[Italian Registry of Dialysis and Transplantation: 1996-2001 experience]. / Registro Italiano Dialisi e Trapianto. Esperienza 1996-2001.

The Italian Registry of Dialysis and Transplantation (RIDT) was born in 1996 under the aegis of the Italian Society of Nephrology, and it is organized as a federation of regional registries. This study aimed to completely revise the epidemiological data collected during the first 5 yrs (1996-2001) of RIDT activity to evaluate the trends of the main epidemiological features. During this period, regional registries were not always able to assure complete and exhaustive information according to RIDT requirements, owing to different levels of organization and functioning. To avoid any possible error in data analysis, information inadequately assessed was refused. The incidence of end-stage renal disease (ESRD) patients on renal replacement therapy (RRT) in Italy has increased from 114 pmp in 1996 to 139 pmp in 2001, that means an increase of 3.5%/yr, corresponding to 5718 patients during 1996 and 8000 patients during 2001. Primary renal diseases (according to the EDTA) in incident ESRD patients are vascular and diabetic nephropathy. Main dialysis modality in incident patients was hemodialysis (HD) (85%), while peritoneal dialysis (PD) was only 15%; pre-emptive transplantation was a very unusual modality. The prevalence of ESRD patients at 31 December was 693 pmp in 1996 and 827 pmp in 2001; among dialysis patients, the corresponding rates were 575 pmp and 657 pmp, respectively. Consequently, the number of dialyzed patients increased, respectively, from 28892 to 37919. The prevalent dialysis modality was bicarbonate dialysis in 74% of cases, followed by hemodiafiltration (HDF) in 15%, continuous ambulatory peritoneal dialysis (CAPD) in 7% and APD in 3%. The gross mortality rate in dialyzed patients was stable during this period, at approximately 14%, the main causes of death being cardiovascular diseases and cachexia.

Day-to-day variability of adequacy indexes in peritoneal dialysis.

BACKGROUND: The achievement of dialysis adequacy targets in peritoneal dialysis (PD) is assessed by the calculation of the Kt/V and creatinine clearance (C(Cr)) obtained by collecting dialysate and urine, usually two or three times a year. Prescription decisions are based on such adequacy assessments, regardless of any variability in the single measurements. The aim of our study was to assess the day-to-day variability of common dialysis adequacy parameters and to evaluate its impact on the adequacy indexes in PD. METHODS: Twenty-four patients (14 CAPD, 10 APD) at two centres were studied by means of a triple dialysate and urine collection for a period of 1 week. Variability in the findings for a given patient was expressed by the coefficient of variation (CV%) calculated for peritoneal (p), renal, and total (tot) adequacy parameters. The target Kt/V and C(Cr) values were recalculated on the basis of variability. RESULTS: Kt/V was less variable (CV 4.0 and 4.4% for peritoneal Kt/V (pKt/V) and total Kt/V (totKt/V) respectively) than C(Cr) (4.7 and 6.0% for peritoneal creatinine clearance (pC(Cr)) and total creatinine clearance (totC(Cr)) respectively) and proved to be a more reliable indicator of adequacy in terms of the CV. Both variability parameters became worse if renal clearance was added to peritoneal clearance. CV in APD proved to be no different from CAPD for all the parameters considered. In our centres dialysis adequacy target correction for variability provided safe values for weekly Kt/V (pKt/V=1.78-2.10 and totKt/V=1.82-2.15 target 1.7-2.0) and C(Cr)/1.73 (pC(Cr)=53.7-64.4 l and totC(Cr)=55.1-66.1 l; target 50-60 l). CONCLUSIONS: Evaluating the adequacy of PD by means of a single measurement should take into account the weekly variability as demonstrated by a triple dialysate and urine collection. Standard adequacy targets can be corrected to allow for variability. Thus one can obtain safe values for prescription decisions based on a single collection result.

Clinical validation of PD Adequest software: modeling error assessment.

OBJECTIVE: PD ADEQUEST software (Baxter Healthcare, Deerfield, IL, U.S.A.) is used in peritoneal dialysis for calculating the indices of dialysis efficiency and for the mathematical simulation of the results of various dialysis regimens. The aim of our study was to quantify the modeling errors and find the methods which give best results. DESIGN: Nonrandomized, repeated measurement, clinical validation study. PATIENTS: The study included 78 patients on continuous ambulatory peritoneal dialysis (PD), daytime ambulatory PD, and automated PD. MEASUREMENTS: We used 207 collections of dialysate and urine associated with peritoneal equilibration tests (PETs) performed with different glucose concentrations (1.36%, 2.27%, 3.86%). The measured urea Kt/V, creatinine clearance (CRCL) and ultrafiltration (UF) were compared with the same data simulated mathematically using the PD ADEQUEST software version 1.4. RESULTS: The Kt/V, CRCL, and UF measured values were significantly correlated and in agreement with modeled data [concordance correlation (rc) was 0.849, 0.839, 0.625 respectively]. The errors (modeled - measured) were: Kt/V = -0.04 +/- 0.27 (p = ns), CRCL = 2.1 +/- 7.7 L (p < 0.001), UF = -121 +/- 711 mL (p = 0.016). Applying ANOVA to both the peritoneal transport data calculated by PD ADEQUEST (mass transfer area coefficient of the solutes, fluid reabsorption, and hydraulic permeability) and the modeling errors, significant differences were found in relation to the PET glucose concentrations. CONCLUSION: PD ADEQUEST proves to be a useful instrument in peritoneal dialysis, although there is undoubtedly still room for improvement in its prediction efficacy, which is influenced by the glucose concentration used in the PET.

Symptoms in hemodialysis patients and their relationship with biochemical and demographic parameters.

Symptoms can markedly influence the hemodialysis patients well-being and quality of life. The aim of this paper is to study the frequency of symptoms at home and how these relate to biochemical and treatment variables. Seventy-three hemodialysis patients were questioned on the absence, occasional presence or daily recurrence (score = 0, 1, 2) of 14 symptoms and a record was made of their biochemical parameters, age, time on treatment and KtIV as a function of each symptom. The following relationships were detected: thirst with high Osm and BUN; asthenia with old age and hypoalbuminemia; insomnia with hypercalcemia; hypersomnia with hypoxemia and hypernatremia; anorexia with hypokalemia; dyspnea with old age, hypernatremia and hypokalemia; dysgeusia with hypoxemia; nausea with alkalemia, hypoxemia and low BUN; vomiting with alkalemia. Pruritus, arthralgia, restless legs syndrome, cramp and tremor showed no relationships. Monitoring acid-base balance and plasma electrolytes could help to alleviate symptoms and ameliorate quality of life of hemodialysis patients.

Repeated exposure to cocaine produces long-lasting deficits in the serotonergic stimulation of prolactin and renin, but not adrenocorticotropin secretion.

To determine whether cocaine-induced deficits in serotonergic function are long-lasting, the neuroendocrine responses to the serotonin (5-hydroxytryptamine, 5-HT) releaser, p-chloroamphetamine were evaluated 1-8 weeks subsequent to 7 days of cocaine exposure (15 mg/kg b.i.d.). In cocaine-pretreated rats, the p-chloroamphetamine-induced elevations of prolactin and renin secretion were significantly reduced for 8 and 4 weeks, respectively. In contrast, the p-chloroamphetamine-induced elevation of adrenocorticotropic hormone (ACTH) secretion was at control values 1 week after cocaine exposure. The data suggest that some cocaine-induced deficits in serotonergic function are long-lasting.

Repeated injections of cocaine inhibit the serotonergic regulation of prolactin and renin secretion in rats.

Alterations in serotonergic function following repeated cocaine injections were examined using neuroendocrine responses to a serotonin (5-HT) releaser and 5-HT agonists. Forty-two hours following administration of cocaine (1-15 mg/kg i.p.) twice daily for 7 or 30 days, male Sprague-Dawley rats were injected with the 5-HT releaser p-chloroamphetamine (PCA; 8 mg/kg i.p.) and blood samples were collected 1 h later for radioimmunoassays of plasma prolactin, plasma renin activity (PRA) and plasma renin concentration (PRC). PCA significantly increased secretion of prolactin and renin. These responses were attenuated in rats pretreated with cocaine for 30 days. In rats receiving cocaine for 7 days, the attenuation of PCA-induced secretion of prolactin and renin was less consistently observed. To determine whether these alterations were due to pre- or postsynaptic effects, rats were injected with cocaine (15 mg/kg i.p.) twice daily for 7 days, and the neuroendocrine responses to the direct 5-HT agonists RU 24969 and m-CPP were examined, 42 h after the last cocaine injection. Pretreatment with cocaine potentiated RU 24969-induced stimulation of plasma prolactin concentration. However, cocaine did not alter the ability of m-CPP to increase plasma prolactin concentrations. The stimulation of renin secretion in response to both 5-HT agonists was not altered by cocaine pretreatment. The data suggest that repeated cocaine impairs the function of serotonergic nerve terminals that regulate these endocrine responses. Furthermore, the 5-HT receptors that mediate prolactin secretion may exhibit supersensitivity.

Prior chronic exposure to cocaine inhibits the serotonergic stimulation of ACTH and secretion of corticosterone.

The effect of long-term pretreatment with cocaine on serotonergic regulation of ACTH (adrenocorticotropic hormone; corticotropin) and secretion of corticosterone in rats was investigated. The following observations were made: (1) Pretreatment with cocaine had no significant effect on basal levels of ACTH and corticosterone in plasma. However, cocaine caused a reduction in the ability of the 5-HT (5-hydroxytryptamine, serotonin) releaser p-chloroamphetamine (PCA) to increase corticosterone in plasma, 42 hr after the last injection of cocaine. (2) Exposure to cocaine for 7 days was sufficient to produce a maximal inhibition of the PCA-induced increase in ACTH in plasma. (3) The inhibitory effect of cocaine on PCA-induced release of ACTH was more marked than on corticosterone. (4) Conversely, the dose-dependent stimulatory effect of two 5-HT1 agonists, RU 24969 (5-methoxy-3-(1,2,3,4-tetrahydro-4-pyridinyl)-1H-indole) and m-CPP (m-chlorophenylpiperazine), on ACTH and corticosterone was not reduced by 7 days of exposure to cocaine. Taken together, these findings indicate that pretreatment with cocaine reduced the function of serotonergic nerve-terminals but not postsynaptic receptors, that stimulate ACTH and secretion of corticosterone.

Acute, but not repeated, cocaine administration decreases renin secretion in the conscious male rat.

The effects of cocaine on renin secretion have been addressed and a previously unreported inhibitory effect has been identified on this neuroendocrine system in the conscious male rat. Acute intraperitoneal administration of cocaine dose-dependently (1.5, 7.5, 15, and 30 mg/kg; at 15 min) produced a significant decrease in both plasma renin activity (PRA) and plasma renin concentration (PRC). The time course of inhibition by cocaine in PRA and PRC revealed maximal effects at 15 min following a 15 mg/kg dose. In contrast, the long term administration of cocaine for 1, 7, or 30 days (15 mg/kg, twice daily, i.p.) did not produce changes in PRC.

Neuroendocrine evidence for denervation supersensitivity of serotonin receptors: effects of the 5-HT agonist RU 24969 on corticotropin, corticosterone, prolactin and renin secretion.

Serotonergic stimulation can increase the secretion of several hormones through the involvement of different serotonin (5-HT) receptor subtypes. RU 24969, a 5-HT agonist with highest affinity at 5-HT1A and 5-HT1B receptors, increased plasma renin activity (PRA) and plasma renin concentration (PRC) as well as plasma corticosterone and prolactin concentrations in a dose-dependent manner. Inasmuch as 5-HT2 receptors mediate the serotonergic stimulation of renin secretion, we examined the ability of two selective 5-HT2 antagonists, ritanserin and LY53857, to inhibit the neuroendocrine effects of RU 24969. To determine whether the 5-HT receptors which are involved in the stimulation of these hormones are pre- or postsynaptic, RU 24969 was also injected to rats whose brain serotonergic neurons were chemically destroyed by i.c.v. injection of 5,7-dihydroxytryptamine. Both ritanserin and LY53857 blocked the effect of RU 24969 on PRA and PRC, but did not inhibit the RU 24969-induced elevation in plasma corticosterone concentrations. Ritanserin did not inhibit the effect of RU 24969 on prolactin levels, but LY53857 produced a partial inhibition of the RU 24969-induced elevation of prolactin concentrations. In rats with chemical lesions of serotonergic neurons the dose-response curves of RU 24969 for PRA and PRC as well as corticotropin, corticosterone and prolactin shifted to the left, suggesting functional up-regulation of postsynaptic 5-HT receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical evaluation of a new water removal measuring device in standard dialysis.

A new device measuring water removal during standard dialysis is evaluated. The filtrate, collected from a small hemofilter inserted into a normal Cuprophan hollow-fiber dialyzer, was used to evaluate the total water removed from the patient. The device was tested in 46 patients undergoing regular dialysis treatment; the body weight loss ranged from 300 to 5,600 ml for a total of 71 dialysis sessions. Results confirmed the reliability of the device, as the mean prediction error was 5.4%. No influence of the dialyzer blood rest volume on the prediction error was observed. The authors propose this system as an alternative to bed or armchair scales and emphasize its usefulness for experimental purposes.

A new hemodialysis monitoring device using filtrate concentrations: a comparison with standard serum techniques.

A new device allowing sampling to be performed at any time, and using the filtrate obtained during hemodialysis is described. The device was used in 27 patients undergoing regular dialysis. Urea, creatinine and potassium were measured in samples taken both from arterial blood and from the device at 10, 40, 120 and 230 minutes after the beginning of the dialysis. The results were compared. A constant bias of about 10% was noted between the two sets of results but statistical analysis showed this was correctable.

A pilot study of the pharmacokinetics and triglyceride lowering activity of acipimox in dialyzed uremic patients.

The pharmacokinetics of acipimox was studied in 6 dialyzed uremic patients given single oral doses of 50 mg. Acipimox was not significantly eliminated outside dialysis, whereas during dialysis it was efficiently cleared with plasma, t 1/2 is about 2.6 hours. Accordingly, a dosage schedule of 50 mg or 100 mg of acipimox after each dialysis session was selected for a second, 4-week study in 14 uremic patients with hypertriglyceridemia. Acipimox plasma levels, monitored during the study, proved in agreement with those expected on a theoretical pharmacokinetic basis. A clear-cut reduction of serum triglyceride levels was also achieved.