Biomedical subjects

Godfrey Clark

Publications and source records attributed to Godfrey Clark.

6 recordsLinked to original sources

PubMed2005

Chronic allograft nephropathy and mycophenolate mofetil introduction in paediatric renal recipients.

Mycophenolate mofetil (MMF) introduction with concurrent reduction in calcineurin inhibitors has been shown to be beneficial in chronic allograft nephropathy (CAN) in adults. MMF was introduced to 19 children with CAN 26.3+/-5.8 (range 3.1-82.6) months after transplantation. Patients were followed up for a mean of 13.2+/-2.9 (range 1.2-51.1) months. The mean initial MMF dose was 660+/-56 mg/m2 per day, increased to 1,042+/-73 mg/m2 per day a year later. Cyclosporin was reduced from 138+/-10 mg/m2 per day at MMF introduction, to 116+/-15 mg/m2 per day at 6 months and 107+/-24 mg/m2 per day at 1 year. Six months prior to MMF introduction GFR deteriorated by -32.7+/-7.3 ml/min per 1.73 m2 per year. Six months after the introduction of MMF, GFR improved by +26.2+/-7.1 ml/min per 1.73 m2 per year (P <0.001). The introduction of MMF significantly reduced both the graft rejection rate (P=0.01) and systolic blood pressure (P=0.01), without a significant change in antihypertensive treatment. Haematological parameters did not significantly differ before and after MMF introduction. The introduction of MMF in paediatric renal transplant recipients with CAN may cause a significant improvement in GFR in both the short-term and the long-term and may well have a beneficial effect on systolic blood pressure. MMF has the potential to enable CNI-sparing protocols to be adopted.

Blood Pressure↗

PubMed2003

Benign intracranial hypertension in children following renal transplantation.

Benign intracranial hypertension (BIH) is a condition characterized by headache, papilledema, and a raised cerebrospinal fluid pressure with normal cranial imaging. It is uncommon in childhood. Previously, there have been reports that children with chronic impairment of renal function may be at greater risk of developing BIH. This study involved retrospective case note analysis of children undergoing renal transplantation over the last 11 years at our institution. Nine children developed BIH after renal transplantation. The prevalence of the condition in our series was 4.4%. Several etiologically relevant risk factors were identified, including medication (nitrofurantoin, minocycline) and excess weight gain. Our results suggest that BIH may be a more frequent complication of the post-operative care of pediatric renal transplant recipients than previously thought. We hope to alert pediatric nephrologists that examination of the fundus for papilledema in all renal transplant patients complaining of headache is essential. If the diagnosis of BIH is delayed, irretrievable visual loss may not be avoided.

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↗

PubMed2002

Management of renal vascular disease in neurofibromatosis type 1 and the role of percutaneous transluminal angioplasty.

BACKGROUND: The effectiveness of percutaneous transluminal angioplasty (PTA) in renal artery stenosis (RAS) associated with neurofibromatosis type 1 (NF1) has not been established. A review of the literature revealed 14 studies, mainly case reports, of which a total of 16 patients had been treated with PTA, all prior to any surgery being undertaken. METHODS: A retrospective case review of 10 children with renal vascular disease secondary to NF was conducted to evaluate the outcome of different treatment modalities, including PTA. Four patients had unilateral disease, while six had bilateral disease, which was associated with middle aortic syndrome in three. Treatment was a combination of antihypertensive drug therapy, PTA and surgery. PTA was performed 15 times on six patients, nine procedures prior to surgery. RESULTS: The success rate for PTA on primary stenoses was 33% with improvement in blood pressure (BP) control in another 33%. Angioplasties performed on stenoses post-surgery had a success rate of 67%. There were no major complications and PTA had no adverse effect on subsequent surgery. The pre-surgery results obtained at a tertiary referral centre are consistent with those reported in the literature. CONCLUSION: PTA is a safe and moderately effective treatment modality for RAS secondary to NF1. Although there is only limited success in primary stenoses as there is no adverse effect on subsequent surgery we feel it should be considered as first line management when clinically indicated.

Adolescent↗

PubMed2002

Improved efficacy of basiliximab over antilymphocyte globulin induction therapy in paediatric renal transplantation.

BACKGROUND: Basiliximab is a chimeric human/mouse monoclonal antibody directed against the alpha chain of the IL-2 receptor, CD25, which has been reported as successfully reducing rejection in adult renal transplant recipients. Reported clinical experience of basiliximab in paediatric renal transplantation is limited. METHODS: Using two intravenous doses on day 0 (pre-operatively) and day 4 with prednisolone and cyclosporin A (dual) maintenance immunosuppression in 42 children undergoing renal transplantation in our unit (SIM group), we have compared patient and graft outcome, rejection rates in the first 6 months, renal function and the incidence of Cytomegalovirus (CMV) infection with 42 consecutive children who previously received antilymphocyte globulin immunoprophylaxis with prednisolone, cyclosporin A and azathioprine (triple) maintenance immunosuppression (ALG group). The two groups were similar, including HLA mismatching, apart from age and size at transplantation (SIM=10.3+/-5.4 years vs ALG=12.4+/-4.2 years, P<0.05). RESULTS: One patient in the SIM group died from food inhalation with a functioning kidney and one patient in the ALG group from Pneumocystis pneumonia and post-transplant lymphoproliferative disorders with a rejecting graft. Both 1- and 2-year actuarial graft survivals were 93% for the SIM group and 86% for the ALG group (NS). Three grafts were lost in the SIM group-none from rejection (thrombosis 2, death 1)-and seven in the ALG group-three from rejection. Occurrence of biopsy documented rejection in the first 6 months after transplantation was 0.15+/-0.22 for the SIM group and 0.35+/-0.51 episodes per pt-month at risk for ALG treatment (P<0.04). Early rejection within 30 post-operative days occurred in only four SIM patients, three of whom had undergone retransplantation. Forty-seven per cent of rejection episodes occurred between days 30 and 44 in SIM treated patients. Switching to tacrolimus was similar in both groups; 24% of the SIM groups were prescribed triple therapy. Estimated glomerular filtration rate was 46.0 and 46.2 ml/min for SIM and ALG groups, respectively, six months after transplantation. Ten per cent of SIM and 19% of ALG treated patients developed clinically significant CMV infection (NS) but none of 16 (R(+)) SIM children had CMV infection compared with 8 out of 15 (R(+)) ALG patients (P<0.01). CONCLUSIONS: Basiliximab immunoprophylaxis and dual therapy reduces rejection episodes in the first six months and maintains graft survival and function after paediatric renal transplantation. Seventy-six per cent of children receiving basiliximab immunoprophylaxis were successfully maintained on long-term dual immunosuppression. This immunosuppressive protocol reduces CMV disease in CMV(+) recipients compared with ALG induction and triple therapy.

Antibodies, Monoclonal↗