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Symptomatic cytomegalovirus infection in seropositive kidney recipients: reinfection with donor virus rather than reactivation of recipient virus.

74 patients receiving cadaver kidney grafts were investigated prospectively for cytomegalovirus (CMV) infection. Among seropositive recipients CMV infection, especially symptomatic and disseminated infection, occurred significantly more frequently when kidneys came from seropositive than from seronegative donors. Since seropositive recipients can become infected with donor virus, the excess is probably accounted for by reinfection. This conclusion was supported by restriction enzyme typing of virus isolates from recipient pairs receiving kidneys from the same donor; proven reinfection with donor strain virus was significantly commoner than proven reactivation of recipient virus. Furthermore, symptoms occurred only in the proven reinfection group. Although the proportion of reinfections that caused symptoms was less than that seen in primary infections, prior natural infection with CMV clearly does not prevent symptomatic reinfection in seropositive recipients, a point which has profound implications for future vaccination strategies in renal allograft recipients and choice of donors.

Long-Term Outcome of Paediatric Renal Transplantation: Follow-Up of 300 Children from 1973 to 2000

Background/Aim: To report our experience of paediatric renal transplantation at Great Ormond Street and Royal Free Hospitals since the inception of the programme. Methods: Retrospective review of the patient and transplant survival and influencing factors in the 300 children transplanted between 1973 and 2000. Results: 300 children had received a total of 354 transplants; 56 were living-related donations. The median age at transplantation was 10.3 (range 1.4–17.9) years. Forty-four percent had congenital structural abnormalities of the urinary tract. Forty-six children required a second and 8 a third transplant before transfer to an adult unit. The overall patient survival at 5, 10, and 20 years was 97, 94, and 72%, respectively. In the overall cohort, the donor type (deceased donor or living-related donor) did not affect mortality, nor did age at transplantation, but those transplanted before 5 years of age had a significantly shorter post-transplant survival time (p < 0.0001). Transplant survival (first transplant) for deceased and living-related donors was 66 and 87% at 5 years (p < 0.01), 51 and 54% at 10 years, and 36% at 20 years (deceased-donor transplants only). Although the overall transplant survival was inferior in children transplanted before 2 years of age (p < 0.03), in the most recent cohort (1990–2000), age did not affect the outcome. On multiple regression analysis, the only predictor of transplant survival was the era of transplantation (p < 0.001). The median final height was within the normal range for males and females; 7 patients received growth hormone after transplantation. Conclusions: The outlook for successful transplantation is improving, and in the last decade was unaffected by age at transplantation. The survival of living-related donor transplants is superior to deceased-donor transplants for the first 5 years. From the above data, we can predict that a 10-year-old child receiving a renal transplant in 2000 and on ciclosporin-based immunosuppression can expect a transplant half-life of 13.1 years from a living-related donor and one of 10.8 years from a deceased-donor transplant.

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

Abstract  SDZ CHI 621 is a murine‐human chimeric monoclonal antibody (mAb) to the interleukin‐2 (IL‐2) receptor (C 5) 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 preopera‐tively and subsequent doses within the first 10 days posttransplant. Daily mAb serum concentrations were analysed by a radioimmunoas‐say method and the percentage of peripheral T‐lymphocytes expressing C 5 from serial blood samples was determined by FACScan. Intravenous administrations were well tolerated. mAb concentration profiles exhibited a biphasic decline with an initial /2 of 14.4 ± 14.2 h, terminal /2 of 13.4 ± 6.0 days, distribution volume (VSS) of 6.9 ± 3.3 1 and clearance of 17.4 ± 7.8 ml/h. The concentration‐effect (mAb‐C 5) relationship indicated that mAb concentrations exceeding a threshold of about 0.7 μg/ml corresponded to complete suppression of C 5 (±0 3 % C 5+ T‐cells). The threshold mAb concentration was exceeded at all dose levels, whereas the duration above the threshold (and thus of C 5 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, C 5 expression returned to baseline (18–44 % CD 5+ T‐cells) within a few days.

Dissociation of absorptions of calcium and phosphate after successful cadaveric renal transplantation.

Calcium and phosphate absorptions were studied by radiotracer techniques in 30 patients after successful cadaveric renal transplantation, and results were compared with those in a group of normal subjects and in groups of patients with chronic renal failure (CRF). Both calcium and phosphate absorptions were impared in patients with CRF, including those receiving haemodialysis. Abnormalities of calcium absorption, however, seemed to occur earlier in the course of advanced renal failure than abnormalities in phosphate absorption. Calcium absorption improved dramatically after successful renal transplantation, while phosphate absorption remained the same. A dissociation between calcium and phosphate absorptions is not often seen clinically, and the mechanisms for it are unknown. Phosphate malabsorption may be a further contributing factor in the development of persistent hypophosphataemia after transplantation.

Conversion of stable renal allografts at one year from cyclosporin A to azathioprine: a randomized controlled study

Abstract. Seventy‐seven stable, nondiabetic, cadaveric renal transplants were randomized at 1 year to convert from cyclosporin A to azathioprine or to continue on cyclosporin A. Prednisolone was increased twofold during the period of conversion, and there was a 3‐week overlap period during which azathioprine and cyclosporin A were given. No grafts were lost due to rejection related to conversion, but 9 of the 33 patients who were randomized to convert experienced rejection episodes and 6 were returned to cyclosporin A. Conversion to azathioprine resulted in a drop in creatinine and improvement in blood pressure control. In the group randomized to stay on cyclosporin A, 6 patients had to be subsequently converted to azathioprine because of cyclosporin A toxicity in spite of well‐controlled plasma levels. The creatinine levels after successful conversion remained stable whereas those of the patients continuing on cyclosporin A showed a progressive decline. We conclude that conversion from cyclosporin A to azathioprine can be achieved safely. Progressive deterioration in graft function with continuing cyclosporin A therapy does occur and should be taken as an indication for conversion.

Survival Rates of Patients Treated by Home and Hospital Dialysis and Cadaveric Renal Transplantation

Of 109 patients admitted to the renal failure programme of the Royal Free Hospital 80·7% were surviving after six years. For patients on home dialysis the four-year rate was 86·2%, more deaths occurring in women than in men. The short-term survival rate of all patients was high—namely, 96·3% at six months and 94·4% at 12 months. Hence large increases in the rate of acceptance of patients as well as successful transplantation are necessary to balance acceptance and loss from this programme.

Plasma LCAT activities in renal allograft recipients

Plasma LCAT activities were measured in 51 renal allograft recipients as well in 18 patients before and after successful renal transplantation. The mean plasma LCAT activity of the 51 patients did not differ significantly from that of 27 normal subjects. When the patients were separated into two groups according to whether they had normal or impaired renal function, there was no significant difference in their mean LCAT activities. Plasma LCAT activities correlated significantly with total cholesterol and total triglyceride concentrations. The sequential study demonstrates that the low plasma LCAT activities in uraemic patients rose towards normal after successful transplantation. At the same time, total cholesterol and HDL-cholesterol concentrations also increased. The increase in LCAT activity after renal transplantation is due to increased concentrations of the enzyme and probably reflects increased turnover of triglyceride-rich lipoproteins.

Splenic abscess in patients on hemodialysis.

We describe two patients on hemodialysis who developed staphylococcal splenic abscesses. Both patients previously had staphylococcal septicemia secondary to infection at the dialysis access site. We postulate that access-site infections may predispose hemodialysis patients to splenic abscess, and that these patients should be investigated for a splenic abscess if they should develop unexplained fever.

Fat clearances and hyperlipidaemia in renal allograft recipients — the role of insulin resistance

The mechanism of hyperlipidaemia in renal allograft recipients was investigated in 19 patients randomly selected from a cohort of 54 patients with functioning renal allografts. Serum cholesterol, triglyceride and high-density lipoprotein cholesterol concentrations as well as plasma immunoreactive insulin levels were measured in fasting blood samples. Intravenous fat tolerance tests were performed before and 15 min after heparin administration. Renal allograft recipients had reduced fractional clearance rates of Intralipid and a positive correlation was demonstrated between plasma immunoreactive insulin levels and serum triglyceride concentrations. Plasma immunoreactive insulins also correlated inversely with fractional clearance rates of Intralipid. It was concluded that both increased production and decreased removal of lipoproteins contribute to the hyperlipidaemia and that insulin resistance due to corticosteroids was the centre of the problem.

Digital vascular imaging and selective renin sampling in evaluation of vascular anatomy in renal transplant recipients.

Sixty-five renal transplant recipients underwent digital vascular imaging of the graft and simultaneous selective venous sampling for plasma renin activity. Renal artery stenosis was found in seven patients but did not appear to be functionally important. Diffuse intrarenal arterial attenuation was found in seven patients and was associated with impaired graft function and perfusion; it may indicate chronic rejection. Lower pole hypoperfusion was found in nine patients without impaired graft function or perfusion; its clinical relevance is uncertain. Aneurysmal dilatation of the main renal artery was found in two patients. Severe hypertension was common in patients with these three major abnormalities, but a causal association between the abnormality and hypertension could rarely be inferred. It may be the abnormalities on digital vascular imaging, especially diffuse intrarenal arterial attenuation and lower pole hypoperfusion, are secondary to severe hypertension. Digital vascular imaging with simultaneous selective venous sampling for plasma renin activity is useful in evaluating the vascular anatomy of the grafted kidney and in assessing any abnormality found. The combined procedure was well tolerated by all patients with no complications and no incidence of acute tubular dysfunction or proteinuria after the investigation.