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.

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.

The new marker YKL-40, a molecule related to inflammation, is associated with cardiovascular events in stable haemodialysis patients.

BACKGROUND: YKL-40 is a glycoprotein associated with inflammatory conditions, including atherosclerosis and endothelial dysfunction. The objective was to analyse serum YKL-40 levels in a haemodialysis population and explore their association with dialysis dosing measures, inflammation, body composition and development of cardiovascular (CV) events. METHODS: We performed a prospective study of 78 chronic haemodialysis patients enrolled in 2013 and followed up until 2018. At baseline, serum YKL-40, inflammatory and nutrition markers and body composition were assessed. During a median follow-up of 43 (interquartile range 24-66) months, CV events were recorded. RESULTS: The mean age of patients was 62 ± 16 years and 66% were men. The mean YKL-40 was 207 ± 106 ng/dL. Higher YKL-40 levels were associated with lower Kt/V urea, convective volume, serum albumin and prealbumin and with higher troponin T. During follow-up, 50% developed CV events. Cox analysis showed an association between CV events and YKL-40, diabetes, hypertension, C-reactive protein, lower prealbumin, ß2-microglobulin, glycosylated haemoglobin and troponin T values. The multivariate Cox analysis confirmed an independent association between CV events and YKL-40 {hazard ratio [HR] 1.067 [95% confidence interval (CI) 1.009-1.211]; P: 0.042}, troponin T [HR 1.037 (95% CI 1.009-1.683); P: 0.007], lower prealbumin [HR 0.827 (95% CI 0.224-0.988); P: 0.009] and diabetes [HR 2.103 (95% CI 1.554-3.172); P: 0.008]. Kaplan-Meier confirmed the association between CV events and YKL-40 (log rank 7.28; P = 0.007). CONCLUSIONS: YKL-40 is associated with CV events in haemodialysis patients. Higher dialysis dose and convective volume are associated with lower serum YKL-40 levels.

Exercise training during hemodialysis sessions: Physical and biochemical benefits.

Chronic inflammation, protein-energy wasting, and poor physical functioning are highly prevalent among patients with chronic kidney disease (CKD). These factors are associated with disability and increase of cardiovascular risk. The aim of this study is to evaluate the effects of exercise training during hemodialysis (HD) sessions on physical functioning, body composition, and nutritional and inflammatory status. We performed a prospective intervention study including patients on prevalent HD therapy. Patients were evaluated at baseline visit by Rehabilitation and Physiotherapy specialists and the exercise program was adapted to each patient's physical capacity. In addition to demographic, clinical, body composition and functional ability data, serum markers regarding nutritional and inflammatory status were collected at baseline and after 3 months of exercise training. We observed a significant improvement after 3-month follow-up in functional ability (6 minute walk test [6MWT] [403.15 ± 105.4 vs 431.81 ± 115.5 m, P < .001], sit-to-stand repetitions in 30 seconds [12.2 ± 4.2 vs 14.1 ± 5.0 repetitions, P = .003] and dynamometry [24.5 ± 11.9 vs 29.5 ± 12.5 kg, P < 0.001]), body composition with increase of body mass index (BMI) (23.7 ± 4.4 vs 24.1 ± 4.7 kg/m2 , P = 0.01) at the expense of lean tissue index (LTI) (14.9 ± 3.7 vs 16.2 ± 2.9 kg/m2 , P = 0.038) and lipid parameters with LDL-cholesterol decrease (70.2 ± 17.9 vs 64.9 ± 21.3 mg/dL, P = .03) and lower serum triglyceride levels (125.8 ± 54.0 vs 108.2 ± 44.6 mg/dL, P = .006). In addition, we found a decrease in iron (155.6 ± 148.2 vs 116.7 ± 110.8 mg, P = .029) and erythropoietin (117.5 ± 84.2 vs 99.2 ± 74.5 µg, P = .023) requirements. The implementation of exercise training programs during HD can improve physical functioning, body composition and lipid and anemia profile. Supervised exercise programs could be included as part of HD patient care to improve physical capacity in these patients.

Mixed cryoglobulinaemia vasculitis after sustained hepatitis C virological response with direct-acting antivirals.

Mixed cryoglobulinaemia (MCG) is one of the most severe extrahepatic hepatitis C virus (HCV)-associated complications, and could involve several organs, including the kidney. MCG prognosis relies on HCV response to antiviral treatment and has changed over the last years, especially after the introduction of new direct acting antivirals (DAA). MCG persistence despite sustained virological response (SVR) is uncommon and has a poorly known meaning and prognosis. We report a case of a patient with chronic HCV infection treated with DAA who developed MCG vasculitis despite the SVR.

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.

Middle molecule elimination in expanded haemodialysis: only convective transport?

BACKGROUND: New high-retention onset dialysers have shown improved efficacy in the elimination of uraemic toxins, and their depurative capacity has been compared with high convective volumes of online haemodiafiltration. Haemodialysis (HD) using high-flux membranes leads to convective transport by internal filtration [direct filtration (DF)/backfiltration (BF)] and allows the removal of middle molecules (MMs). The aim of this study was to assess solute transport mechanisms in expanded HD (HDx). METHODS: In 14 4-h HDx sessions with Theranova-500 dialysers under similar dialysis conditions (blood flow 400 mL/min, dialysate flow 700 mL/min, dialysate temperature 35.5°C), pressures at the inlet and outlet of both dialyser compartments (P bi, P bo, P di and P do) were collected hourly to estimate DF/BF volumes by semi-empirical methods. Uraemic toxins with various molecular weights were measured pre-dialysis, at 1 h (pre-filter and post-filter) and post-dialysis to calculate molecules' reduction over time and dialyser in vivo clearances. RESULTS: Ultrafiltration was 1.47 ± 0.9 L and Kt/V 1.74 ± 0.3. Hydrodynamic data (P bi: 259 ± 39, P bo: 155 ± 27, P di: 271 ± 30, P do: 145 ± 29 mmHg and oncotic pressure 22.0 ± 3.5 mmHg) allowed the estimation of DF/BF rates. DF flow ranged from 29.5 ± 4.2 to 31.3 ± 3.9 mL/min and BF flow ranged from 25.1 ± 2.3 to 23.4 ± 2.6 mL/min. The highest calculated DF volume was 7506.8 ± 935.3 mL/session. Diffusive clearances (K d) of all solutes were higher than their convective transport (all P < 0.001) except for prolactin (23 kDa) clearances, which showed no differences. Total clearances of all solutes were correlated with their K d (ρ = 0.899-0.987, all P < 0.001) and Kt/V correlated with all reduction rates (ρ = 0.661-0.941, P = 0.010 to <0.001). DF flow was only associated with urea (ρ = -0.793, P = 0.001), creatinine (ρ = -0.675, P = 0.008) and myoglobin clearance (ρ = 0.653, P = 0.011). CONCLUSION: Results suggest that diffusive transport is a main mechanism of MM elimination in HDx. HDx offers an efficient depuration of MM without the need for high convective volumes.

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.

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.

Returning to haemodialysis after kidney allograft failure: a survival study with propensity score matching.

BACKGROUND: Patients who return to dialysis after kidney allograft failure (KAF) are classically considered to have lower survival rates than their transplant-naïve incident dialysis counterparts. However, this observation in previous comparisons could be due to poor matching between the two populations. METHODS: To compare survival rates between patients who returned to haemodialysis (HD) after KAF versus transplant-naïve incident HD patients, we performed a retrospective study using the EuCliD® database (European Clinical Database) that collects data from Fresenius Medical Care (FMC) outpatient HD facilities in Spain. Propensity score matching (PSM) was performed to homogenize both populations. RESULTS: This study included 5216 patients from 65 different FMC clinics between 2009 and 2014. Naïve incident HD patients were mostly male, older, comorbid and more commonly had catheters as vascular access. During the study follow-up, 3915 patients exited, of whom 1534 died. The mean survival time for the entire cohort was 4.86 years [95% confidence interval (CI) 4.78-4.94]. Univariate Cox analysis indicated higher mortality risk among transplant-naïve incident HD patients [hazard ratio (HR) 1.728; 95% CI 1.35-2.21; P < 0.001). However, this difference was no longer significant after multivariate adjustment. After applying PSM to minimize the bias due to indication issue, we obtained an adjusted population composed of 480 naïve and 240 KAF patients. The results analysing the PSM-adjusted cohort confirmed similar survival in both cohorts (log-rank, 3.34; P = 0.068; HR 1.382; 95% CI 0.97-1.95; P = 0.069). CONCLUSIONS: When comparing properly matched patient groups, patients who return to HD after KAF present similar survival than survival than transplant-naïve incident patients.

Rationale and design of the PHYSICALFAV trial: a randomized controlled trial to evaluate the effect of preoperative isometric exercise on vascular calibre and maturation of autologous arteriovenous fistulas.

BACKGROUND: A good vascular access (VA) is vital for haemodialysis (HD) patients. HD with an autologous arteriovenous fistula (AVF) is associated with higher survival, lower health care costs and fewer complications. Although a distal forearm AVF is the best option, not all patients are good candidates for this approach and the primary failure rate ranges from 20% to 50%. The optimal AVF depends mainly on the anatomical and haemodynamic characteristics of the artery and the vein chosen for the anastomosis. These characteristics can be modified by performing physical exercise. VA guidelines suggest that isometric exercises should be performed both before and after the AVF is created. While the literature contains few data on the potential efficacy of preoperative exercise, small observational studies point to an improvement in venous and arterial calibre. Postoperative exercise also seems to improve maturation, although there is no consensus on the appropriate exercise protocol. METHODS: The PHYSICALFAV trial (NCT03213756) is an open-label, multicentre, prospective, controlled, randomized trial designed to evaluate the usefulness of preoperative isometric exercise (PIE) in pre-dialysis patients or in prevalent HD patients who are candidates for a new AVF. Patients are randomized 1:1 to the PIE group (isometric exercises for 8 weeks) or the control group (no exercise). The main endpoint is whether the rate of primary failure is lower in the PIE group than in the control group. RESULTS: The trial has already started, with 40 patients having been enrolled as of 21 March 2018; 26.5% of the estimated sample.

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.

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.

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.

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.

Fabry Nephropathy: An Evidence-Based Narrative Review.

Fabry disease (FD) is a rare, X-linked disorder caused by mutations in the GLA gene encoding the enzyme α-galactosidase A. Complete or partial deficiency in this enzyme leads to intracellular accumulation of globotriaosylceramide (Gb3) and other glycosphingolipids in many cell types throughout the body, including the kidney. Progressive accumulation of Gb3 in podocytes, endothelial cells, epithelial cells, and tubular cells contribute to the renal symptoms of FD, which manifest as proteinuria and reduced glomerular filtration rate leading to renal insufficiency. A correct diagnosis of FD, although challenging, has considerable implications regarding treatment, management, and counseling. The diagnosis may be confirmed by demonstrating the enzyme deficiency in males and by identifying the specific GLA gene mutation in male and female patients. Treatment with enzyme replacement therapy, as part of the therapeutic strategy to prevent complications of the disease, may be beneficial in stabilizing renal function or slowing its decline, particularly in the early stages of the disease. Emergent treatments for FD include the recently approved chaperone molecule migalastat for patients with amenable mutations. The objective of this report is to provide an updated overview on Fabry nephropathy, with a focus on the most relevant aspects of its epidemiology, diagnosis, pathophysiology, and treatment options.

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.

Hyperuricemia is associated with progression of chronic kidney disease in patients with reduced functioning kidney mass.

BACKGROUND AND OBJECTIVES: Hyperuricemia plays a major role in the development and progression of chronic kidney disease (CKD). Many large observational studies have indicated that increased serum uric acid level predicts the development and progression of CKD in some population, however this hypothesis has not been yet studied in patients with reduced renal mass. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Retrospective study with a cohort of 324 patients with reduced renal mass from an outpatient basis, followed during 60 (36-98) months. Demographics variables, cardiovascular factors, concomitant medications, albuminuria and uric acid levels were recorded yearly. The primary endpoint was the annual fall of estimated glomerular filtration rate (eGFR) by MDRD-4. The sample was divided into three successive groups (A1: patients with fall of eGFR lower than median, A2: greater than median, B: without fall of eGFR). Factors associated and predictors of kidney function decline were analyzed. RESULTS: One hundred and seventy out of 324 patients suffered a fall of eGFR (group A), (median of fall -1.6ml/min/1.73m2/year (-3.0, -0.7)). Male gender, albuminuria>100mg/day and higher pulse pressure were associated to progression in our cohort (group A). Hyperuricemia was more frequent among patients with higher kidney disease progression (group A2) (33% vs 49%, p=0.04) when comparing to lower progression (group A1). Adjusted Cox regression models showed that hyperuricemia, pulse pressure and albuminuria were independent predictors of kidney disease progression (HR 1.67 (1.06-2.63), p=0.023; 1.02 (1.01-1.03), p=0.001 and HR: 2.14 (1.26-3.64), p=0.005, respectively). Kidney disease progression was higher in patients with unilateral renal atrophy or agenesis than nephrectomy (log rank: 7.433, p=0.006). CONCLUSIONS: Hyperuricemia is independently associated with kidney disease progression in patients with reduce functioning renal mass.