J. F. Botha

A tale of two kidneys – how long can a kidney transplant wait?

This paper compares early graft function (EGF) of the first transplanted kidney (group 1) with the kidney transplanted second (group 2) in kidney pairs from the same cadaver donor. Thirty‐one pairs of kidneys were harvested from cadaver donors between January 1997 and October 1998. 
Each pair was transplanted using a standard technique by the same team of surgeons, one after the other, as a result of limitations in theatre time and staff availability. Incidence of acute rejection (AR), acute tubular necrosis (ATN) and need for post‐transplant dialysis was recorded for both groups, and was compared using the relevant statistical methods. 
Patients in both groups were well matched for age, gender and mode of dialysis pre‐transplant. Human leucocyte antigen (HLA) matching and panel reactive antibody (PRA) status were similar in the two groups (p>0.05). Cold ischaemia time (CIT) in the two groups was 14.1±5.7 and 19.2±6.9 h, respectively, the difference being statistically significant (p<0.05). The incidence of AR was similar in the two groups. However, ATN (on renogram) was significantly more common in group 2 (p<0.05; 12 patients versus 5 patients in group 1). All patients with ATN required post‐transplant dialysis. Hospital stay was significantly prolonged in group 2 patients (p<05; 20±10.6 versus 16.3±6.2 d for group 1). 
Even a relatively short increase in CIT can cause the second transplanted kidney of a pair to have a significantly higher incidence of ATN, resulting in need for dialysis and prolongation of hospital stay. Simultaneous transplantation, in areas lacking organ sharing networks, would not only improve EGF, but also improve long term graft survival. In addition, the reduced requirement for post‐transplant dialysis and a shorter hospital stay would balance any increased demand on resources.

Two further cases of tuberculosis in a renal allograft.

The first patient was a 29-year-old woman with chronic renal failure with crescentic mesangiocapillary glomerulonephritis. She received a cadaveric transplant in April 1996. She had good initial renal function and was maintained on cyclosporine, azathioprine, and prednisone. She unfortunately lost renal allograft function due to chronic rejection after 2.5 years, and she was recommenced on hemodialysis. Immunosuppression was discontinued. The patient developed a persistent intermittent fever and subsequently developed mild graft tenderness and haematuria necessitating a graft nephrectomy. The histology of the graft showed caseating granulomata, with acid-fast bacilli seen on Ziehl-Neelsen staining. No other sites of past or present tuberculosis were identified. The patient was commenced on anti-tuberculous therapy consisting of rifampicin, isoniazid, ethambutol, and pyrazinamide.

Prolonged survival of baboon renal allografts using idarubicin-conjugated anti-CD4 monoclonal antibodies

Abstract Tolerance to organ allografts in rodents and pigs can be easily achieved. However, tolerance induction in a large primate model has been more elusive. In this study, we have used an anti‐CD4, murine monoclonal antibody as a carrier for the cytotoxic drug idarubicin (IDA) to delete or inactivate alloreactive T‐cells responding to a renal allograft in a baboon transplant model. Fourteen Chacma baboons weighing between 15‐25 kg received heterotopic renal allografts. Recipient and donor pairs were selected on the basis of ABO compatibility. Seven animals were given no immunosuppression and served as the control group. The remaining 7 animals received anti‐CD4 IDA. The first 2 animals in this group received 2 mg IVI intraoperatively and three doses at 48‐h intervals thereafter. The last 5 animals received a larger dose of 1 mg/kg, starting 24 h pre‐operatively and again on postoperative days 2 and 5. The untreated animals promptly rejected their allografts with a mean survival of 10 days. The survival of the 2 animals treated with 2 mg anti‐CD4 IDA was 7 days each. However, the animals treated with 1 mg/kg anti‐CD4 IDA survived 7, 18, 20, 40 and > 40 days. Peritransplant administration of anti‐CD4 IDA prolonged renal allograft survival in a large primate model. This unique immunoconjugate has the potential of tolerance induction.

Does rural follow-up of renal allografts give impaired graft survival?

Abstract In this study, we compared the patient and graft survival after renal transplantation in patients followed up in rural centers against those in a major transplant center. There was a greater proportion of patients having a living related donor transplant and having prolonged cold ischemic times in the group followed up in a rural centre. The patient and graft survival at 1, 3 and 5 years were similar for local and rural patients. We conclude that a centralized transplant unit with follow‐up of patients in rural centers optimizes the use of highly skilled personnel.

Does rural follow-up of renal allografts give impaired graft survival in a third-world country?

IN DEVELOPING countries, dialysis and transplantation facilities are a scarce commodity. Groote Schuur Hospital in Cape Town has a large dialysis center and transplant unit, which is the regional transplant unit for the whole of the southern half of South Africa. It serves a population of approximately 5 million people, some of whom live in primitive conditions over a thousand miles from Cape Town. Because of the sophisticated nature of renal transplantation, it has been assumed that careful follow-up is necessary and should be carried out in a unit accustomed to dealing with immunosuppression and the problems associated with renal failure. It was assumed to be less than ideal to send transplanted, immunosuppressed patients back to a rural community to be looked after by a general practitioner, a day hospital, or regional hospital. The aim of this study was to compare the graft survival in patients cared for in a rural center after transplantation with patients in a major academic transplant center.

PROLONGED SURVIVAL OF BABOON RENAL ALLOGRAFTS USING IDARUBICIN CONJUGATED ANTI-CD4 MONOCLONAL ANTIBODIES.

Tolerance to organ allografts in rodents and pigs can be easily achieved. However, tolerance induction in a large primate model has been more elusive. In this study, we have used an anti-CD4, murine monoclonal antibody as a carrier for the cytotoxic drug idarubicin (IDA) to delete or inactivate alloreactive T-cells responding to a renal allograft in a baboon transplant model. Fourteen Chacma baboons weighing between 15-25 kg received heterotopic renal allografts. Recipient and donor pairs were selected on the basis of ABO compatibility. Seven animals were given no immunosuppression and served as the control group. The remaining 7 animals received anti-CD4 IDA. The first 2 animals in this group received 2 mg IVI intraoperatively and three doses at 48-h intervals thereafter. The last 5 animals received a larger dose of 1 mg/kg, starting 24 h preoperatively and again on postoperative days 2 and 5. The untreated animals promptly rejected their allografts with a mean survival of 10 days. The survival of the 2 animals treated with 2 mg anti-CD4 IDA was 7 days each. However, the animals treated with 1 mg/kg anti-CD4 IDA survived 7, 18, 20, 40 and > 40 days. Peritransplant administration of anti-CD4 IDA prolonged renal allograft survival in a large primate model. This unique immunoconjugate has the potential of tolerance induction.