Morbidity In Hemodialysis Patients Research Articles

Exploring Inflammation in Hemodialysis Patients: Persistent and Superimposed Inflammation

Background: Inflammation is frequently elevated, and seems to be episodic in hemodialysis (HD) patients. Whether, its episodic character is due to the temporal variability, in periods free of clinical events, of the inflammatory indices or due, to the acute phase response induced by common inflammatory stimuli, has not been investigated yet in a longitudinal study. This study explores inflammation forms, characteristics and causes which are probably related to the high cardiovascular disease (CVD) morbidity in HD patients. Methods: In 37 HD patients, high-sensitivity C-reactive protein (hs-CRP), serum amyloid A (SAA) and interleukin-6 (IL-6) were weekly measured for 16 consecutive weeks. Inflammatory clinical events, in the week before every measurement, were recorded. Repeated measures ANOVA were applied for statistical analysis. Results: Fifty-one of 533 patient-weeks were positive for a clinical event. Mean ± SD (range) hs-CRP was 7.01 ± 16.06 (0.2–169) mg/l for all the weeks of the study, 38.25 ± 39.35 (2.1–169) mg/l for the weeks with clinical events and 3.70 ± 3.86 (0.2–26.1) mg/l for the weeks free of events. Variations for SAA and IL-6 were similar. ‘Clinical events’ strongly influenced acute-phase proteins and IL-6 levels. The effect of the factor ‘time’ (as assessed by inflammatory indices variation in weekly repeated measurements) was significant for all the 3 indices measured, independently of the factor ‘clinical events’. Conclusions: In periods free of clinical events, microinflammation characterizes HD patients and fluctuates in time. Inflammation due to common clinical events is added, periodically, to this microinflammation. The high level persistent microinflammation as well as the superimposed – due to clinical events – inflammation could be related to the CVD in these patients.

Dialysis Dose Parameters. How Much We Can Improve Them in Our Clinical Practice? Role of Online Conductivity Monitor

The mortality and morbidity of hemodialysis patients is, to a large extent, determined by demographics and by existing comorbidities, but it is obvious that variations in dialysis dose have substantial effects. Using eKt/V, 1.2 monthly comparisons are recommended by European guidelines, but they assume that dose is maintained during all monthly sessions. Because of dialysis‐related problems like hypotension, reduction of blood flow, dialysis time, microclotting of the dialyzer, and vascular access problems, the delivered dose may vary from session to session. New developed devices based on online conductivity clearance reflect the electrolyte clearance and, thus, clearance of urea. The aim of this prospective study was to show the variability of dialysis dose. 24 anuric patients were studied during 3 months: 20.8% were diabetics, mean age 64.7 ± 18.2 years; 16% females. Access blood were AVFi and the effective dialyzed blood flow was set at 350 mL/min, with recirculation <5%. BMI was 25.4 ± 3.8 kg/m2 and body weight was 69.7 ± 12 kg. All patients were dialyzed thrice weekly (245 ± 21 min) with dialysis machine 4008H (Fresenius Medical Care) equipped with online conductivity monitor (OCM) and the hollow fiber high‐flux polysulfone membrane (HF‐80 1.8 m2) and helixone (Fx‐60, 1.6 m2). OCM was validated for our population and reported in other abstracts (r2 = 0.96, p < 0.001). Dialysate flow was maintained at 500 mL/min, with standard dialysate liquid. Each patient was subjected to OCM on regular sessions during 3 months, and blood Kt/V samples were taken on midweek day, once a month. Data were processed and statistically analyzed with SPSS 11.0 software package. Kt/V OCM relation with other baseline characteristics was assessed by using contingency tables, t‐tests, analysis of variance, and linear regression, as appropriate. All the tests were performed for a 0.05 significance level. The conductivity‐based OCM provides an accurate tool to monitor the dose and control of each hemodialysis session and adds to the efficiency of current dialysis adequacy monitoring. OCM device requires little maintenance, and no extra effort is needed. Monthly Kt/V does not reflect the variability of each session. Further studies are necessary to evaluate its influence on morbidity and mortality. Descriptives Variables Minimum Maximum Mean SD Age (year) 31 86 64.75 18.243 Membrane surface 1.6 1.8 1.675 0.0989 Interdialysis weight gain 500 4200 2266.67 1016.673 BMI 18.22 31.03 25.4155 3.83630 Time on dialysis (min) 210 320 245.21 21.340 OCM 0.990 1.880 1.29921 0.201072 dPVV/Kt/V (Daugirdas) 1.00 2.09 1.4067 0.21924 Watson volume (L) 25.8 49.3 36.833 6.3095

Oxidant stress in hemodialysis patients: what are the determining factors?

Oxidant stress contributes to morbidity in hemodialysis patients. Three possible causes of oxidant stress have been suggested: the uremic state, the dialyzer membrane, and bacterial contaminants from the dialysate. Oxidant stress occurs in uremia before dialysis therapy is initiated, as evidenced by increased production of reactive oxygen species, increased levels of oxidized plasma proteins and lipids, and decreased antioxidant defenses. It has been proposed that increased production of reactive oxygen species during hemodialysis is also an important contributor to oxidant stress. Hemodialysis is associated with a transient increase in production of reactive oxygen species, particularly with cellulose membranes. In addition, surveys have shown widespread contamination of dialysate by endotoxin, which may cross membranes and prime production of reactive oxygen species by phagocytic cells. Recent studies, however, show a decrease in protein oxidation from pre- to post-dialysis and a normalization of neutrophil reactive oxygen species production. Taken together, these data suggest that uremia, per se, is the most important cause of oxidant stress in hemodialysis patients. Dialysate quality may also contribute to oxidant stress, but evidence that the dialyzer membrane plays a role is weak.

Soluble Fas is a marker of peripheral arterial occlusive disease in haemodialysis patients.

Peripheral arterial occlusive disease (PAOD) including lower-extremity and cerebrovascular atherosclerosis is a leading cause of morbidity in haemodialysis patients. Recent evidence suggests that the expression of Fas, a molecule implicated in the initiation of apoptosis in various cell types, is increased at sites of atherosclerotic plaques. However, the significance of plasma levels of the soluble form of Fas (sFas) as a marker of peripheral arterial disease has yet to be defined. The present report is based on a cross-sectional analysis of baseline data from an ongoing prospective study designed to evaluate the role of sFas as marker of PAOD in end-stage renal disease (ESRD). We evaluated the association between sFas levels and evidence of PAOD in a cohort of 107 chronic haemodialysis patients. Compared with subjects without evidence of disease (n=56), subjects with PAOD (n=51) had significantly higher plasma levels of sFas (30.0+/-8.9 vs 26.4+/-9.5 ng/ml; P=0.04). Using multiple regression, sFas was found to be associated with PAOD independently of classical risk factors for atherosclerosis (hypercholesterolaemia, diabetes, hypertension, and smoking), markers of inflammation (e.g. C-reactive protein, intercellular cell adhesion molecule type 1), and other risk factors (e.g. age, gender). An increase of one quintile in the plasma concentration of sFas was associated with an odds ratio of PAOD of 1.69 (95% CI: 1.09--2.63, P=0.01). In addition, models that incorporated sFas were significantly better at predicting PAOD than models limited to classical risk factors for atherosclerosis, alone or in combination with CRP levels (P=0.01). Increased plasma levels of sFas are associated with established PAOD. These results suggest that sFas may represent a novel and independent marker of atherosclerosis.

Central venous catheters: infection and patient susceptibility.

Infection is a major cause of morbidity in haemodialysis patients, of which between 25% and 50% of infections are related to vascular access, most commonly central venous catheters (CVCs) (Kessler et al, 1993). The morbidity associated with CVC infection provides a focus for research investigation, as there is limited knowledge available in relation to physiological and psychological parameters that may increase the probability of haemodialysis patients acquiring a CVC-related infection. This study explores these issues and discusses various factors that influence infection. It then describes how organisms which live on and inside our bodies can become parasitic, thus causing an infection. The precautions taken by healthcare professionals to reduce colonization and infection are enumerated, and the value of considering patients' physiological and psychological parameters alongside the more traditional extrinsic infection control approaches is discussed.

Influence of excess weight on mortality and hospital stay in 1346 hemodialysis patients

Body mass index (BMI) at its extremes contributes to morbidity and mortality in the general population. Its influence on morbidity and mortality in patients on hemodialysis is not clearly defined. The BMI in 1346 patients attending limited-care hemodialysis units across the state of Mississippi was determined, and its relation to one-year mortality and hospital stay was assessed using the Cox proportional hazard model. Of these patients, 89% were black, and 11% were white. Thirty-eight percent of patients were overweight (BMI > 27.5), and 13% were underweight (BMI < 20). The highest (27.60 +/- 0.29, mean +/- SE) and the lowest (24.54 +/- 0.48) BMI were noted in black females and white males, respectively. BMI, race, hematocrit (Hct), and biochemical markers of better nutrition positively influenced the survival, whereas age, serum globulin, and diabetes had a negative influence. In a Cox multivariate analysis, BMI, age, diabetes, prealbumin, and creatinine, but not race, serum albumin, Hct, or serum globulin, retained significant influence on survival. Compared with the normal weight (BMI between 20 and 27.5), the one-year survival rate was significantly higher in the overweight patients and lower in the underweight patients. With a one-unit increase in BMI over 27.5, the relative risk for dying was reduced by 30% (P < 0.04), and with a one-unit decrease in BMI below 20, the relative risk was increased by 1.6-fold (P < 0.01). Furthermore, underweight patients had significantly lower levels of biochemical markers of nutrition and higher frequency and longer duration of hospital stay. Adequate dialysis with special attention to proper nutrition aimed to achieve the high end of normal BMI may help to reduce the high mortality and morbidity in hemodialysis patients.

Correlates of Vascular Access Occlusion in Hemodialysis

Vascular access occlusion results in significant morbidity in hemodialysis patients. Age, diabetes, and synthetic grafts (polytetrafluoroethylene [PTFE]) have been associated with vascular access occlusion in univariate analysis. However, the independent risk associated with each of these factors has not been assessed adjusting for confounding among the factors or by other variables, such as blood pressure (BP) or hematocrit. The influence of serum lipoprotein(a) [Lp(a)] and fibronectin on vascular access occlusion has not been widely studied despite their theoretical or demonstrated importance in vascular bypass occlusion. In a cohort study of 124 hemodialysis patients monitored for up to 14 months, we reported that Lp(a) values in the upper tertile (> or = 57 mg/dL) were associated with vascular access occlusion risk in white and Hispanic patients, but not in black patients. We now report an expanded analysis of this data set to determine the independent correlates of vascular access occlusion. Variables tested included age, race, gender, diabetes, access type (PTFE v endogenous), treatment time, systolic BP, hematocrit, heparin and erythropoietin dosage, and serum levels of Lp(a) and fibronectin. In univariate analysis, access occlusion was associated with age, diabetes, PTFE, Lp(a) > or = 57 mg/dL, serum fibronectin, and reduced BP. The independent correlates of first access occlusion were determined with the Cox proportional hazards model. Since the overall model included a significant race x Lp(a) interaction term, we stratified by race. In black patients, risk correlated directly with PTFE (P < 0.01) and inversely with systolic BP (P < 0.001), whereas for white and Hispanic patients, age (P = 0.04) and Lp(a) > or = 57 mg/dL (P = 0.05) were associated with increased risk. In summary, vascular access occlusion was found to be associated with a number of factors. Important independent correlates were PTFE and lower BP in black patients, and age and serum Lp(a) > or = 57 mg/dL in white and Hispanic patients. Diabetes mellitus and increased serum fibronectin may contribute additional risk.

Control of Blood Pressure in Long Slow Hemodialysis

Hypertension is a major cause of mortality and morbidity in hemodialysis patients. A long slow dialysis (8 h/session) was used in 692 unselected patients. It allowed for an excellent control of blood pressure without the need of antihypertensive medications. Cardiovascular morbidity and mortality were lower in the subgroups of patients presenting with a lower predialysis mean arterial pressure. The control of the extracellular volume with a low rate of intradialytic hypotensive episodes is the most probable explanation of this result. Another possible mechanism is the restoration by the large dose of dialysis of the nitric oxide vasodilator action inhibited by the accumulation of dimethylarginine in the serum of uremic patients.

Permanent Vascular Access: A Nephrologist's View

Vascular access complications are the greatest cause of morbidity in hemodialysis patients in the United States. Although arteriovenous fistulas have been recommended as the preferred mode of vascular access, recent data indicate that the majority of patients on hemodialysis in the United States have prosthetic graft fistulas. The most frequent complications of prosthetic graft fistulas are thrombosis and stenosis. Hospitalization rates for fistula complications are higher in patients with diabetes mellitus and of black race. Pathogenesis of intimal hyperplasia may include elaboration of platelet-derived growth factor and mechanical endothelial injury. Screening for stenosis and impaired blood flow in fistulas can be carried out with recirculation measurements, venous and intra-access pressure measurements, and Doppler ultrasound. A combination of the techniques is probably the best current strategy for fistula screening and further evaluation. Surgical thrombectomy and fistula revision remain the standard for comparison of newer approaches to management of complications. Percutaneous angioplasty with or without stent placement, thrombolysis, and use of atherectomy devices may play an increasing role in the treatment of complications, although comparative trials of these modalities need to be performed. No satisfactory long-term pharmacologic means of preventing thrombosis, stenosis, or restenosis have been found for graft arteriovenous fistulas. It is hoped that future directions in the field of vascular access placement and management will include better strategies for allowing primary arteriovenous fistula development, advances in graft materials, improved understanding of the pathogenesis of thrombosis and stenosis, and development strategies to prevent complications.

Prevention of hemodialysis subclavian vein catheter infections by topical povidone-iodine

Subclavian catheter (SCC) related infections are a major cause of morbidity in hemodialysis patients, the vast majority due to staphylococci species. Povidone-iodine (PI) has proven anti-staphylococcal activity. Therefore, a randomized controlled trial of topical PI ointment was undertaken to evaluate the impact of this prophylactic intervention on the incidence of SCC related infections in hemodialysis patients. The role of S. aureus nasal carrier state in the acquisition of infection was also evaluated. Patients requiring SCC for temporary hemodialysis access were randomized to receive the treatment (T; N = 63) or sterile gauze dressings alone (C; N = 66). Catheter duration ranged from 2 to 210 days in both groups, with a mean of 38.6 days in T and 36.2 days in C (NS). Exit site (ES) infections were significantly less in T (5%) versus C (18%) (P less than 0.02); tip colonization (TC) was 17% in T versus 36% in C (P less than 0.01), while the incidence of septicemia (S) was also significantly less in T (2%) versus C (17%; P less than 0.01). S. aureus nasal carriers were at a threefold higher risk of SCC related septicemia (0.009/day) than noncarriers (0.003/day; P less than 0.05). The beneficial effect of PI ointment was most evident in this high risk group of S. aureus carriers: ES = 0% T versus 24% C, TC = 12% T versus 42% C, S = 0% T versus 29% C, P less than 0.05. There were no adverse effects of the treatment. The routine application of topical PI ointment to temporary hemodialysis catheter exit sites is effective in reducing SCC related infections.

Staphylococcus aureus Nasal Carriage in Hemodialysis Patients

Staphylococcus aureus infections remain a major cause of morbidity in hemodialysis patients. Chronic dialysis patients are more prone to staphylococcal infections because of their decreased immunity, increased skin colonization by staphylococci, and the multiple needle punctures required for dialysis. The source of the staphylococci is the anterior nares. Elimination of staphylococcal nasal carriage results in a significantly lower infection rate. Selected clinical studies of topical and oral therapy for eradication of staphylococcal nasal carriage are reviewed. Rifampin has been the most consistently efficacious agent, although emergence of resistance is a potential problem. Trials utilizing newer topical and oral agents for prophylactic eradication of S aureus from the nose are indicated. Promising antibiotics include topical mupirocin, the oral quinolones, and clindamycin.