Factors influencing skin autofluorescence of patients with peritoneal dialysis

Skin autofluorescence (SAF) measurement is a simple, noninvasive method to assess tissue advanced glycation end products (AGE). In patients with end-stage renal disease and in those on hemodialysis AGE production is increased. Less is known about those treated with peritoneal dialysis (PD). In this study we tested if SAF is influenced by clinical and treatment characteristics in PD patients.This cross-sectional study included 198 PD patients (of those, 128 were on traditional glucose-based solutions and 70 patients were partially switched to icodextrin-based PD). SAF measurements were done with a specific AGE Reader device. The impact of patients' age, gender, current diabetes, duration of PD, cumulative glucose exposure, body mass index, smoking habits and use of icodextrin on SAF values were tested with multiple regression analysis.Our analysis revealed that patients' age, current diabetes and icodextrin use significantly increase patients' SAF values (p = 0.015, 0.012, 0.005, respectively). AGE exposure of PD patients with diabetes and on icodextrin solution is increased. Further investigation is required whether this finding is due to the icodextrin itself or for a still unspecified clinical characteristic of PD population treated with icodextrin.     

Determinants of elevated healthcare utilization in patients with COPD

Background

Chronic obstructive pulmonary disease (COPD) imparts a substantial economic burden on western health systems. Our objective was to analyze the determinants of elevated healthcare utilization among patients with COPD in a single-payer health system.

Methods

Three-hundred eighty-nine adults with COPD were matched 1:3 to controls by age, gender and area of residency. Total healthcare cost 5 years prior recruitment and presence of comorbidities were obtained from a computerized database. Health related quality of life (HRQoL) indices were obtained using validated questionnaires among a subsample of 177 patients.

Results

Healthcare utilization was 3.4-fold higher among COPD patients compared with controls (p < 0.001). The "most-costly" upper 25% of COPD patients (n = 98) consumed 63% of all costs. Multivariate analysis revealed that independent determinants of being in the "most costly" group were (OR; 95% CI): age-adjusted Charlson Comorbidity Index (1.09; 1.01 - 1.2), history of: myocardial infarct (2.87; 1.5 - 5.5), congestive heart failure (3.52; 1.9 - 6.4), mild liver disease (3.83; 1.3 - 11.2) and diabetes (2.02; 1.1 - 3.6). Bivariate analysis revealed that cost increased as HRQoL declined and severity of airflow obstruction increased but these were not independent determinants in a multivariate analysis.

Conclusion

Comorbidity burden determines elevated utilization for COPD patients. Decision makers should prioritize scarce health care resources to a better care management of the "most costly" patients.     

Pulmonary hypertension in patients with chronic kidney disease on dialysis and without dialysis: results of the PEPPER-study

Pulmonary hypertension (PH) is common in patients with dialysis-dependent chronic kidney disease and is an independent predictor of mortality. However, specific hemodynamics of the pulmonary circulation, changes induced by hemodialysis and characterization into pre- or postcapillary PH have not been evaluated in patients with chronic kidney disease. We assessed consecutive patients with end-stage chronic kidney disease in WHO FC ≥ II with dyspnea unexplained by other causes on hemodialysis (group 1, n = 31) or without dialysis (group 2, n = 31) using right heart catheterization (RHC). In group 1, RHC was performed before and after dialysis. In end-stage chronic kidney disease, prevalence of precapillary PH was 13% (4/31), and postcapillary PH was discovered in 65% (20/31). All four cases of precapillary PH were unmasked after dialysis. In group 2, two cases of precapillary PH were detected (6%), and postcapillary PH was diagnosed in 22 cases (71%). This is the first study examining a large cohort of patients with chronic kidney disease invasively by RHC for the prevalence of PH. The prevalence of precapillary PH was 13% in patients with end-stage kidney disease. That suggests careful screening for precapillary PH in this selected patient population. RHC should be performed after hemodialysis.     

Cytokines correlate with age in healthy volunteers, dialysis patients and kidney-transplant patients

T-cell functions are currently used as biomarkers for the pharmacodynamic monitoring of immunosuppressive drugs or as disease biomarkers of inflammation/sepsis and organ rejection. In order to evaluate co-factors potentially influencing the expression of the immunological biomarkers, we explored T-cell proliferation, T-cell activation (CD25 and CD71 expressions) and intra-lymphocyte cytokine production (interleukin (IL)-2 and tumor necrosis factor (TNF)-α) in healthy volunteers, dialysis patients and stable kidney-transplant patients treated with standard immunosuppressive therapy, i.e. tacrolimus, mycophenolic acid with or without steroids. Age was positively correlated with TNF-α expression in all three patient populations, and with IL-2 expression in healthy volunteers and kidney-transplant patients. Further age was correlated with inhibition of lymphocyte proliferation in healthy volunteers and with the T-cell activation marker CD25 in kidney-transplant patients. In healthy volunteers lymphocyte proliferation was higher in woman as compared to men. Other biomarkers of T-cell function were independent of the gender. In the kidney-transplant patient group a significantly lower expression of all biomarkers of T-cell functions compared to healthy volunteers and dialysis patients. In dialysis patients we found significant increased IL-2 expression compared to healthy volunteers, while the other T-cell functions were not significantly different. Further time on dialysis had no effect on the level of biomarker expression. In conclusion we found decreased T-cell functions in kidney-transplant patients compared to healthy volunteers and dialysis patients, increased IL-2 expression in dialysis patients compared to healthy volunteers and in all three populations we found a correlation of age and intra-T-lymphocyte TNF-α expression.     

Platelet serotonin concentration in dialysis patients with somatic symptoms of depression

Platelet serotonin (5-HT) concentration was measured in 65 male and 45 female chronic renal patients on hemodialysis (HD) with different somatic symptoms of depression (crying spells, irritability, sleep disturbance, fatigability, loss of appetite, weight loss, somatic preoccupation and loss of libido), to find out the relationship between the severity of symptoms and platelet 5-HT concentration. Male and female patients had significantly lower platelet 5-HT concentration than 62 male and 38 female healthy subjects. Gender-differences in platelet 5-HT values observed in healthy subjects were not found in patients. Platelet 5-HT concentration differed in the groups of patients with the different scores of particular somatic symptoms (loss of appetite and loss of libido), but was similar in patients with other somatic symptoms. There was no relationship between platelet 5-HT concentration and the severity of somatic symptoms, or between platelet 5-HT concentration and age of the patients. Gender-related differences in the occurrence of somatic symptoms were detected in patients with the different degrees of weight loss, somatic preoccupation and loss of libido. Our results suggest that platelet 5-HT concentration could not be used as a biological marker for the severity of somatic symptoms in chronic renal patients on HD.     

The importance of oxidative stress in patients with chronic renal failure whose hypertension is treated with peritoneal dialysis

Increased oxidative stress is a well-known phenomenon in dialysis patients. However, the contribution of hypertension to the oxidative stress in peritoneal dialysis patients has not yet been assessed. The present study aimed to investigate if hypertension had an additional effect on oxidative stress in peritoneal dialysis patients. A total of 50 patients treated with peritoneal dialysis were divided into two groups: The patients with mean of last three blood pressure results as 135/90 mmHg and above were considered hypertensive, the patients with lower blood pressure were considered normotensive. The control group included 25 healthy individuals. Serum malondialdehyde (MDA), advanced oxidation protein product (AOPP), myeloperoxidase (MPO), catalase (CAT) and glutathione peroxidase (GSH-Px) levels were measured in all groups. MDA level, an indicator of lipid peroxidation, was significantly higher in the hypertensive group compared to the control group, while the increase in the normotensive group was not significant. However, the difference between the hypertensive and normotensive groups was significant. The levels of AOPP, an indicator of protein oxidation level, and MPO, an indicator of neutrophil activation, were not different between the groups, while the activities of antioxidant CAT and GSH-Px decreased in both normotensive and hypertensive groups compared to the control group, and there was no significant difference between the patient groups. This study shows that both normotensive and hypertensive peritoneal dialysis patients have increased-oxidative stress and decreased antioxidant levels and hypertension might have an additional effect on oxidative stress by increasing MDA level in peritoneal dialysis patients.     

Cancer in patients receiving dialysis.

The incidence of cancer and related mortality was studied in 1651 patients from six dialysis centres in England over 10 years. The only type of cancer for which there was a significant excess was non-Hodgkin''s lymphoma (four cases observed against an expected incidence of 0.15 (p < 0.001); three deaths against an expected 0.1 (p < 0.001)). This excess could not be attributed to either subsequent transplantation or treatment with immunosuppressive drugs. Since immunodepression is a feature of chronic renal failure, these observations together with those on patints treated with immunosuppressive drugs suggest that immunosuppression favours the development of non-Hodgkin''s lymphoma. Studies in which it is concluded that patients receiving dialysis show an excess of other types of cancer have certain shortcomings; the unusual opportunities for detecting cancer in such patients may account for some of the reported excess.     

Prolactin and zinc in dialysis patients

The objectives of the present study were to investigate the frequencies of hyperprolactinemia and hypozincemia in patients undergoing hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD), the associations between blood levels of zinc (Zn²⁺) and hormones, and dietary zinc intake amount and its relation to zincemia. We studied 28 patients (14 HD and 14 CAPD) who had their blood levels of Zn²⁺, prolactin (PRL), parathyroid hormone (PTH), and gonadotropins (LH, FSH) evaluated. Thirteen patients had dietary nutrient amounts evaluated from a 3-d nutritional record. Hyperprolactinemia occurred in 29% patients (HD = CAPD), hypozincemia in 62% (20% HD and 42% CAPD), and low dietary Zn²⁺ intake in 90% of patients. No correlation among blood concentration of Zn²⁺ and PRL, PTH, LH, and FSH were observed in the two modalities of dialysis or between zincemia and Zn²⁺ ingestion. We concluded that the occurrence of hyperprolactinemia and hypozincemia were not related to dialysis modality and that zincemia did not reflect the observed low dietary intake of Zn²⁺.     

The frequency of Th2 type cells increases with time on peritoneal dialysis in patients with diabetic nephropathy.

We have analysed the frequency of cytokine-producing T cells in different dialysis groups (haemodialysis; HD and peritoneal dialysis; PD) over time. Although we saw no difference in type 1 cytokine production (IL-2 and IFN-gamma) in either dialysis group, there was a clear increase in the percentage of T cells spontaneously producing the type 02 cytokines in the PD group (IL-4, r = 0.558, P < 0.05; IL-10, r = 0.527, p < 0.05). Our patient group was carefully selected to include patients with an ongoing autoimmune disease, insulin dependent diabetes mellitus (IDDM) (DN group) and chronic glomerulonephritis (GN), which are common reasons of end stage renal failure. As expected there was no increase in the spontaneous production of either IL-4 or IL-10 in either disease group with patients undergoing HD treatment. However, there was a clear correlation with the frequency of T cells producing IL-4 (r = 0.755, P < 0.05) and IL-10 (r = 0.725, P < 0.05) and time on dialysis in the PD patients with DN, but not those with GN. Much work has suggested that the pathogenesis of IDDM is associated with a Th1 dominated response. We show here that this response is skewed towards a Th2 response after long term treatment with PD. This work demonstrates that the immunological effects of different dialysis modalities on patients with different diseases vary. This may go some way to explain why certain patient groups have more complications with different dialysis modalities.     

Proteomic analysis in peritoneal dialysis patients with different peritoneal transport characteristics

Peritoneal membranes can be categorized as high, high average, low average, and low transporters, based on the removal or transport rate of solutes. In this study, we used proteomic analysis to determine the differences in proteins removed by different types of peritoneal membranes. Peritoneal transport characteristics in patients who received peritoneal dialysis therapy were assessed by a peritoneal equilibration test. Two-dimensional differential gel electrophoresis technology followed by quantitative analysis was performed to study the variation in protein expression from peritoneal dialysis effluents (PDE) among different groups. Proteins were identified by MALDI-TOF-MS/MS analyses. Further validation in PDE or serum was performed utilizing ELISA analysis. Proteomics analysis revealed ten protein spots with significant differences in intensity levels among different groups, including vitamin D-binding protein, complement C3, apolipoprotein-A1, complement factor C4A, haptoglobin, alpha-1 antitrypsin, immunoglobulin kappa light chain, alpha-2-microglobulin, retinol-binding protein 4 and transthyretin. The levels of vitamin D-binding protein, complement C3, and apolipoprotein-A1 in PDE derived from different groups were greatly varied (P < 0.05). However, no significant difference was found in the serum levels of these proteins among different groups (P > 0.05 for all groups). This study provides a novel overview of the differences in PDE proteomes of four types of peritoneal membranes. Vitamin D-binding protein, complement C3, and apolipoprotein-A1 showed enhanced expression in PDE of patients with high transporter.     

Controlled trial of enalapril in patients with chronic fluid overload undergoing dialysis

About one third of patients receiving dialysis for end stage renal failure have chronic fluid overload despite advice to restrict their oral fluid intake. To investigate the potential of an angiotensin converting enzyme inhibitor in reducing the urge to drink and consequent gain in weight, a double blind, placebo controlled crossover trial of enalapril was conducted in 25 patients receiving dialysis who had fluid overload. The trial comprised a baseline period of four weeks; two periods of treatment, each of four weeks, during which patients received either placebo or enalapril 5 mg twice each week; and a follow up period of four weeks. Five patients withdrew from the trial, one because of an adverse drug reaction to enalapril. A range of biochemical and behavioural variables was measured during the baseline period, at the completion of periods 1 and 2, and during follow up. These variables included gain in weight between dialysis sessions; blood pressure; plasma concentrations of sodium, angiotensin II, and vasopressin; plasma renin and angiotensin converting enzyme activities; osmolality; and estimations of thirst, intake of fluid, and control of drinking. Enalapril caused a significant reduction in gain in weight between dialysis sessions, thirst, and oral intake of fluid in parallel with significantly increased renin activity, significantly decreased angiotensin converting enzyme activity, and decreased concentrations of angiotensin II. Gain in weight and angiotensin converting enzyme activity returned to baseline values once patients stopped taking enalapril.These results suggest that enalapril may act on the renin-angiotensin system and reduce intake of fluid by inhibiting angiotensin converting enzyme.