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  • Canafax DM
  • Torres A
  • Fryd DS
  • Heil JE
  • Strand MH
  • et al.
Transplantation. 1986 Feb;41(2):177-81 doi: 10.1097/00007890-198602000-00009.

We randomized 158 recipients of cadaver renal allografts to cyclosporine-prednisone (83) or antilymphocyte globulin-azathioprine-prednisone (75) to evaluate: the effects of immunosuppression and pretransplant risk factors on the incidence of delayed graft function, the effects of immunosuppression on the resolution of delayed graft function, and the effects of delayed graft function and pretransplanted risk factors on patient and graft survival. Cyclosporine did not increase the incidence of delayed graft function, compared with ALG-azathioprine-treated patients (33% versus 27%, P = 0.550) but doubled the mean (+/- SD) duration of oliguria (11.8 +/- 11.0 versus 5.9 +/- 3.2 days, P = 0.002) and the number of required dialyses (6.6 +/- 7.6 versus 3.2 +/- 1.3, P = 0.031). Retransplanted patients had a higher incidence of delayed graft function that recipients of primary grafts in both the cyclosporine (82% versus 25%, P = 0.001) and ALG-azathioprine (55% versus 22%, P = 0.025) treatment groups. The presence of delayed function reduced one-year graft survival from 89% in all patients without delayed function to 72% (P = 0.011) in all patients with delayed function. Cyclosporine-treated patients had a slightly, but not significantly better one-year graft survival rate than ALG-azathioprine treated patients both with (73% versus 68%, P = 0.750) and without (92% versus 82%, P = 0.069) delayed graft function. A preservation time longer than 24 hr did not increase the incidence of delayed graft function in cyclosporine-treated patients (34% versus 32%, P = 0.811) or ALG-azathioprine-treated patients (27% versus 27%, P = 0.902). Cyclosporine-treated patients given kidneys with greater than 24 hr of preservation time had reduced graft survival only when delayed graft function occurred (67% versus 92%, P = 0.009). In conclusion, (1) cyclosporine did not increase the incidence of delayed graft function over ALG-azathioprine treatment; (2) cyclosporine did significantly slow recovery of kidneys with delayed function; (3) delayed graft function correlated with poorer graft survival rate in both treatment groups; but (4) prolonged preservation time did not increase the incidence of delayed graft function or reduce graft survival.

  • Kaplan MP
  • Toledo PLH
  • Pietroski R
  • et al,
Transplant Proc. 1986;18(3):504-505.
Administration of various agents during donor maintenance procedures can potentially affect posttransplant kidney function as well as donor stability prior to harvesting. This study analyzed the effects of lasix and/or mannitol on the subsequent function of renal allografts from cadaver donors.
  • Duggan KA
  • Macdonald GJ
  • Charlesworth JA
  • Pussell BA
Clin Nephrol. 1985 Dec;24(6):289-91.

Verapamil has proven effective in preventing acute renal failure in animal models if given prior to the insult and hence possibly has a role in the preservation of cadaveric renal tissue for transplantation. Twenty renal donors were randomly assigned to treatment (receiving verapamil 20 mg intravenously) and control groups. Recipients were monitored for renal failure by urine output and serum creatinines on days 1 and 7 and dialysis requirement to one week. Early urine outputs and serum creatinines (day 1) were significantly better in the treated than control group (p greater than 0.01, 0.05 respectively). We conclude therefore that verapamil may prevent post-transplant acute renal failure, but its optimal dosage and route of administration remain to be determined.

  • Alijani MR
  • Cutler JA
  • DelValle CJ
  • Morres DN
  • Fawzy A
  • et al.
Transplantation. 1985 Dec;40(6):659-61 doi: 10.1097/00007890-198512000-00017.

Preservation of thirty-eight consecutive renal allograft donors was studied in a prospective, randomized protocol. Procurement was in-situ cooled, en-bloc nephrectomy accomplished by a single program. Nine pairs were deleted because of nonutilization of one kidney or change in mode of preservation. The remaining twenty nine pairs were implanted by twenty two institutions through usual organ sharing policies. Results showed that posttransplantation dialysis was required in 17% of machine-perfused and 63% of cold-stored allografts, which reached statistical significance (P less than 0.01). This increased number of dialyses in patients receiving the cold-stored kidneys offsets cost savings achieved through transporting cold stored allografts. This study shows machine-perfused renal allografts to be superior to paired, cold-stored allografts when analyzed with respect to early graft function.

  • Hatch DA
  • Barry JM
  • Norman DJ
Transplantation. 1985 Dec;40(6):648-51 doi: 10.1097/00007890-198512000-00014.

Fourteen adult recipients of living-donor kidneys preserved with ice-cold intracellular electrolyte solution were randomly assigned to receive either high fluid replacement (total volume of urine output + 30 ml/hr) or low fluid replacement (constant 125 ml/hr) during the first 48 hr after grafting. High replacement recipients had significantly higher fluid intake and urine output than did low replacement recipients. However, net fluid balance at the end of the 48-hr study period was positive for both groups and not significantly different. Fractional excretion of sodium was directly related to urine output in all patients. Serum osmolality, serum sodium concentration, and urine sodium concentration were not significantly different in the treatment groups. Urine osmolality was significantly higher in the low-replacement group at 24 and 36 hr after transplantation. The i.v. replacement of total urinary output is unnecessary in adult recipients of living-donor kidneys preserved with ice-cold intracellular electrolyte solution because such grafts can conserve sodium and water immediately after transplantation.

  • Hourmant M
  • Soulillou JP
  • Remi JP
  • Sagniez G
  • Guenel J
Presse Med. 1985 Nov 30;14(41):2093-6.

For the past 18 months, cyclosporin A has been used in our renal transplantation center, according to a randomized protocole in which the drug is introduced late (3rd month), following a standard treatment with prednisone, azathioprine and antilymphocyte serum, in a low dosage (4-6 mg/mg/day) and alone. This protocol has been designed to preserve the full benefits of the antilymphocyte serum given immediately after transplantation, to reduce the risk of cyclosporine nephrotoxicity and to allow the withdrawal of corticosteroids. When compared with 27 patients under standard treatment, the 31 patients who received cyclosporin A have an actuarial graft survival rate of 94% at 12 and 18 months, against 68% in the other group. At least one rejection episode was observed in 43% and 51% of patients under respectively cyclosporin A and standard treatment. Renal function remained stable after cyclosporin A was introduced and 1 year post-grafting mean serum creatinine values were similar in both groups. Acute and chronic nephrotoxicity has been the major complication of cyclosporin A. Excellent results (94% graft survival rate at 18 months) can be obtained using the sequential association of antilymphocyte serum and cyclosporin A, without the impairement in renal function that has been observed in other studies where cyclosporin A is given on the day of transplantation.

  • Hall BM
  • Tiller DJ
  • Duggin GG
  • Horvath JS
  • Farnsworth A
  • et al.
Kidney Int. 1985 Aug;28(2):178-86 doi: 10.1038/ki.1985.138.

The outcome of patients with acute renal failure following cadaveric renal transplant has been evaluated in a prospective, controlled trial, comparing treatment with cyclosporine (CSA) to prednisone, azathioprine, and antilymphocyte globulin (AZA). There was a high incidence of acute post-transplant renal failure in both groups: 37 of 51 CSA and 31 of 45 AZA patients, due to the long exposure of kidneys to warm and cold ischemia. Onset of adequate renal function was delayed for three or more weeks in 27 (53%) CSA and only nine (20%) AZA patients, and the only predisposing factor found was donor hypotension. All nine AZA and 18 of the 27 CSA patients with prolonged oliguria subsequently had a spontaneous diuresis. Nine of the CSA patients were changed to azathioprine and prednisone because of suspected CSA toxicity, and eight of these kidneys began functioning within days, even though they had been oliguric for 21 to 83 days. Of these nine patients, five had adequate long-term function on AZA, three developed CMV infections that were fatal to two individuals, and two rejected their grafts. Plasma CSA levels fluctuated widely in all patients, but were not higher in any group, including those with prolonged oliguria. During the oliguric period, biopsy specimens proved rejection was more common in the nine patients who had their CSA stopped than in the other CSA patients, and seven of these nine developed a diffuse interstitial fibrosis that was thought to be a manifestation of CSA toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

  • Canadian Transplant Study Group
Am J Kidney Dis. 1985 Jun;5(6):328-32 doi: 10.1016/s0272-6386(85)80162-1.

The benefit:detriment ratio of Cyclosporine (CsA) in renal transplantation was examined by analysis of the data accumulated within the Canadian Transplant Study Group (CTSG). Transplantation was performed according to commonly defined protocols, and 496 patients were analysed following cadaveric or live-related transplantation. One-year patient and graft survival were 96% and 86%, respectively, following living-related HLA nonidentical transplantation, 92% and 75% following primary cadaveric transplantation, and 97% and 58% following cadaveric retransplantation. A clear beneficial effect of blood transfusion was observed following primary cadaveric renal transplantation (P = 0.04), with a trend towards improved graft survival in donor/recipient pairs matched at the B or Dr locus (89% v 73%, P = NS). Prolonged machine preservation (greater than 24 hours) of the kidney or long (greater than than 45 minutes) surgical anastomosis time, and an elevated serum CsA level adversely influenced allograft function. Graft function in patients receiving CsA stabilized by approximately 6 months posttransplant, and subsequently remained constant as determined by both serum creatinine and calculation of creatinine clearance. Hypertension was more common (P = 0.003) in patients receiving CsA, and vascular complications were more frequent although this difference was not statistically significant. Infectious complications were comparable between the two groups. Two lymphomas were confirmed in patients receiving CsA. The mean cost of CsA throughout the first 12 months posttransplant based on a 60 kg patient weight was $4,490, and reduced by $3,397 each subsequent year of maintenance treatment.

  • Hourmant M
  • Soulillou JP
  • Remi JP
  • et al,
Presse Medicale. 1985;14(41):2093-2096.
For the past 18 months, cyclosporin A has been used in our renal transplantation center, according to a randomized protocol in which the drug is introduced late (3rd month), following a standard treatment with prednisone, azathioprine and antilymphocyte serum, in a low dosage (4-6/kg/day) and alone. This protocol has been designed to preserve the full benefits of the antilymphocyte serum given immediately after transplantation, to reduce the risk of cyclosporin nephrotoxicity and to allow the withdrawal of corticosteroids. When compared with 27 patients under standard treatment, the 31 patients who received cyclosporin A have an actuarial graft survival rate of 94% at 12 and 18 months, against 68% in the other group. At least one rejection episode was observed in 43% and 51% of patients under, respectively, cyclosporin A and standard treatment. Renal function remained stable after cyclosporin A was introduced and 1 year post- grafting mean serum creatinine values were similar in both groups. Acute and chronic nephrotoxicity has been the major complication of cyclosporin A. Excellent results (94% graft survival rate at 18 months) can be obtained using the sequential association of antilymphocyte serum and cyclosporin A, without the impairment in renal function that has been observed in other studies where cyclosporin A is given on the day of transplantation.
  • Lachance SL
  • Barry JM
Journal of Urology. 1985;133(6):950-951.
High doses of furosemide have been reported to reduce the requirement for dialysis following cadaveric kidney transplantation. Depending on recipient age, alternate cadaver kidney transplant recipients received infusions of 200 to 400 mg. furosemide just before restoration of renal circulation. All recipients received infusions of mannitol during the hour before renal revascularization. All 50 kidneys were preserved with intracellular electrolyte solutions. Mean cold storage times (33.4 plus or minus 11.4 hours for recipients given furosemide versus 35.7 plus or minus 12.3 hours for controls) were not significantly different between the 2 groups. There were no significant differences in first week dialysis requirement between recipients given furosemide and controls (75 versus 73 per cent, respectively), first day urine output (2.2 plus or minus 4.2 versus 1.0 plus or minus 0.8 l., respectively), 1-month serum creatinine nadirs (2.1 plus or minus 1.1 versus 1.9 plus or minus 1.1 mg. per dl., respectively) and 1-month function rate (92 versus 92 per cent, respectively). High doses of furosemide did not prevent significant acute tubular necrosis following human cadaveric kidney transplantation when the recipients also received infusions of mannitol.