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Low Dose Cyclosporine (CsA) in the Initial Post-Transplant Period
884
885
CONSERVATIVE TREATMENT OF RENAL ALLOGRAFT RUPTURE USING POLYGLACTINE (PGA) 910 MESH. Dominique K. Chopin, Claude C. Abbou, Henry B. Lottman, Zivko Popov, Philippe R. Lang, Claude M. Buisson, Creteil, France (Presentation to be made by Dr Chopin). Conservative treatment of severe renal allograft rupture remains a surgical challenge since profuse hemorrage may result from these friable kidneys during surgical repair. The rate of transplant nephrectomy has been reported in 55.7 per cent of 149 cases. A surgical technique is proposed in severe renal allograft rupture to achieve control of local bleeding using an external compression with a PGA mesh. The ruptured graft is wrapped in an absorbable mesh specially tailored to the size of the graft which prevent enlargement of the tears or repeat fissures. From January 1984 to July 1986, 110 renal transplants were performed. Minor renal rupture associated with acute rejection, detected by ultrasound and biologic parameters, were treated by conventionnal immunosuppression regiment only in 8 cases (7,2 %). Severe renal rupture requiring immediate surgery occured in 6 cases (5,4 %). In two cases transplant nephrectomy was the only alternative for non-viable grafts. In four cases a conservative treatment using the PGA mesh was a suitable option. Control of local bleeding was achieved in 4 out of 4 cases. Three grafts has been preserved with a satisfactory renal function with a follow-up from 6 to 24 months. The other graft has to be removed for uncontrolled the 30th post operative day. an absorbable mesh do way to control local bleeding rupture. Combining this i ve regiments may improve rupture.
LOW DOSE CYCLOSPORINE (CsA) IN THE INITIAL POST-TRANSPLANT PERIOD. Raja B. Khauli, *Jeffrey Stoff, *Paul Lee, *Andrew Cohen, *David Clive and *Shauneen Valliere, Worcester, MA (Presentation to be made by Dr. Khauli) The use of CsA immediately after transplantation is associated with increased incidence and severity of acute tubular necrosis (ATN) and primary graft non-function. To avoid the potential harmful effect of CsA, recipients of primary cadaveri c grafts were treated with low dose CsA in the immediate post-transplant period, azathioprine (0.5-1 mg/kg/d), and prednisone (0.5 mg/kg/d). Recipients of grafts preserved >24 hours and demonstrating lov1 urine output at surgery were started on ALG (10-20 mg/kg/d) IV, until graft function was established, then CsA was begun (12 n1g/kg/d). Preliminary experience with 6 consecutive patients is reported (follow up=4-8 months). Renal preservation time ranged from 22.9 to 32.9 hrs., mean= 26.6 ±3.8 hrs. In the first group receiving triple therapy (n=4) the initial CsA dose post-transplantation ranged from 5-7 nig/kg/d with a mean of 6±0.8 mg/kg/d. This was slowly increased in the second week to 9±1.2 mg/kg/d then slowly tapered to 4-6 mg/kg/d at 6 months. CsA trough levels (HPLC) in the first week ranged from 75-157 ng/ml with a niean of 116±21 mg/ml. In the second week the CsA levels ranged from 83-818 ng/ml with a mean of 285±332 ng/nil. Nadir creatinine ranged from 1.4 to 2.9 mg% with a mean of 1.9 ±1.2 and time to nadir was 8-16 days, mean 13.8±3.9. No patient required dialysis post-transplantation. Rejections (3 out of 4) were easily reversed with methylprednisolone and all patients are currently alive 1,ith functioning grafts. There were no serious infections noted. In the second group (ALG), one patient had 1° non-function and never received CsA and the other has a functioning graft. Both patients had viral and fungal infections. In conclu·· sion, low CsA dosage in the initial post-transplant period is safe and allows for rapid recovery of graft function, low incidence of CsA nephrotoxicity, 1,ithout cofllpromising long term graft survival.
886
887
ACQUIRED RENAL CYSTIC DISEASE IN PATIENTS ON CHRONIC PERITONEAL DIAJ,YSIS OR CHRONIC HEMODIALYSIS. Bernard Fallon,
INDUCTION OF BLADDER TUMORS UNDER IMMUNOSUPPRESSION BY CYCLOSPORINE A - AN EXPERIMENTAL STUDY *Franz Recker, Herbert Rilbben, *Stephan Enger, Aachen, West Germany The immunosuppressive drug cyclosporin A (CyA) is known to inhibit selective T-cells. In spite of believing the immunosurveillance hypothesis of cancer control thf,t immunosupression which accompanies the administration of CyA should give rise to tumors in experimental animals, until today there is no increased incidence of spontaneous tumor nor greater susceptibility to chemical carcinogens under Cy A. The Cy A induced T-cell selective immunosuppressive influence on known bladder tumor inducing chemical carcinogen BBN should be investigated. 1 iO male wistar rats were divided in three groups. l II Ill
M.n,,,'l:Gregory M. Thompson, M.D.,'°'Mic.hael J. Flanigan, M.D., ancl~'-:Monzer M. Abu-Yousef, M.D., Iowa City, IA (Presentation to be ma
Acquired cystic disease of the kidneys (ACDK) was first described as an entity in 1977. Its presence has been documented in 30-50% of patients on chronic hemodialysis.
Its incidence in patients on cl1ronic peritoneal dialysis has not been adequately studied. We have a large popuL1tion of patients suffering from renal fai1ure of various etiologies wlio have been treated with either peritoneal or hemodialysis for varying time periods. A study has been undertaken to investigate the incidence. of ACDK in both patient groups using u1 trasound as tl1e major investigative modality. Other objectives are: 1) to discover tl1e incidence of ACDK as relatPd tn tl1e cause of chronic rena1. failure and the etiology of renal failure, 2) to discover the incidence and histology of solid renal lesions associated with ACDK, 3) to discover the influence of successful renal transplantation on ACDK. Results: 1) To date, 38 patients have had ultrasound studies performed. ACDK has been found in 13 of 27 (48%) patiencs on hemodialysis and 4 of l] (36%) patients on peritoneal dialysis. 2) The incidence of ACDK increases concomitantly with the duration of dialysis. 3) The incidence of ACDK is not related to the etiology of renal failure. 4) Two patients of 38 studied, and 17 witl1 ACDK have had solid renal lesions, both histologically compatible with renal cell carcinoma. Conclusions: 1) Ultrasound of the kidneys should be performed as a baseline in ull dialysis patients and at annual intervals thereafter. 2) Further studies such as CT or MRI should be performed in those patients in whom solid lesions are suspected on ultrasound. 3) Nephre.ctomy should be performed when solid renal lesions are confirmed. 4) Further studies of ACDK, including attempts to establish an animal model, are necessary.
Cy A
0
5*
12.5*
0.05 %/d
0.05 %/d
0.05 %/d
(10 weeks)
+ BBN (8 weeks)
Tumor portion in bladder
lnfil. 0.7 % 2.5 % Exophyt. 4.2 % 8.0 % * mg/kg body weight/daily
3.3 % 11.6 %
The first time a significantly higher chemical tumor induction
under CyA is described in vivo (infiltrotiv: p-0.004 SD 0.04; exophytical p-0.000 I SD 0.08) Selective T-cell suppression plays a role in the immunological part of carcinogenesis -. The decision of clinical kidney transplantation by patients with renal insufficiency caused by primary urothelial cnrcinoma has care-
fully to be planed.
325A
885
CONSERVATIVE TREATMENT OF RENAL ALLOGRAFT RUPTURE USING POLYGLACTINE (PGA) 910 MESH. Dominique K. Chopin, Claude C. Abbou, Henry B. Lottman, Zivko Popov, Philippe R. Lang, Claude M. Buisson, Creteil, France (Presentation to be made by Dr Chopin). Conservative treatment of severe renal allograft rupture remains a surgical challenge since profuse hemorrage may result from these friable kidneys during surgical repair. The rate of transplant nephrectomy has been reported in 55.7 per cent of 149 cases. A surgical technique is proposed in severe renal allograft rupture to achieve control of local bleeding using an external compression with a PGA mesh. The ruptured graft is wrapped in an absorbable mesh specially tailored to the size of the graft which prevent enlargement of the tears or repeat fissures. From January 1984 to July 1986, 110 renal transplants were performed. Minor renal rupture associated with acute rejection, detected by ultrasound and biologic parameters, were treated by conventionnal immunosuppression regiment only in 8 cases (7,2 %). Severe renal rupture requiring immediate surgery occured in 6 cases (5,4 %). In two cases transplant nephrectomy was the only alternative for non-viable grafts. In four cases a conservative treatment using the PGA mesh was a suitable option. Control of local bleeding was achieved in 4 out of 4 cases. Three grafts has been preserved with a satisfactory renal function with a follow-up from 6 to 24 months. The other graft has to be removed for uncontrolled the 30th post operative day. an absorbable mesh do way to control local bleeding rupture. Combining this i ve regiments may improve rupture.
LOW DOSE CYCLOSPORINE (CsA) IN THE INITIAL POST-TRANSPLANT PERIOD. Raja B. Khauli, *Jeffrey Stoff, *Paul Lee, *Andrew Cohen, *David Clive and *Shauneen Valliere, Worcester, MA (Presentation to be made by Dr. Khauli) The use of CsA immediately after transplantation is associated with increased incidence and severity of acute tubular necrosis (ATN) and primary graft non-function. To avoid the potential harmful effect of CsA, recipients of primary cadaveri c grafts were treated with low dose CsA in the immediate post-transplant period, azathioprine (0.5-1 mg/kg/d), and prednisone (0.5 mg/kg/d). Recipients of grafts preserved >24 hours and demonstrating lov1 urine output at surgery were started on ALG (10-20 mg/kg/d) IV, until graft function was established, then CsA was begun (12 n1g/kg/d). Preliminary experience with 6 consecutive patients is reported (follow up=4-8 months). Renal preservation time ranged from 22.9 to 32.9 hrs., mean= 26.6 ±3.8 hrs. In the first group receiving triple therapy (n=4) the initial CsA dose post-transplantation ranged from 5-7 nig/kg/d with a mean of 6±0.8 mg/kg/d. This was slowly increased in the second week to 9±1.2 mg/kg/d then slowly tapered to 4-6 mg/kg/d at 6 months. CsA trough levels (HPLC) in the first week ranged from 75-157 ng/ml with a niean of 116±21 mg/ml. In the second week the CsA levels ranged from 83-818 ng/ml with a mean of 285±332 ng/nil. Nadir creatinine ranged from 1.4 to 2.9 mg% with a mean of 1.9 ±1.2 and time to nadir was 8-16 days, mean 13.8±3.9. No patient required dialysis post-transplantation. Rejections (3 out of 4) were easily reversed with methylprednisolone and all patients are currently alive 1,ith functioning grafts. There were no serious infections noted. In the second group (ALG), one patient had 1° non-function and never received CsA and the other has a functioning graft. Both patients had viral and fungal infections. In conclu·· sion, low CsA dosage in the initial post-transplant period is safe and allows for rapid recovery of graft function, low incidence of CsA nephrotoxicity, 1,ithout cofllpromising long term graft survival.
886
887
ACQUIRED RENAL CYSTIC DISEASE IN PATIENTS ON CHRONIC PERITONEAL DIAJ,YSIS OR CHRONIC HEMODIALYSIS. Bernard Fallon,
INDUCTION OF BLADDER TUMORS UNDER IMMUNOSUPPRESSION BY CYCLOSPORINE A - AN EXPERIMENTAL STUDY *Franz Recker, Herbert Rilbben, *Stephan Enger, Aachen, West Germany The immunosuppressive drug cyclosporin A (CyA) is known to inhibit selective T-cells. In spite of believing the immunosurveillance hypothesis of cancer control thf,t immunosupression which accompanies the administration of CyA should give rise to tumors in experimental animals, until today there is no increased incidence of spontaneous tumor nor greater susceptibility to chemical carcinogens under Cy A. The Cy A induced T-cell selective immunosuppressive influence on known bladder tumor inducing chemical carcinogen BBN should be investigated. 1 iO male wistar rats were divided in three groups. l II Ill
M.n,,,'l:Gregory M. Thompson, M.D.,'°'Mic.hael J. Flanigan, M.D., ancl~'-:Monzer M. Abu-Yousef, M.D., Iowa City, IA (Presentation to be ma
Acquired cystic disease of the kidneys (ACDK) was first described as an entity in 1977. Its presence has been documented in 30-50% of patients on chronic hemodialysis.
Its incidence in patients on cl1ronic peritoneal dialysis has not been adequately studied. We have a large popuL1tion of patients suffering from renal fai1ure of various etiologies wlio have been treated with either peritoneal or hemodialysis for varying time periods. A study has been undertaken to investigate the incidence. of ACDK in both patient groups using u1 trasound as tl1e major investigative modality. Other objectives are: 1) to discover tl1e incidence of ACDK as relatPd tn tl1e cause of chronic rena1. failure and the etiology of renal failure, 2) to discover the incidence and histology of solid renal lesions associated with ACDK, 3) to discover the influence of successful renal transplantation on ACDK. Results: 1) To date, 38 patients have had ultrasound studies performed. ACDK has been found in 13 of 27 (48%) patiencs on hemodialysis and 4 of l] (36%) patients on peritoneal dialysis. 2) The incidence of ACDK increases concomitantly with the duration of dialysis. 3) The incidence of ACDK is not related to the etiology of renal failure. 4) Two patients of 38 studied, and 17 witl1 ACDK have had solid renal lesions, both histologically compatible with renal cell carcinoma. Conclusions: 1) Ultrasound of the kidneys should be performed as a baseline in ull dialysis patients and at annual intervals thereafter. 2) Further studies such as CT or MRI should be performed in those patients in whom solid lesions are suspected on ultrasound. 3) Nephre.ctomy should be performed when solid renal lesions are confirmed. 4) Further studies of ACDK, including attempts to establish an animal model, are necessary.
Cy A
0
5*
12.5*
0.05 %/d
0.05 %/d
0.05 %/d
(10 weeks)
+ BBN (8 weeks)
Tumor portion in bladder
lnfil. 0.7 % 2.5 % Exophyt. 4.2 % 8.0 % * mg/kg body weight/daily
3.3 % 11.6 %
The first time a significantly higher chemical tumor induction
under CyA is described in vivo (infiltrotiv: p-0.004 SD 0.04; exophytical p-0.000 I SD 0.08) Selective T-cell suppression plays a role in the immunological part of carcinogenesis -. The decision of clinical kidney transplantation by patients with renal insufficiency caused by primary urothelial cnrcinoma has care-
fully to be planed.
325A