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ABSTRACT: Background
Angiotensin-converting enzyme 2 (ACE2) is a novel regulator of the renin-angiotensin system that counteracts the adverse effects of angiotensin II. In heart failure patients, elevated plasma ACE2 activity predicted adverse events and greater myocardial dysfunction. We aimed to describe plasma ACE2 activity and its clinical associations in patients with kidney disease.Methods
Patients recruited from a single centre comprised of chronic kidney disease Stage III/IV (CKD), haemodialysis patients and kidney transplant recipients (KTRs). Plasma ACE2 enzyme activity was measured using a fluorescent substrate assay in plasma, collected at baseline and stored at -80°C. Linear regression was performed in both males and females separately to determine the covariates associated with log-transformed ACE2.ResultsThe median (interquartile range) plasma ACE2 activity in pmol/mL/min was 15.9 (8.4-26.1) in CKD (n = 59), 9.2 (3.9-18.2) in haemodialysis (n = 100) and 13.1 (5.7-21.9) in KTR (n = 80; P < 0.01). In male haemodialysis patients, ACE2 activity was 12.1 (6.8-19.6) compared with 4.4 (2.5-10.3) in females (P < 0.01). Log-transformed ACE2 plasma activity was associated with post-haemodialysis systolic blood pressure in females [β-coefficient 0.04, 95% confidence interval (95% CI) 0.01-0.06, P = 0.006]. In males, log-transformed ACE2 plasma activity was associated with B-type natriuretic peptide (β-coefficient 0.39, 95% CI 0.19-0.60, P < 0.001). Plasma ACE2 activity was not associated with mortality.Conclusions
Plasma ACE2 activity is reduced in haemodialysis patients compared with CKD patients, and in female haemodialysis patients compared with male. The different associations of plasma ACE2 activity between male and female haemodialysis patients indicate that the role of ACE2 in cardiovascular disease may differ by gender.
Nephrology Dialysis Transplantation 03/2013; · 3.40 Impact Factor
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ABSTRACT: The association between blood pressure and cardiovascular outcomes in patients undergoing hemodialysis remains controversial. This may relate in part to the technique and device used and the timing of the blood pressure measurement in relation to the hemodialysis procedure. Emerging evidence indicates that standardized hemodialysis unit blood pressure measurements or measurements obtained at home, either by the patient or using an ambulatory blood pressure monitor, may offer advantages over routine hemodialysis unit blood pressure measurements for determining cardiovascular risk and treatment. This review discusses the available evidence and implications for clinicians and clinical trials.
American Journal of Kidney Diseases 06/2012; 60(3):463-72. · 5.43 Impact Factor
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ABSTRACT: Immunophenotype peripheral blood T cells from renal transplant recipients (RTR) using cellular markers of regulatory T cells (Tregs) and flow cytometry, including Foxp3, and correlate these findings with clinical parameters.
Expression of phenotypic markers of Tregs was assessed by flow cytometric analysis of peripheral blood lymphocytes (PBL) from (i) RTR (n = 95); (ii) patients with end-stage renal failure (ESRF) awaiting transplantation (n = 17); and (iii) normal healthy controls (n = 18).
The percentage of CD4(+) CD25(+) Foxp3(+) cells within the CD4(+) cell population did not significantly alter at different time points post-transplant. However, the percentage of CD4(+) CD25(+) Foxp3(+) cells within the CD4(+) population was significantly lower in RTR compared with patients with ESRF. In contrast, RTR and ESRF had a similar percentage of CD4(+) CD25(+) cells expressing Foxp3. Multivariate analysis of PBL and clinical parameters demonstrated (i) a positive linear relationship between the percentage CD4(+) CD25(+) cells expressing Foxp3 and estimated glomerular filtration rate and (ii) a higher percentage of CD4(+) CD25(+) cells in the CD4(+) cell population in patients with malignancy (the majority were skin cancers). Malignancy also correlated strongly with time post-transplant and age of the RTR.
Immune monitoring of the PBL phenotype in RTR using CD4, CD25 and Foxp3 may stratify RTR and predict graft outcome and function, and risk of complications from immunosuppression. Longitudinal and functional studies of Tregs are essential to extend the findings of the present study.
Nephrology 02/2012; 17(4):415-22. · 1.31 Impact Factor
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Transplantation 10/2011; 92(8):e39. · 4.00 Impact Factor
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ABSTRACT: Long-term acceptance of transplanted organs without requirement for indefinite immunosuppression remains the ultimate goal of transplant clinicians and scientists. This clinical state of allograft acceptance termed "operational tolerance" has been elusive in routine practice. However, there are published reports of recipients where immunosuppression has been discontinued, by intention or patient noncompliance, in which the outcome is a nondestructive immune response and normal function. The question now arises how clinical operational tolerance might be achieved in the majority of recipients. This review provides an overview of current approaches to achieve operational tolerance, including the use of donor bone marrow and depletion of recipient T cells and the resistance of liver transplants to rejection. It also describes the key role of clinical immune monitoring and future approaches to tolerance induction including inhibition of T-cell signaling, manipulation of costimulatory pathways, and expansion of regulatory T cells. The principles of these experimental approaches may ultimately be extended to provide safe and effective control of transplant rejection and induction of clinical operational tolerance.
Transplantation 05/2011; 91(10):1065-74. · 4.00 Impact Factor
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ABSTRACT: Blockade of the inducible costimulator (ICOS) pathway has been shown to prolong allograft survival; however, its utility in xenotransplantation is unknown. We hypothesize that local expression of ICOS-Ig by the xenograft will suppress the T-cell response resulting in significant prolonged graft survival.
Pig iliac artery endothelial cells (PIEC) secreting ICOS-Ig were generated and examined for the following: (1) inhibition of allogeneic and xenogeneic proliferation of primed T cells in vitro and (2) prolongation of xenograft survival in vivo. Grafts were examined for Tregs by flow cytometry and cytokine levels determined by quantitative reverse-transcriptase polymerase chain reaction.
Soluble ICOS-Ig markedly decreased allogeneic and xenogeneic primed T-cell proliferation in a dose-dependent manner. PIEC-ICOS-Ig grafts were significantly prolonged compared with wild-type grafts (median survival, 34 and 12 days, respectively) with 20% of PIEC-ICOS-Ig grafts surviving more than 170 days. Histological examination showed a perigraft cellular accumulation of Forkhead box P3 (Foxp3(+)) cells in the PIEC-ICOS-Ig grafts, these were also shown to be CD3(+)CD4(+)CD25(+). Survival of wild-type PIEC grafts in a recipient simultaneously transplanted with PIEC-ICOS-Ig were also prolonged, with a similar accumulation of Foxp3(+) cells at the periphery of the graft demonstrating ICOS-Ig induces systemic graft prolongation. However, this prolongation was specific for the priming xenograft. Intragraft cytokine analysis showed an increase in interleukin-10 levels, suggesting a potential role in induction/function of CD4(+)CD25(+)Foxp3(+) cells.
This study demonstrates prolonged xenograft survival by local expression of ICOS-Ig, we propose that the accumulation of CD4(+)CD25(+)Foxp3(+) cells at the periphery of the graft and secretion of interleukin-10 is responsible for this novel observation.
Transplantation 05/2011; 91(10):1090-7. · 4.00 Impact Factor
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ABSTRACT: Cardiovascular mortality rates in the general population have decreased over time. We hypothesized that cardiovascular mortality rates in dialysis patients, which are higher than in the general population, have not decreased as much as those in the general population.
Comparison of registry data with population data.
Data for prevalent Australian patients for whom dialysis was the first renal replacement therapy were obtained from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry for 1992-2005. Data for a comparable Australian general population were obtained from the Australian Bureau of Statistics.
Cardiovascular mortality rates per 100 person-years were calculated from ANZDATA Registry data, and age-specific relative risks were calculated relative to cardiovascular mortality rates in the general population.
Included in this cohort were 34,741 dialysis patients with 93,112 person-years of follow-up and 7,267 cardiovascular deaths. Cardiovascular mortality rates decreased over time in the general population and in dialysis patients older than 55 years. In patients aged 55-64 years, cardiovascular mortality rates were 9.0 (95% CI, 7.8-10.3) per 100 person-years in 1992-1994 and 6.4 (95% CI, 5.5-7.3) in 2004-2005; corresponding relative risks were 32.4 (95% CI, 28.2-37.2) and 52.0 (95% CI, 45.2-59.9), respectively. The corresponding cardiovascular mortality rates for dialysis patients aged 65-74 years were 11.6 (95% CI, 10.4-13.0) and 8.3 (95% CI, 7.4-9.3); relative risks were 12.9 (95% CI, 11.6-14.5) and 20.8 (95% CI, 18.7-23.2). Using negative binomial regression, the relative risk associated with dialysis compared with the general population increased over time (P for interaction = 0.001).
Causes of death used to define cardiovascular mortality were not coded using identical systems in the ANZDATA Registry and the Australian population.
Despite decreasing cardiovascular mortality rates in some dialysis patients, the excess cardiovascular risk compared with the general population is increasing.
American Journal of Kidney Diseases 04/2011; 58(1):64-72. · 5.43 Impact Factor
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ABSTRACT: A novel strategy in the management of cardiovascular disease in patients with end-stage kidney disease is the use of biochemical markers to facilitate the detection of cardiovascular abnormalities in the hope that this will allow effective therapy to be instituted earlier. The cardiac troponins and B-type natriuretic peptide are among the best studied of these biochemical markers of cardiovascular disease. However, controversy remains regarding the interpretation of such results and the subsequent clinical application of these biomarkers, particularly when abnormal in patients with end-stage kidney disease. This review addresses some of the important issues to consider with the interpretation of abnormal cardiac troponin and B-type natriuretic peptide results in patients undergoing dialysis.
Nephrology 03/2011; 16(3):251-60. · 1.31 Impact Factor
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ABSTRACT: Renal impairment is a major risk factor for cardiovascular disease. This study addressed clinical predictors of outcome following cardiac surgery, focusing on pre-operative renal dysfunction.
All patients undergoing cardiac surgery at Austin Health from June 1, 2001 to June 30, 2006, were included in the analysis. Logistic regression models were used to evaluate clinical factors predicting "operative mortality" and common post-operative complications.
The operative mortality was 1.36% for coronary artery bypass grafting (CABG) alone (n=1027), 5.07% for valve surgery alone (n=217), 4.43% for combined CABG and valve surgery (n=158) and 11.11% for other cardiac surgical procedures (n=270). Amongst CABG alone patients, pre-operative renal impairment was a strong predictor of operative mortality, with a 35-43% increased risk of death (p=0.005) for every 10 ml/min/1.73 m(2) that the glomerular filtration rate was lower. Peripheral vascular disease, recent myocardial infarction and congestive cardiac failure also predicted operative mortality. Pre-operative renal impairment also increased the rate of various post-operative complications, as well as duration of admission.
Renal dysfunction is significantly associated with increased mortality and morbidity following cardiac surgery and necessitates careful consideration in risk benefit analysis when considering cardiac surgery.
Heart Lung & Circulation 04/2010; 19(8):453-9. · 1.20 Impact Factor
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ABSTRACT: A single detectable cardiac troponin predicts mortality in patients treated with dialysis. There are limited data on changes in troponin concentration over time and the clinical implications of serial troponin measurement.
Serial cardiac troponin T (cTnT) was assayed five times over 12 months in a prospective cohort study of patients with end-stage kidney disease treated with haemodialysis. A concentration of cTnT > or = 0.04 microg/L was considered increased. Mortality and cardiovascular events were analysed by survival analysis, according to the serial troponin results.
From 100 patients who provided a baseline sample for cTnT, 81 completed five serial measurements. The analysis of patients who completed serial cTnT measurements demonstrated that 28 patients (35%) had normal cTnT concentrations in all five samples, 20 patients (24%) had between one and four increased cTnT measurements and 33 patients (41%) had increased concentrations of cTnT in all five samples. The 1.7-y patient survival was 100%, 90% and 78% for patients with zero, one to four, or five out of five concentrations of cTnT increased, respectively (P = 0.037), and the corresponding cardiovascular event-free survival was 100%, 91% and 78%, respectively (P = 0.027).
Serial measurements of cTnT concentration were frequently increased in patients receiving haemodialysis. The number of abnormal measurements over time predicted mortality and cardiovascular adverse events.
Annals of Clinical Biochemistry 06/2009; 46(Pt 4):291-5. · 2.17 Impact Factor
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ABSTRACT: Left ventricular abnormalities contribute to cardiovascular disease in patients with chronic kidney disease and may be detected by measurement of B-type natriuretic peptide in serum.
In a prospective cohort study of predialysis patients, patients who were on dialysis, and kidney transplant recipients, serum was collected and assayed for both B-type natriuretic peptide and its N-terminal fragment. Median levels were compared using nonparametric tests, and predictors of B-type natriuretic peptide were determined by linear regression. Survival analysis and Cox regression were performed to examine the association of levels of B-type natriuretic peptide with cardiovascular events and death.
Levels of B-type natriuretic peptide were highest in patients who were on dialysis. Patients who were receiving dialysis and had known cardiovascular disease, were not on the waiting list for kidney transplantation, or had left ventricular systolic dysfunction on echocardiography had significantly higher levels of B-type natriuretic peptide than patients without these characteristics. Glomerular filtration rate was an important predictor of B-type natriuretic peptide levels for patients who were not on dialysis (predialysis and renal transplant recipients). Left ventricular systolic dysfunction predicted B-type natriuretic peptide levels in patients who were on dialysis. Both forms of B-type natriuretic peptide were associated with a two- to three-fold increased risk for death in patients who were on dialysis.
Levels of B-type natriuretic peptide are greatest in patients who are on dialysis and have cardiovascular comorbidities and are strong predictors of death.
Clinical Journal of the American Society of Nephrology 07/2008; 3(4):1057-65. · 5.23 Impact Factor
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ABSTRACT: To overcome cell-mediated xenorejection by transgenic expression of immunomodulatory molecules by a graft, it is likely that expression of multiple molecules will be required. Previous studies support the use of the immunomodulatory agents indoleamine 2,3-dioxygenase (IDO), CD40Ig, interleukin 10 (IL10), and CTLA4Ig for suppression of rejection responses. We examined the effects of local expression of these molecules by a porcine cell line (PIEC) on indirect murine xenorejection responses in vitro and in vivo.
The PIEC stable lines expressing IDO, CD40Ig, and IL10 as single molecules were generated. In addition, PIEC lines expressing IDO with either CD40Ig, IL10 or CTLA4Ig were generated to produce cell lines expressing two molecules. BALB/c mice were primed with wild type PIEC, followed by harvesting splenocytes used as responder cells and PIEC expressing immunomodulatory molecules as stimulators, in proliferation and cytokine assays. In vivo effects of modified PIEC were examined by transplantation of PIEC lines expressing the immunomodulatory molecules under the renal capsule of naïve mice. PIEC grafts were harvested for histological evaluation at days 7 and 14.
Proliferation of primed BALB/c splenocytes was inhibited most significantly by IDO compared with control cells (49%, P = 0.02). In addition both Th1 (interferon-gamma) and Th2 (IL4 and IL10) cytokines were markedly inhibited in vitro by IDO expression. IL10 expressing cells did not inhibit proliferation as potently (37%, P = 0.03) whilst CD40Ig lead to an increase in proliferative responses (59%, P = 0.02). Co-expression of CD40Ig, IL10, and CTLA4Ig with IDO resulted in further modest reductions in proliferation compared with IDO expression alone. When transplanted under the renal capsule of BALB/c mice, those grafts expressing IDO demonstrated significantly lower levels of lymphocyte infiltration at days 7 and 14 than control grafts and those expressing CD40Ig, CTLA4Ig or IL10 alone. Grafts co-expressing IDO and a second molecule were no better protected than those expressing IDO alone. Graft cell viability (PIECs) was reduced in some IDO expressing grafts suggesting high levels of IDO expression may inhibit PIEC viability, however, grafts co-expressing IDO-CTLA4Ig and IDO-IL10 were not affected in this way.
Indoleamine 2,3-dioxygenase appears to be a potent molecule for protecting xenografts from cell-mediated rejection responses activated via the indirect pathway. Co-expression of IDO with both CTLA4Ig and IL10 warrants further investigation. Overall these findings support pursuing further studies, in larger animal models, to determine whether increased IDO activity within the graft itself can attenuate xenorejection responses.
Xenotransplantation 06/2008; 15(3):174-83. · 2.33 Impact Factor
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ABSTRACT: Vascular-access patency is critical for effective and uninterrupted haemodialysis. Limited literature exists evaluating if a surgical or repeated radiological approach is superior for reocclusion following failure of radiological recanalization. Few consistent early predictors of failure have been identified after radiological intervention for thrombosed vascular access.
138 patients with thrombosed arteriovenous fistulas or prosthetic grafts treated by radiological intervention, over 10 years, were retrospectively investigated. Reocclusion was treated by either repeated thrombolysis or surgery. Radiological patency rates, after first and second episodes of access thrombosis at 12 months after intervention were analysed. Surgical and radiological patency rates for second access thrombosis were compared. The Cox and logistic regression models were used to identify potential factors associated with reocclusion.
In patients who experienced reocclusion within 1 month after radiological intervention, the 3-month repeated radiological patency rate (n = 13) was 38.5%, compared to a 60% surgical patency rate (n = 10), but this did not reach statistical significance. Radiological patency rates after first access thrombosis at 3 and 12 months were 56.6 and 39.5%, respectively. In contrast, radiological patency rates after a second access thrombosis were 51.1 and 24.4%, respectively; a statistical difference in success was not achieved. Native arteriovenous fistulas were 3.23 times as likely to remain patent over 12 months following a first radiological intervention (p < 0.02) and less likely to experience a second reocclusion event (p < 0.01). Anticoagulation was associated with a lower risk of second reocclusion, whilst a history of venous thrombosis was associated with a greater risk (p < 0.02).
Surgery achieves superior patency rates compared to repeated radiological interventions and should be considered if reocclusion occurs within a month following radiological thrombolysis.
American Journal of Nephrology 01/2008; 28(2):181-9. · 2.54 Impact Factor
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Nephrology 03/2007; 12(1):111. · 1.31 Impact Factor
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ABSTRACT: We report a case of intravesical fat entrapment leading to failure of extraperitoneal bladder perforation to heal spontaneously. A 68-year-old woman underwent trans-abdominal hysterectomy complicated by an extraperitoneal bladder perforation. Despite prolonged catheterization, cystographic leakage persisted after 3 months. Bladder imaging and cystoscopy demonstrated a mass of perivesical pelvic fat protruding into the bladder cavity. The patient was symptomatic with pain and persistent urinary tract infection with episodes of sepsis. A transurethral resection of the mass was performed which led to bladder healing and resolution of symptoms.
International Urology and Nephrology 02/2007; 39(3):795-8. · 1.47 Impact Factor
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ABSTRACT: The isolation of porcine hematopoietic stem cells (HSC) would be an important step toward development of porcine-to-human chimerism for induction of tolerance in clinical xenotransplantation. CD34 is a common marker of HSC and has not been developed as a marker in pigs. In this study we have generated and characterized a monoclonal antibody (mAb) that identifies porcine CD34 on a subset of porcine bone marrow (BM) stem/progenitor cells.
The porcine CD34 gene was cloned and a recombinant protein produced. An anti-porcine CD34 mAb was produced that could detect both the recombinant protein and a subset of porcine BM cells. The CD34(+) cells were phenotyped by lineage and HSC associated markers. Furthermore, the CD34(+) cells were analyzed by colony-forming unit (CFU) assay.
Two splice variants of the porcine CD34 gene were cloned and a recombinant protein produced for mAb production. The mAb developed can detect both the recombinant protein and the native CD34 protein on a range of pig tissues, including BM. This subset of BM cells was negative for hematopoietic lineage makers, including CD3, CD14, and CD21 and positive for other known porcine HSC markers, including CD90, CD172a, histocompatibility complex (MHC) class I, and MHC class II. Moreover, the CD34(+) BM cells were enriched for multilineage progenitor cells as determined by CFU assay.
Similar to human and mouse CD34, pig CD34 detects a subset of BM progenitor cells. This mAb will now provide a means for isolating porcine CD34(+) cells to be further analyzed for HSC activity and to assess their potential to develop pig-to-human chimeras to induce xenograft tolerance.
Experimental Hematology 02/2007; 35(1):171-8. · 2.90 Impact Factor
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ABSTRACT: Hyperacute xenograft rejection is a well-defined barrier to clinical pig-to-human xenotransplantation, and intense research in this area has identified potential solutions. In contrast, the next phase of xenograft injury, which can occur days to weeks later, has introduced a new series of immunological and nonimmunological barriers with complex mechanisms. This review addresses mechanisms of the immediate and delayed xenograft response with a focus on the relevant components. The key individual elements include carbohydrate antigens and natural antibodies to these epitopes, the role of the complement and coagulation systems, and the inflammatory cellular xenograft response that is predominantly mediated by the innate immune system. The vascular elements are central targets in this process, and the role of the endothelial cell is discussed. Important recent developments in xenotransplantation include the production of genetically modified pigs (deficient in alphaGal transferase and pigs transgenic for complement regulators) and a progressive understanding of xenograft-induced thrombotic microangiopathy, which threatens the long-term survival of transplanted pig organs and tissue. However, a clear standardized classification of the immunopathological mechanisms involved is essential. Further studies into the delayed xenograft response, using primates, are required before the routine use of pig organs for clinical transplantation.
Critical Reviews in Immunology 02/2007; 27(2):153-66. · 3.32 Impact Factor
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ABSTRACT: Cardiovascular disease (CVD) is a major cause of morbidity and mortality in patients with all forms of chronic kidney disease (CKD). The underlying pathological state is caused by a complex interplay of traditional and nontraditional risk factors that results in atherosclerosis, arteriosclerosis, and altered cardiac morphological characteristics. This multifactorial disease introduces new challenges in predicting and treating patients with CVD sufficiently early in the course of CKD to positively alter patient outcome. Asymptomatic individuals with progressive CVD are a group of patients that deserve focused attention because early detection and intervention may provide the best opportunity for improved outcome. However, identifying CVD in asymptomatic patients with CKD or end-stage renal disease remains a significant hurdle in the management of these patients. Recently, a number of cardiovascular biomarkers were identified as predictors of patient outcome in individuals with CVD and, with additional research, may be used to guide the early diagnosis of and therapy for CVD in patients with CKD. This review examines the pathophysiological characteristics and potential clinical role of these novel cardiovascular biomarkers in risk stratification, risk monitoring, and selection of preventive therapies for patients with CKD.
American Journal of Kidney Diseases 10/2006; 48(3):341-60. · 5.43 Impact Factor
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ABSTRACT: Cardiac troponin levels predict mortality and cardiovascular events in asymptomatic patients receiving dialysis and may be a useful clinical tool to stratify high-risk asymptomatic individuals.
The present study examined levels of troponins I (cTnI) and T (cTnT) in patients with chronic renal impairment, patients receiving dialysis and renal transplant recipients. Patients receiving dialysis on the renal transplant waiting list were compared with those excluded from the list based on medical criteria. Median levels were compared using the Kruskal-Wallis test and proportions compared by chi-squared.
Median troponin levels were higher in patients on dialysis than transplant recipients. Comparing patients receiving dialysis not listed compared with those listed for renal transplant, median cTnI levels were significantly higher (0.03 versus 0.02 microg/L, P < 0.01) whereas median cTnT levels were not. Patients listed for transplantation were younger, had less clinical cardiovascular disease and lower C-reactive protein than those awaiting renal transplantation. The proportion of patients with elevated cTnT was not substantially different between patients awaiting renal transplantation (38%) and those excluded (52%). Levels of cTnI and cTnT were inversely related to renal function in predialysis and transplant patients, but were not related to time on dialysis for those receiving dialysis therapy.
As patients awaiting renal transplantation are clinically screened for cardiovascular disease but have frequently elevated cardiac troponin levels, troponin may be a useful clinical tool to identify high-risk asymptomatic patients on dialysis prior to renal transplantation. The influence of renal function on the interpretation of cardiac troponin and risk prediction requires further evaluation.
Nephrology 10/2006; 11(5):471-6. · 1.31 Impact Factor
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ABSTRACT: Advanced glycation end products (AGEs) have biological properties that may contribute to the premature cardiovascular mortality of haemodialysis patients. This study examines the hypothesis that low molecular weight forms of fluorescent AGEs (LMW fluorescence) predict mortality in haemodialysis patients.
The LMW fluorescence was measured in 85 patients treated with chronic haemodialysis and prospectively followed for 4 years. The primary outcome of all-cause mortality was assessed using Cox proportional hazards regression model.
At the end of the follow-up period 37 (44%) patients died. The median LMW fluorescence level was 24.2 arbitrary units (range: 10.6-148.1 AU) and the receiver operator characteristic (ROC) curve cut-off for mortality was 37.0 AU. The LMW fluorescence predicted death both as a binary variable at the ROC cut-off, and as a continuous log-transformed variable when adjusted for age, albumin and C-reactive protein (CRP). Adjusted for age, albumin and CRP, the hazard ratio for mortality was 3.05 (1.41-6.60, P = 0.005) for LMW fluorescence as a binary variable and 2.71 per log unit (1.37-5.38, P = 0.004) as a continuous log-transformed variable.
The low molecular weight forms of AGEs predict mortality in patients receiving chronic haemodialysis, and may be important in the mechanisms leading to atherosclerosis and inflammation in such patients.
Nephrology Dialysis Transplantation 07/2006; 21(6):1611-7. · 3.40 Impact Factor
