The effect of heparinized catheter lock solutions on systemic anticoagulation in hemodialysis patients.

BACKGROUND: Hemodialysis catheter thrombosis is associated with loss of catheter patency, catheter-related bacteremia and sepsis. To limit these risks, many renal units use heparin as a catheter-locking solution. In this study we investigate the effect of different concentrations of heparin catheter lock solution on systemic anticoagulation in an investigator-blinded randomized study of patients with non-tunneled (temporary) central venous catheters. METHODS: 28 consecutive patients requiring insertion of a temporary non-tunneled dual lumen central venous hemodialysis catheter were randomly allocated to receive either heparin 5,000 IU/ml or heparin 1,000 IU/ml as catheter lock solutions. The primary outcome measure was the difference in activated partial thromboplastin time (APTT) at 10 minutes following catheter locking with heparin 5,000 IU/ml and heparin 1,000 IU/ml. Secondary outcomes included intradialytic blood flow rates, catheter removal due to insufficient hemodialysis blood flow to maintain hemodialysis and catheter-related bacteremia. RESULTS: 13 patients were randomized to the heparin 1,000 IU/ml group with 15 patients randomized to the heparin 5,000 IU/ml group. There was a statistically significant increase in APTT at 10 minutes between groups with median +22.2% (range 0 - 210) rise in APTT in the heparin 1,000 IU/ml group compared with +373.7% (range 133 - 800) in the heparin 5,000 IU/ml group (p < 0.001). There was no statistically significant difference between groups with the secondary outcomes of intradialytic blood flow, catheter failure rates and catheter-related bacteremia rates. CONCLUSIONS: Heparin 1,000 IU/ml catheter lock solution confers a significantly lower risk of systemic heparinization than heparin 5,000 IU/ml without any overtly detrimental effect on intradialytic blood flow, catheter failure rates and catheter-related bacteremia rates.

Vascular access in haemodialysis patients: a modifiable risk factor for bacteraemia and death.

BACKGROUND: Bacteraemia and the development of sepsis syndrome is second only to cardiovascular disease as the leading cause of death in patients on renal replacement therapy. AIM: To determine the contributions of laboratory and clinical variables to the risk of bacteraemia and death in haemodialysis patients. DESIGN: Retrospective analysis. METHODS: We analysed all patients receiving haemodialysis in our renal unit at the beginning of January 2004 (n=263), recording clinical and laboratory variables for each patient at study entry. Bacteraemia and mortality were recorded for the subsequent 18-month period. Multivariate analysis using a Cox proportional hazards model was used to test for independent associations between variables and outcomes. RESULTS: During the study period, 45 patients (17.1%) developed bacteraemia and 65 (24.7%) died. Under multivariate analysis, use of dialysis catheters at study entry was a major factor in the development of bacteraemia and death with hazard ratios (HR) of 5.4 (p<0.001) and 2.8 (p=0.012), respectively, for tunnelled central venous catheters vs. arteriovenous fistulas (AVFs) and 3.1 (p=0.01) and 3.4 (p=0.001), respectively, for non-tunnelled central venous catheters vs. AVFs. Elevated CRP at study entry was independently associated with bacteraemia (HR 1.5 per unit log-CRP, p=0.006). Low serum albumin (HR 0.92, p=0.005) was independently associated with death. DISCUSSION: Use of synthetic vascular access catheters and heightened inflammatory state both have strong independent associations with subsequent bacteraemia and death. Bacteraemia surveillance strategies should be developed, with consideration of vascular access type and baseline inflammatory state as key components.

Assessing the utility of the stop dialysate flow method in patients receiving haemodiafiltration.

BACKGROUND: The stop dialysate flow (SDF) method of post-dialysis urea sampling is the most commonly used method in the UK. It can also be used with a published formula to predict 30 min equilibrated urea accurately. The method has not been validated in patients undergoing haemodiafiltration (HDF). Given the increased use of HDF across Europe, we felt it prudent to assess the utility of the SDF method and prediction equation in this modality. METHODS: Fourteen patients from two renal units were studied. Blood samples were taken at 1 min intervals from the arterial side of the dialysis circuit in the first 5 min after HDF had ceased whilst blood circulation continued. A peripheral sample was taken from the contralateral arm immediately after HDF had ceased and a 30 min sample was taken from the arterial needle. These samples were used to assess the utility of 5 min arterial blood urea and the 30 min prediction formula, respectively. RESULTS: Blood urea measured from the arterial circuit at 5 min correlated closely with the contralateral sample taken immediately post-HDF, with no significant difference (6.45+/-2.11 vs 6.52+/-2.19 mmol/l, P = 0.39). The use of 5 min arterial blood urea and prediction formula allowed an accurate prediction of 30 min urea (R2 = 0.96). CONCLUSIONS: The use of the SDF method with a 5 min post-HDF arterial sample is valid in patients receiving HDF. The previously published prediction formula for estimating 30 min urea is also valid using the 5 min post-HDF sample.

The spectrum of peritoneal fibrosing syndromes in peritoneal dialysis.

A variable degree of diffuse peritoneal fibrosis has been documented in all patients who have been on long-term peritoneal dialysis. Peritoneal dialysis-induced diffuse peritoneal fibrosis varies from opacification and "tanning" of the peritoneum, which may have only a moderate detrimental effect on peritoneal transport kinetics, to a progressive, sclerosing encapsulating peritonitis (SEP), which may lead to cessation of peritoneal dialysis and to death. Fewer than 1% of peritoneal dialysis patients develop overt SEP as manifested by combinations of intestinal obstruction, weight loss, and ultrafiltration failure. The diagnosis of SEP depends on a combination of laparotomy and radiological features in suspected cases and consequently the true incidence of SEP is most likely underestimated. Several predisposing, interrelated risk factors for both peritoneal fibrosis and sclerosing encapsulating peritonitis have been identified: prolonged duration of peritoneal dialysis, history of severe or recurrent episodes of peritonitis, and higher exposure to hypertonic glucose-based dialysis solutions. Nevertheless, the etiology of SEP is unknown and several causal factors may simultaneously or sequentially initiate and maintain a low-grade serositis that leads to uncontrolled fibroneogenesis. The high mortality rate of SEP has emphasized the need to develop preventive strategies. These strategies include early peritoneal catheter removal to avoid refractory peritonitis, the development of more biocompatible dialysis solutions, restriction of the use of hypertonic glucose-based dialysis solutions during and after episodes of peritonitis, and, perhaps, limiting the duration of peritoneal dialysis in at-risk patients. This approach was followed in a Japanese unit where a subgroup of all patients who had been on peritoneal dialysis for more than 5 years and who had poor ultrafiltration and peritoneal calcification on computed tomography (CT) scan were shown to have peritoneal sclerosis on peritoneal biopsy and were therefore electively transferred to hemodialysis. This acquired spectrum of peritoneal fibrosing syndromes leads to long-term complications in peritoneal dialysis, whereas localized fibrous adhesions secondary to prior abdominal surgery may prevent the successful initiation of peritoneal dialysis.

A new method of post-dialysis blood urea sampling: the 'stop dialysate flow' method.

BACKGROUND: A standardized practical method of post-dialysis blood sampling is required to improve the precision of using urea kinetics in the evaluation of haemodialysis dose and to permit comparative audit. The methods recommended in the Renal Association and Dialysis Outcomes Quality Initiative (DOQI) guidelines reduce the blood pump speed to a low rate at the end of haemodialysis before blood sampling after 10 and 15 s respectively. However, these 'low flow' methods compensate only partially for cardiopulmonary recirculation and may be impractical in routine practice because they involve sequential steps and require accurate timing of sampling. Therefore we have evaluated an alternative method of stopping only the dialysate flow at the end of the haemodialysis session before performing post-dialysis blood sampling. METHODS: The study was performed in three phases. Serial measurements of blood urea were obtained from arterial and venous samples taken at times 0, 30, 60, 120, 180, 240, 300 and 360 s after stopping dialysate flow and leaving the extracorporeal blood flow rate unchanged at the end of the haemodialysis session in 10 patients. A peripheral venous sample was also taken from the contralateral arm at 0 s to reflect body water urea concentration at the end of dialysis without the effect of access recirculation and with a minimal effect of cardiopulmonary recirculation. The same haemodialysis prescription was repeated in the same 10 patients using the Renal Association method to permit comparison between the two methods. The practical use of the 'stop dialysate flow' method was then evaluated in 117 regular haemodialysis patients undergoing routine monthly assessment of dialysis adequacy and compared with sampling immediately post-dialysis. RESULTS: Within 4 min of stopping the dialysate flow there was no difference between the blood urea concentrations of arterial and venous samples, indicating cessation of diffusion across the dialysis membrane. Also the blood urea concentrations in all of the arterial and venous samples between 4 and 6 min were constant and were equivalent to the blood urea concentration of the peripheral venous sample taken at 0 s. These data suggest that post-dialysis blood sampling may be performed 5 min after stopping dialysate flow at the end of the haemodialysis session. In contrast, the blood urea concentration in the post-dialysis samples obtained using the Renal Association method were lower than the contralateral arm blood urea concentration taken at 0 s (0.31+/-0.42; P<0.05) and consequently the percentage URR was higher (1.35+/-1.84%). In 117 patients the post-dialysis blood urea sample 5 min after stopping dialysate flow averaged 5.49+/-2.11 mmol/1 compared with 5.07+/-2.05 mmol/l immediately after the end of the haemodialysis session (P<0. 0001). This was equivalent to a reduction in URR from 71.7+/-8.3% with sampling immediately post-dialysis to 69.1+/-9.3% with the 'stop dialysate flow' method. CONCLUSIONS: This study shows that there is a window period between 4 and 6 min after stopping dialysate flow at the end of the haemodialysis session when the blood urea concentration in a sample taken from any part of the extracorporeal circuit remains constantly within the co-efficient of variation of laboratory measurement, and is equivalent to a peripheral venous sample taken immediately at the end of the dialysis session. A 'stop dialysate flow' method with blood sampling after 5 min offers several advantages over 'slow flow' methods, since it allows for cardiopulmonary as well as access recirculation, does not require precise timing of blood sampling, and is simple to perform in a busy renal unit. For these reasons the 'stop dialysate flow' method may be used for routine monitoring of the adequacy of delivered haemodialysis and for comparative audit among haemodialysis centres.

Insertion of internal jugular temporary hemodialysis cannulae by direct ultrasound guidance--a prospective comparison of experienced and inexperienced operators.

OBJECTIVE: Previous studies have shown that inexperienced operators have a lower success rate than experienced operators for insertion of internal jugular cannulae using the anatomical landmark technique. The object of this study was to determine the rate of successful insertion, incidence of immediate complications and incidence of infection for temporary hemodialysis cannulae inserted under ultrasound guidance by experienced and inexperienced operators. METHODS: The reason for insertion, patient age, reason for failed insertion, immediate complications, duration of cannula survival and reason for removal were recorded prospectively for 107 attempted cannulations by 7 operators in 72 subjects with renal failure. Operators were defined as "experienced" (more than 3 years postgraduate clinical experience and more than 25 previous central vein cannulae inserted) or "inexperienced" (less than 3 years postgraduate clinical experience and less than 3 previous central vein cannulae inserted). Rates of successful cannulation and incidence of complications were compared for experienced and inexperienced operators. Cannula survival without infection was analysed by Kaplan-Meier survival for experienced and inexperienced operators. RESULTS: The overall success rate of cannula insertion at first site was 103/107 (96.3%) with no difference between experienced and inexperienced operators (56/58 vs. 47/49). 103 internal jugular temporary haemodialysis cannulae were inserted into 72 subjects. The only immediate complication was incorrect positioning of the cannula in 6 cases requiring manipulation. The median survival of hemodialysis cannulae was 14 days (range 1-111). 64.1% cannulae functioned for as long as required. Of the remainder, 33/36 were removed because of presumed cannula related infection. There was no difference in the median duration of cannula survival between experienced and inexperienced operators (15 days versus 12 days; Mann-Whitney point estimate = -1.00; 95% confidence interval -6.00, 3.00). p = 0.66) or in the probability of cannula survival without infection by Kaplan Meier analysis. CONCLUSION: We conclude that ultrasound guided temporary haemodialysis cannulation is a safe procedure with a high rate of success, the success rate for inexperienced operators is much higher than previous studies of cannulation using the anatomical landmark technique and the rate of cannula removal due to infection is not influenced by operator experience.

Has the prognosis for patients with pauci-immune necrotizing glomerulonephritis improved?

BACKGROUND: Over the past 14 years, important advances have been made in diagnosis and treatment of patients with pauci-immune necrotizing glomerulonephritis (PINGN). The present study set out to evaluate the impact of these advances on prognosis by comparing patient survival during the period 1985-1995 with previously reported results for such patients between 1975 and 1982. METHOD: A retrospective analysis was carried out at two affiliated inner-city renal units on all patients considered to have PINGN during the period 1985 1995. Details of renal and extra-renal disease at presentation and during follow-up, along with treatment regimes, were noted. Figures for renal and patient survival were compared with those previously reported from one of these units. RESULTS: A total of 47 patients were diagnosed over the period 1985 1995, with a median age of 57 years. The overall patient survival (+/- standard error) at 1 and 5 years was 72.3 (+/- 0.06) and 51.2% (+/- 0.12) respectively, with corresponding renal survival (alive and independent of renal replacement therapy) at these times of 61.7 (+/- 0.07) and 49.9% (+/- 0.09) respectively. We identified increased age at presentation and advanced renal failure (requiring dialysis or serum creatinine > 300 micromol/l) as predictors of reduced patient and renal survival. When comparing our results with those previously reported (1975-1982), we found no improvement in prognosis for patients with PINGN during the latter period. CONCLUSIONS: These results suggest that the prognosis for patients with PINGN has not improved despite diagnostic and therapeutic advances. Delay in diagnosis and treatment may compromise the therapeutic potential in PINGN.

Bicarbonate and bicarbonate/lactate peritoneal dialysis solutions for the treatment of infusion pain.

A randomized, double-blind, cross-over study was undertaken to determine the effects of novel bicarbonate (38 mM) and bicarbonate (25 mM)/lactate (15 mM) containing peritoneal dialysis (PD) solutions on infusion pain in patients who experienced inflow pain with conventional lactate (40 mM) solution. Pain was assessed using a verbal rating scale and the validated McGill Pain Questionnaire (MPQ). Eighteen patients were recruited to the study. Both novel solutions resulted in highly statistically significant reductions in inflow pain compared to the control lactate solution, as assessed with both the verbal rating scale and the MPQ. For all pain variables assessed, the bicarbonate/lactate solution was more effective than the bicarbonate solution in alleviating pain. In conclusion, both solutions reduced the infusion pain experienced with control solution, but the bicarbonate/lactate solution appears to be the most effective. In contrast to the most widespread current treatment, which is the manual injection of sodium bicarbonate, the bicarbonate/lactate solution does not have the associated increased risk of peritonitis.

Tenckhoff catheter salvage by closed stiff-wire manipulation without fluoroscopic control.

OBJECTIVE: To describe the results of Tenckhoff catheter salvage by a modified, closed, stiff-wire manipulation technique without the use of general anesthesia or fluoroscopy, and compare this with previously described techniques. DESIGN: Retrospective study in patients treated with continuous ambulatory peritoneal dialysis (CAPD) over a 41-month period. SETTING: Renal unit in an inner city hospital. PATIENTS: Eighteen patients using CAPD who had 22 episodes of outflow failure due to radiologically confirmed malposition of straight two-cuff Tenckhoff catheters. INTERVENTIONS: Closed stiff-wire manipulation of malpositioned Tenckhoff catheter without the use of general anesthesia or fluoroscopy. MAIN OUTCOME MEASURES: Initial success rate of manipulation, catheter and technique (CAPD) survival, and procedure-related complications. RESULTS: Catheter manipulation was technically successful in 21 of 22 cases. An additional six episodes of malposition occurred ranging from 2 to 630 days after the primary manipulation (median 7 days). A second manipulation was carried out in four cases that resulted in long-term success in two. Three patients were forced to discontinue CAPD for reasons other than catheter malposition, and the overall success rate at 1 month (patient successfully performing CAPD) was 59.1% (+/-0.1%). No major complications were experienced during the procedure and no episodes of peritonitis occurred. CONCLUSION: The technique described is relatively straightforward, does not require fluoroscopy or general anesthetic, and its success is comparable to previously reported methods of Tenckhoff catheter salvage. We would recommend this technique of catheter salvage in patients with Tenckhoff catheter malposition in whom conservative treatment has failed.

Comparison of high-efficiency and standard haemodialysis providing equal urea clearances by partial and total dialysate quantification.

BACKGROUND: Short-duration high-efficiency haemodialysis has been utilized increasingly in recent years to deliver adequate blood urea clearances per dialysis session. However, high-efficiency and standard-duration haemodialysis schedules, which achieve equal patient urea clearances, may not represent equivalent dialytic therapy due to solute differences in intercompartmental dysequilibrium during dialysis and differences in dialysis mechanics. METHODS: To circumvent the effects of intercompartmental dysequilibrium and postdialysis rebound solute clearances were measured by direct dialysis quantification (total and partial dialysate collections) rather than blood clearances. High-efficiency haemodialysis (dialyser blood flow rate = 400 ml/min; dialysis time = 170.67 min) was compared with standard haemodialysis (dialyser blood flow rate = 200 ml/min; dialysis time = 240 min) performed in random order in six anuric patients using Fresenius F8 dialysers and the same haemodialysis machine. Such haemodialysis schedules were prescribed to provide equivalent urea clearances. RESULTS: Patient plasma water urea clearances measured by direct dialysis quantification were equivalent, whereas high efficiency haemodialysis achieved significantly lower phosphate clearances (P = 0.01), less net bicarbonate absorption (P = 0.01), and lower beta 2 microglobulin removal (P < 0.001) than standard haemodialysis. Estimated total dialysate effluent volumes with partial dialysate collection and total dialysate collection correlated closely (r = 0.95) and there were no differences between patient urea, creatinine and phosphate clearances measured by partial and total dialysate quantification. CONCLUSIONS: The data indicate that even if high-efficiency and standard haemodialysis provide equal whole-body urea clearances, delivered dialysis therapy is not equivalent. The partial dialysate collection method is as accurate as the cumbersome total dialysate collection approach and may be applied to assess delivered dialysis dose by minor modification of current haemodialysis machines.

Nosocomial transmission of hepatitis C virus within a British dialysis centre.

Patients on renal replacement therapy are recognized as a group at increased risk of infection with hepatitis C virus (HCV). While the risk has been reduced by the use of erythropoietin for treatment of anaemia and the introduction of HCV screening of blood products and potential renal transplant donors, new cases of HCV are still being documented, with patients on hospital haemodialysis appearing to be particularly at risk. The exact mode of transmission of HCV within dialysis units is unclear, although there is evidence to support nosocomial transmission between patients. Third generation HCV antibody testing was performed on all dialysis patients when a new case of HCV was identified within our unit. Stored monthly serum samples were then examined retrospectively to determine when patients became HCV RNA and HCV antibody positive. Viral typing was carried out to identify the HCV strains responsible for transmission. Four new cases of HCV infection are described within a single dialysis shift. Viral typing identified two distinct strains of HCV as being responsible for these infections, both of which had previously been identified in dialysis patients within the unit known to have HCV infection. This information, taken in conjunction with knowledge of the location of each patient for dialysis, suggests two separate episodes of nosocomial transmission of HCV between haemodialysis patients. While evidence of nosocomial transmission of HCV is accumulating, with modern dialytic procedures evidence of transmission through the dialysis machine or equipment used for dialysis is lacking. This stresses the importance of strict applications of universal precautions as the key to prevention of further transmission of HCV infection. This information is obviously applicable not only to dialysis units but all units that may potentially come in contact with HCV patients.

Erythropoietin response and route of administration.

The effect of route of erythropoietin (EPO) administration was assessed in sixteen hemodialysis patients who completed a randomised crossover study of thrice weekly subcutaneous (SC) and intravenous (IV) erythropoietin with an EPO-free washout period separating the two phases of treatment. Route of EPO administration had no significant effect on absolute reticulocyte counts, and change in hemoglobin (Hb) during the first six weeks of therapy, at a constant EPO dose (120 iu/kg/week). Similarly, there was no significant difference in EPO dose requirement between the two routes, both during and after correction of anemia, and after maintenance of target Hb (10-12 g/dl) for an eight-week period (end of maintenance period dose; median [range]; SC EPO: 120 [30-367] iu/kg/week, IV EPO: 124.5 [37-377] iu/kg/week). Following EPO withdrawal, Hb fell at a rate of 0.38 (0.14-0.69) g/dl/week. Route of EPO administration did not influence the incidence of thrombotic and hypertensive side effects, or increases in dialysis heparin requirement and albumin, and decreases in ferritin, alpha-1-antitrypsin and ceruloplasmin during the study period. In conclusion, thrice weekly SC and IV EPO are comparable in terms of efficacy and safety.

Relationships between dialysis quantification and normalized protein catabolic rate in peritoneal dialysis.

Normalized protein catabolic rates (NPCR) and urea clearances (Kt/V urea) correlate significantly in peritoneal dialysis suggesting that the adequacy of dietary protein intake and dialysis dose are interrelated. However, both of these calculated parameters are mathematical functions of the normalized urea appearance rate (GN). NPCR, GN, Kt/V urea, total creatinine clearance, residual renal clearance, and peritoneal urea and creatinine clearances were determined in 29 stable peritoneal dialysis patients with no history of recent peritonitis or other catabolic illness. Multiple linear regression analysis showed that NPCR correlated closely with both GN (r = 0.96; p < 0.0001) and Kt/V urea (r = 0.77; p < 0.0001), whereas GN also correlated with Kt/V urea (r = 0.66; p < 0.0001). Total weekly creatinine clearances rather than Kt/V urea should be utilized in peritoneal dialysis to permit independent estimations of dialysis dose and NPCR, since both Kt/V and NPCR are related closely to GN. Total weekly creatinine clearances correlated with NPCR (r = 0.59; p < 0.0002), which supports the hypothesis that dietary protein intake is dependent on the delivered dialysis dose.

Effect of dialyzer geometry during hemodialysis with cuprophane membranes.

The effect of dialyzer geometry, both flat plate (FP) and hollow fiber (HF), on platelet and granulocyte activation during dialysis with cuprophane membranes was studied in 12 patients. A subset of six patients was restudied after correction of their anemia with recombinant human erythropoietin (EPO). Granulocyte count and aggregation in vitro fell significantly (P less than 0.01) at 20 minutes of dialysis, followed by a gradual return towards pre-dialysis values at 240 minutes. Malondialdehyde (MDA), a product of free radical reactions generated by activated granulocytes, increased significantly during dialysis [predialysis MDA (median, range): 8.4 (5.8 to 11.6) nmol/ml, 240 minutes MDA: 9.7 (6.6 to 12.5) nmol/ml, P less than 0.01 Wilcoxon test). This increase, however, was not affected by dialyzer geometry or EPO therapy. Neither type of dialyzer was associated with significant platelet loss at the end of dialysis. Whole blood platelet aggregation in vitro (spontaneous and collagen-induced) decreased significantly, (P less than 0.01) during dialysis, the fall in spontaneous aggregation being significantly less following EPO therapy [spontaneous aggregation 240 minutes; pre-EPO: 34 (13 to 52)%; post-EPO 50: (16 to 76)%, P less than 0.01)]. The ratio of the platelet release proteins beta-thromboglobulin and platelet factor 4 increased significantly during dialysis, indicating platelet activation in vivo, although there was no effect of dialyzer geometry or EPO. Factor VIII von Willebrand Factor antigen, a putative marker of endothelial damage, was raised pre-dialysis, and increased further during dialysis, irrespective of dialyzer geometry or EPO. In conclusion, dialyzer geometry had no significant effect on granulocyte and platelet counts and activity during hemodialysis with cuprophane membranes.(ABSTRACT TRUNCATED AT 250 WORDS)