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Keshwar Baboolal

Publications and source records attributed to Keshwar Baboolal.

9 recordsLinked to original sources
PubMed2006

The use of oral glucose tolerance tests to risk stratify for new-onset diabetes after transplantation: An underdiagnosed phenomenon.

BACKGROUND: Fasting glucose measurements are insensitive at detecting new-onset diabetes after transplantation (NODAT) and ignore the diagnosis of impaired glucose tolerance (IGT). Both NODAT and IGT confer a higher risk of developing cardiovascular disease. IGT is also a risk factor for NODAT. The aim of this study was to use an oral glucose tolerance test (OGTT) to risk stratify for NODAT and IGT in renal transplant recipients and to relate cardiovascular and phenotypic risk with glycemic dysregulation. METHODS: In all, 858 renal transplant recipients are under follow up at the University Hospital of Wales, Cardiff, UK. Excluded patients had pretransplant diabetes (78), NODAT (89), or were transplanted less than six months (47), leaving 646 recipients. All remaining recipients with two fasting blood glucoses between 5.6 and 6.9 mmol/L were invited to have an OGTT. A diagnosis of NODAT, IGT, and impaired fasting glucose (IFG) was based on World Health Organization guidelines. RESULTS: We identified 134 patients who fulfilled the inclusion criteria, of whom 122 had an OGTT (91% of cohort). In all, 51% of patients were found to have abnormal glucose metabolism: 10% NODAT, 14% combined IGT/IFG, 9% IGT alone, and 18% IFG alone. Clinical phenotype was not predictive of diabetic risk on multivariate analysis. CONCLUSIONS: Our results confirm fasting glucose underestimates the prevalence of NODAT and ignores the prevalence of IGT. These findings suggest routine use of an OGTT in renal transplant recipients is a valuable clinical tool to risk stratify each patient for the development of NODAT and cardiovascular disease.

Adult↗
PubMed2006

Evaluation of the cost effectiveness of sirolimus versus tacrolimus for immunosuppression following renal transplantation in the UK.

INTRODUCTION: Immunosuppressive therapy is required to prevent graft rejection. Calcineurin inhibitors such as tacrolimus are paradoxically toxic to the kidney, whereas sirolimus (rapamycin; Rapamune) is not generally associated with the nephrotoxicity of CNIs. The purpose of this study was to evaluate the relative cost utility of sirolimus versus tacrolimus for the primary prevention of graft rejection in renal transplant recipients in the UK. METHODS: A stochastic simulation model was constructed using clinical trial and observational data comparing the two treatments. Time duration was up to 20 years. Costs were from a UK NHS perspective, valued at 2003 prices and discounted at 6%. Benefits were discounted at 1.5%. Simulated events included patient and graft survival, haemodialysis, peritoneal dialysis, re-transplants and acute rejection. Costs were summed for events and various maintenance therapies. Utility was differentially accredited depending upon survival and using the alternative renal replacement therapies. Outcome was predicted using post-transplant creatinine levels up to 3 years. Extensive statistical economic and sensitivity analyses were undertaken. RESULTS: Over the 10-year horizon, sirolimus gained 0.72 years (discounted) of functioning graft over tacrolimus, resulting in an incremental cost per year of functioning graft that was dominant. Over a 20-year time horizon, the cost effectiveness of sirolimus over tacrolimus further improved with an average discounted gain in years of a functioning graft of 1.8 years, resulting in an incremental cost-utility ratio that was also dominant. The number of haemodialysis events was 48,243 for sirolimus recipients versus 127,829 for those receiving tacrolimus and peritoneal dialysis events 40,872 versus 105,249, respectively. Similar values were obtained when real-life observational data on tacrolimus use in Cardiff, Wales were entered into the model. Using data from Cardiff, sirolimus remained dominant over tacrolimus under all scenarios. CONCLUSION: Our study suggests that sirolimus may be more cost effective than tacrolimus for the primary prevention of graft rejection in renal transplant recipients in the UK. Sirolimus was economically 'dominant' under almost all scenarios investigated. This finding was robust using statistical economic analysis and univariate sensitivity analysis.

Adult↗
PubMed2005

Evaluation of the cost-effectiveness of sirolimus versus cyclosporin for immunosuppression after renal transplantation in the United Kingdom.

OBJECTIVE: The purpose of this study was to evaluate the cost-effectiveness of sirolimus compared with cyclosporin for the postsurgical management of renal transplant recipients, from the perspective of the UK National Health Service and the Personal Social Service. METHODS: A discrete event stochastic simulation model was developed to evaluate both cost-effectiveness and cost utility over 10 and 20 years after transplant using historical data on 937 renal transplant recipients from the University Hospital of Wales in Cardiff, United Kingdom. The simulation was designed to forecast the incidence of acute rejection events, graft failure, retransplant, frequency of hemodialysis (HD) and peritoneal dialysis (PD), and death. Cox proportional hazard models were derived from historical transplant data, in which 1-, 2-, and 3-year post-transplant serum creatinine levels were used as the key drivers for predicting graft success and survival. Costs were reported as year-2003 UK pounds sterling (1 UK pound = US $1.76). Probabilistic sensitivity analysis was conducted and results reported with particular attention to 2 threshold values, 30,000/QALY and 20,000/QALY RESULTS: Over a 10-year time horizon, treatment with sirolimus was projected to produce a gain of 0.60 discounted year of functioning graft with a cost savings of 276 UK pounds per patient. Over a 20-year time horizon these benefits increased to 1.59 discounted years of functioning graft and a cost savings of 7405 UK pounds per patient. Using sensitivity analysis of the 10-year model, the only factors found to cause the probability of exceeding a 30,000 ceiling to be >5% were the proportion of subjects maintaining continuous graft function and the use of low-dose cyclosporin. With the 20-year model, sirolimus maintained cost-effectiveness across most scenarios in sensitivity analysis. CONCLUSIONS: In this model analysis, sirolimus was cost-effective compared with cyclosporin for 10 to 20 years after renal transplantation in the United Kingdom, from the perspective of the UK National Health Service and Personal Social Service.

Adult↗
PubMed2005

Patterns of graft and patient survival following renal transplantation and evaluation of serum creatinine as a predictor of survival: a review of data collected from one clinical centre over 34 years.

BACKGROUND: The pattern of renal transplantation has never been described since the introduction of the technique. The purpose of this study was therefore to characterise the pattern of renal transplantation from 1967 to 2000, focusing on renal graft function as a predictor of survival. METHODS: This study was a retrospective analysis of an electronic database. The setting was a single renal transplant centre in the United Kingdom covering a population of 2.2 million and included patients who received at least one renal transplant over the study period (n = 1516). The main outcome measures were patient and graft survival, acute rejection episodes and patterns of graft function, as measure by creatinine levels. RESULTS: There were 559 (36.8%) female patients; 109 (7.2%) patients had pre-existing diabetes. Patient survival was adversely affected by increased age at transplant (p < 0.001): 5-year patient survival from first transplant was 82% for patients aged 0 to 17 years, 80% for 18 to 49 years and 61% for > 49 years. Pre-existing diabetes also adversely affected survival (p < 0.01): 5-year graft survival was 63% for patients with diabetes versus 74% for those without. Graft survival was significantly associated with serum creatinine levels recorded 1 year post-primary transplant (p < 0.001) and with three or more acute rejection episodes (p < 0.05). Neither gender nor diabetes status were statistically significant in predicting graft survival. The number of acute rejection episodes was significantly greater in patients with pre-existing diabetes than those without (61% versus 42%, respectively; p < 0.001). There were no differences in the number of acute rejection episodes occurring across age groups. CONCLUSION: Patient and graft survival improved markedly over the 34-year study period, although patient survival has changed little since 1990. Serum creatinine levels are a reliable predictor of graft survival.

Adolescent↗
PubMed2003

A phase III prospective, randomized study to evaluate concentration-controlled sirolimus (rapamune) with cyclosporine dose minimization or elimination at six months in de novo renal allograft recipients.

BACKGROUND: This study evaluated the safety and efficacy of sirolimus plus steroids as a maintenance regimen with or without small-dose cyclosporine (CsA) adjunctive therapy in renal transplant recipients. METHODS: A total of 133 recipients of kidney allograft transplantations recruited in the United Kingdom and Ireland were enrolled into the study and are presented in this interim analysis. In the first 3 months, all patients received CsA plus sirolimus and small-dose steroids after transplantation. At 3 months, patients were randomized 1:1 to CsA elimination (e)CsA or CsA dose minimization (m)CsA. Dosing of agents was concentration-controlled and open label. RESULTS: Patient and graft survival were 97.7% and 95.5%, respectively (n = 133), whereas the biopsy-proven acute rejection rate in the first 6 months was 19.5% (26 episodes in 133 patients); incidents of acute rejection rates comprised 22 episodes (16.5%) during the first 3 months of the study and four episodes (3%) after randomization. Eighty-seven patients were randomized to receive eCsA or mCsA. At 6 months, creatinine clearance was significantly higher in the eCsA group versus mCsA group, respectively (65 mL/min vs. 57 mL/min; P = 0.027). There was no significant difference in serum cholesterol, triglycerides, low-density lipoprotein, or high-density lipoprotein levels between the groups. CONCLUSION: These data demonstrate that withdrawal of CsA from a small-dose sirolimus maintenance regimen is safe and is associated with an improvement in renal function. The study also suggests that the addition of small-dose CsA to a sirolimus maintenance regimen does not increase immunosuppressive efficacy.

Acute Disease↗
PubMed2003

Prevalence and management of anemia in renal transplant recipients: a European survey.

The TRansplant European Survey on Anemia Management (TRESAM) documented the prevalence and management of anemia in kidney transplant recipients. Data from 72 transplant centers in 16 countries were screened, involving 4263 patients who had received transplants 6 months, 1, 3 or 5 years earlier. The mean age of transplant recipients was 45.5 years at transplantation. The most common etiology was chronic glomerulonephritis. The most common comorbidities were coronary artery disease, hepatitis B/C, and type 2 diabetes. The mean hemoglobin levels before transplantation were significantly higher in the more recently transplanted recipients. At enrollment, 38.6% of patients were found to be anemic. Of the 8.5% of patients who were considered severely anemic, only 17.8% were treated with epoetin. There was a strong association between hemoglobin and graft function; of the 904 patients with serum creatinine > 2 mg/dL, 60.1% were anemic, vs. 29.0% of those with serum creatinine <or= 2 mg/dL (p < 0.01). Therapy with angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, mycophenolate mofetil (MMF) or azathioprine was also associated with a higher likelihood of anemia. The prevalence of anemia in the transplant recipients was remarkably high and appeared to be associated with impaired renal function and with ACE inhibitors and angiotensin II receptor antagonist use. Further studies should be carried out to interpret whether appropriate management of anemia after kidney transplantation may improve long-term outcome.

Adult↗
PubMed2002

Molecular and structural consequences of early renal allograft injury.

BACKGROUND: Chronic allograft nephropathy is an important cause of graft failure. Many donor and recipient factors contribute to its development. Prospective analysis of these factors has been hindered by the lack of sensitive and specific indicators of renal injury. As a consequence protocol biopsies have been increasingly used in the assessment of renal allograft injury. We performed protocol renal allograft biopsies to prospectively examine the role of important determinants and mediators of chronic allograft nephropathy. METHODS: A total of 51 consecutive cadaveric renal transplant recipients entered a randomized prospective study of tacrolimus (Tac) versus cyclosporine (CsA) microemulsion based immunosuppression. Study patients underwent protocol renal allograft biopsies at the time of engraftment and at 3, 6 and 12 months post-transplantation. Biopsies were analyzed by quantitative polymerase chain reaction (PCR) for mRNA for transforming growth factor-beta (TGF-beta), thrombospondin, and fibronectin. Measurements of renal structural injury were estimated by quantitative assessment of interstitial fibrosis and glomerulosclerosis. Changes in profibrotic growth factors and renal structural injury were related to donor and recipient determinants by stepwise regression analysis. RESULTS: Longitudinal assessment of renal injury demonstrated an early and progressive increase in mRNA for TGF-beta, thrombospondin (TSP) and fibronectin (FBN): TGF-beta baseline, 1.9 +/- 0.2 log copies; TGF-beta 6 months, 2.5 +/- 0.2 log copies, P < 0.05 6 months vs. baseline; TSP baseline, 1.9 +/- 0.2 log copies; TSP 6 months, 2.4 +/- 0.2 log copies, P < 0.05 6 months vs. baseline; FBN baseline, 2.0 +/- 0.2 log copies; FBN 12 months, 2.3 +/- 0.2 log copies, P < 0.05 12 months vs. baseline. This increase in profibrotic growth factors within the allograft was associated with a significant increase in interstitial fibrosis (Vvi) on renal biopsies: Vvi baseline, 13 +/- 1%; Vvi 3 months, 18 +/- 1%; Vvi 6 months, 28 +/- 2%; Vvi 12 months, 34 +/- 2%; P < 0.05 3, 6, and 12 months vs. baseline. Histological analysis demonstrated chronic allograft nephropathy in 4% biopsies at 3 months, 12% at 6 months and in 49% at 12 months. These changes in renal structure were not associated with any change in creatinine clearance (CCr): CCr 3 months, 56 +/- 2 mL/min, CCr 24 months, 56 +/- 2 mL/min; P=NS. Stepwise regression analysis of key donor and recipient determinants of chronic renal injury identified calcineurin inhibitors and acute rejection episodes as important factors involved in the development of chronic renal injury. In particular, the use of cyclosporine compared to tacrolimus was associated with a tenfold increase in TGF-beta mRNA (TGF-beta mRNA at 6 months, CsA vs. Tac, 3 +/- 0.3 vs. 2 +/- 0.3 log copies, P < 0.05), interstitial fibrosis (Vvi at 6 months, CsA vs. Tac, 33 +/- 4% vs. 24 +/- 2%, P < 0.05). Changes in growth factors and renal structure predicted impaired renal function (CCr at 12 months, CsA vs. Tac, 53 +/- 4 mL/min vs. 62 +/- 2 mL/min, P < 0.05). Similarly, acute rejection episodes were associated with an accelerated development of interstitial fibrosis (Vvi at 6 months, acute rejection vs. no rejection, 34 +/- 3% vs. 25 +/- 2%; P < 0.05), but not with changes in TGF-beta, thrombospondin or fibronectin expression. CONCLUSION: Our results suggest that structural injury develops early in the natural history of the renal allograft and is mediated, in part, by the early up-regulation of profibrotic growth factors. We have determined that calcineurin inhibitors, in particular cyclosporine, and acute rejection episodes are key factors in the development of renal structural injury.

Adult↗