Richard F. M. Wood

A controlled trial of cyclosporine in renal transplantation with conversion to azathioprine and prednisolone after three months.

Thirty-five patients given an HLA-DR-incompatible cadaver kidney that was diuresing immediately after transplantation were randomly allocated to treatment with cyclosporine alone for 3 months followed by conversion to azathioprine and prednisolone (AP), or to conventional treatment with AP. Although many patients had to be converted to AP before 90 days because of rejection requiring more than two treatment courses of high-dose i.v. methylprednisolone, 16 of 21 grafts were functioning at 3 months, and 12 of 14 grafts in the control group were functioning. However 3 further grafts were lost from chronic rejection in the control group, and none were lost from chronic rejection in the cyclosporine group. All but one patient on cyclosporine had depressed renal function, and in all these patients function improved on conversion to AP. This depression of renal function is attributed both to cyclosporine nephrotoxicity and to a low-grade rejection reaction, the latter suggesting that the addition of steroids to cyclosporine might be beneficial in some patients. The strategy of a three-month course of cyclosporine followed by conversion to AP provides satisfactory immunosuppression, and it may be of value if long-term side effects of cyclosporine emerge with further experience.

Arteriovenous fistulas for dialysis: blood flow, viscosity, and long-term patency.

A prospective study of the influence of blood flow at the time of operation on subsequent performance of dialysis fistulas is reported. Flow was measured in 33 consecutive arteriovenous fistulas using an electromagnetic flowmeter. During the mean follow-up time of 7 months (range, 2–12 months), 19 fistulas were used for dialysis, 9 have not yet been used, 4 were never used because of thrombosis or failure to develop adequately, and 1 patient died before using the fistula for hemodialysis. There were 9 complications (thrombosis, stenosis, and failure to develop). Operative blood flow for these 9 fistulas averaged 221 ml/min as compared to 214 ml/min for the group with no subsequent problems. No critical flow rate below which the fistula would not develop could be defined. An analysis of influences on flow rate at the time of operation showed that there was a significant correlation between flow and blood pressure, vessel dimensions, and whole blood viscosity, but it was not possible to predict fistula failure from these data.A prospective study of the influence of blood flow at the time of operation on subsequent performance of dialysis fistulas is reported. Flow was measured in 33 consecutive arteriovenous fistulas using an electromagnetic flowmeter. During the mean follow-up time of 7 months (range, 2–12 months), 19 fistulas were used for dialysis, 9 have not yet been used, 4 were never used because of thrombosis or failure to develop adequately, and 1 patient died before using the fistula for hemodialysis. There were 9 complications (thrombosis, stenosis, and failure to develop). Operative blood flow for these 9 fistulas averaged 221 ml/min as compared to 214 ml/min for the group with no subsequent problems. No critical flow rate below which the fistula would not develop could be defined. An analysis of influences on flow rate at the time of operation showed that there was a significant correlation between flow and blood pressure, vessel dimensions, and whole blood viscosity, but it was not possible to predict fistula failure from these data.

The effect of renal ischemia on cyclosporine clearance in rabbits

The renal handling of cyclosporine was studied in ischemically damaged kidneys in New Zealand White rabbits and nonischemic control animals. CsA, 25 mg/kg/day, was administered intravenously for 10 days starting with the day of operation. Blood CsA (B CsA) was higher in the ischemic group compared with the controls (median: 285 micrograms/L, range 95-785 micrograms/L vs. 170 micrograms/L, range 110-185 micrograms/L, P = 0.05) on day 1 after operation. B CsA dropped rapidly to a level equivalent to the controls by day 4 (median: 105 micrograms/L, range 60-280 micrograms/L vs. 195 micrograms/L, range 70-215 micrograms/L, P = NS). Median CsA clearance (C CsA) as a percentage of creatinine clearance (C Cr) was some ten-fold greater in the ischemic animals (6.32%, range 2.93-18.41% vs. 0.55%, range 0.13-0.78%, P less than 0.001) on day 1. The ratio gradually declined, approaching the value in controls by day 10 (0.86%, range 0.24-7.21% vs. 0.23%, range 0.16-0.73%, P = 0.05). The data suggest that renal impairment has an important effect on CsA blood levels. In the clinical situation this may be of particular importance during both oliguria and the recovery from acute tubular necrosis.

Phlebography in the salvage of dialysis fistulae

Provision of long-term satisfactory vascular access for haemodialysis is an increasing problem. The functional life of an arteriovenous fistula can be greatly extended by an active salvage policy to which radiology makes an invaluable contribution. Forty-seven consecutive patients with vascular access problems were studied, 11 undergoing forearm phlebography and 36 phlebography of a malfunctioning fistula. Of the 11 patients with forearm phlebograms, only one patient had a fistula constructed that was not used for dialysis, despite demonstration of a patent forearm venous system; and in three patients operation was avoided after demonstration of inadequate veins. Only three of the 36 fistulograms failed to give useful information, whereas in seven patients operation was avoided by demonstration of a normal fistulogram.

The reversal of established enhancement in rat cardiac allografts.

SUMMARY Established enhancement in rat cardiac allografts was challenged in a variety of ways in an attempt to provoke rejection. Incompatible skin grafts, injections of sensitised lymphocytes, and the administration of the macrophage-stimulating agent Corynebacterium parvum proved ineffective. However, levamisole, which stimulates both macrophages and sensitised lymphocytes, caused rejection in four of a group of six AS rats bearing enhanced (August x AS)F, hybrid heart allografts. A combination of C. parvum and levamisole provoked rejection in all four animals in which it was used. The results suggest that an increased activity of both lymphocytes and macrophages is required to break established enhancement.