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Biomedical subjects

P J Griffin

Publications and source records attributed to P J Griffin.

At least 19 recordsLinked to original sources
PubMed1999

Renal effects of amlodipine in normotensive renal transplant recipients.

Renal effects of amlodipine in normotensive renal transplant recipients. The use of cyclosporin A (CsA) has improved the success of renal transplantation, but is associated with hypertension and significant renal toxicity. Previous reports suggest that calcium channel blockers may be useful in opposing the adverse effects of CsA. We have evaluated the effects of amlodipine (5 mg, once daily for 8 weeks) on renal function in 27 normotensive renal transplant recipients with stable renal function, in a double-blind, placebo-controlled, multicentre, cross over study. Amlodipine significantly reduced serum creatinine concentration relative to placebo (mean+/-SD: 168+/-65 vs 177+/-66 micromol/l; P=0.002) and there was a strong trend towards an increase in effective renal plasma flow on amlodipine relative to placebo (238+/-92 vs 217+/-87 ml/min; P=0.055). Glomerular filtration rate and lithium clearance were unaffected. Trough CsA blood concentration was unaffected. Amlodipine was well tolerated, with a low incidence of adverse events, and did not affect blood pressure or heart rate. In conclusion, amlodipine reduced serum creatinine in normotensive renal transplant recipients after only 8 weeks treatment, and was well tolerated in concomitant administration with CsA.

Adolescent↗
PubMed1996

Pharmacokinetics and immunodynamics of chimeric IL-2 receptor monoclonal antibody SDZ CHI 621 in renal allograft recipients.

SDZ CHI 621 is a murine-human chimeric monoclonal antibody (mAb) to the interleukin-2 (IL-2) receptor (CD25) intended for prophylactic immunosuppression against acute rejection in the first several weeks following kidney transplantation. A multicentre, prospective, dose-finding study was conducted in 37 primary, mismatched cadaver kidney transplant patients to assess its tolerability, pharmacokinetics and immunodynamics. Successive cohorts of patients were stratified to receive total doses of 20, 30, 40 or 60 mg (n = 4, 4, 14, 15, respectively) administered as 15- or 20-mg intravenous infusions with the first dose given preoperatively and subsequent doses within the first 10 days posttransplant. Daily mAb serum concentrations were analysed by a radioimmunoassay method and the percentage of peripheral T-lymphocytes expressing CD25 from serial blood samples was determined by FACScan. Intravenous administrations were well tolerated. mAb concentration profiles exhibited a biphasic decline with an initial t1/2 of 14.4 +/- 14.2 h, terminal t1/2 of 13.4 +/- 6.0 days, distribution volume (Vss) of 6.9 +/- 3.31 and clearance of 17.4 +/- 7.8 ml/h. The concentration-effect (mAb-CD25) relationship indicated that mAb concentrations exceeding a threshold of about 0.7 microgram/ml corresponded to complete suppression of CD25 (< or = 3% CD25+ T-cells). The threshold mAb concentration was exceeded at all dose levels, whereas the duration above the threshold (and thus of CD25 suppression) rose with increasing dose: 20 mg, 20 +/- 7 days; 30 mg, 32 +/- 6 days; 40 mg, 37 +/- 10 days; and 60 mg, 53 +/- 17 days. As mAb concentrations declined below the threshold following the last dose, CD25 expression returned to baseline (18-44% CD25+ T-cells) within a few days.

Adolescent↗
PubMed1996

Reduced dose OKT3 prophylaxis in sensitised kidney recipients.

Prophylactic use of the monoclonal antibody OKT3 has been studied for the prevention of rejection in sensitised renal transplant recipients. Patients receiving a full dose (FD) regimen were compared to a subsequent consecutive group of patients receiving a reduced dose (RD) regimen. The characteristics of the two groups were not significantly different with regard to age, HLA mismatch and panel-reactive antibody (PRA) status. The number of days that OKT3 was given was 12.9 +/- 1.8 for the FD regimen and 11.3 +/- 2.8 for the RD regimen. The total dose of OKT3 given was 64.4 +/- 9 mg (FD) and 38.3 +/- 8.5 mg (RD). Patient survival at 12 months was 8/8 for FD and 17/17 for RD. Graft survival at 12 months was 7/8 for FD and 17/17 for RD. Creatinine at 24 months was 185 +/- 68 and 201 +/- 81 mumol/l for FD and RD, respectively. A reduced dose regimen of OKT3 produced excellent and comparable results to the standard recommended full-dose regimen. The cost per patient was reduced 40% from 5676 pounds for FD to 3344 pounds for RD.

Adult↗
PubMed1995

Prolonged action of a chimeric interleukin-2 receptor (CD25) monoclonal antibody used in cadaveric renal transplantation.

A high affinity chimeric CD25 mAb (chRFT5: SDZ CHI 621) blocking interleukin-2 binding to the interleukin-2 receptor alpha-chain was evaluated in a phase I/II study in human renal cadaveric transplantation. The chRFT5 was well tolerated with no immediate adverse effects during 6 spaced infusions (from before transplantation to day 24) in 24 patients escalating from 2.5- to 25-mg dosages. The chRFT5 had a long terminal half-life with a mean of 13.1 days. There was good correlation between the detection of chRFT5 in the serum by radioimmunoassay, the coating and suppression of CD25 on T cells, and antibody activity in patient serum samples. The chRFT5 activity persisted in vivo for up to 120 days. No antibody response to the chRFT5 was detected in any of the patients, even though two patients who required treatment with antithymocyte globulin or OKT3 developed xenogeneic antiglobulin responses while chRFT5 was still present in vivo. There was a 33% incidence of rejection and the first rejection episode always occurred during chRFT5 therapy. Patients who did not reject during therapy did not reject during the first year following transplantation. Equal numbers of patients received dual and triple immunosuppressive therapy together with chRFT5. Posttransplant lymphoproliferative disorder developed in 2 patients, both on triple therapy, at 9 months after transplantation. The disorder did not develop in any patient receiving dual therapy, and no further cases have been observed to a minimum of 2 years' follow-up. No other viral, fungal, or bacterial infectious complications were prevalent in patients treated with chRFT5.

Adult↗
PubMed1994

Pancreatic transplantation as a small programme.

Seventeen pancreatic transplantations were performed in 17 patients with diabetic renal failure over a 6-year period. Ten patients received a simultaneous kidney transplant, the other seven having undergone previous successful renal transplantation. The actuarial pancreatic survival rate at 12 months was 63 per cent and the patient survival rate 92 per cent. The kidney transplant 12-month survival rate (86 per cent) did not differ significantly from that in a group of 22 diabetic patients receiving kidney transplants alone during the same period. Patients with a successful pancreatic transplantation had an increase in quality of life but most developed one or more complications; sometimes these required prolonged hospitalization. Pancreatic transplantation should be restricted to patients with diabetic renal failure who are particularly unstable or exhibit progressive diabetic complications. A small programme can be successful in directing what is an expensive procedure towards patients who are most likely to benefit.

Adult↗
PubMed1994

Transplanting patients with abnormal lower urinary tracts.

Since 1977, 23 patients with bladder or bladder outlet dysfunction leading to renal failure have received 28 kidney transplants in our institution. Three patients were provided with an ileal conduit, but the remainder were transplanted using their own bladder following urodynamic assessment and bladder reconstruction. Graft and patient survival were good when compared to a group of patients with normal lower urinary tracts, actuarial graft survival at 5 years being 70% for both groups and patient survival being 82% and 90%, respectively. Patients who develop renal failure from detrusor/sphincter dysfunction can be transplanted successfully once the cause of the renal failure has been identified and corrected.

Adolescent↗
PubMed1993

Is there an optimal time for the first cyclosporin dose in renal transplantation?

It is customary for patients undergoing kidney transplantation to receive their first dose of cyclosporin either just before or during the transplant operation. This ensures the early establishment of good levels of immunosuppression but might depress early graft function and contribute towards the development of acute tubular necrosis. In a controlled clinical trial, we have studied the effects of withholding cyclosporin for 12 h in patients undergoing cadaveric renal transplantation. Consecutive adult recipients of a cadaveric renal transplant were randomised to receive their first dose of cyclosporin (10 mg/kg p.o.) 6 h prior to transplant surgery or 12 h afterwards. All patients received azathioprine (1.5 mg/kg i.v.) and methylprednisolone (0.5 g i.v.) in addition during surgery. From the 2nd day onwards both groups were treated with an identical triple immunosuppressive regimen. The 27 patients who received their first dose of cyclosporin post-operatively had significantly better immediate and subsequent function than did the 26 patients who received their cyclosporin at the time of surgery. The delayed dosing was associated with improved graft survival and no increase in the frequency of rejection episodes. This regimen is recommended for all patients receiving triple therapy.

Adult↗
PubMed1990

Calcium-channel blockers and other factors influencing delayed function in renal allografts.

A retrospective analysis was undertaken to examine the influence of calcium-channel blocking drugs on early renal allograft function. Delayed function was defined as the need for dialysis or a reduction in serum creatinine of less than 15% within 4 days of transplantation. The drug histories of 172 patients were examined. After exclusions, the data from 138 patients were analysed. No patient was taking any calcium-channel blocking drug other than nifedipine. Thirty-one patients were taking nifedipine at the time of transplantation and these had a delayed function rate of 16% compared with 40% for 107 patients not taking nifedipine (chi 2, P less than 0.05). Delayed function occurred in 61% of cases when the donor age was over 50 years compared with 29% with younger donors (chi 2, P less than 0.05). A total ischaemic time of longer than 24 h and administration of inotropic support to the donor were associated with delayed function (chi 2, P less than 0.05). Administration to the donor of mannitol, steroids, phenoxybenzamine and heparin had no effect on the rate of delayed function. Recipients treated with low-dose dopamine in the perioperative period had no advantage. Elevated trough whole blood concentrations of cyclosporin in the first week after transplant were associated with delayed function (Mann-Whitney U, P less than 0.05).

Adult↗
PubMed1989

Epidermal dysplasia and cyclosporine therapy in renal transplant patients: a comparison with azathioprine.

The prevalence of dysplastic cutaneous lesions was determined in a group of 68 renal transplant patients whose immunosuppressive therapy included cyclosporine but not azathioprine. The mean age of the patients was 41 years (range 17-67), and the mean transplant time was 44 months (range 24-75). Dysplastic cutaneous lesions were found in 14 out of 68 patients, a prevalence of 20.6%. Although the lesions arose on sun-exposed sites, there was no apparent correlation with previous sun-exposure. The cumulative prevalence of dysplastic cutaneous lesions in 64 patients who had received cyclosporine for between 24 and 72 months was compared with 33 renal transplant patients who had been treated with azathioprine over a similar period of time. The overall prevalence of cutaneous dysplasia was 22% in the cyclosporine group and 9% in the azathioprine group. The cumulative prevalence of cutaneous dysplasia in the cyclosporine group was greater at all time points studied. In contrast to previous reports, we have found no evidence that the risk of cutaneous malignancy in patients treated with cyclosporine is less than that found in patients maintained on azathioprine.

Adolescent↗