Comparing outcome predictability of markers of malnutrition-inflammation complex syndrome in haemodialysis patients.

BACKGROUND: Markers of malnutrition-inflammation complex syndrome (MICS) are reported to predict mortality and hospitalization in maintenance haemodialysis (MHD) patients. However, it is not clear which one is a more sensitive and stronger predictor of outcome. METHODS: We examined the utility of 10 markers of MICS as predictors of prospective mortality and hospitalization, which included malnutrition-inflammation score (MIS), a fully quantitative score adopted from subjective global assessment, and serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), albumin, pre-albumin, total iron binding capacity, creatinine, total cholesterol and normalized protein nitrogen appearance. A cohort of 378 MHD patients, who were randomly selected from eight DaVita dialysis facilities in the South Bay Los Angeles area, was studied. RESULTS: Patients, aged 54.5+/-14.7 years, included 53% men, 47% Hispanics, 30% African-Americans and 55% diabetics, who had undergone MHD for 37+/-34 months. Over a 12-month follow-up, 39 patients died and 208 were hospitalized at least once. Multivariate Cox and Poisson models that included 11 covariates [gender, age, race, ethnicity, diabetes, dialysis vintage, Charlson co-morbidity index (CCI), insurance status, Kt/V, body mass index and history of cardiovascular disease] were explored for the highest quartiles of inflammatory markers or the lowest quartiles of nutritional markers. The magnitude of relative risk of death and hospitalization was greatest for MIS, CRP and IL-6. In extended multivariate models that included all 10 MICS markers and 11 additional covariates simultaneously, CRP, MIS and CCI were the only consistent predictors of mortality and hospitalization, and their outcome predictabilities were superior to serum albumin. CONCLUSIONS: The MIS appears to be a useful, short-term tool to risk-stratify MHD patients and may circumvent the need for measuring inflammatory markers such as CRP or IL-6.     

Revisiting mortality predictability of serum albumin in the dialysis population: time dependency, longitudinal changes and population-attributable fraction.

BACKGROUND: Hypoalbuminaemia is a marker of malnutrition-inflammation complex syndrome (MICS) and a strong predictor of cardiovascular (CV) death in maintenance haemodialysis (MHD) patients. However, serum albumin may change over time. Hence, its time-varying associations with outcome may be different. METHODS: Associations between 3-month averaged serum albumin levels, measured in a single laboratory using bromocresol green, and CV mortality were studied longitudinally in a 2-year cohort of 58,058 MHD patients. Mortality predictability of fixed baseline and trimonthly-varying serum albumin concentrations were compared. RESULTS: Hazard ratios (HRs) of CV death strictly increased across decrements of baseline serum albumin, whereas the HR for time-varying serum albumin decrements below 3.8 g/dl did not differ. A drop in serum albumin in the first 6 months was associated with increasing all-cause and CV death risks in the subsequent 18 months, while a rise in serum albumin was a predictor of better survival independent of baseline serum albumin. The multivariate adjusted population-attributable fraction of death due to baseline serum albumin <3.8 g/dl was 19%. CONCLUSIONS: Time-varying hypoalbuminaemia predicts all-cause and CV death differently from fixed measures of serum albumin in MHD patients. An increase in serum albumin over time is associated with better survival independent of baseline serum albumin or other MICS surrogates. If this association is causal, an intervention that could increase serum albumin >3.8 g/dl might reduce the number of MHD deaths in the USA by approximately 10,000 annually. Nutritional interventions examining benefits of increasing serum albumin in MHD patients are urgently needed.     

Oxidative stress and ferritin levels in haemodialysis patients.

BACKGROUND: Increased oxidative stress (OS) and inflammation are associated with atherosclerotic coronary artery disease in haemodialysis (HD) patients. Ferritin may have other effects in addition to its role in storing intracellular iron. This study was performed to determine any relationships between markers of OS, nutrition and inflammation in HD patients with normal and high ferritin levels. METHODS: Our cohort comprised 34 maintenance dialysis patients on erythropoietin therapy and 22 healthy controls. HD patients were divided into two groups: 17 with normal (<800 ng/ml) and 17 with high (>800 ng/ml) ferritin levels, and we measured lipid profile, albumin, highly sensitive C-reactive protein (hsCRP), anti-oxidant enzymes [whole blood glutathione peroxidase (Gpx), serum superoxide dismutase (SOD), paraoxonase, arylestherase (AE) and total anti-oxidant status (TAOC)], anti-oxidants (vitamin C) and lipid peroxidation products [red blood cell malondialdehyde (RBC MDA)]. RESULTS: Compared with controls, the HD patients had higher serum urea, blood pressure, triglyceride, hsCRP, RBC MDA, SOD and TAOC values and lower albumin, low-density lipoprotein cholesterol, apolipoprotein AI, paraoxonase, AE and whole blood Gpx activities. Serum vitamin C, uric acid, apolipoprotein B, total- and high-density lipoprotein cholesterol, apolipoprotein B MDA, and lymphocyte levels in the HD patients with normal and high ferritin levels were similar. The OS markers of HD patients did not differ, whether or not they received intravenous iron supplementation or had transferrin saturations < 50% or > or = 50%. CONCLUSION: HD patients are in a higher oxidative state, which results in the reduction of total anti-oxidant capacity and also have an increased inflammation status. We could not find a relationship between ferritin level and OS markers in HD patients receiving erythropoietin.     

A registry of haemodialysis patients and the progress of haemodialysis services in Lithuania.

Background. Until 1990, haemodialysis (HD) in Lithuania wasunderdeveloped, but after independence, development of HD started.Until 1996, no precise data about HD patients in Lithuania wereavailable. In order to create a registry of HD, we started tocollect data about dialysis services and HD patients in 1996.Every collection of data was followed by distribution and discussionof the results within the nephrological community. This studydescribes the changes of Lithuanian HD between 1996–2002. Methods. Between 1996 till 2002 all HD centres in Lithuaniawere annually visited and data were collected about all HD patients(response rate of 100%). The evaluation of the results duringour observational study was made according to the European BestPractice Guidelines. During annual conferences for nephrologists,the guidelines and data of our HD registry were presented. Results. There was an increase in the number of HD stations(from 25 p.m.p. to 75 p.m.p., P<0.001), in HD patients (from60 p.m.p. to 237 p.m.p., P<0.001) and in the incidence ofnew HD patients (from 54.3 p.m.p. to 103 p.m.p., P<0.01).The mean age of HD patients increased from 47.2±16.1years in 1996 to 56.0±14.9 in 2002 (P<0.001). Themain underlying cause of ESRD was chronic glomerulonephritis,but its rate decreased from 54.5% in 1996 to 27.5% in 2002 (P<0.001).The percentage of diabetics increased from 7.1% to 16.4%, P<0.05,and in hypertensive nephropathy from 3.1% to 10.9%, P<0.05.We observed improvement of the quality of HD in Lithuania duringthese 5 years. The percentage of patients on bicarbonate HDincreased from 7.1% in 1996 to 100% in 2002 (P<0.001). Thepercentage of patients receiving more than 12 h HD/week increasedfrom 30.8% in 1996 to 53.5% in 2002 (P<0.001). The mean Kt/Vin 1999 was 0.81±0.53, but it increased in 2002 to 1.22±0.27,P<0.001. In 2002, 84.6% of all HD patients were examinedfor HB_sAg, 82.3% for anti–HCV, 31.2% for anti-HB_s and57.1% for anti-HB_c. The percentage of patients receiving phosphatebinders increased from 65.2% in 1996 to 84.4% in 1997 and 90.5%in 2002. Serum parathyroid hormone (PTH) levels were measuredin 27.3% of HD patients in 1999 but in 85.2% of patients in2002. The mean haemoglobin (Hb) concentration increased from92±15.4 g/l to 105±14.7 g/l; the percentage ofpatients with Hb>100 g/l increased from 27.5% to 64% in 2001.The percentage of HD patients receiving epoetin was 94.6% in2001 as compared with 78% in 1997. There was a marked increasein the use of intravenous iron (from 7.5% patients in 1997 to70.8% in 2000). The mean weekly dose of Epo was lower in HDpatients receiving intravenous iron than in patients receivingoral iron. Conclusions. Over the period of 1996–2002 the HD servicessignificantly expanded in Lithuania. The introduction of EuropeanBest Practice Guidelines and the establishment of a HD registrywith feedback of the results stimulated the significant progressin the quality of HD and in the management of the patients.     

Analysis of drug prescription in chronic haemodialysis patients.

BACKGROUND: Information concerning medication use in Asian haemodialysis patients is sparse. We surveyed prescribed medications and examined the relation between the number of medications and mortality and clinical characteristics in chronic haemodialysis patients, in Okinawa, Japan. METHODS: We conducted a cross-sectional multicentre survey in August 1999 and patients were observed during 13 months of follow up. RESULTS: The clinical demographics of 850 chronic haemodialysis patients in seven dialysis units were obtained. Compared with the mean number of medications prescribed in ambulatory patients treated in general practice reported from Ministry of Health and Welfare of Japan (2.7 (n=20 716)), the mean number medications in haemodialysis patients was larger (7.2 (n=850)). The three most prescribed drug types in haemodialysis patients were those related to calcium and phosphate metabolism (88%), antihypertensive agents (71%), and erythropoietin (60%). Among the 850 patients, 38 died during the 13-month follow-up period. The number of medications was positively associated with mortality after adjusting for age, sex, and other clinical factors: the hazard ratio was 1.14 (95% confidence interval 1.03-1.26, P=0.007). A multiple linear regression analysis using the number of medications as a dependent factor and sex and other clinical characteristics as independent factors revealed that male sex (P=0.04), diabetes mellitus (P<0.0001), and duplication of drugs (P<0.0001) were positively correlated with the number of medications. CONCLUSIONS: Multiple drug use was observed in haemodialysis patients. The number of prescribed drugs was a significant predictor of short-term mortality. Male sex, diabetes mellitus, and duplication of drugs were correlated with increases in the number of medications.     

Efficacy of low‐dose i.v. iron therapy in haemodialysis patients

Aim: i.v. iron therapy is more effective in maintaining adequate iron status in haemodialysis (HD) patients than oral iron therapy (OIT). However, data on lower doses of i.v. iron therapy are insufficient. Methods: A non‐randomized, open‐label study was performed to compare the efficacy of low‐dose (≤50 mg/week of iron sucrose) i.v. iron therapy (LD‐IVIT) with OIT in HD patients with 100–800 µg/L serum ferritin levels over 4 months. Results: Eighty‐nine patients in the LD‐IVIT group (40 men, 49 women; aged 61 ± 13 years) and 30 patients in the oral iron therapy group (17 men, 13 women; aged 59 ± 7 years) were evaluated. After 4 months of each treatment, serum ferritin levels increased from 398 ± 137 to 529 ± 234 µg/L in the LD‐IVIT group (P < 0.01) but decreased from 351 ± 190 to 294 ± 175 µg/L in the OIT group (P < 0.01). In the LD‐IVIT group, transferrin saturation (from 28% ± 11% to 30% ± 14%, P = 0.49), weekly doses of recombinant human erythropoietin (from 5822 ± 2354 to 5636 ± 2306 IU/week, P = 0.48) and haemoglobin (from 101 ± 9 to 103 ± 9 g/L, P = 0.15) levels remained stable. Conclusion: LD‐IVIT may be one of the regimens that may be considered for maintaining iron status in HD patients. However, efficacy of LD‐IVIT should be verified by further randomized study.     

Low-dose continuous iron therapy leads to a positive iron balance and decreased serum transferrin levels in chronic haemodialysis patients

Background. Iron balance is critical for adequate erythropoiesis,but its optimal therapeutic regimen remains to be defined. Continuousmaintenance therapy with iron has been proposed for dialysispatients on recombinant human erythropoietin (rHuEpo) in thehope that the regimen is adequate and safe. Methods. We determined serum ferritin, transferrin, transferrinsaturation (TSAT), serum transferrin receptors, albumin andC-reactive protein (CRP) in a 3-year prospective study in 30chronic haemodialysis patients on dialysis treatment for 132±111months (18 males, 12 females; mean age 56±14 years).Beginning in the year 2000, they regularly received low-dosemaintenance iron supplementation (i.v. iron gluconate 31.25mg/week) for 12 months (Period 1 or first treatment phase),followed by a 6-month withdrawal (Period 2 or stop phase) andthen by continuous maintenance iron therapy (i.v. iron gluconate31.25 mg/week) for another 9 months (Period 3 or re-challengephase). Results. A significant increase in serum ferritin and TSAT wasobserved, with values exceeding 500 ng/ml and 50% in 10/30 (33%)and 7/30 (23%) of subjects, respectively, in Period 1, and in11 and 5% in Period 3. A significant decrease in serum transferrinwas documented during Period 1, followed by an increase in Period2 and a decrease in Period 3. Serum albumin remained stable.Serum transferrin was always negatively correlated with ferritin(r = –0.41, P<0.001) and weakly correlated with serumtransferrin receptors (r = 0.178, P<0.05), but was not correlatedwith serum albumin or CRP. Regression equations based on pre-treatmentserum ferritin values were developed for predicting the valueof serum ferritin at any time following the beginning of continuousiron supplementation. They fitted a linear relationship formales (y = 81 + 21.5 x time) and for females (y = 65 + 22 xtime). Percentile charts for quantitative tracking of serumferritin increases and decreases in patients have also beendeveloped from values measured at different times. These chartsshow box-plot distributions of expected ferritin against time. Conclusions. Even continuous low-dose maintenance iron therapy,with only 31.25 mg weekly over 1 year, cannot prevent the riskof iron overload in patients with moderate anaemia. Furthermore,this treatment is responsible for decreases in serum transferrin,unrelated to changes in serum albumin, possibly of concern forhypo-transferrinaemia as an independent risk factor for irontoxicity.     

Removal of clodronate by haemodialysis in end-stage renal disease patients

BACKGROUND: Clodronate is a potent calcium-lowering drug. The effect ofhaemodialysis on clodronate pharm-acokinetics is unknown. METHODS: The removal of clodronate by haemodialysis was determined in10 end-stage renal disease patients (ESRD). A 2-h infusion of300 mg of clodronate was followed immediately by a 4-h haemodialysis.Vascular access was by AV fistula. A 1.5-m² cuprophane hollow-fibredialyser was applied. Blood flow was 205±15ml/min, dialysateflow 523±29 ml/min. Clodronate was determined by high-performanceliquid chromatography in total collected dialysate, and in bloodbefore and after the dialyser at initiation, 2 h, and 4 h ofHD. RESULTS: The initial predialyser serum concentration of clodronate was13.6 ± 4 ug/ml. It decreased to 4.9 ± 0.5 ug/mland 2.6 ± 0.5 ug/ml at 2h and 4h respectively. The clearanceof clodronate (86 ± 10 ml/min) remained unchanged duringHD. Clodronate in total collected dialysate per single 4-h HDwas 105 ± 16 mg (35% of injected dose). CONCLUSIONS: We conclude that clodronate is effectively removed from plasmaby HD. The present data together with information provided byprevious studies suggest that 300 mg of clodronate given asan 2-h infusion immediately prior to haemodialysis is an adequatedosage for ESRD patients.     

Impairments of the biological properties of serum albumin in patients on haemodialysis

BACKGROUND: End-stage renal disease (ESRD) is associated with enhanced oxidative stress and may contribute to substantial cardiovascular complications in dialysis patients. Recent studies suggested that human serum albumin (HSA), the major plasma protein, may possess a direct vasculoprotective antioxidant effect. In this study, we investigated if such protective effect is impaired in uremic milieu. METHODS: Thirty-one ESRD patients on maintenance haemodialysis and 22 age-matched healthy controls were recruited. Serum albumin was purified and changes in biological properties of HSA were analysed by several biochemistry techniques, spectrophotometric measurements, ligand-binding assays and western blot analysis. RESULTS: We found that both dityrosine (0.25 +/- 0.1 vs 0.15 +/- 0.07, P < 0.001), and carbonyl (10.5 +/- 1.88 nmol/mg vs 5.29 +/- 1.21 nmol/mg, P < 0.001) contents were increased in the uremic HSA. Decreased thiol activity of plasma was also noted and may be related to dimerization of HSA. In addition, uremic HSA had shown impaired ligand-binding capability such as haemin (0.37 x 10(7)/M vs 2.18 x 10(7)/M, P < 0.001), bilirubin (0.08 x 10(6)/M vs 0.15 x 10(6)/M, P < 0.05) and cis-parinaric acid (3.8 x 10(7)/M vs 2.9 x 10(7)/M, P < 0.05). Furthermore, using two different systems namely copper mediated oxidation of human low density lipoproteins and the free radicals mediated haemolysis test, we have demonstrated that the observed changes of uremic HSA can affect its antioxidant properties. CONCLUSION: In conclusion, the present study demonstrated that the quality and integrity of HSA molecule in dialysis patients were subtly altered and impaired its biological properties. Oxidative alterations of this major plasma protein might adversely affect its vasculoprotective effects in dialysis patients.     

Coronary calcification and its association with mortality in haemodialysis patients

Aim:   Coronary artery calcification (CAC) has been associated with higher mortality in chronic renal disease. The purpose of this study was to assess coronary artery calcium score (CaCs) in haemodialysis patients and to correlate calcium scores with clinical parameters and mortality.
Methods:   A cross-sectional study was conducted in 59 haemodialysis patients. CaCs was assessed by multidetector-row computed tomography and stratified as: CaCs of less than 10 Agatston units (U), no calcification; CaCs of 10–400 U, mild-to-moderate; and CaCs of more than 400 U, severe calcification. The effects of age, haemodialysis duration and biochemical and inflammatory markers on CaCs logarithm were evaluated by multiple linear regression analysis. Cox regression analysis was used to measure the impact of CaCs of more than 400 on 2-year mortality.
Results:   Coronary calcifications were detected in 64.5% of patients, and the median of CaCs was 31.7 U (0–589.7) with a range of 0–5790.0 U. Twenty-one (35.5%) patients had mild-to-moderate and 17 (29%) severe CaCs. Patients with severe CaCs were older and showed a higher prevalence of ischaemic heart disease and a higher body mass index ( P  = 0.04). A trend towards higher C-reactive protein levels was found in patients with severe CaCs. Advanced age was the only variable that influenced CaCs logarithm independently. The effect of severe CaCs on 2-year mortality did not persist after adjustment for other covariates.
Conclusion:   Coronary calcification was highly prevalent in these uraemic patients on chronic haemodialysis. A correlation was evidenced between CaCs and advanced age, but severity of the CAC score did not have an impact on 2-year mortality of this cohort.     

Accumulation of trimethylamine and trimethylamine-N-oxide in end-stage renal disease patients undergoing haemodialysis.

BACKGROUND: Trimethylamine (TMA) is a short-chain tertiary aliphatic amine that is derived from the diet either directly from the consumption of foods high in TMA or by the intake of food high in precursors to TMA, such as trimethylamine-N-oxide (TMNO), choline and L-carnitine. The clinical significance of TMA may be related to its potential to contribute to neurological toxicity and 'uraemic breath' in patients with end-stage renal disease (ESRD). METHODS: Concentrations of TMA and TMNO in plasma from 10 healthy adults (not on haemodialysis) and 10 adults with ESRD undergoing haemodialysis (pre- and post-dialysis) were determined by gas chromatography-mass spectrometry. RESULTS: The concentrations of TMA and TMNO in pre-dialysis plasma (1.39+/-0.483 and 99.9+/-31.9 microM, respectively) were significantly (P<0.05) higher than the corresponding levels in healthy subjects (0.418+/-0.124 and 37.8+/-20.4 microM, respectively). However, there were no significant differences between post-dialysis and healthy subject plasma concentrations. In the ESRD patients, there was a significant (P<0.05) reduction in plasma TMA (from 1.39+/-0.483 to 0.484+/-0.164 microM) and TMNO (from 99.9+/-31.9 to 41.3+/-18.8 microM) during a single haemodialysis session. CONCLUSIONS: TMA and TMNO accumulate between haemodialysis sessions in ESRD patients, but are efficiently removed during a single haemodialysis session.     

Illness representations and quality of life scores in haemodialysis patients.

BACKGROUND: Health-related quality of life (QoL) in haemodialysis (HD) patients is a significant predictor of mortality and hospitalization. Patients' adaptation to a chronic disease is determined by their beliefs about illness and treatment. In this cross-sectional study we examined the impact of illness representations on QoL of HD patients and the influence of HD duration on this relationship. METHODS: Eighty-two clinically stable HD patients completed the Short Form-36 Health Survey (mean age 47.9+/-12.1, mean treatment duration 72+/-50.6, 53.6% males). Illness representations were assessed by a structured interview containing questions derived from The Revised Illness Perception Questionnaire. RESULTS: Our results indicate a relatively low QoL of HD patients, with an important proportion of patients scoring less than 43 for the physical component summary (65.9%) and less than 51 for the mental component summary (58.5%). HD patients consider their illness as having a chronic course, which they understand and control quite well. A higher personal control is associated with a lower emotional response and a better understanding of the disease. However, the perceived negative consequences of the disease upon patients' personal lives are considerable, as is their emotional response. Four of the six components of illness representations were strongly related to QoL parameters. On multiple regression analysis, between 15 and 31% in the variance of the physical and mental component of QoL was explained by three dimensions of illness representations: the perceived course of the disease, personal control and emotional response. Only the emotional response dimension of the illness representations is related to treatment duration (r = -0.48, P<0.01). CONCLUSION: Our study demonstrates important relationships between illness representations and QoL in end-stage renal disease patients treated by HD. Future research will have to plan for interventions that could alter illness representations in order to confirm the real impact of illness representations upon patients' QoL.     

Comparison of residual renal function in patients undergoing twice-weekly versus three-times-weekly haemodialysis

Aim:   Patients with end-stage renal disease (ESRD) often start long-term haemodialysis (HD) thrice weekly, regardless of the level of residual renal function (RRF). In this study, we investigated whether ESRD patients having sufficient RRF can be maintained on twice-weekly HD, and how they fare compared to patients without RRF on thrice-weekly HD.
Methods:   We analyzed 74 patients who had undergone long-term HD and maintained on the same dialysis frequency from February 1998 to July 2005, and followed until December 2005. We compared the clinical variables between twice-weekly and thrice-weekly HD patients and a second analysis testing the residual urine output as an independent predictor for twice-weekly HD.
Results:   After a mean follow up of 18 months, twice-weekly HD patients ( n  = 23) had lower serum β2-microglobulin than thrice-weekly HD patients ( n  = 51). Moreover, the twice-weekly group had a slower decline of RRF, as indicated by their higher urine output and creatinine clearance, fewer intradialytic hypotensive episodes, and required less frequent hospitalization. There was no difference between the two groups in cardiothoracic ratio or indices of nutrition and inflammation. Multivariable logistic regression identified age (odds ratio (OR), 1.866; 95% CI, 1.093–3.183), dry body mass index (OR, 0.790; 95% CI, 0.625–0.999), and urine output (OR, 1.093; 95% CI, 1.026–1.164) as predictors for maintaining twice-weekly HD.
Conclusion:   Our data suggest that when patients who have sufficient urine output are given twice-weekly HD, they maintain dialysis adequacy and exhibit better preservation of RRF than patients on thrice-weekly HD.     

Insulin resistance and muscle wasting in non-diabetic end-stage renal disease patients.

BACKGROUND: Insulin resistance (IR) is prevalent in uraemia. Recent experimental studies suggested IR to be a central mechanism for uraemic malnutrition. However, it is not known whether IR is related to muscle wasting in non-diabetic end-stage renal disease (ESRD) patients. METHODS: We cross-sectionally assessed IR and muscle wasting in 21 non-diabetic ESRD patients who admitted for the initiation of dialysis. For the assessment of muscle wasting, lean body mass was measured (LBMm) by dual energy X-ray absorptiometry and compared with the estimated LBM (LBMe) from the prediction equation derived from healthy controls using the ratio of LBMm/LBMe. For measurement of IR, the homoeostasis model (HOMA-IR) was used. In addition, among patients who chose continuous ambulatory peritoneal dialysis, muscle was sampled during catheter insertion from the rectus abdominis to measure 14-kDa actin fragments, a marker of muscle protein degradation. RESULTS: Patients with a low LBMm/LBMe ratio (<1.00) showed higher HOMA-IR and fat mass (FM) (% body weight) and lower LBM (% body weight) than those with a high LBMm/LBMe ratio (>or=1.00). LBMm/LBMe ratio was negatively correlated with HOMA-IR, regardless of obesity. By multiple regression analysis, HOMA-IR was an independent factor affecting LBMm/LBMe ratio. Furthermore, in the muscle samples, patients with high HOMA-IR had lower LBMm/LBMe ratios and stronger bands for the 14-kDa actin fragments than did patients with low HOMA-IR. CONCLUSION: These results suggest that IR seems to be associated with muscle wasting in non-diabetic ESRD patients.     

Association between residual renal function, inflammation and patient survival in new peritoneal dialysis patients.

BACKGROUND: The recent ADEMEX study (Paniagua R, Amato D, Vonesh E et al. J Am Soc Nephrol 2002; 13: 1307-1320) indicates that peritoneal small solute clearance is not as critical for the survival of peritoneal dialysis (PD) patients as thought previously. On the other hand, low residual renal function (RRF), inflammation and an increased peritoneal transport rate (PTR) as evaluated by the peritoneal equilibration test (PET) are reported to be associated with increased mortality in PD patients, but the relationships between these factors and their separate and combined impact on the survival of PD patients are not clear. In this retrospective analysis, we evaluated possible relationships between RRF, inflammation and initial PTR in patients starting PD and the impact of these factors on patient survival. METHODS: A total of 117 patients with initial assessments for RRF, serum C-reactive protein (CRP) and PET at a mean period of 0.4+/-0.2 months (range 0.1-1.0 months) after start of PD were included in this study. Based on RRF (cut-off point, 4 ml/min/1.73 m(2)), serum CRP (cut-off point, 10 mg/l), and the dialysate to plasma creatinine ratio at 4-h of dwell (mean+1 SD), the patients were divided into different groups: low RRF and high RRF group, high CRP and normal CRP group and high PTR and other PTR group, respectively. RESULTS: Of 117 patients, 54 patients (46%) were in low RRF (<4 ml/min/1.73 m(2)) group, 36 patients (31%) were in high serum CRP (> or = 10 mg/l) group and 17 patients (15%) were in high PTR group. Forty-nine patients (42%) had one of these characteristics, 26 patients (22%) had two of these characteristics, two patients (2%) had three, and 40 patients (34%) had none of these characteristics. Patients with low RRF were older and had a higher prevalence of high CRP, lower normalized protein equivalent of total nitrogen appearance (nPNA), lower total Kt/V(urea) and lower total creatinine clearance (CCr) whereas patients with high CRP were older and had a higher proportion of men, lower serum albumin, lower nPNA, lower RRF and lower total CCr. Patients with high PTR had lower serum albumin, higher RRF and higher total CCr compared with patients with other PTR. Upon logistic multiple regression analysis, age and RRF were identified as factors affecting inflammation. Overall patient survival was significantly lower in the patients with low RRF, with high CRP, and in patients with more than two of the following: low RRF, high CRP and high PTR. In contrast, in patients with none of the discriminators low RRF, high CRP and high PTR, the 5-year survival was 100%. A high PTR was associated with decreased survival during the initial year on PD, but not thereafter. Patients who died during the follow-up period had a higher prevalence of high CRP and lower serum albumin, lower RRF, lower Kt/V(urea) and lower total CCr. Upon Cox proportional hazards multivariate analysis, age and RRF were predictors of mortality. CONCLUSIONS: These results indicate that in patients starting PD, low initial RRF is associated with inflammation, and low RRF and inflammation are both associated with high overall mortality. A high PTR was associated with higher mortality, but only during the initial year on PD, whereas Kt/V(urea) did not predict mortality. These results indicate the importance of RRF and inflammation as predictors of mortality in PD patients whereas the predictive power of PTR as such may lose its significance if these two parameters are taken into consideration.     

Control of serum phosphate by oral lanthanum carbonate in patients undergoing haemodialysis and continuous ambulatory peritoneal dialysis in a short-term, placebo-controlled study.

BACKGROUND: Hyperphosphataemia in dialysis patients is associated with significant morbidity. We assessed the ability of lanthanum carbonate to control phosphate levels in patients undergoing haemodialysis or continuous ambulatory peritoneal dialysis (CAPD) in a short-term, placebo-controlled study. METHODS: This was a double-blind, placebo-controlled, parallel-group study consisting of three phases: a 2 week washout period; a 4 week, open-label, dose-titration phase; and a 4 week, double-blind, placebo-controlled phase. After washout, patients (n = 59) received lanthanum (375 mg/day), titrated up to a maintenance dose (maximum: 2250 mg) that achieved control of serum phosphate levels between 1.3 and 1.8 mmol/l (4.03-5.58 mg/dl). After titration, patients were randomized to receive their maintenance dose of lanthanum (n = 17) or placebo (n = 19) for 4 weeks. Control of serum phosphate was the primary efficacy assessment. Levels of calcium, parathyroid hormone, calcium x phosphate product and lanthanum as well as adverse events were evaluated. RESULTS: By the end of titration, 70% of patients had serum phosphate levels < or =1.8 mmol/l. Lanthanum carbonate continued to control serum phosphate levels in the double-blind phase. At the end of the study, 64.7% of lanthanum carbonate-treated patients were controlled compared with 21.4% in the placebo group. Results in patients receiving CAPD were similar to those seen in the group as a whole. Mean parathyroid hormone levels (P = 0.41) and calcium x phosphate product (P<0.001) were both higher in the placebo than the lanthanum carbonate group. CONCLUSIONS: Lanthanum carbonate is an effective phosphate binder able to control serum phosphate and calcium x phosphate product.     

Economic appraisal of maintenance parenteral iron administration in treatment of anaemia in chronic haemodialysis patients

BACKGROUND.: Iron deficiency is common in haemodialysis patients and adequatesupplementation by the oral or parenteral route has been limitedby drug side-effects, absorption, and cost. Intermittent doses of intravenous iron dextran complex are recommendedin patients with inadequate iron stores despite maximal toleratedoral dose. We conducted a prospective study with economic analysisof a regular maintenance intravenous iron regimen in this groupof patients. METHODS.: Fifty patients comprising one-half of our haemodialysis populationrequired intravenous iron treatment, i.e. they failed to achievean arbitrary goal serum ferritin 100 µg/l despite maximaltolerated oral iron dose. After a loading dose of intravenousiron dextran complex (IV-FeD) based on Van Wyck's nomogram (400±300mg) they received a maintenance dose of 100 mg IV-FeD once every2 weeks. Initial goal serum ferritin was set at 100–200µg/l. If no increase in haemoglobin was achieved at thislevel, transferrin saturation was measured to assess bioavailableiron, and when less than 20%, goal serum ferritin was increasedto 200–300 µg/l. Recombinant human erythropoietin(rHuEpo) was used where needed to maintain haemoglobin in the9.5–10.5 g/l range only if ferritin requirements weremet. RESULTS.: Mean haemoglobin rose from 87.7±12.1 to 100.3±13.1g/l (P<0.001, Cl 7.7–17.9) at mean follow-up of 6 months(range 3–15 months). In patients on rHuEpo, dose per patientwas reduced from 96±59 u/kg per week to 63±41u/kg per week, repres enting a 35% dose reduction (P<0.05,Cl 1–65). An annual cost reduction of $3166 CDN was projected;however, in the first year this is offset by the cost of theloading dose of IV-FeD required at the beginning of treatment.No adverse reactions were encountered. CONCLUSIONS.: Iron deficiency is very common in our haemodialysis population,especially in those patients receiving rHuEpo. A carefully monitoredregimen of maintenance parenteral iron is a safe, effective,and economically favourable means of iron supplementation inpatients with insufficient iron stores on maximum toleratedoral supplements.     

Inflammation, mineral metabolism and progressive coronary artery calcification in patients on haemodialysis.

BACKGROUND: Coronary artery calcification (CAC) is an extensive and common complication in patients with end-stage renal disease (ESRD). The aim of this study was to assess prospectively the change in CAC over a 2-year period and to identify the factors that may be associated with CAC progression in ESRD patients. METHODS: The final analysis was performed on 40 of 43 stable haemodialysis patients who initially entered into the study. The study population underwent multirow spiral computed tomography to derive CAC scores at baseline and after a minimum of 12 months (24 months in 30 patients, 18 months in four, and 12 months in the remaining six patients). To provide a stable estimate that was unbiased with respect to the baseline CAC, square root-transformed CAC scores were used for the analyses of the changes in CAC. RESULTS: The median CAC score was 191 (range, 0-2403) mm3 at baseline and increased to 253 (range, 0-2745) mm3 at follow-up (P < 0.001) and the median annualized change in square root-transformed CAC score was 1.48 (range, -0.95-8.64) mm3/year. The annualized change of the square root-transformed CAC score positively correlated with the time-integrated levels of C-reactive protein (R = 0.521, P = 0.001), phosphorus (R = 0.433, P = 0.005) and calcium x phosphorus product (R = 0.394, P = 0.012), but did not correlate with the levels of fetuin-A or lipid parameters. Even after adjusting for age, gender and baseline CAC score, C-reactive protein levels were independently associated with CAC progression. CONCLUSION: These data suggest that chronic inflammation as well as altered mineral metabolism contributes to a rapid progression of CAC in ESRD patients. Additional, larger scale studies are required to confirm our findings.     

The serum from dialysis patients with acute coronary syndrome up-regulates the expression of TLR2 and its downstream effectors in human renal glomerular endothelial cells

Background: This study was to investigate the expression of toll-like receptor 2 and its downstream effectors in endothelial cells in response to the serum from maintenance hemodialysis (MHD) patients with acute coronary syndrome (ACS). Methods: Human renal glomerular endothelial cells (HRGEC) were treated in vitro with serum from the healthy subjects (control group), the MHD patients with stable angina pectoris (SAP group), or the MHD patients with ACS (ACS group). The cells in ACS group were cultured in the presence or absence of TLR2 signaling blockers for 18?h. The mRNA level for TLR2, nuclear factor-κB (NF-κB), interleukin-6 (IL-6) and vascular cell adhesion molecule-1 (VCAM-1) were examined by real-time qPCR, the localization of TLR2 was detected by immunocytochemistry, and the secretion of IL-6 and VCAM-1 were measured by enzyme-linked immunosorbent assay. Results: The mRNA level of TLR2, NF-κB and IL-6 were statistically higher in the ACS group when compared with those in SAP group and healthy controls (p?<?0.05), but not significantly different between SAP and healthy controls. The secretion of IL-6 in ACS group was increased when compared with SAP group and control subjects (p?p?<?0.05). Conclusion: This study revealed that the TLR2 signaling may mediate pro-inflammatory response in the MHD patients occurring with ACS.