Circulating soluble adhesion molecules in ANCA-associated vasculitis.

BACKGROUND: To evaluate whether changes in concentrations of soluble (s) E-selectin, sP-selectin, sL-selectin, intercellular adhesion molecule 1 (sICAM-1), and vascular cell adhesion molecule 1 (sVCAM-1) reflect disease activity in patients with ANCA-associated vasculitis and whether serum levels of these adhesion molecules are related to the degree of renal failure in patients with chronic renal failure (CRF). SUBJECTS AND METHODS: A sandwich ELISA was used to measure these soluble adhesion molecules in (i) sera from 20 patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (10 patients with Wegener's granulomatosis (WG) and 10 patients with microscopic polyangiitis (MPA)), obtained at the time of diagnosis and during the remission period; (ii) sera from 40 patients with CRF not undergoing haemodialysis. RESULTS: At the time of diagnosis, serum levels of sE-selectin, sICAM-1 and sVCAM-1 (88+/-42 ng/ml, 437+/-184 ng/ml, 1720+/-1174 ng/ml respectively) were significantly higher in patients with ANCA-associated vasculitis than in healthy controls (P<0.0001, P=0.002 and P=0.001 respectively). Serum sP-selectin values did not differ from those obtained in normal donors. In contrast, sL-selectin levels (940+/-349 ng/ml) were significantly lower in patients than those recorded in healthy controls (P<0.0001). A significant decrease in concentrations of sE-selectin, sP-selectin, sICAM-1, and sVCAM-1 was observed between active and remission phases (P<0.0001, P=0.002, P=0.001 and P=0.001 respectively). No significant differences were observed in sL-selectin levels between active and remission phases. sL-selectin concentrations (802+/-306 ng/ml) during the remission phase remained lower than those observed in healthy controls (P<0.0001). No correlation was observed between serum creatinine and sE-selectin, sP-selectin, sICAM-1 and sVCAM-1 in patients of the CRF group. A slight negative correlation was established between creatinine and sL-selectin concentration. CONCLUSIONS: Increased serum levels of sE-selectin, sICAM-1, and sVCAM-1 and decreased levels of sL-selectin in active ANCA-associated vasculitis, and the normalization of sE-selectin, sICAM-1, and sVCAM-1 during the remission phase suggest that the concentration of soluble levels of these adhesion molecules reflects disease activity. The decrease in sP-selectin levels between active and inactive phases also suggest that this receptor may reflect clinical activity. The lack of correlation between serum levels of sE-selectin, sP-selectin, sICAM-1, and sVCAM-1 and the degree of renal failure in patients with CRF suggests that the mechanism of clearance of these molecules is not renal.     

Soluble adhesion molecules in children and young adults on chronic hemodialysis

Children on chronic hemodialysis (HD) present with impaired immunity that may result from disturbances in leukocyte migration, caused by changes in expression of adhesion molecules on endothelium and immunocompetent cells. However, it is still not clear whether the type of dialyzer or a single dialysis session influences the concentrations of soluble adhesion molecules in these patients. We evaluated by ELISA serum levels of soluble (s) VCAM-1, ICAM-1, L-selectin, and P-selectin in 22 patients on cuprophane HD (CU), 8 on polysulfone HD (PS), 10 on vitamin E-modified cellulose HD (VE), and 15 controls. In all HD patients, sVCAM-1 levels were elevated compared with controls and were higher in CU than in VE. The sICAM-1 concentrations were increased in VE compared with controls, but remained unchanged in CU and PS. The sL-selectin levels were reduced in all HD patients. The mean values of sP-selectin were comparable in CU, PS, and controls. The lowest levels were observed in VE. In CU patients, sVCAM-1, sICAM-1, and sP-selectin concentrations rose after HD. A single PS session had no impact on adhesion molecules, whereas a VE session increased the level of sVCAM-1. The type of dialysis membrane may change the profile of adhesion molecule concentrations, thus influencing the immune system of a child on HD. The increase in levels of adhesion molecules in the course of a single HD session, which was pronounced in CU and VE patients, suggests poor biocompatibility of these dialyzers.     

Lipid Abnormalities and Oxidized LDL in Chronic Kidney Disease Patients on Hemodialysis and Peritoneal Dialysis

Dyslipoproteinemia and oxidative modification of low-density lipoprotein (oxLDL) contribute to the development of oxidative stress and atherosclerosis in chronic kidney disease (CKD). On the contrary, high-density lipoprotein cholesterol (HDL-C), especially HDL3-C subtype, has protective effect against oxidative damage. There is limited evidence referring HDL-C subclass levels in patients on dialysis. This study was designed to compare lipid abnormalities and oxLDL levels in hemodialysis (HD) and peritoneal dialysis (PD) patients. Serum lipids, HDL subclasses, and oxLDL were measured in 55 patients with CKD-stage 5 (31 patients on HD and 24 patients on PD) and in 21 normal controls (NC). The results showed that in dialysis patients, triglycerides were higher than in controls (p < 0.0001) and HDL-C was significantly lower (p < 0.0001). The HDL2-C subclass concentration did not differ significantly between patients and controls, while HDL3-C was lower in patients (11 ± 0.5 mg/dL) than in NC (23 ± 1, p < 0.0001). oxLDL levels were markedly increased in patients (1.92 ± 0.29 mg/L) compared to NC (0.22 ± 0.05, p < 0.0001). Patients on PD had higher levels of cholesterol (p < 0.001) and apolipoprotein B (p < 0.05) than patients on HD. However, HDL-C, HDL-C subclasses, and oxLDL concentrations did not differ significantly between PD and HD patients. It is concluded that patients with CKD have a nearly 10-fold elevation of oxLDL compared with NC. Patients on PD have differences in the lipid profile compared with patients on HD; however, both modalities seem to possess similar potential to atherosclerosis development.     

Increased levels of soluble TNF-alpha receptors and cellular adhesion molecules in patients undergoing bioincompatible hemodialysis

BACKGROUND: The study aimed to differentiate the effects of hemodialysis (HD) and chronic renal failure (CRF) on the levels of circulating tumor necrosis factor-alpha (TNF-alpha) and TNF-alpha receptors p55 and p75, soluble vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), soluble endothelial-leukocyte adhesion molecule-1 (sE-selectin) and sP-selectin in 18 patients on regular HD treatment with cuprophane membrane in relation to 15 non-dialyzed CRF patients and 15 healthy controls. METHODS: The serum concentrations were determined with standard ELISA assays. RESULTS: Blood serum p75 and p55 were approximately tenfold increased in CRF (36.7 +/- 6.2 and 27.1 +/- 5.6 ng/ml) and HD patients (45.6 +/- 18.4 and 28.7 +/- 5.9 ng/ml) before the HD session (HD 0), during (HD 20) the session (45.7 +/- 18.4 and 28.5 +/- 7.3 ng/ml) and after (HD 240) the HD session (52.1 +/- 17.4 and 30.9 +/- 8.2 ng/ml) in comparison to control values (5.6 +/- 1.3 and 2.4 +/- 0.8 ng/ml, respectively) (p < 0.01). The highest increment of p75 at the end of HD session (HD 240) was also significantly higher than at preceding time points (HD 0 and 20) (p < 0.05). However, the remaining study parameters did not change during an HD session. Also, there were no relevant changes in TNF-alpha levels if (HD 0) 22.7 +/- 21.5 ng/ml and (HD 240) 21.1 +/- 18.9 ng/ml were compared. Chronic HD status was related to the increase of sVCAM-1 and sICAM-1 levels. Prior to HD, T0 sVCAM-1 and sICAM-1 concentrations were 2,180.4 +/- 761.8 and 567.3 +/- 218.8 ng/ml, during HD (T20): 2,172.7 +/- 759.2 and 602.3 +/- 379.9 ng/ml, and after HD (T240): 2,401.6 +/- 756.4 and 648.3 +/- 183.5 ng/ml, respectively (p < 0.05 vs. controls and CRF patients). sVCAM-1 and sICAM-1 serum levels (1,262.2 +/- 472.9 and 165.6 +/- 50.4 ng/ml) were similar in CRF patients and healthy controls (854.4 +/- 241.5 and 217.6 +/- 74.2 ng/ml, respectively). Even though serum sE- and sP-selectin in CRF patients did not differ from the control (39.8 +/- 21.3 vs. 42.1 +/- 18.9 ng/ml and 187.9 +/- 66.9 vs. 198.8 +/- 62.2 ng/ml, respectively), their levels were increased in HD patients up to 111.9 +/- 54.6 and 453.2 +/- 231.1 ng/ml in patients prior to HD, 118.7 +/- 66.2 and 350.8 +/- 114.8 ng/ml during the HD session and then 132.3 +/- 61.1 and 368.3 +/- 126.6 ng/ml, respectively, after its completion (p < 0.05 in comparison with CRF patients and controls). CONCLUSIONS: The increased circulating TNF-alpha receptors appear more associated with the uremic milieu than HD-related systemic inflammation, whereas increased soluble cellular adhesion molecules in patients undergoing bioincompatible HD may be related to the enhanced systemic inflammation specifically due to maintenance HD.     

Hemodialysis procedure does not affect the levels of sICAM-1 and sVCAM-1 in patients with end stage renal disease

Atherosclerosis is by far the leading cause of mortality and morbidity in patients with end stage renal disease undergoing chronic hemodialysis (HD). Vascular endothelial cell adhesion molecules like the intercellular adhesion molecule-1 (ICAM-1) and the vascular cell adhesion molecule-1 (VCAM-1) are involved in the pathogenesis of atherosclerosis. Their soluble forms (sICAM-1, sVCAM-1) are considered potential serum markers of endothelial activation and atherosclerosis. The aim of this study was to clarify the influence of the HD procedure on the levels of sICAM-1 and sVCAM-1 in patients with end stage renal disease. We evaluated 35 clinically stable patients (18 males, 17 females, mean age 61 +/- 12) on chronic HD treatment. Diabetes mellitus coexisted in eight patients and arterial hypertension in 23 patients. Blood was drawn before, every hour during, and after a single HD session in each patient. Low-flux cuprophane dialyzers (GFS 12, Gambro, Lund, Sweden) were used in 22 and high-flux polysulfone dialyzers (Hemoflow F 60S, Fresenius, Oberursel, Germany) in 13 cases. At 30 min into the HD session (n=31, 20 low-flux HD, 11 high-flux HD) blood was drawn simultaneously from the entrance and the exit line of the dialyzer. From all these samples, serum concentrations of sICAM-1 and sVCAM-1 were determined by commercially available enzyme immunoassays (ELISA, R&D Systems, Minneapolis, USA). Results were corrected according to hemoconcentration, where appropriate. Plasma levels of sVCAM-1 were elevated in patients with end stage renal disease before the beginning of the dialysis session when compared to healthy controls (1449 +/- 497 ng/mL vs. 691 +/- 118 ng/mL). On the contrary, such an elevation was not found in the case of sICAM-1 (231 +/- 58.5 ng/mL vs. 236.4 +/- 96.8 ng/mL in healthy controls). These levels remained stable in all measurements throughout the dialysis procedure. Furthermore, serum sICAM-1 and sVCAM-1 levels remained unaltered after the passage of the dialyzer. The levels of sICAM-1 and sVCAM-1 were not influenced by the existence of diabetes mellitus, hypertension, or by the utilization of biocompatible, high flux dialyzers. Our study confirms that in chronic HD patients serum levels for sVCAM-1 are elevated. The levels of adhesion molecules are not affected by the HD procedure. These findings probably can be attributed to a decreased renal clearance or catabolism of sICAM-1 and sVCAM-1 and to the different sources of the two molecules. Neither coexisting diabetes mellitus nor arterial hypertension influences the circulating levels of these adhesion molecules. The functional role of sVCAM-1 and sICAM-1, the exact renal contribution to their metabolism, and their role as markers of atherosclerosis in chronic renal disease need further evaluation.     

Asymmetric Dimethylarginine in Hemodialysis,Hemodiafiltration, and Peritoneal Dialysis

Asymmetric dimethylarginine (ADMA) is a mediator of endothelial dysfunction. Production and elimination of ADMA may be affected by the type of renal replacement therapy used and oxidative stress. Plasma ADMA, advanced glycation end products (AGE), and homocysteine were assessed in 59 subjects: 20 hemodialysis (HD) patients, 19 patients undergoing peritoneal dialysis (PD), and 20 controls. Results were compared between the groups. The effect of 8 weeks of HD and high‐volume predilution hemodiafiltration (HDF) was compared in a randomized study. HD patients showed higher ADMA (1.20 [0.90–1.39 µmol/L]) compared to controls (0.89 [0.77–0.98], P < 0.01), while ADMA in PD did not differ from controls (0.96 [0.88–1.28]). AGE and homocysteine were highest in HD, lower in PD (P < 0.01 vs. HD), and lowest in controls (P < 0.001 vs. HD and PD). PD patients had higher residual renal function than HD (P < 0.01). The decrease in ADMA at the end of HD (from 1.25 [0.97–1.33] to 0.66 [0.57–0.73], P < 0.001) was comparable to that of HDF. Switching from HD to HDF led to a decrease in predialysis homocysteine level in 8 weeks (P < 0.05), while ADMA and AGE did not change. Increased ADMA levels in patients undergoing HD, as compared to PD, may be caused by higher oxidative stress and lower residual renal function in HD. Other factors, such as diabetes and statin therapy, may also be at play. The decrease in ADMA at the end of HD and HDF is comparable. Switching from HD to HDF decreases in 8 weeks the predialysis levels of homocysteine without affecting ADMA.     

Markers for endothelial dysfunction,but not markers for oxidative stress correlate with classical risk factors and the severity of coronary artery disease

Objective. Endothelial dysfunction and oxidative stress are involved in atherogenesis. In the search for predictors of vascular disease markers for endothelial dysfunction and oxidative stress were analyzed. Methods. Of 208 consecutive patients 22% were controls (CO) without coronary artery disease (CAD), 52% presented with stable angina (SAP) and 26% had acute coronary syndromes (ACS). Nitric oxide (NO), thrombomodulin (TM), von Willebrand factor (vW), sVCAM-1, sICAM-1, sP-selectin, sE-selectin, sL-selectin and C-reactive protein (CRP) were determined as markers for endothelial dysfunction, glutathione (GSH), glutathione peroxidase (Gpx), myeloperoxidase (Mpx), lipid peroxides (Lpx), 8-isoprostane (Iso), superoxide dismutase (SOD), total antioxidant capacity (TAC) and homocysteine (Hc) as markers for oxidative stress. Results. The increases of TM, vW, sVCAM-1, CRP, SOD and Mpx correlated with the CAD status in the order CO?<?SAP?<?ACS, whereas NO and sL-selectin were inversely correlated (p?<?0.05, resp.). The other markers remained unchanged. For several markers a significant relationship to risk factors was detected. Conclusions. Markers for endothelial dysfunction rather than those for oxidative stress may serve as indicators for the presence and severity of CAD.     

Platelet Activity and Serum Homocysteine Levels in Patients with End-Stage Renal Failure with Regard to Dialysis Modality

Background. Recent evidence suggests that the activation of platelets and their interaction with circulating cells are important independent risk factors for atherosclerosis. In non-uremic patients with symptomatic peripheral vascular disease, a relationship between serum homocysteine (Hcy) levels and platelet activity had been reported. The purposes of this study were to evaluate of effects of dialysis modality on platelet activity in patients with end-stage renal failure and to investigate the relationship between platelet activity, Hcy, and left ventricular hypertrophy (LVH). Material and Methods. In age and sex matched 19 healthy subjects, 20 hemodialysis (HD) patients, and 18 continuous ambulatory peritoneal dialysis (CAPD) patients, the expression of platelet surface receptors CD41, CD61, CD42a, and CD62P were investigated. CD62P expression was statistically significantly increased in HD patients compared with CAPD patients and controls (34.4 ± 22.5%; 17.3 ± 19.6%, 12.0 ± 15.6%, respectively, p < 0.05), but not in CAPD patients compared with controls. There was a positive correlation between CD62 expression and duration of dialysis in HD patients (r = 0.498, p = 0.026). Mean plasma Hcy levels in dialysis patients were higher than reference levels. However, we could not find any relationship between CD62 expression, Hcy, and LVH in both groups (p > 0.05). Conclusions. Hemodialysis and peritoneal dialysis (PD) have a different impact on the expression of CD62: peritoneal dialysis seems to have a more favorable effect. It may be possible that the differences in biocompatibility between PD and HD potentially contribute to differences in CD62 expression.     

Circulating soluble adhesion molecules in systemic vasculitis

The plasma levels of soluble intercellular adhesion molecule-1(sICAM-1), E-selectin (sE-selectin), and vascular cell adhesionmolecule-1 (sVCAM-1), might reflect endothelial activation andinjury and would therefore be useful markers of disease activityin vasculitis. To investigate this we measured the levels ofsICAM-1, sE-selectin, and sVCAM-1 by two-site ELISAs in theplasma of patients with (a) active vasculitis (n = 16), (b)vasculitis in remission (n = 15), (c) chronic renal failure(CRF) (n = 10), and (d) normal healthy controls (n = 10). PlasmasICAM-1 levels were significantly higher in patients with activevasculitis, 323 ng/ml (193–607) compared with patientswith inactive vasculitis, 199 ng/ml (131–297); P = 0.0006and healthy controls, 188 ng/ml (138–259); P =0.0002.Plasma sE-selectin levels were also significantly higher inthe patients with active vasculitis, 45 ng/ml (15–65)compared with patients with inactive vasculitis, 25 ng7sol;ml(15–55); P=0.027 but not when compared with healthy controls,35 ng/ml (20–55); P=0.16. There was no difference in plasmasVCAM-1 levels between patients with active vasculitis, OD 0.56(0.45–0.85) and inactive disease, OD 0.58 (0.47–0.79)(P=0.12) or with healthy controls OD 0.49 (0.42–0.68)(P=0.48). There were no significant differences between theplasma levels of any of the soluble adhe sion molecules betweenpatients with active vasculitis and patients with chronic failure.In patients with a vasculitis there was a significant correlationbetween sICAM-1 and plasma C-reactive protein (CRP) (r=0.60,P=<0.01) and plasma von Willebrand factor (vWF) (r=0.42,P<0.05). Likewise there was a cor relation between sE-selectinand CRP (r=0.45, P<0.02) but not with vWF. There was a significantcorrelation between sICAM-1 and sE-selectin (r=0.38, P<0.05),but not between sICAM-1 and sVCAM-1 or sE- selectin and sVCAM-1.No correlation was found between sVCAM-1 levels and CRP andvWF concentrations or between the levels of any of the solubleadhesion molecules and serum creatinine. Plasma levels of sICAM-iand of sE-selectin but not of sVCAM-1 reflect disease activityin vasculitis and may be markers of endothelial and or tissueinjury in these disorders.     

Brain Natriuretic Peptide and Its Relationship to Left Ventricular Hypertrophy in Patients on Peritoneal Dialysis or Hemodialysis Less Than 3 Years

An increase of brain natriuretic peptide (BNP) levels is commonly observed in patients on dialysis. Increased circulating levels of BNP are related to future cardiac events and associated with shorter survival in patients on chronic hemodialysis (HD). During the first 1 or 2 years on dialysis, patients on peritoneal dialysis (PD) have been shown to have an improvement in left ventricular hypertrophy, blood pressure, and volume status. This study compares BNP levels and cardiac status of PD and HD patients without cardiovascular disease and on dialysis for less than 36 months. The correlation between plasma BNP concentration and findings of echocardiography before HD scans were examined and compared with findings of PD. Twenty-two HD patients (15 men, 7 women; mean age, 52.5 ± 13.9 years) and 19 PD patients (10 men, 9 women; mean age, 47.6 ± 11.3 years) were studied. There were no significant differences between HD and PD patients with regard to age, gender, duration of dialysis, left ventricular mass, left ventricular mass index (p > 0.05). Plasma BNP levels were markedly greater in HD patients (467.8 ± 466.5 pg/mL) than those of PD patients (143.1 ± 165.2 pg/mL). Urine output was significantly higher in PD patients compared with HD patients (p < 0.05). A positive correlation between systolic blood pressure, diastolic blood pressure, and plasma BNP in HD patients (r: 0.653, p: 0.001; r: 0.493, p: 0.023, respectively) was detected. Additional studies are needed to investigate whether lower BNP level in PD patients is an advantage.     

K/DOQI guideline requirements for calcium, phosphate, calcium phosphate product, and parathyroid hormone control in dialysis patients: can we achieve them?

Background: Mineral metabolism has emerged as an important predictor of morbidity and mortality in dialysis patients. Kidney Disease Outcomes Quality Initiative (K/DOQI) clinical practice guidelines for bone metabolism and disease in chronic kidney disease (CKD) recommend that, in Stage 5 CKD, the target levels for calcium (Ca) (corrected for serum albumin), phosphate (P), calcium × phosphate (Ca × P) product and parathyroid hormone (PTH) levels should be maintained at 8.4–9.5 mg/dl, 3.5–5.5 mg/dl, < 55 mg²/dl² and 150–300 pg/ml, respectively. Objectives: To evaluate our ability to achieve K/DOQI guidelines for bone metabolism and disease targets in our patients and to compare them between patients on hemodialysis (HD) and peritoneal dialysis (PD) and also with those reported in the literature. Methods: We reviewed bone metabolism laboratory parameters in 57 HD patients and 69 PD patients, who had been on dialysis for more than 9 months. Results: The percentage of patients whose serum Ca, P, Ca × P product and PTH were within K/DOQI recommended target ranges were 46%, 53%, 77% and 28% in HD patients and 52%, 65%, 77% and 23% in PD patients, respectively. There were no significant differences between HD and PD patients in the percentage of all parameters that were within K/DOQI recommended target ranges. The percentage of our HD patients who had Ca, P, and PTH levels within recommended target range was similar to those in previous reports. Conclusion: In our unit, the management of bone and mineral metabolism in HD and PD patients is still far short of meeting K/DOQI guidelines. These findings appear similar in HD and PD patients. Our findings resemble those reported in the literature.     

Leptin and resistin levels and their relationships with glucose metabolism in children with chronic renal insufficiency and undergoing dialysis

AIM: The aim of the present study is: (i) to evaluate the serum concentrations of leptin and resistin in the paediatric patients with chronic renal impairment (CRI), on haemodialysis (HD) and on peritoneal dialysis (PD) treatment; (ii) to examine the relationship between these hormones; and (iii) to investigate the possible influence of these hormones on the insulin resistance and sensitivity indexes as well as on serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) levels. METHODS: In total, 52 patients (15 patients with CRI, 24 PD patients and 13 HD patients) and 23 healthy age- and sex-matched control subjects were included in the present study. RESULTS: Homeostasis model assessment of insulin resistance (HOMA-IR) was higher than 2.5 in 47.1% of the patients. IGF-1 levels of patients with CRI, PD and HD patients were significantly lower than those in the controls (P < 0.001, P < 0.001, P < 0.001, respectively). The leptin levels of patients with CRI and on PD and HD treatment were significantly higher than the control group (P = 0.038, P = 0.002, P = 0.006, respectively). Similarly, serum resistin levels of patients with CRI and those of PD and HD patients were higher when compared with healthy controls (P = 0.037, P < 0.001, P = 0.005, respectively). CONCLUSION: Leptin and resistin levels were increased in the children with CRF; however, this elevation was not found to be associated with hyperinsulinism. Further studies to explain the mechanisms and consequences of the accumulation of these hormones in CRF may provide the therapeutical approach aiming to normalize their circulating levels.     

The absorption of iron is disturbed in recombinant human erythropoietin-treated peritoneal dialysis patients

Background. Intravenous iron supplementation is often necessary in recombinant human erythropoietin (r-HuEPO)-treated haemodialysis (HD) patients, but rarely in r-HuEPO-treated peritoneal dialysis (PD) patients. This may be due to differences in iron absorption or blood loss. Method. Iron absorption (whole-body counting after ingestion of a radiolabelled iron test dose) and iron metabolism were compared in eight iron-replete r-HuEPO-treated PD patients (serum ferritin 100-500 &mgr;g/l) and 68 healthy iron-replete controls (sufficient iron in bone marrow specimen). Results. Mucosal uptake (13.4±9.8), mucosal transfer (0.34±0.18) and iron retention (4.9±4.0) in PD patients was significantly lower than in controls (42.9±18.8%, P<0.0001, 0.63±0.18, P<0.0001, and 28.0±16.7%, P<0.0001). Conclusion. Iron absorption is impaired in PD patients, as we have shown previously for HD patients. One reason for higher iron needs in HD patients may be higher blood losses due to the dialysis procedure and blood sampling for laboratory tests.     

Assessment of female sexual function and quality of life in predialysis,peritoneal dialysis,hemodialysis, and renal transplant patients

Introduction  Chronic renal failure (CRF) and renal replacement treatments have a negative effect on sexual function and quality of life (QoL). The literature on female sexual dysfunction (FSD) in patients with CRF is limited. The aim of this study is to compare the sexual function and QoL in predialysis (PreD), dialysis, and transplant patients. Materials and methods  A total of 106 women including 21 PreD, 45 dialysis, 20 renal transplantation (Tx), and 20 control patients were enrolled in the study. The Female Sexual Function Index (FSFI) and SF-36 scales were used to assess all patients, and demographic and clinical variables were documented. The FSFI and QoL scale scores were compared among the groups. Results  The rates of FSD were 50, 81, 66.7, 75, and 50% in the control, PreD, peritoneal dialysis (PD), hemodialysis (HD) and Tx patients respectively. Total FSFI scores for desire, arousal and orgasm scores in the PreD group were significantly lower than those in Tx and control patients (P < 0.05). Physical components of QoL in CRF patients were significantly worse than in the control group (P < 0.0001). On logistic regression analysis, age, glucose and creatinine were significantly associated with FSD. Conclusion  This preliminary study documented that Tx is the most effective way to retain good sexual function in women, and a diagnosis of FSD should be made routinely in CRF patients.     

Vasoactive hormones in uraemic patients with chronic hypotension

Background. We evaluated the possible role of an imbalance between vasoconstrictor and vasodilator hormones in the pathophysiology of chronic hypotension in uraemia. Methods. Fourteen hypotensive haemodialysed patients, 14 normotensive haemodialysed patients, and 17 control subjects were included in this study. Plasma renin activity (PRA) and plasma levels of catecholamines, angiotensin II (AII), atrial natriuretic peptide (ANP), and arginine vasopressin (AVP) were measured. Results. The mean time on haemodialysis (HD) was longer in hypotensive patients than in normotensive patients (P <0.01). Catecholamine levels were higher in the whole group of HD patients than in controls (P <0.01). Catecholamine levels were higher in hypotensive patients than in normotensive patients, but the differences reached significance only for adrenaline (P <0.05). PRA and plasma AII levels were higher in hypotensive patients than in the other two groups (P <0.05), while no differences were observed between normotensive patients and controls. Plasma ANP and AVP levels were higher in HD patients than in controls (P <0.01), but there were no differences between hypotensive and normotensive patients. In HD patients, mean blood pressure inversely correlated with PRA (r=-0.9, P <0.01) and plasma AII levels (r=-0.80, P <0.01). Conclusion. Our results indicate that in HD patients with chronic hypotension there is an activation of the sympathetic and the renin-angiotensin systems. This activation is probably secondary in an attempt to compensate the vascular resistance to pressor stimuli reported in these patients.     

The Effects of Vitamin E-Coated Membrane Dialyzer Compared to Simvastatin in Patients on Chronic Hemodialysis

Background: We investigated the effects of the use of vitamin E-coated membrane (VEM) dialyzer in comparison to simvastatin on markers of chronic inflammation, oxidative stress, and endothelial cell apoptosis in ten patients on chronic hemodialysis (HD), aiming at distinguishing the different treatment effects and their time sequence on these pathogenetic routes. Methods: Ten HD patients were sequentially submitted to a 6-month treatment with the use of VEM and 10 mg of simvastatin daily, interrupted by a 3-month washout period. At baseline, at 3, and 6 months of each trial, serum C-reactive protein (CRP), apolipoprotein (Apo) A1 and B, lipoprotein-a [Lp(a)], high-sensitivity interleukin-6 (hsIL-6), monocyte chemoattractant protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), soluble Fas (sFas), soluble Fas ligand (sFasL), and plasma oxidized low-density lipoproteins (oxLDL) levels were determined. Results: VEM treatment resulted in a significant decrease in CRP, IL-6, sICAM-1 at 3 months, and oxLDL at 6 months, compared to baseline. Simvastatin resulted in a significant decrease in CRP, which correlated with decreases in both total (r = 0.87, p < 0.05) and low-density lipoprotein cholesterol, IL-6, sICAM-1, sVCAM-1, oxLDL, and sFas at 6 months, compared to baseline. Simvastatin effects on sVCAM-1 (mean difference = 652 ng/mL; 95% CI = 294 to 2686; p < 0.05) and sFas (mean difference = 1284 pg/mL; 95% CI = 510 to 1910; p < 0.05) differed significantly from the corresponding VEM effects. Conclusions: The 6-month use of VEM resulted in more direct and immediate anti-inflammatory effects compared with those caused by the 6-month treatment with simvastatin. Simvastatin caused a more intense decrease in the markers of inflammation, which was in part correlated with its lipid-lowering effects.     

Nutritional assessment of children on haemodialysis: value of IGF-I, TNF-&agr; and IL-1{beta}

Background: Protein-energy malnutrition (PEM) is associated with increased morbidity and mortality in haemodialysis (HD) patients. Insulin-like growth factor I (IGF-I) has proved to be a sensitive marker of malnutrition, while interleukin-1 (IL-1{beta}) and tumour necrosis factor (TNF) have been found to be raised in catabolic states. Methods: We have investigated the nutritional status of 17 chronic renal failure (CRF) paediatric patients (8 boys, 9 girls) on maintenance HD. Eight predialysis CRF children (5 boys and 3 girls; mean creatinine 5.1±3.2 mg/dl) and 10 healthy children served as control groups. PEM was defined according to anthropometric measurements (triceps skinfold thickness (TST), mid-arm circumference (MAC), and mid-arm muscle circumference (MAMC). These were correlated with serum IGF-I, IL-1 TNF-&agr; transferrin, and albumin (all sampled before the HD session). Results: In the HD group, TST was reduced in 41.2% of the patients, whereas MAC and MAMC were reduced in 82.4 and 76.5% respectively. TST was depleted in only one of the predialysis CRF children. The degree of reduction in MAC and MAMC were 62.5 and 62.5% respectively. Median serum IGF-I level was decreased in both HD and predialysis CRF patients (205.1 interquartile range (IQR) 194.4 &mgr;g/l and 258.8 IQR 155.0 &mgr;g/l respectively) compared to the healthy children (418.0 IQR 310.5&mgr;g/l) (P=0.0009 and P=0.01 respectively). Within the HD group, IGF-I levels were lower in patients with malnutrition defined according to TST (145.0 IQR 125.5 &mgr;g/l) compared to children with normal TST (201.2 IQR 218.8 &mgr;g.l) (P=0.05). IGF-I levels of the HD patients with malnutrition according to TST was also lower than predialysis CRF patients and healthy children (P=0.04 and P=0.002 respectively). Serum IL-1{beta} was undetectable in all groups. Median serum TNF-&agr; levels were higher in HD and predialysis CRF patients compared to healthy children, albeit statistically insignificant. There was no correlation between TNF-&agr;, transferrin or albumin and anthropometric parameters. Conclusions: Our results support the high prevalence of malnutrition in CRF children, which becomes more pronounced when treatment by HD is initiated. We suggest that determination of IGF-I levels in childhood HD patients in conjunction with anthropometric measurements is useful for identification of malnutrition. We have not been able to demonstrate the catabolic effects of cytokines on this state of protein-energy malnutrition.     

Intestinal bacteria-derived putrefactants in chronic renal failure

Background. Phenols and indoles are fermentation products and putrefactants of intestinal bacterial origin. They present a problem in chronic renal failure and hemodialysis patients because they accumulate in the body as uremic toxins. Methods. A comparative study was performed in groups of patients with chronic renal failure (CRF) before the initiation of dialysis, hemodialysis patients (HD), and healthy adults to investigate changes in intestinal flora and to measure the blood levels of uremic toxins. Results. The level of Escherichia coli was significantly increased in the CRF and HD groups compared with the healthy controls (P= 0.02, controls vs CRF before dialysis; P= 0.0014, controls vs HD). Fecal concentrations of phenol and scatole were most highly elevated in the HD group, and the difference between the CRF and HD groups was significant (P= 0.02 for phenol; P= 0.01 for scatole). Serum concentrations of phenol, p-cresol, and indican were significantly elevated in the CRF group (P= 0.01; P= 0.008; and P < 0.0001 vs controls, respectively). For indican, a correlation was found between fecal and serum concentrations only in the HD group (correlation coefficient of 0.821; P= 0.04). In the CRF group, a correlation was obtained between the urine and serum concentrations of phenol and p-cresol (0.852, P= 0.01; 0.758, P= 0.02, respectively). A correlation was also found between the serum concentrations of indican and serum creatinine (SCr) (0.610; P= 0.004) and β2-microglobulin (β2-MG) (0.739; P= 0.005). Conclusions. An abnormal balance of intestinal bacterial flora and increased intestinal bacteria-derived putrefactants were observed in the CRF group. The increased concentration of toxins with renal sclerosing effects, such as indican, may contribute to further deterioration of renal function. Received: September 14, 2001 / Accepted: February 13, 2002     

Comparison of novel risk factors for cardiovascular disease between hemodialysis patients with and without protein-energy wasting

Purpose

The present study was designed to compare novel risk factors for cardiovascular diseases (CVD) between hemodialysis (HD) patients with or without protein-energy wasting (PEW) for determining novel risk factors for CVD in HD patients with PEW.

Methods

In this cross-sectional study, 291 HD patients were randomly selected from among 2,302 adult HD patients in Tehran hemodialysis centers. The presence of PEW in HD patients was determined by subjective global assessment. In addition, 4 mL blood was obtained before dialysis and analyzed for serum concentrations of novel risk factors for CVD, including C-reactive protein (CRP), soluble intercellular adhesion molecule type 1 (sICAM-1), soluble vascular cell adhesion molecule type 1 (sVCAM-1), sE-selectin, malondialdehyde (MDA), nitric oxide (NO), endothelin-1 and lipoprotein (a) [Lp (a)].

Results

Serum CRP and sICAM-1 were significantly higher in HD patients with PEW as compared to those without PEW (P < 0.01), whereas there were no significant differences in serum sVCAM-1, sE-selectin, MDA, NO, endothelin-1 and Lp (a) between the two groups. Serum CRP and sICAM-1 were significantly higher in HD patients with PEW type IIa and IIb than in those with PEW type I (P < 0.01).

Conclusion

The present study indicates that serum CRP and sICAM-1, as two CVD risk factors, increase in HD patients with PEW as compared to those without PEW and these increases occur in HD patients with PEW type IIa and IIb who have inflammation.     

Clinical morbidity in pediatric dialysis patients: data from the Network 1 Clinical Indicators Project

The Health Care Financing Administration (HCFA) has gathered clinical data on end stage renal disease (ESRD) patients since 1994, but details are only available on patients ≥18 years. In this report, we present morbidity data collected prospectively over 12 months from all children (1–18 years) maintained on either hemodialysis (HD) or peritoneal dialysis (PD) within the six-state New England area. During this year, 17 observations were recorded on 14 HD patients (age 13.4± 11.3 years) and 36 observations were made on 25 PD patients (age 11.5±4.8 years; mean ± SD). These patients were generally highly functional, attending school at least part time in nearly all cases. Dialysis adequacy index (DAI), defined as the delivered KT/V divided by DOQI guideline values, indicated that patients were well dialyzed (HD 1.41±0.1 and PD 1.10±0.1; mean ± SE). When all dialysis patients were grouped and analyzed, the DAI did not correlate with number of hospitalizations, degree of anemia, serum albumin, or type of dialysis. The number of hospitalizations were greater the younger the patient (P<0.01). The need for antihypertensive medications was higher in the children maintained on HD (94%) compared to children on PD (58%) (P<0.01). Lastly, while serum ferritin did not correlate with serum iron, hematocrit or Epo dosage, it was inversely related to serum albumin (P<0.03). We conclude that, in children, (1) exceeding suggested dialysis adequacy may not improve patient morbidity, (2) the need for antihypertensive medications appears greater in children maintained on HD, and (3) inflammation may play a role in determining serum albumin independent of nutrition. Received: 3 April 2001 / Revised: 26 June 2001 / Accepted: 10 July 2001