Calcium‐phosphate and parathyroid intradialytic profiles: A potential aid for tailoring the dialysate calcium content of patients on different hemodialysis schedules

Severe hyperparathyroidism is a challenge on hemodialysis. The definition of dialysate calcium (Ca) is a pending issue with renewed importance in cases of individualized dialysis schedules and of portable home dialysis machines with low‐flow dialysate. Direct measurement of calcium mass transfer is complex and is imprecisely reflected by differences in start‐to‐end of dialysis Ca levels. The study was performed in a dialysis unit dedicated to home hemodialysis and to critical patients with wide use of daily and tailored schedules. The Ca‐phosphate (P)‐parathyroid hormone (PTH) profile includes creatinine, urea, total and ionized Ca, albumin, sodium, potassium, P, PTH levels at start, mid, and end of dialysis. “Severe” secondary hyperparathyroidism was defined as PTH > 300 pg/mL for ≥3 months. Four schedules were tested: conventional dialysis (polysulfone dialyzer 1.8–2.1 m²), with dialysate Ca 1.5 or 1.75 mmol/L, NxStage (Ca 1.5 mmol/L), and NxStage plus intradialytic Ca infusion. Dosages of vitamin D, calcium, phosphate binders, and Ca mimetic agents were adjusted monthly. Eighty Ca‐P‐PTH profiles were collected in 12 patients. Serum phosphate was efficiently reduced by all techniques. No differences in start‐to‐end PTH and Ca levels on dialysis were observed in patients with PTH levels < 300 pg/mL. Conversely, Ca levels in “severe” secondary hyperparathyroid patients significantly increased and PTH decreased during dialysis on all schedules except on Nxstage (P < 0.05). Our data support the need for tailored dialysate Ca content, even on “low‐flow” daily home dialysis, in “severe” secondary hyperparathyroid patients in order to increase the therapeutic potentials of the new dialysis techniques.     

Impact of advanced dialysis technology on the prevalence of dialysis‐related amyloidosis in long‐term maintenance dialysis patients

Dialysis‐related amyloidosis (DRA) is a unique type of amyloidosis (beta‐2 microglobulin) predominantly in end‐stage renal disease. Its clinical manifestations add to increased morbidity and reduced quality of life. There seems to be a relative risk reduction in DRA manifestations when hemodialysis (HD) patients are treated with advanced HD technology, but changes of the course of DRA are uncertain. The aim of our investigation was to evaluate the prevalence and severity of carpal tunnel syndrome (CTS) in long‐term dialysis patients receiving either conventional or high‐flux, online‐produced ultrapure dialysis fluid. The cross‐sectional study included 147 HD patients (at least 10 years). The definitive diagnosis of CTS was made histologically or by the coexistence of CTS with other radiological DRA manifestations (bone cysts, arthropathies). The two HD patient groups did not differ significantly in age at start of HD, gender, major co‐morbid diseases, anuria, and dialysis vintage. The conventional HD group had significantly higher circulating beta‐2 microglobulin and C‐reactive protein (CRP) levels. The prevalence of DRA was 68% for the conventional HD group and 28% for the advanced HD group. Duration of dialysis treatment was the only significant risk factor for the development of clinical DRA manifestations in both study groups, but CTS, bone cysts, or arthropathies occurred significantly earlier in conventional HD patients. The prevalence and severity of DRA have decreased with advances in dialysis technology during the last two decades, although its occurrence is simply delayed.     

Survival with short‐daily hemodialysis: Association of time,site, and dose of dialysis

In thrice‐weekly hemodialysis, survival correlates with the length of time (t) of each dialysis and the dose (Kt/V), and deaths occur most frequently on Mondays and Tuesdays. We studied the influence of t and Kt/V on survival in 262 patients on short‐daily hemodialysis (SDHD) and also noted death rate by weekday. Contingency tables, Kaplan‐Meier analysis, regression analysis, and stepwise Cox proportional hazard analysis were used to study the associations of clinical variables with survival. Patients had been on SDHD for a mean of 2.1 (range 0.1–11) years. Mean dialysis time was 12.9 ± 2.3 h/wk and mean weekly stdKt/V was 2.7 ± 0.5. Fifty‐two of the patients died (20%) and 8‐year survival was 54 ± 5%. In an analysis of 4 groups by weekly dialysis time, 5‐year survival continuously increased from 45 ± 8% in those dialyzing <12 hours to 100% in those dialyzing >15 hours without any apparent threshold. There was no association between Kt/V and survival. In Cox proportional hazard analysis, 4 factors were independently associated with survival: age in years Hazard Ratio (HR)=1.05, weekly dialysis hours HR=0.84, home dialysis HR=0.50, and secondary renal disease HR=2.30. Unlike conventional HD, no pattern of excessive death occurred early in the week during SDHD. With SDHD, longer time and dialysis at home were independently associated with improved survival, while Kt/V was not. Homedialysis and dialysis 15+ h/wk appear to maximize survival in SDHD.     

Plasma myeloperoxidase,NT‐proBNP,and troponin‐I in patients on CAPD compared with those on regular hemodialysis

Myeloperoxidase (MPO) is a hemoprotein that is released during inflammation and may lead to irreversible protein and lipid modification, increasing levels of oxidized low density lipoprotein, and promoting athrogenesis. Recently, it has been considered as a risk factor for cardiovascular diseases. Similarly, the measurement of carotid intima‐media thickness gives an indication about the degree of atherosclerosis and prediction of clinical cardiovascular events. Elevated white blood cells counts may indicate a state of acute inflammation and follow its progression. Dialysis patients are at a high risk of developing cardiovascular disease compared with healthy subjects. The role of N‐terminal pro‐brain natriuretic peptide and increased cardiac troponin in identification and prognostication of cardiovascular diseases in end‐stage renal disease patients has been investigated. The current study aimed to evaluate plasma MPO and its possible relationship with carotid intima‐media thickness, troponin I, N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), and insulin resistance as measured by homeostatic model assessment (HOMA index) in a cohort of Saudi patients who are undergoing hemodialysis (HD) vs. continuous ambulatory peritoneal dialysis for end‐stage renal disease. Plasma MPO was significantly higher in patients on continuous ambulatory peritoneal dialysis (CAPD) than in those on HD and in normal subjects (P<0.001). Conversely, NT‐proBNP plasma levels were significantly higher in patients on HD (both predialysis and postdialysis) than in those on CAPD (P<0.01) and than normal subjects. Similarly, plasma troponin‐I levels were significantly higher in patients on HD compared with those of CAPD and than normal subjects (P<0.001). Plasma troponin‐I and NT‐proBNP levels were positively correlated in the 3 groups namely those on CAPD, Pre‐HD, and post‐HD (r: 0.464 and P=0.047; r: 0.330 and P=0.013; and r: 0.452 and P=0.024), respectively. There was no correlation between the MPO level and carotid intima‐media thickness (P>0.05). However, plasma MPO level correlated positively with the white blood cell count in patients on CAPD and in those on HD (P<0.05). Our findings suggest an increased oxidative stress in CAPD patients compared with HD patients, while the reported difference in plasma NT‐proBNP and troponin‐I may be related to the rapid decline of residual renal function in HD and type of membrane used in the HD dialysis procedure itself.     

The long‐term effects of arteriovenous fistula creation on the development of pulmonary hypertension in hemodialysis patients

The aim of this prospective study was to evaluate long‐term effects of arteriovenous fistula (AVF) on the development of pulmonary arterial hypertension (PAH) and the relationship between blood flow rate of AVF and pulmonary artery pressure (PAP) in the patients with end‐stage renal disease (ESRD). This prospective study was performed in 20 patients with ESRD. Before an AVF was surgically created for hemodialysis, the patients were evaluated by echocardiography. Then, an AVF was surgically created in all patients. After mean 23.50 ± 2.25 months, the second evaluation was performed by echocardiography. Also, the blood flow rate of AVF was measured at the second echocardiographic evaluation. Pulmonary arterial hypertension was defined as a systolic PAP above 35 mmHg at rest. Mean age of 20 patients with ESRD was 55.05 ± 13.64 years; 11 of 20 patients were males. Pulmonary arterial hypertension was detected in 6 (30%) patients before AVF creation and in 4 (20%) patients after AVF creation. Systolic PAP value was meaningfully lower after AVF creation than before AVF creation (29.95 ± 10.26 mmHg vs. 35.35 ± 7.86 mmHg, respectively, P: 0.047). However, there was no significant difference between 2 time periods in terms of presence of PAH (P>0.05). Pulmonary artery pressure did not correlate with blood flow rate of AVF and duration after AVF creation (P>0.05). In hemodialysis patients, a surgically created AVF has no significant effect on the development of PAH within a long‐term period. Similarly, blood flow rate of AVF also did not affect remarkably systolic PAP within the long‐term period.     

Confounding factors for early death in incident end‐stage renal disease patients: Role of emergency dialysis start

Hemodialysis (HD) has been associated with higher 1‐year mortality than peritoneal dialysis (PD) after dialysis start. Confounding effects of late referral, emergency dialysis start, or start with central venous catheter on this association have never been studied concomitantly. Survival was studied among the 495 incident dialysed patients in our department from 1995 to 2006 and followed at least 1 year until December 31, 2007. Nested Cox models adjusted on patient characteristics explored factors associated with 1‐year and ≥1‐year mortality. Hemodialysis patients were 332 (67.1%), 104 (21.0%) were late referred (<6 months), 167 (33.7%) started dialysis in emergency, and 144 (29.1%) started with central venous catheter. When adjusted only on age, sex, and comorbidities, HD was associated with poor 1‐year outcome: adjusted hazard ratio (aHR) for death in HD vs. PD was 1.77, P=0.02. In fully adjusted model, among first dialysis feature variables, only emergency dialysis start was significantly associated with 1‐year mortality: aHR 1.53, P=0.02. Dialysis modality was not associated with 1‐year mortality rates in this fully adjusted model: aHR in HD vs. PD became 1.03, P=0.91. In ≥1‐year period, HD was associated with lower mortality than PD (aHR 0.61, P=0.004), whereas other first dialysis features were not associated with death. Other factors associated with death were age, type 2 diabetes, peripheral vascular disease, heart failure, and hepatic failure. Negative association between HD and 1‐year survival on dialysis was explained by confounders. Emergency dialysis start was strongly associated with early mortality on dialysis. Its prevention may improve patient survival.     

Calculation of the clearance requirements for the development of a hemodialysis‐based wearable artificial kidney

Wearable artificial kidney (WAK) has been considered an alternative to standard hemodialysis (HD) for many years. Although various novel WAK systems have been recently developed for use in clinical applications, the target performance or standard dose of dialysis has not yet been determined. To calculate the appropriate clearance for a HD‐based WAK system for the treatment of patients with end‐stage renal disease with various dialysis conditions, a classic variable–volume two‐compartment kinetic model was used to simulate an anuric patient with variable target time‐averaged creatinine concentration (TAC), daily water intake volume, daily dialysis pause time, and patient body weight. A 70‐kg anuric patient with a HD‐based WAK system operating for 24 h required dialysis clearances of creatinine of at least 100, 50, and 25 mL/min to achieve TACs of 1.0, 2.0, and 4.0 mg/dL, respectively. The daily water intake volume did not affect the clearance required for dialysis under various conditions. As the pause time per day for the dialysis increased, higher dialysis clearances were required to maintain the target TAC. The present study provided theoretical dialysis doses for an HD‐based WAK system to achieve various target TACs through relevant mathematical kinetic modeling. The theoretical results may contribute to the determination of the technical specifications required for the development of a WAK system.     

Doppler echocardiograph evaluation of pulmonary hypertension in patients undergoing hemodialysis

Pulmonary hypertension (PH) has been reported in hemodialysis (HD) patients, but data regarding its incidence and mechanisms are scarce. The aims of this study was to evaluate the prevalence of unexplained PH in long-term HD patients, and to examine some possible etiologic factors for its occurrence. The prevalence of PH was estimated by Doppler echocardiography in a cohort of 86 stable patients on HD via arteriovenous access for more than 12 months. All the patients underwent full clinical evaluation, chest radiography, and a standard 12-lead echocardiograph. Laboratory investigation included a mean of 12 months (serum calcium, phosphorus, parathormone (PTH), alkaline phosphatase, lipids, and hemoglobin). Pulmonary hypertension was defined as pulmonary artery systolic pressure >35 mmHg as determined by Doppler echocardiography using the modified Bernoulli equation. Pulmonary hypertension was detected in 23 patients (26.74%). Of those with PH, left ventricular hypertrophy was seen in 13 patients (56.52%), and valvular calcifications in 6 patients (26.08%). There were no significant differences between both groups with regard to age, sex, duration of dialysis, shunt location, and all the biological parameters of the study. The presence of PH was not related to the level of PTH, or the severity of other metabolic abnormalities. This study demonstrates a high prevalence of PH among patients with ESRD receiving long-term HD via surgical arteriovenous access. The role of the vascular access, anemia, or secondary hyperparathyroidism as the etiology of PH in HD patients did not hold in this study.     

Management of hypertension in hemodialysis patients

The relationship of hypertension with adverse outcomes is uncertain in the hemodialysis population. If hypertension is an etiologically significant cardiovascular risk factor in hemodialysis patients, the first step would be to assess the level of BP accurately. BP obtained at home over a week and averaged using a validated oscillometric automatic device can prove valuable. To the extent BP lowering influences cardiovascular outcomes, home BP of 150/90 mm Hg would warrant therapy, since it correlates with target organ damage and hypertension diagnosed by ambulatory BP monitoring. To manage hypertension, limiting dietary sodium intake and individualizing dialysate sodium delivery would be first steps. The magnitude of reduction in BP with dietary sodium restriction and the whether dialysate sodium can be safely limited in those who are hypotension-prone is unclear. Antihypertensive drug therapies can effectively reduce BP and are needed by the vast majority of hemodialysis patients. Whether control of hypertension translates into better outcomes is not known, but collective evidence suggests that hypertension should be controlled in hemodialysis patients.     

Effect of alternate night nocturnal home hemodialysis on anemia control in patients with end‐stage renal disease

Nocturnal home hemodialysis (NHHD) has shown promising results in various clinical parameters. Whether NHHD provide benefit in anemia management remains controversial. This study aims to investigate whether anemia and erythropoiesis‐stimulating agent (ESA) requirement are improved in patients receiving alternate night NHHD compared with conventional hemodialysis (CHD). In this retrospective controlled study, a clinical data of 23 patients receiving NHHD were compared with 25 in‐center CHD patients. Hemoglobin level, ESA requirement, iron profile, and dialysis adequacy indexes were compared between the two groups. Hemoglobin level increased from baseline of 9.37 ± 1.39 g/dL to 11.34 ± 2.41 g/dL at 24 months (P < 0.001) and ESA requirement decreased from 103.44 ± 53.55 U/kg/week to 47.33 ± 50.62 U/kg/week (P < 0.001) in NHHD patients. ESA requirement further reduced after the first year of NHHD (P = 0.037). Standard Kt/V increased from baseline of 2.02 ± 0.28 to 3.52 ± 0.30 at 24 months (P < 0.001). At 24 months, hemoglobin level increased by 1.98 ± 2.74 g/dL in the NHHD group while it decreased by 0.20 ± 2.32 g/dL in the CHD group (P = 0.007). ESA requirement decreased by 53.49 ± 55.50 U/kg/week in NHHD patients whereas it increased by 16.22 ± 50.01 U/kg/week in CHD patients (P < 0.001). Twenty‐six percent of NHHD patients were able to stop ESA compared with none in the CHD group. Standard Kt/V showed greater increase in the NHHD group. (1.49 ± 0.36 in NHHD vs. 0.18 ± 0.31 in CHD, P = 0.005). NHHD with an alternate night schedule improves anemia and reduces ESA requirement as a result of enhanced uremic clearance. This benefit extended beyond the first year of NHHD.     

Anti‐inflammatory effects of linagliptin in hemodialysis patients with diabetes

Inflammation and glycemic control are important prognosis‐related factors for hemodialysis (HD) patients; moreover, inflammation affects insulin secretion. Here, we evaluated the anti‐inflammatory effects of monotherapy with linagliptin—a dipeptidase‐4 inhibitor—in HD patients with type 2 diabetes. We examined 21 diabetic HD patients who were not receiving oral diabetes drugs or insulin therapy and with poor glycemic control (glycated albumin [GA] level, >20%). Linagliptin (5 mg) was administered to the patients daily. The levels of prostaglandin E2 (PGE2), interleukin‐6 (IL‐6), high‐sensitivity C‐reactive protein, GA, blood glucose, and active glucagon‐like peptide‐1 were determined before and 6 months after treatment. Body weight and serum levels of albumin, hemoglobin, total cholesterol, and low‐density lipoprotein cholesterol were also recorded before and after treatment. The levels of PGE2 and GA were significantly decreased 1 month after starting linagliptin therapy, whereas the IL‐6 levels were significantly decreased 6 months after starting linagliptin therapy. After 6 months of treatment, the PGE2 levels decreased from 188 ± 50 ng/mL to 26 ± 5 ng/mL; IL‐6 levels, from 1.5 ± 0.4 pg/mL to 0.6 ± 0.1 pg/mL; and GA levels, from 21.3% ± 0.6% to 18.0% ± 0.6%. Glucagon‐like peptide‐1 levels increased 2.5‐fold during the treatment. Over the 6‐month treatment period, body weight and levels of high‐sensitivity C‐reactive protein, blood glucose, albumin, hemoglobin, and cholesterol did not change; none of the patients exhibited hypoglycemia. The anti‐inflammatory effects of linagliptin monotherapy indicate that it may serve as a useful glucose control strategy for HD patients with diabetes.     

The relevance of convection in clinical practice: a critical review of the literature

Convective treatments (high-flux hemodialysis (HD), hemodiafiltration and hemofiltration) are characterized by enhanced removal of middle and large molecular weight solutes compared with conventional low-flux HD. As these molecules are claimed to play an important role in the genesis of many complications of chronic HD, the availability of these techniques represented an intriguing innovation and a possible means to improve the still poor prognosis of HD patients. Here we will critically review the most important published studies comparing convective treatments with low-flux HD on chronic morbidity, preservation of residual renal function, and long-term survival.     

Enhanced expression of hemoglobin scavenger receptor and heme oxygenase‐1 is associated with aortic valve stenosis in patients undergoing hemodialysis

A high prevalence and a rapid progression of aortic valve stenosis (AS) in patients undergoing hemodialysis (HD) has been reported. In these circumstances, intraleaflet hemorrhage of aortic valve may be related to the development of AS in HD patients. We immunohistochemically examined the relationship among intraleaflet hemorrhage, neovascularization, hemoglobin scavenger receptor (CD163), and heme oxygenase‐1 (HO‐1) using surgically resected aortic valve specimens from AS patients undergoing HD. The study population consisted of 26 HD patients and 25 non‐HD patients with severe AS who had undergone aortic valve replacement. Frozen aortic valve samples surgically obtained from AS patients were stained immunohistochemically with antibodies against smooth muscle cells, macrophages, glycophorin‐A (a protein specific to erythrocyte membranes), CD31, CD163, and HO‐1. Morphometric analysis demonstrated that the CD163‐positive macrophage score, the number of CD31‐positive microvessels, and the percentage of glycophorin‐A and HO‐1‐positive area were significantly higher in HD patients than in non‐HD patients (CD163‐positive macrophage score, P < 0.0001; CD31‐positive microvessels, P < 0.0001; glycophorin‐A, P < 0.0001; HO‐1, P < 0.0001). Double immunostaining for CD163 or HO‐1 and macrophages revealed that the majority of CD163‐ or HO‐1‐positive cells were macrophages. Furthermore, CD163‐positive macrophage score was positively correlated with glycophorin‐A, HO‐1‐positive area, and the number of CD31‐positive microvessels (glycophorin‐A, R = 0.66, P < 0.0001; HO‐1, R = 0.50, P < 0.0005; microvessels, R = 0.38, P < 0.01). These findings suggest a positive association among intraleaflet hemorrhage, neovascularization, and enhanced expression of CD163 and HO‐1 as a response to intraleaflet hemorrhage in stenotic aortic valves in AS patients undergoing HD.     

A meta‐analysis of sodium profiling techniques and the impact on intradialytic hypotension

Introduction Hemodialysis has improved in recent years, however, despite such improvements, intra‐dialytic hypotensive episodes still persist which can lead to a reduction in the overall effectiveness of the treatment. Profiling sodium levels during dialysis can improve vascular refilling and therefore may prevent hypotensive events. A number of profiling methods exist and this meta‐analysis set out to examine the effectiveness of these methods. Methods To assess the effectiveness of hemodialysis sodium profiling techniques. A review and meta‐analysis analytical framework was used. A search was conducted using Medline, Embase and CINAHL, Scopus and Web of Knowledge between 1946 and 2014 of published English‐language peer reviewed randomized control studies. In total 10 articles were retrieved and included in the review. All data was abstracted with a standardized data collection form. Stata 11.2 (Stata Corp) was used to analyse the data. Actual numbers of hypotensive events were pooled between studies. Analysis of subgroups was performed on sodium profile type. The data were further investigated using meta‐regression. Publication bias was also tested. Findings Stepwise profiling was shown to be statistically significantly effective in reducing intradialytic episodes. Results demonstrated that linear sodium profiling was not effective in reducing hypotensive events during dialysis. Discussion This review has shown that using stepwise profiling is more effective at reducing intra‐dialytic symptoms than other profiling methods. There was no evidence that linear profiling method was any more effective than conventional dialysis and in fact the results showed the reverse.     

Risk of major depression in patients with chronic renal failure on different treatment modalities: A matched‐cohort and population‐based study in Taiwan

The influence of different treatment modalities on the risk of developing major depression in patients with chronic renal failure (CRF) is not well understood. We aimed to explore the incidence of major depression among patients with CRF who were on different dialysis modalities, who had received renal transplantation (RT), and those who had not yet received any of the aforementioned renal replacement therapies. We conducted a population‐based retrospective cohort study using a national health insurance research database. This study investigated 89,336 study controls, 17,889 patients with chronic kidney disease on conservative treatment, 3823 patients on hemodialysis (HD), 351 patients on peritoneal dialysis (PD), and 322 patients who had RT. We followed all individuals until the occurrence of major depression or the date of loss to follow‐up. The PD group had the highest risk (hazard ratio [HR] 2.43; 95% confidence interval [CI] 1.26–4.69), whereas the RT group had the lowest risk (HR 0.18; 95% CI 0.03–1.29) of developing major depression compared with the control group. Patients initiated on PD had a higher risk of developing major depression than patients initiated on HD (pairwise comparison: HR 2.20; 95% CI 1.09–4.46). Different treatment modalities are associated with different risks of developing major depression in patients with CRF. Among renal replacement therapies, patients who have had RT have the lowest risk of developing major depression. Patients who initiate renal therapy on PD may have a higher risk of major depression compared with patients who initiate renal therapy on HD.