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Sleeping disorders are very common in patients with chronic kidney disease on dialysis (CKD5D) and are an emerging risk factor able to predict mortality. Parathyroid hormone (PTH) although considered a pivotal uremic toxin has rarely been associated with sleep disorders in uremia. In a study from our laboratory PTH concentrations failed to distinguish patients with sleep disorders from those without. In a study performed by Chou et al a 97% prevalence of insomnia was found in patients undergoing hemodialysis requiring parathyroidectomy. Surgery reduced PTH and increased sleeping hours within 3 months. The aim of this study was to study the effects of parathyroidectomy on the sleep disorders of insomniacs on maintenance hemodialysis. The study was performed in 16 insomniac patients on maintenance hemodialysis who successfully underwent surgery with autotransplantation of autologous parathyroid tissue (40 mg) under the skin of the forearm. Patients (5 F and 11 M) were studied from 1 month before surgery to 1 year after. Sleep disorders were assessed by means of a 27-item questionnaire--Sleep Disorder questionnaire (SDQ)--that identified sleeping disorders according to Diagnostic and Statistical Manual of Mental Disorders - IV Edition (DSM-IV) criteria. The Charlson Comorbidity Index (CCI) was also measured along with systolic and diastolic blood pressure, Hb, PTH, Ca, P. A 95.5% prevalence of sleep disorders was found pre operatively. Patients slept 4.90+/-1.2 hours, Ca averaged 10.09+/-0.54 mg/dL, Phosphate 5.5+/-1.93, CCI 9.8+/-1.1, PTH 1498+/-498 ng/mL. After 1 year follow-up 2 out 16 patients had normal sleep, 6 out 16 patients had subclinical sleep disorders and 8 remained insomniacs (p=0.008, Mc Nemar Test for paired data, insomniacs vs. no disturbance + subclinical disorders). Sleeping hours increased up to 6.0+/-1.24 (p<0.05), PTH was normalized, the Charlson Comorbidity Index was reduced (p<0.05) as were plasma calcium and phosphate (p<0.01). The study indicates that insomnia in patients with severe hyperparathyroidism on maintenance hemodialysis is ameliorated by parathyroidectomy.

Background: During haemodialysis the blood-membrane contact causes a release of platelet granule content, which contains platelet-derived growth factor AB (PDGF-AB). In view of the potential role of this in altering biocompatibility during haemodialysis, we evaluated the intra- and post-dialytic changes in PDGF-AB serum levels during haemodialysis sessions performed with cellulose diacetate (CDA) and polysulfone (PS) membranes respectively., Methods: PDGF-AB, platelet factor 4 (PF4), beta thromboglobulin (betaTG), and mean platelet volume (MPV) levels were determined in 30 patients, each of whom underwent six dialysis sessions: three with a CDA and three with a PS membrane. Blood samples were taken at times 0, 15, 30, 120, 180, and 240 min during dialysis and at 1, 4, and 20 h after the end of the session. Statistical analysis was performed using a one-way ANOVA and Student's t test., Results: PDGF-AB at 15 min was increased to +41+/-9% with CDA vs +20+/-5% with PS (P<0.001) from the T0 values, and at 120 min it was +19+/-8% with CDA vs -25+/-9% with PS (P<0.001) from T0 levels. At 240 min it was +95+/-14% with CDA vs +49+/-15% with PS (P<0.001) from the T0 values, returning to basal only 20 h after the end of the session. betaTG at 15 min was +60+/-8% for CDA vs +24+/-7.5% for PS (P<0.001) from the T0 values. PF4 showed a similar trend to betaTG. MPV at 30 min from the start of dialysis was 7.4+/-0.3 fl with CDA and 8+/-0.3 fl with PS (P<0.001), and at 240 min MPV was 7.9+/-0.3 fl with CDA and 8.4+/-0.3 fl with PS (P<0.001)., Conclusions: Platelet activation and platelet release reactions are lower with PS than with CDA membranes. PDGF-AB, released during and after dialysis, represents a clear biocompatibility marker. Its slow return to basal values and its action on vascular cells make it a potential risk factor for atherosclerosis in uraemic patients.

Background: During haemodialysis blood membrane contact causes the release of the content of platelet alpha-granules, which contain platelet-derived growth factor (PDGF). In view of its possible role in accelerated atherosclerotic processes, we evaluated the intra- and post-dialytic changes in PDGF-AB serum levels during haemodialysis sessions performed using a cellulosic membrane., Methods: Using the ELISA method, PDGF-AB, platelet factor-4 (PF4) and beta-thromboglobulin (beta-TG) levels were determined in peripheral blood, as well as in arterial and venous haemodialyser lines, in 10 patients each of whom underwent five consecutive dialysis sessions with a CU membrane. Blood samples were taken at 0, 15, 30, 60, 120, 180 and 240 min during dialysis and at 1, 4 and 20 h after the end of the session. In the same group of patients the levels of the same molecules were also determined after a heparin bolus injection of 4500 IU, blood samples were taken at 0, 15 and 30 min after injection of the bolus., Results: PDGF-AB serum levels increased, remained consistently high during the haemodialysis session (in particular +134+/-20% after 30 min, P<0.001, and +140+/-5% after 240 min, P<0.001) and returned to basal values only after 20 h following the end of the session. PF4 and beta-TG showed a similar trend to PDGF. The heparin bolus injection caused only a small increase (+15+/-5% at 30 min) in PDGF-AB serum levels., Conclusions: PDGF-AB is released during dialysis mainly as consequence of the blood-membrane contact and it returns only slowly to basal values.

The present study reports on a biological model based on fibroblast proliferation applied to 3 different types of flat-plate dialysis membrane, in order to ascertain whether the artificial materials currently used in hemodialysis cause in vitro cellular proliferation. The study plan we followed involved plate membrane isolation from non-used dialyzers and used dialyzers, observed through scanning electron microscopy (SEM) both before and after testing with human fibroblasts by means of cell culture. Fibroblast growth was assessed by phase contrast light microscopy examination and cytometric DNA content evaluation. Our investigations proved that the artificial materials we considered interact with fibroblast cultures. Noticeable proliferative response was observed both after contact with unused material and on mediation by the protein layer absorbed on the membrane surface at the end of dialysis sessions. In this last case fibroblast proliferative activity appeared higher than that observed with unused membranes, showing that the soluble molecules entrapped in the protein layer appeared able to exert a biological activity even in vitro tests.

Cellular immunity represents an interesting biological model for biocompatibility evaluation of artificial materials owing to its sensitivity to contact with the external environment and its capability of modulating response reactions to foreign agents. Advanced methodologies such as flow cytometry and the immunoenzyme techniques in particular have given new insights into lymphocyte structure and functions, enabling analysis of the in vivo modification of these cells. By means of these sophisticated techniques we investigated lymphocyte activation and proliferation during one single haemodialysis session. Findings clearly show that increases in HLA antigen density (class I and II), DNA synthesis, and interleukin-2 receptor serum concentration (Il-2R) take place during the dialysis procedure, and reach their maximum during the first hour of extracorporeal circulation. The relationship between dialysis procedure and cellular immunity appears noticeable and is of potential value in the evaluation and quantification of the biocompatibility of different dialysis membranes.