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ABSTRACT: Background: Analyses of national registry-based datasets have demonstrated the association of longer haemodialysis treatment times with lowered mortality risk. Methods: We performed a prospective cohort study of 451 incident haemodialysis patients and examined the effect of targeting higher dialysis dose with extended treatment time, on 10-year patient outcomes. Results: Mean treatment time (TT) was 233 ± 22.8 minutes (median 235, range 180-296). Overall patient survival was 95% at 1 year, 75% at 3 years, 56% at 5 years and 25% at 10 years. Increasing TT was associated with incremental 10-year patient survival (TT >=241 minutes 39.7%, TT 226-240 minutes 19.6% and TT <=225 minutes 14.7%; p<0.001). Single pool Kt/V and TT were strong independent predictors of patient survival in Cox multivariate analysis (p<0.0001). At 10 years, each 0.1-unit increase in spKt/V and 20-minute increase in TT were associated with a 20% and 32% decrease in the relative risk of death, respectively. Survival benefits of higher dialysis dose and longer TT were cumulative, with highest survival exhibited by patients achieving both Kt/V >1.6 and TT >=241 minutes, and lowest survival exhibited by patients receiving Kt/V <1.2 and TT <=225 minutes. Conclusion: Extended treatment times are associated with higher patient survival irrespective of dialysis dose. Further study of extended treatment time and effect on patient outcomes is needed.
Journal of nephrology 11/2012; · 1.65 Impact Factor
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Michelle Willicombe,
Paul Brookes,
Ruhena Sergeant,
Eva Santos-Nunez,
Corinna Steggar,
Jack Galliford, Adam McLean,
Terence H Cook,
Tom Cairns,
Candice Roufosse,
David Taube
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ABSTRACT: The importance of human leukocyte antigen (HLA) matching in renal transplantation is well recognized, with HLA-DR compatibility having the greatest influence. De novo DQ donor-specific antibodies (DSAbs) are the predominant HLA class II DSAb after transplantation. The aim of this study was to establish the incidence and outcomes after the development of DQ DSAbs along with the impact of class II HLA mismatch on their development.
We retrospectively analyzed 505 patients who received a renal-alone transplant between 2005 and 2010. We excluded patients who received an ABO- and HLA-incompatible allograft, which we defined as those with a positive crossmatch or preformed DSAbs detected by single-antigen beads only.
Of 505 patients, 92 (18.2%) developed DSAbs, with 50 (54.3%) of these 92 patients having DQ DSAbs. Patients who developed DQ DSAbs were at significant risk for antibody-mediated rejection, transplant glomerulopathy, and allograft loss (P<0.0001). Of 505 patients, 108 (21.4%) were matched at both the DR and DQ loci, 284 (56.2%) were mismatched at both loci, 38 (7.5%) were matched at DR alone, and 75 (14.9%) were matched at DQ alone. Patients mismatched at both DR and DQ were at risk for developing class II DSAbs when compared with those mismatched at either DR or DQ alone, P=0.001, and were at risk for antibody-mediated rejection, P=0.001.
DQ DSAbs are associated with inferior allograft outcomes. This study shows the importance of establishing the DQ match before transplantation to define immunologic risk.
Transplantation 06/2012; 94(2):172-7. · 4.00 Impact Factor
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ABSTRACT: A kidney transplant recipient developed chronic antibody-mediated rejection (ABMR) with clinically significant transplant glomerulopathy while under careful clinical monitoring. The patient developed a de novo donor-specific antibody (DSA) posttransplantation, and a protocol renal biopsy showed C4d deposition with no histological evidence of rejection. Subsequently he developed peritubular capillary basement membrane multilayering, with negative C4d and DSA. Finally, he developed proteinuria and transplant glomerulopathy, with reappearance of DSA and C4d. Despite having a de novo antibody and progressive antibody-mediated damage, this patient under close histological and serological surveillance did not fulfill Banff criteria for acute or chronic ABMR until his disease was advanced. This case illustrates the limitations of current Banff criteria in this setting, due to the fluctuating nature of DSA and C4d staining.
Clinical nephrology 05/2012; · 1.17 Impact Factor
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Nicola Kumar,
Christopher S R Baker,
Kakit Chan,
Neill Duncan,
Iqbal Malik,
Andrew Frankel,
Damien R Ashby, Adam McLean,
Andrew Palmer,
Tom D Cairns,
David Taube
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ABSTRACT: Recent interest has focused on wait listing patients without pretreating coronary artery disease to expedite transplantation. Our practice is to offer coronary revascularization before transplantation if indicated.
Between 2006 and 2009, 657 patients (427 men, 230 women; ages, 56.5 ± 9.94 years) underwent pretransplant assessment with coronary angiography. 573 of 657 (87.2%) patients were wait listed; 247 of 573 (43.1%) patients were transplanted during the follow-up period, 30.09 ± 11.67 months.
Patient survival for those not wait listed was poor, 83.2% and 45.7% at 1 and 3 years, respectively. In wait-listed patients, survival was 98.9% and 95.3% at 1 and 3 years, respectively. 184 of 657 (28.0%) patients were offered revascularization. Survival in patients (n = 16) declining revascularization was poor: 75% survived 1 year and 37.1% survived 3 years. Patients undergoing revascularization followed by transplantation (n = 51) had a 98.0% and 88.4% cardiac event-free survival at 1 and 3 years, respectively. Cardiac event-free survival for patients revascularized and awaiting deceased donor transplantation was similar: 94.0% and 90.0% at 1 and 3 years, respectively.
Our data suggest pre-emptive coronary revascularization is not only associated with excellent survival rates in patients subsequently transplanted, but also in those patients waiting on dialysis for a deceased donor transplant.
Clinical Journal of the American Society of Nephrology 08/2011; 6(8):1912-9. · 5.23 Impact Factor
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Albert Power,
Neill Duncan,
Seema K Singh,
Wendy Brown,
Elizabeth Dalby,
Claire Edwards,
Kathleen Lynch,
Virginia Prout,
Tom Cairns,
Megan Griffith, Adam McLean,
Andrew Palmer,
David Taube
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ABSTRACT: Sodium citrate has antibacterial and anticoagulant properties that are confined to the catheter when used as a catheter lock. Studies of its use as a catheter lock have suggested its efficacy in preventing infection and bleeding complications compared with sodium heparin.
Open-label randomized controlled trial of 2 catheter locks to examine the hypothesis that sodium citrate catheter locks will reduce catheter-related bacteremia and exit-site infection.
232 consenting long-term hemodialysis patients in 4 satellite dialysis units to a large dialysis program with protocolized treatment and targets. All patients were using twin-catheter single-lumen Tesio-Caths (MedComp, Harleysville, PA).
6 months' use of 46.7% sodium citrate (citrate) or 5% heparin (heparin) locked postdialysis in the dead space of the central venous catheter.
Primary end point of catheter-related bacteremia and exit-site infection. Secondary end points of catheter thrombosis defined by the use of urokinase lock and infusion, new catheter insertion, catheter-related admission, blood transfusions, parenteral iron, and erythropoietin requirements.
Catheter-related bacteremia did not differ in the 2 groups, with an incidence of 0.7 events/1,000 catheter-days. There was no significant difference in rates of exit-site infection (0.7 versus 0.5 events/1,000 catheter-days; P = 0.5). The secondary end point of catheter thrombosis defined by the use of a urokinase lock was significantly more common in the citrate group, with an incidence of 8 versus 4.3/1,000 catheter-days (P < 0.001). Other secondary end points did not differ. Citrate treatment was curtailed compared with heparin because of a greater incidence of adverse events, with a mean treatment duration before withdrawal of 4.8 +/- 2.0 versus 5.7 +/- 1.2 months, respectively (P < 0.001).
Low baseline catheter-related bacteremia and exit-site infection event rates may have underpowered this study. High adverse-event rates may have been related to high-concentration citrate that led to increased overspill and reduction in lock volume. This may also explain the increased rates of thrombosis in this group.
Widespread and long-term use of 46.7% citrate catheter locks with Tesio-Cath access is not justified by this study.
American Journal of Kidney Diseases 04/2009; 53(6):1034-41. · 5.43 Impact Factor
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Jack Galliford,
Rawya Charif,
Ka Kit Chan,
Marina Loucaidou,
Tom Cairns,
H Terence Cook,
Anthony Dorling,
Nadey Hakim, Adam McLean,
Vassilios Papalois,
Ranjan Malde,
Fiona Regan,
Martin Redman,
Anthony N Warrens,
David Taube
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ABSTRACT: ABO incompatible (ABOi) live-donor renal transplantation is a successful and accepted form of treatment for patients with renal failure. Although there is significant controversy as to how antiblood group antibodies should be removed and their resynthesis prevented, subsequent immunosuppressive regimes have all involved steroids. We and other groups have successfully used steroid sparing regimes for conventional ABO compatible transplantation and this study describes the use of our steroid sparing protocol in ABOi transplantation.
We have transplanted 10 ABOi patients using 1 week of steroids (prednisolone 1 mg/kg for 4 days, 0.5 mg/kg for 3 days and then stopped), tacrolimus and mycophenolate mofetil. Steroids were reintroduced in the event of rejection.
Patient- and allograft-survival 1 year posttransplantation is 100%. Three patients experienced antibody-mediated rejection within 2 weeks of transplantation, which was successfully reversed. There has been no late rejection. Allograft function was similar to our live-donor ABO compatible transplant patients receiving a similar steroid sparing regime (12-month mean creatinine 131+/-15 micromol/L vs. 138+/-48 micromol/L; mean CrCl 63.2+/-22 mL/min vs. 56.7+/-20 mL/min).
This study shows that ABOi live-donor transplantation can be successfully accomplished using a steroid-sparing protocol.
Transplantation 11/2008; 86(7):901-6. · 4.00 Impact Factor
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Richard Borrows,
Marina Loucaidou,
Gary Chusney,
Sarah Borrows,
Jen Van Tromp,
Tom Cairns,
Megan Griffith,
Nadey Hakim, Adam McLean,
Andrew Palmer,
Vassilios Papalois,
David Taube
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ABSTRACT: Anaemia is common following renal transplantation and is associated with the development of congestive heart failure (CHF). However the prevalence of anaemia in the first year following transplantation and the association between anaemia occurring early and the development of CHF have been understudied.
In this study, 132 incident patients undergoing tacrolimus and mycophenolate mofetil-based renal transplantation were studied for the prevalence of, and risk factors for, anaemia and CHF in the early period post transplantation.
Anaemia occurred in 94.5% and 53.1% of patients at 1 week and 12 months, respectively, and was associated with allograft dysfunction, hypoalbuminaemia, higher mycophenolic acid (MPA) levels, bacterial infection and hypoalbuminaemia. The association with hypoalbuminaemia may reflect the presence of chronic inflammation post-transplantation. Of patients displaying haemoglobin <11 g/dl, 41.1% and 29.4% were treated with erythropoiesis stimulating agents (ESAs) at 1 and 12 months respectively. CHF developed in 26 patients beyond 1 month post-transplantation, with echocardiographic left ventricular systolic function preserved in all but one. CHF was associated with anaemia and lower haemoglobin, allograft dysfunction, duration of dialysis and left ventricular hypertrophy on echocardiography prior to transplantation, suggesting the aetiology of CHF may involve the interplay of diastolic cardiac dysfunction, pre-load mismatch and after-load mismatch.
Modification of risk factors may improve anaemia management post transplantation. Reducing the prevalence of anaemia may in turn reduce the incidence of CHF-these observations support the need for clinical trials to determine how anaemia management may impact CHF incidence.
Nephrology Dialysis Transplantation 06/2008; 23(5):1728-34. · 3.40 Impact Factor
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Richard Borrows,
Gary Chusney,
Marina Loucaidou,
Anthony James,
Shruti Goel,
Sarah Borrows,
Jen Van Tromp,
Tom Cairns,
Megan Griffith,
Nadey Hakim, Adam McLean,
Andrew Palmer,
Vassilios Papalois,
David Taube
The Journal of Clinical Pharmacology 09/2007; 47(8):1035-42. · 2.91 Impact Factor
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Richard Borrows,
Gary Chusney,
Marina Loucaidou,
Anthony James,
Jen Van Tromp,
Tom Cairns,
Megan Griffith,
Nadey Hakim, Adam McLean,
Andrew Palmer,
Vassilios Papalois,
David Taube
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ABSTRACT: There is increasing evidence that monitoring predose plasma levels of mycophenolic acid (MPA) is of benefit in renal transplant recipients treated with mycophenolate mofetil (MMF). Concomitant treatment with oral antibiotics leads to a 10% to 30% reduction in MPA area under the curve (AUC)0-12, probably by reducing enterohepatic recirculation (EHR). Because of the timing of EHR (6 to 12 hours postdose), the magnitude of predose MPA level reduction may be disproportionately larger than that of AUC0-12. However, changes in predose MPA levels and the time course over which these changes occur and resolve during antibiotic treatment have not been studied. The purpose of this study was to define the extent and time course of MPA predose level reduction during antibiotic therapy. A total of 64 MMF-treated renal transplant recipients (with tacrolimus cotherapy) were prospectively studied. Clinically indicated cotherapy with either oral ciprofloxacin or amoxicillin with clavulanic acid resulted in a reduction in 12 hour predose MPA level to 46% of baseline within 3 days of antibiotic commencement. No demographic or biochemical variables were associated with the magnitude of MPA level reduction. No further fall in MPA level was seen by day 7, but MPA levels recovered spontaneously to 79% of baseline after 14 days of antibiotics. Levels normalized within 3 days of antibiotic cessation. No changes in daily MMF dose (normalized for body weight) were made during antibiotic treatment. This data should help the clinician to recognize the extent of MPA predose level reduction during antibiotic therapy, and to avoid inappropriate MMF dose escalation and potential risk of toxicity.
Therapeutic Drug Monitoring 03/2007; 29(1):122-6. · 2.49 Impact Factor
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Richard Borrows,
Gary Chusney,
Marina Loucaidou,
Anthony James,
Jose Stichbury,
Jen Van Tromp,
Tom Cairns,
Megan Griffith,
Nadey Hakim, Adam McLean,
Andrew Palmer,
Vassilios Papalois,
David Taube
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ABSTRACT: It is suggested that specific methods of Tacrolimus monitoring rather than immunoassays which over-estimate Tacrolimus levels, should be used in transplant recipients. There is limited data, however, comparing clinical outcomes of renal transplantation using each of these techniques. In this study, 40 renal transplant recipients with Tacrolimus monitoring by Microparticle Enzyme Immunoassay (MEIA; target trough level 10-15 ng/ml) were compared with 40 patients monitored by High Performance Liquid Chromatography with Tandem Mass Spectrometry (HPLC-MS; target trough level 8-13 ng/ml). All received anti CD25 antibody induction and Mycophenolate Mofetil in a steroid sparing protocol. No demographic differences were seen between MEIA and HPLC-MS groups. All patients were followed for 6 months. Patient survival was 100% in both groups; graft survival was 100% in the MEIA group and 97.5% in the HPLC-MS group. The groups did not differ in the number of dose changes required in the first 6 months or in the number of patients displaying Tacrolimus levels within target range at three and six months. Delayed graft function occurred in 14 patients in the MEIA group and 12 patients in the HPLC-MS group (P = NS). Biopsy-proven acute rejection occurred in 4 patients in the MEIA group and 1 patient in the HPLC-MS group (P = 0.17). Biopsy proven acute Tacrolimus nephrotoxicity occurred in 6 patients in the MEIA group, and 7 in the HPLC-MS group (P = NS). No difference was seen in serum creatinine or estimated creatinine clearance at 3 or 6 months. No difference between groups was seen in systolic or diastolic blood pressure, or total cholesterol at 3 or 6 months. 2 patients in the MEIA group developed CMV disease and 1 developed posttransplantation diabetes mellitus. CMV and posttransplantation diabetes were not seen in the HPLC-MS group. 2 patients in each group developed reversible tremor. This study suggests that renal transplantation with HPLC-MS monitoring of Tacrolimus is safe and effective.
Therapeutic Drug Monitoring 05/2006; 28(2):269-73. · 2.49 Impact Factor
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Richard Borrows,
Kakit Chan,
Marina Loucaidou,
Christopher Lawrence,
Jen Van Tromp,
Tom Cairns,
Megan Griffith,
Nadey Hakim, Adam McLean,
Andrew Palmer,
Vassilios Papalois,
David Taube
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ABSTRACT: Steroid sparing with tacrolimus and mycophenolate mofetil (MMF) is associated with good short-term renal transplant outcomes. However, late allograft dysfunction and failure remain concerns. In this study, 101 consecutive patients underwent renal transplantation with tacrolimus, MMF, and 7 days of corticosteroids only. After a median follow-up of 51 months (range 36-62), overall patient survival is 97%, and overall survival with graft function is 91%. The acute rejection rate at 12 months was 19%. Late rejection was uncommon, with only three further episodes beyond 12 months. Graft function was stable during the study, with a mean creatinine of 140 micromol/L and mean estimated creatinine clearance of 57 ml/min at the end of follow-up. Six patients developed posttransplant diabetes mellitus (three cases beyond 12 months). This steroid avoidance regimen is associated with excellent medium-term patient and graft outcomes, and a low incidence of side effects.
Transplantation 02/2006; 81(1):125-8. · 4.00 Impact Factor
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Richard Borrows,
Gary Chusney,
Anthony James,
Jose Stichbury,
Jen Van Tromp,
Tom Cairns,
Megan Griffith,
Nadey Hakim, Adam McLean,
Andrew Palmer,
Vassilios Papalois,
David Taube
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ABSTRACT: There are data suggesting an association between mycophenolic acid (MPA) levels and acute rejection and toxicity in renal transplant recipients treated with mycophenolate mofetil (MMF), and therefore, knowledge of factors determining MPA levels may aid in accurate adjustment of MMF dosage. A total of 4970 samples taken 12 hours postdose were analyzed for MPA by immunoassay at regular intervals from the first week posttransplantation in 117 renal transplant patients immunosuppressed with MMF and tacrolimus in a steroid-sparing regimen (prednisolone for the first 7 days only). MPA levels rose in the first 3 months and stabilized thereafter; dose-normalized MPA levels rose throughout the first 12 months and subsequently stabilized. Multivariate analysis by means of a population-averaged linear regression showed positive associations between MPA level and total daily dose (P < 0.001) but not individual dose or total daily dose corrected for body weight. Positive associations were also seen with serum albumin (P = 0.01), tacrolimus trough level (P = 0.01), and female gender (P = 0.002). The association with tacrolimus levels diminished with time. Negative associations were seen between MPA level and higher estimated creatinine clearance (P < 0.001), and also with increasing alanine transaminase levels (P = 0.002), the use of oral antibiotics (P < 0.001), and infective diarrhea (P < 0.001). The latter findings may be related to changes in enterohepatic recirculation of MPA. Many clinical variables show associations with trough MPA levels. An understanding of these factors may aid therapeutic monitoring of MMF.
Therapeutic Drug Monitoring 08/2005; 27(4):442-50. · 2.49 Impact Factor
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ABSTRACT: Evidence suggests that steroid sparing in renal transplantation is associated with good outcomes, although there are limited data regarding steroid sparing in Tacrolimus and Mycophenolate Mofetil (MMF)-based regimes. In this study we describe the use of these agents in 101 consecutive patients undergoing renal transplantation using only a 7-day course of prednisolone. Median follow-up was 33 months (range 18-44). Patient and graft survival at 1 year were 100% and 98%, respectively. The acute rejection rate at both 6 and 12 months was 19%, with two episodes beyond 12 months. Anti-CD25 monoclonal antibody (anti-CD25 mAb) was administered to 25 patients at high immunological risk: a trend toward a lower rejection rate was seen in these patients compared with those at lower risk but not receiving induction therapy (8% vs. 22%; p = 0.11). Two patients experienced recurrent rejection. Of the twenty-three rejection episodes in total, 26% showed vascular involvement. Allograft function was preserved at 12 months with a mean creatinine of 144 micromol/L and mean estimated glomerular filtration rate (GFR) of 55 mL/min. At 12 months, the incidence of post-transplant diabetes mellitus was 3.5%. This steroid-sparing regime is associated with excellent patient and graft outcomes, and a low incidence of side effects.
American Journal of Transplantation 12/2004; 4(11):1845-51. · 6.39 Impact Factor
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ABSTRACT: Cyclophosphamide has transformed the outcome of ANCA-associated vasculitis, but it is highly toxic. Recent studies have suggested that pulsed intravenous cyclophosphamide (pCyc) is an effective alternative with less complications, but may lead to an increased rate of relapse. However, these studies used relatively short courses of treatment with cyclophosphamide. In this study we used a prolonged course of low-dose intravenous cyclophosphamide for 18-24 months for ANCA-associated vasculitis, evaluated the effectiveness of pCyc and analysed the outcome of a prolonged treatment on the rate of relapse.
A retrospective analysis of all the patients treated with pCyc from 1995 to 2002 was performed.
Thirty-seven patients were followed for an average of 38 months. Thirty-four of 37 patients (91.9%) achieved complete remission at 3 months. Eight (21%) episodes of relapse occurred in 7 patients. The cyclophosphamide was well tolerated with a low rate of infections (18.9%) and 1 death (2.7%) due to sepsis whilst on cyclophosphamide.
In this study, pCyc was effective in achieving rapid remission and had a low complication rate. If prolonged, this treatment may reduce the rate of relapse.
Nephron Clinical Practice 02/2004; 97(4):c154-9. · 2.04 Impact Factor
