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Influence of Pancreas Transplantation Alone on Native Renal Function
Influence of Pancreas Transplantation Alone on Native Renal Function T. Genzini, G.S. Marchini, A.J.B.A. Chang, I. Antunes, A. Hayashi, H. Abensur, L. Kataoka, F. Crescentini, J. Egı´dio Romão Jr, E.B. Rangel, and M. Perosa ABSTRACT Pancreas transplantation alone (PTA) has become an accepted treatment of nonuremic diabetic patients, when the risks of secondary complications of diabetes mellitus are greater than those of the surgical procedure and the posttransplant immunosuppression. As a decrease in native renal function is expected, we followed this parameter among patients who underwent PTA. From January 1997 through January 2005, we performed 69 PTA in 66 patients. All patients showed glucose hyperlability with hypoglycemic unawareness, or two or more diabetic complications as well as creatinine clearance (CrCl) ⱖ 45 mL/min. Immunosuppression was based on tacrolimus, mycophenolate mofetil and prednisone. Twenty-four hour CrCl were performed after all successful PTA. We divided patients in two groups according to the pretransplant CrCl: group 1, CrCl ⱕ 70 mL/min (n ⫽ 20) and group 2, CrCl ⬎ 70 mL/min (n ⫽ 25). The data were analyzed using Student’s t-test (P ⱕ .05 was considered significant). Twenty-one patients were excluded from the analysis because of death (n ⫽ 5) or graft loss (n ⫽ 8) during the first year or follow-up shorter than 1 year (n ⫽ 8). The mean value of CrCl decreased 28.8% (85.0 ⫾ 31 versus 60.5 ⫾ 36 mL/min; P ⬍ .001). There was also a 39.3% reduction among group 1 subjects (P ⫽ .003), including 10 who displayed CrCl ⱕ 30 mL/min. There was also a 24.4% reduction among group 2 (P ⫽ .008), but no patient developed end-stage renal disease. In conclusion, native renal function decreased significantly after PTA, but was well tolerated among patients with CrCl ⬎ 70 mL/min. Patients with CrCl ⬍ 70 mL/min show a significant risk of worsened renal function.
P
ANCREAS TRANSPLANTATION alone (PTA) has become an accepted procedure in nonuremic diabetic patients, when the risks of secondary complications of diabetes mellitus exceed those of the surgical procedure and the posttransplant immunosuppression.1–3 Renal function is an essential parameter for recipient selection for a decrease is expected due to volume depletion and side effects of immunosuppressive drugs.4 – 6 During the period of this study, our renal function selection criteria for PTA was a creatinine clearance (CrCl) ⱖ 45 mL/min. The price of this approach was the risk of posttransplant renal failure. To address this issue, we examined the native renal function of PTA patients.
all cases, the pancreas was procured from a heart-beating cadaveric donor in conjunction with multiple organ retrieval. Organs were cold preserved in University of Wisconsin solution. Patients were selected based on ABO blood type compatibility and a negative cross-match. In all cases, the whole pancreas with a duodenal segment was placed intraperitoneally with systemic venous drainage. Exocrine secretion was drained to the bladder in 55 (80%) and to the intestine in 13 (19%) cases. One graft was removed because of immediate pancreatic injury after reperfusion. Immunosuppression consisted of a 7- to 10-day course of OKT3 or ATG induction followed by tacrolimus, mycophenolate mofetil, and corticosteroids. Tacrolimus levels were adjusted to achieve whole blood levels of 8 to 12 ng/mL in the first year, and 5 to 8 ng/mL thereafter. To follow native renal function, 24 hour CrCl were performed after
PATIENTS AND METHODS From January 1997 through January 2005, we performed 69 PTA in 66 patients who underwent a comprehensive pretransplant evaluation. They were considered suitable for PTA due to glucose hyperlability with hypoglycemic unawareness or two or more diabetic complications, as well as displaying CrCl ⱖ 45 mL/min. In
From HEPATO—Hepatology and Organ Transplantation, Albert Einstein Hospital, São Paulo, Brazil. Address reprint requests to Giovanni Scala Marchini, Av. Mandaqui 63, Bairro do Limão, São Paulo/SP, Brazil CEP: 02550-000. E-mail: [email protected]
© 2006 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/06/$–see front matter doi:10.1016/j.transproceed.2006.06.083
Transplantation Proceedings, 38, 1939 –1940 (2006)
1939
1940
GENZINI, MARCHINI, CHANG ET AL Table 1. Comparison of PTA Patients According to Creatinine Clearance
Age (mean) Follow-up (mean) CrCl pre- vs posttransplantation (mean decrease; P) ESRD Dialysis KAPT
Group 1 (n ⫽ 20) (CrCl ⬍ 70 mL/min)
Group 2 (n ⫽ 25) (CrCl ⬎ 70 mL/min)
32 y 15.1 mo 57.3 ⫾ 9 vs 34.8 ⫾ 32 mL/min 39.3%; P ⫽ .003 n ⫽ 10 (50%) n ⫽ 5 (25%) n ⫽ 3 (15%)
30 y 16.9 mo 107.1 ⫾ 25 vs 81.0 ⫾ 23 mL/min 24.4%; P ⫽ .008 n⫽0 n⫽0 n⫽0
Abbreviations: CrCl, creatinine clearance; ESRD, end-stage renal disease; KAPT, kidney after pancreas transplantation.
all successful PTA, using a colorimetric method. The collected data were compared with pretransplant CrCl. We also divided the patients into two groups according to the pretransplant CrCl: group 1, CrCl ⱕ 70 mL/min (n ⫽ 20) and group 2, CrCl ⬎ 70 mL/min (n ⫽ 25). The data were analyzed using Student’s t-test (mean value ⫾ standard deviation); a P ⱕ .05 was considered significant.
know, nephrotoxicity remains as one of the major side effects of calcineurin inhibitors, leading some centers to avoid PTA for patients with CrCl ⬍ 70 mL/min. Fioretto et al6 demonstrated histologic improvement in diabetic nephropathy 10 years after PTA in patients with incipient nephropathy. However, patients with moderate renal lesions may not benefit from long-term normoglycemia if they develop renal insufficiency and require dialytic therapy. Half of our patients with CrCl below 70 mL/min evolved to ESRD, in contrast to those with CrCl above 70 mL/min, who showed satisfactory renal function. Similar results have been described by other authors,7 emphasizing that there is no secure pretransplant CrCl which may ensure a favorable renal functional evolution after PTA. However, CrCl above 70 mL/min seems to be the safer choice. In conclusion, native renal function decreased significantly after PTA. The decrease was well tolerated in patients with CrCl above 70 mL/min. Patients with CrCl below 70 mL/min showed a significant risk of renal function deterioration either requiring dialysis or a kidney after pancreas transplant. In this last group, PTA would be advisable only if a backup living kidney donor is available.
RESULTS
Twenty-one patients were excluded from the analysis, because of death (n ⫽ 5), graft loss (n ⫽ 8) before 1 year, or follow-up of less than 1 year (n ⫽ 8). Of the remaining 45 patients, the mean time between pre- and posttransplant CrCl was 16 months (range ⫽ 12 to 72 months). Overall mean CrCl decreased 28.8% (85.0 ⫾ 31 versus 60.5 ⫾ 36 mL/min; P ⬍ .001). When group 1 was analyzed, there was a 39.3% reduction. 57.3 (⫾9) versus 34.8 (⫾32) mL/min, (P ⫽ .003). Ten patients (50%) showed a decrease in CrCl below 30 mL/min, five started dialytic therapy and another three already had kidney after pancreas transplantation. Among group 2, there was a 24.4% reduction in CrCl (107.1 ⫾ 25 versus 81.0 ⫾ 23 mL/min; P ⫽ .008), but no patient developed end-stage renal disease (ESRD; Table 1). DISCUSSION
It is well established that native renal function is significantly affected by pancreas transplantation. As we already
REFERENCES 1. Bartlett ST, Schweitzer EJ, Johnson LB, et al: Equivalent success of simultaneous pancreas kidney and solitary pancreas transplantation: a prospective trial of tacrolimus immunosuppression with percutaneous biopsy. Ann Surg 224:440, 1996 2. IPTR 2003 Mid Year Update. Available: www.iptr.umn.edu/ 3. Sutherland DER, Gruessner RWG, Dunn DL, et al: Lessons learned from more than 1,000 pancreas transplants at a single institution. Ann Surg 233:463, 2001 4. Bilious RW, Mauer SM, Sutherland DER, et al: The effects of pancreas transplantation on the glomerular structure of renal allografts in patients with insulin-dependent diabetes. N Engl J Med 321:80, 1989 5. Fioretto P, Mauer SM, Bilious RW, et al: Effects of pancreas transplantation on glomerular structure in insulin-dependent diabetic patients with their own kidneys. Lancet 342:1193, 1993 6. Fioretto P, Steffes MW, Sutherland DER, et al: Successful pancreas transplantation alone reverses established lesions of diabetic nephropathy in man. Am Soc Nephrol 8:111A, 1997 7. Mazur MJ, Rea DJ, Griffin MD, et al: Decline in native renal function early after pancreas transplantation alone. Transplantation 77:844, 2004
P
ANCREAS TRANSPLANTATION alone (PTA) has become an accepted procedure in nonuremic diabetic patients, when the risks of secondary complications of diabetes mellitus exceed those of the surgical procedure and the posttransplant immunosuppression.1–3 Renal function is an essential parameter for recipient selection for a decrease is expected due to volume depletion and side effects of immunosuppressive drugs.4 – 6 During the period of this study, our renal function selection criteria for PTA was a creatinine clearance (CrCl) ⱖ 45 mL/min. The price of this approach was the risk of posttransplant renal failure. To address this issue, we examined the native renal function of PTA patients.
all cases, the pancreas was procured from a heart-beating cadaveric donor in conjunction with multiple organ retrieval. Organs were cold preserved in University of Wisconsin solution. Patients were selected based on ABO blood type compatibility and a negative cross-match. In all cases, the whole pancreas with a duodenal segment was placed intraperitoneally with systemic venous drainage. Exocrine secretion was drained to the bladder in 55 (80%) and to the intestine in 13 (19%) cases. One graft was removed because of immediate pancreatic injury after reperfusion. Immunosuppression consisted of a 7- to 10-day course of OKT3 or ATG induction followed by tacrolimus, mycophenolate mofetil, and corticosteroids. Tacrolimus levels were adjusted to achieve whole blood levels of 8 to 12 ng/mL in the first year, and 5 to 8 ng/mL thereafter. To follow native renal function, 24 hour CrCl were performed after
PATIENTS AND METHODS From January 1997 through January 2005, we performed 69 PTA in 66 patients who underwent a comprehensive pretransplant evaluation. They were considered suitable for PTA due to glucose hyperlability with hypoglycemic unawareness or two or more diabetic complications, as well as displaying CrCl ⱖ 45 mL/min. In
From HEPATO—Hepatology and Organ Transplantation, Albert Einstein Hospital, São Paulo, Brazil. Address reprint requests to Giovanni Scala Marchini, Av. Mandaqui 63, Bairro do Limão, São Paulo/SP, Brazil CEP: 02550-000. E-mail: [email protected]
© 2006 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/06/$–see front matter doi:10.1016/j.transproceed.2006.06.083
Transplantation Proceedings, 38, 1939 –1940 (2006)
1939
1940
GENZINI, MARCHINI, CHANG ET AL Table 1. Comparison of PTA Patients According to Creatinine Clearance
Age (mean) Follow-up (mean) CrCl pre- vs posttransplantation (mean decrease; P) ESRD Dialysis KAPT
Group 1 (n ⫽ 20) (CrCl ⬍ 70 mL/min)
Group 2 (n ⫽ 25) (CrCl ⬎ 70 mL/min)
32 y 15.1 mo 57.3 ⫾ 9 vs 34.8 ⫾ 32 mL/min 39.3%; P ⫽ .003 n ⫽ 10 (50%) n ⫽ 5 (25%) n ⫽ 3 (15%)
30 y 16.9 mo 107.1 ⫾ 25 vs 81.0 ⫾ 23 mL/min 24.4%; P ⫽ .008 n⫽0 n⫽0 n⫽0
Abbreviations: CrCl, creatinine clearance; ESRD, end-stage renal disease; KAPT, kidney after pancreas transplantation.
all successful PTA, using a colorimetric method. The collected data were compared with pretransplant CrCl. We also divided the patients into two groups according to the pretransplant CrCl: group 1, CrCl ⱕ 70 mL/min (n ⫽ 20) and group 2, CrCl ⬎ 70 mL/min (n ⫽ 25). The data were analyzed using Student’s t-test (mean value ⫾ standard deviation); a P ⱕ .05 was considered significant.
know, nephrotoxicity remains as one of the major side effects of calcineurin inhibitors, leading some centers to avoid PTA for patients with CrCl ⬍ 70 mL/min. Fioretto et al6 demonstrated histologic improvement in diabetic nephropathy 10 years after PTA in patients with incipient nephropathy. However, patients with moderate renal lesions may not benefit from long-term normoglycemia if they develop renal insufficiency and require dialytic therapy. Half of our patients with CrCl below 70 mL/min evolved to ESRD, in contrast to those with CrCl above 70 mL/min, who showed satisfactory renal function. Similar results have been described by other authors,7 emphasizing that there is no secure pretransplant CrCl which may ensure a favorable renal functional evolution after PTA. However, CrCl above 70 mL/min seems to be the safer choice. In conclusion, native renal function decreased significantly after PTA. The decrease was well tolerated in patients with CrCl above 70 mL/min. Patients with CrCl below 70 mL/min showed a significant risk of renal function deterioration either requiring dialysis or a kidney after pancreas transplant. In this last group, PTA would be advisable only if a backup living kidney donor is available.
RESULTS
Twenty-one patients were excluded from the analysis, because of death (n ⫽ 5), graft loss (n ⫽ 8) before 1 year, or follow-up of less than 1 year (n ⫽ 8). Of the remaining 45 patients, the mean time between pre- and posttransplant CrCl was 16 months (range ⫽ 12 to 72 months). Overall mean CrCl decreased 28.8% (85.0 ⫾ 31 versus 60.5 ⫾ 36 mL/min; P ⬍ .001). When group 1 was analyzed, there was a 39.3% reduction. 57.3 (⫾9) versus 34.8 (⫾32) mL/min, (P ⫽ .003). Ten patients (50%) showed a decrease in CrCl below 30 mL/min, five started dialytic therapy and another three already had kidney after pancreas transplantation. Among group 2, there was a 24.4% reduction in CrCl (107.1 ⫾ 25 versus 81.0 ⫾ 23 mL/min; P ⫽ .008), but no patient developed end-stage renal disease (ESRD; Table 1). DISCUSSION
It is well established that native renal function is significantly affected by pancreas transplantation. As we already
REFERENCES 1. Bartlett ST, Schweitzer EJ, Johnson LB, et al: Equivalent success of simultaneous pancreas kidney and solitary pancreas transplantation: a prospective trial of tacrolimus immunosuppression with percutaneous biopsy. Ann Surg 224:440, 1996 2. IPTR 2003 Mid Year Update. Available: www.iptr.umn.edu/ 3. Sutherland DER, Gruessner RWG, Dunn DL, et al: Lessons learned from more than 1,000 pancreas transplants at a single institution. Ann Surg 233:463, 2001 4. Bilious RW, Mauer SM, Sutherland DER, et al: The effects of pancreas transplantation on the glomerular structure of renal allografts in patients with insulin-dependent diabetes. N Engl J Med 321:80, 1989 5. Fioretto P, Mauer SM, Bilious RW, et al: Effects of pancreas transplantation on glomerular structure in insulin-dependent diabetic patients with their own kidneys. Lancet 342:1193, 1993 6. Fioretto P, Steffes MW, Sutherland DER, et al: Successful pancreas transplantation alone reverses established lesions of diabetic nephropathy in man. Am Soc Nephrol 8:111A, 1997 7. Mazur MJ, Rea DJ, Griffin MD, et al: Decline in native renal function early after pancreas transplantation alone. Transplantation 77:844, 2004