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Biomedical subjects

R Selgas

Publications and source records attributed to R Selgas.

At least 19 recordsLinked to original sources

Pegylated interferon-alpha2a kinetics during experimental haemodialysis: impact of permeability and pore size of dialysers.

BACKGROUND: Therapeutics in end-stage renal disease (ESRD) patients undergoing haemodialysis (HD) has to consider potential drug clearance during the dialysis procedure. Pegylated interferon-alpha (PEG-IFN-alpha), a middle-size protein drug active against viral hepatitis, allows convenient once-weekly dosing due to prolonged plasma half-life. AIM: To investigate the impact of permeability and dialyser pore size on PEG-IFN-alpha blood levels during experimental HD. METHODS: Polymethylmetacrylate (PMMA) membrane 1.6 m2 dialysers with three different permeabilities/pore sizes were selected. RESULTS: A 40 kDa PEG-IFN-alpha2a (PEGASYS) was not cleared (< 5%) through low-flux/small pore size (25 A;B3A) and high-flux/middle-large pore size (60 A;BKP) dialysers, and was partially (approximately 15%) through intermediate permeability/large pore size (100 A;BKF) dialysers. In contrast, unmodified 17 kDa IFN-alpha2a(Roferon-A) was removed (65%-95%) through BKP or BKF, but not B3A, PMMA dialysers. Moreover, 12 kDa PEG-IFN-alpha2b(PegIntron) was cleared (40%-80%) through PMMA dialysers with pore sizes > or = 60 angstroms. When B3A or BKP were replaced every hour PEG-IFN-alpha2a plasma levels remained constant throughout three experimental-HD-sessions, but PEG-IFN-alpha2b was cleared partially every BKP replacement. Porosity differ among high-flux dialysers. Neither PEG-IFN-alpha2a nor PEG-IFN-alpha2b were removed after three HD sessions through (27/31/33 A) pore size polysulphone dialysers. Although PEG-IFN-alpha2a was not cleared through middle pore-size (43 A/AN69ST) polyacrylonitrile dialyser, PEG-IFN-alpha2b was partially removed. CONCLUSIONS: The pharmacokinetics of Peg-IFN-alpha may vary in a patient on dialysis.

Antiviral Agents↗

[Evaluation of osteodystrophy parameters in a pre-dialysis unit].

A cross-sectional study was developed with 100 of the first-time pre-dialysis patients visiting the Princesa University Hospital's Advanced Chronic Kidney Disease (ACKD) unit, with the aim of analysing various parameters of osteodystrophy at this time. Parameters evaluated were: age, gender, renal function, osteodystrophy serum parameters, comorbidity index (ICED) and the patients' origin to establish correlations between these parameters. Mean iPTH levels were higher irrespective of the patients' origin, and were significantly higher in men than in women, the former also having poorer renal function and higher comorbidity score. The mean levels of calcium, phosphorous, alkaline phosphatase and CO2 did not justify this rise in iPTH. Nutritional parameters NPNA and albumin were adequate in spite of ageing. At early stages of ESRD, iPTH could be elevated and ACKD units play an important part its early detection and subsequent treatment.

Aged↗

[Influence of different pharmacological agents in the ex vivo proliferation of mesothelial cells obtained from the peritoneal effluent of patients treated with peritoneal dialysis].

UNLABELLED: Mesothelial cells (MC) are the first peritoneal membrane barrier in contact with dialysate. The aim of this study was to analyze the in vitro capacity of different pharmacological agents to modify the ex vivo proliferation of MC obtained from the peritoneal effluent of patients treated with peritoneal dialysis (PD). MATERIAL AND METHODS: Thirty cultures of MC taken from nocturnal peritoneal effluent were performed. After identification, MC are subcultured in 24 multi-well plates, adding the different exogenous agents. Proliferative capacity and cell morphology were estimated on day 16th of culture. The agents evaluated were insulin, IGF-1, tamoxifen, labetalol, carvedilol, enalapril and losartan. RESULTS: Insulin shows a dose-dependent effect on MC growth, with a limit that is stimulated by the addition of fetal bovine serum (FBS). Concentrations higher than 100 micrograms/ml, are not associated with further growth, even with cell damage. In contrast, the wide range of IGF-1 dose used did not affect to MC proliferation. Tamoxifen causes negative effects on MC growth just a very high doses, not resembling doses in clinical practice. Labetalol does not modify MC proliferation used under therapeutic calculated range. However, concentrations higher than 40 micrograms/ml showed a negative influence on growth, behaving as lethal doses that over 100 micrograms/ml. The addition of FBS attenuates this effect. These effects were very similar to that caused by carvedilol addition. Enalapril and losartan act as antiproliferative agents for MC. This effect is potentiated with angiotensin II, reaching lethal concentrations increasing the dose. In conclusion, mesothelial cell growth ex vivo taken from nocturnal peritoneal effluent on PD patients is an useful tool to explore the effects of any pharmacological agent on the biology of the cell of the peritoneum. The agents used had any influence in the proliferation capacity of mesothelial cells.

Ascitic Fluid↗

[Prognostic significance of programmed dialysis in patients who initiate renal substitutive treatment. Multicenter study in Spain].

BACKGROUND: The aim of our study was to analyse patient characteristics, mortality and costs, all of them in relation to whether starting dialysis was planned or unplanned. METHODS: A total of 362 patients (227 male and 135 female) from five hospitals of the National Health System, who were started on chronic renal replacement therapy (RRT) during 1996 and 1997 were included. Patients who were started on RRT after acute renal failure were excluded. We carried out a retrospective analysis of the demographic characteristics, patients' conditions at the time of initiating dialysis and outcome and costs at six and thirty-six months of treatment. Patients were classified as planned (PL-D) or unplanned dialysis (UNPL-D), depending on whether or not the patient had a vascular or peritoneal access ready to use for initiating RRT. RESULTS: One hundred and eighty-six patients (51.4%) started on dialysis in the PL-D group whereas 176 (48.6%) did it as UNPL-D. In this latter group, 135 (37.3% of the total) had previously been monitored by a nephrologist, and 41 (11.3%) initiated dialysis without previous nephrological follow-up. UNPL-D was associated with older age (p < 0.001), non-nephrological follow-up (p < 0.001), diabetes (34.7% vs 22.6%) (p = 0.011), haemodialysis as a first mode of RRT (94.9 vs 81.7%) (p < 0.001), higher comorbidity risk (p < 0.001), dialysis initiation with uraemic symptoms or fluid overload (p < 0.001), increased blood transfusion requirement (p < 0.001) and lower serum albumin (p < 0.001), creatinine clearance (p < 0.001), haemoglobin concentration (p < 0.001), and weight (p = 0.002). In the PL-D group the main primary renal diseases were glomerular and polycystic disease, whereas interstitial and diabetic nephropathy were higher in UNPL-D group (p = 0.005). Multivariate analysis showed that previous non nephrological follow-up, uraemic symptoms, interstitial nephritis as primary renal disease correlated with UNPL-D initiation, and it was followed by choosing haemodialysis as first RRT. UNPL-D was also associated with increased number of days of hospitalization at the initiation of dialysis, and during the first 6 months (p < 0.001), increase of hospitalization days (p = 0.009), and increased 6-month-mortality (10.2% vs 3.2%) (p = 0.015, log rank test), and three-year mortality (24.2 vs 36.9%) (p = 0.006, log rank test). The costs of UNPL-D were fivefold that of the PL-D group. CONCLUSION: UNPL-D has been associated with worse overall clinical conditions at the initiation of chronic replacement therapy, choosing haemodialysis as first RRT, increased morbi-mortality and subsequent increase of costs.

Adolescent↗

[Use of icodextrin for diurnal exchange in patients undergoing automatic peritoneal dialysis. Comparison with glucose solutions].

Icodextrin (IC) is an osmotic agent that produces sustained ultrafiltration (UF) during long dwell time periods in peritoneal dialysis patients. The aim of this study was to evaluate the effects of 7.5% IC for the diurnal exchange in automated peritoneal dialysis (APD) patients and to compare them with that of 2.27% glucose solutions. Seventeen patients treated on APD during 13.9 +/- 12.7 months were included. The study was divided into three eight weeks phases. During the baseline period patients used 2.27% glucose for the daytime, second, IC 7.5% was prescribed for the day-exchange, and finally 2.27% glucose solution was used for the last eight weeks. Daytime UF increased in all patients during IC use (-53 +/- 22 to 270 +/- 304 ml/day, p < 0.01). Patients with higher peritoneal permeability capacity obtained more benefits. Daytime urea KT/V and weekly creatinine clearance (WCC) augmented significantly during IC use, but the increase of weekly urea KT/V and WCC was not significant (2.18 +/- 0.45 to 2.26 +/- 0.41 and 62.7 +/- 18 to 66.6 +/- 15 l/week/1.73 m2; respectively). On IC, nightly glucose load significantly decreased (289 +/- 82 to 266 +/- 94 g, p < 0.05), returning to previous value after withdrawal. Plasma osmolality did not change, although plasma sodium levels decreased during IC use (140 +/- 3 to 136 +/- 2, p < 0.001). Serum amylase levels significantly declined during IC use (279 +/- 151 to 29 +/- 9 U/l), returning to previous values after transfer to glucose. Peritoneal function transport parameters and peritoneal protein losses did not change. IC metabolite plasma levels increased during the use of this solution, returning to previous values after withdrawal. In conclusion, IC dialysate is an excellent alternative to glucose dialysate for the day-exchange in APD patients. Daytime UF increased in all patients, but those with higher peritoneal permeability capacity obtained more benefits. The decrease of the glucose peritoneal load overnight and the reduction for more than 50% of exposure time of the peritoneal membrane to glucose solutions, probably make IC solution a more biocompatible fluid.

Adult↗

Comparisons of hemodialysis and CAPD in patients over 65 years of age: a meta-analysis.

This meta-analysis had the aim of studying the available studies on comparison between Hemodialysis and Peritoneal Dialysis in the elderly. The final objective was to reach, if possible, evidence for potential differences. In the case that no differences could be demonstrated, contribute to accept that HD and PD are similar techniques to be offered to elderly people requiring dialysis. The question formulated was this: Do we have adequately contrasted data on results for survival, hospitalization rate, quality of life and morbidity on hemodialysis and peritoneal dialysis in the elderly (more than 65 years old)? As data sources we selected eight papers that compared the general results of these two dialysis techniques. Different elements were considered in this selection because none reached the two first levels in the hierarchy of sources of evidence, and only two reached the third level--that of prospective studies; this is because an oral presentation of data has been included in a meta-analysis. Another four papers--uni- or multicenter retrospective studies compared the results obtained with PD and HD. The remaining two papers--reports from nationwide registries that compare of mortality rates, adjusted for co-morbid conditions and age, present specific results on groups of elderly patients. Three papers compare particular aspects of the two techniques, including nutritional status, psychiatric and psychosocial aspects and rehabilitation, in this case comparing PD with home hemodialysis patients. Finally, we have included the opinions of healthy elderly people on dialysis issues. This meta-analysis of these different studies suggests that the mortality and hospitalization rate of elderly people treated by PD is similar to that of similar people treated by HD. In consequence, we have no reasons to select either therapy on behalf of the patient. The nephrologist should consider and inform the patient and family about the relative advantages and disadvantages of both techniques and tailor dialysis technique choice to the specific individual to assure the best results. Local circumstances should also be considered.

Aged↗

Hemodialysis vascular assessment by an ultrasound dilution method (transonic) in patients older than 65 years.

UNLABELLED: Malfunction of vascular access is one of the most frequent causes of morbidity and mortality in hemodialysis patients (HD). Early diagnosis makes possible the most frequent vascular access (VA) used in HD patients. The arteriovenous fistula (AVF), both autologous or heterologous, is the appropriate correction by an interventional radiologist or by surgery, before thrombosis appears. For this purpose, a follow-up of VA is mandatory. New technologies offer non-invasive methods for this purpose. In HD sessions ultrasound 'on line' and ultrasound-dilution techniques permit us to monitor vascular access in HD patients. Also transonic technology has been validated for this purpose, although the limitations of its use among elderly patients is unknown. Using the Transonic HD01 monitor, we studied vascular access in 45 patients in HD older than 65 years, and compared them with 47 patients who were younger than 65 years. The parameters analyzed were: effective flow Qt, recirculation, venous pressure and access flow. We found no significant differences between these parameters but in both groups found that the effective flow measure by Transonic was lower than that measured by a blood pump. Both groups contained patients who had no recirculation but had an access flow that was lower than expected. To rule out stenosis of VA in those patients, we performed an Eco Doppler confirming that all patients had stenosis. With this method, one can determines the access flow and thus predicts the possibility of future thrombosis. CONCLUSION: Our data confirm that one can evaluate VA in patients older than 65 years with Transonic HD01 monitor, and also in patients younger than 65 years. Due to the special characteristics of the vessels in elderly patients, Transonic HD01 monitor is a good method by which to monitor VA in them.

Aged↗

Cultures of human osteoblastic cells from dialysis patients: influence of bone turnover rate on in vitro selection of interleukin-6 and osteoblastic cell makers.

The factors contributing to renal osteodystrophy are still incompletely characterized. A variety of cytokines and growth factors appear to have ill-defined roles in this disease. Our aim is to compare osteoblastic cell growth and different osteoblastic markers in vitro with histomorphometric bone parameters and some serum bone-turnover markers in vivo in dialysis patients with either high- (HTBD) or low-turnover (LTBD) bone disease. Six patients were diagnosed to have LTBD, and another five patients, HTBD. Intact parathyroid hormone (PTH) and osteocalcin (OC) levels in serum were greater in patients with HTBD than in those with LTBD. Osteoblastic cells isolated from iliac crest biopsy specimens were grown in culture medium for different times up to 13 days. Osteoblastic cell growth (cell number and area under the cell growth curve) was greater in patients with HTBD than in those with LTBD. Static and dynamic bone formation parameters correlated with serum PTH levels. No correlation was found between PTH and osteoblastic cell proliferation. OC, C-terminal type I procollagen, and alkaline phosphatase osteoblastic secretion in vitro were similar in the HTBD and LTBD groups. However, interleukin-6 (IL-6) secretion was greater in cells isolated from patients with LTBD. Our results indicate that osteoblastic cell growth and osteoblastic IL-6 secretion are related to bone turnover in patients with osteodystrophy. Our findings support the hypothesis that factors other than PTH level might have an important role in affecting osteoblastic function in renal osteodystrophy.

Adult↗

Anorexia in end-stage renal disease: pathophysiology and treatment.

Anorexia is a frequent complication of uraemic syndrome, which contributes to malnutrition in dialysis patients. Uraemic anorexia has been associated with many factors. This paper reviews the current knowledge about mechanisms responsible for uraemic anorexia, the treatments and new drugs used to control the loss of appetite. Traditionally, anorexia in dialysis patients has been considered as a sign of uraemic toxicity, therefore, two hypotheses have been proposed, the 'middle molecule' and 'peak-concentration' hypotheses, both of which are still unproved. Recently, our group proposed the tryptophan-serotonin hypothesis, which is based on a disorder in the amino acid profile acquired in the uraemic status. This is characterised by low concentrations of large neutral and branched chain amino acids (LNAA/BCAA) in the cerebrospinal fluid. This situation permits a high level of tryptophan transport across the blood-brain barrier, causing an increase in the synthesis of serotonin (responsible for appetite inhibition). There are two main treatment targets for anorexia in dialysis patients. The first is to decrease the free plasma tryptophan concentration and transport across the blood brain barrier to the cerebrospinal fluid, thus decreasing the intracerebral serotonin levels. Nutritional formulae enriched with LNAA and BCAA have this effect. Secondly, plasma levels of cytokines with cachectin effect (TNF-alpha), should be decreased. This also induces a decrease in LNAA and BCAA levels. In this group are megestrol acetate, anti-TNF-alpha antibodies, thalidomide, pentoxifyilline, n-3 fatty acids and possibly nandrolone decanoate. Additionally, other targets should be explored including antagonists of cholecystokinin (a potent anorexigen retained by renal failure), analogues of neuropeptide Y (the most potent orexigen), cannabinoids, cyproheptadine, hydrazine sulfate. In conclusion, uraemic anorexia is a complex complication associated with malnutrition, high morbidity and mortality. The pharmacological treatment should address key points in the pathogenesis of uraemic anorexia, reducing intra-cerebral concentration of serotonin with LNAA/BCAA oral diet formulae and the plasma levels of pro-inflammatory molecules. Others forms of treatment should also be explored.

Anorexia↗

Prevalence of hepatitis B, hepatitis C, GB virus C/hepatitis G and TT viruses in predialysis and hemodialysis patients.

Patients with chronic renal failure on hemodialysis have a high risk of infections with viruses such as hepatitis B (HBV), hepatitis C (HCV), GB virus C/hepatitis G (GBV-C/HGV) and TT (TTV) viruses. The prevalence of HBV, HCV, GBV-C/HGV and TTV in patients with chronic renal failure who are on conservative management before entering into a hemodialysis program (predialysis) in comparison with hemodialyzed patients was studied to elucidate whether the high prevalence of these viruses is influenced by that observed in the predialysis stage. The presence of hepatitis B virus surface antigen (HBsAg), HCV RNA, GBV-C/HGV RNA and TTV DNA was analyzed in sera from 80 patients with chronic renal failure (35 on predialysis and 45 on hemodialysis). HBsAg, HCV RNA, GBV-C/HGV RNA and TTV DNA were detected in one (2.8%), six (17.1%), eight (22.5%) and 16 (45.7%) of the 35 patients on predialysis. Two (5.7%) of these patients were coinfected with HCV and GBV-C/HGV, whereas six (17.1%) had GBV-C/HGV and TTV coinfection. In the 45 hemodialyzed patients, HBsAg, HCV RNA, GBV-C/HGV RNA and TTV DNA were detected in one (2.2%), two (4.4%), seven (15.5%) and 26 (57.7%). One (2.2%) patient had HBV and TTV coinfection, two (4.4%) HCV and TTV coinfection whereas four (8.8%) were coinfected with GBV-C/HGV and TTV. No differences regarding age, gender, previous surgery and number of transfusions were found between infected and uninfected patients within and between both groups. In conclusion, the prevalence of the viruses studied in predialysis may influence their prevalence in dialysis units.

Aged↗

Alpha replacement method for displaced peritoneal catheter: a simple and effective maneuver.

Displacement of the peritoneal catheter tip is one of the most frequent causes of catheter malfunction. As a consequence, appropriate peritoneal effluent drainage is impossible. Alternatives to catheter exchange or invasive abdominal intervention did not appear until the alpha maneuver was described by Yoshihara et al. We review our experience with this maneuver over the last 7 years. We used the alpha maneuver in 24 peritoneal dialysis (PD) patients (13 men and 11 women) with a mean age of 52 +/- 16 years. Some patients required several repeat procedures (total procedures: 32). The mean time between placement of the catheter and performance of the alpha maneuver was 6.5 +/- 7.9 months. In all patients, the technique was indicated for problems with peritoneal effluent drainage, after verification of catheter tip displacement by radiologic examination. In 6 patients, the initial maneuver was unsuccessful and had to be repeated. The first maneuver was effective in 11 of 24 cases (46%) and unsuccessful in the other 13 (54%). No differences in sex, renal disease, or age were seen between the two groups. The mean time between catheter placement and tip displacement detection was significantly lower in the cases of ineffective maneuver (2.7 +/- 4.3 months) than in those that met with success (10.8 +/- 9 months). In other words, 84% of unsuccessful maneuvers were performed in the first 3 months of catheter life. Of the 11 patients successfully treated, 6 continued on PD for 14.7 +/- 6.3 months. Two other patients were transplanted with normal-functioning catheters, and two more left PD (after 10 and 17 months) for reasons unrelated to the catheter. One patient required a catheter change owing to breakdown in the Silastic after disruption by the metallic guide, which perforated the catheter wall. The 13 ineffective maneuvers involved 7 omentum entrapments, 1 procedure that was repeated effectively 15 days later, and 5 definite failures requiring catheter change. The failure rate may therefore be considered to be 20.8%, taking into consideration that omentum entrapment should not be an indication for the procedure. We conclude that the alpha maneuver for a displaced peritoneal catheter is a simple and effective procedure that can be applied at the patient's bedside. In consequence, it should be the technique of first choice in these situations. Only when the alpha maneuver fails should invasive methods, including catheter change, be considered.

Catheterization↗

Effect of bicarbonate/lactate peritoneal dialysis solutions on human mesothelial cell proliferation ex vivo.

Peritoneal membrane suffers structural and functional changes over time on peritoneal dialysis (PD)--in part, owing to the dialysis solutions currently used. Low pH seems to be an important element associated with solution bioincompatibility. Bicarbonate-containing fluids open new perspectives on this issue. The present study compared the effects of bicarbonate/lactate (Bic/Lac) solution (25 mmol/L bicarbonate, 15 mmol/L lactate) and lactate (Lac) solution (40 mmol/L lactate) on mesothelial cell (MC) growth in culture. Eight stable PD patients were asked to collect peritoneal effluent from an 8-hour dwell on two separate days, within an interval shorter than one week. For the first dwell, Lac solution was infused; for the second dwell, Bic/Lac solution was instilled. Human MCs were isolated from the effluent, seeded in 25-cm2 tissue culture flasks, and grown ex vivo. Morphology of the cells was also evaluated. In all effluents, MCs were present in mean amounts of 26,939 +/- 21,267 cells (Bic/Lac) and 25,986 +/- 15,286 cells [Lac, p = nonsignificant (NS)]. Morphology of the MCs was similar with both solutions (87.5% typical). After initial culture, MCs from 6 patients using Bic/Lac (75%) and 3 patients using Lac (37.5%) reached confluence. At this time, the number of MCs from the 3 patients who showed MC growth with both solutions was slightly higher with Bic/Lac-buffered fluid (Lac: 1,154,125 +/- 213,333 cells; Bic/Lac: 1,198,291 +/- 806,713 cells). To summarize: 3 patients showed MC growth under both solutions; 3 patients showed MC growth only under Bic/Lac solution; and 2 patients showed no MC growth at all. After cells were seeded in 24-well plates, the MC growth curve was performed in 4 cases of Bic/Lac solution use and in 3 cases of Lac solution use. Although no significant differences were observed between the solutions, the final number of MCs obtained was higher with Bic/Lac solution use. In conclusion, MCs released into peritoneal effluent under bicarbonate/lactate-buffered peritoneal dialysis solution are associated with a greater ex vivo proliferation capacity than those released under lactate solution in the same patient. This finding may demonstrate better biocompatibility for Bic/Lac solution.

Bicarbonates↗

Helicobacter pylori infection: a new cause of anorexia in peritoneal dialysis patients.

OBJECTIVE: Helicobacter pylori (HP) infection has frequently been found in dialysis patients. Chronic infections induce overproduction of pro-inflammatory substances. Inflammation has been associated with cachexia and anorexia. We explored the relationship between HP infection, anorexia, and malnutrition in peritoneal dialysis (PD) patients. PATIENTS AND METHODS: The study included 48 clinically stable PD patients divided into four groups: HP+ with anorexia (group I, n = 12); HP+ without anorexia (group II, n = 4); HP- with anorexia (group III, n = 5); and HP- without anorexia (group IV, n = 27). Infection with HP was diagnosed by breath test. Anorexia was evaluated using a personal interview and an eating motivation scale (VAS). The VAS included five questions that are answered before and after eating. The questions concern desire to eat, hunger, feeling of fullness, prospective consumption, and palatability. Biochemical markers of nutrition and inflammation were also determined. RESULTS: At baseline, group I showed lower scores for desire to eat, hunger sensation, prospective consumption, and palatability. They also showed lower lymphocyte counts, prealbumin, transferrin, serum albumin, normalized equivalent of protein-nitrogen appearance (nPNA), and residual renal function (RRF). In addition, the same group showed higher levels of C-reactive protein (CRP) and more sensation of fullness than the remaining groups. In the entire series, we found significant linear correlations between the following markers of nutrition and certain questions on the VAS: albumin with before-lunch desire to eat (r = 0.38, p < 0.05), and prealbumin with before-lunch hunger (r = 0.41, p < 0.05) and after-lunch hunger (r = -0.35, p < 0.05). Negative linear correlations were found between albumin and fullness before lunch (r = -0.45, p < 0.01), and between prealbumin and before-lunch desire to eat (r = -0.39, p < 0.05). Negative linear correlations were also seen between CRP and albumin (r = -0.35, p < 0.05) and between CRP and prealbumin (r = -0.36, p < 0.05). Similarly, CRP showed a negative correlation with before-lunch desire to eat (r = -0.38, p < 0.05) and afterlunch desire to eat (r = -0.45, p < 0.01). After HP eradication, group I showed a significant increase in markers of nutrition and in VAS scores for almost all questions. Simultaneously, they showed a decrease in CRP level. Significant differences were also found in lymphocyte count (1105 +/- 259.4 cells/mm3 vs 1330.8 +/- 316 cells/mm3, p < 0.05), nPNA (0.9 +/- 0.16 g/kg/day vs 1.07 +/- 0.3 g/kg/day, p < 0.05), prealbumin (26.7 +/- 6.5 mg/dL vs 33.9 +/- 56.6 mg/dL, p < 0.01), albumin (3.48 +/- 0.3 g/dL vs 3.67 +/- 0.35 g/dL, p < 0.05), CRP (1.16 +/- 1.14 mg/dL vs 0.88 +/- 1.2 mg/dL, p < 0.054), before-lunch desire to eat (56.6 +/- 6.8 vs 72.2 +/- 4, p < 0.001), after-lunch desire to eat (5.4 +/- 2.6 vs 12.3 +/- 2, p < 0.01), hunger before lunch (55.4 +/- 5.4 vs 73.1 +/- 4.6, p < 0.001), hunger after lunch (5.8 +/- 2.9 vs 11 +/- 4, p < 0.01), fullness before lunch (36.6 +/- 10.3 vs 18.7 +/- 8.8, p < 0.001), consumption after lunch (5 +/- 4.7 vs 17.5 +/- 18, p < 0.05), and palatability (61 +/- 5.3 vs 74.1 +/- 4.1, p < 0.001). CONCLUSION: Infection with HP is associated with anorexia, inflammation, and malnutrition in PD patients. Eradication of HP significantly improves this syndrome. Residual renal function seem to have a protective effect on appetite preservation. The present study supports the hypothesis of the involvement of inflammation in the pathogenesis of malnutrition in PD patients.

Adult↗

Cholinergic modulation of growth hormone responses to growth hormone-releasing hormone in uraemic patients on peritoneal dialysis.

BACKGROUND: Hypothalamic cholinergic neurotransmission plays a major role in the regulation of GH secretion. Pyridostigmine, a cholinesterase inhibitor, is able to decrease hypothalamic somatostatinergic tone and release GH in normal subjects. Blockade of muscarinic receptor with pirenzepine blunts the GH release in several clinical situations. However, little information is available on the role played by central cholinergic pathways in GH regulation in uraemic patients. OBJECTIVE: We aimed to assess GH responses to GHRH after pretreatment with pyridostigmine and pirenzepine in a group of uraemic patients undergoing peritoneal dialysis (PD). GH responses of the patients treated with recombinant human erythropeitin (rhEPO) were compared to patients without treatment. DESIGN: We studied 14 male patients on PD and nine control subjects. All subjects underwent three endocrine test in random order after an overnight fast. Each subject received GHRH (100 microg, i.v. in bolus at 0 minutes). Sixty minutes before the injection of GHRH subjects were given oral placebo, pyridostigmine (120 mg), or pirenzepine (100 mg). MEASUREMENTS: Blood samples for GH were collected at -60, 0, 15, 30, 45, 60 and 90 minutes The hormonal secretory responses were studied by a time-averaged (area under the curves, AUC) and time-independent (peak values) analysis. RESULTS: Baseline GH concentrations were similar in patients and controls. GH responses to placebo plus GHRH were also comparable in patients and controls (peak 26.6 +/- 3.8 vs. 33.2 +/- 4.4 mU/l, AUC 28.2 +/- 3.4 vs. 27.8 +/- 4.6 mU/h/l). Pyridostigmine administration induced a significant potentiation of GH responses to GHRH both in patients (peak 43.2 +/- 5.2 mU/l, AUC 47.6 +/- 6.0 mU/h/l; P < 0.01) and in control subjects (peak 79.2 +/- 8.6 mU/l, AUC 78.0 +/- 9.4 mU/h/l; P < 0.01). However, the increment in GH peak and AUC was significantly (P < 0.05) greater in controls in relation to values found in patients. Pirenzepine administration induced an abolishment of GH release after GHRH stimulation both in PD patients (peak 5.4 +/- 2.6 mU/l, AUC 6.0 +/- 2.4 mU/h/l; P < 0.01) and in healthy controls (peak 3.8 +/- 0.6 mU/l, AUC 4.0 +/- 0.4 mU/h/l; P < 0.05). Responses to pyridostigmine plus GHRH and pirenzepine plus GHRH were similar in patients on chronic therapy with recombinant human erythropeitin and in patients without rhEPO therapy. CONCLUSION: These results suggest that the cholinergic regulation of GH release is preserved in uraemic patients on peritoneal dialysis. The significantly lower increase in GH response to GHRH induced by pyridostigmine suggests that cholinergic stimulatory tone is attenuated in patients in relation to control subjects. Long-term therapy with rhEPO seems not to affect GH responses to cholinergic stimulation or blockade.

Adult↗

Parathormone secretion in peritoneal dialysis patients with adynamic bone disease.

The prevalence of low-turnover lesions in patients undergoing peritoneal dialysis (PD) is high. Our aims are to evaluate the prevalence of adynamic bone disease (ABD) in PD patients, analyze risk factors, and define the association of serum parathyroid hormone (PTH) levels measured under different plasma calcium concentrations with this lesion. Fifty-seven patients were studied by bone biopsy (BB). ABD was found in 63.2%, and 36.8% showed high-turnover bone disease (HTBD). Patients with HTBD had a lower prevalence of diabetes, younger age, lower accumulated oral calcium salt intake, and greater calcitriol doses, serum osteocalcin level, and ultrafiltration than patients with ABD. Both mean baseline PTH levels from the previous year and PTH level at time of BB were greater in patients with HTBD than those with ABD (357 +/- 267 pg/mL versus 89 +/- 67 pg/mL; 390 +/- 337 pg/mL versus 88 +/- 78 pg/mL, respectively; P < 0.05). However, the magnitude of the increase from baseline serum PTH levels in response to hypocalcemia was greater in patients with ABD than in those with HTBD (166.4% +/- 134% versus 83.5% +/- 73.6%; P < 0.05). We found that PTH levels less than 150 pg/mL in patients with ABD showed a sensitivity of 91. 6%, specificity of 95.2%, and positive predictive value (PPV) of 97%. In the HTBD group, PTH levels greater than 450 pg/mL had a specificity and PPV of 100%. Our data confirm that ABD is the most prevalent lesion in PD patients, and PTH secretion capacity is maintained in these patients. The definitive diagnosis and management strategies for many patients requires a BB, especially when HTBD is unlikely.

Adult↗