Anuric Hemodialysis Patients Research Articles

Assessing the Sympatholytic Effects of SGLT2 Inhibitors in Anuric Haemodialysis Patients Using Microneurography: Study Protocol for a Mechanistic Proof-of-Concept Trial

Introduction: Sodium-glucose co-transporter 2 inhibitors (SGLT2is) have been shown to provide effective cardiorenal protection, reducing mortality in conditions such as heart failure and chronic kidney disease. While several mechanisms have been identified, recent research has shed light on the drug’s ability to attenuate sympathetic nervous system (SNS) activity. Controversy exists on whether this is due to the extra-renal effects of the drug, or simply due to its renoprotective effects. However, recent trials have highlighted the persistent efficacy of SGLT2i despite declining renal function. Therefore, investigating the ability of SGLT2i to attenuate the SNS independently of the kidney could lead to more insight into its mechanism of action. So far, there has been limited research done on investigating the extra-renal effects of SGLT2i in human subjects on dialysis where the glycosuric renal effects of SGLT2i are negligible. This current study therefore aims to investigate the effects of SGLT2i on the SNS in anuric haemodialysis patients. Methods: We developed a protocol for a mechanistic study to investigate the extra-renal effects of SGLT2i on the SNS. The study will be an investigator-led, open-label, prospective study involving 20 adult (aged ≥18 years) haemodialysis patients with a residual urine output of ≤250 mL/day. Participants will be administered empagliflozin 25 mg/day for 6 weeks. Baseline SNS activity will be measured before and after administration by microneurography to assess central SNS outflow. Secondary outcomes such as changes from baseline in SNS stressor response, heart rate variability, and endothelial function will also be examined. We hypothesize that the use of empagliflozin will result in reduced sympathetic drive in anuric haemodialysis patients. Discussion: This will be the first study evaluating the effects of SGLT2i on the SNS in haemodialysis subjects. This study aims to enhance our understanding of the potential role of SGLT2i-induced SNS reduction in the setting of markedly reduced renal function. The study has received ethics approval from the Royal Perth Hospital Human Research Ethics Committee (RGS0000003840) (Australian New Zealand Clinical Trials Registry [ANZCTR] ID: ACTRN12623001237673).

Incidence of hyperkalemia in anuric hemodialysis patients treated with sacubitril/valsartan.

Sacubitril/valsartan is increasingly used in hemodialysis patients due to its cardioprotective benefits. However, its impact on serum potassium levels in anuric patients undergoing hemodialysis remains controversial. We conducted a retrospective data from patients undergoing hemodialysis at two dialysis centers. A total of 71 out of 332 patients receiving hemodialysis treatment were enrolled. Mean serum potassium (mean value of 6-8 determinations), peak serum potassium (maximum K value observed during follow-up observations), and other biochemical parameters were recorded at baseline and during the follow-up period. After 6 months of follow-up, mean serum potassium increased from 4.84 ± 0.45 mmol/L at baseline to 5.07 ± 0.46 mmol/L at 3 months and 5.04 ± 0.46 mmol/L at 6 months (p < 0.001). Notably, no significant group differences were found in peak serum potassium concentrations between baseline and 6 months after sacubitril/valsartan therapy (5.69 ± 0.56 vs. 5.75 ± 0.41, p = 0.419). Prior to starting sacubitril/valsartan treatment, none of the patients had severe hyperkalemia; however, after 3 and 6 months of sacubitril/valsartan therapy, two (2.80%) and three (4.20%) patients experienced severe hyperkalemia, respectively; however, this difference was not statistically significant. Additionally, there was a significant reduction in blood pressure; however, serum sodium, bicarbonate, and Kt/V values did not change significantly during either period. Sacubitril/valsartan therapy is associated with an increase in serum potassium levels in anuric hemodialysis patients. Nevertheless, the proportion of patients with severe hyperkalemia did not increase significantly. This suggests that the use of sacubitril/valsartan in anuric patients on hemodialysis is relatively safe.

Long-term cardiac effect of sacubitril-valsartan in hemodialysis patients with a reduced ejection fraction after aortic valve replacement for aortic stenosis: a case report with literature review

BackgroundAlthough the angiotensin receptor-neprilysin inhibitor sacubitril-valsartan has demonstrated a valuable effect on cardiac function in patients with heart failure with a reduced ejection fraction, the effect of this agent in hemodialysis patients is not well known.Case presentationSacubitril-valsartan was administered to two anuric hemodialysis patients, an 81-year-old woman and a 79-year-old man, after aortic valve replacement for aortic stenosis. Following sacubitril-valsartan administration, the two patients’ N-terminal pro-brain natriuretic peptide levels decreased from 110,373 to 47,742 and 22,723 to 7692 pg/mL within one month, respectively, and were sustained within the lower levels thereafter. Although the patients’ left ventricular ejection fractions were 40.0% and 28.4%, respectively, these values did not change at seven and four months after sacubitril-valsartan administration (41.0% and 30.0%, respectively) but increased gradually to 56.6% and 54.9% at 11 and 13 months, respectively, and were sustained at the same levels thereafter.ConclusionsLong-term sacubitril-valsartan administration can improve cardiac function in hemodialysis patients with a reduced ejection fraction.

Evaluation of ABCG2-mediated extra-renal urate excretion in hemodialysis patients

Two-thirds of urate is excreted via the renal pathway and the remaining one-third via the extra-renal pathway, the latter mainly via the intestine in healthy individuals. ABCG2, a urate exporter, is expressed in various tissues including the kidney and intestine, and its dysfunction leads to hyperuricemia and gout. ABCG2 is regarded as being responsible for most of the extra-renal urate excretion. However, the extra-renal urate excretion capacity via ABCG2 remains undefined in end-stage kidney diseases. Therefore, we evaluated the capacity of extra-renal ABCG2 using 123 anuric hemodialysis patients whose urate excretion depended on only the extra-renal pathway. ABCG2 function in each participant was estimated based on ABCG2 dysfunctional variants. We computed the uric acid pool (PoolUA) from bodyweight and serum urate level (SUA) using previously reported radio-isotopic data, and we analyzed the association between ABCG2 function and the PoolUA. SUA and PoolUA increased significantly with ABCG2 dysfunction, and extra-renal ABCG2 could excrete up to approximately 60% of the daily uric acid turnover in hemodialysis patients. Our findings indicate that the extra-renal urate excretion capacity can expand with renal function decline and highlight that the extra-renal pathway is particularly important in the uric acid homeostasis for patients with renal dysfunction.

Protein/Fiber Index Modulates Uremic Toxin Concentrations in Hemodialysis Patients.

Background: Indoxyl sulfate (IS) and p-cresyl sulfate (PCS), two uremic toxins (UTs), are associated with increased mortality in patients with chronic kidney disease (CKD). These toxins are produced by the microbiota from the diet and excreted by the kidney. The purpose of this study was to analyze the effect of diet on IS and PCS concentration in hemodialysis (HD) patients. Methods: We performed a prospective monocentric study using a seven-day diet record and determination of serum IS and PCS levels in HD patients. We tested the association between toxin concentrations and nutritional data. Results: A total of 58/75 patients (77%) completed the diet record. Mean caloric intake was 22 ± 9.2 kcal/kg/day. The protein/fiber index was 4.9 ± 1.8. No correlation between IS or PCS concentration and protein/fiber index was highlighted. In the 18 anuric patients (31%) in whom residual renal function could not affect toxin concentrations, IS and PCS concentrations were negatively correlated with fiber intake and positively correlated with the protein/fiber index. In a multivariate analysis, IS serum concentration was positively associated with the protein/fiber index (p = 0.03). Conclusions: A low protein/fiber index is associated with low concentrations of uremic toxins in anuric HD patients. Diets with an increased fiber intake must be tested to determine whether they reduce PCS and IS serum concentrations.

Pulmonary artery pressure as a method for assessing hydration status in an anuric hemodialysis patient \u2013 a case report

BackgroundSetting the dry weight and maintaining fluid balance is still a difficult challenge in dialysis patients. Overhydration is common and associated with increased cardiac morbidity and mortality. Pulmonary hypertension is associated with volume overload in end-stage renal dysfunction patients. Thus, monitoring pulmonary pressure by a CardioMEMS device could potentially be of guidance to physicians in the difficult task of assessing fluid overload in hemodialysis patients.Case presentation61-year old male with known congestive heart failure deteriorated over 3 months’ time from a state with congestive heart failure and diuresis to a state of chronic kidney disease and anuria. He began a thrice/week in-hospital hemodialysis regime. As he already had implanted a CardioMEMS device due to his heart condition, we were able to monitor invasive pulmonary artery pressure during the course of dialysis sessions. To compare, we estimated overhydration by both bioimpedance and clinical assessment. Pulmonary artery pressure correlated closely with fluid drainage during dialysis and inter-dialytic weight gain. The patient reached prescribed dry weight but remained pulmonary hypertensive by definition. During two episodes of intradialytic systemic hypotension, the patient still had pulmonary hypertension by current definition.ConclusionThis case report observes a close correlation between pulmonary artery pressure and fluid overload in a limited amount of observations. In this case we found pulmonary artery pressure to be more sensitive towards fluid overload than bioimpedance. The patient remained pulmonary hypertensive both as he reached prescribed dry weight and experienced intradialytic hypotensive symptoms. Monitoring pulmonary artery pressure via CardioMEMS could hold great potential as a real-time guidance for fluid balance during hemodialysis, though adjusted cut-off values for pulmonary pressure for anuric patients may be needed. Further studies are needed to confirm the findings of this case report and the applicability of pulmonary pressure in assessing optimal fluid balance.

MON-PO432: Daily Sodium Intake in Anuric Hemodialysis Patients and Interdialytic Weight Gain

MON-PO432: Daily Sodium Intake in Anuric Hemodialysis Patients and Interdialytic Weight Gain

Use of Renin-Angiotensin System Blockers Increases Serum Potassium in Anuric Hemodialysis Patients

Background: Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are increasingly used in uremic patients (pts). However, their effect on serum potassium (sK) concentrations in anuric pts on chronic hemodialysis treatment (HD) is controversial. The aim of the study was to evaluate sK before and after the start of ACEi/ARB therapy. Methods: In the period 1/1/2015 – 31/12/2015, 112 out of 240 prevalent HD pts on thrice weekly HD treatment followed at our institution started the ACEi/ARB therapy. The mean age was 67 ± 14 years, 67/112 were men, dialysis vintage was 6–212 months. In the 3 months before (PRE; N° 36 HD sessions) and after (POST; N° 36 HD sessions) the start of ACEi/ARB therapy, the following variables were evaluated in pre dialysis after the long interdialysis interval: sK (mean of 12 determinations; mmol/L), maximum sK (maximum K value observed during observations; sKmax; mmol/L), serum sodium (sNa; mmol/L), pre dialysis systolic blood pressure (SBP; mm Hg) and diastolic blood pressure (DBP; mm Hg), body weight (BW; Kg), interdialytic weight gain (IWG; Kg), Kt/V, serum bicarbonate concentrations (sBic; mmol/L), protein catabolic rate (PCRn; g/KgBW/day). SBP, DBP, IWG are the mean of the 24 HD sessions. Out of 112 patients, 102 were on antihypertensive therapy. The duration of HD and blood and dialysate flow rates were kept constant. Data are expressed as mean ± SD. Student t test for paired and unpaired data for normally distributed variables, Mann-Whitney test for medians, χ² test for categorical data were employed to compare groups. A significant difference was defined as p < 0.05. Results: sK increased from 5.0 ± 0.4 mmol/L PRE to 5.7 ± 0.5 mmol/L POST (p < 0.0001). sKmax increased from 5.3 ± 0.5 mmol/L PRE to 6.2 ± 0.6 mmol/L POST (p < 0.0001). The percentage of pts with normal sK concentrations decreased from 82% PRE to 29% POST (p < 0.0001). Mild hyperkalemia increased from 18 to 52% (p < 0.001); in 31% of the patients, it was necessary to reduce the K dialysate concentration. None of the patients had severe hyperkalemia PRE, but 19% developed severe hyperkalemia POST (p < 0.0001) necessitating treatment withdrawal. Mean sK in these pts varied from 5.2 ± 0.3 mmol/L PRE to 6.5 ± 0.2 mmol/L at the moment of withdrawal (p < 0.0001) and sKmax from 5.5 ± mmol/L PRE to 6.9 ± 0.3 mmol/L (p< 0.0001). After withdrawal of ACEi/ARB, sK and sKmax concentrations decreased to basal levels within 1 month. There were no significant changes of BW, IWG, SBP, DBP, Na, Hb, Kt/V, sBic, and PCRn in both periods. Conclusions: ACEi/ARB therapy is associated with an increased risk of hyperkalemia in anuric hemodialysis patients. The proportion of patients with normal sK concentrations decreased from 82 to 29% and with mild hyperkalemia increased from 18 to 52%. Severe hyperkalemia necessitating the interruption of ACEi/ARB therapy developed in 19% of patients. This suggests great caution in the widest utilization of this class of drugs in HD patients.

Pain management in chronic kidney disease: The pharmacokinetics and pharmacodynamics of hydromorphone and hydromorphone-3-glucuronide in hemodialysis patients

To describe the pharmacokinetics of hydromorphone (HM) and its primary metabolite hydromorphone-3-glucuronide (H3G) both on and off dialysis in relation to the pharmacodynamic measurements of pain. Prospective, open-label, observational study. Canadian, university-based renal program. Twelve anuric hemodialysis patients with chronic pain, established on immediate-release HM. HM and H3G plasma concentrations were measured during and between hemodialysis treatments using a reverse-phase high-performance liquid chromatography assay with liquid chromatography/mass spectrometer/mass spectrometer detection. The McGill Pain Questionnaire (MPQ) and a Visual Analogue Scale (VAS) were used to measure pain. Noncompartmental analyses were conducted. Adverse effects were recorded. HM did not substantially accumulate (accumulation factor R = 2.7 (1.6)), most likely due to the rapid conversion to H3G. Conversely, H3G accumulated between dialysis treatments (R = 12.5 (12.1)) but appeared to be effectively removed during hemodialysis (1.8 (0.7), p = 0.03). HM resulted in > 65 percent reduction in pain over dosing intervals. Mean MPQ pain scores decreased from 39.8 (18.2) to 12.3 (16.2) on dialysis and from 35.0 (18.5) to 15.5 (13.6) between dialysis treatments. Mean VAS pain scores decreased from 7.5 (2.5) to 3.0 (1.5) on dialysis and from 5.9 (3.2) to 4.4 (1.6) between dialysis treatments. No clinically significant opioid toxicity was observed. The accumulation of H3G between hemodialysis treatments was associated with greater sensory-type pain (r = 0.76, p < 0.0001) and reduced duration of analgesia. HM may be a safe and effective opioid for use in selected hemodialysis patients.

Febuxostat and Increased Dialysis as a Treatment for Severe Tophaceous Gout in a Hemodialysis Patient.

Uric acid accumulates in renal failure and is thought to be a uremic toxin—that is, higher levels of uric acid are more damaging to the kidneys. Urate crystals can precipitate in the kidney tubules, cause urate stones, and promote inflammatory changes in the renal interstitium and vascular endothelium. Uric acid is also a small non-protein-bound molecule and therefore easily dialyzable. Here, we present the case of an anuric hemodialysis patient with severe tophaceous gout who regained some renal function and whose gout burden significantly decreased resulting in marked improvement in functional status using a new gout medication, febuxostat, and increased frequency of dialysis.

Relationship between relative interdialytic weight gain and serum leptin levels, nutrition, and inflammation in chronic hemodialysis patients.

Excessive relative interdialytic weight gain (RIDWG, %) is an important risk factor for long-term adverse cardiovascular outcomes in chronic hemodialysis (HD) patients. On the other hand, it may also be an index of good appetite and nutritional status. We aimed to assess the relationship between RIDWG and appetite, nutrition, inflammation parameters of chronic HD patients. 100 chronic anuric HD patients were enrolled in this prospective study between January 2013 and January 2014. Patients with hospitalization, major surgery, obvious infectious/inflammatory disease, end-stage liver disease, malignancies, and malabsorption syndromes were excluded. Patients were divided into 3 groups according to their RIDWG levels; group 1 = RIDWG < 3%, group 2 = RIDWG: 3 - 5%, and group 3 = RIDWG > 5%. Group 3 patients were younger (p = 0.011) and had a lower body mass index (BMI) (p = 0.014). Nutrition and inflammation parameters including malnutrition inflammation score (MIS), serum albumin, prealbumin, triceps skinfold thickness, hs-CRP, and TNF-α ere not significantly different between the groups. Leptin and leptin/BMI ratio were significantly lower in group 3 (p = 0.001). RIDWG was negatively correlated with age (p = 0.001, r = -0.371), BMI (p = 0.001, r = -0.372), leptin (p = 0.001, r = -0.369), leptin/BMI (p = 0.001, r = -0.369). After adjustment for BMI in linear regression analyis, leptin/BMI remained significantly correlated with RIDWG (p = 0.024). This study revealed that RIDWG was associated with younger age, lower BMI and dry weight, and lower serum leptin levels. More detailed studies are needed to validate and dissect the mechanisms of these findings.

Clinical manifestation of hypercalcemia caused by adrenal insufficiency in hemodialysis patients: a case-series study.

The goal of this study was to clarify the clinical manifestation of hypercalcemia due to hypoadrenalism in hemodialysis (HD) patients. We retrospectively analyzed the clinical characteristics of five HD patients who had presented with hypercalcemia due to adrenal insufficiency (age: 69 ± 7 [58-75] years old, time on HD: 13 ± 11 [2-32] years). We conducted corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) stimulation tests. We also examined serum bone turnover markers before and after glucocorticoid replacement. All patients had critical illnesses at the onset of hypercalcemia. They had at least one symptom, such as eosinophilia, hypoglycemia, or fever. The prevalence of hypercalcemia due to adrenal insufficiency was 1.3% in maintenance HD patients on admission. The causes of adrenal insufficiency were isolated ACTH deficiency, pituitary apoplexy, pituitary atrophy, glucocorticoid withdrawal syndrome, and unilateral adrenalectomy. Serum calcium (Ca) levels corrected by serum albumin were maximally increased to 12.9 to 14.3 mg/dL in four anuric HD patients and mildly elevated to 10.4 mg/dL in a patient with residual diuresis. Their basal serum cortisol levels ranged from <1.0 to 15.4 μg/dL. Single CRH injections failed to increase serum cortisol in any of the patients. Glucocorticoid replacement acutely normalized serum Ca and decreased levels of carboxy-terminal telopeptide of type I collagen, a marker of bone resorption. Adrenal insufficiency could therefore be an occult cause of hypercalcemia in anuric HD patients who are critically ill.

Effect of gradually lowering dialysate sodium concentration on the interdialytic weight gain, blood pressure, and extracellular water in anuric hemodialysis patients

Background: The majority of hemodialysis (HD) patients are overhydrated and have high interdialytic weight gain (IDWG) which induces increased blood pressure (BP). The positive sodium balance resulting from a high sodium diet, a high dialysate sodium concentration (DNa), or a combination of both is major causes of this disease. We evaluated the effects of lowering DNa on IDWG, BP, and volume status in anuric HD patients with dietary sodium restriction. Methods: Thirty-two patients were enrolled in this study and the period was divided by phase 1 and 2 according to DNa which decreased from 140 to 135 mEq/L at a rate of 1 mEq/L per month; phase 1, 140 mEq/L; phase 2, 135 mEq/L. We compared the IDWG, BP, volume status measured by multifrequency bioimpedance spectroscopy, and adverse events such as intradialytic hypotension, cramps, and headache of both phases. Results: The IDWG was significantly reduced by 0.39 ± 0.38 kg (p = 0.000). Pre-dialysis BP showed significant reduction (systolic pressure 146 ± 18 vs. 138 ± 22 mmHg; p = 0.012, diastolic pressure 80 ± 10 vs. 75 ± 11 mmHg; p = 0.008). Pre-dialysis extracellular water (ECW) was reduced significantly by 0.13 ± 2.22 L (p = 0.02). There was no significant increase in adverse events (all p > 0.05). Conclusions: This study showed that gradually lowering DNa could bring a significant reduction in pre-dialysis IDWG, BP, and ECW without increased adverse events. Large and crossover designed study will be needed to demonstrate the clear causal relationship.

Urinary and plasma galectin-3 in heart failure - insights in renal handling

Purpose: Galectin-3 (Gal-3) is used as a biomarker for heart failure (HF). The use of Gal-3 is complicated by its strong interaction with renal function. We aimed to clarify the relationship between plasma and urinary Gal-3 levels in HF patients compared to control subjects. Methods: We measured Gal-3 levels in plasma (P-Gal3) and urine (U-Gal3) in 101 patients with stable chronic HF; mean LVEF 35±8%, mean age 64±10 years. We calculated eGFR by the sMDRD formula, and calculated renal supply, handling and excretion of Gal-3. Furthermore, we studied Gal-3 levels in a control group of 20 healthy controls and 109 hemodialysis patients, without urine production. Results: In HF patients, mean P-Gal3 was 17.2 ng/mL (15.5-19.3) compared to 10.5 ng/mL (8.9-12.4) in control subjects (P<0.001). eGFR in these two study groups was 80 and 90 ml/min/1.73m2, respectively. Mean U-Gal3 in HF patients was 36.6 ng/mL (19.7-49.5) compared to 37.2 ng/mL (21.2-50.3) in control subjects (P=0.882), a non-significant difference, also when corrected for urine creatinine (P=0.892). The proportion of actually excreted Gal-3 (fractional Gal-3 excretion of the filtered load) in HF patients was significantly lower than in control subjects (5.0% vs. 7.6%; P=0.016). This corresponds with a higher Gal-3 excretion rate of the kidney of control subjects (6.7 vs. 4.0 mL/min; P<0.01). In anuric hemodialysis patients, we observed substantially higher P-Gal3 levels (mean 72.5 ng/mL) (see figure). ![Figure][1] Plasma and urinary galectin-3 Levels Conclusions: HF patients have elevated P-Gal3 levels and reduced renal Gal-3 excretion. We postulate that impaired renal Gal-3 excretion may lead to accumulation of P-Gal3. This was most apparent in dialysis patients without urine production and highly elevated P-Gal3. Further mechanistic studies should describe renal handling of Gal-3. [1]: pending:yes

Iodinated Contrast Media Can Induce Long-Lasting Oxidative Stress in Hemodialysis Patients

PurposeDue to their comorbidities, dialysis patients have many chances to undergo radiologic procedures using iodinated contrast media. We aimed to assess time-sequenced blood oxidative stress level after contrast exposure in hemodialysis (HD) patients compared to those in the non-dialysis population.Materials and MethodsWe included 21 anuric HD patients [HD-coronary angiography (CAG) group] and 23 persons with normal renal function (nonHD-CAG group) scheduled for CAG, and assessed 4 oxidative stress markers [advanced oxidation protein products (AOPP); catalase; 8-hydroxydeoxyguanosine; and malondialdehyde] before and after CAG, and subsequently up to 28 days.ResultsIn the nonHD-CAG group, only AOPP increased immediately after CAG and returned to baseline within one day. However, in the HD-CAG group, all four oxidative stress markers were significantly increased starting one day after CAG, and remained elevated longer than those in the nonHD-CAG group. Especially, AOPP level remained elevated for a month after contrast exposure.ConclusionOur study showed that iodinated contrast media induces severe and prolonged oxidative stress in HD patients.

Cushing's Syndrome after Hemodialysis for 21 Years

Hyperkalemia and weight loss are critical clinical problems for hemodialysis patients. There have been no documented reports of adrenal Cushing's syndrome with central obesity and hypokalemia in a hemodialysis patient. The aim of the study was to report a patient with Cushing's syndrome after chronic hemodialysis, review the published literature, and discuss the significance of hypokalemia and obesity in anuric hemodialysis patients from the perspective of cortisol metabolism. A 61-yr-old woman who had been on hemodialysis for 21 yr presented with persistent hypokalemia and central obesity. In 2002, her dry weight was 48.1 kg, but thereafter she gained weight to 60 kg. Adrenal Cushing's syndrome was diagnosed from endocrinological findings such as increased cortisol secretion without a circadian rhythm and suppression of plasma ACTH. Spironolactone was administered (25 to 50 mg/d), and her serum potassium became normal. Then, left adrenalectomy was performed by laparoscopic surgery. The resected specimen contained a well-circumscribed adrenal adenoma expressing P450c17. After surgery, hypokalemia improved gradually without medication, and her weight gain stopped. This is the first documented case of adrenal Cushing's syndrome in a patient on long-term hemodialysis, although several authors have reported a relation between hypokalemia and primary hyperaldosteronism in hemodialysis patients.

Successful treatment of hypertension in anuric hemodialysis patients with a direct Renin inhibitor, aliskiren.

Objective: A direct renin-inhibitor (DRI), aliskiren, was administered to anuric patients to investigate whether it can be a new optional therapy against hypertension in hemodialysis (HD) patients.Patients: The patients that received aliskiren comprised 8 males and 2 females with a mean ± SD age of 63 ± 8 years (43-72 years). They were exposed to dialysis therapy for 118 ± 73 months (8-251 months), with diabetes mellitus in 4 cases, chronic glomerulonephritis in 4 cases, and other diagnoses in 2 cases.Methods: After the plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were measured before an HD session, aliskiren, 150 mg as an initial dose, was administered to the patients. PRA and PAC were also examined a week after initiating aliskiren. The blood pressure (BP) levels at the start of each HD session for a period of 2 weeks (6 HD sessions) were compared between before and after administration of aliskiren. The change of doses in other antihypertensive agents was also counted.Results: The averaged reduction of mean blood pressure was 4 ± 5 mmHg, and doses of antihypertensives other than aliskiren were reduced in 4 patients. Of the examined parameters, only the reduction rate of PRA x PAC seemed correlated with the BP lowering effect of aliskiren, which was calculated as the sum of the mean BP reduction in mmHg and drug reduction with 1 tablet (capsule)/day considered to be 10 mmHg.Conclusion: A DRI, aliskiren, was effective even in anuric dialysis patients, and monitoring of PRA and PAC was valuable for selecting cases responsive to aliskiren.

Calcium mass balances during standard bicarbonate hemodialysis and long-hour slow-flow bicarbonate hemodialysis

Dialysate calcium (Ca) concentration should be viewed as part of the integrated therapeutic regimen to control renal osteodystrophy and maintain normal mineral metabolism. Thus, a correct ionized calcium mass balance (Ca++MB) during hemodialysis (HD) is crucial in the treatment of renal osteodystrophy. The GENIUS single-pass batch dialysis system (Fresenius Medical Care, Germany) consists of a closed dialysate tank of 90 L; it offers the opportunity of effecting mass balances of any solute in a very precise way. The present study has a crossover design: 11 stable anuric HD patients underwent 2 bicarbonate HD sessions, 1 of 4 hours (4h) and the other of 8 hours (8h) in a random sequence, always at the same interdialytic interval, at least 1 week apart. The GENIUS system and high-flux FX80 dialyzers (Fresenius Medical Care, Germany) were used. The volume of blood and dialysate processed, volume of ultrafiltration and dialysate Ca concentrations (1.50 mmol/L) were prescribed to be the same. Trends of plasma Ca++, blood pH and bicarbonates during dialysis, as well as Ca++MBs were determined. Plasma parathyroid hormone (PTH) levels at the start and end of the 2 treatments were measured. Ca++MBs (mean ± SD) were +284.6 ± 137.4 mg and +297.7 ± 131.6 mg (p=0.307) in the 4h and 8h treatments, respectively. No single session out of the 22 had a negative Ca++MB for the patient. Mean plasma Ca++, blood pH and bicarbonate levels were not statistically significantly different when comparing the start and end of the sessions of the 2 treatments. Mean plasma Ca++, blood pH and bicarbonate levels increased significantly along the time points in both 4h and 8h HD sessions (repeated measures ANOVA: p<0.0001). Mean plasma PTH levels were not statistically significantly different when comparing the start and end of the sessions of the 2 treatments. The differences between predialysis and postdialysis plasma PTH levels were not statistically significantly different either in 4h or 8h sessions (Wilcoxon's test: p=NS), even though a trend toward lower postdialysis plasma PTH levels was observed in both 4h and 8h treatments. Our data show incontrovertibly that, when dialyzing with a dialysate Ca concentration of 1.50 mmol/L, 4h standard bicarbonate HD and 8h slow-flow bicarbonate HD always achieve a quite similar positive Ca++MB for the patients.

Removal of uraemic retention solutes in standard bicarbonate haemodialysis and long-hour slow-flow bicarbonate haemodialysis

Several studies already stressed the importance of haemodialysis (HD) time in the removal of uraemic toxins. In those studies, however, also the amount of dialysate and/or processed blood was altered. The present study aimed to investigate the isolated effect of the factor time t (by processing the same total blood and dialysate volume in two different time schedules) on the removal and kinetic behaviour of some small, middle and protein-bound molecules. The present study had a crossover design: 11 stable anuric HD patients underwent two bicarbonate HD sessions (~ 4 and ~ 8 h) in a random sequence, at least 1 week apart. The GENIUS single-pass batch dialysis system and the high-flux FX80 dialysers (Fresenius Medical Care, Bad Homburg, Germany) were used. The volume of blood and dialysate processed, volume of ultrafiltration, and dialysate composition were prescribed to be the same. For each patient, blood was sampled from the arterial line at 0, 60, 120, 180 and 240 min (all sessions), and at 360 and 480 min (8-h sessions). Dialysate was sampled at the end of HD from the dialysate tank. The following solutes were investigated: (i) small molecules: urea, creatinine, phosphorus and uric acid; (ii) middle molecule: β(2)M; and (iii) protein-bound molecules: homocysteine, hippuric acid, indole-3-acetic acid and indoxyl sulphate. Total solute removals (solute concentration in the spent dialysate of each analyte × 90 L - the volume of dialysate) (TSR), clearances (TSR of a solute/area under the plasma water concentration time curve of the solute) (K), total cleared volumes (K × dialysis time) (TCV), and dialyser extraction ratios (K/blood flow rate) (ER) were determined. The percent differences of TSR, K, TCV and ER between 4- and 8-h dialyses were calculated. Single-pool Kt/Vurea, and post-dialysis percent rebounds of urea, creatinine and β(2)M were computed. TSR, TCV and ER were statistically significantly larger during prolonged HD for all small and middle molecules (at least, P < 0.01). Specifically, the percent increases of TSR (8 h vs 4 h) were: for urea 22.6.0% (P < 0.003), for creatinine 24.8% (P < 0.002), for phosphorus 26.6% (P < 0.001), and for β(2)M 39.2% (P < 0.005). No statistically significant difference was observed for protein-bound solutes in any of the parameters being studied. Single-pool Kt/Vurea was 1.41 ± 0.19 for the 4-h dialysis sessions and 1.80 ± 0.29 for the 8-h ones. The difference was statistically significant (P < 0.0001). Post-dialysis percent rebounds of urea, creatinine and β(2)M were statistically significantly greater in the 4-h dialysis sessions (at least, P < 0.0002). The present controlled study using a crossover design indicates that small and middle molecules are removed more adequately from the deeper compartments when performing a prolonged HD, even if blood and dialysate volumes are kept constant. Hence, factor time t is very important for these retention solutes. The kinetic behaviour of protein-bound solutes is completely different from that of small and middle molecules, mainly because of the strength of their protein binding.

Malnutrition-Inflammation Score and Endothelial Dysfunction in Hemodialysis Patients

The aim of this study was to find out the relationship between Malnutrition-Inflammation score (MIS) and the endothelial function parameters, including measurements of flow-mediated vasodilatation (FMD) in the brachial artery and serum vascular cell adhesion molecule-1 (VCAM-1). Furthermore, predictors of FMD were also assessed. A total of 70 anuric hemodialysis patients were enrolled in this cross-sectional study. Measurements of FMD, serum VCAM-1, oxidized low density lipoprotein cholesterol (oxLDL) were done before the mid-week dialysis session from all participants at the time of MIS calculation. Patients were divided into 3 groups according to MIS (the MIS was ≤4 in group I, 4< and ≤7 in group II, and >7 in group III) and compared for above parameters. Patients with higher MIS had higher serum high sensitive C-reactive protein, oxLDL and VCAM-1 levels whereas these patients had lower serum albumin, hemoglobin levels, and FMD rates. MIS was positively correlated with high sensitive C-reactive protein, oxLDL and VCAM-1 levels. However, there was a negative correlation between MIS and FMD. MIS and oxLDL were found as an independent significant predictors of FMD (P = .014 and P = .018, respectively) in a multivariate analysis. MIS is a useful tool in prediction of the severity of endothelial dysfunction. Furthermore, decrease in MIS by the modifiable parameters and also treatment of oxLDL could be expected to improve endothelial dysfunction in hemodialysis patients.