Role of fosfomycin tromethamine in modulating non-specific defence mechanisms in chronic uremic patients towards ESBL-producing Escherichia coli.

Antimicrobial agents and polymorphonuclear cells (PMNs) have the potential to interact in such a way that improve the therapy for infectious diseases. In immunocompromised patients highly susceptible to microbial infections with high morbidity and mortality, several metabolic and functional alterations in PMNs, mostly related to microbicidal activity, are observed. Therefore, the antibiotic of choice should have a good antimicrobial effect without impairing host defences. The aim of this study is to evaluate in vitro effects of sub-inhibiting fosfomycin tromethamine (FT) concentrations on the primary functions of PMNs from healthy subjects and immunocompromised patients (haemodialysed and renal transplant recipients), against an ESBL-producing Escherichia coli, the most common aetiological agent in urinary tract infections (UTIs). FT is considered a first line drug in the eradication of UTIs due to its appropriate antimicrobial spectrum, oral bioavailability and minimal risk of microbial resistance. Our results provide evidence that FT is able to induce enhancement of the depressed phagocytic response of PMNs from patients on chronic haemodialysis and from renal transplant recipients, restoring their primary functions in vitro against ESBL-producing E. coli. All these data permit the conclusion that uremic-infected patients might additionally benefit from the immunomodulating properties of FT.

Co-detection and discrimination of JCV and BKV DNA by duplex nested-PCR in renal transplant recipients.

AIM: Several studies have disclosed a correlation between human polyomavirus BK (BKV) and interstitial nephritis in renal transplant recipients. It has recently been hypothesized that some cases of nephropathy may be associated with human polyomavirus JC (JCV). METHODS: In this paper we describe the development of duplex nested-PCR assay which allows the simultaneous detection and discrimination of genomic sequences of JCV and BKV ''large T antigen'', resulting in amplicons of 150 bp and 278 bp, respectively. Thus, the presence of JCV and BKV DNA in urine and serum samples from 51 renal transplant recipients and 29 healthy controls was investigated and related to immunosuppressive regimens and renal function. RESULTS: The comparison between the incidence of the of BKV and/or JCV infections (detected by viruria and/or viraemia) in renal transplant recipients and the control group revealed a highly significant increase of the incidence of BKV infection in immunosuppressed patients vs healthy subjects (62.7% vs 27.6%; p=0.005). In particular, we found a significant increase of BKV-DNA viruria in renal transplant recipients vs healthy subjects (49% vs 17.2%; p=0.01), in agreement with the BKV urinary shedding in renal transplant recipients of the literature (5-45%). CONCLUSION: The nested-PCR technique is a valid diagnostic tool to detect viral presence in urine and its systemic diffusion. Our assay links the high sensitivity of nested amplification with the simultaneous detection and discrimination of genomic sequences of JC and BK polyomaviruses and thus provides a handy, rapid and sensitive means for DNA analysis of large numbers of samples.

Efficacy of an educational program on dialysis, renal transplantation, and organ donation on the opinions of high school students: a randomized controlled trial.

AIM: Organ shortage is a rate-limiting factor for transplantation. The aim of this study was to evaluate the impact of an educational program targeted to high school students on opinions concerning organ donation. METHODS: Sixteen public high schools in Torino, Italy, were randomized (2001 to 2002) as interventions (n = 8) or controls (n = 8). Intervention was composed of first questionnaire, first lesson (one to two classes; 2 hours, by a trained nephrology fellow); second lesson (all classes together; coordinated by a nephrologist, with patients and trainees); second questionnaire. Control included questionnaires. Statistical analysis compared the opinions in the questionnaires after stratification for age, sex, and type of school. RESULTS: Fourteen schools completed the program (seven interventions: 937 first and 808 second questionnaires; controls: 739 and 659). Television (82.5%) and newspapers (43.2%) were the main sources of information; knowledge on renal transplantation (grafts feasible per patient, average duration) was low; only 12.2% of the students gave correct answers. The opinions on living donation were highly positive (76.8%) with no difference in control, intervention schools, first and second questionnaires, according to sex, age, or type of school. The opinions on cadaveric transplantation were affected by the educational intervention with a drop in negative answers (from 33.7% to 16%), with an increase in positive (from 31.5% to 42.9%) and in uncertain ones (from 34.8% to 41.1%) among the intervention schools; 98% of the students appreciated the program. CONCLUSION: The positive effect on student opinions suggests the need to develop educational approaches as a part of our routine clinical work.

How many organs should one patient receive? The ethics of transplantation in the medical school.

BACKGROUND: Interest in the humanities in the medical school is growing; while several medical schools, mainly of Anglo-Saxon background, have developed dedicated courses, the experience in Italy is limited. METHODS: Since the academic year 2000 to 2001, a discussion of ethical problems was implemented in the nephrology course (fourth year of the Medical School of Torino, Italy; overall 6 years). In 2002 to 2003, a case entitled "Retransplantation of Multiple Organs (Prog Transplant 2002)" was discussed in 2 hours of small-group tutorial teaching: a boy received a renal graft at age 5, failed at age 7 due to recurrent glomerulonephritis, required a heart-kidney graft at age 11, and a second heart-kidney graft at 17. Student opinions were gathered by anonymous semistructured questionnaires at the beginning of the lessons as a basis for discussion. RESULTS: Following the lessons all students returned the questionnaires (n = 104). In the absence of competition for allocation, retransplantation was approved by 76.2%, unacceptable for 1% (22.9% uncertain-blank). With a waiting list of 10 patients, the opinions changed: 32.4% approved transplantation, 6.7% didn't approve it, 60.9% were uncertain. A theoretical categorization into deontological or utilitaristic approaches favored the first (41.9% vs 26.7%), with a high prevalence of blank-uncertain (31.5%); 21.9% of the students would change their opinion was that study head of the Transplant Department. CONCLUSION: Ethical aspects of the medical profession have been discussed with interest by medical school students; the high prevalence of uncertain answers and requests to develop specific tools underline the importance of this educational approach.

To give or to receive? Opinions of teenagers on kidney donation.

BACKGROUND: The attitude toward living donation varies widely in the world, for economic and cultural reasons. In Italy, as in other Mediterranean settings, the role of living kidney donation is minor. AIM: To analyze the reasons for this attitude, we gathered data in a general population sample of high school students in a large northern Italian industrial city (Torino, about 900,000 inhabitants). METHODS: Semistructured questionnaires (n = 1676), gathered in 2001 to 2002 in 14 high schools, in the context of an educational program on dialysis, renal transplantation, and organ donation, were analyzed presumably reflecting opinions gathered before the educational intervention. RESULTS: Most students, in the case of a close relative or partner needing dialysis, answer that they would donate a kidney (yes: 78.2%, no: 2.9%, uncertain-blank: 18.9%); receiving a living donor kidney is felt as disturbing: only 57.5% of the students would accept it (no: 5.9%, uncertain-blank: 36.6%), mainly because of fear of long-term problems for the donor. Donation from an older to a younger person is seen more positively than vice versa. CONCLUSION: In our settings, the attitude of the teenagers on living donation is positive; however, while "giving" is positively seen, the presence of unresolved fears is witnessed by the lower acceptance of the idea of "taking." These data suggest to focus on the risks of kidney donation in educational campaigns and in patient-physician information. The positive attitude shared by the teenagers supports the working hypothesis that lack of information is one of the determinants of the low living donor transplantation rate in our area.

[Epstein Barr viral load monitoring in mononuclear lymphocytes and serum of renal transplant recipients using a quantitative PCR protocol]. / Monitoraggio della carica virale dell'EBV nei linfomonociti e nel siero di trapiantati renali mediante un protocollo di PCR quantitativa.

BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD), ranging from lymphoid hyperplasia to clonal malignancy, are severe complications arising in solid organ transplant patients; their reported incidence ranges from 1 to 20%, according to factors such as type of transplanted organ and age of recipients. A strong correlation between Epstein-Barrvirus (EBV) infection, the grade and type of immunosuppression and the development of PTLD has been recognized. The detection and quantification of EBV-DNA load in peripheral blood have been utilized as prognostic markers for the development of PTLD, showing a correlation between high levels of EBV-DNA in the blood and the development of PTLD. In this study, we monthly monitored EBV viral load in 15 renal transplant recipients for six months. The number of EBV-DNA copies was measured in peripheral blood mononuclear cells (PBMC) and serum samples by a quantitative PCR protocol developed in our laboratory. METHODS: Our EBV-DNA quantification protocol employs a previous screening of samples containing a significant number of viral DNA copies (>=1000 copies/105 PBMC or 100 mL serum) by semi-quantitative PCR followed by a precise quantification of the only significant samples by quantitative-competitive (QC)-PCR. RESULTS: Our 15 renal transplant patients neither developed PTLD nor had recurrent acute illnesses or acute graft rejections during the study. The results obtained in the monthly follow up of EB viral load in PBMC samples confirmed its fluctuation in asymptomatic patients reported in the literature. In particular, 5/14 (35.7%) of EBV seropositive patients had an EBV-DNA load equal to 1000 EBV copies /105 PBMC, and 1/14 (7.1%) reached 5000 EBV copies /105 PBMC at least once in our study. In the EBV seronegative patient, EBV-DNA in PBMC samples was always undetectable (less than 100 DNA copies/105 PBMC). EBV-DNA load in all serum samples was less than threshold value of our quantification protocol (<100 DNA copies/100 mL serum). With regard to the immunosuppressive treatment, it should be noted that 66.7% of the six patients in whom EBV load reached values equal to or higher than 1000 DNA copies/105 PBMC, were on FK506 whereas only 33.3% of them were on CyA. CONCLUSIONS: Since the high positive predictive value of EB viral load in peripheral blood for diagnosis of PTLD reported by several Authors, and the described absence of correlation between the serological evidence of EBV reactivation and EB viral load, EBV viral load measurement in PBMC and serum samples using quantitative PCR techniques is a powerful diagnostic tool to monitor transplanted patients at risk of developing PTLD.

Epstein Barr viral load monitoring by quantitative PCR in renal transplant patients.

Post-transplant lymphoproliferative disorders (PTLD), ranging from lymphoid hyperplasia to clonal malignancy, are a severe complication arising in solid organ transplant patients. Their reported incidence ranges from 1 to 20%, according to factors such as type of transplanted organ and the age of recipients. A strong correlation between Epstein Barr virus (EBV) infection, the grade and type of immunosuppression and the development of PTLD has been recognized. The detection and quantification of EBV-DNA load in peripheral blood have been utilized as prognostic markers for the development of PTLD, showing a correlation between high levels of EBV-DNA in the blood and the development of PTLD. In this study, we monitored EBV viral load monthly in 15 renal transplant recipients for six months. The number of EBV-DNA copies was measured in peripheral blood mononuclear cells (PBMC) and serum samples by a quantitative PCR protocol developed in our laboratory that employes a previous screening of samples containing a significant number of viral DNA copies (> or =1000 copies/10(5) PBMC or 100 microl serum) by semi-quantitative PCR followed by a precise quantification of the only significant samples by quantitative-competitive (QC)-PCR. Our 15 renal transplant patients neither developed PTLD nor had recurrent acute illnesses or acute graft rejections during the study. The results obtained in the monthly follow up of EB viral load in PBMC samples confirmed its fluctuation in asymptomatic patients reported in literature. In particular, 5/14 (35.7%) of EBV seropositive patients had an EBV-DNA load equal to 1000 EBV copies /10(5) PBMC (roughly corresponding to 10.000 copies/microg PBMC DNA), and 1/14 (7.1%) reached 5000 EBV copies /10(5) PBMC (roughly corresponding to 50.000 copies/microg PBMC DNA), at least once in our study. In the EBV seronegative patient, EBV-DNA in PBMC samples was always undetectable (less than 100 DNA copies/10(5) PBMC). EBV-DNA load in all serum samples was less than threshold value of our quantification protocol (<100 DNA copies/100 microl serum), supporting the literature data. With regard to immunosuppressive treatment, 66.7% of the six patients in whom EBV load reached values equal to or higher than 1000 DNA copies/10(5) PBMC, were on FK506 whereas only 33.3% of them were on CyA. In conclusion, further investigations are needed to better understand the role of EBV infection in the pathogenesis of PTLD in immunosuppressed patients. Given the high positive predictive value of EB viral load in peripheral blood for diagnosis of PTLD reported by several authors, and the described absence of correlation between the serological evidence of EBV reactivation and EB viral load, EBV viral load measurement in PBMC and serum samples using quantitative PCR techniques is a powerful diagnostic tool to monitor transplanted patients at risk to develop PTLD.

[Percutaneous renal biopsy with a semi-automate device]. / La biopsia renale percutanea con sistema semi-automatico.

BACKGROUND: The percutaneous renal biopsy is a fundamental investigation in the diagnostic procedure for renal diseases. The introduction of the kidney localisation by real-time ultrasounds made the procedure more effective and safe. The use of semi-automated and automated biopsy devices seems to go in the same way. METHODS: In this paper a retrospective investigation is made on 118 renal biopsies performed at our Nephrology Unit from 1990 to 1999 with the semi-automated device Biopty Bard and with direct ultrasounds guidance. The number of post-biopsy complications have been evaluated. RESULTS: Any major complications (as surgical interventions and deaths) have been observed. The number of minor complications was low and in agreement with the literature data (post-biopsy macrohematuria = 6.8%, hemoglobin loss =/>20% = 0.8%, hematoma = 5.1%, lumbar pain 0.8%). The 98.4% of renal biopsies were diagnostic and 91.4% had a number of glomeruli =/>5. CONCLUSIONS: The automated ultrasound-guided procedure is a feasible and reliable technique for percutaneous renal biopsy. It gives a greater yield of diagnostic tissue without increasing the rate of clinical complications, even in Nephrology Units, such as ours, that perform a small number of biopsies every years.

Impact of co-amoxiclav on polymorphonuclear granulocytes from chronic hemodialysis patients.

Phagocyte-dependent host defenses are frequently impaired in maintenance hemodialysis patients who show an increased susceptibility to infections. In these individuals, the course of infections can be more aggressive than in normal hosts, and the antibiotic of choice should have a high antimicrobial effect without impairing host defenses. Hence, in uremic patients, the antibiotic enhancement of phagocyte functions may be of potential clinical importance in the outcome of bacterial infections. Because we demonstrated previously that co-amoxiclav had beneficial properties that result in enhancement of the microbicidal functions of human polymorphonuclear cells (PMNs) from healthy subjects, we investigated the influence of this combination on the activities of PMNs from chronic hemodialysis patients against Klebsiella pneumoniae, a human pathogen that can pose severe problems in patients whose immunity is impaired. PMNs from chronic dialysis patients showed a diminished in vitro phagocytic efficiency with a reduced phagocytosis and bactericidal activity towards intracellular K. pneumoniae compared with that seen in PMNs from healthy subjects. When co-amoxiclav was added to PMNs from chronic hemodialysis patients, it was able to restore the depressed primary functions of PMNs, resulting in a significant high increase in both phagocytosis or killing activity. A similar pattern was detected with PMNs collected from hemodialysis patients treated with co-amoxiclav. The results of the present study provide evidence that co-amoxiclav is able to induce stimulation of depressed phagocytic response of PMNs from patients on chronic hemodialysis, restoring their primary functions both in vitro and in vivo.

Improved phagocyte response by co-amoxiclav in renal transplant recipients.

BACKGROUND: Infectious diseases are a major source of morbidity and mortality for immunosuppressed transplant recipients and the antimicrobial chemotherapy can be often less effective in these individuals, because the contribution of underlying host defenses is absent. METHODS: The influence of co-amoxiclav on the functions of polymorphonuclear granulocytes (PMNs) from renal transplant recipients were investigated. RESULTS: PMNs from renal transplant recipients showed a diminished phagocytic activity with reduced phagocytosis and bactericidal activity against intracellular Klebsiella pneumoniae, compared to that seen with PMNs from healthy subjects. Co-amoxiclav significantly elicited the functions of PMNs from uremic patients, resulting in an increased percentage of ingested klebsiellae and in a higher bactericidal effect (98-99%), compared with the drug-free control system. When PMNs were collected from renal transplant recipients treated with co-amoxiclav a significant high increase in both phagocytosis and killing activity were detected, showing the co-amoxiclav capability of "restoring" even in vivo the depressed primary functions of PMNs. CONCLUSIONS: The interesting beneficial properties of co-amoxiclav, which result in restoring the phagocyte-dependent response in renal transplant patients both in vitro and in vivo, may make this drug more suitable for the treatment of infections in patients with defects of phagocyte functions.

Bradykinin and nitric oxide generation by dialysis membranes can be blunted by alkaline rinsing solutions.

BACKGROUND: Bradykinin (BK) generation following the first contact of blood with the dialysis materials is thought to enhance hypersensitivity reactions (HSRs). Some of the effects of BK are mediated by nitric oxide (NO). We have recently reported that the pH of diluted blood modulates the kinin system. The present study was aimed to investigate the role of the pH of culture media and filter-washing solutions and BK and NO generation, either in vitro and ex vivo. METHODS: BK was measured by a specific enzyme-linked immunosorbent assay (ELISA), and NO synthase (NOS) activity by 3H-citrulline production after incubation with 3H-arginine and nitrites by using the Griess reagent. In in vitro experiments, NOS activity was detected in endothelial cells (ECs) cultured with graded BK concentrations at various pH values. Blood from 30 patients in regular dialysis was ex vivo circulated in one single passage through minifilters prerinsed with pH 7 or pH 8 phosphate buffer (PB) solutions. The out-flowing blood was tested for BK and nitrite content and was incubated with cultured ECs to evaluate its capacity to modulate NOS activity. RESULTS: BK induced in vitro a dose-dependent increase in NOS activity of ECs, which was mediated by tyrosine kinase phosphorylation. NO generation was enhanced at pH 7.2, which remained unchanged at pH 7.6. In ex vivo experiments, blood out-flowing after one passage on filters washed with pH 7 PB solutions had increased BK levels (P < 0.0001), increased nitrites (P < 0.05), and enhanced EC NOS activity (P < 0. 05) in comparison to data found when filters were washed with pH 8 PB. Only when the filters were rinsed with a solution at pH 7 did PAN DX and AN69 membranes show a distinct BK generation capability, and cuprophane a peculiar capability to enhance NOS. Such effects were prevented when dialyzers were prerinsed with pH 8 PB. Multiple regression analysis showed that the pH of the uremic blood was the driving factor for BK and NOS activation (r = 0.54, P < 0.02). CONCLUSIONS: BK and NO generation are modulated by environmental pH. Rinsing the blood and dialysate compartments of filters with an alkaline solution prior to use may mitigate the activation of mediators likely to be involved in some HSRs.

[Assessment of reticulocyte hemoglobin content as a guide for iron supplementation in hemodialyzed patients]. / Valutazione del contenuto emoglobinico reticolocitario (CHr) come guida alla supplementazione marziale nei pazienti emodializzati.

BACKGROUND: In literature the reliability of reticulocyte hemoglobin content (CHr) has been recently emphasized to detect "functional" iron deficiency induced by erythropoietin therapy. METHODS: In the present work the behavior of CHr in 68 uremic patients hemodialysis has been evaluated. RESULTS: Its values appeared poorly correlated (R2 = 0.32) to the hypochromic erythrocyte percent values, and furthermore CHr sensitivity seemed poor, with pathologic low values detected in three cases only, all characterized by reduced mean corpuscular volume (MCV). CONCLUSIONS: In the cases personally observed, MCV and CHr are weakly correlated (R2 = 0.15); reticulocyte hemoglobin absolute value in personal opinion does not appear as a reliable index of iron deficiency, being rather dependent on reticulocyte volume.

Patient's needs in substitutive dialysis treatment. Some psycho-social and organizational considerations.

BACKGROUND: The observations here presented come from an action-research project carried out at the Dialysis Centre of Ivrea. The work is focused on the articulation between subjective (the felt experience) and objective variables (the structure and intervention typology) with the aim of understanding patient's needs from an organizational point of view. METHODS: A questionnaire to evaluate the needs of dialytic patients and the burden that these have on the health service and staff, was formulated by the nurses. RESULTS: The results showed how the patient's clinical history indicate, significantly, not only personal and subjective aspects (e.g. interpersonal relationships), but also how they construct their relationships with the hospital and its services (including the hospital staff). CONCLUSIONS: Data open up certain reflections on what role communication and information play within the hospital structure. Efficient communication contributes both to reduce the anxiety level and to improve the organizational climate therefore influencing service quality.

Cefonicid 'restores' the depressed activities of polymorphonuclear cells from chronic haemodialysis patients and renal transplant recipients in vitro.

BACKGROUND: Chronic haemodialysis patients and renal transplant recipients are highly susceptible to infection characterized by high morbidity and mortality and related to an impairment of the phagocytic response. SUBJECTS AND METHODS: In order to elucidate how cefonicid, a cephalosporin with a broad spectrum of activity and once-daily dosage, influences this phagocytic response, the effects of the drug upon the functions of human PMNs from both healthy individuals and immunocompromised patients were investigated. RESULTS: In vitro, PMNs from haemodialysed patients and renal transplant recipients showed a diminished phagocytic efficiency with reduced phagocytosis and bactericidal activity towards intracellular Klebsiella pneumoniae when compared with that seen in PMNs from healthy subjects. Cefonicid significantly affected the activity of PMNs from healthy volunteers, resulting in either an increased percentage of ingested klebsiellae or a reduced intracellular bacterial load when compared with the control, drug-free system. When cefonicid was added to PMNs from uraemic patients a pattern similar to that observed with phagocytes from healthy subjects was detected: the antibiotic was able to 'restore' the depressed primary functions of PMNs, resulting in a significant increase in both phagocytosis and killing activity. CONCLUSIONS: Cefonicid, with its several immunoproperties observed in this study, possesses interesting beneficial properties which make it suitable for the treatment of infections in patients with impaired components of the immune system.

[Estimation of total body water from routine urea kinetics]. / La stima dell'acqua corporea totale per la cinetica dell'urea di routine.

The comparison of total body water obtained by Watson formula with results of bioelectrical impedance (BIA) shows a fair approximation (Delta% = 1.0 +/- 8.45). However, when compared to other literature formulas the BIA values are higher (8 divided by 23%), and this discrepancy needs further analysis. Urea kinetics was computed using as input data for distribution volume both the Watson anthropometrical and the BIA TBW values: the clearance results do not differ significantly (Delta% = 0.74 +/- 8.35). The Kt/V index results are nearly identical (Delta% = 0.12 +/- 1.17), due to a mathematical loop: a wrong input of volume induces a comparable error of the clearance result, while their ratio is unchanged. For practical routine to monitoring dialysis adequacy the Watson anthropometrical formula has proven as a satisfactory simple approach. Periodical BIA determination provides useful informations mainly when the anthropometrical estimation are doubtful and the comparison of data may increase the kinetic reliability.

[Needs of patients undergoing dialysis. Psychosocial and administrative considerations]. / I bisogni del paziente in trattamento dialitico sostitutivo. Alcune riflessioni psicosociali ed organizzative.

A questionnaire to evaluate the needs of dialytic patients and the burden that these have on the health service and staff, was formulated by the nurses. The results showed how the patient's case history indicate, significantly, not only personal and subjective aspects (e.g. interpersonal relationships), but also how they construct their relationships with the hospital and its service (including the hospital staff). This opens up certain reflections on what role communication and information play within the hospital structure.

[Epstein-Barr virus infection and lymphoproliferative disorders in patients after renal transplantation]. / Infezione da virus di Epstein-Barr e disordini linfoproliferativi in portatori di trapianto renale.

We have studied EBV infection in renal transplant patients during the first year after transplantation. At trasplantation all patients were EBV seropositive and reactivation of EBV infection was demonstrated in 54% cases after one year. CMV active infection was also demonstrated in 42% of patients with EBV reactivation. No correlation was observed between EBV reactivation and age, sex, immunosuppressive treatment, degree of immunosuppression or donor/recipient HLA matching. A correlation between immunosuppressive treatment, EBV infection and lymphoproliferative disorders (LD) is described in literature, however none of our patients developed LD so far, probably due to the different immunosuppressive protocol employed.

[Proposal of new formulas for three-point urea kinetics, compared with traditional kinetics and direct dialysis quantification]. / Proposta di nuove formule per la cinetica dell'urea a tre punti, a confronto con la cinetica tradizionale (UKM) e con la quantificazione diretta della dialisi (DDQ).

Classical urea kinetic model (UKM) has been followed by several proposals to determine dialysis adequacy either by direct quantification (DDQ), either by simplified two-points formulas (pre- and post-dialysis BUN), or by mUKM, a modified three-point algorithm (pre-post and pre-next dialysis), where urea distribution volume is input to obtain clearance and urea generation rate. Our new formulas (mUKM2) are derived from urea mass balance, and avoid iterative calculation: their results are similar to those obtained by UKM and mUKM when the standard post-dialysis BUN value is employed. On the contrary, when the equilibrated net-rebound value (Cpwnr) is employed their results are very close to the reference DDQ model: however the new approach is simpler and more practical, to measure dialysis dose taking account of the urea rebound phenomenon.