The coexistence of diabetic retinopathy and diabetic nephropathy is associated with worse kidney outcomes.

Background: Up to 50-60% of patients with diabetes have non-diabetic kidney disease (NDKD) on kidney biopsy. Diabetic retinopathy (DR) is a microvascular complication of diabetes frequently associated with diabetic nephropathy (DN). The objective of the current study was to investigate the kidney outcomes and survival in patients with biopsy diagnoses of DN and NDKD according to the presence of DR. Methods: We conducted an observational, multicentre and retrospective study of the pathological findings of renal biopsies from 832 consecutive patients with diabetes from 2002 to 2014 from 18 nephrology departments. The association of DR with kidney replacement therapy (KRT) or survival was assessed by Kaplan-Meier and Cox regression analyses. Results: Of 832 patients with diabetes and renal biopsy, 768 had a retinal examination and 221/768 (22.6%) had DR. During a follow-up of 10 years, 288/760 (37.9%) patients with follow-up data needed KRT and 157/760 (20.7%) died. The incidence of KRT was higher among patients with DN (alone or with NDKD) and DR [103/175 (58.9%)] than among patients without DR [88/216 (40.7%), P < .0001]. The incidence of KRT was also higher among patients with only NDKD and DR than among those without DR [18/46 (39.1%) versus 79/331 (23.9%), P < .0001]. In multivariate analysis, DR or DN were independent risk factors for KRT {hazard ratio [HR] 2.48 [confidence interval (CI) 1.85-3.31], P < .001}. DN (with or without DR) was also identified as an independent risk factor for mortality [HR 1.81 (CI 1.26-2.62), P = .001]. Conclusions: DR is associated with a higher risk of progression to kidney failure in patients with histological DN and in patients with NDKD.

An Exceptional Case of Light Chain Only Variant of Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits Secondary to Chronic Lymphocytic Leukemia: A Case Report and Review of the Literature.

We present the case of an 86-year-old Caucasian male with an 11-year history of low-grade chronic lymphocytic leukemia (CLL) presenting with nephrotic syndrome (NS). Renal biopsy findings showed a diffuse mesangial and endocapillary proliferative glomerulonephritis (GN) lesion with fine granular deposits, consistent with a rare morphologic variant of proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID)-lambda light chain (LC) only. Monthly combination therapy of rituximab (500 mg/m2 on day 1), fludarabine (30 mg/m2 on days 1-3), and cyclophosphamide (750 mg/m2 on days 1-3) was administered. Five courses of this regimen resulted in hematological remission, as well as a partial renal response with a reduction in the spot urine protein-to-creatinine ratio (UPCR) of 815.3 mg/g (reduction > 50% proteinuria without improvement in kidney function). This condition is a rare morphological variant of PGNMID, poorly described in CLL patients. We review the literature and suggest that this case provides sheds light on the unknown pathophysiological mechanisms of monoclonal immunoglobulins (MIg)-mediated glomerular damage in CLL patients, and may be helpful for the investigation of a more effective treatment.

The impact of the correction of hyponatremia during hospital admission on the prognosis of SARS-CoV-2 infection.

Background: SARS-CoV-2 infection is frequently associated with hyponatremia (plasma sodium <135 mmol/L), being associated with a worse prognosis. The incidence of hyponatremia is estimated to be 20-37% according to the series, but there are no data on the prognosis after correction of hyponatremia. Therefore, our objectives were: to analyse the incidence and severity of hyponatremia at hospital admission, and to determine the association of this hyponatremia with the prognosis of COVID-19. Methods: Observational and retrospective cohort study. Patients who were admitted with a diagnosis of COVID-19 infection and hyponatremia, in the period March-May 2020, were included. We recorded epidemiological, demographic, clinical, biochemical, and radiological variables of SARS-CoV-2 infection and hyponatremia at the time of diagnosis and during hospitalization. The clinical follow-up ranged from admission to death or discharge. Results: 91 patients (21.8%) of the 414 admitted for SARS-CoV-2 infection presented hyponatremia (81.32% mild hyponatremia, 9.89% moderate and 8.79% severe). The absence of correction of hyponatremia 72-96 h after hospital admission was associated with higher mortality in patients with COVID-19 (Odds Ratio 0.165; 95% confidence interval: 0.018-0.686; p = 0.011). 19 patients (20.9%) died. An increase in mortality was observed in patients with severe hyponatremia compared with moderate and mild hyponatremia during hospital admission (37.5% versus 11.1% versus 8.1%, p = 0.041). Conclusion: We conclude that persistence of hyponatremia at 72-96 h of hospital admission was associated with higher mortality in patients with SARS-Cov-2.

Introduccion: La infección por SARS-CoV-2 se asocia con frecuencia con hiponatremia (sodio plasmático <135 mmol/l), relacionándose con peor pronóstico. La incidencia de la hiponatremia se estima en 20­37% según las series, pero no existen datos sobre el pronóstico tras la corrección de la hiponatremia. Por ello, nuestros objetivos fueron: analizar la incidencia y gravedad de la hiponatremia al ingreso hospitalario, y determinar la asociación de dicha hiponatremia con el pronóstico del COVID-19. Material y método: Estudio de cohorte observacional y retrospectivo. Se incluyeron pacientes que ingresaron con diagnóstico de infección por COVID-19 e hiponatremia, en el periodo marzo-mayo 2020. Registramos variables epidemiológicas, demográficas, clínicas, analíticas y radiológicas de la infección por SARS-CoV-2 e hiponatremia al momento del diagnóstico y durante la hospitalización. El seguimiento clínico comprendió desde el ingreso hasta el exitus o el alta. Resultados: 91 pacientes (21,8%) de los 414 ingresados por infección del SARS-CoV-2 presentaron hiponatremia (81,32% hiponatremia leve, 9,89% moderada y 8,79% grave). La ausencia de corrección de la hiponatremia a las 72­96 horas del ingreso hospitalario estuvo asociado a mayor mortalidad en los pacientes con COVID-19 (OR 0,165; 95% intervalo de confianza: 0,018­0,686; p = 0,011). Fallecieron 19 pacientes (20,9%). Se observó un aumento de la mortalidad en pacientes con hiponatremia grave en comparación con hiponatremia moderada y leve durante el ingreso (37,5% versus 11,1% versus 8,1%, respectivamente, p = 0,041). Conclusiones: La persistencia de la hiponatremia tras las primeras 72­96 horas del ingreso hospitalario fue asociada a mayor mortalidad+- en los pacientes con SARS-Cov-2.

Impacto de la corrección temprana de la hiponatremia en el pronóstico de la infección del síndrome respiratorio agudo grave del coronavirus 2 (SARS-CoV-2) / The impact of the correction of hyponatremia during hospital admission on the prognosis of SARS-CoV-2 infection

IntroducciónLa infección por el coronavirus del síndrome respiratorio agudo grave de tipo 2 (SARS-CoV-2) se asocia con frecuencia con hiponatremia (sodio plasmático<135mmol/l), relacionándose con peor pronóstico. La incidencia de la hiponatremia se estima en 20-37% según las series, pero no existen datos sobre el pronóstico tras la corrección de la hiponatremia. Por ello, nuestros objetivos fueron: analizar la incidencia y gravedad de la hiponatremia al ingreso hospitalario y determinar la asociación de dicha hiponatremia con el pronóstico de la enfermedad por coronavirus de 2019 (COVID-19).Material y métodoEstudio de cohorte observacional y retrospectivo. Se incluyeron pacientes que ingresaron con diagnóstico de infección por COVID-19 e hiponatremia en el periodo marzo-mayo de 2020. Registramos variables epidemiológicas, demográficas, clínicas, analíticas y radiológicas de la infección por SARS-CoV-2 e hiponatremia en el momento del diagnóstico y durante la hospitalización. El seguimiento clínico comprendió desde el ingreso hasta el exitus o el alta.ResultadosNoventa y un pacientes (21,8%) de los 414 ingresados por infección del SARS-CoV-2 presentaron hiponatremia (81,32% hiponatremia leve, 9,89% moderada y 8,79% grave). La ausencia de corrección de la hiponatremia a las 72-96horas del ingreso hospitalario estuvo asociado a mayor mortalidad en los pacientes con COVID-19 (odds ratio 0,165; 95% intervalo de confianza: 0,018-0,686; p=0,011). Fallecieron 19 pacientes (20,9%). Se observó un aumento de la mortalidad en pacientes con hiponatremia grave en comparación con hiponatremia moderada y leve durante el ingreso (37,5% versus 11,1% versus 8,1%, respectivamente; p=0,041).ConclusionesLa persistencia de la hiponatremia tras las primeras 72-96horas del ingreso hospitalario se asoció a mayor mortalidad en los pacientes con SARS-CoV-2. (AU)

IntroductionSARS-CoV-2 infection is frequently associated with hyponatremia (plasma sodium<135mmol/L), being associated with a worse prognosis. The incidence of hyponatremia is estimated to be 20–37% according to the series, but there are no data on the prognosis after correction of hyponatremia. Therefore, our objectives were: to analyze the incidence and severity of hyponatremia at hospital admission, and to determine the association of this hyponatremia with the prognosis of COVID-19.Material and methodObservational and retrospective cohort study. Patients who were admitted with a diagnosis of COVID-19 infection and hyponatremia, in the period March–May 2020, were included. We recorded epidemiological, demographic, clinical, biochemical, and radiological variables of SARS-CoV-2 infection and hyponatremia at the time of diagnosis and during hospitalization. The clinical follow-up ranged from admission to death or discharge.Results91 patients (21.8%) of the 414 admitted for SARS-CoV-2 infection presented hyponatremia (81.32% mild hyponatremia, 9.89% moderate and 8.79% severe). The absence of correction of hyponatremia 72–96h after hospital admission was associated with higher mortality in patients with COVID-19 (Odds Ratio .165; 95% confidence interval: .018-.686; P=.011). 19 patients (20.9%) died. An increase in mortality was observed in patients with severe hyponatremia compared with moderate and mild hyponatremia during hospital admission (37.5% versus 11.1% versus 8.1%, P=.041).ConclusionsWe conclude that persistence of hyponatremia at 72–96h of hospital admission was associated with higher mortality in patients with SARS-CoV-2. (AU)

Expanded hemodialysis: Is anticoagulation of the dialysis circuit different from online hemodiafiltration and high-flux hemodialysis?

Expanded hemodialysis (HDx) has a high capacity for removing medium and medium-large molecules; however, there are no specific recommendations during HDx for anticoagulation of the dialysis circuit. We aimed to evaluate the differences in the efficacy of anticoagulation procedures using the venous port and 40 mg enoxaparin in HDx compared to high-flux hemodialysis (HF-HD) and postdilution online hemodiafiltration (HDF). We compared anticoagulant activity in 11 patients in HDx, HF-HD, and HDF under similar dialysis conditions. In the 33 dialysis sessions, 40 mg enoxaparin was administered through the venous port, and pre- and postdialysis antifactor Xa activity (aXa) and activated partial thromboplastin time (APTT), postdialysis clotting time of the vascular access, visual clotting score of the dialyzer, and any complications with the extracorporeal circuit or bleeding were registered. APTT postdialysis in HDx was not significantly different from that in HF-HD and HDF. Postdialysis aXa in HDx was not significantly different from that in HF-HD and HDF. We found no significant differences in visual clotting score of the dialyzer. Enoxaparin administered through the venous port was sufficient for anticoagulation within the extracorporeal circuit in HDx, HF-HD, and HDF. There were no differences in postdialysis aXa or APTT, most likely because when low molecular-weight heparin is applied through venous port, lesser enoxaparin concentration reaches the dialyzer. Thus, we conclude that the dose of enoxaparin administered through the venous port should not be adjusted according to dialysis technique.

The impact of the correction of hyponatremia during hospital admission on the prognosis of SARS-CoV-2 infection. / Impacto de la corrección temprana de la hiponatremia en el pronóstico de la infección del síndrome respiratorio agudo grave del coronavirus 2 (SARS-CoV-2).

INTRODUCTION: SARS-CoV-2 infection is frequently associated with hyponatremia (plasma sodium<135mmol/L), being associated with a worse prognosis. The incidence of hyponatremia is estimated to be 20-37% according to the series, but there are no data on the prognosis after correction of hyponatremia. Therefore, our objectives were: to analyze the incidence and severity of hyponatremia at hospital admission, and to determine the association of this hyponatremia with the prognosis of COVID-19. MATERIAL AND METHOD: Observational and retrospective cohort study. Patients who were admitted with a diagnosis of COVID-19 infection and hyponatremia, in the period March-May 2020, were included. We recorded epidemiological, demographic, clinical, biochemical, and radiological variables of SARS-CoV-2 infection and hyponatremia at the time of diagnosis and during hospitalization. The clinical follow-up ranged from admission to death or discharge. RESULTS: 91 patients (21.8%) of the 414 admitted for SARS-CoV-2 infection presented hyponatremia (81.32% mild hyponatremia, 9.89% moderate and 8.79% severe). The absence of correction of hyponatremia 72-96h after hospital admission was associated with higher mortality in patients with COVID-19 (Odds Ratio .165; 95% confidence interval: .018-.686; P=.011). 19 patients (20.9%) died. An increase in mortality was observed in patients with severe hyponatremia compared with moderate and mild hyponatremia during hospital admission (37.5% versus 11.1% versus 8.1%, P=.041). CONCLUSIONS: We conclude that persistence of hyponatremia at 72-96h of hospital admission was associated with higher mortality in patients with SARS-CoV-2.

Patiromer in a Patient with Severe Hyperkalemia on Incremental Hemodialysis with 1 Session per Week: A Case Report and Literature Review.

Hyperkalemia is common in patients with ESRD, undergoing hemodialysis (HD), and is associated with an increase in hospitalization and mortality. Residual kidney function in long-term dialysis patients is associated with lower morbidity and mortality in HD patients. Although the 2015 National Kidney Foundation-Kidney Disease Outcomes Quality Initiate (NKD-KDOQI) guidelines allow the reduction in the weekly HD dose for patients with a residual kidney urea clearance (Kur) >3 mL/min/1.73 m2, very few centers adjust the dialysis dose based on these criteria. In our center, the pattern of incremental hemodialysis (iHD) with once-a-week schedule (1 HD/W) has been an option for a group of patients showing very good results. This pattern is maintained as long as residual diuresis is >1,000 mL/24 h, Kur is >4 mL/min, and there is no presence of edema or volume overload, as well as no analytical parameters persistently outside the advisable range (serum phosphorus >6 mg/dL or potassium [K+] >6.5 mmol/L). Management of hyperkalemia in HD patients includes reduction of dietary intake, dosing of medications that contribute to hyperkalemia, and use of cation-exchange resins such as calcium or sodium polystyrene sulfonate. Two newer potassium binders, patiromer sorbitex calcium and sodium zirconium cyclosilicate, have been safely used for potassium imbalance treatment in patients with ESRD in HD with a conventional regimen of thrice weekly, but has not yet been studied in 1 HD/W schedules. We present the case of a 76-year-old woman in iHD (1 HD/W) treated with patiromer for severe HK and describe her clinical characteristics and outcomes. In addition, we review the corresponding literature. Based on these data, it can be anticipated that the use of patiromer may overcome the risk of hyperkalemia in patients with incident ESRD treated with less-frequent HD regimens.

Efficacy of enoxaparin in preventing coagulation during high-flux haemodialysis, expanded haemodialysis and haemodiafiltration.

BACKGROUND: Low-molecular-weight heparins (LMWHs) are easily dialysable with high-flow membranes; however, it is not clear whether the LMWH dose should be adjusted according to the membrane type and dialysis technique. This study aimed to evaluate the influence of the dialyser on anticoagulation of the extracorporeal dialysis circuit. METHODS: Thirteen patients received the same dose of LMWH through the arterial port via three dialysis techniques: high-flux haemodialysis (HF-HD), online haemodiafiltration (HDF) and expanded haemodialysis (HDx). All dialysis was performed under similar conditions: duration, 4 h; blood flow, 400 mL/min; and dialysate flow, 500 mL/min. Antifactor Xa (aXa) activity and activated partial thromboplastin time (APTT) were measured before and after the dialysis. Clotting time of the vascular access site after haemodialysis, visual clotting score of the dialyser and any complications with the extracorporeal circuit or bleeding were registered. RESULTS: Post-dialysis aXa activity in HF-HD (0.26 ± 0.02 U/mL) was significantly different from that in HDF (0.21 ± 0.02 U/mL, P = 0.024), and there was a trend in HDx (0.22 ± 0.01 U/mL, P = 0.05). APTT post-dialysis in HF-HD (30.5 ± 0.7 s) was significantly different from that in HDx (28.2 ± 0.64 s, P = 0.009) and HDF (28.8 ± 0.73 s, P = 0.009). CONCLUSIONS: AXa activity in HDF was significantly lower than that in HF-HD, possibly because of more losses of LMWH through the dialyser. Given the higher anticoagulant loss in HDF and probably in HDx than in HF-HD, the enoxaparin dose administered may be adjusted according to the dialysis technique.

Risk factors for non-diabetic renal disease in diabetic patients.

BACKGROUND: Diabetic patients with kidney disease have a high prevalence of non-diabetic renal disease (NDRD). Renal and patient survival regarding the diagnosis of diabetic nephropathy (DN) or NDRD have not been widely studied. The aim of our study is to evaluate the prevalence of NDRD in patients with diabetes and to determine the capacity of clinical and analytical data in the prediction of NDRD. In addition, we will study renal and patient prognosis according to the renal biopsy findings in patients with diabetes. METHODS: Retrospective multicentre observational study of renal biopsies performed in patients with diabetes from 2002 to 2014. RESULTS: In total, 832 patients were included: 621 men (74.6%), mean age of 61.7 ± 12.8 years, creatinine was 2.8 ± 2.2 mg/dL and proteinuria 2.7 (interquartile range: 1.2-5.4) g/24 h. About 39.5% (n = 329) of patients had DN, 49.6% (n = 413) NDRD and 10.8% (n = 90) mixed forms. The most frequent NDRD was nephroangiosclerosis (NAS) (n = 87, 9.3%). In the multivariate logistic regression analysis, older age [odds ratio (OR) = 1.03, 95% CI: 1.02-1.05, P < 0.001], microhaematuria (OR = 1.51, 95% CI: 1.03-2.21, P = 0.033) and absence of diabetic retinopathy (DR) (OR = 0.28, 95% CI: 0.19-0.42, P < 0.001) were independently associated with NDRD. Kaplan-Meier analysis showed that patients with DN or mixed forms presented worse renal prognosis than NDRD (P < 0.001) and higher mortality (P = 0.029). In multivariate Cox analyses, older age (P < 0.001), higher serum creatinine (P < 0.001), higher proteinuria (P < 0.001), DR (P = 0.007) and DN (P < 0.001) were independent risk factors for renal replacement therapy. In addition, older age (P < 0.001), peripheral vascular disease (P = 0.002), higher creatinine (P = 0.01) and DN (P = 0.015) were independent risk factors for mortality. CONCLUSIONS: The most frequent cause of NDRD is NAS. Elderly patients with microhaematuria and the absence of DR are the ones at risk for NDRD. Patients with DN presented worse renal prognosis and higher mortality than those with NDRD. These results suggest that in some patients with diabetes, kidney biopsy may be useful for an accurate renal diagnosis and subsequently treatment and prognosis.

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

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

Evaluation of the efficacy of a medium cut-off dialyser and comparison with other high-flux dialysers in conventional haemodialysis and online haemodiafiltration.

BACKGROUND: Online haemodiafiltration (OL-HDF) has been shown to reduce all-cause mortality versus conventional haemodialysis (HD); however, it is not always available. In these situations, a novel class of membranes with a higher pore size, medium cut-off (MCO) dialysers, could be promising. The aim of this study is to evaluate the efficacy of an MCO dialyser in the removal of small and medium-size molecules and compare it with standard high-flux (HF) dialysers in HD and OL-HDF. METHODS: In this crossover study, 18 prevalent HD patients were studied in three single mid-week dialysis treatments during three consecutive weeks as follows: first week with OL-HDF with a standard HF dialyser, second week with conventional HD with a standard HF dialyser and third week with conventional HD with an MCO dialyser. Reduction ratios (RRs) of different-sized molecules and albumin losses were collected for the different dialysers. RESULTS: MCO HD provided a greater reduction of middle and larger middle molecules compared with standard HF HD [rate reduction (RR) ß2-microglobulin 74.7% versus 69.7%, P=0.01; RR myoglobin 62.5% versus 34.3%, P=0.001; RR prolactin 60% versus 32.8%, P=0.001; RR α1-glycoprotein 2.8% versus -0.1%, P=0.01]. We found no difference in the clearance of small and larger middle molecules comparing MCO HD with OL-HDF. Albumin losses were 0.03  g/session with MCO HD and 3.1  g/session with OL-HDF (P=0.001). CONCLUSION: MCO HD is superior to standard HF HD in the removal of middle and larger middle molecules and it is not inferior to OL-HDF in the clearance of small and larger middle molecules. Thus it could be an alternative in patients in which it is not possible to perform OL-HDF.

Any grade of relative overhydration is associated with long-term mortality in patients with Stages 4 and 5 non-dialysis chronic kidney disease.

BACKGROUND: Overhydration (OH) is associated with mortality in chronic kidney disease (CKD). A relative overhydration adjusted for extracellular water (OH/ECW) measured by bioimpedance >15% has shown an increased mortality risk in haemodialysis but few studies have been developed in advanced CKD. Our objective was to evaluate the effect of OH on mortality in patients with Stage 4 or 5 non-dialysis CKD. METHODS: We performed a prospective study of 356 patients enrolled in 2011 and followed up until 2016. At baseline we collected general characteristics, serum inflammatory and nutrition markers, cardiovascular events (CVEs) and body composition using bioimpedance spectroscopy. During a median follow-up of 50 (24-66) months we collected mortality data. RESULTS: The mean creatinine was 3.5 ± 1.3 mg/dL, median proteinuria was 0.5 [interquartile range (IQR) 0.2-1.5] g/24 h, median OH was 0.6 (IQR -0.4-1.5) L and mean relative OH (OH/ECW) was 2.3 ± 0.8%. We found that 32% of patients died. The univariate Cox analysis showed an association between mortality and age, diabetes, previous CVEs, Charlson comorbidity index, low albumin and pre-albumin, high C-reactive protein (CRP), low lean tissue and high OH/ECW. Multivariate Cox analysis confirmed an association between mortality and age {exp(B) 1.1 [95% confidence interval (CI) 1.0-1.3]; P = 0.001}, Charlson comorbidity index [exp(B) 1.1 (95% CI 1.0-1.2); P = 0.01], CRP [exp(B) 1.1 (95% CI 1.0-1.2); P = 0.04], OH/ECW [exp(B) 3.18 (95% CI 2.09-4.97); P = 0.031] and low lean tissue [exp(B) 0.82 (95% CI 0.69-0.98); P = 0.002]. Kaplan-Meier analysis confirmed higher mortality in patients with OH/ECW >0% (log rank 11.1; P = 0.001). CONCLUSION: Any grade of relative OH measured by OH/ECW >0% is associated with long-term mortality in patients with Stage 4 or 5 non-dialysis CKD.

Comparison of urea recirculation and thermodilution for monitoring of vascular access in patients undergoing hemodialysis.

Introduction It is important to monitor vascular access in patients with stage 5 chronic kidney disease receiving hemodialysis. Access recirculation can help to detect a need for intervention. OBJECTIVES: To compare urea recirculation with recirculation by thermodilution using blood temperature monitoring to predict a need for intervention of vascular access over a 6-month period. METHODS: We analyzed urea recirculation and blood temperature monitoring simultaneously in 61 patients undergoing hemodialysis. During the 6-month follow-up, we recorded all cases of angioplasty or surgery (thrombectomy or reanastomosis). In line with previous studies, we considered a value to be positive when urea recirculation was >10% and blood temperature monitoring >15%. Receiver operating characteristic curves were constructed. RESULTS: Mean urea recirculation was 9.5% ± 6.6% and mean blood temperature monitoring 12.9% ± 4.3% (p = 0.001). Urea recirculation >10% had a sensitivity of 80% and specificity of 78%. Blood temperature monitoring >15% had a sensitivity of 33% and specificity of 85%. During follow-up, 25% of patients developed need for intervention of vascular access. We found an association between vascular access dysfunction and urea recirculation. The Kaplan-Meier analysis confirmed an association between urea recirculation and risk of vascular access dysfunction (log rank = 17.2; p = 0.001). We were unable to confirm this association with blood temperature monitoring (log rank = 0.879; p = 0.656). CONCLUSION: Urea recirculation is better predictor of vascular access dysfunction than thermodilution.

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.

Is High-Volume Online Hemodiafiltration Associated With Malnutrition?

Chronic malnutrition is a common problem in patients with end-stage renal disease on hemodialysis. Some studies have reported albumin loss into dialysis fluid during postdilution online hemodiafiltration (OL-HDF). The aim of the study was to assess the nutritional status of patients on high-volume OL-HDF and to demonstrate that higher convective clearances are not associated with malnutrition due to possible loss of nutrients with ultrafiltration. Demographic and clinical data, corporal composition with bioimpedance spectroscopy, dialysis features, albumin loss into dialysis fluid and laboratory parameters were collected in twenty-eight patients with ESRD undergoing postdilution OL-HDF with stable convective volumes over 28 L/session. Convective volume (CV) in the last six months was 32.51 ± 3.52 L per session. Cross-sectional analysis of dialysis features showed 32.7 ± 3.34 L of CV and high reduction rates of beta-2-microglobulin (84.2 ± 3.8%) and cystatin-C (81.6 ± 3.47%). Beta-2-microglobulin reduction showed a positive correlation with prealbumin levels (P = 0.048). CV was only correlated with cystatin-C reduction (P = 0.025). Estimated albumin loss into dialysis fluid (1.82 ± 1.05 g/session) was not related to laboratory or bioimpedance nutritional parameters, or to CV. Among patients with higher CV, serum albumin levels maintained more stability during the observational period. High volume OL-HDF results in better convective clearances and is not associated with malnutrition. Albumin and nutrients loss into dialysis fluid should not be a limiting factor of the substitution volume.

Pulmonary Hypertension Is Associated with Mortality and Cardiovascular Events in Chronic Kidney Disease Patients.

BACKGROUND: We evaluated the prevalence, determinants and prognosis value of pulmonary hypertension (PH) in non-dialysis chronic kidney disease (CKD) patients. METHODS: This is a prospective study with stages 3-5 non-dialysis-dependent CKD patients. PH was estimated by Doppler echocardiography and defined as a pulmonary artery systolic pressure above 35 mm Hg. RESULTS: Three hundred fifty-three patients were recruited, of whom 94 (26.6%) had PH. Prevalence of PH increased with the decline of renal function: 21.6, 24.1, and 31.7% in stages 3, 4, and 5, respectively. Independent predictors of PH were age, estimated glomerular filtration rate (eGFR), history of cardiovascular (CV) events, the presence of an arteriovenous fistulae (AVF), and left ventricular (systolic and diastolic) dysfunction. Over a median follow-up of 22 months, 71 patients died (20%). After multivariate adjustment for age, gender, previous CV disease, diastolic and systolic dysfunction, PH remained as an independent predictor of all-cause mortality (hazards ratio [HR] 1.84, 95% CI 1.06-3.18, p = 0.02). One hundred patients (28%) had a new onset CV event. After adjustment for age, gender, previous CV disease, systolic and diastolic dysfunction, PH maintains its independent association with CV events (HR 2.77, 95% CI 2.00-3.25, p < 0.001). CONCLUSIONS: PH prevalence rises as kidney function declines. Main determinants of PH are age, eGFR, previous CV disease, the presence of an AVF and left ventricular systolic or diastolic dysfunction. PH is an independent predictor of all-cause mortality and CV events.

Allopurinol and progression of CKD and cardiovascular events: long-term follow-up of a randomized clinical trial.

BACKGROUND: Asymptomatic hyperuricemia increases renal and cardiovascular (CV) risk. We previously conducted a 2-year, single-blind, randomized, controlled trial of allopurinol treatment that showed improved estimated glomerular filtration rate and reduced CV risk. STUDY DESIGN: Post hoc analysis of a long-term follow-up after completion of the 2-year trial. SETTING & PARTICIPANTS: 113 participants (57 in the allopurinol group and 56 in the control group) initially followed up for 2 years and 107 participants followed up to 5 additional years. INTERVENTION: Continuation of allopurinol treatment, 100mg/d, or standard treatment. OUTCOME: Renal event (defined as starting dialysis therapy and/or doubling serum creatinine and/or ≥50% decrease in estimated estimated glomerular filtration rate) and CV events (defined as myocardial infarction, coronary revascularization or angina pectoris, congestive heart failure, cerebrovascular disease, and peripheral vascular disease). RESULTS: During initial follow-up, there were 2 renal and 7 CV events in the allopurinol group compared with 6 renal and 15 CV events in the control group. In the long-term follow-up period, 12 of 56 participants taking allopurinol stopped treatment and 10 of 51 control participants received allopurinol. During long-term follow-up, an additional 7 and 9 participants in the allopurinol group experienced a renal or CV event, respectively, and an additional 18 and 8 participants in the control group experienced a renal or CV event, respectively. Thus, during the initial and long-term follow-up (median, 84 months), 9 patients in the allopurinol group had a renal event compared with 24 patients in the control group (HR, 0.32; 95% CI, 0.15-0.69; P=0.004; adjusted for age, sex, baseline kidney function, uric acid level, and renin-angiotensin-aldosterone system blockers). Overall, 16 patients treated with allopurinol experienced CV events compared with 23 in the control group (HR, 0.43; 95% CI, 0.21-0.88; P=0.02; adjusted for age, sex, and baseline kidney function). LIMITATIONS: Small sample size, single center, not double blind, post hoc follow-up and analysis. CONCLUSIONS: Long-term treatment with allopurinol may slow the rate of progression of kidney disease and reduce CV risk.

Clinical, biochemical, and genetic characterization of type III hereditary angioedema in 13 Northwest Spanish families.

BACKGROUND: A new variant of hereditary angioedema has been reported during the last decade. Three main characteristics distinguish it from classic hereditary angioedema: normal C1 inhibitor activity, predominance in women, and different genetic alterations. OBJECTIVE: To assess the symptoms, laboratory findings, and treatment of a population with type III hereditary angioedema from Northwest Spain. METHODS: We studied 29 patients (26 female and 3 male) from 13 different families. RESULTS: The 26 female patients showed a similar clinical pattern to the classic forms of hereditary angioedema, and 22 of these patients had the estrogen-dependent phenotype. Three patients had a negative family history, and 1 of the parents was confirmed as an asymptomatic carrier in 2 of them. All had functional C1 inhibitor activity within the normal range in periods without high estrogen levels, but during attacks (in female patients) and pregnancy, activity decreased to below 50%. One male patient had normal C1 inhibitor activity during attacks, and he was initially diagnosed as having idiopathic angioedema. The C4 and antigenic C1 inhibitor levels were always normal. All studied patients had the c.1032C>A, Thr309Lys mutation in the factor XII gene. The mutation was also found in asymptomatic relatives: 5 of 6 men studied and 1 of 8 women studied. CONCLUSION: Positive family history is a diagnosis criterion, but it could be lacking because there may be asymptomatic relatives, primarily males.