Impact of Serum Magnesium Levels on Kidney and Cardiovascular Prognosis and Mortality in CKD Patients.

INTRODUCTION: In the general population, hypomagnesemia has been associated with cardiovascular events and hypermagnesemia with overall mortality. In chronic kidney disease (CKD) the evidence is not so strong. The objective of our study was to investigate the relationship between serum magnesium (SMg) concentration and cardiovascular morbidity and mortality, all-cause mortality, and the progression to kidney failure in a population with CKD. METHODS: Observational study of a cohort of 746 patients with CKD. Baseline characteristics and analytical profile were collected at the first visit, and patients were followed for a mean of 42.6 months. RESULTS: A cohort of 746 patients were analyzed, age 70 ± 13 years, 62.9% were male, 45.2% had CKD grade 3, and 35.9% grade 4. The mean SMg concentration was 2.09 ± 0.33 mg/dL, with a close correlation between SMg concentration and serum creatinine, phosphorus, and intact parathyroid hormone (iPTH) values. Use of calcitriol was associated with higher SMg (SMgH) concentration, while calcium supplements and proton pump inhibitors (PPIs) were associated with lower SMg concentration. For risk of cardiovascular events, patients with hypermagnesemia had an overall higher risk on a crude analysis (Log Rank 4.83, P = .28) and adjusted analysis (HR = 1.34, CI 1.02-1.77, P = .037). For risk of all-cause mortality, patients with hypermagnesemia had an overall higher risk on crude analysis (Log Rank 13.11, P > .001) and adjusted analysis (HR = 1.5424, IC = 1.002-2.319, P = .049). After performing a propensity score matching for SMg concentration, we achieved two comparable groups of 287 patients, finding again higher all-cause mortality in the hypermagnesemia group (LogRank 15.147, P < .001), that persisted in the Cox model adjusted for calcium, phosphorus, and iPTH. No association was found between SMg concentration and initiation of kidney replacement therapy (KRT). CONCLUSIONS: Magnesium concentration increases with decreasing kidney function. Hypermagnesemia predicts cardiovascular events and all-cause mortality in this same population. Thus, magnesium supplementation should be used with caution in these patients.

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.

Body Composition Affects Urea Distribution Volume Estimated by Watson's Formula.

OBJECTIVE: Dialysis machines use the Watson formula (Vwatson) to estimate the urea distribution volume (UDV) to calculate the online Kt/V for each dialysis session. However, the equation could give rise to inaccuracies. The present study analyzes whether body composition affects UDV estimated by Vwatson in comparison to bioimpedance spectroscopy (Vbis) as the reference method. DESIGN: This is a transversal study performed in the setting of a hemodialysis unit. SUBJECTS: Prevalent hemodialysis patients. INTERVENTION: The same day, UDV was measured using Vwatson and Vbis. We compared their results. MAIN OUTCOME MEASURE: Differences between UDV using Watson equation and Vbis. RESULTS: We included 144 prevalent patients. Vwatson overestimated the volume with regard to Vbis (Vwatson - Vbis) by 2.5 L (1.8 L; P = .001). We found an excellent correlation between the 2 methods. A higher mean Vwatson - Vbis value was correlated to older age (P = .03), body mass index (P = .01), fat tissue index (P = .001), lower lean tissue index (P = .001), lower extracellular water (P = .01), and intracellular water (P = .001). CONCLUSION: Body composition affects UDV estimated by Vwatson, thus modifying the result of Kt/V. In young patients who present more lean tissue and less fat tissue, Kt/V is underestimated with Vwatson.

Body composition affects the response to erythropoiesis-stimulating agents in patients with chronic kidney disease in dialysis.

BACKGROUND: The response to erythropoiesis-stimulating agents (ESA) in patients with chronic kidney disease (CKD) is variable. The body mass index (BMI) variations can modify the response to ESA. The objective was to assess the effect of body composition on the response to ESA in dialysis patients. METHODS: This is an observational cross-sectional study. Prevalent hemodialysis and peritoneal dialysis (PD) patients were selected. In the same day, a single blood test, a body composition analysis using bioimpedance spectroscopy and anthropometric measurements were performed. We collected ESA doses. We analyzed erythropoietin resistance index (ERI). The ERI was calculated dividing the weekly weight-adjusted (kg) dose of ESA (IU) by the hemoglobin level (g/dL). RESULTS: The study was comprised of 218 patients (58% men; age 65 (16) years old; 80% hemodialysis, 20% PD). There was an inverse correlation between ERI and BMI (p=0.01), fat tissue index (FTI) (p=0.01) and prealbumin (p=0.04). We found an independent association between higher ERI levels and lower FTI and prealbumin values. CONCLUSION: Response to ESA is influenced by body composition. Fat tissue favors the body's response to ESA.

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.

Factors related to the absence of anemia in hemodialysis patients.

BACKGROUND: A small number of hemodialysis (HD) patients have normal hemoglobin (Hb) levels without the need for erythropoiesis-stimulating agents (ESAs). The factors associated with this condition have been little studied. The objective of this prospective study was to determine these factors in a prevalent population of HD patients. MATERIALS AND METHODS: All patients who had normal Hb levels and who had not received ESAs in the last 6 months (non-ESA group) were included. Epidemiological and laboratory data were collected and we performed an abdominal ultrasound to assess hepatic and renal cysts. This group was compared to a control group of 205 prevalent HD patients on ESA therapy (control group). RESULTS: We included 45 patients (16% from the whole group) in the non-ESA group. In this group, there was a higher proportion of men (76.5 vs. 61%), patients were younger (61.1 ± 14.7 vs. 67.5 ± 15.2 years), had a longer duration of renal replacement therapy (RRT) (9.4 ± 8.3 vs. 5.3 ± 5.8 years) and had a higher prevalence of adult polycystic kidney disease (APKD) and hepatitis C virus (HCV) liver disease (42.2 vs. 10.2%), p < 0.01. In the non-ESA group, HCV+ patients had a lower prevalence of APKD (2.2 vs. 38.4%) and hepatic cysts (2.2 vs. 19.2%), but significantly higher endogenous erythropoietin levels (55.8 ± 37.1 vs. 30.9 ± 38.4 mU/ml). No significant differences in anemia, iron metabolism, insulin, IGF-1 and renin were found between non-ESA and control groups. Non-ESA patients had a significantly higher number of renal (90.6 vs. 36.5%) and hepatic cysts (12.5 vs. 3.4%), and these were also larger in size (3.3 ± 2.4 vs. 1.5 ± 0.8 cm). In the multivariate Cox analysis, independent predictor factors for absence of anemia in HD patients were number of renal cysts >10 cysts (95% CI 1.058-1.405; p = 0.00), HCV+ liver disease (95% CI 1.147-1.511; p = 0.05) and time on RRT (95% CI 1.002-1.121; p = 0.05). CONCLUSIONS: The absence of anemia in HD patients is not infrequent. Its frequency is higher in men and younger patients with long-term RRT, in patients with HCV+ liver disease and in APKD. It is associated with increased endogenous erythropoietin production and the presence of renal and hepatic cysts.

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.

Intradialytic hypotension and relationship with cognitive function and brain morphometry.

BACKGROUND: The haemodynamic stress brought about by dialysis could justify the loss of structural and functional integrity of the central nervous system (CNS). The main objective of this study was to analyse the relationship between intradialytic hypotension (IDH) and cognitive function and brain morphometry. METHODS: The cross-sectional KIDBRAIN study (Cohort Study of Morphological Changes of the Brain by MRI in Chronic Kidney Disease Patients) included 68 prevalent patients with no history of neurological disorders (cerebrovascular disease and cognitive impairment) undergoing haemodialysis (HD). We analysed 18 non-consecutive dialysis sessions (first three of each month over a 6-month period) and various definitions of IDH were recorded. Global cognitive function (GCF) was assessed using the Mini-Mental State Examination (MMSE) and parameters of structural integrity of the CNS were obtained using volume morphometry magnetic resonance imaging analysis [grey matter (GM), white matter (WM) and hippocampus). RESULTS: A greater number of sessions with IDH were associated with less volume of WM (r = -0.359,P = 0.003) and hippocampus (r = -0.395, P = 0.001) independent of cardiovascular risk factors according to multivariable linear regression models (ß = -0.198, P = 0.046 for WM; ß = -0.253, P = 0.017 for hippocampus). The GCF by the MMSE was 27.3 ± 7.3.1 and was associated with WM volume (ß = 0.403, P = 0.001) independent of GM and hippocampus volume. Symptomatic IDH was associated with GCF (r = -0.420, P < 0.001) in adjusted analysis (ß = -0.339, P = 0.008). CONCLUSIONS: Even when asymptomatic, IDH is associated with a lower WM and hippocampus volume and reduced GCF in patients undergoing HD, thus suggesting greater vulnerability of the brain to the haemodynamic stress that may be generated by a dialysis session.

[Monoclonal gammopathy of undetermined significance and evolution to myeloma: Experience in 153 patients]. / Gammapatía monoclonal de significado incierto y evolución a mieloma múltiple: Experiencia en 153 pacientes.

INTRODUCTION: Based on risk factors, the Mayo Clinic Multiple Myeloma Group (MCMMG) established a model of progression from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) at 20 years. It is also described that MGUS with a progressive increase of monoclonal protein (M-protein) and/or immunoparesis (IMP) may be more predisposed to progress to myeloma. Our objective was to make a review of MGUS, to see how those who presented IMP and/or progression of their M-protein, contrasting them with MGUS that presented intermediate/high and high risk according to MCMMG. METHODOLOGY AND MATERIALS: A review of the MGUS objectified during the realization of a serum proteinogram (SPEP) was carried out during 2010-2014, in our area. Serum immunoglobulins, serum immunofixation (IFs), and serum free light chain ratio (FLCr) were determined for all MGUS. RESULTS: Of the 153 MGUS that are followed up for 4 years, 6 progress to MM. Of these 6 MM, 5 progress from MGUS with intermediate/high risk taking into account the MCMMG. Of these 5, 3 have IMP or progression of their M-protein. 2 present IMP plus progression of their M-protein. The sixth MM evolves from a MGUS without any risk factor, but with progression of its M-protein plus IMP. CONCLUSIONS: IMP and/or M-protein progression are important risk factors to be taken into account in the MGUS, in the first years after diagnosis, due to their possible evolution to MM.

Intradialytic hypotension definitions with mortality prediction capacity in a cohort of haemodialysis patients. / Definiciones de hipotensión intradiálisis con poder predictivo de mortalidad en una cohorte de hemodiálisis.

INTRODUCTION: Intradialytic hypotension (IDH) is a common complication and is associated with higher morbidity and mortality in patients on haemodialysis. However, there is a lack of uniformity in definitions of IDH. The main objective of this study is to analyse clinical and dialysis related factors with several IDH definitions, and its relationship with morbidity and mortality in a cohort of haemodialysis patients. METHODOLOGY: Observational study with a 30-month follow-up period that includes 68 prevalent patients on haemodialysis with at least six months of treatment. We analysed 18 non-consecutive dialysis sessions (first three of each month of a six-month period), and different definitions of IDH were recorded. A positive event of IDH was defined if any definition occurred in more than 25% of the sessions studied. Using survival analysis, we analysed the prediction capacity of each IDH definition (Nadir90, Nadir100, Fall20, Fall30, Fall20Nadir90, Fall30Nadir90, KDOQI, HEMO). The relationship with non-fatal cardiovascular disease and global mortality was estimated using different Cox proportional models. RESULTS: We found IDH definitions that occurred significantly more frequently (Nadir100: 339.8/1,000 sessions, Nadir90: 172.3/1,000 sessions) than others (KDOQI: 98/1,000 sessions, HEMO 129.9/1,000 sessions). We registered 13 fatal events with a mean follow-up of 27.12±6.84 months. A greater number of sessions with IDH according to the Nadir90 definition was a predictive factor of mortality (Log rank 5.02, p=0.025), independent according to adjusted models (HR: 3.23 [95% CI: 1.08-9.6], p=0.035). The definitions Nadir100 (HR: 4.54 [95% CI: 1.25-16.4], p=0.02) and Fall30Nadir90 (HR: 3.08 [95% CI: 1.07-8.8], p=0.03) were independent predictors of non-fatal cardiovascular disease in adjusted models. CONCLUSIONS: Intradialytic hypotension, even asymptomatic, is a predictor of mortality and non-fatal cardiovascular disease in prevalent patients on haemodialysis.

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.

Removal capacity of different high-flux dialyzers during postdilution online hemodiafiltration.

INTRODUCTION: The aim of this study is to compare molecule removal and albumin leakage in postdilution online hemodiafiltration with different high-flux dialyzers. METHODS: We studied seven high-flux dialyzers (Polyflux 210H®, Evodial 2.2®, FxCordiax1000®, Elisio21H®, TS-2.1SL®, XevontaHi20®, VitaPES 210-HF®) in 6 patients. The reduction ratio (RR) of small- and middle-sized molecules was calculated. Dialysate samples were collected to estimate the albumin leakage. FINDINGS: Global differences between dialyzers were observed in the RR of ß2 microglobulin (P =0.003) and prolactin (P =0.013). The mean loss of albumin in the dialysate per session varied between 114 ± 67 mg (with Evodial 2.2) and 2621 ± 1363 mg per session (with XevontaHi20). We found global differences between dialyzers in total albumin loss (P = 0.05). DISCUSSION: We demonstrated that the performance of high-flux dialyzers was different among the types and that not all high-flux dialyzers should be considered equal.

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.

Vascular access clinic results before and after implementing a multidisciplinary approach adding routine Doppler ultrasound. / Consulta de acceso vascular: resultados antes y después de la instauración de un programa multidisciplinar con realización de ecografía doppler de rutina.

BACKGROUND: A multidisciplinary approach and Doppler ultrasound (DU) assessment for the creation and maintenance of arteriovenous fistulas (AVF) for haemodialysis can improve prevalence and patency. The aim of this study was to analyse the impact of a new multidisciplinary vascular access (VA) clinic with routine DU. MATERIAL AND METHODS: We analysed the VA clinic results from 2014 and 2015, before and after the implementation of a multidisciplinary team protocol (vascular surgeon/nephrologist) with routine DU in preoperative mapping and prevalent AVF. RESULTS: We analysed 345 and 364 patients from 2014 and 2015 respectively. The number of surgical interventions was similar in both periods (p=.289), with a trend towards an increase in preventive surgical repair of AVF in 2015 (17 vs. 29, p=.098). 155 vs. 169 new AVF were performed in 2014 and 2015, with a significantly lower primary failure rate in 2015 (26.4 vs. 15.3%, p=.015), and a non-significant increase in radiocephalic AVF, 25.8 vs. 33.2% (n=40 vs. 56), p=.159. The concordance between the indication at the clinic and the surgery performed also increased (81.3 vs. 93.5%, p=.001). Throughout 2015 fewer complementary imaging test were requested from the clinic (78 vs. 35, p <.001), with a corresponding reduction in costs (€87,716 vs. €59,445). CONCLUSIONS: Multidisciplinary approach with routine DU can improve VA results, with a decrease in primary failure rate, higher likelihood of radiocephalic AVF, better management of dis-functioning AVF and lower radiological test costs.

Effectiveness of direct-acting antivirals in Hepatitis C virus infection in haemodialysis patients. / Eficacia de los antivirales de acción directa en la infección por el virus de la hepatitis C en pacientes en hemodiálisis.

Hepatitis C virus (HCV) infection is highly prevalent among patients on haemodialysis and leads to a poorer prognosis compared to patients who do not have said infection. Treatment with interferon and ribavirin is poorly tolerated and there are limited data on the experience with new direct-acting antivirals (DAAs). The aim of this study is to retrospectively analyse the current prevalence of HCV infection and efficacy and safety results with different DAA regimens in the haemodialysis population of 2hospital areas. This is a multicentre, retrospective and observational study in which HCV antibodies were analysed in 465 patients, with positive antibody findings in 54 of them (11.6%). Among these, 29 cases (53.7%) with genotypes 1 and 4 were treated with different DAA regimens, including combinations of paritaprevir/ritonavir, ombitasvir, dasabuvir, sofosbuvir, simeprevir, daclatasvir and ledipasvir, with/without ribavirin. Mean age was 53.3±7.9 years, 72.4% of patients were male and the most important aetiology of chronic kidney disease involved glomerular abnormalities. In 100% of cases, a sustained viral response was achieved after 24 weeks, regardless of DAA regimen received. Adverse effects were not relevant and no case required stopping treatment. In 15 cases, ribavirin was combined with the DAA. In these cases, the most significant adverse effect was anaemic tendency, which was reflected in the increase of the dose of erythropoietin stimulating agents, although none required transfusions. In summary, we conclude that new DAAs for the treatment of HCV in haemodialysis patients are highly effective with minimal adverse effects; it is a very important advance in HCV management. These patients are therefore expected to have a much better prognosis than they have had until very recently.

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.

Importance of Body Water in the Efficacy of Convective Solute Transport in Online Hemodiafiltration.

High-volume online hemodiafiltration (OL-HDF) has been associated with improved patient survival compared to conventional hemodialysis in recent trials, where the importance of convective volume (CV) in this benefit is noted. The purpose of this study was to determine the corporal composition parameters influencing the efficacy of CV in the removal of different molecular weight (MW) molecules. Demographic data, corporal composition parameters with bioimpedance spectroscopy, dialysis features and the reduction rates of different MW molecules in a four-hour OL-HDF session were collected in 61 patients. We observed a significant negative correlation of ß2-microglobulin, cystatin-C, myoglobin and prolactin reduction rates with body surface area, weight, total body extracellular (ECW) and intracellular water (ICW), lean tissue mass and body cellular mass. The multivariable regression analysis identified ECW and ICW as the only corporal composition factors independently associated to the relative elimination of ß2-microglobulin (Beta: -0.801, P = 0.002 for ECW and Beta: -1.710, P = 0.001 for ICW), cystatin-C (Beta: -0.656, P = 0.010 for ECW and Beta: -1.511, P = 0.004 for ICW) and myoglobin (Beta: -0.745, P = 0.014 for ECW and Beta: -2.103, P = 0.001 for ICW), in addition to CV. Prolactin reduction was only associated with ICW (Beta: -1.540, P = 0.028). When adjusting CV with ECW and ICW, only the ratio CV/ECW was an independent predictor for higher elimination of ß2-microglobulin, cystatin-C and myoglobin. The corporal composition parameters independently associated to the reduction of medium-sized molecules are the extracellular and intracellular water. The ratio "convective volume/extracellular water" predicts higher efficacy of convective transport. Adjusting the convective volume to patient features could be useful to monitor the efficacy of OL-HDF and to prescribe individualized therapies.

Anemia management and treatment response in patients on hemodialysis: the MAR study.

BACKGROUND: Anemia management guidelines describe the importance of anemia as a risk factor in hemodialysis and the need for clinical prospective studies focused on this role of anemia. Response to treatment with iron and epoetin is multifactorial, and results are still far from the targets set by the guidelines. The Morbidity and Mortality Anemia Renal study (MAR) is a multicenter prospective cohort study of hemodialysis (HD), designed to assess the burden of anemia on morbidity and mortality. We report here a cross-sectional analysis of the management of anemia, and response-to-treatment factors. METHODS: A total of 1,710 patients were included (60% male, mean age 64.4 +/- 13.6 years, mean 16.2 +/- 11.1 months on HD) with a high comorbidity (hypertension 75.8%, diabetes 25.9%, heart failure 13.9% and coronary disease 16.7%) and a mean Charlson Index of 6.5 +/- 2.3. RESULTS: There were 28.7% of patients who had started epoetin before end-stage renal disease (pre-ESRD), 81.4% of patients displayed Hb <11 g/dL when initiating HD with a mean Hb of 9.7 g/dL. Only 67.9% of prevalent HD patients attained a hemoglobin (Hb) level above 11 g/dL, 89.5% achieved a ferritin level above 100 ng/mL, 76.7% a transferrin saturation index (TSI) above 20%, and 61.1% met all 3 objectives. The multivariate analysis identified the following risk factors for Hb <11g/dL: low albumin (odds ratio, OR = 1.75), HD efficacy below objectives (OR = 1.44) and female sex (OR = 1.36), corrected for comorbidity, epoetin treatment, transfusion, surgery or hospital admission. CONCLUSIONS: As compared with previous surveys, we found an improved but still inadequate anemia management in Spanish HD patients. Our results are comparable with those of Euro-DOPPS. Several modifiable factors related to a lower Hb concentration were assessed. On behalf of the MAR Study Group.

Haematuria on the Spanish Registry of Glomerulonephritis.

Recent studies suggest a pathogenic role for glomerular haematuria among renal function. However, there is no data on the prevalence of haematuria from a large renal biopsy registry. We analysed the prevalence of gross (GH) and microscopic (mH) haematuria in 19,895 patients that underwent native renal biopsies from the Spanish Registry of Glomerulonephritis. Haematuria's overall incidence was 63% (GH 8.6% and mH 55.1%), being more frequent in males (64.7% vs. 62.4%). GH was more prevalent in patients <18 years (21.3% vs. 7.7%). The commonest clinical presentation associated with GH was acute kidney injury (31.5%) and IgA Nephropathy (IgAN) (33.6%) was the most frequent histological finding. GH patients showed a significantly (p < 0.05) lower eGFR and proteinuria levels as compared with patients with mH and without haematuria. Moreover, mH was more prevalent in adults (56.3%). Nephrotic syndrome was the commonest clinical presentation in mH patients (32.2%) and IgAN (18.5%) the most frequent histological finding. In conclusion, haematuria, is a frequent urinalysis finding in patients underwent native renal biopsy. The most frequent histological finding in both GH and mH is IgAN. Whereas, GH is more frequent in young males with acute kidney injury, mH is commoner among adults with nephrotic syndrome.

Creatine-kinase and dialysis patients, a helpful tool for stratifying cardiovascular risk?

BACKGROUND AND AIMS: Hemodialysis patients have an enhanced risk for cardiovascular events. Cardiac biomarkers provide useful information for stratifying their risk. However the prognosis value of creatine kinase MB isoenzyme (CKMB) has not yet been validated in this population. The aim of the present study is to determine the predictable value of CK-MB in hemodialysis. METHODS: A cohort of 211 hemodialysis patients (58.3% male, median age 73 (60-80) years) were followed for 39 (19-56) months. Cardiac biomarkers including CKMB were recorded at baseline. Factors associated to CKMB and prognosis value of this biomarker was studied. RESULTS: The median value of CKMB was 1 (1-2) ng/mL with no patient exceeding normal laboratory values. Previous heart disease, diabetes mellitus, peripheral vascular disease and systolic and diastolic dysfunction were associated with higher levels of CKMB. Ninety-four patients (44.5%) cardiovascular events were recorded. CKMB levels ≥2ng/mL was independently associated to cardiovascular events during the follow up after adjusting. Adding CKMB to a model including several variables for predicting cardiovascular events, resulted in 17% improvement in risk discrimination (IDI) with a relative IDI of 9.9% (p=0.04). CONCLUSIONS: CKMB is a good marker for stratifying cardiovascular risk in hemodialysis patients and adds prognosis information to other well known independent predictors for cardiovascular events.