Tubular biomarkers in proteinuric kidney disease: histology correlation and kidney prognosis of tubular biomarkers.

Background: Proteinuria is not only a biomarker of chronic kidney disease (CKD) but also a driver of CKD progression. The aim of this study was to evaluate serum and urinary tubular biomarkers in patients with biopsied proteinuric kidney disease and to correlate them with histology and kidney outcomes. Methods: A single-center retrospective study was conducted on a cohort of 156 patients from January 2016 to December 2021. The following urinary and serum biomarkers were analyzed on the day of kidney biopsy: beta 2 microglobulin (ß2-mcg), alpha 1 microglobulin (α1-mcg), neutrophil gelatinase-associated lipocalin (NGAL), urinary kidney injury molecule-1 (uKIM-1), monocyte chemoattractant protein-1 (MCP-1), urinary Dickkopf-3 (uDKK3), uromodulin (urinary uUMOD), serum kidney injury molecule-1 (sKIM-1) and serum uromodulin (sUMOD). A composite outcome of kidney progression or death was recorded during a median follow-up period of 26 months. Results: Multivariate regression analysis identified sUMOD (ß-0.357, P < .001) and uDKK3 (ß 0.483, P < .001) as independent predictors of interstitial fibrosis, adjusted for age, estimated glomerular filtration rate (eGFR) and log proteinuria. Elevated levels of MCP-1 [odds ratio 15.61, 95% confidence interval (CI) 3.52-69.20] were associated with a higher risk of cortical interstitial inflammation >10% adjusted for eGFR, log proteinuria and microhematuria. Upper tertiles of uDKK3 were associated with greater eGFR decline during follow-up. Although not a predictor of the composite outcome, doubling of uDKK3 was a predictor of kidney events (hazard ratio 2.26, 95% CI 1.04-4.94) after adjustment for interstitial fibrosis, eGFR and proteinuria. Conclusions: Tubular markers may have prognostic value in proteinuric kidney disease, correlating with specific histologic parameters and identifying cases at higher risk of CKD progression.

Sodium-glucose cotransporter 2 inhibition in primary and secondary glomerulonephritis.

BACKGROUND: The role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the management glomerular/systemic autoimmune diseases with proteinuria in real-world clinical settings is unclear. METHODS: This is a retrospective, observational, international cohort study. Adult patients with biopsy-proven glomerular diseases were included. The main outcome was the percentage reduction in 24-h proteinuria from SGLT2i initiation to 3, 6, 9 and 12 months. Secondary outcomes included percentage change in estimated glomerular filtration rate (eGFR), proteinuria reduction by type of disease and reduction of proteinuria ≥30% from SGLT2i initiation. RESULTS: Four-hundred and ninety-three patients with a median age of 55 years and background therapy with renin-angiotensin system blockers were included. Proteinuria from baseline changed by -35%, -41%, -45% and -48% at 3, 6, 9 and 12 months after SGLT2i initiation, while eGFR changed by -6%, -3%, -8% and -10.5% at 3, 6, 9 and 12 months, respectively. Results were similar irrespective of the underlying disease. A correlation was found between body mass index (BMI) and percentage proteinuria reduction at last follow-up. By mixed-effects logistic regression model, serum albumin at SGLT2i initiation emerged as a predictor of ≥30% proteinuria reduction (odds ratio for albumin <3.5 g/dL, 0.53; 95% CI 0.30-0.91; P = .02). A slower eGFR decline was observed in patients achieving a ≥30% proteinuria reduction: -3.7 versus -5.3 mL/min/1.73 m2/year (P = .001). The overall tolerance to SGLT2i was good. CONCLUSIONS: The use of SGLT2i was associated with a significant reduction of proteinuria. This percentage change is greater in patients with higher BMI. Higher serum albumin at SGLT2i onset is associated with higher probability of achieving a ≥30% proteinuria reduction.

Obesity, chronic kidney disease progression and the role of the adipokine C1q/TNF related protein-3 / Relación entre la adipoquina C1q/TNF-Related Protein 3, obesidad y progresión de la enfermedad renal crónica

Introduction and aims: Obesity is a risk factor for incident chronic kidney disease (CKD). C1q/TNF related protein 3 (CTRP3) is an adipokine with multiple effects and may modulate the association between obesity and vascular diseases. The aim of the study is to explore potential links between obesity, CTRP3 levels and CKD progression. Methods: Patients with stage 3 and 4 CKD without previous cardiovascular events were enrolled and divided into groups according to body mass index (BMI) and sex. Demographic, clinical, analytical data and CTRP3 levels were collected at baseline. During follow-up, renal events (defined as dialysis initiation, serum creatinine doubling or a 50% decrease in estimated glomerular filtration rate were registered). Results: 81 patients were enrolled. 27 were obese and 54 non-obese. Baseline CTRP3 was similar between both groups (90.1±23.8 vs 84.5±6.2; p=0.28). Of the sum, 54 were men and 27 women, with higher CTRP3 in women (81.4±24.7 vs 106±24.7;p<0.01). During a mean follow-up of 68 months, 15 patients had a renal event. Patients in the higher CTRP3 tertile had less events but without statistical significance (p=0.07). Obese patients in the higher CTRP3 tertile significantly had less renal events (p=0.049). By multiple regression analysis CTRP3 levels could not predict renal events (HR 0.98; CI95% 0.96–1.06). Conclusions: CTRP3 levels are higher in woman than men in patients with CKD, with similar levels between obese and non obese. Higher CTRP3 levels at baseline were associated with better renal outcomes in obese patients. (AU)

Introducción: La obesidad es un factor de riesgo de la enfermedad renal crónica (ERC) incidente. La proteína 3 relacionada con C1q/TNF (CTRP3) es una adipoquina que puede modular la asociación entre obesidad y enfermedades vasculares. El objetivo del estudio es explorar los posibles vínculos entre obesidad, CTRP3 y progresión de ERC. Métodos: Pacientes con ERC estadio 3 y 4 sin eventos cardiovasculares previos fueron reclutados y divididos según el índice de masa corporal y sexo. Los datos demográficos, clínicos, analíticos y los niveles de CTRP3 se recopilaron basalmente. Durante el seguimiento se registraron eventos renales (inicio de diálisis, duplicación de la creatinina o una disminución del 50% en la filtración glomerular estimada). Resultados: Se reclutaron 81 pacientes, 27 obesos y 54 no obesos. LA CTRP3 inicial fue similar en ambos grupos (90,1±23,8 vs. 84,5±6,2; p=0,28). Del total, 54 eran varones y 27 mujeres, con mayor CTRP3 en mujeres (81,4±24,7 vs. 106±24,7; p<0,01). Durante un seguimiento medio de 68 meses, 15 pacientes sufrieron un evento renal. Los pacientes en el tercil superior de CTRP3 tuvieron menos eventos, pero sin significación estadística (p=0,07). Los pacientes obesos en el tercil superior de CTRP3 tuvieron significativamente menos eventos renales (p=0,049). Por análisis de regresión múltiple, los niveles de CTRP3 no pudieron predecir eventos renales (HR: 0,98; IC 95%: 0,96-1,06). Conclusiones: Los niveles de CTRP3 son más altos en mujeres que en varones en pacientes con ERC, con niveles similares entre obesos y no obesos. Valores iniciales mayores de CTRP3 se asociaron con mejores resultados renales en pacientes obesos. (AU)

Obesity, chronic kidney disease progression and the role of the adipokine C1q/TNF related protein-3.

INTRODUCTION AND AIMS: Obesity is a risk factor for incident chronic kidney disease (CKD). C1q/TNF related protein 3 (CTRP3) is an adipokine with multiple effects and may modulate the association between obesity and vascular diseases. The aim of the study is to explore potential links between obesity, CTRP3 levels and CKD progression. METHODS: Patients with stage 3 and 4 CKD without previous cardiovascular events were enrolled and divided into groups according to body mass index (BMI) and sex. Demographic, clinical, analytical data and CTRP3 levels were collected at baseline. During follow-up, renal events (defined as dialysis initiation, serum creatinine doubling or a 50% decrease in estimated glomerular filtration rate were registered). RESULTS: 81 patients were enrolled. 27 were obese and 54 non-obese. Baseline CTRP3 was similar between both groups (90.1±23.8 vs 84.5±6.2; p=0.28). Of the sum, 54 were men and 27 women, with higher CTRP3 in women (81.4±24.7 vs 106±24.7;p<0.01). During a mean follow-up of 68 months, 15 patients had a renal event. Patients in the higher CTRP3 tertile had less events but without statistical significance (p=0.07). Obese patients in the higher CTRP3 tertile significantly had less renal events (p=0.049). By multiple regression analysis CTRP3 levels could not predict renal events (HR 0.98; CI95% 0.96-1.06). CONCLUSIONS: CTRP3 levels are higher in woman than men in patients with CKD, with similar levels between obese and non obese. Higher CTRP3 levels at baseline were associated with better renal outcomes in obese patients.

Use of renin–angiotensin–aldosterone system blockade in controversial chronic kidney disease populations

Renin–angiotensin–aldosterone system blockers have shown to be effective in controlling blood pressure and proteinuria, slowing the progression to end stage renal disease and reducing cardiovascular risk, so they are the mainstream treatment of hypertension in chronic kidney disease. Their beneficial effects have been proven in multiple randomized clinical trials on different study populations, but there has recently been some controversial data on its use in some subgroups of patients, especially those with advanced chronic kidney disease. In some other populations such as patients with non-proteinuric nephropathies or the elderly, who can be more susceptible to its adverse events, their benefits have also been questioned.The aim of the present review is to collect available published data on the effect of renin–angiotensin–aldosterone system blockers in some controversial populations and provide perspective on future research areas in this field. (AU)

Los bloqueantes del sistema renina-angiotensina-aldosterona han demostrado ser efectivos en el control de la tensión arterial y la proteinuria, enlenteciendo la progresión a enfermedad renal terminal, y reduciendo el riesgo cardiovascular, por lo que son el tratamiento de primera línea de la hipertensión en pacientes con enfermedad renal crónica. Sus efectos beneficiosos han sido demostrados en múltiples ensayos clínicos en diferentes poblaciones de estudio, pero recientemente se han publicado datos controvertidos a cerca de su uso en determinados subgrupos de pacientes, especialmente aquellos con enfermedad renal crónica avanzada. En otras poblaciones como los pacientes con nefropatías no proteinúricas o en ancianos, que pueden ser especialmente sensibles a sus efectos secundarios, sus beneficios han sido, así mismo cuestionados.El objetivo de la presente revisión es recoger la evidencia disponible sobre el efecto de los bloqueantes del sistema renina-angiotensina-aldosterona en poblaciones controvertidas y arrojar perspectivas en cuanto a posibles áreas de investigación en este campo. (AU)

Use of renin-angiotensin-aldosterone system blockade in controversial chronic kidney disease populations.

Renin-angiotensin-aldosterone system blockers have shown to be effective in controlling blood pressure and proteinuria, slowing the progression to end stage renal disease and reducing cardiovascular risk, so they are the mainstream treatment of hypertension in chronic kidney disease. Their beneficial effects have been proven in multiple randomized clinical trials on different study populations, but there has recently been some controversial data on its use in some subgroups of patients, especially those with advanced chronic kidney disease. In some other populations such as patients with non-proteinuric nephropathies or the elderly, who can be more susceptible to its adverse events, their benefits have also been questioned. The aim of the present review is to collect available published data on the effect of renin-angiotensin-aldosterone system blockers in some controversial populations and provide perspective on future research areas in this field.

COVID-19: clinical course and outcomes of 36 hemodialysis patients in Spain.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia emerged in Wuhan, China in December 2019. Unfortunately, there is a lack of evidence about the optimal management of novel coronavirus disease 2019 (COVID-19), and even less is available in patients on maintenance hemodialysis therapy than in the general population. In this retrospective, observational, single-center study, we analyzed the clinical course and outcomes of all maintenance hemodialysis patients hospitalized with COVID-19 from March 12th to April 10th, 2020 as confirmed by real-time polymerase chain reaction. Baseline features, clinical course, laboratory data, and different therapies were compared between survivors and nonsurvivors to identify risk factors associated with mortality. Among the 36 patients, 11 (30.5%) died, and 7 were able to be discharged within the observation period. Clinical and radiological evolution during the first week of admission were predictive of mortality. Among the 36 patients, 18 had worsening of their clinical status, as defined by severe hypoxia with oxygen therapy requirements greater than 4 L/min and radiological worsening. Significantly, 11 of those 18 patients (61.1%) died. None of the classical cardiovascular risk factors in the general population were associated with higher mortality. Compared to survivors, nonsurvivors had significantly longer dialysis vintage, increased lactate dehydrogenase (490 U/l ± 120 U/l vs. 281 U/l ± 151 U/l, P = 0.008) and C-reactive protein levels (18.3 mg/dl ± 13.7 mg/dl vs. 8.1 mg/dl ± 8.1 mg/dl, P = 0.021), and a lower lymphocyte count (0.38 ×103/µl ± 0.14 ×103/µl vs. 0.76 ×103/µl ± 0.48 ×103/µl, P = 0.04) 1 week after clinical onset. Thus, the mortality among hospitalized hemodialysis patients diagnosed with COVID-19 is high. Certain laboratory tests can be used to predict a worsening clinical course.

Obesity and chronic kidney disease progression-the role of a new adipocytokine: C1q/tumour necrosis factor-related protein-1.

BACKGROUND: Obesity is a risk factor for incident chronic kidney disease (CKD) in the general population. C1q/tumour necrosis factor-related protein 1 (CTRP1) is a new adipokine with multiple vascular and metabolic effects and may modulate the association between obesity and vascular diseases. The aim of the study is to explore potential links between obesity, CTRP1 levels and CKD progression. METHODS: Patients with Stages 3 and 4 CKD without previous cardiovascular events were enrolled and divided into two groups according to body mass index (BMI). Demographic, clinical and analytical data and CTRP1 levels were collected at baseline. During follow-up, renal events [defined as dialysis initiation, serum creatinine doubling or a 50% decrease in estimated glomerular filtration rate (Modification of Diet in Renal Disease)] were registered. RESULTS: A total of 71 patients with CKD were divided into two groups: 25 obese (BMI >30 kg/m2) and 46 non-obese. CTRP1 in plasma at baseline was higher in obese patients [median (interquartile range) 360 (148) versus 288 (188) ng/mL, P = 0.041]. No significant association was found between CTRP1 levels and CKD stage, presence of diabetes, aldosterone and renin levels, or blood pressure. Obese patients had higher systolic blood pressure (P = 0.018) and higher high-sensitivity C-reactive protein (P = 0.019) and uric acid (P = 0.003) levels, without significant differences in the percentage of diabetic patients or albuminuria. During a mean follow-up of 65 months, 14 patients had a renal event. Patients with CTRP1 in the lowest tertile had more renal events, both in the overall sample (log rank: 5.810, P = 0.016) and among obese patients (log rank: 5.405, P = 0.020). Higher CTRP1 levels were associated with slower renal progression (hazard ratio 0.992, 95% confidence interval 0.986-0.998; P = 0.001) in a model adjusted for obesity, aspirin, albuminuria and renal function. CONCLUSIONS: CTRP1 levels are higher in obese than in non-obese patients with CKD. High CTRP1 levels may have a renal protective role since they were associated with slower kidney disease progression. Interventional studies are needed to explore this hypothesis.

Pentoxifylline, progression of chronic kidney disease (CKD) and cardiovascular mortality: long-term follow-up of a randomized clinical trial.

BACKGROUND: Pentoxifylline could reduce proteinuria and slow renal disease progression. We previously conducted a single-blind, randomized, controlled trial that showed that pentoxifylline decreases inflammatory markers and stabilizes renal function. SETTING AND PARTICIPANTS: 91 participants (46 in the pentoxifylline group and 45 in the control group) followed up for 7 additional years. STUDY DESIGN: Post hoc analysis of a long-term follow-up after completion of the 12-months trial. INTERVENTION: Pentoxifylline treatment (400 mg/twice a day) or standard treatment. OUTCOME: Renal event (defined as starting dialysis therapy and/or doubling serum creatinine and/or ≥ 50% decrease in estimated glomerular filtration rate) and cardiovascular mortality. RESULTS: During follow-up, a renal event was recorded in 24 patients from control group (13 initiated dialysis therapy and serum creatinine doubled in 11) and 11 patients from PTF group (7 initiated dialysis and serum creatinine doubled in 4) (log Rank: 5.822, p = 0.016). The possible protector effect of PTF was more significant in albuminuric patients and was independently of diabetes mellitus presence. Treatment with PTF reduced the renal events by 35% compared to the control group in a Cox model adjusted for diabetes mellitus, albuminuria and basal renal function (HR 0.65 (0.45-0.94), p = 0.022). Cardiovascular mortality was significantly reduced in PTF treatment (2 patients vs. 10 in control group) (log Rank 5.0977, p = 0.024). PTF treatment reduced cardiovascular mortality in 55% adjusted for diabetes mellitus and age (HR 0.45 (0.21-0.98), p = 0.044) (Table 3). LIMITATIONS: Small sample size, single center, not double blind and post hoc follow-up analysis. CONCLUSIONS: Long-term treatment with pentoxifylline may slow the rate of progression of kidney disease and reduce cardiovascular risk.

Los altos volúmenes convectivos se asocian a la mejoría del perfil metabólico en los pacientes diabéticos en hemodiafiltración online / High convective volumes are associated with improvement in metabolic profile in diabetic patients on online haemodiafiltration

Antecedentes y objetivo: La hemodiafiltración onine (HDF-OL) con altos volúmenes de transporte convectivo mejora la supervivencia en los pacientes en hemodiálisis. Se ha propuesto limitar el volumen convectivo en los pacientes diabéticos por la carga de glucosa administrada con el líquido de sustitución. El objetivo del estudio fue analizar la influencia del volumen de sustitución en la evolución del perfil metabólico y la composición corporal de los pacientes diabéticos incidentes en HDF-OL. Material y métodos: Estudio observacional prospectivo en 29 pacientes diabéticos incidentes en HDF-OL posdilución. Basalmente se recogieron datos clínicos y demográficos, parámetros analíticos metabólicos, nutricionales e inflamatorios, y la composición corporal por bioimpedancia espectroscópica (BIS). Cada 4 meses se recogieron parámetros analíticos y el volumen de sustitución medio por sesión, y en 23 pacientes se realizó otra BIS al menos un año después. Se calcularon variaciones de hemoglobina glucosilada (HbA1c), triglicéridos, colesterol total, c-LDL, c-HDL, albúmina, prealbúmina y proteína C reactiva (PCR) al año, 2 años, 3 años y al final del seguimiento. Se calcularon las variaciones cuatrimestrales y anuales como periodos independientes, y se analizaron los cambios de composición corporal. Resultados: La edad al inicio fue a los 69,7±13,6 años; el 62,1% eran varones, de 72,3 ± 13,9 kg, 1,78 ± 0,16 m2, y con 48 (35,5-76) meses en diálisis. El 81,5% recibía insulinoterapia, el 7,4% antidiabéticos y el 51,9% estatinas. El volumen de sustitución medio fue de 26,9 ± 2,9L/sesión y el periodo de seguimiento (tiempo en HDF-OL) fue de 40,4 ± 26 meses. Se observó una correlación significativa entre el volumen de sustitución medio y un incremento de los niveles de c-HDL (r = 0,385, p = 0,039) y prealbúmina (r = 0,404, p = 0,003) a lo largo del seguimiento. El volumen convectivo se asoció a la reducción de los niveles de PCR al año (r = -0,531, p = 0,005), a los 2 años (r = -0,463, p = 0,046) y al final del seguimiento (r = -0,498, p = 0,007). Los pacientes con volumen de sustitución >26,9L/sesión tuvieron mayor descenso en los niveles de triglicéridos y PCR, y un aumento de las cifras de c-HDL. Estos pacientes con > 26,9 L/sesión finalizaron el estudio con niveles más altos de c-HDL (48,1 ± 9,4mg/dL vs. 41,2 ± 11,6 mg/dL, p = 0,025) y más bajos de PCR (0,21 [0,1-2,22] mg/dL vs. 1,01 [0,15-6,96] mg/dL, p = 0,001), sin diferencias al inicio.Las comparaciones entre el volumen de sustitución y los cambios analíticos por periodos cuatrimestrales [n = 271] mostraron una correlación significativa con un descenso de HbA1c (r = -0,146, p = 0,021), al igual que las comparaciones por periodos anuales [n=72] (r = -0,237, p = 0,045). Un volumen de sustitución medio anual >26,6L/sesión (29,3 ± 1,7L/sesión vs. 23,9 ± 1,9 L/sesión) se asoció a un descenso de HbA1c (-0,51 ± 1,24% vs. 0,01 ± 0,88%, p = 0,043). No se observó correlación entre el volumen de sustitución y las variaciones en el peso, IMC o parámetros de la BIS.Conclusión: No existe suficiente evidencia para limitar el transporte convectivo en los pacientes diabéticos en HDF-OL por el contenido de glucosa del líquido de sustitución

Background and objective: Online haemodiafiltration (OL-HDF) with high convective transport volumes improves patient survival in haemodialysis. Limiting the amount of convective volume has been proposed in patients with diabetes mellitus due to glucose load that is administered with replacement fluid. The objective of the study was to analyse the influence of substitution volume on the evolution of the metabolic profile and body composition of incident diabetic patients on OL-HDF.Material and methods: Prospective observational study in 29 incident diabetic patients on postdilution OL-HDF. Baseline data included clinical and demographic data, laboratory parameters (metabolic, nutritional and inflammatory profile) and body composition with bioimpedance spectroscopy (BIS). Laboratory parameters and mean substitution volume per session were collected every 4 months, and in 23 patients a further BIS was performed after a minimum of one year. Variations in glycosylated haemoglobin (HbA1c), triglycerides, total cholesterol, LDL-c, HDL-c, albumin, prealbumin and C reactive protein (CRP) were calculated at one year, 2 years, 3 years, and at the end of follow-up. Quarterly and annual variations were calculated as independent periods, and changes in body composition were analysed. Results: Age at baseline was 69.7±13.6 years, 62.1% were male, 72.3 ± 13.9 kg, 1.78 ± 0.16 m2, with 48 (35.5-76) months on dialysis. Approximately 81.5% received insulin, 7.4% antidiabetic drugs and 51.9% statins. Mean substitution volume was 26.9 ± 2.9L/session and follow-up period (time on OL-HDF) was 40.4 ± 26 months.A significant correlation was observed between mean substitution volume and the increase in HDL-c (r=0.385, p=0.039) and prealbumin levels (r = 0.404, p = 0.003) throughout follow-up. Moreover, substitution volume was correlated with a reduction in CRP levels at one year (r = -0.531, p = 0.005), 2 years (r = -0.463, p = 0.046), and at the end of follow-up (r = -0.498, p = 0.007). Patients with mean substitution volume > 26.9 L/session had a higher reduction in triglycerides and CRP, and an increase in HDL-c levels. These patients with > 26.9L/session finished the study with higher HDL-c (48.1 ± 9.4 mg/dL vs. 41.2 ± 11.6 mg/dL, p = 0.025) and lower CRP levels (0.21 [0.1-2.22] mg/dL vs. 1.01 [0.15-6.96] mg/dL, p = 0.001), with no differences at baseline.Quarterly comparisons between substitution volume and laboratory changes [n = 271] showed a significant correlation with a reduction in HbA1c (r = -0.146, p = 0.021). Similar findings were obtained with annual comparisons [n = 72] (r = -0.237, p = 0.045). An annual mean substitution volume over 26.6 L/session (29.3 ± 1.7L/session vs. 23.9 ± 1.9L/session) was associated with a reduction in HbA1c (-0.51 ± 1.24% vs. 0.01 ± 0.88%, p = 0.043). No correlation was observed between substitution volume and changes in weight, body mass index or BIS parameters.Conclusion: There is not enough evidence to restrict convective transport in diabetic patients on OL-HDF due to the glucose content of the replacement fluid

Influencia de la concentración de calcio en el líquido de hemodiálisis sobre el control de la tensión arterial / Influence of calcium concentration in haemodialysis fluid on blood pressure control

Introducción: La hipertensión arterial es altamente prevalente en los pacientes en hemodiálisis. Implica un mayor riesgo cardiovascular y es fundamental su control. A pesar de medidas dietéticas, optimización de la pauta de hemodiálisis y tratamiento farmacológico, existe un porcentaje de pacientes en nuestras unidades que continúan hipertensos. Es por ello que nos planteamos que la reducción de calcio en el líquido de diálisis puede ayudar al manejo de los pacientes hipertensos en hemodiálisis. Material y métodos: Se seleccionaron todos los pacientes hipertensos de nuestra unidad de hemodiálisis. Se comprobó estado de normovolemia mediante bioimpedancia espectroscópica y se disminuyó la concentración de calcio del líquido de hemodiálisis a 2,5 mEq/l, con un seguimiento de 12 meses. Resultados: Cumplieron criterios de hipertensión arterial no volumen-dependiente 24 pacientes (edad 61±15 años, varones el 48%, diabetes el 43%). Se observó una disminución significativa en la tensión arterial sistólica y diastólica a los 6 y 12 meses de la reducción de la concentración del calcio de diálisis, sin acompañarse de mayor inestabilidad hemodinámica (tensión arterial sistólica basal 162 ± 14; a los 6 meses 146 ± 18; a los 12 meses 141 ± 21 mmHg; p = 0,001) (tensión arterial diastólica basal 76 ± 14; a los 6 meses 70 ± 12; a los 12 meses 65 ± 11mmHg; p = 0,005) Existió un aumento de los niveles plasmáticos de PTH de forma no significativa. No se evidenciaron efectos secundarios. Conclusiones: La hemodiálisis con calcio en el líquido de 2,5mEq/l es una alternativa terapéutica eficaz y segura para el control de hipertensión arterial de difícil manejo en los pacientes de hemodiálisis

Background: Hypertension is a highly prevalent disorder among patients undergoing haemodialysis. It contributes to greater cardiovascular risk and must be controlled. However, despite dietary measures, haemodialysis regimen optimisation and pharmacological treatment, some patients in our units continue to maintain high blood pressure levels. The objective of the study is to demonstrate that reducing calcium in dialysis fluid can help treat hypertension patients undergoing haemodialysis. Material and methods: We selected all of the hypertensive patients from our haemodialysis unit. We checked their normovolemic status by means of bioimpedance spectroscopy, decreasing the haemodialysis fluid's calcium concentration to 2.5 mEq/l, with a follow-up period of 12 months. Results: A total of 24 patients met the non-volume dependent hypertension criteria (age 61±15 years, males 48%, diabetes 43%). A significant systolic and diastolic blood pressure decrease was observed at 6 and 12 months as a result of reducing the dialysis calcium concentration; this was not accompanied by greater haemodynamic instability (baseline systolic blood pressure: 162 ± 14 mmHg; at 6 months: 146 ± 18 mmHg; at 12 months: 141 ± 21 mmHg; P = .001) (baseline diastolic blood pressure: 76 ± 14 mmHg; at 6 months: 70 ± 12 mmHg; at 12 months: 65 ± 11 mmHg; P = .005). A non-significant increase in plasma parathyroid hormone levels was also found. No side effects were observed. Conclusions: Adding 2.5 mEq/l of calcium to dialysis fluid is a safe and effective therapeutic alternative to control hard-to-manage hypertension among haemodialysis patients

Influence of calcium concentration in haemodialysis fluid on blood pressure control. / Influencia de la concentración de calcio en el líquido de hemodiálisis sobre el control de la tensión arterial.

BACKGROUND: Hypertension is a highly prevalent disorder among patients undergoing haemodialysis. It contributes to greater cardiovascular risk and must be controlled. However, despite dietary measures, haemodialysis regimen optimisation and pharmacological treatment, some patients in our units continue to maintain high blood pressure levels. The objective of the study is to demonstrate that reducing calcium in dialysis fluid can help treat hypertension patients undergoing haemodialysis. MATERIAL AND METHODS: We selected all of the hypertensive patients from our haemodialysis unit. We checked their normovolemic status by means of bioimpedance spectroscopy, decreasing the haemodialysis fluid's calcium concentration to 2.5mEq/l, with a follow-up period of 12 months. RESULTS: A total of 24 patients met the non-volume dependent hypertension criteria (age 61±15 years, males 48%, diabetes 43%). A significant systolic and diastolic blood pressure decrease was observed at 6 and 12 months as a result of reducing the dialysis calcium concentration; this was not accompanied by greater haemodynamic instability (baseline systolic blood pressure: 162±14 mmHg; at 6 months: 146±18 mmHg; at 12 months: 141±21 mmHg; P=.001) (baseline diastolic blood pressure: 76±14 mmHg; at 6 months: 70±12 mmHg; at 12 months: 65±11 mmHg; P=.005). A non-significant increase in plasma parathyroid hormone levels was also found. No side effects were observed. CONCLUSIONS: Adding 2.5mEq/l of calcium to dialysis fluid is a safe and effective therapeutic alternative to control hard-to-manage hypertension among haemodialysis patients.

High convective volumes are associated with improvement in metabolic profile in diabetic patients on online haemodiafiltration. / Los altos volúmenes convectivos se asocian a la mejoría del perfil metabólico en los pacientes diabéticos en hemodiafiltración online.

BACKGROUND AND OBJECTIVE: Online haemodiafiltration (OL-HDF) with high convective transport volumes improves patient survival in haemodialysis. Limiting the amount of convective volume has been proposed in patients with diabetes mellitus due to glucose load that is administered with replacement fluid. The objective of the study was to analyse the influence of substitution volume on the evolution of the metabolic profile and body composition of incident diabetic patients on OL-HDF. MATERIAL AND METHODS: Prospective observational study in 29 incident diabetic patients on postdilution OL-HDF. Baseline data included clinical and demographic data, laboratory parameters (metabolic, nutritional and inflammatory profile) and body composition with bioimpedance spectroscopy (BIS). Laboratory parameters and mean substitution volume per session were collected every 4 months, and in 23 patients a further BIS was performed after a minimum of one year. Variations in glycosylated haemoglobin (HbA1c), triglycerides, total cholesterol, LDL-c, HDL-c, albumin, prealbumin and C reactive protein (CRP) were calculated at one year, 2 years, 3 years, and at the end of follow-up. Quarterly and annual variations were calculated as independent periods, and changes in body composition were analysed. RESULTS: Age at baseline was 69.7±13.6 years, 62.1% were male, 72.3±13.9kg, 1.78±0.16m2, with 48 (35.5-76) months on dialysis. Approximately 81.5% received insulin, 7.4% antidiabetic drugs and 51.9% statins. Mean substitution volume was 26.9±2.9L/session and follow-up period (time on OL-HDF) was 40.4±26 months. A significant correlation was observed between mean substitution volume and the increase in HDL-c (r=0.385, p=0.039) and prealbumin levels (r=0.404, p=0.003) throughout follow-up. Moreover, substitution volume was correlated with a reduction in CRP levels at one year (r=-0.531, p=0.005), 2 years (r=-0.463, p=0.046), and at the end of follow-up (r=-0.498, p=0.007). Patients with mean substitution volume >26.9L/session had a higher reduction in triglycerides and CRP, and an increase in HDL-c levels. These patients with >26.9L/session finished the study with higher HDL-c (48.1±9.4mg/dL vs. 41.2±11.6mg/dL, p=0.025) and lower CRP levels (0.21 [0.1-2.22] mg/dL vs. 1.01 [0.15-6.96] mg/dL, p=0.001), with no differences at baseline. Quarterly comparisons between substitution volume and laboratory changes [n=271] showed a significant correlation with a reduction in HbA1c (r=-0.146, p=0.021). Similar findings were obtained with annual comparisons [n=72] (r=-0.237, p=0.045). An annual mean substitution volume over 26.6L/session (29.3±1.7L/session vs. 23.9±1.9L/session) was associated with a reduction in HbA1c (-0.51±1.24% vs. 0.01±0.88%, p=0.043). No correlation was observed between substitution volume and changes in weight, body mass index or BIS parameters. CONCLUSION: There is not enough evidence to restrict convective transport in diabetic patients on OL-HDF due to the glucose content of the replacement fluid.

Impacto de la anticoagulación y antiagregación plaquetaria en la anemia y los eventos hemorrágicos y ateroscleróticos de pacientes con enfermedad renal crónica en estadios 3 y 4 / Impact of anticoagulation and platelet antiaggregation on anaemia and haemorragic events in patients with chronic kidney disease stages 3 and 4

Introducción y objetivo: Existe controversia sobre el riesgo/beneficio de anticoagular/antiagregar a pacientes con enfermedad renal crónica (ERC). Analizamos el impacto de la anticoagulación/antiagregación en pacientes con ERC sobre el riesgo hemorrágico, cardiovascular y la mortalidad. Pacientes y métodos: Se estudió a 232 pacientes (81 controles, 91 anticoagulados y 60 antiagregados) con ERC en estadios 3 y 4, que fueron seguidos durante un tiempo medio de 33,7 ± 14,8 meses. Se recogieron eventos hemorrágicos, cardiovasculares y mortalidad. Resultados: La hemoglobina sérica y los niveles de ferritina fueron significativamente mayores en pacientes controles (hemoglobina 13,7 ± 1,6; 13,3 ± 1,8 y 12,7 ± 1,9g/dl; p = 0,004; ferritina 170 ± 145; 140 ± 138; 105 ± 99μg/l; p = 0,023). Durante el seguimiento hubo 36 eventos hemorrágicos: 4 en pacientes control, 23 en anticoagulados y 9 en antiagregados (log rank 12,5; p = 0,002). En un modelo de Cox ajustado para edad, función renal y niveles de hemoglobina, la anticoagulación aumentó el riesgo de sangrado 4veces (HR 4,180; 1,955-8,937; p = 0,001) y la antiagregación en casi 3veces (HR 2,780; 1,257-6,149; p = 0,012). Se registraron 64 eventos cardiovasculares, 21 de los cuales fueron clasificados como eventos ateroscleróticos: 10 en el grupo de antiagregación, 8 en el grupo control y 3 en el grupo de anticoagulación (log rank: 8,351; p = 0,015). El tratamiento anticoagulante demostró un efecto protector frente al riesgo de padecer eventos ateroscleróticos (HR 0,136; 0,033-0,551; p = 0,005), mientras que el tratamiento antiagregante no lo modificó (HR 1,566; 0,569-4,308; ns). Conclusiones: La anticoagulación y la antiagregación aumentan el riesgo hemorrágico en pacientes con ERC y empeoran la anemia. La anticoagulación disminuye el riesgo de eventos cardiovasculares ateroescleróticos en más de un 85% y la antiagregación no lo modifica

Background and objective: There is controversy concerning the risk/benefit of anticoagulation/antiaggregation in chronic kidney disease (CKD) patients. We analysed the impact of anticoagulation/antiaggregation on anaemia and haemorrhagic events in CKD patients. Patients and methods: A total of 232 CKD patients stages 3 and 4 were followed during a mean follow-up time of 36.7 ± 11.6 months: 81 patients did not receive any anticoagulation or antiaggregation treatment, 91 received anticoagulation treatment and 60 patients received platelet antiaggregation. Haemorrhagic and cardiovascular events were recorded. Results: Haemoglobin and ferritine levels were significantly higher in patients who did not receive anticoagulation or antiaggregation (Hb 13.7 ± 1.6, 13.3 ± 1.8 and 12.7±1.9g/dl, p=0.004; ferritine 170 ± 145, 140 ± 138, 105 ± 99μg/l, p=0.023). During follow up, 36 haemorrhagic events were registered: 4in the control group, 23 in the anticoagulation group and 9in the antiaggregation group (log rank 12.5; p=0.002). In a Cox model adjusted by age, renal function and haemoglobin levels, the anticoagulation increased the risk of bleeding by 4times (HR 4.180, 1.955-8.937); p=0,001) and antiaggregation by almost 3times (HR 2.780, 1.257-6.149, p=0.012). A total of 64 cardiovascular events were registered, 21 of which were classified as atherosclerotic events: 10 in the antiaggregation group, 8in the control group and 3in the anticoagulation group (log rank: 8.351; p=0.015). Anticoagulation treatment showed a reduction in the risk of atherosclerotic events (HR 0.136, 0.033-0.551, p=0.005) while platelet antiaggregation did not modified this risk (HR 1,566, 0.569-4.308). Conclusions: Anticoagulation and antiaggregation increase haemorrhagic risk in patients with CKD and worsen anaemia. Anticoagulation reduces atherosclerotic events by more than 85% while platelet antiaggregation does not modify this risk

Impacto de la aplicación del 8 JNC y de las guías KDIGO-2013 en el control de la hipertensión arterial y los lípidos en una consulta de Nefrología / Impact of the application of the JNC 8 and KDIGO-2013 guidelines on hypertension and lipid control in a Nephrology outpatient clinic

OBJETIVO: Estudio observacional retrospectivo con pacientes consecutivos con ERC para valorar el grado de cumplimiento de los objetivos terapéuticos en hipertensión arterial y dislipidemia recomendados por las guías JNC 8 y KDIGO-2013 ERC, y el impacto de su aplicación con respecto a las guías previas. RESULTADOS: Se recogieron 618 pacientes, edad media 67 ± 15 años, el 61,33% varones. El FGe medio era 45,99 ± 18,94ml/min, la mediana de albúmina/creatinina 26 (0-151) mg/g. Un 87,6% recibían tratamiento antihipertensivo y un 50,2% estatinas. Según las guías KDIGO, 520 pacientes (84,14%) deberían recibir estatinas, pero solo 304 (58,46%) las recibían. Los pacientes en tratamiento con estatinas tenían más DM e hipertensión arterial, más antecedentes cardiovasculares y menor nivel de colesterol total y colesterol-LDL. El 97,7% de los pacientes eran menores de 60 años o tenían FGe < 60 ml/min/1,73m2 o diabéticos, grupo que según el informe JNC 8 tiene objetivo de presión arterial < 140/90 mmHg. Cumplían dicho objetivo 289 pacientes (47,85%). Según el JNC 7, estos pacientes tenían un objetivo más exigente, < 130/90 mmHg, lo que reduciría el número de pacientes cumplidores a 136 (22,52%). Los pacientes reclasificados eran mayores, tenían más antecedentes cardiovasculares y menos DM. CONCLUSIÓN: Las nuevas guías KDIGO de tratamiento de la dislipidemia suponen un incremento en la indicación del tratamiento con estatinas, sobre todo en pacientes con elevado riesgo cardiovascular. Las guías JNC 8 mejoran el porcentaje de pacientes con la presión arterial controlada, sobre todo a expensas de los pacientes más mayores y con mayor riesgo cardiovascular, en los que en la actualidad las cifras objetivo de la presión arterial son controvertidas

OBJECTIVE: Observational retrospective study with consecutive patients with CKD to assess the degree of accomplishment of the therapeutic objectives in hypertension and dyslipidaemia recommended by JNC 8 and KDIGO-2013 CKD guidelines the impact of their implementation compared with previous guidelines. RESULTS: 618 patients were included, mean age 67 ± 15 years, 61.33% male. Mean eGFR was 45.99 ± 18.94 ml/min, with median albumin/creatinine 26 (0-151) mg/g. A total of 87.6% received antihypertensive treatment and 50.2% received statins. According to KDIGO guidelines, 520 patients (84.14%) should receive statins, but only 304 (58.46%) were receiving them. Patients on statin treatment had more diabetes and hypertension, and a greater cardiovascular history and lower levels of total and LDL-cholesterol. A total of 97.7% of patients were under 60 years of age or had eGFR < 60 ml/min/1.73m2 or were diabetic, so according to the JNC 8 report, they should have a target blood pressure < 140/90 mmHg. A total of 289 patients did (47.85%). According to the JNC 7 report, this group had a tighter target blood pressure < 130/90 mmHg, reducing the number of patients who fulfilled the target: 136 (22.52%). Patients reclassified were older, had a greater cardiovascular history and less DM. CONCLUSION: The new KDIGO guidelines for dyslipidaemia treatment increase the indication of statin therapy, especially in patients at high cardiovascular risk. The JNC 8 guidelines improve the percentage of patients with controlled blood pressure, especially the elderly and patients with increased cardiovascular risk, in whom the target blood pressure is currently controversial

Impact of the application of the JNC 8 and KDIGO-2013 guidelines on hypertension and lipid control in a Nephrology outpatient clinic. / Impacto de la aplicación del 8.o JNC y de las guías KDIGO-2013 en el control de la hipertensión arterial y los lípidos en una consulta de Nefrología.

OBJECTIVE: Observational retrospective study with consecutive patients with CKD to assess the degree of accomplishment of the therapeutic objectives in hypertension and dyslipidaemia recommended by JNC 8 and KDIGO-2013 CKD guidelines the impact of their implementation compared with previous guidelines. RESULTS: 618 patients were included, mean age 67±15 years, 61.33% male. Mean eGFR was 45.99±18.94ml/min, with median albumin/creatinine 26 (0-151)mg/g. A total of 87.6% received antihypertensive treatment and 50.2% received statins. According to KDIGO guidelines, 520 patients (84.14%) should receive statins, but only 304 (58.46%) were receiving them. Patients on statin treatment had more diabetes and hypertension, and a greater cardiovascular history and lower levels of total and LDL-cholesterol. A total of 97.7% of patients were under 60 years of age or had eGFR<60ml/min/1.73m2 or were diabetic, so according to the JNC 8 report, they should have a target blood pressure<140/90mmHg. A total of 289 patients did (47.85%). According to the JNC 7 report, this group had a tighter target blood pressure<130/90mmHg, reducing the number of patients who fulfilled the target: 136 (22.52%). Patients reclassified were older, had a greater cardiovascular history and less DM. CONCLUSION: The new KDIGO guidelines for dyslipidaemia treatment increase the indication of statin therapy, especially in patients at high cardiovascular risk. The JNC 8 guidelines improve the percentage of patients with controlled blood pressure, especially the elderly and patients with increased cardiovascular risk, in whom the target blood pressure is currently controversial.

Aspirin for Primary Prevention of Cardiovascular Disease and Renal Disease Progression in Chronic Kidney Disease Patients: a Multicenter Randomized Clinical Trial (AASER Study).

BACKGROUND: Patients with chronic kidney disease (CKD) are at high risk for developing cardiovascular events. However, limited evidence is available regarding the use of aspirin in CKD patients to decrease cardiovascular risk and to slow renal disease progression. STUDY DESIGN: Prospective, multicenter, open-label randomized controlled trial. SETTING AND PARTICIPANTS: One hundred eleven patients with estimated glomerular filtration rate (eGFR) 15-60 ml/min/1.73 m2 without previous cardiovascular events. INTERVENTION: Aspirin treatment (100 mg/day) (n = 50) or usual therapy (n = 61). Mean follow-up time was 64.8 ± 16.4 months. OUTCOMES: The primary endpoint was composed of cardiovascular death, acute coronary syndrome (nonfatal MI, coronary revascularization, or unstable angina pectoris), cerebrovascular disease, heart failure, or nonfatal peripheral arterial disease. Secondary endpoints were fatal and nonfatal coronary events, renal events (defined as doubling of serum creatinine, ≥ 50% decrease in eGFR, or renal replacement therapy), and bleeding episodes. RESULTS: During follow-up, 17 and 5 participants suffered from a primary endpoint in the control and aspirin groups, respectively. Aspirin did not significantly reduce primary composite endpoint (HR, 0.396 (0.146-1.076), p = 0.069. Eight patients suffered from a fatal or nonfatal coronary event in the control group compared to no patients in the aspirin group. Aspirin significantly reduced the risk of coronary events (log-rank, 5.997; p = 0.014). Seventeen patients in the control group reached the renal outcome in comparison with 3 patients in the aspirin group. Aspirin treatment decreased renal disease progression in a model adjusted for age, baseline kidney function, and diabetes mellitus (HR, 0.272; 95% CI, 0.077-0.955; p = 0.043) but did not when adjusted for albuminuria. No differences were found in minor bleeding episodes between groups and no major bleeding was registered. LIMITATIONS: Small sample size and open-label trial. CONCLUSIONS: Long-term treatment with low-dose aspirin did not reduce the composite primary endpoint; however, there were reductions in secondary endpoints with fewer coronary events and renal outcomes. ClinicalTrials.gov Identifier: NCT01709994.

Impact of anticoagulation and platelet antiaggregation on anaemia and haemorragic events in patients with chronic kidney disease stages 3 and 4. / Impacto de la anticoagulación y antiagregación plaquetaria en la anemia y los eventos hemorrágicos y ateroscleróticos de pacientes con enfermedad renal crónica en estadios 3 y 4.

BACKGROUND AND OBJECTIVE: There is controversy concerning the risk/benefit of anticoagulation/antiaggregation in chronic kidney disease (CKD) patients. We analysed the impact of anticoagulation/antiaggregation on anaemia and haemorrhagic events in CKD patients. PATIENTS AND METHODS: A total of 232 CKD patients stages 3 and 4 were followed during a mean follow-up time of 36.7 ± 11.6 months: 81 patients did not receive any anticoagulation or antiaggregation treatment, 91 received anticoagulation treatment and 60 patients received platelet antiaggregation. Haemorrhagic and cardiovascular events were recorded. RESULTS: Haemoglobin and ferritine levels were significantly higher in patients who did not receive anticoagulation or antiaggregation (Hb 13.7 ± 1.6, 13.3 ± 1.8 and 12.7±1.9g/dl, p=0.004; ferritine 170 ± 145, 140 ± 138, 105 ± 99µg/l, p=0.023). During follow up, 36 haemorrhagic events were registered: 4in the control group, 23 in the anticoagulation group and 9in the antiaggregation group (log rank 12.5; p=0.002). In a Cox model adjusted by age, renal function and haemoglobin levels, the anticoagulation increased the risk of bleeding by 4times (HR 4.180, 1.955-8.937); p=0,001) and antiaggregation by almost 3times (HR 2.780, 1.257-6.149, p=0.012). A total of 64 cardiovascular events were registered, 21 of which were classified as atherosclerotic events: 10 in the antiaggregation group, 8in the control group and 3in the anticoagulation group (log rank: 8.351; p=0.015). Anticoagulation treatment showed a reduction in the risk of atherosclerotic events (HR 0.136, 0.033-0.551, p=0.005) while platelet antiaggregation did not modified this risk (HR 1,566, 0.569-4.308). CONCLUSIONS: Anticoagulation and antiaggregation increase haemorrhagic risk in patients with CKD and worsen anaemia. Anticoagulation reduces atherosclerotic events by more than 85% while platelet antiaggregation does not modify this risk.