Kidney transplantations at King Faisal Specialist Hospital and Research Centre.

During the five year period from 1987G to 1991G, 161 kidney transplantations were performed at King Faisal Specialist Hospital and Research Centre (KFSH&RC); 79 from cadaveric donors (CD) and 82 from living related donors (LRD). All cadaveric kidneys except one were harvested within Saudi Arabia and 67% were from Saudi nationals. The immunosuppresive protocol was a triple drug regimen comprising cyclosporin-A (CyA), azathioprine (Aza), and prednisone. The actuarial graft survival rates at one and three years were 85% and 76% for the cadaveric donor transplants and 96% and 91%, respectively for the living related donor transplants (P<0.01). The corresponding patient survival rates for cadaveric donor transplants (CDTxs) were 97% and 94% and for the living related donor transplants (LRDTxs), 99% and 97% (NS). These results compare well with the best results in the Western world. The most serious surgical complications were vascular thromboses (five cases) and infections of the arterial anastomosis line with bleeding (two cases), all leading to loss of the cadaveric graft. The most common causes of death were virus infection, varicella, cytomegalovirus, and hepatitis B and C. The organ donation rate, from cadaveric donors as well as living related donors, is stil low in Saudi Arabia. Lack of organs is the main obstacle to an expansion of this promising transplantation activity. Continuous education of the multinational medical profession as well as the lay population is necessary to improve the situation.

Successful outcome of segmental human pancreatic transplantation with enteric exocrine diversion after modifications in technique.

Segmental pancreatic transplantation is now the most widely favoured form of pancreatic transplantation, but the major difficulty with this procedure is the handling of the exocrine secretion. The use of a pancreaticoenteric anastomosis for exocrine diversion has been re-evaluated and several ancillary measures to reduce the risk of fistula and bacterial contamination have been applied. In three consecutive patients there have been no complications related to the exocrine pancreas. The pancreatic and renal grafts of these patients are functioning well 7, 3, and 2 months, respectively, after transplantation.

Metabolism of carbamazepine and its epoxide metabolite in human and rat liver in vitro.

The epoxidation of carbamazepine (CBZ) and the hydration of the primary epoxide metabolite was studied in microsomes isolated from ten human livers. To study the epoxide hydrolase activity a high-performance liquid-chromatographic method was developed for the analysis of dihydro-CBZ-trans-diol. There was a pronounced variation between the specimens in the activity of both enzymes. There appeared to be a positive correlation between the activity of the two enzymes. In rats pretreated with either CBZ or phenobarbital for 4 days, the microsomal epoxidation of CBZ was induced. The epoxide hydrolase activity was also increased, although less so than in epoxidation.

Reduced steroid doses in cadaveric renal transplantation.

Commencing 1978, we reduced the initial dose of prednisolone to 40 mg/day against a former 120-200 mg/day for cadaver kidney recipients aged 60 years and above. The patient and graft survivals at 1 year which earlier had been 59 and 47% is 69 and 46% after the change (NS). From August 1980, we reduced the initial prednisolone dose to 30 mg/day for all recipients of cadaver kidneys. From the same time, all patients were given 5 units of leukocyte poor blood prior to the transplantation, and in addition, RATG (Stanford) was given during 2 weeks immediately following the transplantation. Preceding the reduction the patient and graft survivals at 6 months were 91 and 62% while they were 88 and 88% after the reduction (NS). The intravenous dose of methylprednisolone, which is used for the treatment of acute rejection, was reduced twice in this period, first from 6 to 3 g, and then to 1.75 g total dose. The proportion of rejections, successfully treated, had remained unchanged. Our preliminary results support the notion that it is possible to use lower steroid doses than previously in conjunction with cadaveric kidney transplantations. However, we have introduced other alterations of the routines which could have influenced the results.

Immunosuppression by Cyclosporin A in human renal transplant recipients.

Nine renal transplant recipients were treated with Cyclosporin A (CyA). Seven of them were high risk patients (diabetics or above 55 years of age) receiving cadaveric grafts. Two were recipients of related grafts and azathioprine had been shown to give them severe GI symptoms. Secondary anuria developed presumably due to nephrotoxicity caused by CyA in 2 of the recipients of cadaveric kidneys. The patients were converted to conventional immunosuppressive drugs and after 2-3 weeks, renal function had recovered in both patients. Seven patients have been maintained on a combination of CyA and oral prednisolone. Four of these patients experienced one or more rejection episodes, all were reversible on treatment with methylprednisolone. Two patients had episodes of increased serum creatinine due to nephrotoxicity by CyA. Recovery occurred when the dose was reduced. Other side effects observed were: Hirsutism (3 patients), gingival hyperplasia (1), tremor (2) and leukopenia (1). Four patients had infectious complications and one died of cytomegalovirus pneumonia. Six patients are well having serum creatinine levels ranging from 89-181 mumol/1, 1 to 11 months after transplantation.

Bone marrow transplantation for aplastic anemia and acute leukemia at Huddinge Hospital.

Eight patients with aplastic anemia were transplanted with marrow from HLA-identical donors. Two patient rejected their grafts and died while 5 patients (71%) show no ill effects 3 months, 10 months, and more than 1, 2 and 4 years after the transplantation. Three of the patients who received unirradiated donor buffy coat after transplantation developed chronic graft-versus-host disease (GVHD) which, however, resolved following treatment with Prednisolone and Azathioprine. One patient with end-stage acute myeloid leukemia, who was transplanted with marrow from an identical twin, died 6 days after the transplantation of bleedings and sepsis. Eight patients with acute non-lymphoblastic leukemia (ANL) were transplanted, while in remission, with marrow from HLA-identical siblings. One patient died of interstitial pneumonia 3 months after transplantation, while another patient recovered from GVHD of the gut at 5 months after the transplantation. Seven out of 8 patients with ANL (88%) are home and well between 2 and 12 months after the transplantation.

Further experience with antihuman lymphocyte globulin (Behring): no effect on cadaveric renal graft survival.

In 1977 we reported that 1 year cadaveric renal graft survival was improved in patients treated with high dose anti-human lymphocyte globulin (AHLG) (Behring). Such a beneficial effect of this agent was not confirmed in the present study with an enlarged series of patients and with a longer follow-up time. Nor was there any gain in respect of renal function or any steroid sparing effect. The only indication of an immunosuppressive effect is that the rejection episodes possibly occurred later in the patients given the high dose AHLG.

Attempt at enzyme replacement in Gaucher disease by renal transplantation.

In Gaucher disease there is a deficiency of the lysosomal enzyme, cerebroside-beta-glucosidase, as a result of which cerebroside (glucosylcereamide) accumulates in various organs. In northern Sweden 22 patients with a juvenile form of this disease have been identified. In one such patient, a girl of 10 years, we have attempted enzyme replacement by renal transplantation. After this operation the hepatic glucocerebroside content fell significantly. In another child afflicted with Gaucher disease in whom splenectomy was performed for severe splenomegaly and hypersplenism there was a progressive increase in the level of this lipid. These findings suggest that enzyme replacement was achieved by transplantation of a normal organ.

Attempt at enzyme replacement by organ transplantation: renal transplantation in Gaucher disease.

Following renal transplantation, hepatic glucocerebroside deposits in a child with Gaucher disease were reduced. This suggests that enzyme replacement had been achieved.

Secondary hyperparathyroidism and its sequelae in renal transplant recipients. Long term findings in a series of conservatively managed patients.

The prevalence and duration of secondary hyperparathyroidism in 42 renal transplant recipients, and the sequelae of this condition, were studied. Immediately before transplantation, an elevated PTH-value was recorded in 76% of the patients, postoperatively there was a marked drop. Early after successful transplantation, 57% of the patients had hypercalcemia. At follow-up 3 years later, moderate hypercalcemia persisted in half of the patients but only 3 patients had significantly elevated PTH. The quality of renal graft function was not inferior in the hypercalcemic patients. Subperiosteal bone resorption and soft tissue calcifications were more common among the hypercalcemic patients. Our data suggest that secondary hyperparathyroidism can be managed conservatively in most renal transplant recipients. If progressive bone changes occur, surgical removal of parathyroid tissue should be considered.

The significance of HLA-A and -B matching for cadaver-kidney survival in Stockholm 1970--1976.

The significance of HLA-matching for the survival of cadaver kidneys, transplanted between January 1970 and June 1976 to 170 uraemic patients has been assessed. When the patients were divided into groups according to degree of HLA compatibility it was found that the groups so obtained were comparable neither with regard to the quality of the transplants nor to the immunosuppressive therapy given. This was due to multiple changes in policy in 1973. When the case material was divided into patients treated before and after 1973, comparable groups were obtained within each series. The only correlation found was that, in the chronologically later groups, 2 year survival rate of transplants with E-G match (3--4 incompatibilities) was inferior to that of transplants with C-D match (1-2 incompatibilities).

A controlled trial of antihuman lymphocyte globulin (Behring) in cadaveric renal transplantation: improvement in graft and patient survival at one year using a high-dose regimen.

A controlled study of the effect of antihuman lymphocyte globulin (AHLG) on patient and kidney transplant survival has been performed. The AHLG was administered as an adjuvant to the routine immunosuppressive drugs in either high (30 mg/kg) or low (15 mg/kg) doses, control patients received no AHLG. The clinical condition of the recipients and the quality and the degree of immunological compatibility of the transplants were comparable. During the period of the study, the results of all first-time cadaver-kidney transplantations to non-diabetic uraemic patients were included. The actuarial graft survival rates at 12 months for the three groups (high dose, low dose and control) were 67%, 49% and 35%. The corresponding patient survival rates were 91%, 66% and 65% respectively. The difference between the results in the high dose AHLG and in the control group was significant (p less than 0.05).

Rejection of isolated pancreatic allografts in patients with with diabetes.

Four patients with diabetes mellitus of juvenile onset but without uremia have been treated with segmental transplantation of the body and tail of pancreas. The indications were hyperlabile diabetes or progressive loss of vision. The grafts were procured from cadaveric donors four to 16 minutes after circulary arrest and were subsequently stored in the cold for approximately four hours. In one patient, the pancreatic duct was ligated, while in the other three, drainage was attained by suturing the transected end of the pancreas into a jejunal Roux-en-Y loop. Three of the grafts failed within six weeks as a result of irreversible refection, and one graft failed because of the early onset of venous thrombosis. The first sign of graft rejection was an increase in the postprandial blood sugar level, an increase in the fasting blood sugar level occurring several days later. Neither hyperamylasemia nor fever was observed. Radioisotope scans and angiograms were of great value in establishing the diagnosis of graft rejection. All of the patients survived after graft removal.