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Nicole M Isbel

Publications and source records attributed to Nicole M Isbel.

26 records · Page 2Linked to original sources
PubMed2004

Efficacy and side-effect profile of sevelamer hydrochloride used in combination with conventional phosphate binders.

BACKGROUND: Poor phosphate control is common among patients with end-stage renal disease. Sevelamer hydrochloride has been demonstrated to be a safe and effective phosphate binder when used as a monotherapy. However, cost limits its usefulness in many countries. Data assessing its effectiveness and safety in combination with conventional phosphate binders are lacking. METHODS: Dialysis patients meeting the following inclusion criteria participated in this study: (i) hyperphosphataemia >1.8 mmol/L (5.6 mg/dL); and (ii) an inability to tolerate currently available binders. The trial was conducted in three phases each lasting 3 months: (i) an observation phase (patients continued on their regular phosphate binders); (ii) a titration phase (sevelamer was added at a dose of 403 mg three times daily with meals, titrated to a maximum of 1209 mg three times daily); and (iii) a maintenance phase. RESULTS: Twenty-five patients were recruited into the study. Eighteen patients completed all three trial phases. Mean serum phosphate dropped from 2.11 +/- 0.06 mmol/L (6.6 +/- 0.2 mg/dL) during the observation period to 1.91 +/- 0.01 mmol/L (5.9 +/- 0.003 mg/dL) during the maintenance phase (P=0.02). Calcium x phosphate product fell from 5.49 +/- 0.17 mmol2/L2 (68.64 +/- 2.11 mg2 dL2) to 4.89 +/- 0.27 mmol2/L2 (61.36 +/- 3.35 mg2 dL2) (P=0.02). There was no significant change in serum calcium or parathyroid hormone. Total serum cholesterol fell from 3.8 mmol/L (3.4-4.37) 147 mg/dL (131-169) to 3.55 mmol/L (2.97-4.2) 137 mg/dL (115-162) (P=0.02). Serum low-density lipoprotein cholesterol also fell significantly from 1.67 +/- 0.10 mmol/L (65 +/- 4 mg/dL) to 1.52 +/- 0.11 mmol/L (59 +/- 4 mg/dL) (P=0.04). The average prescribed dose of sevelamer was 2.4 g/day. Elemental calcium dropped from 3.4 g/day (1.4 to 4.6) to 1.2 g/day (0.6-2.4) (P=0.04). Seventy-two per cent of patients reported mild flatulence, nausea and indigestion. Three patients discontinued treatment because of adverse effects. CONCLUSIONS: Sevelamer in combination with conventional phosphate binders is effective in lowering serum phosphate and calcium-phosphate product in patients with refractory hyperphosphataemia. Beneficial effects on lipid profile were also observed. Mild gastrointestinal upset is common.

Aluminum Hydroxide↗
PubMed2003

Frequency and severity of acute rejection in live- versus cadaveric-donor renal transplants.

BACKGROUND: Live donors are an increasingly important source of kidneys for transplantation in Australia. The aim of this study was to compare the rate and severity of rejection between patients receiving kidney transplants from live versus cadaveric donors. METHODS: A retrospective analysis was undertaken of all patients receiving live-donor (n=109) and cadaveric-donor (n=389) renal transplants at our institution between April 1, 1994, and March 31, 2000. Follow-up was completed on all patients until graft loss, death, or May 31, 2001. RESULTS: The baseline characteristics of the live-donor and cadaveric groups were similar, except for recipient age (mean+/-SD, 36.3+/-15.6 vs. 44.5+/-14.4 years, respectively; P<0.001); donor age (46.1+/-11.3 vs. 36.1+/-16.4 years, P<0.001); pretransplant dialysis duration (1.36+/-2.1 vs. 3.4+/-4.4 years, P<0.001); and the proportions of patients receiving first allografts (95% vs. 88%, respectively; P<0.05), antibody induction (8% vs. 20%, P<0.01), and mycophenolate mofetil (MMF) (60% vs. 37%, P<0.001). Acute rejection was observed in 48 (44%) live-donor and 108 (28%) cadaveric transplants (P=0.001). Cadaveric donor type was independently predictive of less acute rejection both on logistic regression (adjusted odds ratio [AOR], 0.47; 95% confidence interval [CI], 0.30-0.73; P=0.001) and multivariate Cox proportional hazards model analysis (hazard ratio, 0.49; 95% CI, 0.34-0.69; P<0.001). Patients receiving cadaveric-donor transplants were also significantly less likely to receive antibody therapy for rejection (univariate, 18% vs. 9%; P=0.006; multivariate AOR, 0.45; 95% CI, -0.25-0.82; P<0.01), independent of recipient age, gender, race, transplant number, human leukocyte antigen mismatch, sensitization, induction therapy, delayed graft function, MMF use, tacrolimus or cyclosporine A use, sirolimus-everolimus use, year of transplant, donor age, or dialysis duration. However, donor type did not independently influence graft survival, immunologic graft survival, or patient survival. CONCLUSIONS: Live-donor kidney transplant recipients had a higher rate and severity of rejection and a shorter rejection-free period than cadaveric renal transplant recipients. Further consideration of the reasons for this difference and the use of alternative immunosuppressive strategies for live-donor transplants are recommended.

Acute Disease↗
PubMed2002

The effect of obesity on renal transplant outcomes.

BACKGROUND: Although obesity has been associated with improved survival on dialysis, its effects on renal transplant outcomes remain unclear. Previous studies have reported conflicting findings and have been limited by the use of outdated patient data, univariate analyses, and liberal transplant selection criteria. The present study aimed to evaluate the effect of obesity on renal transplant outcomes in a rigorously screened population. METHODS: A retrospective analysis was undertaken of all patients transplanted at the Princess Alexandra Hospital from 1 April 1994 to 31 March 2000. Patients were rigorously screened for cardiovascular disease before acceptance for transplantation. The effects of obesity on renal transplant outcomes were assessed by logistic and multivariate Cox regressions. RESULTS: Of the 493 patients transplanted, 59 (12%) were obese (body mass index [BMI] 30 kg/m ). Obese patients were more likely to experience superficial wound breakdown (14% vs. 4%, P<0.01) and complete wound dehiscence (3% vs. 0%, P<0.01). Wound infections also tended to be more frequent in obese recipients (15% vs. 8%, P=0.11). There were no significant differences between the two groups with respect to operative duration, postoperative complications, hospitalization, delayed graft function, or acute rejection episodes. Five-year actuarial survival rates were comparable between the two groups with respect to graft survival (83% vs. 84%, P=NS) and patient survival (91% vs. 91%, P=NS). On multivariate analysis, BMI was an independent risk factor for wound breakdown (odds ratio 1.21, 95% CI 1.09-1.34, P<0.001), but not for other posttransplant complications, hospitalization, graft loss, or patient survival. CONCLUSIONS: The only significant adverse effect of obesity on renal transplant outcomes was an increase in wound complications, which were generally of minor consequence. Provided that adequate care is taken to avoid transplanting patients with significant cardiovascular disease, obese recipients can achieve excellent long-term patient and graft survivals that are on par with their nonobese counterparts. Denying patients access to renal transplantation on the basis of obesity per se does not appear to be justified.

Adult↗
PubMed2002

Is mycophenolate mofetil less safe than azathioprine in elderly renal transplant recipients?

BACKGROUND: Mycophenolate mofetil (MMF) is a potent immunosuppressive agent that has been shown to be superior to azathioprine in preventing early acute rejection in the general renal transplant population. However, it is uncertain whether these benefits also apply to older renal transplant recipients, who are known to be more susceptible to infectious complications and have considerably lower rates of rejection and immunological graft loss. METHODS: A retrospective analysis was undertaken of all elderly (> or =55 years old) renal transplant recipients who underwent renal transplantation at the Princess Alexandra Hospital (1994-2000) and received either MMF (n=60) or azathioprine (n=55) in combination with prednisolone and cyclosporin. Data were analyzed on an intention-to-treat basis using a multivariate Cox proportional hazards model. RESULTS: The azathioprine- and MMF-treated groups were well matched at baseline with respect to demographic characteristics, end-stage renal failure causes and transplant characteristics. Compared with the MMF cohort, azathioprine-treated patients experienced a shorter time to first rejection [hazard ratio (HR) 4.47, 95% CI 1.53-13.1, P<0.01]. However, azathioprine-treated patients were also less likely to develop opportunistic infections (HR 0.11, 95% CI 0.03-0.41, P=0.001). No differences were observed between the two groups with respect to hospitalization rates, intensive care admissions, hematological complications, or posttransplant malignancies. Actuarial 2-year survival rates for the azathioprine- and MMF-treated patients were 100 and 87%, respectively (P<0.001). The principal cause of death in the MMF cohort was infection. Using a multivariate Cox regression analysis of patient survival, an adjusted hazard ratio of 0.01 (95% CI 0.001-0.08, P=0.001) was calculated in favor of azathioprine. Overall graft survival also tended to be better in patients receiving azathioprine (HR 0.27, 95% CI 0.06-1.33, P=0.11), CONCLUSIONS: In elderly renal transplant recipients, the combination of MMF, cyclosporin, and prednisolone appears to result in a worse outcome compared with the less potent combination of azathioprine, cyclosporin, and prednisolone. Future prospective studies need to specifically evaluate the risk/benefit ratios of newer, more potent immunosuppressive protocols, such as MMF-based regimens, in this important and sizeable patient subgroup.

Aged↗
PubMed2002

Urine macrophage migration inhibitory factor reflects the severity of renal injury in human glomerulonephritis.

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that plays a pathogenic role in experimental crescentic glomerulonephritis (GN). Renal expression of MIF is also upregulated in human GN and correlates with leukocytic infiltration, histologic damage, and renal dysfunction. The study presented here examined whether MIF can be measured in urine and if so, whether the urine MIF concentration reflects the degree of renal injury. Urine and serum MIF was measured by enzyme-linked immunosorbent assay in 10 normal healthy volunteers and in a cohort of 63 patients with GN (2 thin basement membrane disease [TBM], 15 membranous GN, 10 focal segmental glomerular sclerosis, 20 IgA glomerularnephritis, 11 crescentic GN, 10 systemic lupus erythematosis World Health Organization class IV). Renal MIF expression was assessed by immunostaining of biopsy tissue. MIF was detected in urine from normal volunteers (mean +/- SD; 191 +/- 132 pg MIF/micromol creatinine). The urine MIF concentration was unchanged in patients with nonproliferative nephropathies (343 +/- 397 pg MIF/micromol Cr) but was increased 3.4-fold in proliferative nephropathies (645 +/- 527 pg MIF/micromol Cr; P < 0.05 versus normal and nonproliferative). Stratified analysis showed the greatest increase in urine MIF in crescentic GN (4.5-fold). In contrast, serum MIF levels were not different between normal patients and any patient group. Immunostaining demonstrated a significant increase in renal MIF expression in proliferative glomerulonephritides that was associated with macrophage and T cell infiltration. There was a significant correlation between the urine MIF concentration and renal MIF expression, but not with serum MIF, indicating a renal origin for the excreted urine MIF. The urine MIF concentration also correlated with the degree of renal dysfunction, histologic damage, and leukocytic infiltration, but not with the amount of proteinuria. In conclusion, this study shows that the urine MIF concentration is significantly increased in proliferative forms of GN and correlates with the degree of renal injury. Urine MIF levels reflect MIF expression within the kidney and may be a useful noninvasive tool for monitoring patients with crescentic GN, particularly in disease exacerbation.

Adult↗
PubMedDate not supplied

Predictors of decline of residual renal function in new peritoneal dialysis patients.

OBJECTIVE: The aim of this study was to prospectively evaluate the risk factors for decline of residual renal function (RRF) in an incident peritoneal dialysis (PD) population. DESIGN: Prospective observational study of an incident PD cohort at a single center. SETTING: Tertiary-care institutional dialysis center. PARTICIPANTS: The study included 146 consecutive patients commencing PD at the Princess Alexandra Hospital between 1 August 1995 and 1 July 2001 (mean age 54.8 +/- 1.4 years, 42% male, 34% diabetic). Patients with failed renal transplants (n = 26) were excluded. MAIN MEASUREMENTS: Timed urine collections (n = 642) were performed initially and at 6-month intervals thereafter to measure RRF. The development of anuria was also prospectively recorded. RESULTS: The mean (+/- SD) follow-up period was 20.5 +/- 14.8 months. The median slope of RRF decline was -0.05 mL/minute/month/1.73 m2. Using binary logistic regression, it was shown that the 50% of patients with more rapid RRF loss (< -0.05 mL/min/month/1.73 m2) were more likely to have had a higher initial RRF at commencement of PD [adjusted odds ratio (AOR) 1.83, 95% confidence interval (CI) 1.39-2.40] and a higher baseline dialysate/ plasma creatinine ratio at 4 hours (D/P creat; AOR 44.6, 95% CI 1.05-1900). On multivariate Cox proportional hazards model analysis, time from commencement of PD to development of anuria was independently predicted by baseline RRF [adjusted hazard ratio (HR) 0.81, 95% CI 0.60-0.81], D/P creat (HR 2.87, 95% CI 2.06-82.3), body surface area (HR 6.23, 95% CI 1.53-25.5), dietary protein intake (HR 2.87, 95% CI 1.06-7.78), and diabetes mellitus (HR 1.65, 95% CI 1.00-2.72). Decline of RRF was independent of age, gender, dialysis modality, urgency of initiation of dialysis, smoking, vascular disease, blood pressure, medications (including angiotensin-converting enzyme inhibitors), duration of follow-up, and peritonitis rate. CONCLUSIONS: The results of this study suggest that high baseline RRF and high D/P creat ratio are risk factors for rapid loss of RRF. Moreover, a shorter time to the onset of anuria is independently predicted by low baseline RRF, increased body surface area, high dietary protein intake, and diabetes mellitus. Such at-risk patients should be closely monitored for early signs of inadequate dialysis.

Anuria↗
PubMedDate not supplied

A comparison of peritoneal equilibration tests performed 1 and 4 weeks after PD commencement.

OBJECTIVE: The aim of this study was to prospectively evaluate the ability of a peritoneal equilibration test (PET) performed in the first week of peritoneal dialysis (PD) to predict subsequent transport status, as determined by a PET at 4 weeks and >1 year after PD commencement. DESIGN: Prospective observational study of an incident PD cohort at a single center. SETTING: Tertiary-care institutional dialysis center. PARTICIPANTS: The study included 50 consecutive patients commencing PD at the Princess Alexandra Hospital between 25/2/2001 and 14/5/2003 (mean age 60.9 +/- 12.2 years, 54% male, 92% Caucasian, 38% diabetic). All patients were initially prescribed continuous ambulatory PD. MAIN MEASUREMENTS: Measurements performed during paired PETs included dialysate-to-plasma ratios of urea (D/P urea) and creatinine (D/P creatinine) at 4 hours, the ratio of dialysate glucose concentrations at 0 and 4 hours (D/D0 glucose), and drain volumes at 4 hours. RESULTS: When paired 1-week and 1-month PET data were analyzed, significant changes were observed in measured D/P urea (0.91 +/- 0.07 vs 0.94 +/- 0.07 respectively; p < 0.05), D/P creatinine (0.55 +/- 0.12 vs 0.66 +/- 0.11, p < 0.001), and D/D0 glucose (0.38 +/- 0.08 vs 0.36 +/- 0.10, p < 0.05). Using Bland-Altman analysis, the repeatability coefficients were 0.17, 0.20, and 0.13, respectively. Agreement between 1-week and 1-month PET measurements with respect to peritoneal transport category was moderate for D/D0 glucose (weighted kappa 0.52), but poor for D/P urea (0.30), D/P creatinine (0.35), and drain volumes (0.20). The PET measurements performed more than 1 year following PD commencement (n = 28) generally agreed closely with 1-month measurements, and poorly with 1-week measurements. CONCLUSIONS: Peritoneal transport characteristics change significantly within the first month of PD. PETs carried out during this time should be considered preliminary and should be confirmed by a PET 4 weeks later. Nevertheless, performing an early D/D0 glucose measurement at 1 week predicted ultimate transport status sufficiently well to facilitate early clinical decision-making about optimal PD modality while patients were still receiving PD training. On the other hand, the widespread practice of using measured drain volumes in the first week to predict ultimate transport category is highly inaccurate and not recommended.

Female↗