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Biomedical subjects

Nicole M Isbel

Publications and source records attributed to Nicole M Isbel.

At least 19 recordsLinked to original sources
PubMed2007

Estimated donor glomerular filtration rate is the most important donor characteristic predicting graft function in recipients of kidneys from live donors.

We hypothesized that predictors of outcome in live donor transplants were likely to differ significantly from deceased donor transplants, in which cold ischaemia time, cause of donor death and other donor factors are the most important predictors. The primary aim was to explore the independent predictors of graft function in recipients of live donor kidneys (LDK). Our secondary aim was to determine which donor characteristics are the most useful predictors. A retrospective analysis was undertaken of all patients receiving live donor (n = 206) renal transplants at our institution between 31 May 1994 and 15 October 2002. Twelve patients were excluded from the analysis. Follow-up was completed on all patients until graft loss, death or 22 November 2003. We explored predictors of Nankivell glomerular filtration rate (GFR) at 6 months by multivariate linear regression. In the 194 patients studied, the mean recipient 6-month Nankivell GFR was 59 +/- 15 ml/min/1.73 m(2). Independent predictors of recipient GFR in at 6 months were donor Cockcroft-Gault GFR (CrCl; beta 0.16; CI 0.13 to 0.29; P < 0.0001), steroid resistant rejection (beta-6.07; CI -12.05 to -0.09; P = 0.006) and delayed graft function (DGF) (beta-10.0; CI -19.52 to -0.49; P = 0.039). Renal function in an LDK transplant recipients is predicted by donor GFR, episodes of steroid resistant rejection and DGF. Importantly, donor Cockcroft-Gault GFR is the most important characteristic for predicting the recipient renal function.

Adult↗
PubMed2006

Deceased donor renal transplantation--does side matter?

BACKGROUND: The aim of the present study was to determine whether the deceased donor kidney side (left or right kidney) was predictive of subsequent kidney transplant outcomes. METHODS: A retrospective analysis was undertaken of the left-right deceased donor kidney pairs transplanted into recipients with end-stage renal failure in Queensland between 1 April 1994 and 31 March 2004. RESULTS: A total of 201 left-right deceased donor kidney pairs were transplanted into 402 patients. The baseline characteristics of the recipients in the two groups were comparable, except that the patients receiving right kidneys had lower body mass indices and shorter cold ischaemic times. No differences were seen between the left and right kidney recipient groups with respect to operative duration (3.02 +/- 0.67 vs 3.12 +/- 0.72 h, P = 0.16), warm ischaemic time (0.62 +/- 0.18 vs 0.65 +/- 0.21, P = 0.09), delayed graft function (4 vs 6%, respectively, P = 0.26) or a composite vascular, haemorrhagic, ureteric and infective post-operative complication end-point (22 vs 22%, P = 0.90). Estimated glomerular filtration rates were almost identical at 1 month (52.7 +/- 39.6 vs 51.0 +/- 24.0 ml/min/1.73 m(2), P = 0.34) and remained comparable thereafter. Respective death-censored graft survival rates for left and right kidney recipients were 100 and 100% at 1 year, 99.4 and 96.4% at 3 years and 96.3 and 95.5% at 5 years, respectively (P = 0.67). CONCLUSIONS: Although left and right deceased donor kidneys present different operative challenges, the present results suggest that the probability of early post-operative complications, delayed graft function, impaired early and medium-term renal allograft function or death-censored graft failure is comparable between left and right kidney recipients.

Adult↗
PubMed2006

Increased targeting of cardiovascular risk factors in patients with chronic kidney disease does not improve atheroma burden or cardiovascular function.

BACKGROUND: Although multiple risk factor intervention (MRFI) is recommended to reduce the increased morbidity and mortality of cardiovascular disease (CVD) in chronic kidney disease (CKD), its efficacy is unknown. We studied the efficacy of a MRFI program in CKD. METHODS: This randomized controlled study of 200 patients with stage 4 or 5 CKD compared a physician-supervised, nurse-driven MRFI clinic (focused on dyslipidemia, hyperhomocysteinemia, blood pressure [BP], anemia, and hyperphosphatemia) with conventional care in CKD. One hundred eleven subjects completed 2 years of follow-up (median follow-up 674 days [interquartile range {IQR} 348-719 days]). Outcome measures were atheroma burden (carotid intimamedia thickness [IMT]) and endothelial function (brachial artery reactivity [BAR]). RESULTS: The MRFI group showed significant improvements, compared with usual care, in serum low-density lipoprotein cholesterol (-30.9 mg/dL vs -12.7 mg/dL, P = .001), homocysteine (-6.95 vs -0.67 micromol/L, P < .001), systolic BP (-6.9 vs -0.2 mm Hg, P = .049), and diastolic BP (-4.8 vs -1.0 mm of Hg, P = .043). No significant changes were seen in serum phosphate or hemoglobin level. Despite observed improvements in risk factors, no differences from baseline were demonstrated for IMT (-0.00 vs -0.01 mm, P = .533) or BAR (0.09% vs 0.22%, P = .834). Forty-two patients reached a composite end point of CVD death, acute coronary syndrome, revascularization, nonfatal stroke, and amputation and this was similar between groups (23 vs 19 events, P = .475). CONCLUSIONS: A MRFI program was not associated with improvement in vascular structure or function in stage 4 or 5 patients with CKD.

Adult↗
PubMed2006

Risk stratification of patients with chronic kidney disease: results of screening strategies incorporating clinical risk scoring and dobutamine stress echocardiography.

BACKGROUND: Cardiac disease is the principal cause of death in patients with chronic kidney disease (CKD). Ischemia at dobutamine stress echocardiography (DSE) is associated with adverse events in these patients. We sought the efficacy of combining clinical risk evaluation with DSE. METHODS: We allocated 244 patients with CKD (mean age 54 years, 140 men, 169 dialysis-dependent at baseline) into low- and high-risk groups based on two disease-specific scores and the Framingham risk model. All underwent DSE and were further stratified according to DSE results. Patients were followed over 20 +/- 14 months for events (death, myocardial infarction, acute coronary syndrome). RESULTS: There were 49 deaths and 32 cardiac events. Using the different clinical scores, allocation of high risk varied from 34% to 79% of patients, and 39% to 50% of high-risk patients had an abnormal DSE. In the high-risk groups, depending on the clinical score chosen, 25% to 44% with an abnormal DSE had a cardiac event, compared with 8% to 22% with a normal DSE. Cardiac events occurred in 2.0%, 3.1%, and 9.7% of the low-risk patients, using the two disease-specific and Framingham scores, respectively, and DSE results did not add to risk evaluation in this subgroup. Independent DSE predictors of cardiac events were a lower resting diastolic blood pressure, angina during the test, and the combination of ischemia with resting left ventricular dysfunction. CONCLUSION: In CKD patients, high-risk findings by DSE can predict outcome. A stepwise strategy of combining clinical risk scores with DSE for CAD screening in CKD reduces the number of tests required and identifies a high-risk subgroup among whom DSE results more effectively stratify high and low risk.

Adult↗
PubMed2006

A randomized controlled trial of fludrocortisone for the treatment of hyperkalemia in hemodialysis patients.

BACKGROUND: Previous small uncontrolled studies suggested that fludrocortisone may significantly decrease serum potassium concentrations in hemodialysis patients, possibly through enhancement of colonic potassium secretion. The aim of this study is to evaluate the effect of oral fludrocortisone on serum potassium concentrations in hyperkalemic hemodialysis patients in an open-label randomized controlled trial. METHODS: Thirty-seven hemodialysis patients with predialysis hyperkalemia were randomly allocated to administration of either oral fludrocortisone (0.1 mg/d; n = 18) or no treatment (control; n = 19) for 3 months. The primary outcome measure was midweek predialysis serum potassium concentration, which was measured monthly during the trial. Prospective power calculations indicated that the study had an 80% probability of detecting a decrease in serum potassium levels of 0.7 mEq/L (0.7 mmol/L). RESULTS: Baseline patient characteristics were similar, except for slightly longer total weekly dialysis hours in the fludrocortisone group (13.0 +/- 1.3 versus 12.1 +/- 1.0; P = 0.02). At the end of the study period, no significant changes in serum potassium concentrations were observed between the fludrocortisone and control groups (4.8 +/- 0.5 versus 5.2 +/- 0.7 mEq/L [mmol/L], respectively; P = 0.10). Similar results were obtained when changes in serum potassium levels over time were examined between the 2 arms by using repeated-measures analysis of variance, with or without adjustment for total weekly dialysis hours. Secondary outcomes, including predialysis mean arterial pressure, interdialytic weight gain, serum sodium level, and hospitalization for hyperkalemia, were not significantly different between groups. There were no observed adverse events. CONCLUSION: Administering fludrocortisone to hyperkalemic hemodialysis patients is safe and well tolerated, but does not achieve clinically important decreases in serum potassium levels.

Administration, Oral↗
PubMed2006

A randomized controlled trial of coiled versus straight swan-neck Tenckhoff catheters in peritoneal dialysis patients.

BACKGROUND: Current clinical practice guidelines recommend that no particular type of peritoneal dialysis (PD) catheter has been proved superior to another. However, a recent Cochrane review recommended the need for a large, well-designed, randomized, controlled trial of straight versus coiled PD catheters because of the paucity and suboptimal quality of previously performed trials. METHODS: A randomized controlled trial was undertaken at 2 metropolitan teaching hospitals comparing the effects of straight versus coiled PD catheters on time to catheter malposition (primary outcome), catheter-associated infection, technique failure, and all-cause mortality. RESULTS: One hundred thirty-two PD patients were enrolled and randomly assigned to insertion of a coiled (n = 62) or straight catheter (n = 70). There was no significant difference in time to laparoscopic reposition between the 2 cohorts (log-rank score, 0.41; P = 0.52). However, median technique survival was significantly worse for coiled catheters (1.5 years; 95% confidence interval [CI], 1.2 to 1.8) compared with straight catheters (2.1 years; 95% CI, 1.8 to 2.5; P < 0.05), primarily because of increased risk for inadequate dialytic clearance with the former. On univariate Cox proportional hazards model analysis, insertion of a coiled PD catheter was associated significantly with a greater risk for technique failure (unadjusted hazard ratio, 1.86; 95% CI, 1.03 to 3.36). No difference was observed between the 2 groups with respect to catheter-associated infections or overall patient survival. CONCLUSION: Coiled catheters do not influence the risk for drainage failure caused by catheter malposition compared with straight catheters, but are associated with significantly increased risk for PD technique failure, primarily because of inadequate dialytic clearance.

Aged↗
PubMed2005

Does uric acid have a pathogenetic role in graft dysfunction and hypertension in renal transplant recipients?

BACKGROUND: Uric acid (UA) may play a pathogenetic role in hypertension and kidney disease. We explored the prevalence of hyperuricemia and the relationship of UA to graft function and hypertension in prevalent renal transplant recipients (RTR). METHODS: Baseline and follow-up data were collected on 90 RTR (mean age 51 yrs, 53% male, median transplant duration 7 years). Graft function was estimated using MDRD Study Equation 7. RESULTS: At baseline, 70% RTR had hyperuricemia (UA >7.0 mg/dl (0.42 mmol/L) in men and >6.0 mg/dl (0.36 mmol/L) in women) compared to 80% after 2.2 years (P=0.06). UA was not associated with blood pressure (BP) level but was higher in RTR with a history of hypertension compared to those without (8.6+/-1.8 vs. 7.3+/-2.2 mg/dl, [0.51+/-0.11 vs. 0.43+/-0.13 mmol/L], P=0.003) and in RTR on > or =3 antihypertensive medications compared to those taking less (9.1+/-1.6 vs. 7.6+/-1.8 mg/dL, [0.54+/-0.1 vs. 0.45+/-0.11 mmol/L], P<0.001). A history of hypertension was independently predictive of UA (beta 0.06, [95% CI 0.02 to 0.10], P=0.007) in addition to sex, cyclosporine dose, prednisolone dose, estimated glomerular filtration rate (eGFRMDRD) and beta-blocker therapy. UA was independently predictive of follow-up eGFRMDRD (beta -22.2 [95% CI -41.2 to -3.2], P=0.02) but did not predict change in eGFRMDRD over time. UA was independently associated with requirement for antihypertensive therapy (beta 0.34, [95% CI 1.05 to 1.90], P=0.02). CONCLUSIONS: Hyperuricemia is common in RTR and is associated with need for antihypertensive therapy and level of graft function.

Adult↗
PubMed2005

Free fatty acids are associated with obesity, insulin resistance, and atherosclerosis in renal transplant recipients.

BACKGROUND: Insulin resistance (IR) may be implicated in the pathogenesis of atherosclerosis in renal transplant recipients (RTRs) and be contributed to, in part, by free fatty acids (FFAs), produced in excess in centrally obese individuals. The aim of this study was to determine the prevalence of IR and the relationships between FFAs, central obesity, and atherosclerosis in a cohort of prevalent RTRs. METHODS: Observational data were collected on 85 RTRs (mean age 54 years; 49% male, 87% Caucasian). Fasting serum was analyzed for FFAs, glucose, and insulin; IR was calculated using the homeostasis model assessment (HOMA-IR) score. Vascular structure was assessed by carotid intima-media thickness (IMT) measurement. Linear regression analyses were performed to determine the factors associated with IR and atherosclerosis. RESULTS: IR occurred in 75% of RTRs, and FFA levels were independently associated with its occurrence (beta: -0.55, 95% CI: -1.02 to -0.07, P = 0.02). Other variables independently associated with IR were male sex, body mass index, central obesity, diabetes, systolic blood pressure and corticosteroid use. There was a significant correlation between FFA levels and IMT (r = 0.3, P=0.01). On multivariate analysis, IMT correlated with elevated FFA (beta: 0.07, 95% CI: 0.02-0.12, P = 0.007), diabetes mellitus (P = 0.05), older age (P < 0.002), and a body mass index >25 kg/m (P = 0.002). CONCLUSIONS: FFAs are associated with the development of IR and may be involved in the pathogenesis of atherosclerosis in RTRs. Additional studies are required to explore these associations further before considering whether an interventional trial aimed at lowering FFA would be a worthwhile undertaking.

Atherosclerosis↗
PubMed2005

Randomized trial of FX high flux vs standard high flux dialysis for homocysteine clearance.

BACKGROUND: Cardiovascular disease is the major cause of death in the end-stage renal disease population. Novel risk factors such as homocysteine (Hcy) are of considerable interest in this group as hyperhomocysteinaemia is highly prevalent in the setting of renal impairment. Folic acid-vitamin B group therapies are only partially effective treatments. Hcy is highly protein-bound and thus poorly dialysed. Dialyzers with albumin-leaking properties have been shown to result in lowering of plasma Hcy. As the FX-class (Advanced Fresenius Polysulfone dialyzer) has greater clearance of larger molecular weight substances but is non-albumin-leaking, we explored the capacity of this new technology membrane to reduce plasma Hcy levels. METHODS: A prospective randomized cross-over trial in 35 prevalent haemodialysis patients, one group receiving 12 weeks dialysis using FX dialyzer then 12 weeks with standard high flux dialysis (SHF) and the other group SHF followed by FX dialyzer. All patients received vitamin B(6) 25 mg and folic acid 5 mg daily throughout the study. RESULTS: The primary outcome was plasma Hcy pre-dialysis at week 12. FX vs SHF showed no significant difference, 25+/-6.6 vs 25.9+/-5.8 microg/l, Delta95% CI = -2.77 to 4.59, P = 0.31. There was a non-significant trend toward a decrease in Hcy in both groups (27.43+/-7.68 to 25.91+/-5.78 micromol/l for SHF, P = 0.23 and 26.0+/-4.58 to 25.0+/-6.61 micromol/l for FX, P = 0.28). Analysis by repeated measures method demonstrated a statistically significantly lower Hcy with FX vs SHF dialyzer (adjusted beta = -1.30, 95% CI = -2.41 to -0.19, P = 0.022). K(t)/V(urea) was higher in FX vs SHF (1.35+/-0.18 vs 1.22+/-0.2; P = 0.013). Folate and B(6) levels did not change. CONCLUSIONS: The primary outcome analysis did not show any significant difference in pre-Hcy comparing FX and SHF membranes. Although our secondary analysis demonstrated a statistically significant difference between membranes, the magnitude of the difference (1.3 mumol/l) is not clinically significant. Thus the use of the FX dialyzer did not result in a clinically significant benefit in relation to improving pre-dialysis Hcy compared with standard high-flux dialysis.

Adult↗
PubMed2005

Derivation and validation of a disease-specific risk score for cardiac risk stratification in chronic kidney disease.

OBJECTIVE: Cardiac events (CE; cardiac death, non-fatal myocardial infarction and acute coronary syndrome) are the principal causes of death in patients with chronic kidney disease (CKD). We sought to devise and validate a cardiac risk score to risk-stratify patients with CKD. METHODS: Clinical history and biochemical data were obtained in 167 CKD patients. CE were recorded over a median follow-up of 22 months. The hazard ratio (HR) of each independent variable using Cox regression analysis was used to derive a cardiac risk score for the prediction of events. The cardiac risk score was then applied to a validation population of 99 CKD patients to confirm its validity in predicting CE. RESULTS: CE occurred in 20 patients in the derivation group. The independent predictors of CE were cardiac history (HR 9.83, P = 0.001), body mass index (BMI; HR 1.15, P = 0.002), dialysis duration (HR 1.24, P = 0.004) and serum phosphate (HR 4.29, P = 0.001). The resulting cardiac risk score (range 26-67) gave an area under the receiver operating characteristic curve of 0.86. CE occurred in 25 patients in the validation group; the ROC curve area was similar (0.84, P = 0.11). An optimal cardiac risk score cut-off of 50 assigned high risk to 29% of the derivation and 35% of the validation group (P = 0.26). CE occurred in 35 and 57% of the high-risk derivation and validation groups, respectively (P = 0.09), and in 2 and 8% of the low-risk groups (P = 0.15). CONCLUSION: Application of a cardiac risk score using cardiac history, dialysis duration, BMI and phosphate identifies CKD patients at risk of future CE.

Adult↗
PubMed2005

Mycophenolic acid pharmacokinetics and related outcomes early after renal transplant.

AIMS: The pharmacokinetics of mycophenolic acid and its glucuronide are complex. This study investigated the pharmacokinetics, pharmacodynamics and protein binding of mycophenolic acid and its glucuronide metabolite, early post-transplant in renal allograft recipients. METHODS: Forty-two de novo renal transplant recipients receiving mycophenolate mofetil and concomitant cyclosporin (n = 32) or tacrolimus (n = 10) participated in the study. Blood samples were taken on day 5 post-transplant for measurement of free and total concentrations of mycophenolic acid, mycophenolic acid glucuronide and relevant biochemistry. Associations between free fraction and biochemistry were investigated. Free and total 6-h area under the concentration-time curve (AUC0-6) of mycophenolic acid was assessed relative to clinical outcomes in the first month post-transplant. RESULTS: Kinetic variability of free and total mycophenolic acid and its glucuronide was greater in patients on cyclosporin (12- to 18-fold variation) than on tacrolimus (four- to fivefold) cotherapy. Cyclosporin-treated patients also had significantly lower predose total mycophenolic acid concentrations than tacrolimus-treated patients (median 0.8 mg l(-1) and 1.6 mg l(-1), respectively, P = 0.002). Mycophenolic acid glucuronide predose concentration correlated positively with mycophenolic acid glucuronide AUC0-6 (r > 0.95). Mycophenolic acid free fraction varied 11-fold, from 1.6% to 18.3%, whilst the glucuronide free fraction varied threefold, from 17.4% to 54.1%. Urea and creatinine concentrations correlated positively (r > 0.46), whilst albumin correlated negatively (r = -0.54) with free fraction of mycophenolic acid. Similar relationships were found for the free fraction of mycophenolic acid glucuronide. Mycophenolic acid free fraction was on average 70% higher in patients with albumin concentrations below a specified albumin cut-off concentration of 31 g l(-1)[free fraction = 7 +/- 4% for lower albumin and 4 +/- 3% for higher albumin, respectively; P = 0.001; 95% confidence interval (CI) for the difference 1.9, 4.2]. Neither free nor total mycophenolic acid AUC0-6 was related to rejection (P > 0.07). Free AUC0-6 was significantly higher in those patients with thrombocytopenic, leukopenic and/or infectious outcomes than in those without (mean +/- SD 1.9 +/- 0.3 mg h(-1) l(-1) and 1.1 +/- 0.1 mg h(-1) l(-1), P = 0.0043; 95% CI for the difference 0.3, 1.4). CONCLUSIONS: The marked variability in mycophenolic acid/glucuronide pharmacokinetics occurring early post-transplant during the current study was greater in cyclosporin (12-18-fold) than in tacrolimus (four- to fivefold) treated patients. Concomitant cyclosporin was associated with total mycophenolic acid concentrations approximately half that of tacrolimus. Patients with marked renal impairment had the highest free fractions reported to date. The exposure to unbound mycophenolic acid was significantly related to infections and haematological toxicity.

Adult↗
PubMed2005

Impact of obesity on renal transplant outcomes.

Obesity is a frequent and important consideration to be taken into account when assessing patient suitability for renal transplantation. In addition, posttransplant obesity continues to represent a significant challenge to health care professionals caring for renal transplant recipients. Despite the vast amount of evidence that exists on the effect of pretransplant obesity on renal transplant outcomes, there are still conflicting views regarding whether obese renal transplant recipients have a worse outcome, in terms of short- and long-term graft survival and patient survival, compared with their non-obese counterparts. It is well established that any association of obesity with reduced patient survival in renal transplant recipients is mediated in part by its clustering with traditional cardiovascular risk factors such as hypertension, dyslipidaemia, insulin resistance and posttransplant diabetes mellitus, but what is not understood is what mediates the association of obesity with graft failure. Whether it is the higher incidence of cardiovascular comorbidities jeopardising the graft or factors specific to obesity, such as hyperfiltration and glomerulopathy, that might be implicated, currently remains unknown. It can be concluded, however, that pre- and posttransplant obesity should be targeted as aggressively as the more well-established cardiovascular risk factors in order to optimize long-term renal transplant outcomes.

Body Mass Index↗
PubMed2005

Obesity is associated with worsening cardiovascular risk factor profiles and proteinuria progression in renal transplant recipients.

Obesity is associated with adverse cardiovascular (CV) parameters and may be involved in the pathogenesis of allograft dysfunction in renal transplant recipients (RTR). We sought the spectrum of body mass index (BMI) and the relationships between BMI, CV parameters and allograft function in prevalent RTR. Data were collected at baseline and 2 years on 90 RTR (mean age 51 years, 53% male, median transplant duration 7 years), categorized by BMI (normal, BMI < or = 24.9 kg/m2; pre-obese, BMI 25-29.9 kg/m2; obese, BMI > or = 30 kg/m2). Proteinuria and glomerular filtration rate (eGFR(MDRD)) were determined. Nine percent RTR were obese pre-transplantation compared to 30% at baseline (p < 0.001) and follow-up (25 +/- 2 months). As BMI increased, prevalence of metabolic syndrome and central obesity increased (12 vs 48 vs 85%, p < 0.001 and 3 vs 42 vs 96%, p < 0.001, respectively). Systolic blood pressure, fasting blood glucose and lipid parameters changed significantly with BMI category and over time. Proteinuria progression occurred in 65% obese RTR (23 (13-59 g/mol creatinine) to 59 (25-120 g/mol creatinine)). BMI was independently associated with proteinuria progression (beta 0.01, p = 0.008) but not with changing eGFR(MDRD.) In conclusion, obesity is common in RTR and is associated with worsening CV parameters and proteinuria progression.

Adult↗
PubMed2005

Glomerulonephritis--management in general practice.

BACKGROUND: Glomerulonephritis (GN) is an important cause of both acute and chronic kidney disease, however the diagnosis can be difficult due to the variability of presenting features. OBJECTIVE: This article aims to develop a structured approach to the investigation of patients with markers of kidney disease, and promote the recognition of patients who need further assessment. Consideration is given to the importance of general measures required in the care of patients with GN. DISCUSSION: Glomerulonephritis is not an everyday presentation, however recognition and appropriate management is important to prevent loss of kidney function. Disease specific treatment of GN may require specialist care, however much of the management involves treatment of the associated complications such as oedema, achievement of target blood pressure and proteinuria reduction, and prevention and treatment of associated complications.

Adult↗
PubMed2004

Disseminated pyogenic Mycoplasma pneumoniae infection in a renal transplant recipient, detected by broad-range polymerase chain reaction.

Although extrapulmonary manifestations of Mycoplasma pneumoniae infection are generally immune-mediated, disseminated infections occasionally occur. We describe a renal transplant recipient who developed disseminated pyogenic M. pneumoniae infection that was detected by broad-range polymerase chain reaction and that manifested by prosthetic arterial graft infection, psoas abscess, and septic arthritis.

Adult↗
PubMed2004

The effect of oral iron admiinistration on mycophenolate mofetil absorption in renal transplant recipients: a randomized, controlled trial.

BACKGROUND: Oral iron supplements are frequently prescribed to renal transplant recipients in the early posttransplant period. A recent trial in seven healthy volunteers demonstrated a significant 91% reduction in mycophenolate mofetil (MMF) absorption when coadministered with oral iron. However, the effect of iron on MMF absorption in renal transplant patients has not been studied. METHODS: An open-label, randomized, controlled trial was undertaken in which new renal transplant recipients were randomly allocated to receive iron supplements with a morning dose of MMF, iron supplements given 4 hr after MMF at midday, or no iron supplements. Blood samples were taken for estimation of mycophenolic acid (MPA) area under the curve (AUC) at day 5 posttransplant. The primary endpoint was the day 5 MPA AUC, with secondary endpoints including acute rejection and MMF toxicity in the first 4 weeks posttransplant. Prospective power calculations indicated that a minimum of 13 patients in each group would be required to have a 90% probability of detecting a clinically significant reduction (10 mg/hr/L) in MPA AUC for iron-treated patients. RESULTS: Forty patients completed the study. There were no differences in baseline demographic data between the groups. The mean+/-standard deviation MPA AUC measurements for the groups receiving no iron (n=13), iron and MMF together (n=14), and iron and MMF spaced apart (n=13) were 34.5+/-8.7, 33.7+/-11.4, and 32.1+/-8.1 microg/hr/mL, respectively (P=0.82). Rates of acute rejection, cytopenia, infection, and gastrointestinal intolerance were comparable between the groups. CONCLUSIONS: There is no significant effect of oral iron supplements on MMF absorption as determined by measured blood concentrations. The practice of routinely giving oral iron in such patients seems safe from an immunosuppression drug-interaction standpoint.

Adult↗
PubMed2004

Increases in peritoneal small solute transport in the first month of peritoneal dialysis predict technique survival.

BACKGROUND: Peritoneal transport of small solutes generally increases during the first month of peritoneal dialysis (PD). The aim of this study was to prospectively evaluate the ability of the peritoneal equilibration test (PET), carried out 1 and 4 weeks after the commencement of PD, to predict subsequent technique survival. METHODS: Fifty consecutive patients commencing PD at the Princess Alexandra Hospital between 1 February 2001 and 31 May 2003 participated in the study. Paired 1 week and 1 month PET data were collated and correlated with subsequent technique survival. RESULTS: A significant increase was observed in the dialysate : plasma creatinine ratio at 4 h (D/P Cr) between 1 and 4 weeks after the onset of PD (0.55 +/- 0.12 vs 0.66 +/- 0.11, P <0.001). Mean death-censored technique survival was superior in patients who experienced > or =20% rise in D/P Cr during the first month of PD compared with those who did not (2.3 +/- 0.2 vs 1.6 +/- 0.2 years, P <0.05). Using a multivariate Cox proportional hazards model analysis, the significant independent predictors of death-censored technique survival were an increase in D/P Cr of greater than 20% during the first month (adjusted hazard ratio [HR] 0.20, 95% CI 0.05-0.75), the absence of diabetes mellitus, the absence of ischaemic heart disease, body mass index and baseline peritoneal creatinine clearance. CONCLUSIONS: A 20% or greater rise in D/P Cr during the first month of commencing PD is independently predictive of PD technique survival. Further investigations of the mechanisms underlying this phenomenon are warranted.

Biological Transport↗