Biomedical subjects

Mark Mentser

Publications and source records attributed to Mark Mentser.

5 recordsLinked to original sources

PubMed2005

Risk factors for short- and long-term survival of primary cadaveric renal allografts in pediatric recipients: a UNOS analysis.

BACKGROUND: Pediatric kidney graft survival rates have improved in the United States. This study evaluates early and late risk factors for cadaveric graft loss in pediatric recipients. METHODS: From January 1994 to December 2002, 2,597 primary cadaveric kidney-alone transplants (donor age 5-45 years, recipient age 2-20 years) were reported to the United Network for Organ Sharing (UNOS). The analysis includes follow-up information based on OPTN data as of October 14, 2003. Odds ratio of early graft loss and relative risk of late graft loss are estimated using logistic regression and Cox proportional hazards model, respectively. RESULTS: Graft survival rates significantly improved during 1999-2002 (95% and 79% at 1-year and 3-years, respectively) compared with those of 1994-1998 (88% and 76% at 1-year and 3-years, respectively) (log rank P=0.02). After adjusting for other variables, the factors that significantly affected early transplant outcome adversely within 3 months posttransplant were prolonged cold ischemia time (>36 hours, odds ratio [OR]=3.38 vs. 0-36 hours) and young recipient age (2-5 years old, OR=2.02 vs. 6-12 years). Beyond 3 months, significant risk factors were African-American recipients (relative risk [RR]=1.93 vs. others), teenage recipients (13-20 yrs, RR=1.50 vs. 6-12 yrs), and patients with focal glomerulosclerosis (FGS) (RR=1.27 vs. others). CONCLUSIONS: The short-term graft survival rate of pediatric cadaveric kidney transplants has significantly improved, yet the long-term outcome has changed little. The long-term outcomes for teenagers (13-20 yrs), patients with FGS, and African-Americans lag significantly behind other groups. In order to improve long-term graft survival in these high-risk patients, newer preventive or treatment strategies must be developed.

Acute Disease↗

PubMed2005

Experience with autogenous arteriovenous access for hemodialysis in children and adolescents.

The National Kidney Foundation's DOQI-NKF recommendation to construct an autogenous arteriovenous access (AAVA) for chronic hemodialysis whenever possible can be a challenge in the pediatric population. This report reviews recent surgical experience in this patient subgroup. From March 1999 to April 2004, 47 consecutive children requiring permanent vascular access had construction of AAVA. There were 16 girls and 31 boys, with a mean age of 14.6 years (range 5-20). The surgeon preoperatively mapped veins with ultrasound in all patients. Access sites were radial-cephalic (n = 16), upper arm brachial-cephalic (n = 15), transposed upper arm brachial-basilic (n = 7), and transposed femoral vein (n = 9). An operating microscope was used to construct three radial-cephalic accesses in individuals with small arteries. Three forearm cephalic veins were transposed (one at the original surgical procedure and two postoperatively). Five upper arm cephalic veins were transposed (three at the original surgical procedure and two postoperatively). Femoral vein accesses were constructed for either exhausted access in the upper extremities (n = 7) or patient preference (n = 2). Primary patency at 1 and 2 years was 100% and 96%, respectively. Secondary patency at 1 and 2 years was 100%. One individual with a radial-cephalic AAVA and severe radial artery calcification required an inflow procedure. Thirty-five accesses are currently in use (functionally patent), eight are in individuals with successful renal transplants, and two are maturing; one individual declines using the access. Two accesses are secondarily patent (thrombosed and repaired 12 and 29 months after construction, respectively), and one access thrombosed after 27 months (abandoned). Construction of an AAVA is possible in virtually all pediatric age individuals if attention is given to preoperative vein mapping, selective use of an operating microscope, and creation of a transposed femoral vein when upper extremity access is neither possible nor desired.

Adolescent↗

PubMed2003

Everolimus in pediatric de nova renal transplant patients.

BACKGROUND: The steady-state pharmacokinetics of everolimus were longitudinally assessed in pediatric de novo kidney allograft recipients during a 6-month period. METHODS: Nineteen patients received everolimus 0.8 mg/m2 (maximum 1.5 mg) twice daily as a dispersible tablet in water in addition to cyclosporine and corticosteroids. Everolimus and cyclosporine trough concentrations were obtained on days 3, 5, 6, and 7 and at months 1, 2, 3, and 6; an everolimus pharmacokinetic profile was obtained on day 7 and month 3. RESULTS: There were 9 boys and 10 girls with a median age of 9.9 (range, 1-16) years. Steady-state pharmacokinetic parameters were as follows (median, range): C(min) (trough level), 4.7 (2.3- 9.5) ng/mL; peak concentration, 13.5 (5.9-22.2) ng/mL; area under the concentration-time curve (AUC), 77 (53-147) ng x hr/mL; and apparent oral clearance, 10.2 (5.5-15.6) L/hr/m2. Clearance (unadjusted for demographic factors) was positively correlated with age (r=0.66), body surface area (r=0.68), and weight (r=0.67). There were no trends in C(min) or AUC versus patient age when everolimus was dosed on a mg/m2 basis. Everolimus C(min) were stable over time with median values of 3.9, 3.4, and 3.1 ng/mL at months 1, 3, and 6, respectively. Intra- and interpatient variability in AUC was 29% and 35%, similar to that in adults. During the observation period, eight patients maintained stable AUCs and nine patients had increases or decreases, generally between 30% and 50% compared with the AUC at week 1. The concurrent median cyclosporine C(min) were generally at the lower end of conventional target ranges: 156, 83, and 69 ng/mL at months 1, 3, and 6, respectively. There were no graft losses and only three mild or moderate, reversible rejection episodes occurred. Everolimus was generally safe and well tolerated. CONCLUSIONS: These data support the use of body surface area-adjusted dosing for everolimus in pediatric patients. Although exposure is generally stable over time with moderate variability in AUC, therapeutic monitoring would be a helpful adjunct for individualizing everolimus exposure, assessing regimen adherence, and adjusting doses as the child matures.

Adolescent↗

PubMed2002

A multicenter, open-label, pharmacokinetic/pharmacodynamic safety, and tolerability study of basiliximab (Simulect) in pediatric de novo renal transplant recipients.

BACKGROUND: Basiliximab (Simulect) has been shown to be safe and effective in adult renal transplant recipients, when used in combination with cyclosporine (Neoral) and corticosteroids. We report on the safety and preliminary efficacy of basiliximab in pediatric de novo renal transplant recipients. METHODS: This was an open-label, 12-month study of basiliximab in 41 patients (2 cohorts: <9 and 9 to <16 years). In phase 1, two intravenous (IV) bolus injections of basiliximab (12 mg/m ) were administered (before and 4 days postsurgery). In phase 2, two injections (<40 kg, 10 mg and > or =40 kg, 20 mg) were administered at the same time points. Most patients (26/41 [63%]) received cadaveric kidneys. Almost half of the patients had three human leukocyte antigen mismatches with the organ donors. Concurrent immunosuppression included Neoral and corticosteroids. Azathioprine was allowed after 28 days. RESULTS: All patients completed the 1-year study. The acute tolerability of basiliximab via IV bolus injection was good, without evidence of cytokine-release syndrome or acute local reactions. All patients experienced adverse events, but most (71%) were mild or asymptomatic. No deaths or malignancies occurred. The incidence and types of serious adverse events (59%) and serious infections (44%) were as expected in this patient population, and few were drug-related (7% and 5%, respectively). Thirty-eight patients (93%) had infections, mostly urinary tract infections, as expected for renal transplant patients. Six patients (15%) had drug-related adverse events. Biopsy-confirmed acute rejection episodes occurred in 6/41 (15%) of patients during the first 6 months posttransplantation and in 9/41 (22%) patients during the first 12 months. Five patients (12%) experienced graft loss, none of which were preceded by acute rejection episodes. CONCLUSIONS: Basiliximab is safe and well tolerated when administered by IV bolus injection in de novo pediatric renal transplant recipients. These preliminary data suggest that basiliximab, given in combination with cyclosporine and corticosteroids, is an effective immunosuppressive regimen for the prevention of acute rejection in pediatric renal transplantation.

Adolescent↗

PubMed2002

A rational dosing algorithm for basiliximab (Simulect) in pediatric renal transplantation based on pharmacokinetic-dynamic evaluations.

BACKGROUND: The pharmacokinetics and immunodynamics of basiliximab were assessed in 39 pediatric de novo kidney allograft recipients to rationally chose a dose regimen for this age group. METHODS: In study part 1, patients were given 12 mg/m(2) of basiliximab by bolus intravenous injection before surgery and on day 4. An interim pharmacokinetic evaluation supported a fixed-dose approach for study part 2 in which infants and children received two 10-mg doses and adolescents received two 20-mg doses. Blood samples were collected over a 12-week period for analysis of basiliximab and soluble interleukin-2 receptor concentrations, flow cytometry, and screening for anti-idiotype antibodies. RESULTS: Basiliximab clearance in infants and children (n=25) was reduced by approximately half compared with adults from a previous study and was independent of age (1-11 years), weight (9-37 kg), and body surface area (0.44-1.20 m(2) ). Clearance in adolescents (12-16 years, n=14) approached or reached adult values. CD25-saturating basiliximab concentrations were maintained for 31+/-12 days in study part 1 with mg/m(2) dosing and for 36+/-14 days in study part 2 based on the fixed-dose regimen ( P=0.31). A single patient experienced a rejection episode during CD25 saturation. The duration of CD25 saturation in patients who experienced a rejection episode after desaturation did not differ from those who remained rejection-free for the full 6-month period: 34+/-6 days (n=6) vs. 35+/-14 days (n=33 patients); P=0.74. Anti-idiotype antibodies were detected in two patients; however, this did not influence the clearance of basiliximab or the duration of CD25 saturation. CONCLUSIONS: To achieve similar basiliximab exposure as is efficacious in adults, pediatric patients <35 kg should receive two 10-mg doses and those > or =35 kg should receive two 20-mg doses of basiliximab by intravenous infusion or bolus injection. The first dose is given before surgery and the second on day 4 after transplantation.

Algorithms↗