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Biomedical subjects

Diane M Cibrik

Publications and source records attributed to Diane M Cibrik.

8 recordsLinked to original sources
PubMed2006

Therapeutic drug monitoring of mycophenolic acid in solid organ transplant patients treated with mycophenolate mofetil: review of the literature.

Mycophenolate mofetil (MMF) has conventionally been administered at a fixed dose without routinely monitoring blood levels of mycophenolic acid (MPA), the active metabolite. The contribution of therapeutic drug monitoring (TDM) during MMF therapy remains controversial. A literature review was performed to explore the usefulness of TDM for MPA in solid organ transplantation. In addition, emphasis was placed on the potential clinical benefits and limitations of TDM for MPA. Available studies have limitations and report conflicting results. Although early after transplantation MPA area under the curve might have predictive value for the risk of acute rejection, predose levels appear less reliable. With regard to MPA toxicity, most studies showed no correlation between MPA pharmacokinetics and adverse effects. TDM is hampered by several factors such as the considerable intra-subject variability of MPA pharmacokinetics and the increasing number of different drug combinations. Proposed target ranges are restricted to the early posttransplant period when MMF is used in combination with cyclosporine. The current review of the literature indicates no clear support for a substantial clinical benefit of TDM and more data from prospective randomized trials are needed.

Area Under Curve↗
PubMed2003

Renal allograft survival in transplant recipients with focal segmental glomerulosclerosis.

Previous literature suggests that the recurrence of focal segmental glomerulosclerosis (FSGS) after renal transplantation is more common in recipients who have received an HLA-identical living-related (LRD) transplant. To address the question if FSGS patients can safely receive a 6-antigen match LRD kidney transplant, we analyzed death-censored renal allograft survival data of FSGS patients from the United States Renal Data System database (USRDS). Using the USRDS and the U.S. Scientific Renal Transplant Registry between the years 1988-97, we found 19259 adult primary renal transplant recipients, of which 2414 patients had FSGS as their primary diagnosis as compared to 16845 patients who had other types of glomerulonephritis (GN). A Cox proportional hazard model was used to estimate death-censored graft survival among FSGS patients with a zero mismatch LRD kidney transplant. The model included a triple interaction term comparing FSGS vs. GN vs. living donation (LD) vs. cadaveric donation (CAD) vs. zero mismatch (six antigen or HLA-identical) vs. mismatch. Annually adjusted death censored graft loss rates per 1000 patients (ADGL) were calculated. Focal segmental glomerulosclerosis patients receiving a zero mismatch LRD kidney transplant had the lowest ADGL rate, losing 10.5 grafts per 1000 patients per year. Not significantly different but higher (14.3) was the ADGL rate for LD, zero mismatch GN recipients. The ADGL rate was significantly higher in FSGS recipients who received a LD, mismatched transplant (36.5). Focal segmental glomerulosclerosis patients who received a CAD, zero mismatched graft (44.1), or CAD, mismatched graft (63.2), had significantly higher ADGL rates. Zero mismatch LRD kidney transplants are not a risk factor for graft loss in FSGS patients but are associated with significantly better death-censored graft survival as compared to CAD 6-antigen match or mismatched donations.

Glomerulosclerosis, Focal Segmental↗
PubMed2002

Evaluation of pancreatic allograft dysfunction by laparoscopic biopsy.

BACKGROUND: Histologic evaluation of a failing pancreatic allograft is necessary for accurate classification of graft dysfunction. Unlike percutaneous or transcystoscopic techniques, laparoscopic biopsy allows visualization of the allograft in addition to obtaining tissue for histologic examination. METHODS: We retrospectively reviewed all laparoscopic pancreas transplant biopsies performed over a 15-month period ending February 2002. RESULTS: There were 12 laparoscopic pancreas biopsies performed in 11 patients between 6 weeks and 8 years (mean 2.5+/-2.8 years) after transplant. Indications for biopsy were hyperglycemia (n=8), hyperamylasemia (n=3), and graft tenderness (n=1). Adequate tissue was obtained in 11 of 12 biopsies. Two patients received definitive treatment at the time of laparoscopy (pseudocyst debridement, ovarian cyst excision). CONCLUSIONS: Laparoscopic pancreas transplant biopsy allows safe visualization of the allograft and effective specimen retrieval, and in some cases provides the opportunity for therapeutic intervention.

Adult↗
PubMed2002

Renal allograft survival in patients with oxalosis.

BACKGROUND: Primary hyperoxaluria is a rare autosomal recessive metabolic disease that often progresses to end-stage renal disease (ESRD). Liver transplantation is curative for patients with the alanine: glyoxylate aminotransferase deficiency. For oxalosis patients with minor enzyme deficiencies, renal transplantation may be the therapy of choice although concern exists about recurrence of oxalosis in the transplanted kidney. To date, previous data has been conflicting with most reports indicating poor renal allograft survival for oxalosis patients who receive a renal transplant alone. To determine whether graft survival in renal transplant recipients with oxalosis is similar to other transplant recipients with other forms of ESRD, we analyzed the United States Renal Data System (USRDS) registry comparing death-censored graft survival for transplant recipients with oxalosis to a reference group with ESRD secondary to glomerulonephritis (GN). METHODS: Using the USRDS and the U.S. Scientific Renal Transplant Registry data, we found 190 adult renal transplant recipients from 1988 to 1998 who had oxalosis as their primary diagnosis for their ESRD. Among the patients with oxalosis, 56 patients had a liver transplant followed by a kidney transplant (LKTx) and 134 patients had a kidney transplant alone (KTA). A Cox proportional hazard model was used to estimate patient survival and death-censored graft survival for patients with oxalosis who received a LKTx or a KTA. Unadjusted death-censored graft survival for oxalosis patients with a cadaveric or living-donor KTA or with a LKTx was obtained from Kaplan-Meier analysis. Recipients of solitary kidney transplants with GN served as the reference group. RESULTS: Oxalosis patients receiving a KTA had a significantly worse adjusted death-censored graft survival (47.9%) compared with patients with GN (61%) at 8 years posttransplantation (P <0.001). In contrast, oxalosis patients who received a LKTx had a significantly higher death-censored graft survival (76%) compared with oxalosis patients who received a KTA (47.9%, P<0.001) and had a trend toward better death-censored graft survival compared with patients with GN (P =0.05). In addition, oxalosis patients who received a living-donor KTA had significantly worse death-censored graft survival compared with oxalosis patients who received a LKTx (22% vs. 64%, P<0.01). Patient survival for oxalosis recipients with a KTA or a LKTx was not significantly different. CONCLUSIONS: Patients with oxalosis who receive a LKTx have superior death-censored graft survival compared with oxalosis patients who receive a cadaveric or living-donor KTA and trended toward better graft survival compared with GN patients.

Adult↗
PubMed2002

Interaction between donor and recipient age in determining the risk of chronic renal allograft failure.

OBJECTIVES: Donor age is a known risk factor for chronic allograft failure (CAF) in renal transplant recipients. We have recently shown that advanced recipient age is also a risk factor for CAF. To investigate the interaction between donor and recipient age, we analyzed 40,289 primary solitary Caucasian adult renal transplants registered at the United States Renal Data System (USRDS) from 1988 to 1997. DESIGN: CAF was defined as allograft loss beyond 6 months posttransplantation, censored for death, recurrent disease, acute rejection, thrombosis, noncompliance, infection, or technical problems. Cox proportional hazards models were used to investigate the risk of allograft loss secondary to CAF. All models were corrected for 15 covariates including donor and recipient demographics, ischemic time, and human leukocyte antigen match. Donor and recipient age were categorized, and relative risk for allograft loss of the interaction between the obtained categorical covariates was evaluated. SETTING: Retrospective data analysis using the USRDS. PARTICIPANTS: All primary Caucasian renal transplant recipients from 1988 to 1997. RESULTS: Patients aged 55 and older who received donor kidneys had a 110% increased risk of CAF (relative risk (RR) = 2.1, 95% confidence interval (CI) = 1.9-2.3, P< .001) and recipients aged 65 and older had a 90% increased risk for CAF (RR = 1.9, 95% CI = 1.61-2.1, P< .001), compared with the youngest reference groups. In addition, there was an additive and, in the long term, synergistic interaction between donor and recipient age in determining allograft loss. CONCLUSIONS: Donor and recipient age had an independent, equivalently detrimental effect on renal allograft survival. An overall additive and, in the long term (beyond 36 months posttransplant), synergistic deleterious effect on renal allograft survival was observed for the interaction of donor and recipient age.

Adult↗
PubMed2001

Survival improvement among patients with end-stage renal disease: trends over time for transplant recipients and wait-listed patients.

Both transplant and dialysis outcomes have improved over recent years. In addition, transplantation has been shown to confer a survival benefit over maintenance dialysis. The study presented here addresses the question of whether the survival benefit of transplantation over maintenance dialysis has changed in the most recent eras. This study was based on data collected by the United States Renal Transplant Scientific Registry and the United States Renal Data System. The study sample consisted of 104,000 patients placed on the renal transplant waiting list between 1988 and 1996, of which 73,707 subsequently received renal transplants. The annualized adjusted mortality rates per 1000 patient-years were calculated by calendar year of placement on the renal transplant waiting list and for kidney transplant recipients. The resulting data were plotted, and linear curve fitting was used to estimate the slope of the change of the adjusted mortality rates by year during the period studied, 1988 to 1996. Overall annual adjusted death rates in the wait-listed patients and transplant recipients per 1000 patient-years decreased for both groups throughout the study period. From 1989 to 1996, the relative risk (RR) for patient death had decreased by 30% for transplant recipients and 23% for wait-listed patients (RR = 0.70 and 0.77; P < 0.0001 each). Slope analysis of the cause-specific mortality rates for cardiovascular disease and infection showed nearly equivalent, linear decreases for both groups. Mortality rates have improved overall and by categories of major cause of death for both renal transplant recipients and patients on the renal transplant waiting list. These favorable trends most likely represent equal advances in transplantation, dialysis, and general medical care.

Adult↗
PubMed2000

Effect of mycophenolate mofetil on long-term outcomes in African american renal transplant recipients.

African American renal transplant recipients have poorer graft survival. A study using the United States Renal Data Registry documented an improvement in graft survival for patients who took mycophenolate mofetil (MMF) compared with azathioprine (AZA). This analysis did not address the impact of MMF on African American renal transplant recipients. The present study aimed to quantify potential beneficial effects of MMF therapy on long-term renal allograft survival in African Americans. With the use of the United States Renal Data Registry, all adult Caucasian and African American patients who had received a primary renal transplant between 1988 and 1997 were analyzed by Kaplan-Meier analysis and Cox proportional hazard models. Primary study end points were death with a functioning graft and graft failure censored for death. A total of 57,926 patients were studied. For African Americans, 3-yr patient survival was 96.3 versus 93.2% (P<0.001) for MMF and AZA, respectively. Three-yr death-censored graft survival for African Americans was 85.8 versus 75.1% (P<0.001) for MMF and AZA, respectively. For Caucasians, 3-yr patient survival was 97.3 versus 93.2% for MMF and AZA, respectively. Three-yr death-censored graft survival for Caucasians was 90.1 versus 86.4% (P<0.001) for MMF and AZA, respectively. By multivariate analysis, MMF was associated with a significant reduction in the relative risk for all study end points in African Americans. MMF therapy is associated with both improved patient and death-censored graft survival in African American renal transplant recipients. This benefit is comparable to the benefit of MMF in Caucasian renal transplant recipients.

Adult↗