre la aparición de eventos cardiovasculares en HD. El objetivo secundario es determinar la influencia del índice de tejido graso y del índice de conicidad en los eventos cardiovasculares. Métodos: Estudio prospectivo en el que se incluyeron 100 pacientes en HD. El tiempo de seguimiento es de 3 años. Se recogieron eventos cardiovasculares y mortalidad. Se definió SM según los criterios de ATPIII e IDF. Resultados: La prevalencia del SM definido por ATPIII es 32 % y por IDF 29 %. La concordancia entre las dos definiciones es elevada (índice kappa 0,79, intervalo de confianza 95 % 0,65-0,92). El riesgo de desarrollar un evento cardiovascular es mayor en pacientes con SM (log rank 6,185, p = 0,013), con índice de tejido graso mayor 11,5 kg/m² (log rank 10,220, p = 0,001) y con índice de conicidad mayor 1,2 (log rank 6,393, p = 0,011). En el análisis de Cox, ajustado a la edad y sexo, los pacientes con SM tienen el doble de riesgo de ingresar por un evento cardiovascular (odds ratio 1,93, 1,022-3,6, p = 0,043). La mortalidad fue 35 % en los 3 años de seguimiento sin diferencias entre los grupos con y sin SM. Conclusiones: El SM es una patología muy prevalente en pacientes en HD y su presencia duplica el riesgo de hospitalización por eventos cardiovasculares a corto plazo. Background: Metabolic syndrome (MS) is a cardiovascular risk factor and is associated with mortality in the general population and in patients with chronic kidney disease. However, few studies have been carried out in patients on haemodialysis (HD). Objectives: The objective of the study is to analyse the effect of MS on the occurrence of cardiovascular events in HD. The secondary objective is to determine the influence of the fat tissue index and conicity index on cardiovascular events. Methods: A prospective study including 100 patients on HD. The follow-up period was 3 years. Cardiovascular events and mortality were recorded. MS was defined in accordance with ATPIII and IDF criteria. Results: MS prevalence as defined by the ATPIII was 32%, and by the IDF, 29%. The concordance between the two definitions was high (kappa index 0.79, 95% confidence interval 0.65 to 0.92). The risk of cardiovascular events was higher in patients with MS (Log Rank 6.185, p = 0.013), with a fat tissue index greater than 11.5 kg/m² (log rank 10.220, p=.001) and a conicity index greater than 1.2 (log rank 6.393, p=.011). In the Cox analysis, adjusted for age and sex, patients with MS had twice the risk of being admitted due to a cardiovascular event (odds ratio 1.93, 1.022 to 3.6, p=.043). Mortality was 35% in the 3 year follow-up period with no differences between the groups with and without MS. Conclusions: MS is a very prevalent disease in HD patients and its presence doubles the risk of hospitalisation due to cardiovascular events in the short term.

Antecedentes: El síndrome metabólico (SM) es un factor de riesgo cardiovascular y de mortalidad en la población general y en pacientes con enfermedad renal crónica. Sin embargo, apenas se ha estudiado en pacientes en hemodiálisis (HD). Objetivos: El objetivo del estudio es analizar el efecto del SM sobre la aparición de eventos cardiovasculares en HD. El objetivo secundario es determinar la influencia del índice de tejido graso y del índice de conicidad en los eventos cardiovasculares. Métodos: Estudio prospectivo en el que se incluyeron 100 pacientes en HD. El tiempo de seguimiento es de 3 años. Se recogieron eventos cardiovasculares y mortalidad. Se definió SM según los criterios de ATPIII e IDF. Resultados: La prevalencia del SM definido por ATPIII es 32 % y por IDF 29 %. La concordancia entre las dos definiciones es elevada (índice kappa 0,79, intervalo de confianza 95 % 0,65-0,92). El riesgo de desarrollar un evento cardiovascular es mayor en pacientes con SM (log rank 6,185, p = 0,013), con índice de tejido graso mayor 11,5 kg/m² (log rank 10,220, p = 0,001) y con índice de conicidad mayor 1,2 (log rank 6,393, p = 0,011). En el análisis de Cox, ajustado a la edad y sexo, los pacientes con SM tienen el doble de riesgo de ingresar por un evento cardiovascular (odds ratio 1,93, 1,022-3,6, p = 0,043). La mortalidad fue 35 % en los 3 años de seguimiento sin diferencias entre los grupos con y sin SM. Conclusiones: El SM es una patología muy prevalente en pacientes en HD y su presencia duplica el riesgo de hospitalización por eventos cardiovasculares a corto plazo.

La malnutrición es un problema frecuente y un factor de riesgo de mortalidad en pacientes en hemodiálisis. Sin embargo, no existe un consenso para evaluarla. Objetivo: Evaluar la relación entre el estado nutricional medido por bioimpedancia espectroscópica (BIS) y los parámetros analíticos nutricionales, así como la evolución nutricional, valorada como sus modificaciones, en un año. Métodos: Estudio prospectivo observacional de 124 pacientes en hemodiálisis (edad 61,2 [±15,8] años, varones 62,9 %, diabéticos 33,1 %). Los parámetros analíticos nutricionales y la BIS se realizaron basalmente y al año. Resultados: El índice de masa magra (IMM) basal (medio 13,3 ± 3,6 kg/m²) se correlaciona de forma directa con el sexo masculino (p =0,01) e inversamente con la edad (p = 0,006). Basalmente el índice de masa grasa (IMG) (medio 11,2 ± 6,1 kg/m²)se correlaciona de forma directa con el índice de masa corporal (p < 0,001) y el sexo femenino (p = 0,004). No encontramos asociación con la comorbilidad o los parámetros inflamatorios. No observamos correlación entre las modificaciones de masa magra o masa grasa con las modificaciones de parámetros nutricionales. Los pacientes con ganancia de IMM (> 0 kg/m²) presentan albúmina sérica basal más baja (p = 0,017), menor IMM basal (p < 0,001) y mayor IMG basal (p = 0,027). Los pacientes con pérdida de IMG (< 0 kg/m²) presentan menores cifras de tensión arterial sistólica(p = 0,04). Conclusión: La valoración del estado nutricional mediante parámetros analíticos no presenta una buena relación con los parámetros de composición corporal ni con sus modificaciones.

La malnutrición es un problema frecuente y un factor de riesgo de mortalidad en pacientes en hemodiálisis. Sin embargo, no existe un consenso para evaluarla. Objetivo: Evaluar la relación entre el estado nutricional medido por bioimpedancia espectroscópica (BIS) y los parámetros analíticos nutricionales, así como la evolución nutricional, valorada como sus modificaciones, en un año. Métodos: Estudio prospectivo observacional de 124 pacientes en hemodiálisis (edad 61,2 [±15,8] años, varones 62,9 %, diabéticos 33,1 %). Los parámetros analíticos nutricionales y la BIS se realizaron basalmente y al año. Resultados: El índice de masa magra (IMM) basal (medio 13,3 ± 3,6 kg/m²) se correlaciona de forma directa con el sexo masculino (p =0,01) e inversamente con la edad (p = 0,006). Basalmente el índice de masa grasa (IMG) (medio 11,2 ± 6,1 kg/m²)se correlaciona de forma directa con el índice de masa corporal (p < 0,001) y el sexo femenino (p = 0,004). No encontramos asociación con la comorbilidad o los parámetros inflamatorios. No observamos correlación entre las modificaciones de masa magra o masa grasa con las modificaciones de parámetros nutricionales. Los pacientes con ganancia de IMM (> 0 kg/m²) presentan albúmina sérica basal más baja (p = 0,017), menor IMM basal (p < 0,001) y mayor IMG basal (p = 0,027). Los pacientes con pérdida de IMG (< 0 kg/m²) presentan menores cifras de tensión arterial sistólica(p = 0,04). Conclusión: La valoración del estado nutricional mediante parámetros analíticos no presenta una buena relación con los parámetros de composición corporal ni con sus modificaciones. Malnutrition is a common problem and a risk factor of mortality in haemodialysis patients. However, there is no consensus for its assessment. Objective: To assess the relationship between nutritional status, measured by bioimpedance spectrometry (BIS), and laboratory markers of nutritional status, as well as nutritional evolution and its changes after 1 year. Methods: We performed an observational prospective study on 124 haemodialysis patients (aged 61.2 [±15.8] years, 2.9% were males, 33.1% were diabetic. Laboratory markers of nutritional status and BIS were implemented at baseline and after one year. Results: At baseline, lean mass index (LMI) (13.3 [±3.6] Kg/m²) was inversely correlated with age (P=.006), and directly with male gender (P=.01). At baseline, the fat mass index (FMI) (mean 11.2 ± 6.1kg/m²) correlates directly with the body mass index (P0kg/m²) have lower baseline serum albumin (P=.017), lower baseline LMI (P

12 p.-4 fig.-4 tab., Rationale & objective: A previous study that evaluated associations of kidney biopsy findings with disease progression in patients with C3 glomerulopathy (C3G) proposed a prognostic histologic index (C3G-HI) that has not yet been validated. Our objective was to validate the performance of the C3G-HI in a new patient population., Study design: Multicenter, retrospective cohort study., Setting & participants: 111 patients fulfilling diagnostic criteria of C3G between January 1995 and December 2019, from 33 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases (GLOSEN)., Predictors: Demographic, clinical parameters, C3G-HI total activity score, and the C3G-HI total chronicity score., Outcome: Time to kidney failure., Analytical approach: Intraclass correlation coefficients and κ statistic were used to summarize inter-rater reproducibility for assessment of histopathology in kidney biopsies. The nonlinear relationships of risk of kidney failure with the total activity score and total chronicity score were modeled using Cox proportional hazards analysis that incorporated cubic splines., Results: The study group included 93 patients with C3 glomerulonephritis and 18 with dense-deposit disease. Participants had an overall meanage of 35±22 (SD) years. Forty-eight patients (43%) developed kidney failure after a mean follow-up of 65±27 months. The overall inter-rater reproducibility was very good for the total activity score (intraclass correlation coefficient [ICC]=0.63) and excellent for total chronicity score (ICC=0.89). Baseline estimated glomerular filtration rate (eGFR), 24-hour proteinuria, and treatment with immunosuppression were the main determinants of kidney failure in a model with only clinical variables. Only tubular atrophy and interstitial fibrosis were identified as predictors in a model with histological variables. When the total activity score and total chronicity score were added to the model, only the latter was identified as an independent predictor of kidney failure., Limitations: Only a subset of the kidney biopsies was centrally reviewed. Residual confounding., Conclusions: We validated the performance of C3G-HI as a predictor of kidney failure in patients with C3G. The total chronicity score was the principal histologic correlate of kidney failure., Work in this study was supported by the Instituto de Salud Carlos III /Fondo Europeo de Desarrollo Regional (ISCIII/FEDER) grant PI16/01685 and Red de Investigación Renal (RedInRen) (RD12/0021/0029) (to MP), the Autonomous Region of Madrid (S2017/BMD-3673) (to MP); EGdeJ is supported by the Spanish “Ministerio de Ciencia, Innovación y Universidades" (RYC-2013-13395 and RTI2018-095955-B-100).

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.