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.

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.

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.

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.

Interarm systolic blood pressure as a predictor of cardiovascular events in patients with chronic kidney disease.

BACKGROUND: Increased interarm systolic blood pressure difference (IASBPD) is associated with mortality and cardiovascular (CV) events both in the general population and in patients at high CV risk. The aim of the present study was to assess the value of IASBPD ≥ 10 mmHg for predicting CV events in patients with chronic kidney disease (CKD). METHODS: The study sample comprised 652 patients with CKD (age 67 ± 15 years, 58.1% men). Follow-up was 19 ± 5 months. We recorded increased IASBPD and related factors and assessed the predictive value of this variable for CV events. RESULTS: We recorded diabetes mellitus in 136 patients (20.8%), history of CV disease in 213 (32.6%) and dyslipidaemia in 327 (50.1%). The mean glomerular filtration rate was 45.9 ± 18.9 mL/min/1.73 m(2), and the median albumin/creatinine ratio was 26(0-151) mg/g. IASBPD was ≥10 mmHg in 184 patients (28.1%). The factors associated with IASBPD ≥10 mmHg were age, systolic blood pressure levels, history of congestive heart failure, lower levels of high-density lipid cholesterol and higher use of hypertensive drugs. Fifty-eight patients (8.5%) developed a CV event during the follow-up. IASBPD ≥10 mmHg [HR, 1.802, 95%CI (1.054-3.079); P = 0.031] was an independent predictor of CV events. CONCLUSIONS: Increased IASBPD is an independent predictor of CV events in CKD patients.

Management of resistant hypertension: aldosterone antagonists or intensification of diuretic therapy?

OBJECTIVE: No consensus has been established as to which is the best fourth-line agent in patients with resistant hypertension (RHT). The aim of the present study was to assess the effect of intensifying diuretic treatment with loop diuretic (furosemide) or aldosterone antagonist (spironolactone) on blood pressure (BP) control in RHT. METHODS: The study population comprised 30 patients with RHT who were divided into two treatment arms. Fifteen patients received furosemide 40 mg/day and 15 patients received spironolactone 25 mg/day. Ambulatory BP monitoring was performed baseline, 3 and 6 months. RESULTS: Baseline BP was 162 ± 8/90 ± 6 mmHg, 70% men, mean age 63.3 ± 9.1 years 56.1% diabetic and estimated glomerular filtration rate (eGFR) 55.8 ± 16.5 mL/min per 1.73 m(2) . There were no significant differences between groups at baseline in age, gender, percentage diabetics, eGFR, BP, number of antihypertensive drugs, or aldosterone levels. At 6 months, systolic BP decreased by 24 ± 9.2 mmHg (from 163.6 ± 8.6 to 139.6 ± 8.1 mmHg) in the spironolactone group, compared with 13.8 ± 2.8 mmHg (from 162 ± 7.9 to 148 ± 6.4 mmHg) in the furosemide group (P < 0.01). Diastolic BP fell 11 ± 8.1 mmHg in the spironolactone group compared with 5.2 ± 2.2 mmHg in the furosemide group (P < 0.01). Significant reduction in urinary albumin creatinine ratio (from 173 ± 268 to 14 ± 24 mg/g, P < 0.01) was observed in the spironolactone group at 6 months. Multiple regression analysis showed that only treatment with spironolactone was associated with control of BP < 140/90 mmHg at 6 months. No severe adverse events were recorded. CONCLUSION: Spironolactone is more effective than furosemide for control of BP in RHT patients, with a positive added effect on albuminuria. Spironolactone is safe in patients with mild kidney impairment, although serum potassium should be closely monitored, especially in diabetics.

Effect of dual blockade of the renin-angiotensin system on the progression of type 2 diabetic nephropathy: a randomized trial.

BACKGROUND: Blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers has been shown to lessen the rate of decrease in glomerular filtration rate in patients with diabetic nephropathy. STUDY DESIGN: A multicenter open-label randomized controlled trial to compare the efficacy of combining the angiotensin-converting enzyme inhibitor lisinopril and the angiotensin II receptor blocker irbesartan with that of each drug in monotherapy (at both high and equipotent doses) in slowing the progression of type 2 diabetic nephropathy. SETTING & POPULATION: 133 patients with type 2 diabetic nephropathy (age, 66 ± 8 years; 76% men) from 17 centers in Spain. INTERVENTION: Patients were randomly assigned (1:1:2) to lisinopril (n = 35), irbesartan (n = 28), or the combination of both (n = 70). OUTCOMES: The primary composite outcome was a >50% increase in baseline serum creatinine level, end-stage renal disease, or death. RESULTS: Baseline values for mean estimated glomerular filtration rate and blood pressure were 49 ± 21 mL/min/1.73 m(2) and 153 ± 19/81 ± 11 mm Hg. Mean geometric baseline proteinuria was protein excretion of 1.32 (95% CI, 1.10-1.62) g/g creatinine. After a median follow-up of 32 months, 21 (30%) patients in the combination group, 10 (29%) in the lisinopril group, and 8 (29%) in the irbesartan group reached the primary outcome. HRs were 0.96 (95% CI, 0.44-2.05; P = 0.9) and 0.90 (95% CI, 0.39-2.02; P = 0.8) for the combination versus the lisinopril and irbesartan groups, respectively. There were no significant differences in proteinuria reduction or blood pressure control between groups. The number of adverse events, including hyperkalemia, was similar in all 3 groups. LIMITATIONS: The study was not double blind. The sample size studied was small. CONCLUSIONS: We were unable to show a benefit of the combination of lisinopril and irbesartan compared to either agent alone at optimal high doses on the risk of progression of type 2 diabetic nephropathy.

Detection of patients at high risk for non-occlusive mesenteric ischemia in hemodialysis.

BACKGROUND: Nonocclusive mesenteric ischemia (NOMI) is an emerging condition in hemodialysis (HD) patients not widely studied. MATERIALS AND METHODS: A retrospective study was conducted between 2003 and 2011. NOMI cases were recorded, and demographic, clinical, biochemical, and HD parameters were collected. This group was compared with a control group (n = 93). Risk factors, prognosis, and survival were analyzed. RESULTS: There were 57 episodes of NOMI (incidence, 2.29 episodes per 100 patients/y). Cecum was the most frequently affected segment. Nineteen patients (33%) underwent surgery. Twenty-six patients (59%) did not survive the acute episode. Cecal damage was the only protective factor associated with mortality (relative risk [RR], 0.712; P = 0.044). The incidence of NOMI was related to erythropoietin resistance index, diabetes mellitus, and longer time on HD compared with control group (RR, 6.92, P = 0.009; RR, 9.98, P = 0.005; and RR, 1.017, P < 0.001, respectively). Mortality in survival NOMI patients was higher at 4-y follow-up compared with that in the control group (log-rank, 15.5; P < 0.0001). CONCLUSIONS: NOMI is associated with erythropoietin resistance index, diabetes mellitus, and longer time on HD. Hypotension must be avoided in these high-risk patients to prevent NOMI.

Urate reduction and renal preservation: what is the evidence?

Hyperuricemia is common among chronic kidney disease (CKD) patients. Experimental evidence suggests that uric acid itself may harm patients with CKD by contributing to CKD progression. Although controversial, these observations are supported by many large observational studies indicating that increased serum uric acid level predicts the development and progression of CKD in a variety of populations. Interventional studies also suggest that reducing uric acid levels in asymptomatic hyperuricemic patients with CKD is safe and might slow CKD progression. However, these studies are limited in scope and have included a relatively small number of participants. Thus, although these data suggest treating asymptomatic hyperuricemia, further studies are needed before we can advise reducing uric acid levels in patients with CKD.

Type of vascular access and survival among very elderly hemodialysis patients.

The use of central venous catheters (CVC) for hemodialysis (HD) is associated with higher mortality compared to arteriovenous access (AV). However, studies analyzing the influence of the type of vascular access on the survival of very elderly patients (≥75 years) initiating HD are few and involve only a limited number of patients. We studied a cohort of 5,466 incident patients who started HD; of these, 1,841 were aged ≥75. Types of vascular access for HD were classified as either CVC, which included both tunneled and non-tunneled catheters, or AV, which included AV fistula and grafts. The outcome of the study was all-cause mortality during the follow-up period. In the whole cohort, AV use was associated with a survival advantage over CVC use (88 and 63% at 2 and 5 years, respectively, in patients with an AV as compared to 75 and 48% in patients with a CVC) (p < 0.0001). Among patients ≥75, CVC use was associated with a higher number of deaths compared to AV use. Patients ≥75 with an AV showed a greater survival as compared to patients ≥75 with a CVC (80 and 53% at 2 and 5 years, respectively, vs. 68 and 43%; p < 0.0001). Multivariate analysis revealed that CVC use and the presence of arrhythmia were independent risk factors of death in patients ≥75, whereas obesity was associated with greater survival. In conclusion, the type of vascular access has a significant influence on the survival of very elderly patients (≥75) initiating HD. CVC use was associated with poorer survival compared to AV access.

Utility of bioimpedance spectroscopy (BIS) in the management of refractory hypertension in patients with chronic kidney disease (CKD).

BACKGROUND: Expansion of extracellular volume (ECV) is a frequent cause of resistant hypertension (RHT) in patients with chronic kidney disease (CKD). The aim of this exploratory study was that of applying bioimpedance spectroscopy (BIS) for the identification of CKD patients with RHT and expansion of ECV, while trying to control blood pressure (BP) using an intensification of diuretic treatment. METHODS: We included 50 patients with RHT and CKD who underwent BIS. In order to control BP, diuretic treatment was intensified in those patients with expansion of the ECV. In all other cases, another antihypertensive drug was added. RESULTS: The mean age was 68.2 ± 10.4 years, 68% were male and 58% were diabetic. The mean estimated glomerular filtration rate (eGFR) was 50.7 ± 22.4 mL/min/1.72 m(2). Baseline systolic BP was 167.2 ± 8.6 mmHg and diastolic BP was 84.8 ± 9.5 mmHg. The mean number of antihypertensive drugs received was 3.8 ± 0.9. Expansion of ECV was recorded in 30 (60%) patients and was more frequent in diabetics and in patients with more albuminuria. At 6 months of follow-up, a decline of 21.4 ± 7.1 mmHg was observed in systolic BP in the patients with expansion of ECV, compared with a decrease of 9.4 ± 3.4 mmHg in the normal ECV group (P < 0.01). We did not find differences in the decrease in diastolic BP between the groups. Nine patients (30%) with ECV expansion who increased diuretic therapy reached the target blood pressure (BP) of <140/90 mmHg, when compared with only two patients (10%) who had normal ECV and in whom other antihypertensive drug was added. A total decrease in body water of 1.9 ± 1.1 L was observed in patients with ECV expansion who intensified diuretic treatment at the expense of a decline in ECV of 1.1 ± 1 L. eGFR remained stable in both groups (47.1 ± 21.1 versus 54.1 ± 25.2 mL/min/1.73 m(2); P = 0.37). CONCLUSIONS: An increase in ECV as measured by BIS frequently occurs in RHT in patients with CKD. Diabetic and severe proteinuric patients are more exposed to expansion of ECV. BIS is a potentially useful method for identifying and treating patients with RHT and expansion of ECV. The hypothesis generated by this exploratory study needs to be tested in a randomized clinical trial.

Intraindividual interleukin-6 variations on the cardiovascular prognosis of patients with chronic renal disease.

In chronic kidney disease (CKD) patients on dialysis, plasma interleukin (IL)-6 levels predict mortality better than other markers. Impact of intraindividual changes of inflammatory markers on cardiovascular (CV) events in CKD patients is unknown. The aim of this study is to demonstrate the relation between CV outcomes and variations of C-reactive protein (CRP), IL-6, IL-1ß, and tumor necrosis factor (TNF)-α in CKD. Ninety patients (mean age: 68.5 ± 12.8 years) at different stages (1-4) of CKD were evaluated. Serum CRP, IL-6, IL-1ß, and TNF-α were measured basally and after taking statins or angiotensin II receptor blockers. Three patterns were defined for each marker (baseline, mean of two measurements, and variation of the marker: increase or decrease after 6 months). During follow-up (mean time: 72.7 ± 19.8 months), 14 patients died, 11 were included on dialysis program, and 29 suffered a CV event. Patients with persistently elevated IL-6 values had higher risk to develop CV events [OR = 1.21 (1.11-1.32), p = 0.001]. Mean of two measurements of IL-6 was a better predictor for events than a single measurement of IL-6, CRP, TNF-α, and IL-1ß. A mean of two determinations of plasma IL-6 greater than 6 pg/mL and previous peripheral vascular disease was related to an increased risk for CV events [2.34 (1.05-5.22), p = 0.037 and 2.95 (1.27-6.93), p = 0.011, respectively] in an adjusted Cox regression model. IL-6 is a better inflammatory marker than CRP, TNF-α, and IL1ß at predicting CV events in CKD nondialysis patients. Mean of two measurements is better than simple determinations at predicting CV outcome.

Baseline characteristics of patients with chronic kidney disease stage 3 and stage 4 in Spain: the MERENA observational cohort study.

BACKGROUND: To obtain information on cardiovascular morbidity, hypertension control, anemia and mineral metabolism based on the analysis of the baseline characteristics of a large cohort of Spanish patients enrolled in an ongoing prospective, observational, multicenter study of patients with stages 3 and 4 chronic kidney diseases (CKD). METHODS: Multicenter study from Spanish government hospital-based Nephrology outpatient clinics involving 1129 patients with CKD stages 3 (n = 434) and 4 (n = 695) defined by GFR calculated by the MDRD formula. Additional analysis was performed with GFR calculated using the CKD-EPI and Cockcroft-Gault formula. RESULTS: In the cohort as a whole, median age 70.9 years, morbidity from all cardiovascular disease (CVD) was very high (39.1%). In CKD stage 4, CVD prevalence was higher than in stage 3 (42.2 vs 35.6% p < 0.024). Subdividing stage 3 in 3a and 3b and after adjusting for age, CVD increased with declining GFR with the hierarchy (stage 3a < stage 3b < stage 4) when calculated by CKD-EPI (31.8, 35.4, 42.1%, p 0.039) and Cockcroft-Gault formula (30.9, 35.6, 43.4%, p 0.010) and MDRD formula (32.5, 36.2, 42.2%,) but with the latter, it did not reach statistical significance (p 0.882). Hypertension was almost universal among those with stages 3 and 4 CKD (91.2% and 94.1%, respectively) despite the use of more than 3 anti-hypertensive agents including widespread use of RAS blockers. Proteinuria (> 300 mg/day) was present in more than 60% of patients and there was no significant differences between stages 3 and 4 CKD (1.2 ± 1.8 and 1.3 ± 1.8 g/day, respectively). A majority of the patients had hemoglobin levels greater than 11 g/dL (91.1 and 85.5% in stages 3 and 4 CKD respectively p < 0.001) while the use of erythropoiesis-stimulating agents (ESA) was limited to 16 and 34.1% in stages 3 and 4 CKD respectively. Intact parathyroid hormone (i-PTH) was elevated in stage 3 and stage 4 CKD patients (121 ± 99 and 166 ± 125 pg/mL p 0.001) despite good control of calcium-phosphorus levels. CONCLUSION: This study provides an overview of key clinical parameters in patients with CKD Stages 3 and 4 where delivery or care was largely by nephrologists working in a network of hospital-based clinics of the Spanish National Healthcare System.

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.

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.