High prevalence in Switzerland of pure red-cell aplasia due to anti-erythropoietin antibodies in chronic dialysis patients: report of five cases

Background. Pure red-cell aplasia (PRCA) after erythropoietin (Epo) administration due to the appearance of neutralizing anti-Epo antibodies has been reported in over 200 cases between 1998 and 2002. However, large intercountry disparities were observed in the occurrence of this syndrome. Methods. On behalf of the Swiss Society of Nephrology, a survey was conducted in all the dialysis units of Switzerland in order to collect information on the occurrence, diagnostic and evolution data of the cases observed. A questionnaire was send to the nephrologists in charge of each of the 69 dialysis units in January 2003. The clinical and biological data of the suspected cases were analysed and compared with the data provided to health authorities and pharmaceutical companies. Results. A total of five cases were identified as true PRCA with demonstrated positive anti-Epo antibodies. They occurred between November 1998 and February 2002, were all treated by haemodialysis and had received Epo subcutaneously. The median appearance time of refractory anaemia after Epo initiation was 10 months (range: 7-54 months). Two cases had been treated exclusively with epoietin-α, one solely with epoietin-β and the two others with a combination of both. With five cases out of a total of about 2500 dialysis patients and 2300 Epo-treated dialysis patients or an exposure rate to Epo of 9900 dialysis patient-years during a 4.3 year period, this prevalence is among the highest of those reported in European countries. Conclusions. The prevalence of PRCA after Epo administration in dialysis patients appears particularly high in Switzerland. Among the potential explanations, the most plausible are the high percentage of dialysis patients treated with Epo, the almost exclusive subcutaneous administration, the larger market distribution of the epoietin-α brand, the eventual disruption of the cold chain and the setting-up of a systematic national surve

High prevalence in Switzerland of pure red-cell aplasia due to anti-erythropoietin antibodies in chronic dialysis patients: report of five cases

Background. Pure red-cell aplasia (PRCA) after erythropoietin (Epo) administration due to the appearance of neutralizing anti-Epo antibodies has been reported in over 200 cases between 1998 and 2002. However, large intercountry disparities were observed in the occurrence of this syndrome. Methods. On behalf of the Swiss Society of Nephrology, a survey was conducted in all the dialysis units of Switzerland in order to collect information on the occurrence, diagnostic and evolution data of the cases observed. A questionnaire was send to the nephrologists in charge of each of the 69 dialysis units in January 2003. The clinical and biological data of the suspected cases were analysed and compared with the data provided to health authorities and pharmaceutical companies. Results. A total of five cases were identified as true PRCA with demonstrated positive anti-Epo antibodies. They occurred between November 1998 and February 2002, were all treated by haemodialysis and had received Epo subcutaneously. The median appearance time of refractory anaemia after Epo initiation was 10 months (range: 7-54 months). Two cases had been treated exclusively with epoietin-α, one solely with epoietin-β and the two others with a combination of both. With five cases out of a total of about 2500 dialysis patients and 2300 Epo-treated dialysis patients or an exposure rate to Epo of 9900 dialysis patient-years during a 4.3 year period, this prevalence is among the highest of those reported in European countries. Conclusions. The prevalence of PRCA after Epo administration in dialysis patients appears particularly high in Switzerland. Among the potential explanations, the most plausible are the high percentage of dialysis patients treated with Epo, the almost exclusive subcutaneous administration, the larger market distribution of the epoietin-α brand, the eventual disruption of the cold chain and the setting-up of a systematic national surve

Statistical analysis of large amount of data aimed at the development of a index to predict intra-dialysis hypotensive events

Background: The increase of aged patients with concurrent comorbities imply also a growth in end stage renal diseases incidence. HaemoDialysis (HD) has than a large medical, social and economical impact for health care systems. The personalization of the therapy is strategic to reduce costs and it can be performed basing on the information acquired by the collection the clinical data related to the treatment. The current work attempts to the extraction of an intradialytic hypotensive (IDH) events prediction index through the statistical mining of HD data coming from a multicentric study involving four different Italian and Swiss clinical centers. This work is part of the Project DialysIS, founded by a Cross-border Cooperation Programme (INTERREG IT/CH 2007–2013). Methods: Data referred to a total of 516 sessions performed on 70 adult patients undergoing dialysis treatment were collected. Clinical prescriptions, hydration status, dialysis machine data and hematochemical data were recorded in a flexible structured database. A statistical analysis was performed to find risk factors for IDH onset. The enrolled patients were classified in IDH prone and resistant, defining Hypotension Prone (HP), a patient who suffered of IDH in 2 or more session and Hypotension Resistant (HR) a patient who suffered at most 1 IDH episode. F and T test was performed on data to determine the significantly different parameters among the two groups. The new index J was defined as a weighted patient-specific combination these parameters, and was calculated for each session of each patient. Results: Using these patient specific coefficients, J results able to predict the 100% of treatments characterized by IDH events, with 38% of false positives (session at risk of IDH, without IDH onset). Conclusions: The J index can point out the risk to develop cardiovascular instabilities during each single treatment based on longitudinal observations of the patient specific parameters

Evaluation of the reliability of different methods for the determination of the hydration status in haemodialysis patients

Background: Determination of hydration status in Haemodialysis patients is crucial to correctly assess the dry weight and calculate the amount of excess fluid to be removed by ultrafiltration (UF). The Total Body Water (TBW) can be estimated by different techniques, from mathematical equations to bioimpedance analysis. Several formulas were used to estimate initial Total Body Water (TBW0) based on demographic or anthropometric data. The aim of this study was to compare the different available methods to identify the most objective and reliable method to be used for a correct identification of the TBW in patients undergoing haemodialysis. This work is part of the project DialysIS, founded by a Cross-border Cooperation Programme (INTERREG IT/CH 2007–2013). Methods: TBW0 was calculated by using a classical basic anthropometric formula (TBW-A), the Watson formula (TBW-W) and the Watson formula modified with a correctional term (TBW-Wc), accounting for the part of fluids not drained by the kidneys. The last equation was applied using either real end session weight (TBW-WcR) or the clinically prescribed dry weight (TBW-WcP). TBW0 was computed using the listed methods for 450 haemodialysis sessions pertinent to 70 patients dialyzed in two different dialysis centres (A. Manzoni Hospital, Lecco, Italy; EOC Lugano, Switzerland). Results: The modified Watson formula, thanks to the correctional term, allows obtaining more precise measurements: TBW0 values were comprised between those determined with TBW-A (overestimation) and those achieved by TBW-W (underestimation). The differences among the set of values were statistically significant; exception made for those obtained using TBW-WcR and TBW-WcP. Conclusions: TBW-WcP enables to reach estimations of the TBW initial value comparable to the ones calculated considering the real end session dry weight (TBW-WcR), with the advantage to be suitably used in a predictive algorithm. The anthropometric formula, as well as Watson equation without correctional term, showed to be less robust methods

Preliminary results of dialysis study: single pool variable-volume calcium kinetic model

Background: The primary aim of the international study DialysIS (Dialysis therapy between Italy and Switzerland) is the increased personalization of hemodialytic treatments through a modellistic approach. Within the DialysIS study, we investigated the use of a single-pool variable-volume Ca kinetic model to assess the intradialytic calcium mass balance (Ca2 + MB) in chronic and stable dialysis patients. Methods: 34 patients on thrice-weekly bicarbonate high-flux hemodialysis were studied during 240 dialysis sessions (mean 6.5 ± 1.9 for each patient; range 3–9). All patients were dialyzed with a nominal d[Ca] of 1.50 mmol/l. Ionized calcium concentrations of plasma water (Ca2 + pw) and dialysate (Ca2 + di) were determined at the beginning and end of each session; calcium dialysance (DCa) was estimated from conductivity dialysance. The most useful variable for validating this methodology was considered being the difference between end-dialysis ionized plasma water calcium concentration measured value, normalized to pH 7.40 (adjCa2 + pwtM), and predicted by the model (Ca2 + pwtP) applying: Ca2 + pwtP = 1/∙(Ca2 + di-(Ca2 + di–∙Ca2 + pw0)∙(VtCa/V0Ca) (DCa∙∙(1/Qfecv-1/Qpwi))) With  (Donnan’s factor) equal to 0.938. Results shown as mean ± standard deviation when normal, median (range) when non-normal. Results: A mean negative Ca2 + MB (–0.83 ± 1.33 mmol) and a statistically significant temporary parathyroid hormone (PTH) reduction was found (PTHt-PTH0: –128 (–488 ÷ 432) pg/ml p <0.01). Figure 1 shows the difference between the distribution of the predicted values, the adjusted values (Ca2+pwtP – adjCa2+pwtM: 0.016 (–0.08 ÷ 0.16) mmol/l)and the non-corrected values (Ca2+pwtP – Ca2+pwtM: 0.073 (–0.03 ÷ 0.20) mmol/l). Conclusions: The very low differences between predicted and adjusted Capwt suggest that it is possible to model and predict Ca2+MB during dialysis with a nominal dialysate calcium concentration of 1.5 mmol/l and a final calcium level in physiological range

Preliminary results of dialysis study: accuracy of a single pool variable-volume calcium kinetic model with different calcium dialysate concentrations

Background: The primary aim of the international study DialysIS (Dialysis therapy between Italy and Switzerland) is the increased personalization of hemodialytic treatments through a modellistic approach. Within the DialysIS study, we compare the accuracy of a single-pool variable volume calcium kinetic model (SPVV-CaKM) using two different dialysate calcium concentrations (CaD). Methods: Pre- and post-treatment relevant variables of 34 patients treated with nominal CaD of 1.5 mmol/l (Group 1) and 22 patients with nominal CaD of 1.75 mmol/l (Group 2) were analyzed. The accuracy was evaluated determining the difference between predicted (Ca2+pwtP) and measured (Ca2+pwt) plasma water ionized calcium concentrations at the end of the dialysis sessions. To account for the changes in blood pH during dialysis session, which is known to affect plasma water ionized calcium concentrations, Ca2+pwt values were normalized at pH of 7.40. Results: Fig. 1 indicate that the predicted values almost overlap t he normalized values for Group 1, while it’s significantly higher for Group 2. Conclusion: The SPVV-CaKM is accurate in Group 1 while it overestimates the Ca2+pwt Group 2. The Ca2+pwt of the two groups doesn’t seem to account for the increased CaD. This suggests the presence of an additional compartment. Our hypothesis is that the administered calcium, predicted by our model, that doesn’t appear plasma could be deposited in bones and/or soft tissues. It is then theoretically possible to estimate the total calcium deposition or accumulation from the difference between predicted and measured post-treatment values

PRELIMINARY RESULTS OF DIALYSIS STUDY: ACCURACY OF A SINGLE POOL VARIABLE-VOLUME CALCIUM KINETIC MODEL WITH DIFFERENT CALCIUM DIALYSATE CONCENTRATIONS

INTRODUCTION AND AIMS: The primary aim of the international DialysIS study (Dialysis therapy between Italy and Switzerland) is to imptove the personalization of hemodialysis treatments through a modeling approach. Within the DialysIS study, we compared the accuracy of a single-pool variable volume calcium kinetic model (SPVV-CaKM) using two different dialysate calcium concentrations (CaD). METHODS: Pre- and post-treatment relevant variables of 31 patients treated with nominal CaD of 1.5 mmol/l (Group 1) and 22 patients with nominal CaD of 1.75 mmol/l (Group 2) were analyzed. The accuracy of the model was evaluated by determining the difference between predicted (Ca2+pwtP) and measured (Ca2+pwt) plasma water ionized calcium concentrations at the end of the dialysis sessions. To account for the changes in blood pH during dialysis session, which is known to affect plasma water ionized calcium concentrations, Ca2+pwt values were normalized at pH of 7.40. RESULTS: In Group 1 we found: Ca2+D = 1.26 + 0.04 mmol/l; a rise in Ca2+pw from 1.18 + 0.07 at the start to 1.32 + 0.04 mmol/l at the end of the dialysis session with a mean difference between Ca2+pwtP (1.33 + 0.04 mmol/l) and Ca2+pwt of 0.01 + 0.04 mmol/l. In Group 2 we found : Ca2+D = 1.41 + 0.04 mmol/l; a similar rise in Ca2+pw (from 1.18 + 0.07 mmol/l to 1.36 + 0.06 mmol/l) but with a mean difference between Ca2+pwtP (1.48 + 0.04 mmol/l) and Ca2+pwt of 0.12 + 0.05 mmol/l.CONCLUSIONS: The SPVV-CaKM was highly accurate when using a dialysate calcium concentration of 1.5 mmol/l while it wildly overestimated the post-treatment plasma water concentration when using a higher dialysate calcium concentration; the measured post-treatment values in the two groups did not seem to account for the increased dialysate calcium concentration, suggesting the presence of an additional compartment. We hypothesize that the administered calcium that according to our model did not appear in the plasma could be deposited in bones and/or soft tissues. It is then theoretically possible to estimate the total calcium deposition or accumulation from the difference between predicted and measured post-treatment in Ca2+pw values