Prevalence of Clinical and Subclinical Thyroid Disease in a Peritoneal Dialysis Population

♦ Aims: We investigated dialysis duration, dose of erythropoietin (EPO), and clinical manifestations in peritoneal dialysis (PD) patients with subclinical hypothyroidism.♦ Methods: This cross-sectional study, performed in 3 centers, assessed 122 adult patients on PD for more than 6 months with regard to demographic data, dialysis duration, thyroid function, biochemical data, EPO dose, and clinical manifestations. Thyroid dysfunction was determined by serum thyroid-stimulating hormone, free thyroxine, total thyroxine, total triiodothyronine, antithyroid peroxidase antibodies, and auto-antibodies against thyroglobulin.♦ Results: Of the 122 study patients, 98 (80.3%) were assessed as having euthyroidism; 19 (15.6%), subclinical hypothyroidism; and 5 (4.1%), subclinical hyperthyroidism. The proportion of women (74.2% vs. 57.1%, p = 0.038), the mean duration of PD (58.1 months vs. 37.9 months, p = 0.032), and the weighted mean monthly EPO dose (1.22 μg/kg vs. 1.64 μg/kg, p = 0.009) were significantly higher in the subclinical hypothyroidism group than in the euthyroidism group, but the prevalences of coronary artery disease and cerebrovascular disease were not. From the multivariate model, PD duration was more significant than sex as a risk factor for subclinical hypothyroidism (p = 0.0132).♦ Conclusions: Subclinical hypothyroidism is frequent in PD patients, especially female patients and patients with a longer PD duration. Compared with euthyroid patients, patients with subclinical hyperthyroidism need a higher dose of EPO to maintain a stable hemoglobin level.     

The Effect of Glycated Hemoglobin and Albumin-Corrected Glycated Serum Protein on Mortality in Diabetic Patients Receiving Continuous Peritoneal Dialysis

♦ Objective:

To explore the effect of glycated hemoglobin (HbA1c) and albumin-corrected glycated serum proteins (Alb-GSP) on the mortality of diabetic patients receiving continuous peritoneal dialysis (PD).

♦ Methods:

In this single-center retrospective cohort study, incident diabetic PD patients from January 1, 2006, to December 31, 2010, were recruited, and followed up until December 31, 2011. The effect of HbA1c and Alb-GSP on mortality was evaluated by Cox proportional hazards models.

♦ Results:

A total of 200 patients (60% male, mean age 60.3 ± 10.6 years) with a mean follow-up of 29.0 months (range: 4.3 – 71.5 months) were recruited. Sixty-four patients died during the follow-up period, of whom 21 died of cardiovascular disease (CVD). Mean values for HbA1c, GSP and Alb-GSP were 6.7% (range: 4.1 – 12.5%), 202 μmol/L (range: 69 – 459 μmol/L), and 5.78 μmol/g (range: 2.16 – 14.98 μmol/g), respectively. The concentrations of GSP and Alb-GSP were closely correlated with HbA1c (r = 0.41, p < 0.001 and r = 0.45, p < 0.001, respectively). In multivariate Cox proportional hazards models, patients with HbA1c ≥ 8% were associated with increased risk of all-cause mortality (hazard ratio [HR] = 2.29, 95% confidence interval [CI]: 1.06 – 4.96, p = 0.04), but no increased mortality in patients with 6.0% ≤ HbA1c ≤ 7.9%. Patients with Alb-GSP ≤ 4.50 μmol/g had increased all-cause and non-cardiovascular mortality (HR = 2.42, 95% CI: 1.13 – 5.19, p = 0.02; and HR = 2.98, 95% CI: 1.05 – 8.48, p = 0.04 respectively).

♦ Conclusions:

Increased HbA1c and decreased Alb-GSP may be associated with poorer survival in diabetic PD patients, with a non-significant trend observed for poorer survival with the highest level of Alb-GSP.     

Persistent Sterile Peritoneal Inflammation After Catheter Removal for Refractory Bacterial Peritonitis Predicts Full-Blown Encapsulating Peritoneal Sclerosis

♦ Background: Encapsulating peritoneal sclerosis (EPS) is the most serious complication of peritoneal dialysis, having high morbidity and mortality. To improve outcomes, early diagnosis is needed to direct treatment during the early inflammatory phase. However, in the early inflammatory phase, clinical features are nonspecific, and no reliable diagnostic criteria have been established. Because bacterial peritonitis and termination of dialysis are two important risk factors triggering the progression of EPS, patients with refractory bacterial peritonitis necessitating dialysis catheter removal are at particularly high risk of developing EPS. Many of these patients might indeed experience non-resolving sterile peritonitis (probably the inflammatory phase of EPS) before progression to full-blown disease (that is, the presence of intestinal obstruction). We undertook a retrospective study to compare, in this particular situation, the clinical characteristics of patients with or without sterile peritoneal inflammation, assessing their clinical outcomes in terms of short-term mortality and the chance of developing full-blown EPS.♦ Methods: Our retrospective review included 62 patients whose dialysis catheter was removed because of refractory peritonitis between January 2005 and December 2010.♦ Results: Of the 62 patients identified, 39 (63%) had persistent sterile peritoneal inflammation (“high-risk” group, n = 39), and 23 (37%) had resolution of inflammation without significant intra-abdominal collection after catheter withdrawal (“control” group, n = 23). Compared with the control group, the high-risk group had a significantly longer PD duration (71.6 ± 43.3 months vs 42.3 ± 29.9 months, p = 0.003), a higher dialysate-to-plasma ratio (D/P) of creatinine (0.768 ± 0.141 vs 0.616 ± 0.091, p = 0.004), and a higher computed tomography score for EPS (7.69 ± 2.98 vs 1.00 ± 1.00, p < 0.001). During the 6-month study period, the high-risk group had a higher chance of developing full-blown EPS (31% vs 0%, p = 0.002) and a higher 6-month all-cause mortality (36% vs 4.3%, p = 0.004).♦ Conclusions: Persistent sterile peritoneal inflammation was common after dialysis catheter removal for refractory bacterial peritonitis, and the patients with such inflammation were at high risk of progression to full-blown EPS.     

The First Peritonitis Episode Alters the Natural Course of Peritoneal Membrane Characteristics in Peritoneal Dialysis Patients

♦ Objective:

Little or no evidence is available on the impact of the first peritonitis episode on peritoneal transport characteristics. The objective of this study was to investigate the importance of the very first peritonitis episode and distinguish its effect from the natural course by comparison of peritoneal transport before and after infection.

♦ Participants:

We analyzed prospectively collected data from 541 incident peritoneal dialysis (PD) patients, aged > 18 years, between 1990 and 2010. Standard Peritoneal Permeability Analyses (SPA) within the year before and within the year after (but not within 30 days) the first peritonitis were compared. In a control group without peritonitis, SPAs within the first and second year of PD were compared.

♦ Main outcome measurements:

SPA data included the mass transfer area coefficient of creatinine, glucose absorption and peritoneal clearances of β-2-microglobulin (b2m), albumin, IgG and α-2-macroglobulin (a2m). From these clearances, the restriction coefficient to macromolecules (RC) was calculated. Also, parameters of fluid transport were determined: transcapillary ultrafiltration rate (TCUFR), lymphatic absorption (ELAR), and free water transport. Crude and adjusted linear mixed models were used to compare the slopes of peritoneal transport parameters in the peritonitis group to the control group. Adjustments were made for age, sex and diabetes.

♦ Results:

Of 541 patients, 367 experienced a first peritonitis episode within a median time of 12 months after the start of PD. Of these, 92 peritonitis episodes were preceded and followed by a SPA within one year. Forty-five patients without peritonitis were included in the control group. Logistic reasons (peritonitis group: 48% vs control group: 83%) and switch to hemodialysis (peritonitis group: 22% vs control group: 3%) were the main causes of missing SPA data post-peritonitis and post-control. When comparing the slopes of peritoneal transport parameters in the peritonitis group and the control group, a first peritonitis episode was associated with faster small solute transport (glucose absorption, p = 0.03) and a concomitant lower TCUFR (p = 0.03). In addition, a discreet decrease in macromolecular transport was seen in the peritonitis group: mean difference in post- and pre-peritonitis values: IgG: -8 μL/min (p = 0.01), a2m: -4 μL/min (p = 0.02), albumin: -10 μL/min (p = 0.04). Accordingly, the RC to macromolecules increased after peritonitis: 0.09, p = 0.04.

♦ Conclusions:

The very first peritonitis episode alters the natural course of peritoneal membrane characteristics. The most likely explanation might be that cured peritoneal infection later causes long-lasting alterations in peritoneal transport state.     

The Mutual Relationship Between Peritonitis and Peritoneal Transport

♦ Background:

Preservation of the peritoneum is required for long-term peritoneal dialysis (PD). We investigated the effect of multiple peritonitis episodes on peritoneal transport.

♦ Methods:

Prospectively collected data from 479 incident PD patients treated between 1990 and 2010 were analyzed, using strict inclusion criteria: follow-up of at least 3 years with the availability of a Standard Peritoneal Permeability Analysis (SPA) in the first year after start of PD and within the third year of PD, without peritonitis preceding the first SPA. For the purpose of the study, we only included patients who remained peritonitis-free (n = 28) or who experienced 3 or more peritonitis episodes (n = 16).

♦ Results:

At baseline the groups were similar with regard to small solute and fluid transport. However, the frequent peritonitis group had lower peritoneal protein clearances compared to the no peritonitis group, resulting in lower dialysate concentrations of proteins: albumin 196.5 mg/L vs 372.5 mg/L, IgG 36.4 mg/L vs 65.0 mg/L, and α-2-macroglobulin (A2M) 1.9 mg/L vs 3.6 mg/L, p <0.01. No differences in serum concentrations were present. A comparison between the transport slopes over time in both groups showed a positive time trend of mass transfer area coefficient (MTAC) creatinine (p = 0.03) and glucose absorption (p = 0.09) and a negative trend of transcapillary ultrafiltration (p = 0.06), when compared to the no peritonitis group. Frequent peritonitis did not affect free water transport.

♦ Conclusions:

Slow initial peritoneal transport rates of serum proteins result in lower dialysate concentrations, and likely a lower opsonic activity, which is a risk factor for peritonitis. Patients with frequent peritonitis show an increase in small solute transport and a concomitant decrease of ultrafiltration. In long-term peritonitis-free PD patients, small solute transport decreased, while ultrafiltration increased. This suggests that frequent peritonitis leads to an increase of the vascular peritoneal surface area without all the structural membrane alterations that may develop after long-term PD.     

Impact of Arterial Stiffness on Adverse Cardiovascular Outcomes and Mortality in Peritoneal Dialysis Patients

♦ Background: Cardiovascular (CV) disease is a major cause of morbidity and mortality in patients with end-stage renal disease. In recent years, arterial stiffness has taken on great importance in the pathophysiology of CV diseases. The independent predictive value of arterial stiffness for CV events and for all-cause and CV mortality has been demonstrated in the general population and in hemodialysis patients. Our aim in this study was to determine the relationship of arterial stiffness with mortality and fatal and nonfatal CV events in peritoneal dialysis (PD) patients.♦ Methods: In this prospective observational cohort study with 2 years of follow-up, we studied a cohort of 156 PD patients with a mean follow-up of 19.2 ± 6.4 months. At baseline, echocardiography and standard clinical and biochemical analyses were performed in all patients and in 28 healthy subjects. Aortic stiffness index beta (ASIβ, a surrogate marker of arterial stiffness) was calculated as follows: ♦ Results: During the follow-up period, 25 of the patients (16.0%) died, and 10 of those deaths had CV causes. Nonfatal CV events occurred in 15 patients. The median ASIβ was greater in PD patients than in control subjects (4.2 vs. 3.5; interquartile range: 3.2 – 5.5 vs. 2.5 – 4.8; p = 0.028]. In the fully adjusted multivariate Cox regression analysis (co-variates: age, sex, albumin, hemoglobin, diabetes mellitus, comorbid CV disease, left ventricular mass index, residual glomerular filtration rate, dialysate-to-plasma ratio of creatinine, Kt/V urea, left ventricular ejection fraction, duration of dialysis, smoking), ASIβ independently predicted fatal and nonfatal CV events (hazard ratio: 1.239; 95% confidence interval: 1.103 to 1.392), but not all-cause mortality.♦ Conclusions: Our results provide the first direct evidence that arterial stiffness is an independent risk predictor of adverse CV outcome in PD patients.     

Decreased Circulating Klotho Levels in Patients Undergoing Dialysis and Relationship to Oxidative Stress and Inflammation

♦ Introduction: It has been reported that klotho deficiency is associated with oxidative stress and inflammation in experimental kidney disease models. Patients with endstage renal disease (ESRD) are particularly characterized by increased oxidative stress and inflammation. However, little is known about the relationship between these features and klotho in patients with ESRD.♦ Methods: We conducted a single-center, cross-sectional study of 78 patients receiving peritoneal dialysis (PD). Serum concentrations of klotho, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and 8-isoprostane were measured by enzyme-linked immunosorbent assay. To define factors independently associated with klotho, we determined Spearman’s correlation coefficients for between co-variates and conducted multiple linear regression analyses.♦ Results: Patients were classified by median concentration of klotho. In patients with klotho levels > 329.6 pg/mL, serum 8-isoprostane and IL-6 levels were significantly higher than in those with klotho levels < 329.6 pg/mL. In correlation analyses, log 8-isoprostane (γ = –0.310, p = 0.006) and log IL-6 (γ = –0.343, p = 0.002) were inversely correlated with log klotho. After adjustment for age, gender, mean arterial pressure, log intact parathyroid hormone, and log IL-6, log 8-isoprostane was independently associated with log klotho (β = –0.158, p = 0.040). However, the significant relationship between klotho and IL-6 was not seen in an adjusted model.♦ Conclusions: This study showed that circulating klotho levels were significantly associated with 8-isoprostane levels in patients undergoing PD, suggesting a potential link between klotho deficiency and enhanced oxidative stress in ESRD patients.     

“NEPP” Peritoneal Dialysis Regimen Has Beneficial Effects on Plasma CEL and 3-DG,But Not Pentosidine,CML, and MGO

♦ Background: Standard peritoneal dialysis (PD) solutions contain high levels of glucose and glucose degradation products (GDPs), both contributing to the formation of advanced glycation end products (AGEs). We studied the contribution to plasma GDP and AGE levels of 2 PD regimens that differ in glucose and GDP loads: high load [standard PD (sPD) using 4 glucose–lactate exchanges] and low load [1 amino acid exchange, 1 icodextrin exchange, and 2 glucose–bicarbonate/lactate exchanges (“NEPP”)].♦ Methods: In a prospective crossover study (2 periods of 24 weeks), new continuous ambulatory PD patients were randomized to NEPP–sPD (n = 23) or to sPD–NEPP (n = 27).♦ Results: After the start of PD, absolute increases were observed in plasma levels of 3-deoxyglucosone (3-DG, 220.4 nmol/L, p < 0.0001) and in N_ε-(carboxymethyl) lysine (CML) in plasma proteins (0.02 μmol/L CML per 1 mol/L lysine, p < 0.0001). During the first 6 weeks, 3-DG tended to increase more with sPD treatment (p = 0.08), and CML, with NEPP treatment (p = 0.002). In both groups, N_ε-(carboxyethyl)lysine (CEL) in plasma proteins declined significantly with the start of PD. Treatment with NEPP resulted in higher levels of methylglyoxal (MGO) and lower levels of 3-DG and CEL. Pentosidine in the albumin fraction tended to increase less during NEPP treatment.♦ Conclusions: A low glucose and GDP PD regimen (NEPP) resulted in plasma levels of 3-DG and CEL that were lower than those with a glucose-based sPD regimen. Starting PD with NEPP was associated with a steeper increase in CML, and continuing treatment with NEPP resulted in higher MGO levels.     

Peritoneal Morphology After Long-Term Peritoneal Dialysis with Biocompatible Fluid: Recent Clinical Practice in Japan

♦ Background: Morphology changes of the peritoneal membrane after long-term peritoneal dialysis (PD) consist of denudation of peritoneal mesothelial cells, interstitial sclerosis, and hyalinizing vasculopathy. Those changes are considered to be the result of uremia and bioincompatible effects of conventional acidic lactate-buffered dialysate with glucose degradation products (GDPs). In the last decade, biocompatible dialysate with neutral pH and low GDPs has become widely used. Clinical practice has been modified in Japan, especially for anuric patients, and now includes the use of hybrid therapy. The impact on peritoneal morphology has not been well reported.♦ Objective: The aim of the present study was to investigate the long-term effect on peritoneal morphology and function of biocompatible fluid use and current clinical practice in Japan, including hybrid dialysis therapy.♦ Methods: We evaluated peritoneal biopsy specimens from patients who had undergone PD for more than 3 years. We used the average peritoneal thickness (APT) of the submesothelial compact zone as a marker of interstitial sclerosis and the lumen/vessel diameter ratio (L/V ratio) at postcapillary venules as a marker of hyalinizing vasculopathy. Demography and other data for the patients, including dialysate-to-plasma (D/P) ratio of creatinine, were obtained at baseline and every 6 months by peritoneal equilibration test.♦ Results: Between 2002 and 2009, 110 patients started PD therapy with biocompatible dialysate at Tokyo University Hospital. Among them, 11 patients (8 men, 3 women; age: 54.2 ± 11.8 years; 1 with diabetes mellitus) were enrolled into this morphology study. The mean duration of PD in this group was 61 ± 11.3 months, and the mean time to peritoneal biopsy was 58 ± 15.1 months. The median APT was 180 μm (96 – 1424 μm), and the median L/V ratio was 0.66 (0.46 – 0.74). No obvious correlations between APT, L/V ratio, and PD duration were detected. The D/P creatinine of the 11 patients was maintained at a favorably low value, comparable with that of the other 99 patients.♦ Conclusions: Peritoneal dialysis therapy using biocompatible dialysate in conjunction with modification of clinical practice may minimize the progression of peritoneal interstitial sclerosis and hyalinizing vasculopathy, preserving favorable peritoneal function for more than 3 years.     

Reduced Residual Renal Function is Associated with Endothelial Dysfunction in Patients Receiving Peritoneal Dialysis

♦ Background: Endothelial dysfunction, which contributes to atherosclerosis and arteriosclerosis, commonly accompanies end-stage renal disease (ESRD). However, little is known about the role of residual renal function (RRF) in endothelial protection in ESRD patients. This study aimed to investigate the relationship between endothelial function and RRF in patients undergoing peritoneal dialysis (PD).♦ Methods: This was a cross-sectional study involving 72 prevalent PD patients. Demographic and clinical data were recorded and residual glomerular filtration rate (GFR), Kt/V urea, and serum concentrations of inflammatory markers were measured. Endothelial function was assessed by brachial artery endothelium-dependent vasodilation [flow-mediated dilation (FMD)] to reactive hyperemia following 5 minutes of forearm ischemia.♦ Results: In patients with FMD% above the median value (FMD > 2.41%), residual GFR was significantly higher compared to that in patients with FMD% below the median [1.50 (0 – 9.64) vs 0.48 (0 – 3.89) mL/min/1.73 m², P = 0.026]. Correlation analyses revealed that residual GFR (ρ = 0.381, P = 0.001) and total Kt/V urea (γ = 0.408, P < 0.001) were positively correlated with FMD%, whereas PD duration (γ = –0.351, P = 0.003), high-sensitivity C-reactive protein (ρ = –0.345, P = 0.003), pulse pressure (γ = –0.341, P = 0.003), and age (γ = –0.403, P < 0.001) were inversely correlated with FMD%. In contrast, there was no correlation between peritoneal Kt/V urea and FMD%. In multivariate linear regression analysis adjusted for these factors, residual GFR was found to be an independent determinant of FMD% (β = 0.317, P = 0.017).♦ Conclusion: This study shows that RRF is independently associated with endothelial dysfunction in ESRD patients on PD, suggesting that RRF may contribute to endothelial protection in these patients.     

Mortality Rates Do Not Differ Among Patients Prescribed Various Vitamin D Agents

♦ Background: Limited well-controlled research exists examining the impact of different formulations of oral vitamin D on clinical outcomes in dialysis patients, specifically those on peritoneal dialysis. For this retrospective mortality analysis, we compared mortality rates of patients on 3 of the most commonly prescribed vitamin D agents.♦ Methods: We examined 2 years (7/1/2008 to 6/30/2010) of oral medication records of peritoneal dialysis patients from a large US dialysis organization. Patients were identified whose physicians prescribed a single form of vitamin D (calcitriol, paricalcitol, or doxercalciferol) for ≥ 90% of all patient-months. We excluded incident patients (< 90 days on dialysis) and patients whose physicians treated < 5 peritoneal dialysis patients at a dialysis facility, and we assessed mortality.♦ Results: The analysis inclusion criteria identified 1,707 patients. The subset in this analysis included 12.6% of all prevalent peritoneal dialysis patients and 11.8% of prevalent patient-months. Patients with physicians who predominately prescribed calcitriol had a lower mortality rate: 9.33 (confidence interval (CI) 7.06, 11.60) deaths per 100 patient-years than the doxercalciferol, 12.20 (CI 9.34, 15.06) or paricalcitol, 12.27 (CI 9.27, 15.28) groups. However, these differences were not statistically significant. A Cox proportional hazards model, adjusting for differences in age, vintage, gender, race, body mass index, and comorbidities also showed no significant differences.♦ Conclusions: For this peritoneal dialysis population, instrumental variable analyses showed no significant difference in mortality in patients taking the most common oral vitamin D formulations (calcitriol, doxercalciferol, paricalcitol).     

Associations Between Serum-Intact Parathyroid Hormone,Serum 25-Hydroxyvitamin D,Oral Vitamin D Analogs and Metabolic Syndrome in Peritoneal Dialysis Patients: A Multi-Center Cross-Sectional Study

♦ Introduction: Although previous studies have suggested associations between serum intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25(OH)D) and metabolic syndrome (MS) in the general population, these associations are still uncharacterized in peritoneal dialysis (PD) patients.♦ Methods: In total, 837 prevalent PD patients from 5 centers in China were enrolled between April 1, 2011 and November 1, 2011. The demographic data, biochemical parameters and medical records were collected, except for serum 25(OH)D which was measured in 347 of 837 patients. The definition of MS was modified from National Cholesterol Education Program Third Adult Treatment Panel (NCEP-ATPIII).♦ Results: 55.4% of 837 patients were found to have MS. The median concentration of iPTH, 25(OH)D and doses of oral vitamin D analogs for participants with MS was significantly lower than those without MS. The iPTH, 25(OH)D values and doses of vitamin D analogs were all associated with one or more components of MS. After multivariate adjustment, low serum iPTH values and oral vitamin D analogs, rather than serum 25(OH)D, were significantly associated with the presence of MS, abnormal fasting blood glucose (FBG) and high-density lipoprotein cholesterol (HDL-C). Compared to iPTH < 130pg/mL, iPTH 130-585 pg/mL and > 585pg/mL were associated with a lower risk of MS with adjusted odds ratio (OR) of 0.59 and 0.33, respectively. Taking vitamin D analogs was also associated with a lower risk of MS with adjusted OR of 0.55.♦ Conclusions: Serum iPTH and the use of active vitamin D supplements rather than serum 25(OH)D were independently associated with the presence of MS in patients on PD.     

Oral Astaxanthin Supplementation Prevents Peritoneal Fibrosis in Rats

♦ Background:

Preventing peritoneal damage during peritoneal dialysis is critical. Reactive oxygen species (ROS) have an important role in peritoneal damage; however, few studies have investigated this. We aimed to determine the effects of oral astaxanthin (AST) supplementation in a peritoneal fibrosis (PF) rat model.

♦ Methods:

Thirty-seven Sprague–Dawley rats were divided into 5 groups: Control 1 (fed a normal diet without stimulation), Control 2 (fed an AST-supplemented diet without stimulation), Group 1 (fed a normal diet with 8% chlorhexidine gluconate [CG] stimulation for 3 weeks), Group 2 (fed a 0.06% AST-supplemented diet with CG stimulation), and Group 3 (fed a 0.06% AST-supplemented diet that was initiated 4 weeks before CG stimulation). Peritoneal fibrosis, vascular proliferation, and fibrosis-related factor expression were examined.

♦ Results:

Peritoneal thickness was significantly suppressed by AST supplementation. Astaxanthin diminished the number of CD68-, 8-hydroxy-2′-deoxyguanosine (8-OHdG)-, and monocyte chemoattractant protein-1 (MCP-1)-positive cells. Type 3 collagen, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and MCP-1 mRNA expression was significantly lower in Group 3 than in Group 1. Increased transforming growth factor-β (TGF-β) and Snail mRNA expression, vascular density, and the number of α-smooth muscle actin (α-SMA)-positive cells were also decreased in Group 3.

♦ Conclusion:

Astaxanthin suppressed PF development through the inhibition of inflammation and oxidation in PF rats. It appears that the anti-oxidative agent AST may be useful for the prevention of peritoneal damage.     

The Association Between Arterial Stiffness and Fluid Status in Peritoneal Dialysis Patients

♦ Objectives: In this study our aim was to evaluate the relationship between degree of fluid status and arterial stiffness measured by pulse wave velocity (PWV) in peritoneal dialysis (PD) patients. Fluid status was determined by different methods including fluid overload measured by bioimpedance (Body Composition Monitor, BCM), calf normalized resistivity (CNR), plasma N-terminal fragment of B-type natriuretic peptide (NT-proBNP) and extracellular to intracellular water ratio (ECW/ICW).♦ Methods: Sixty PD patients were evaluated. They were stratified into normo- and hypervolemic groups according to their fluid overload (FO). CNR was calculated from resistance at 5 kHz using calf bioimpedance spectroscopy. Arterial stiffness was assessed by PWV. Additionally, all patients underwent transthoracic echocardiography and had levels of NT-proBNP measured.♦ Results: PWV was higher in the hypervolemic compared to normovolemic patients (9.99 ± 2.4 m/sec vs 7.48 ± 2.3 m/sec, p < 0.001). Hypervolemic patients had higher NT-proBNP levels (3065 ± 981 pg/mL vs 1095 ± 502 pg/mL, p < 0.001), a higher ratio of ECW/ICW; (0.93 ± 0.11 vs 0.81 ± 0.08, p < 0.001) and lower CNR (13.7 ± 2.4 vs 16.0 ± 3.3 W m³/kg^*10^-2, p = 0.005). NT-pro BNP level, ECW/ICW ratio, relative FO, and left ventricular (LV) mass index were positively and CNR negatively correlated with PWV. Relative FO and CNR independently predicted PWV in multivariate analysis adjusted for age, duration of PD, body mass index and mean arterial pressure.♦ Conclusions: Arterial stiffness is increased in fluid-overloaded PD patients. Our results indicated that fluid status is an independent predictor of PWV.     

Serum 25-Hydroxyvitamin D Level Could Predict the Risk for Peritoneal Dialysis-Associated Peritonitis

♦ Background:

As an immune system regulator, vitamin D is commonly deficient among patients on peritoneal dialysis (PD), which may contribute to their impaired immune function and increased risk for PD-related peritonitis. In this study, we aimed to investigate whether vitamin D deficiency could predict the risk of peritonitis in a prospective cohort of patients on PD.

♦ Methods:

We collected 346 prevalent and incident PD patients from 2 hospitals. Baseline demographic data and clinical characteristics were recorded. Serum 25-hydroxyvitamin D (25[OH]D) was measured at baseline and prior to peritonitis. The mean doses of oral active vitamin D used during the study period were also recorded. The outcome was the occurrence of peritonitis.

♦ Results:

The mean age of patients and duration of PD were 58.95 ± 13.67 years and 28.45 (15.04 – 53.37) months, respectively. Baseline 25(OH)D level was 16.15 (12.13 – 21.16) nmol/L, which was closely associated with diabetic status, longer PD duration, malnutrition, and inflammation. Baseline serum 25(OH)D predicted the occurrence of peritonitis independently of active vitamin D supplementation with a hazard ratio (HR) of 0.94 (95% confidence interval [CI] 0.90 – 0.98) after adjusting for recognized confounders (age, gender, dialysis duration, diabetes, albumin, residual renal function, and history of peritonitis). Compared to the low tertile, middle and high 25(OH)D level tertiles were associated with a decreased risk for peritonitis with HRs of 0.54 (95% CI 0.31 – 0.94) and 0.39 (95% CI 0.20 – 0.75), respectively.

♦ Conclusions:

Vitamin D deficiency evaluated by serum 25(OH)D rather than active vitamin D supplementation is closely associated with a higher risk of peritonitis.     

Intestinal Calcium Absorption in Exogenous Hypercortisonism: ROLE OF 25-HYDROXYVITAMIN D AND CORTICOSTEROID DOSE

Pharmacologic doses of corticosteroids impair intestinal calcium absorption and contribute to negative calcium balance. However, the relationship between the impaired calcium absorption and a possible defect in the conversion of vitamin D to its physiologically active form, 1,25-dihydroxyvitamin D, is unknown. We compared fractional calcium absorption (double-isotope method, 100-mg carrier) and serum 25-hydroxyvitamin D (25-OH-D) (Haddad method) in 27 patients receiving pharmacologic doses of prednisone with 27 age-, sex-, and season-matched normal subjects. In patients receiving high daily doses of prednisone (15-100 mg/day), calcium absorption (P < 0.02) and serum 25-OH-D (P < 0.001) were decreased. However, in patients receiving low doses (8-10 mg/day) or high doses (30-100 mg) of prednisone on an alternate-day schedule, both of these parameters were normal. Calcium absorption in the patients treated with daily prednisone correlated inversely with the dose of corticosteroids (r = −0.52, P < 0.025) and, in all steroid-treated patients, correlated directly with serum 25-OH-D (r = 0.58, P < 0.01). In four patients who received high-dose corticosteroid therapy for an average of 4 wk, serum 25-OH-D decreased by 35.5% from pretreatment values. Administration of a physiologic or near-physiologic dose of synthetic 1,25-dihydroxyvitamin D₃ (0.4 μg daily for 7 days) to patients receiving high-dose corticosteroids led to an increase in calcium absorption in all patients. These results suggest that calcium malabsorption in the corticosteroid-treated patients is due to a dose-related abnormality of vitamin D metabolism and not to a direct effect of corticosteroids on depressing transmucosal intestinal absorption of calcium.     

Microbiology and Outcomes of Peritonitis in Northern India

♦ Background: Peritoneal dialysis (PD) is an established treatment modality for end-stage renal disease (ESRD). Peritonitis remains a serious complication in PD patients and an important cause of drop-out from the program. Types of pathogens and their drug resistance patterns may determine the outcome of peritonitis. The present study was undertaken to determine the microbiology of peritonitis in PD patients, antibiotic resistance in commonly isolated bacterial pathogens and clinical outcomes.♦ Method: We enrolled 211 patients with ESRD undergoing PD who developed peritonitis during 2002 to 2011. PD fluids were cultured and antibiotic susceptibility test of the bacterial isolates was performed.♦ Result: A total of 303 peritonitis episodes with an overall incidence of 0.41 episodes per patient-year were recorded. Gram-positive, gram-negative, fungi, Mycobacterium tuberculosis and ≥ 2 organisms were isolated from 102 (33.7%), 89 (29.4%), 41 (13.5%), 11 (3.6%) and five (1.6%) episodes respectively; 55 (18.2%) episodes were culture negative. Coagulase-negative Staphylococcus spp. (CONS) was the most common isolate. Catheter loss and hospital admission in gram-negative peritonitis were significantly higher than in gram-positive peritonitis (36/89 (40.4%) vs 20/102 (19.6%), p < 0.001; and 56/89 (62.9%) vs 42/102 (41.2%), p = 0.004 respectively). Antibiotic susceptibility tests showed 54.3% of Enterobacteriaceae isolates were extended spectrum β-lactamase (ESBL) producers, 23.5% of Acinetobacter species and 11.5% of Pseudomonas aeruginosa were metallo-β-lactamase (MBL) producers; 15.4% of enterococci and 28.6% of staphylococci were resistant to vancomycin and methicillin respectively. Mortality was significantly higher in patients having peritonitis due to vancomycin-resistant enterococci, ESBL- and MBL-producing bacteria.♦ Conclusion: Emerging antimicrobial resistance calls for prompt diagnosis and aggressive empiric therapy based on the local sensitivity data.     

Lifetime Costs for Peritoneal Dialysis and Hemodialysis in Patients in Taiwan

♦ Background: This study compared the lifetime costs for peritoneal dialysis (PD) and hemodialysis (HD) patients in Taiwan.♦ Methods: Using the National Health Insurance (NHI) database of all end-stage renal disease patients on maintenance dialysis registered from July 1997 to December 2005, we matched eligible PD patients with eligible HD patients on age, sex, and diabetes status. The matched patients were followed until 31 December 2006. Patients were excluded if they were less than 18 years of age, had been diagnosed with cancer before dialysis, or had been dialyzed at centers or clinics other than hospitals. Outcomes—including life expectancy, total lifetime costs, and costs per life-year paid by the NHI—were estimated and compared.♦ Results: The 3136 pairs of matched PD and HD patients had a mean age of 53.2 ± 15.4 years. The total lifetime cost for PD patients (US$139 360 ± US$8 336) was significantly lower than that for HD patients (US$185 235 ± US$9 623, p < 0.001). Except for patients with diabetes (who had a short life expectancy), the total lifetime cost was significantly lower for PD patients than for HD patients regardless of sex and age (p < 0.01).♦ Conclusion: In Taiwan, the total lifetime costs paid by the NHI were lower for PD than for HD patients.     

Deficiency of Carnitine in Cachectic Cirrhotic Patients

Carnitine is synthesized from lysine and methionine. In the rat, inadequate intake of either of these essential amino acids causes carnitine depletion. Inasmuch as protein deficiency is common in the hospital population, we have investigated the possible occurrence of nosocomial carnitine deficiency. Fasting serum carnitine concentration was measured in 16 normal and 247 patients in 16 disease groups. Normal range of carnitine was 55-103 μM. Only the cirrhotic group showed significant (P < 0.05) hypocarnitinemia. 14 of 36 hospitalized cirrhotics had subnormal values for serum carnitine. The creatinine/height index, midarm muscle circumference, and triceps skin-fold thickness indicated protein-calorie starvation in the 14 hypocarnitinemic liver patients. In six of the hypocarnitinemic cirrhotics (average serum level 50% of normal), spontaneous dietary intakes of carnitine, lysine, and methionine were measured and found to be only 5-15% as great as in six normocarnitinemic, healthy controls. When these six cirrhotic and six normal subjects were given the same lysine-rich, methionine-rich, and carnitine-free nutritional intake, the normals maintained normal serum carnitine levels and excreted 100 μmol/day, whereas the cirrhotics' serum level fell to 25% of normal, and urinary excretion declined to 15 μmol/day.     

Lower Education Level Is a Major Risk Factor for Peritonitis Incidence in Chronic Peritoneal Dialysis Patients: A Retrospective Cohort Study with 12-Year Follow-Up

♦ Background: Peritoneal dialysis (PD)-related peritonitis remains an important complication in PD patients, potentially causing technique failure and influencing patient outcome. To date, no comprehensive study in the Taiwanese PD population has used a time-dependent statistical method to analyze the factors associated with PD-related peritonitis.♦ Methods: Our single-center retrospective cohort study, conducted in southern Taiwan between February 1999 and July 2010, used time-dependent statistical methods to analyze the factors associated with PD-related peritonitis.♦ Results: The study recruited 404 PD patients for analysis, 150 of whom experienced at least 1 episode of peritonitis during the follow-up period. The incidence rate of peritonitis was highest during the first 6 months after PD start. A comparison of patients in the two groups (peritonitis vs null-peritonitis) by univariate analysis showed that the peritonitis group included fewer men (p = 0.048) and more patients of older age (≥65 years, p = 0.049). In addition, patients who had never received compulsory education showed a statistically higher incidence of PD-related peritonitis in the univariate analysis (p = 0.04). A proportional hazards model identified education level (less than elementary school vs any higher education level) as having an independent association with PD-related peritonitis [hazard ratio (HR): 1.45; 95% confidence interval (CI): 1.01 to 2.06; p = 0.045). Comorbidities measured using the Charlson comorbidity index (score >2 vs ≤2) showed borderline statistical significance (HR: 1.44; 95% CI: 1.00 to 2.13; p = 0.053).♦ Conclusions: A lower education level is a major risk factor for PD-related peritonitis independent of age, sex, hypoalbuminemia, and comorbidities. Our study emphasizes that a comprehensive PD education program is crucial for PD patients with a lower education level.