Sodium zirconium cyclosilicate: a new potassium binder for the treatment of hyperkalemia.

Hyperkalemia is one of the most common electrolyte disturbances, especially among some groups of patients, such as in those with chronic kidney disease, diabetes or heart failure. Hyperkalemia has been associated with increased risks of mortality, arrhythmias, hospitalization and costs, as well as the need to down titrate/discontinue renin-angiotensin-aldosterone system inhibitors (RAASIs), despite their well-known cardiovascular and nephroprotective benefits. Current potassium binders have limitations (slow onset of action, limited selectivity for potassium binding, risk of drug interactions or gastrointestinal intolerance). Sodium zirconium cyclosilicate (SZC) is a new potassium binder recently approved for the treatment of chronic hyperkalemia. It is a nonabsorbable, inorganic crystal which selectively binds potassium and ammonium in exchange of Na+ and H+ in the whole gastrointestinal tract, achieving a rapid correction of serum potassium levels (within 2 days) and maintaining normokalemia in the long term (up to 1 year), with a good safety profile (common adverse reactions include gastrointestinal events and a dose-dependent risk of edema), excellent tolerability and a low potential for drug interactions. Its potassium-lowering efficacy is maintained irrespective of the use of RAASIs. In summary, SZC is a new potassium binder recently approved for the treatment of hyperkalemia. Its differences with respect to currently available potassium binders make SZC an attractive therapeutic option.

Mortality due to bleeding, myocardial infarction and stroke in dialysis patients.

Essentials Mortality due to bleeding vs. arterial thrombosis in dialysis patients is unknown. We compared death causes of 201 918 dialysis patients with the general population. Dialysis was associated with increased mortality risks of bleeding and arterial thrombosis. Clinicians should be aware of the increased bleeding and thrombosis risks. SUMMARY: Background Dialysis has been associated with both bleeding and thrombotic events. However, there is limited information on bleeding as a cause of death versus arterial thrombosis as a cause of death. Objectives To investigate the occurrence of bleeding, myocardial infarction and stroke as causes of death in the dialysis population as compared with the general population. Methods We included 201 918 patients from 11 countries providing data to the ERA-EDTA Registry who started dialysis treatment between 1994 and 2011, and followed them for 3 years. Age-standardized and sex-standardized mortality rate ratios for bleeding, myocardial infarction and stroke as causes of death were calculated in dialysis patients as compared with the European general population. Associations between potential risk factors and these causes of death in dialysis patients were investigated by calculating hazard ratios (HRs) with 95% confidence intervals (CIs) by the use of Cox proportional-hazards regression. Results As compared with the general population, the age-standardized and sex-standardized mortality rate ratios in dialysis patients were 12.8 (95% CI 11.9-13.7) for bleeding as a cause of death (6.2 per 1000 person-years among dialysis patients versus 0.3 per 1000 person-years in the general population), 13.4 (95% CI 13.0-13.9) for myocardial infarction (22.5 versus 0.9 per 1000 person-years), and 12.4 (95% CI 11.9-12.9) for stroke (14.3 versus 0.7 per 1000 person-years). Conclusion Dialysis patients have highly increased risks of death caused by bleeding and arterial thrombosis as compared with the general population. Clinicians should be aware of the increased mortality risks caused by these conditions.

[Anemia of chronic kidney disease: Protocol of study, management and referral to Nephrology]. / Anemia en la enfermedad renal crónica: protocolo de estudio, manejo y derivación a Nefrología.

The objective of this protocol is to know which test are needed to study an anaemia in a patient with chronic kidney disease, the differential diagnosis of renal anaemia, to know and correct other deficiency anaemias, and the criteria for referral to Nephrology or other specialties of the anaemic patient with chronic kidney disease.

Efficacy of a simple dosage scheme to convert from shorter-acting erythropoiesis-stimulating agent to continuous erythropoietin receptor activator in kidney transplantation patients.

INTRODUCTION: Anemia after kidney transplantation (KT) has a negative impact on graft and patient survival. Anemia management includes iron supplements and erythropoiesis-stimulating agents (ESAs). Most ESAs require short frequency of administration and conversion to ESAs with longer half-life are complex. OBJECTIVE: This study was performed to assess the efficacy of continuous erythropoietin receptor activator (CERA) in hemoglobin (Hb) maintenance after conversion from shorter-acting ESAs with a simple conversion scheme in kidney transplant recipients. METHOD: This is an open-label, prospective, single-arm, single-center, 12-month follow-up study including 77 anemic KT patients with stable renal function. Baseline and monthly measurements of Hb, iron, and creatinine were performed. The conversion scheme from darbepoetin alfa or epoetin was as follows: <30 µg or 5000 IU/week was switched to 75 µg/mo; between 30-50 or 5000-8000 was switched to 100 µg/mo; >50 µg or 8000 IU was changed to 150 µg/month of CERA. Dose adjustments were performed to maintain Hb levels between 10 g/dL and 12 g/dL. RESULTS: The mean age was 57 ± 19 years. The mean time of conversion after KT was 61 ± 49 months. Before conversion, 62.9% of patients were administered epoetin and 37.1% with darbepoetin alfa. Baseline Hb is noted at 10.6 ± 1.3 g/dL. Thirteen percent of patients started receiving CERA at doses of 50 µg/mo, 66% at 75 µg/mo, 13% at 100 µg/mo, and 8% at 150 µg/mo. During the first month, 21% required dose adjustment (6% were increased, 15% were decreased). The final Hb was 11.2 ± 0.8 g/dL. Iron and creatinine levels remained stable during the follow-up examination. CONCLUSION: We propose a simple scheme of conversion from short-acting ESAs to a once-monthly dose of CERA that provides sustained Hb levels within the recommended target with small dose adjustments and low CERA doses.

Montelukast treatment (cysteinyl leukotriene receptor antagonist) in a model of food allergy: modifications in lymphatic cell population from rectal mucosa.

OBJECTIVE: The aim is to determine immunopathological modifications in rectal mucosa from rabbits after local challenge in ovalbumin (OVA) sensitized animals previously treated with montelukast. EXPERIMENTAL DESIGN: thirty two rabbits divided into four groups: G1: normal; G2: subcutaneously OVA sensitized; G3: sensitized, locally OVA challenged and sampled 4 hours after challenge; and G4: sensitized, locally OVA challenged and treated 4 hours before challenge with montelukast (0.15 mg/kg). Specific anti-OVA IgE levels were evaluated by passive cutaneous anaphylaxis test (PCA). In each group 200 high microscopical power fields (HPF) were counted. Results were expressed as arithmetic mean and SE. Anti -CD4, CD5, micro chain monoclonal antibodies were used. Avidin biotin horseradish peroxidase system was used. RESULTS: CD 4: G1: 8.3 +/- 0.06; G2: 13.4 +/- 0.08, G3: 8.25 +/- 0.06, G4: 11.8 +/- 0.02. CD 5: G1: 7.3 +/- 0.05; G2: 9.4 +/- 0.05, G3: 11.3 +/- 0.06, G4: 8.1 +/- 0.06. mu chain: G1: 10.4 +/- 0.06; G2: 3.8 +/- 0.02, G3: 6.0 +/- 0.10, G4: 2.2 +/- 0.10. In all cases, experimental groups (G3 vs. G4) presented statistical significant differences (p < 0.05). CD4+, CD5+ cells and mu chain+ decrease in experimental group (G4), probably due to lymphocyte migration inhibition to challenged mucosa. mu chain+ cell decrease could be based on B cell activation and expression of different surface immunoglobulins. Cells expressing mu chain decreased in G2 and G3 likely due to activation of B cells and subsequent expression of other immunoglobulin chains in cell surface. CONCLUSIONS: We conclude that obtained data are important to elucidate immunopathology of local anaphylactic reaction in rectal mucosa from systemic sensitized animals after treatment with montelukast.

[Prevalence of cardiovascular disease in uraemia and relevance of cardiovascular risk factors]. / Prevalencia de enfermedad cardiovascular en la uremia y relevancia de los factores de riesgo cardiovascular.

AIM: To evaluate the prevalence of cardiovascular disease (CVD) and its association with cardiovascular risk factors, as well as their control in end-stage renal disease (ESRD) patients under maintenance hemodialysis (HD). PATIENTS AND METHODS: A total of 265 patients with ESRD on maintenance HD from a University Hospital and 4 dialysis units were included in this multicenter and cross-sectional study that analyzed the prevalence of CVD and the possible association with classic and new cardiovascular risk factors. Usual biochemical and haemathological parameters were analyzed, as well as plasma levels of homocysteine, troponin-I, BNP, lipoprotein(a), C reactive protein, IL-6, fibrinogen, asymmetrical dimethylarginine (ADMA), advanced oxidation protein products (AOPP), malondialdehyde, adiponectin, osteoprotegerin, and fetuin. In a subset of patients an echocardiography and carotid artery Doppler echography were also performed. RESULTS: The prevalence of CVD was 52.8%. Factors positively associated with prevalent CVD were age, BMI, left ventricular hypertrophy, hypertension, dyslipidemia and diabetes mellitus, dialysis vintage, Charlson s comorbility index, levels of fibrinogen, osteoprotegerin, BNP and CRP, as well as carotid intima-media thickness, left ventricular mass and pulse pressure. Factors negatively associated with prevalent CVD were: previous renal transplant, ejection fraction or levels of LDL-c and phosphorous. In the multivariate analysis dyslipidemia, left ventricular hypertrophy, age and LDL-c (negatively) were associated with CVD. CONCLUSIONS: In HD patients the prevalence of CVD is high and is associated with the presence of cardiovascular risk factors and subclinical CVD.

[Guidelines for automated manual infusion: a practical way of prescribing postdilution on-line hemodiafiltration]. / Pauta de infusión manual automatizada: una forma práctica de prescribir la hemodiafiltración on-line posdilucional.

Post-dilution on-line hemodiafiltration (OL-HDF) is the most efficient infusion mode to obtain maximum clearances of uremic toxins, with a recommended manual infusion flow (Qi) of 25% of the blood flow with the main limitation that causes alarms by hemoconcentration throughout the session. Recent technical advances allow automatic prescription of Qi if hematocrit and total protein (TP) values are specified. As these analytical results are not possible to obtain in each dialysis session, a practical way to prescribe Qi is to make an automatic prescription adjusting the hematocrit and total protein values at the beginning of the session to obtain the manual prescription required and we will call it automatic-manual prescription. The aim of this study was to compare manual Qi with automatic-manual Qi in postdilution OL-HDF. 30 patients (16 men and 14 women), 59.9 +/- 15 years old, in hemodialysis program for 50.1 +/- 67 months were included. Every patient underwent four OL-HDF sessions, two with manual Qi (4008-S and 5008 monitors) and two with automatic-manual Qi (A-M), one with the same Qi and one with manual Qi +20 (A-M+20). The same usual dialysis parameters were maintained: helixone dialyzer, dialysis time of 266 +/- 39 minutes, blood flow of 420 +/- 36. Recirculation, Kt and intradialysis alarms were measured at each session. No significant differences in the fistula recirculation or dialysis dose measured using Kt. Total infusion volume was 24.9 +/- 4 (4008 S), 23.4 +/- 4 L (5008) with manual Qi, 23.6 +/- 4 L (A-M) Qi (NS) and 25.8 +/- 5 L (A-M+20). Only 14% of patients had no incidents. The number of alarms was significantly higher with manual prescription 55 alarms with 4008 and 40 with 5008 vs. AM (11) p < 0.01) and A-M+20 (16 alarms) We concluded that automatic-manual Qi is a practical way for post-dilutional OL-HDF prescription where the same efficiency and total reinfusion volume with an important reduction of intradialysis alarms are obtained, allowing to rise Qi by 20% without increasing intradialysis alarms.

[Anemia in chronic kidney disease and its cardiovascular implications]. / Anemia en la insuficiencia renal crónica y sus implicaciones cardiovasculares.

Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD). Anemia is a common complication of CKD and it is an important independent risk factor for the development and progression of left ventricular hypertrophy (LVH) and heart failure. Anemia is also independently and synergistically associated with an enhanced risk of cardiovascular morbidity and mortality in CKD patients. The availability of erythropoiesis stimulating agents (ESA), such as recombinant human erythropoietin, has greatly improved the management of anemia in CKD patients. By increasing hemoglobin levels, ESA therapy has demonstrated to significantly improve quality of life and decrease morbidity and mortality among these patients. Earlier studies suggested that partial correction of anemia in CKD patients with LVH induced a partial regression of LV mass, while mainly uncontrolled and small-sized studies have suggested that anemia treatment with ESA in CKD patients with congestive heart failure improved NYHA class, cardiac function and reduced hospitalization rates. On the other hand, recent randomized controlled trials have reported no benefit of full anemia correction on LVH and no benefit, or even worse outcomes, in CKD patients versus partial anemia correction. Thus, recent anemia guidelines recommend target haemoglobin levels between 11-12 g/dl in CKD patients receiving ESA.

[How much should dialysis time be increased when catheters are used?]. / ¿Cuánto tiempo es necesario aumentar la prescripción de hemodiálisis con la utilización de catéteres?

SUMMARY: The use of central catheters in hemodialysis patients as a permanent vascular access has increased during the last years, reaching numbers of around 7% of prevalent patients and between 25% of incident patients. Although the current catheters allow higher sanguineous flows with smaller incidence of infectious complications and dysfunction, the dose of dialysis that is reached is still inferior to that obtained with native arterio-venous fistula (AVF) and grafts. The aim of the present study was to evaluate the possible additional time supposed by dialysis using central venous catheters with respect to habitual vascular access as a consequence of the lesser blood flow (Qb) and the irregularity of its function (frequent lowering of the Qb and necessity of inverting the lines on many occasions). A total of 48 patients (31 men/17 women) with an average age of 61,6 +/- 14 years old (rank: 28-83), 20 with tunnelled catheter and the remaining with AVF, were included in the study. All the patients were dialyzed in the modality of high flux hemodialysis with a polisulphone of 1,9 m2 dialyzer, dialysis time of 240 minutes, dialysate flow 500 ml/min and monitors equipped with ionic dialysance (ID) with the objective of obtaining a Kt of 45 litres with each one of the different vascular accesses. The patients with AVF received 3 sessions, with variations of Qb to 300, 350 and 400 ml/min. The patients with tunnelled catheter received two sessions, to the maximum Qb, one with normal connection and other with inverted one. In the results obtained it is possible to emphasize that only the patients with AVF and 400 ml/min reached the objective of 45 L of Kt. The patients with AVF needed to increase 12 minutes of hemodialysis with a Qb of 350 ml/min and 28 minutes with a Qb of 300 ml/min; the catheters on normal position needed to increase 24 minutes and finally in the inverted catheters an increase of 59 minutes was necessary to reach the same Kt objective. We concluded that the patients dialyzed with central catheters on average needed to increase by 30 minutes the time of dialysis if the catheter worked in a normal position but 60 minutes if the arterio-venous lines were inverted so as to reach the minimum dose of dialysis.

Prevalence and clinical characteristics of HIV type 1-infected patients receiving dialysis in Spain: results of a Spanish survey in 2006: GESIDA 48/05 study.

End-stage renal diseases (ESRD) are becoming more frequent in HIV-infected patients. In Europe there is little information about HIV-infected patients on dialysis. A cross-sectional multicenter survey in 328 Spanish dialysis units was conducted in 2006. Information from 14,876 patients in dialysis was obtained (81.6% of the Spanish dialysis population). Eighty-one were HIV infected (0.54%; 95% CI, 0.43-0.67), 60 were on hemodialysis, and 21 were on peritoneal dialysis. The mean (range) age was 45 (28-73) years. Seventy-two percent were men and 33% were former drug users. The mean (range) time of HIV infection was 11 (1-27) years and time on dialysis was 4.6 (0.4-25) years. ESRD was due to glomerulonephritis (36%) and diabetes (15%). HIV-associated nephropathy was not reported. Eighty-five percent were on HAART, 76.5% had a CD4 T cell count above 200 cells, and 73% had undetectable viral load. Thirty-nine percent of patients met criteria for inclusion on the renal transplant (RT) waiting list but only 12% were included. Sixty-one percent had HCV coinfection. HCV-coinfected patients had a longer history of HIV, more previous AIDS events, parenteral transmission as the most common risk factor for acquiring HIV infection, and less access to the RT waiting list (p < 0.05). The prevalence of HIV infection in Spanish dialysis units in 2006 was 0.54% HCV coinfection was very frequent (61%) and the percentage of patients included on the Spanish RT waiting list was low (12%).

[Kt as control and follow-up of the dose at a hemodialysis unit]. / Kt como control y seguimiento de la dosis en una unidad de hemodiálisis.

To ensure our patients are receiving an adequate dose in every dialysis session there must be a target to achieve this in the short or medium term. The incorporation during the last years of the ionic dialysance (ID) in the monitors, has provided monitoring of the dialysis dose in real time and in every dialysis session. Lowrie y cols., recommend monitoring the dose with Kt, recommending at least 40 L in women and 45 L in men or individualizing the dose according to the body surface area. The target of this study was to monitor the dose with Kt in every dialysis session for 3 months, and to compare it with the monthly blood test. 51 patients (58% of our hemodialysis unit), 32 men and 19 women, 60.7+/-14 years old, in the hemodialysis programme for 37.7+/-52 months, were dialysed with a monitor with IC. The etiology of their chronic renal failure was: 3 tubulo-interstitial nephropathy, 9 glomerulonephritis, 12 vascular disease, 7 polycystic kidney disease, 7 diabetic nephropathy and 13 unknown. 1,606 sessions were analysed during a 3 month period. Every patient was treated with the usual parameters of dialysis with 2.1 m2 cellulose diacetate (33.3%), 1.9 m2 polisulfone (33.3%) or 1.8 m2 helixone, dialysis time of 263+/-32 minutes, blood flow of 405+/-66, with dialysate flow of 712+/-138 and body weight of 66.7+/-14 kg. Initial ID, final ID and Kt were measured in each session. URR and Kt/V were obtained by means of a monthly blood test. The initial ID was 232+/-41 ml/min, the final ID was 197+/-44 ml/min, the mean of Kt determinations was 56.6+/-14 L, the mean of Kt/V was 1.98+/-0.5 and the mean of URR was 79.2+/-7%. Although all patients were treated with a minimum recommended dose of Kt/V and URR when we used the Kt according to gender, we observed that 31% of patients do not get the minimum dose prescribed (48.1+/-2.4 L), 34.4% of the men and 26.3% of the women. If we use the Kt individualized for the body surface area, we observe that 43.1% of the patients do not get the minimum dose prescribed with 4.6+/-3.4 L less than the dose prescribed. We conclude that the monitoring of dialysis dose with the Kt provides a better discrimination detecting that between 30 and 40% of the patients perhaps do not get an adequate dose for their gender or body surface area.

[Control of hypertension refractory to medical management by means of short daily hemodialysis]. / Control de HTA refractaria a tratamiento médico con hemodiálisis corta diaria.

Hypertension is a very frequent complication in patients in hemodialysis. A high percentage of the patients on standard hemodialysis remain hypertense in spite of intensive pharmacologic treatment. We presented the case of a hypertense patient with difficult control in spite of antihypertensive treatment with five drugs and several secondary complications. The change to a short daily hemodialysis was successful to hypertension control and allowed a gradual suspension of drugs.

Chronic hypotension in hemodialysis patients: role of functional vascular changes and vasodilator agents.

AIMS: The aim of this study was to evaluate the hemodynamic pattern, vascular compliance, as well as the levels of vasoregulatory hormones and markers of inflammation and oxidative stress in a group of chronic hypotensive (CH) patients undergoing hemodialysis (HD) and to compare them with a group of normotensive HD patients. MATERIAL AND METHODS: 14 normotensive and 10 CH hemodialysis patients were included in the study. Hemodynamic characteristics were evaluated by means of the pulse waveform analysis. Plasma levels of nitrites, interleukin-6 (IL-6), malondialdehyde (MDA), PTH-related peptide (PTHrp), catecholamines, angiotensin II and endothelin were measured. RESULTS: Blood pressure (BP) and peripheral vascular resistances (PVR) were lower in the hypotensive group (p < 0.001 and p = 0.005, respectively), whereas cardiac output was similar in both groups. Large (C1) (p = 0.001) and small (C2) (p = 0.022) artery elasticity indices were higher in hypotensive patients. In the whole group, C1 and C2 inversely correlated with mean BP (MBP). Plasma levels of nitrites (p = 0.011) were higher in hypotensive patients and inversely correlated with MBP (r = -0.516, p = 0.012). Time on HD correlated with plasma nitrites (r = 0.478, p = 0.024) and inversely with MBP (r = -0.598, p = 0.003). CONCLUSIONS: CH in HD patients is characterized by decreased PVR, a preserved cardiac output and greater vascular compliance. CH is associated with longer time on HD and higher plasma levels of nitrites/nitrates, suggesting that an enhanced production of nitric oxide induced by long-term HD, could be involved in CH. These findings suggest that functional vascular changes, likely related to an enhanced production of vasodilator agents, are responsible for CH in HD patients.

[Prevalence of kidney insufficiency in primary care population in Spain: EROCAP study]. / Prevalencia de insuficiencia renal en Centros de Atención Primaria en España: Estudio EROCAP.

This cross-sectional, multicenter study investigated the prevalence of chronic kidney disease and associated disorders, in an adult population sample (> 18 years old) attending Primary Care services in Spain. Estimated glomerular filtration rate (Modification Diet in Renal Disease equation) was used for analysis of kidney disease prevalence according to NFK-KDOQI (The National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) stages. Data were collected on serum creatinine, other laboratory parameters blood pressure, and medical history of cardiovascular risk factors or disease (hypertension, dislypidemia, diabetes, congestive heart failure, coronary artery disease, stroke or peripheral arteriopathy) in 7,202 patients attending Primary Care Centers. 47.3% were males, mean age 60,6 +/- 14,3 years, BMI 28.2 +/- 5.3, with 27,6% overweight (27-30 kg/m2) and 32,1% obese (BMI>or=30 kg/m2), The prevalence of cardiovascular risks factors were: absence in 17.3%, one factor 26.9% two 31.2%, and 23.6% presented three or more The frequency of CV risk factors was: hypertension (66.7%), dyslipidemia (48%) and diabetes (31.5%). Congestive heart failure, coronary artery disease, stroke or peripheral vascular disease frequency was lower than 10% The prevalence of eGFR < 60 ml/min x 1.73 m2 was: stage 3 (30-59 ml/min/1.73 m2) 19.7%; stage 4 (15-29 ml/min/1.73 m2) 1.2%; stage 5 no dialysis (GFR < 15 ml/min) 0.4%. This prevalence increased with age in both sexes and 33,7% of patients attending Primary Care services over 70 years presented a eGFR < 60 ml/min. Of the total patients with eGFR < 60 ml/min 37.3% had normal serum creatinine levels. This study documents the substantial prevalence of significantly abnormal renal function among patients at Primary Care level. Early identification and appropriate nephrological management of these patients with renal disease is an important opportunity for an adequate prescription of drugs that interfere with renal function, to delay the progression of renal disease and modify CV risk factors.