Simultaneous Transplantation of Pancreas and Kidney in Patients with Advanced Diabetic Complications

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<ul><li><p>Simultaneous Transplantation of Pancreas and Kidney in Patients with Advanced Diabetic Complications I. B. BREKKE &amp; A. L. FLATMARK Department of Surgery, Rikshospitalet, The National Hospital, Oslo, Norway </p><p>Brekke IB, Flatmark AL. Simultaneous transplantation of pancreas and kidney in patients with advanced diabetic complications. Scand J Gastroenterol 1986, 2l(suppl 126). 1-4 </p><p>From June 1983 to October 1985, 25 uremic diabetic patients aged 24 to 52 (mean 38) years were treated with combined pancreas and kidney transplantation. Mean duration of diabetes was 24 years. and end-stage renal disease was associated with severe extrarenal diabetic complications in all recipients. All transplants were har- vested from cadaveric, heart-beating donors aged 5-55 years. The segmental pancreas transplant was duct-occluded with neoprene before it was transplanted to the left iliac fossa. Immunosuppressive treatment was given with cyclosporine and steroids in all cases while azathioprine was added in the last 5 cases. The one year survival of patient, kidney and pancreas was 96, 79 and 60 per cent respectively. Of 17 patients with functioning pancreas transplants, 13 are insulin independent and have normal or near normal glucose homeostasis. Based on the excellent patient survival and the improvement in quality of life experienced by the recipients, i t is concluded that simultaneous transplantation of pancreas and kidney should be the treatment of choice for uremic diabetic patients when a living related kidney donor is unavailable. </p><p>Key words: Diabetes mellitus; diabetic nephropathy; kidney transplantation; pan- creas transplantation; uremia </p><p>Inge B . Brekke, Department of Surgery, Rikshospitalet, The National Hospital, 0027 Oslo 1 , Norway </p><p>INTRODUCTION </p><p>In the western world, diabetes is one of the lead- ing causes of kidney failure, and diabetic end- stage renal disease is usually associated with extra- renal diabetic complications such as ophthalmic, neurologic and cardiovascular lesions. There is sufficient evidence to state that these late com- plications of diabetes are the consequence of dia- betic metabolic disorders not fully corrected by conventional insulin treatment (1,2). A suc- cessful renal transplantation will cure uremia, but the progress of extrarenal diabetic organ damage will continue if the responsible metabolic disorder is not corrected. This is reflected in previous reports on relatively poor prognosis for uremic diabetic patients treated with renal transplan- tation (3) or hemodialysis (4) when compared with non-diabetic uremic patients. </p><p>In the assumption that normalization of carbo- hydrate metabolism may stop or retard further progression of diabetic organ damage and have a beneficial effect on patient survival, we have since June 1983 treated uremic type I diabetic patients with simultaneous pancreas and kidney trans- plantation. Our transplant procedure and our experience with a total of 25 recipients of com- bined transplants are reported. </p><p>PATIENTS AND METHODS </p><p>Uremic type I diabetic patients were accepted for simultaneous kidney and pancreas transplan- tation when a living related kidney donor was unavailable. In the 27 months period from June 1983 to October 1985, 25 patients aged 24-52 (mean 38) years received combined transplants. </p><p>Scan</p><p>d J </p><p>Gas</p><p>troe</p><p>nter</p><p>ol D</p><p>ownl</p><p>oade</p><p>d fr</p><p>om in</p><p>form</p><p>ahea</p><p>lthca</p><p>re.c</p><p>om b</p><p>y M</p><p>cMas</p><p>ter </p><p>Uni</p><p>vers</p><p>ity o</p><p>n 12</p><p>/19/</p><p>14Fo</p><p>r pe</p><p>rson</p><p>al u</p><p>se o</p><p>nly.</p></li><li><p>2 I . B. Brekke &amp; A . L. Flarmark </p><p>Thus, 60% of all Norwegian diabetic kidney recip- ients in this period also received a pancreas. </p><p>Duration of diabetes ranged from 7 to 37 (mean 24) years, and 14 patients were established on dialysis treatment at the time of transplantation. Most recipients had severe extrarenal diabetic complications. Advanced diabetic retinopathy was present in all patients, and most of them had markedly reduced vision, while four were totally blind. Prior to transplantation, peripheral poly- neuropathy was demonstrated in all recipients. Three recipients had symptomatic coronary heart disease, and three had suffered cerebral strokes. </p><p>All grafts were harvested from cadaveric heart- beating donors (aged 5-55 years). After in situ perfusion, a segment of the pancreas, containing the corpus and cauda pancreatis, was removed together with the splenic vessels (Fig. 1A). The kidneys were then removed by standard tech- niques, and the organs were stored in Euro-Col- lins solution until transplanted. </p><p>The pancreatic duct was occluded with neo- prene (Fig. lB), and the graft vessels were anas- </p><p>A </p><p>B splenic ar tery </p><p>spienic vein </p><p>Fig. 1 . A. The donor pancreatectomy. B. Occlusion of the pancreatic duct by neoprene injection. </p><p>Fig. 2. The recipient operation. After performing the vascular anastomoses extraperitoneally, the pancreas is placed intraperitoneally through a peritoneal incision. </p><p>tomosed extraperitoneally to the iliac vessels in the left iliac fossa. The pancreas was then placed partly intraperitoneally through a peritoneal incision. The kidney was subsequently trans- planted to the right iliac fossa in the standard fashion (Fig. 2). Ischemia time for the pancreas transplants varied from three to eight hours, for the kidneys from six to eleven hours. </p><p>Immunosuppressive treatment consisted of cyclosporine and prednisolone, and in the last five cases azathioprine was added. Rejection episodes were treated with methylprednisolone in bolus doses. Dextran 500ml was given every second day for 14 days postoperatively as prophylaxis against graft vessel thrombosis. </p><p>Early pancreas graft function was monitored with blood glucose, insulin and C-peptide rneas- urements. Long-term graft function was followed with measurements of glycosylated hemoglobin (HbA ,), glucose tolerance and glucagon tests. </p><p>RESULTS </p><p>Good primary function was achieved in all pan- creas and kidney transplants, but the very first </p><p>Scan</p><p>d J </p><p>Gas</p><p>troe</p><p>nter</p><p>ol D</p><p>ownl</p><p>oade</p><p>d fr</p><p>om in</p><p>form</p><p>ahea</p><p>lthca</p><p>re.c</p><p>om b</p><p>y M</p><p>cMas</p><p>ter </p><p>Uni</p><p>vers</p><p>ity o</p><p>n 12</p><p>/19/</p><p>14Fo</p><p>r pe</p><p>rson</p><p>al u</p><p>se o</p><p>nly.</p></li><li><p>Pancreas Transplantarion 3 </p><p>pancreas transplanted ceased to function after 4 days, probably due to a technical failure. Four pancreas transplants were subsequently rejected, and one functioning pancreas was removed because of local infection. Two patients experi- enced acute loss of pancreas graft function at 10 and 12 months respectively. Angiographic exam- inations showed occluded graft artery in both cases. </p><p>Currently (October 1, 1985) 17 recipients have functioning pancreatic transplants. However, four of these need some insulin substitution to maintain satisfactory blood sugar control. Two of these patients were insulin independent for more than one year. </p><p>A total of five renal transplants were lost, four were rejected, and one was lost in an unsuccessful attempt to repair a stenosed graft artery. </p><p>One patient with extremely advanced athero- sclerosis died three months after the trans- plantation of septicemia caused by an infected lower limb gangrene. All other recipients are alive. This gives a 96% one year patient survival. The cumulative one year graft survival was 79% for the kidney and 60% for the pancreas. </p><p>All recipients with functioning grafts have experienced an immense improvement in general well-being and quality of life. Those who are insulin independent are normoglycemic with H b A , within the normal range, although glucose tolerance tests were not normalized in all patients. Insulin and C-peptide concentrations in per- ipheral blood were high in most patients, probably due to the extraportal release of these substances from the pancreas transplant. </p><p>DISCUSSION </p><p>Since the introduction of clinical pancreas trans- plantation in 1966, technical failures related to problems in handling of the exocrine pancreas have been a major cause of graft loss (5-7). Efforts to solve these problems have led to trials of several surgical techniques which are variations of two principal procedures, enteric or urinary tract drainage of the pancreatic duct and duct occlusion. Suppression of exocrine pancreatic </p><p>function by duct occlusion eliminates the risks associated with ductal anastomoses. The present series shows that the technically simple duct- occlusion method with neoprene (8) allows pan- creas transplantation to be performed with mini- mal risk of technical failures or serious post- operative complications. The 96% one year survival of the uremic diabetic patients treated with combined pancreas and kidney transplan- tation in this study is in fact about 10% higher than for our non diabetic recipients of necro kidney transplants from the same period. This dem- onstrates the safety of the procedure and indicates that the combined transplantation should be the treatment of choice for diabetic patients with end stage renal disease when a living related kidney donor is unavailable. </p><p>Ideally, pancreas transplantation should be per- formed before irreversible organ damage has occurred. However, not all diabetic patients develop severe diabetic complications, and pan- creas transplantation will probably not become a standard treatment for early diabetes. Although considerable improvements have been achieved during the last few years thanks to new immuno- suppressive drugs and safer surgical techniques, pancreas graft survival is still inferior to that of the kidney graft. With the current transplant tech- niques and available immunosuppressive therapy, the best results are reached when pancreas is transplanted simultaneously with a kidney from the same donor (9), and this has been our pre- ferred procedure throughout the period of this study. </p><p>Knowledge on if, or to what degree, the com- bined transplantation will affect the extrarenal diabetic complications usually present in late stage diabetes, is scarce. Preliminary results indi- cate that peripheral neuropathy is reversible, at least to a certain extent, and that further pro- gression of retinopathy may be stopped or retarded (10). Advanced diabetic angiopathy, however, is probably irreversible. It is therefore of vital importance for the diabetic patient that the combined transplantation is performed at an early stage of renal failure, preferably before blindness, coronary heart disease and other severe complications are established. </p><p>Scan</p><p>d J </p><p>Gas</p><p>troe</p><p>nter</p><p>ol D</p><p>ownl</p><p>oade</p><p>d fr</p><p>om in</p><p>form</p><p>ahea</p><p>lthca</p><p>re.c</p><p>om b</p><p>y M</p><p>cMas</p><p>ter </p><p>Uni</p><p>vers</p><p>ity o</p><p>n 12</p><p>/19/</p><p>14Fo</p><p>r pe</p><p>rson</p><p>al u</p><p>se o</p><p>nly.</p></li><li><p>4 I . B. Brekke &amp; A . L . Flatmark </p><p>ACKNOWLEDGEMENT </p><p>The financial support by Norges Diabetesforbund is gratefully acknowledged. </p><p>REFERENCES </p><p>1 . Deckert T, Poulsen JE, Larsen M. Acta Med Scand </p><p>2. Brownlee M, Cahill GF Jr. Atherosclerosis Rev </p><p>3. Jervell J et al. Joint Scandinavian Study. Lancet </p><p>(suppl) 1979, 624, 48-53 </p><p>1919, 4 , 29-70 </p><p>1978, 2, 915-917 </p><p>4. Jacobs C, Brunner FP, Brynger H et al. Diabetic Nephropathy 1983, 2 , 12-15 </p><p>5. Sutherland DER, Goetz FC, Kendall DM, Najarian JS. Transplant Proc 1985, 17, 325-330 </p><p>6. Dubernard JM, Traeger J, Piatti PM, Gelet A, El Yafi S, Martin X et al. Transplant Proc 1985, 17, </p><p>7. Tyden G, Wilczek H, Lundgren G, 0stman J , Cun- narsson R et al. Transplant Proc 1985, 17, 331-335 </p><p>8. Brekke IB, Bergan A, Heen L, Flatmark A. Trans- plant Proc 1984, 16, 739-740 </p><p>9. Brekke IB, Dyrbekk D, Jakobsen A, Jervell J , S0dal G, Flatmark A. Transplant Proc (in press) </p><p>10. Brekke IB, Canes T, Syrdalen P, Egge K, Dyrbekk D, Flatmark A. Life Support Syst (in press) </p><p>312-314 </p><p>Scan</p><p>d J </p><p>Gas</p><p>troe</p><p>nter</p><p>ol D</p><p>ownl</p><p>oade</p><p>d fr</p><p>om in</p><p>form</p><p>ahea</p><p>lthca</p><p>re.c</p><p>om b</p><p>y M</p><p>cMas</p><p>ter </p><p>Uni</p><p>vers</p><p>ity o</p><p>n 12</p><p>/19/</p><p>14Fo</p><p>r pe</p><p>rson</p><p>al u</p><p>se o</p><p>nly.</p></li></ul>