GVHD-associated chronic kidney disease after allogeneic haematopoietic cell transplantation.

Chronic kidney disease (CKD) has been related to allogeneic haematopoietic cell transplantation (HCT) as a late effect caused by a variety of factors. We retrospectively evaluated the development of CKD in 230 patients, aged 34 (5-65) years, who had undergone allogeneic HCT for haematological disease, using sibling or unrelated donors and myeloablative or reduced conditioning regimens. Pre-HCT glomerular filtration rate (GFR) was within normal limits (108±28 mL/min/1.73 m(2)) in patients who did not develop CKD and 95±24 mL/min/1.73 m(2) in those with CKD postHCT, while the GFR 12 months post transplant declined to 104±26 and 69±19 mL/min/1.73 m(2), respectively. CKD incidence was 20.4%, with a median time of development of 6 (3-18) months post transplant. On multivariate analysis, risk factors for CKD were the presence of chronic GVHD (cGVHD; P=0.001), unrelated donor transplantation (P=0.008), post-transplant event of acute kidney injury (AKI) (P=0.002) and older age (P=0.002). In long-term survivors stable significant predictors for CKD were older age at transplantation, cGVHD and AKI. CKD did not influence non-relapse mortality. In our study, cGVHD emerges as an important cause of kidney injury in HCT survivors, regardless of administration of nephrotoxic agents.

Use of fondaparinux as an anticoagulant during hemodialysis: a preliminary study.

OBJECTIVE: To study the effect of fondaparinux, a new antithrombotic agent, as an anticoagulant during a 4-hour conventional hemodialysis session. materials and methods: Fondaparinux was administered as an anticoagulant to 16 chronic hemodialysis patients during a single 4-hour hemodialysis session at an intravenous bolus dose of 2.5 mg. Eight patients were using high-flux polyester polymer alloy (PEPA) dialyzers (Group A) and the remainder low-flux polysulfone dialyzers (Group B), whilst all had received conventional doses of tinzaparin sodium as an anticoagulant during the previous month. The dialyzers were primed with 1 l of normal saline containing 5,000 IU of unfractionated heparin. Blood samples for the measurement of INR, APTT (activated partial thromboplastin time) and anti-Xa levels were taken before the study dialysis session (pre), 5 min postdialysis (post), and before the next dialysis session (next). Mean fibrin/clot formation in the extracorporeal circuit and dialyzer was assessed macroscopically by visual inspection and was graded using a 4-point scale. RESULTS: Predialysis anti-Xa levels were 0.04 A+/- 0.03 IU/ml in Group A, and 0.025 A+/- 0.025 IU/ml in Group B (p = NS). Postdialysis anti-Xa levels were significantly higher than predialysis levels in both groups (Group A = 0.16 A+/- 0.04 IU/ml, Group B = 0.46 A+/- 0.12 IU/ml, p < 0.02 for both) and significantly higher in Group B compared to Group A (p < 0.025). Anti-Xa levels before the next dialysis session were 0.06 A+/- 0.04 IU/ml in Group A and 0.25 A+/- 0.06 IU/ml in Group B (p < 0.0001 between Groups A and B). APTT values were significantly higher in postdialysis than predialysis samples for both groups (higher by 27.0 A+/- 26.0% in Group A and 24.3 A+/- 31.9% in Group B). No significant differences were found when comparing APTT values in pre, post and next samples between Groups A and B. No differences were also found between pre, post and next samples for INR values, either within or between groups. Mean fibrin/ clot formation score in the extracorporeal circuit at the end of the study dialysis session was significantly higher in patients of Group A than those of Group B (p < 0.05). Dialysis had to be terminated before the completion of 4 hours in 2 patients of Group A because of the presence of extensive fibrin/clots in the circuit and dialyzer. CONCLUSIONS: Our findings indicate that fondaparinux sodium at an intravenous dose of 2.5 mg can be used successfully as an anticoagulant during a 4-hour conventional hemodialysis session in patients dialyzed with low-flux polysulfone dialyzers, but not in those dialyzed with high-flux dialyzers. However, anti-Xa levels in the former patients were still increased before the next dialysis session, potentially exposing the patients to an increased risk of bleeding.

Hemoglobin changes at the initiation of high-flux hemodialysis.

BACKGROUND: The aim of the present study was to assess hemoglobin changes occurring at the beginning of high-flux hemodialysis (HD). METHODS: In a group of 20 chronic HD patients (group A), total hemoglobin (tHb), hematocrit (Hct) and total serum proteins (TP) were measured in blood samples drawn from an arterial fistula needle before the initiation of high-flux HD, and from an arterial line 5 min after HD with the dialysate in the bypass mode. 31 chronic stable HD patients (group B) served as controls. In group B patients, tHb was measured in blood samples drawn from an arterial fistula needle before the initiation of high-flux HD, and from arterial and venous lines simultaneously 5 min later. Blood flow rates in groups A and B were set from the beginning of the study to 300 ml/min, while the bicarbonate dialysate flow rate and ultrafiltration rate in group B patients was set to 700 ml/min and zero, respectively. The same high-flux dialyzer was used for all patients (FLX-18, membrane PEPA 1.8 m(2)). RESULTS: A comparison of baseline (pre-dialysis) values with those derived from an analysis of the arterial line in groups A and B at 5 min revealed that tHb decreased by 0.6 +/- 0.2 g/dl (5.2 +/- 1.7%, p < 0.001) and 0.7 +/- 0.7 g/dl (5.4 +/- 6.2%, p < 0.001), respectively. At the same time, Hct and TP in group A decreased by 1.32 +/- 0.7% (3.8 +/- 2.0%, p <0.001) and 0.3 +/- 0.1 g/dl (4.8 +/- 1.4%, p < 0.001), respectively. Blood volume (BV) and plasma volume (PV) in group A patients at 5 min as calculated from tHb and TP values increased by 5.6 +/- 1.9 and 5.2 +/- 1.7%, respectively, while BV in group B patients increased by 6.1 +/- 7.0% (not significant when compared to group A). tHb did not change significantly in 14 patients (group C) studied immediately after adopting the supine position and 5 min later in the absence of HD. CONCLUSION: A 5% decrease in tHb was observed 5 min after the initiation of high-flux HD with a zero ultrafiltration rate, and was due to an increase in BV.

Comparison of two low-molecular weight heparins (LMWHs), tinzaparin and bemiparin, during hemodialysis.

The anticoagulant effects of two LMWHs, tinzaparin sodium and bemiparin sodium, were compared during two study dialysis (SD) sessions (SD1 with tinzaparin and SD2 with bemiparin) in ten chronic hemodialysis patients. Prior to SD1, patients had received 3,500 IU of tinzaparin in each dialysis session for two weeks. After SD1, they were switched to 3,500 IU of bemiparin for two weeks and the second study dialysis session (SD2) was carried out. Patients used the same dialyzers during the whole study period and no changes were made in any of the other hemodialysis parameters. Blood samples for the measurement of PT, aPTT and anti-Xa activity were taken before the study dialysis sessions (sample 0), and again at two and four hours after the initiation of dialysis (samples 2-h and 4-h, respectively). PT values showed no change between the SD1 and SD2 sessions, but aPTT values were significantly higher in the 2-h and 4-h samples of the SD1 session compared to corresponding values in SD2 samples (p < 0.005). Anti-Xa activity was higher in the 2-h and 4-h samples of the SD2 session compared to the SD 1 session (p = 0.005 and p = 0.012, respectively). At four hours, only patients receiving bemiparin had a mean anti-Xa activity higher than 0.40 IU/mg (mean 0.51 +/- 0.76). However, fibrin/clot formation in the extracorporeal circuit during each study period as assessed by visual inspection, did not differ significantly between sessions. It is concluded that the anticoagulant profile of bemiparin sodium during hemodialysis treatment is superior to that of tinzaparin.

Tunneled double-lumen silicone hemodialysis catheter placement in three patients with permanent pacemaker wires: a case study.

Permanent pacemaker wires have been described as a cause of central vein stenosis. Furthermore, in hemodialysis (HD) patients with transvenous pacemakers, permanent vascular access (VA) created at the ipsilateral arm is not always successful. We report the use of tunneled double-lumen silicone HD catheters, as permanent VA in three HD patients wearing permanent transvenous pacemakers. In one patient, the catheter was inserted ipsilateral to the pacemaker site. Catheter-related infections were the most significant complications.

Experience with the use of uncuffed double-lumen silicone hemodialysis catheters.

AIM: This study aimed to describe our experience with the use of uncuffed double-lumen silicone hemodialysis catheters (USHDCs) that were used in 54 cases as a temporary vascular access (VA). SUBJECTS AND METHODS: We recorded, retrospectively, all the USHDCs (size 13.5 French (F), length 15, 20 and 24 cm) that were inserted in our dialysis unit from July 2003 to September 2004. Catheter and patient characteristics, as well as catheter related complications, were recorded. RESULTS: There were 88 catheters used in 54 cases (44 patients). The catheters remained in place for a total of 2537 days (range 8-127 days, mean 46.9 +/- 31.1). For catheter placement, the internal jugular veins (group A) or the femoral veins (group B) were used in a non-randomized manner. In group A, in 17 cases, 31 catheters were used for a total of 1169 days (mean 68.7 +/- 28.5), while in group B, in 37 cases, 57 catheters were used for a total of 1368 days (mean 36.9 +/- 27.1; p < 0.001). In group B, 81% of cases (30/37) were ambulatory from the time of insertion. Mean urea reduction ratio (URR) in well functioning catheters (blood flow > or = 200 ml/min) was 65.5 +/- 4.6% in group A and 56.9 +/- 6.2% in group B; p < 0.001. Catheter-related bacteremia was observed in five group A cases and in seven group B cases (p = ns). Three cases of minor bleeding at the insertion site and three cases of ipsilateral leg edema were recorded in group B patients. In group A, only one case of bleeding at the insertion site was recorded. CONCLUSION: Uncuffed double-lumen silicone hemodialysis catheters (USHDCs), 13.5 F in size, provided a very efficient temporary VA when placed in the jugular vein. Femoral placement of these catheters can also be used successfully in non bed-ridden patients, but delivering a lower dialysis dose.

Combined treatment with low-dose pravastatin and fish oil in post-renal transplantation dislipidemia.

BACKGROUND: The most common cause of post-transplant dyslipidemia is the use of corticosteroids and cyclosporin-A (CyA). The HMG-CoA reductase inhibitors have emerged as the agents of first choice in the treatment of post-transplant hyperlipidemia in combination with low fat diet. The objective of this study was to evaluate the efficacy of combined treatment with low-dose pravastatin and fish oil in post-renal transplantation dislipidemia. PATIENTS AND METHODS: Twenty-four renal transplant patients, 15 men and 9 women aged from 30 to 60 years with stable renal function were included in this study. All patients were transplanted from living related donors and were given a stable triple immunosuppressive therapy, with methylprednisolone, azathioprine and CyA. All patients were also given a standard diet containing 1 g/kg BW protein, reducing the daily fat to less than 30%, and maintaining at least a 1:1 ratio of saturated to polyunsaturated (or monounsaturated) fats. A dosage of 20 mg pravastatin (pravachol) and 1 g of fish oil (prolipid) were added to the diet after dinner, according to our protocol. Blood samples were taken after each study period for total cholesterol, LDL-cholesterol, triglycerides, Apo A(1), Apo B, Lp(a), creatinine, CPK and fibrinogen determination. RESULTS: At the end of the therapeutic protocol with pravastatin a significant reduction (p < 0.02) of total and LDL-cholesterol was observed, but no significant change in triglycerides, HDL, Lp(a), Apo A(1), Apo B and fibrinogen was shown. At the end of the therapeutic protocol with pravastatin and fish oil supplement significant changes were seen in TC (p < 0.02), TG (p < 0.03), LDL-C (p < 0.03), Apo A(1) (p < 0.04) and Apo B (p < 0.05) concentrations. There were no significant changes in HDL-C and Lp(a) concentrations. Renal function and cyclosporine levels were not changed during and after the study. CPK was increased only in one case. CONCLUSIONS: It is suggested that if the response to the diet is inadequate, the use of combined treatment with low-dose pravastatin and fish oil is a more effective strategy than the pravastatin treatment alone for changing the lipid profile after renal transplantation.

Hypertension in chronic hemodialysis patients: current view on pathophysiology and treatment.

BACKGROUND: Hypertension accounts for 65 - 85% of patients beginning dialysis, and dialysis alone controls hypertension in over 50% of patients. PATIENT AND METHODS: We have surveyed the status of BP control in 113 hemodialysis patients, 66 men and 47 women, aged 59 +/- 13 years old, with a mean duration on hemodialysis 42 +/- 44 months. The following measurements were recorded: predialysis mean arterial pressure (pre-MAP), post-dialysis MAP (post-MAP), percentage of change in MAP, pre-dialysis weight, post-dialysis weight, fluid removed by ultrafiltration during each dialysis session, interdialytic weight gain and excess weight over the desirable dry weight. RESULTS: Our results showed a hypertension prevalence of 59% (hypertension defined as pre-MAP +/- 110 mmHg). MAP was not different between men and women, and only 4.5% of patients had isolated systolic hypertension. All hypertensive patients were on treatment with antihypertensives. Reduction in post-MAP by > or = 5% (controlled by ultrafiltration) was found in 68.5% of hypertensive and in 87.5% of normotensive patients. Age, primary renal disease, time on dialysis and adequacy of dialysis were not correlated with pre-MAP. Excess volume and interdialytic weight gain were found to correlate with pre-MAP (p = 0.03). Also, the weekly dosage of EPO had a significant correlation with pre-MAP (p = 0.03). No differences were found among four classes of antihypertensive drugs regarding the BP control. Patients with hypertension requiring one drug achieved a significantly (p < 0.05) lower pre-MAP than the group of patients receiving three or more drugs. In conclusion, hemodialysis population shows high prevalence of hypertension, resistant to antihypertensive treatment. CONCLUSION: Current methods of hemodialysis are not effective in controlling BP. This implies that more insight into the role of excess volume and vasomotor systems in the pathogenesis of dialysis hypertension is warranted.

Survival and complications of 225 catheters used in continuous ambulatory peritoneal dialysis: one-center experience in Northern Greece.

This study reports our experience with permanent peritoneal catheters. From July 1983 until December 1997, 225 catheters were implanted surgically in 207 patients (120 males, 87 females) with mean age of 58+/-16 years (range: 2-82 years), and a mean duration of continuous peritoneal dialysis (CAPD) of 21.9+/-21.3 months (range: 1-145 months). Two hundred and seventeen catheters were used in 199 patients suffering from end-stage renal disease (ESRD), and 8 catheters in 8 patients with end-stage heart failure resistant to medical therapy. One patient used 3 catheters and 16 patients used 2 catheters. The catheters used were: Tenckhoff, 2; Oreopoulos-Zellerman-1 (OZ-1), 10; OZ-2, 205; and OZ-pediatric, 8. All catheters were implanted by the same surgical team, through a paramedian incision under local anesthesia. By life table analysis, the actuarial survival rates at 1 year, 2 years, 3 years, and 5 years were 97%, 92%, 87%, and 82% respectively for all catheters. The catheter-related complications were: 5 obstructions, 2 dislodgments, 13 dialysate leaks (6 early; 7 late), 90 exit-site/tunnel infections (in 56 patients), 2 cuff extrusions, and 37 hernias (in 31 patients). Eighteen catheters were replaced for persistent peritonitis (15 cases), dislodgment (1 case), obstruction (1 case), and accidental shortening (1 case). The total observation period was 4526 patient-months. The overall incidence of peritonitis was one episode per 15 patient-months, and of exit-site/tunnel infections was one episode per 50 patient-months, with a significant improvement during the last years. We conclude that OZ catheters implanted surgically through a paramedian incision have a very high survival rate and a low complication rate.