Alba Santos

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.

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-1β, 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-1β, 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-1β. 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 IL1β at predicting CV events in CKD nondialysis patients. Mean of two measurements is better than simple determinations at predicting CV outcome.

Haematuria increases progression of advanced proteinuric kidney disease

Background Haematuria has been traditionally considered as a benign hallmark of some glomerular diseases; however new studies show that haematuria may decrease renal function. Objective To determine the influence of haematuria on the rate of chronic kidney disease (CKD) progression in 71 proteinuric patients with advanced CKD (baseline eGFR <30 mL/min) during 12 months of follow-up. Results The mean rate of decline in eGFR was higher in patients with both haematuria and proteinuria (haemoproteinuria, HP, n=31) than in patients with proteinuria alone (P patients, n=40) (-3.8±8.9 vs 0.9±9.5 mL/min/1.73m2/year, p<0.05, respectively). The deleterious effect of haematuria on rate of decline in eGFR was observed in patients <65 years (-6.8±9.9 (HP) vs. 0.1±11.7 (P) mL/min/1.73m2/year, p<0.05), but not in patients >65 years (-1.2±6.8 (HP) vs. 1.5±7.7 (P) mL/min/1.73m2/year). Furthermore, the harmful effect of haematuria on eGFR slope was found patients with proteinuria >0.5 g/24 h (-5.8±6.4 (HP) vs. -1.37± 7.9 (P) mL/min/1.73m2/year, p<0.05), whereas no significant differences were found in patients with proteinuria < 0.5 g/24 h (-0.62±7.4 (HP) vs. 3.4±11.1 (P) mL/min/1.73m2/year). Multivariate analysis reported that presence of haematuria was significantly and independently associated with eGFR deterioration after adjusting for traditional risk factors, including age, serum phosphate, mean proteinuria and mean serum PTH (β=-4.316, p=0.025). Conclusions The presence of haematuria is closely associated with a faster decrease in renal function in advanced proteinuric CKD patients, especially in younger CKD patients with high proteinuria levels; therefore this high risk subgroup of patients would benefit of intensive medical surveillance and treatment.

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

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.

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.

Daily Home Hemodialysis Is an Available Option for Renal Replacement Therapy in Spain

The objective of the present study was to analyze the characteristics and survival of patients from our hospital who started home hemodialysis. We analyzed all patients receiving home hemodialysis from 1969 to 2015 (51 patients; age 45 ± 23 years; men 77%). We collected characteristics, hospital admission, and mortality. After a median follow‐up of 43 (22–76) months, we found 0–1 hospital admissions per year. Sixty‐nine percent received a kidney transplant, and the global mortality was 10%. Survival at 5 years was 96%. Mean equivalent renal urea clearance was 15.6 ± 4.2 mL/min, the β‐2 microglobulin reduction rate was 67 ± 18%, the number of antihypertension drugs was 0.7 ± 0.3, and the erythropoietin resistance index was 3.7 ± 2.1 IU/kg/week/g/dL. Daily home hemodialysis is a viable option for renal replacement therapy and should be offered alongside other therapies.

Infarto renal en paciente con aneurisma ventricular antiguo

Correspondencia: Borja Quiroga Gili Servicio de Nefrología. Hospital General Universitario Gregorio Marañón. Doctor Esquerdo, 46. 28007 Madrid. borjaqg@gmail.com 3,8 mmol/l, alanina-aminotranferasa, 66 UI/l; aspartatotransaminasa, 97 UI/l; bilirrubina, 0,9 mg/dl, gammaglutamil-transferasa, 28 UI/l; fosfatasa alcalina, 43 UI/l; lactatodeshidrogenasa (LDH), 2124 UI/l; creatina-cinasa, 1210 UI/l: proteína C reactiva, 1,1 mg/dl. El sistemático de orina presentaba únicamente 5-10 leucocitos por campo.

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.Introduction and objective: Higher infusion volumes (IV) in online hemodiafiltration (OL-HDF) are associated with better survival. The IV depends mainly on blood flow (Qb). The objectives of our study were to evaluate the influence of the caliber of arteriovenous fistula (AVF) puncture needles on the total convective volume and other characteristics of OL-HDF, and to investigate possible adverse effects. Material and methods: Prospective intervention study analyzing six sessions of postdilution OL-HDF with 14G needles and six sessions with 15G needles in the same patients, to compare results of efficacy and safety. The monitor, the dialyser, the arterial and venous pressures, the conductivity and the flow of the dialysis fluid were kept equal in each patient. Efficacy through mean blood flow for maximal blood and venous pressures of −220 mmHg and 220 mmHg respectively, total convective volume, and percentages of creatinine, urea and 2-microglobulin reduction, were measured. Adverse effects such as measured pain with an analog scale, postdialysis coagulation times and complications were analyzed. Results: A total of 34 patients, 55 ± 16 years old, 63% male, were studied. The use of 14G needles was associated with higher Qb (471.1 ± 36.7 ml/min vs 354.8 ± 25.8 ml/min, p < 0.001) and higher total convective volume (29.7 ± 5.7 liters with G14 vs 24.1 ± 3.6 liters with G15, p < 0.001) compared to 15G needles. The percentages of creatinine, urea and 2-microglobulin reduction were significantly higher in the 14G needles sessions (73.94 ± 6.03%, 82.54 ± 6.41% and 84.07 ± 4.83%) than 15G needles sessions (70.31 ± 6.67%, 78.80 ± 6.52% and 81.45 ± 5.16%), p = 0.031, 0.029 and 0.047 respectively. On the analog pain scale, no significant differences were found between both needles (4.03 ± 2.09 with 14G and 3.57 ± 2.04 with 15G, p = 0.386). No significant differences between the coagulation times of arterial and venous punctures with the two types of needles were found. As complications, only two punctured bleedings that required new coagulation were recorded, one with a 14G needle and one with a 15G needle. Please cite this article in press as: Galán I, et al. Influence of the vascular access punction needle caliber in the efficacy of online hemodiafiltration. Nefrologia. 2017. http://dx.doi.org/10.1016/j.nefro.2017.04.006 ∗ Corresponding author. E-mail address: isabelgalancarrillo@gmail.com (I. Galán). ttp://dx.doi.org/10.1016/j.nefro.2017.04.006 211-6995/© 2017 Published by Elsevier España, S.L.U. on behalf of Sociedad Española de Nefrologı́a. This is an open access article under he CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). ARTICLE IN PRESS NEFRO-388; No. of Pages 6 2 n e f r o l o g i a 2 0 1 7;x x x(x x):xxx–xxx Conclusion: The use of 14G needles improves the efficacy of OL-HDF without increasing the associated adverse effects. In light of the results, widespread use of 14G needles in OL-HDF whenever possible can be recommended.

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

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

Low lean tissue mass is an independent risk factor for mortality in patients with stages 4 and 5 non-dialysis chronic kidney disease.

Abstract Background: Mortality in patients with stages 4 and 5 chronic kidney disease (CKD) is higher than in the general population. Body composition predicts mortality. Our objective was to evaluate the effect of body composition on mortality in patients with stages 4 and 5 non-dialysis CKD. Methods: We performed a prospective study of 356 patients with stages 4 and 5 non-dialysis CKD. At baseline, we recorded general characteristics, history of cardiovascular events, body composition, serum inflammatory markers, nutrition and cardiac biomarkers. Body composition was analysed using bioimpedance spectroscopy. We recorded the lean tissue index (LTI), fat tissue index (FTI) and overhydration (OH). During a median (range) follow-up of 22 (3–49) months, we recorded mortality, cardiovascular events and progress to renal replacement therapy. Results: At baseline, mean (± standard deviation) age was 67 ± 13 years (men 64%; diabetes 36%). Mean body mass index was 28.2 ± 12.8 kg/m2, the FTI was 12.3 ± 5.6 kg/m2, the LTI was 15.7 ± 3.4 kg/m2 and median (interquartile range) OH was 0.6 (−0.4 to 1.5) L. Sixty-four (18%) patients died during follow-up. The univariate Cox analysis showed an association between mortality and age, low LTI, high Charlson comorbidity index, previous cardiovascular events, OH, low albumin and prealbumin levels, and high C-reactive protein levels. Kaplan–Meier analysis revealed higher survival in patients with a higher LTI (log-rank, 9.47; P = 0.002). The multivariate Cox analysis confirmed an association between mortality and low LTI (P = 0.031), previous cardiovascular events (P = 0.003) and high Charlson comorbidity index (P = 0.01). We did not find any association between body composition and cardiovascular events or renal replacement therapy. Conclusions: A low LTI is an independent factor for mortality in patients with stages 4 and 5 CKD.