Manel Vera

Acute renal failure secondary to imatinib mesylate treatment in chronic myeloid leukemia

A 58-year-old woman with chronic myeloid leukemia (CML), and previous intolerance to interferon was treated with the BCR-ABL tyrosine kinase protein inhibitor imatinib mesylate. Coincidentally, with the start of treatment, the patient developed acute renal failure, with acute tubular necrosis being observed on histopathology. Imatinib was stopped and three hemodialysis sessions were performed, which was followed by a progressive improvement of the renal function and normalization of the urine output. One year later the patient still has mild chronic renal failure and remains in chronic phase of CML on hydroxyurea treatment.

TLR4 and NALP3 inflammasome in the development of endothelial dysfunction in uraemia

The increased cardiovascular risk present in chronic kidney disease (CKD) is related to the development of endothelial dysfunction, whose mechanisms are still unclear. Accumulation of toxins and proinflammatory cytokines may constitute danger‐associated molecular patterns (DAMP) to which endothelial cells are continuously exposed. Potential involvement of mechanisms recognizing DAMP, such as TLR and inflammasomes, has been explored.

Elimination of large uremic toxins by a dialyzer specifically designed for high-volume convective therapies.

Background: Unlike conventional hemodialysis treatments, which rely almost solely on diffusion-related mechanisms for solute removal, hemodiafiltration (HDF) allows more efficient removal of higher molecular weight toxins due to convective transport mechanisms. To facilitate the removal of these toxins in HDF treatment modalities, dialyzers with highly efficient high-flux membranes are necessary. This study assessed the large uremic toxin removal ability of a high-flux dialyzer (FX CorDiax 60) specifically designed to facilitate convective therapies compared with a standard high-flux dialyzer (FX 60). Methods: In an open, randomized, cross-over, single-center, controlled, prospective clinical study, 30 adult chronic hemodialysis patients were treated by post-dilution online HDF with the FX 60 or the FX CorDiax 60 dialyzer. All other dialysis parameters were kept constant in both study arms. The reduction rate (RR) of blood urea nitrogen, phosphate, β2-microglobulin (β2-m), myoglobin, prolactin, α1-microglobulin, α1-acid glycoprotein, albumin and total protein as well as the elimination into dialysate was intraindividually compared for the two dialyzer types. Results: For FX CorDiax 60 versus FX 60, the RR was significantly higher for blood urea nitrogen (86.23 ± 4.14 vs. 84.89 ± 4.59%, p = 0.015), β2-m (84.67 ± 3.79 vs. 81.30 ± 4.82%, p < 0.0001), myoglobin (75.23 ± 10.48 vs. 58.60 ± 12.1%, p < 0.0001), prolactin (72.96 ± 9.68 vs. 56.91 ± 13.01%, p < 0.0001) and α1-microglobulin (20.89 ± 18.27 vs. 13.60 ± 12.50%, p = 0.016). There were no significant differences in the RR for phosphate, α1-acid glycoprotein, albumin and total protein. Mass removal was significantly higher with the FX CorDiax 60 than with the FX 60 for β2-m (0.26 ± 0.09 vs. 0.24 ± 0.09 g, p = 0.0006), myoglobin (1.83 ± 0.89 vs. 1.51 ± 0.76 mg, p = 0.0017), prolactin (0.17 ± 0.13 vs. 0.14 ± 0.08 mg, p = 0.02) and albumin (4.25 ± 3.49 vs. 3.01 ± 2.37 g, p = 0.03). Conclusions: This study demonstrates that treating patients with an FX CorDiax 60 instead of an FX 60 dialyzer in post-dilution HDF mode significantly increases the elimination of middle molecules.

Nocturnal, every-other-day, online haemodiafiltration: an effective therapeutic alternative

BACKGROUND Longer and more frequent dialysis sessions have demonstrated excellent survival and clinical advantages, while online haemodiafiltration (OL-HDF) provides the most efficient form of dialysis treatment. The aim of this study was to evaluate the beneficial effects of a longer (nocturnal) and more frequent (every-other-day) dialysis schedule with OL-HDF at the same or the highest convective volume. METHODS This prospective, in-centre crossover study was carried out in 26 patients, 18 males and 8 females, 49.2±14 years old, on 4-5 h thrice-weekly post-dilution OL-HDF, switched to nocturnal every-other-day OL-HDF. Patient inclusion criteria consisted of stable patients with good vascular access and with good prospects for improved occupational, psychological and social rehabilitation. Patients were randomly assigned into two groups: Group A received the same convective volume as previously for 6 months followed by a higher convective volume for a further 6 months, while Group B received the same schedule in reverse order. RESULTS Nocturnal every-other-day OL-HDF was well tolerated and 56% of patients who were working during the baseline period continued to work throughout the study with practically no absenteeism. The convective volume was 26.7±2 L at baseline, 27.5±2 with the unchanged volume and 42.9±4 L with the higher volume. eKt/V increased from 1.75±0.4 to 3.37±0.9. Bicarbonate, blood urea nitrogen (BUN) and creatinine values decreased, while phosphate levels fell markedly with a 90% reduction in phosphate binders. Blood pressure and left ventricular hypertrophy (LVH) improved and the use of anti-hypertensive drugs decreased. In both groups, BUN, creatinine and β2-microglobulin reduction ratios improved. Different removal patterns were observed for myoglobin, prolactin and α1-acid glycoprotein. CONCLUSIONS Nocturnal every-other-day OL-HDF could be an excellent therapeutic alternative since good tolerance and occupational rehabilitation, marked improvement in dialysis dose, nutritional status, LVH, phosphate and hypertension control and a substantial reduction in drug requirements were observed. In this crossover study, different removal patterns of large solutes were identified.

NFκB in the Development of Endothelial Activation and Damage in Uremia: An In Vitro Approach

Impaired hemostasis coexists with accelerated atherosclerosis in patients with chronic kidney disease (CKD). The elevated frequency of atherothrombotic events has been associated with endothelial dysfunction. The relative contribution of the uremic state and the impact of the renal replacement therapies have been often disregarded. Plasma markers of endothelial activation and damage were evaluated in three groups of patients with CKD: under conservative treatment (predialysis), on hemodialysis, and on peritoneal dialysis. Activation of p38 MAPK and the transcription factor NFκB was assessed in endothelial cell (EC) cultures exposed to pooled sera from each group of patients. Most of the markers evaluated (VCAM-1, ICAM-1, VWF, circulating endothelial cells) were significantly higher in CDK patients than in controls, being significantly more increased in the group of peritoneal dialysis patients. These results correlated with the activation of both p38 MAPK and NFκB in EC cells exposed to the same sera samples, and also to the peritoneal dialysis fluids. Hemodialysis did not further contribute to the endothelial damage induced by the uremic state observed in predialysis patients, probably due to the improved biocompatibility of the hemodialysis technique in recent years, resulting in lower cellular activation. However, peritoneal dialysis seemed to exert a significant proinflammatory effect on the endothelium that could be related to the high glucose concentrations and glucose degradation products present in the dialysis fluid. Although peritoneal dialysis has been traditionally considered a more physiological technique, our results raise some doubts with respect to inflammation and EC damage.

The association between Crohn disease and the myelodysplastic syndromes. Report of 3 cases and review of the literature.

We report 3 patients who developed Crohn disease and myelodysplastic syndrome concurrently and review 9 previously reported cases of this association. Demographic and clinical features, treatment, and outcome are presented from previous reports and our own 3 cases. Of the 12 patients, 8 were men, and the mean age was 68.8 years (range, 28-83 yr). The geographic origin was heterogeneous. Pancytopenia was found in 5 patients, anemia in 5, and bicytopenia in 2. The classification types of myelodysplastic syndrome were variable. The marrow karyotype was reported in 10 patients: it was abnormal in 5, with chromosome 20 abnormalities in 3. Crohn disease and myelodysplasia were diagnosed simultaneously in 5 patients, whereas Crohn disease antedated myelodysplasia in 4 patients (interval, 8 mo-30 yr) and myelodysplasia antedated Crohn disease in 3 patients (interval, 2 mo-4 yr). Signs and symptoms of Crohn disease improved in most patients upon specific medical treatment. However, the outcome of myelodysplastic syndrome was not favorable in 10 of 11 patients in whom it was reported, with 4 deaths due to myelodysplasia-related complications. Notably, the activity of myelodysplasia in 1 of our own patients paralleled the clinical activity of Crohn disease, and hematologic abnormalities of the myelodysplasia resolved upon successful treatment of the Crohn disease, thus strengthening the hypothesis of a pathogenetic link between the disorders. The possibility of myelodysplastic syndrome should be considered in patients with Crohn disease over the age of 50 years who have peripheral blood cytopenias. Likewise, a diagnosis of Crohn disease should be considered in patients with myelodysplastic syndrome who develop gastrointestinal symptoms such as chronic and/or bloody diarrhea. In patients with such an association, the possibility of improvement of the myelodysplasia upon successful therapy of Crohn disease should not be ruled out.

Influence of the ionic dialysance monitor on Kt measurement in hemodialysis.

BACKGROUND Ionic dialysance can provide accurate monitoring of dialysis dose during each hemodialysis session. Increasingly, hemodialysis machines incorporate devices that measure ionic dialysance, allowing the dialysis dose to be determined noninvasively in real time and in each session. Because Kt product was proposed as a measure of hemodialysis dose to avoid the reverse J-shaped curve between urea reduction ratio or Kt/V and mortality, we investigated whether ionic dialysance values and Kt measurements are affected by different ionic dialysance monitors (Diascan and online clearance monitoring [OCM]) and dialysis machines. STUDY DESIGN Four-period crossover. SETTING & PARTICIPANTS 31 adult long-term hemodialysis patients using 2 different ionic dialysance monitors in 4 dialysis machines: Diascan in Hospal Integra and Gambro AK-200 machines and OCM in Fresenius 4008S and 5008 machines. PREDICTORS Ionic dialysance monitor and machine used in 4 hemodialysis sessions for each participant. OUTCOMES Kt and Kt/V measured by using ionic dialysance and serum urea nitrogen. RESULTS Mean values for initial and final ionic dialysance were similar for Integra and AK-200 machines, both measured by using Diascan, and for the 4008S and 5008 machines, both measured by using OCM; however, OCM values tended to be greater in the 4008S and 5008 machines. Kt measured in the 4008S and 5008 machines was greater (59.6 +/- 12 and 58.6 +/- 11 L, respectively) than with the Integra and AK-200 machines (53.4 +/- 11 and 53.8 +/- 11 L). Mean urea reduction ratio and Kt/V were 78.0% +/- 8% and 1.89 +/- 0.43 for Diascan monitors and 79.6% +/- 8% and 1.99 +/- 0.44 for OCM monitors, respectively (P < 0.01). Differences between monitors in Kt determination were caused in part by a real difference in dialysis effectiveness (6%) and in part by an intermethod difference (4%). Kt adjusted by Kt/V differences was recalculated, and because of good correlation between Diascan and OCM, we were able to apply a formula (Kt(OCM) = 1.08 Kt(Diascan) - 2; r =0.95) that allowed both Kt quantification methods to be compared. LIMITATIONS Nonblinded nonrandomized small sample. CONCLUSIONS Kt is a valid method for judging dialysis dose in real time by using ionic dialysance measurements. Adjustments to correct intermethod differences may be necessary to ensure generalizability among ionic dialysance monitors.

Mid-Dilution Hemodiafiltration: A Comparison with Pre- and Postdilution Modes Using the Same Polyphenylene Membrane

As a change from Diapes to polyphenylene membrane in the mid-dilution filter has recently been developed, the aim of this study was to compare mid-dilution using this new dialyzer versus pre- and postdilution. The prospective study included 20 patients who underwent 4 hemodiafiltration (HDF) sessions: 1.7 m2 polyphenylene and predilution infusion flow (Qi) 200 ml/min, 1.7 m2 and postdilution Qi 100 ml/min, 1.9 and 2.2 m2 mid-dilution both with Qi 200 ml/ min. The urea and creatinine reduction ratios were slightly higher in postdilution. The β2-microglobulin (85.8%), myoglobin (73.6%), prolactin (67.8%) and retinol-binding protein (29.2%) reduction ratios with 1.9 m2 mid-dilution, which was similar to 2.2 m2 mid-dilution, were significantly higher than with the post- and predilution modes. Mid-dilution appears to be a good HDF alternative that allows a better removal of larger molecules than postdilution and, mainly, predilution. Mid-dilution using 1.9 or 2.2 m2 dialyzers, at the same convective volume, showed a similar removal.

Valoración de la superficie del dializador en la hemodiafiltración on-line. Elección objetiva de la superficie del dializador

INTRODUCTION Online hemodiafiltration (OL-HDF) is currently the most effective technique. Several randomized studies and meta-analyses have observed a reduction in mortality as well as a direct association with convective volume. Currently, it has not been well established whether a larger dialyzer surface area could provide better results in terms of convective and depurative effectiveness. The aim of this study was to assess the effect of larger dialyzer surface areas on convective volume and filtration capacity. MATERIAL AND METHODS A total of 37 patients were studied, including 31 men and 6 women, who were in the OL-HDF program using a 5008 Cordiax monitor with auto-substitution. Each patient was analyzed in 3 sessions in which only the dialyzer surface area varied (1.0, 1.4 or 1.8 m(2)). The concentrations of urea (60 Da), creatinine (113 Da), β2-microglobulin (11800 Da), myoglobin (17200 Da) and α1-microglobulin (33000 Da) were determined in serum at the beginning and end of each session in order to calculate the percent reduction of these solutes. RESULTS The convective volume reached was 29.8 ± 3.0 with 1.0 m(2), 32.7 ± 3.1 (an increase of 6%) with 1.4 m(2), and 34.7 ± 3.3 L (an increase of 16%) with 1.8 m(2) (p<.001). The increased surface of the dialyzer showed an increase in the dialysis dose as well as urea and creatinine filtration. The percentage of β2m reduction increased from 80.0 ± 5.6 with 1.0 m(2) to 83.2 ± 4.2 with 1.4 m(2) and to 84.3 ± 4.0% with 1.8 m(2). As for myoglobin and a1-microglobulin, significant differences were observed between smaller surface area (1.0 m(2)) 65.6 ± 11 and 20.1 ± 9.3 and the other two surface areas, which were 70.0 ± 8.1 and 24.1 ± 7.1 (1.4 m(2)) and 72.3 ± 8.7 and 28.6 ± 12 (1.8 m(2)). CONCLUSION The 40% and 80% increases in surface area led to increased convective volumes of 6 and 16% respectively, while showing minimal differences in both the convective volume as well as the filtration capacity when the CUF was higher than 45 ml/h/mmHg. It is recommended to optimize the performance of dialyzers with the minimal surface area possible when adjusting the treatment prescription.

Practical Utility of On-Line Clearance and Blood Temperature Monitors as Noninvasive Techniques to Measure Hemodialysis Blood Access Flow

Background/Aims: Access blood flow (Qa) measurements are recommended by the current guidelines as one of the most important components in vascular access maintenance programs. This study evaluates the efficiency of Qa measurement with on-line conductivity (OLC-Qa) and blood temperature monitoring (BTM-Qa) in comparison with the gold standard saline dilution method (SDM-Qa). Subjects and Methods: 50 long-term hemodialysis patients (42 arteriovenous fistulas/8 arteriovenous grafts) were studied. Bland-Altman and Lin’s coefficient (ρc) were used to study accuracy and precision. Results: Mean values were 1,021.7 ± 502.4 ml/min SDM-Qa, 832.8 ± 574.3 ml/min OLC-Qa (p = 0.007) and 1,094.9 ± 491.9 ml/min with BTM-Qa (p = NS). Biases and ρc obtained were –188.8 ml/min (ρc 0.58) OLC-Qa and 73.2 ml/min (ρc 0.89) BTM-Qa. The limits of agreement (bias ± 1.96 SD) obtained were from –1,119 to 741.3 ml/min (OLC-Qa) and –350.6 to 497.2 ml/min (BTM-Qa). Conclusions: BTM-Qa and OLC-Qa are valid noninvasive and practical methods to estimate Qa, although BTM-Qa was more accurate and had better concordance than OLC-Qa compared with SDM-Qa.