Janusz Walaszewski

Steroid withdrawal at 3 months after kidney transplantation: a comparison of two tacrolimus-based regimens.

The 6 month prospective, randomized study compared the steroid‐sparing potential of two tacrolimus‐based regimens after renal transplantation. A total of 489 patients were randomized (1:1) to receive tacrolimus/mycophenolate mofetil (MMF)/steroids (n = 243; group Tac/MMF/S) or tacrolimus/azathioprine/steroids (n = 246; group Tac/Aza/S). At 3 months, steroids were tapered off in 267 (54.6%) patients free from steroid‐resistant acute rejection and with serum creatinine concentrations <160 μmol/l. The incidence of biopsy‐confirmed acute rejection at month 3 was lower in group Tac/MMF/S compared with group Tac/Aza/S (18.1% vs. 26.0%,P = 0.035). Moreover, more patients in the Tac/MMF/S group met the criteria for steroid withdrawal than in the Tac/Aza/S group (60.5% vs. 48.8%; P < 0.01). The incidence of acute rejection during months 4–6 was low in all groups, both for patients on steroid‐free dual therapy (Tac/MMF: 2.7%, Tac/Aza: 0.8%) and for patients who continued steroid maintenance therapy (Tac/MMF/S: 3.5%, Tac/Aza/S: 7.1%). Moreover, kidney function was well preserved in steroid‐free patients with month 6 median serum creatinine levels of 119.5 μmol/l (Tac/MMF), and 115.1 μmol/l (Tac/Aza). For patients who continued to receive steroids, month 6 median creatinine levels were 130.5 μmol/l (Tac/MMF/S) and 132.8 μmol/l (Tac/Aza/S). The criteria for the selection of patients to discontinue steroids were adequate. Both tacrolimus‐based regimens allowed the safe discontinuation of steroids in low‐risk patients at month 3. The Tac/MMF combination was superior in the prevention of acute rejections and more patients met the chosen criteria for steroid withdrawal.

Transplantation of kidneys harvested from non‐heart‐beating donors: early and long‐term results

Abstract  The purpose of this retrospective study was to evaluate results of non‐heart‐beating donor (NHBD) kidney transplantation. Between Jan 1986 and Dec 1994,80 out of 582 cadaveric kidneys were harvested from NHBD (31.9 min ± 24 after cardiac arrest). The results in the NHBD group (76 recipients) were compared with those obtained after transplantation of kidneys harvested from heart‐beating donors (HBD) with respect to early graft function, and the graft and recipients survival. Both groups were matched for sex, age, PRA level, number of HLA mismatches, and cold ischemia time. Triple immunosuppression therapy was used in both groups. Acute tubular necrosis (ATN) was observed significantly more frequently in the NHBD group (50 of 76 recipients vs 33 of 100 in the HBD group). The striking finding of this study was that the occurrence of primary non‐function was the same in both groups and that the main cause of it was acute rejection. The 1‐year patient and graft survival rates were 98.7 % and 81.6 % for the NHBD group and 99 % and 90 % for the HBD group, respectively. There was also no statistical difference in the serum creat‐inine concentration in both groups. We concluded that despite an increased incidence of ATN in the NHBD kidney recipients, the long‐term results are good and comparable with those in the HBD group.

Surgical complications observed in simultaneous pancreas-kidney transplantation : Thirteen years of experience of one center

SIMULTANEOUS pancreas and kidney transplantation (SPKTx) is the procedure of choice for a majority of transplant candidates with end-stage renal disease and diabetes mellitus. Recent evidence supports its benefits on the maintenance of normoglycemia and the arrest or even possibily of reversal of diabetic complications, such as vasculopathy, nephropathy, and neuropathy. However, pancreas transplant has been associated with the highest surgical complication rate of all the routinely performed organ transplant procedures. A significant number of pancreas grafts are lost early post-transplant secondary to surgical complications. Over the last decade, the operative procedure has been refined and immunosuppressive regiments have improved such that 1-year graft survival routinely exceeds 75%. The purpose of this study was to assess our improved results and to determine other risk factors that may help us decrease the complication rate further.

Simultaneous pancreas-kidney transplantation: analysis of donor factors

There are no urgent indications for simultaneous pancreas-kidney transplantation. So our policy is to harvest only a pancreas in good biologic condition. The criteria for acceptance of a pancreas donor are: age 15 to 40 years, ICU stay < 7 days, no clinical signs of infection, negative virologic status, no history of hypotension or cardiac arrest, serum amylase elevation below three times normal values, controllable hyperglycemia, no history of pancreatic disease, no history of abdominal trauma damaging the organ, no history of alcohol addiction, BMI < 25, no functional or anatomical lesions of the kidneys, and expected ischemia time less than 12 hours. The proper selection of a pancreas donor allows one to achieve good insulin secretion immediately after transplantation. In 2000 to 2002 all 20 pancreases transplanted at transplant center displayed immediate secretory function after transplantation.

36-Month follow-up of 75 renal allograft recipients treated with steroids, tacrolimus, and azathioprine or mycophenolate mofetil

OBJECTIVES The aim of this retrospective study was to assess the incidence of acute rejection episodes (AR), diabetes mellitus (DM), and serum creatinine (SCr) among renal transplant recipients treated with tacrolimus (Tac), steroids (S), and mycophenolate mofetil (MMF) or azathioprine (Aza). METHODS Seventy-five renal allograft recipients enrolled in the COSTAMP study were followed for a period of 3 years. Patients were randomized to receive either Tac and MMF (n = 41) or Tac and Aza (n = 34) concomitantly with steroids. Follow-up assessments were performed at 3, 6, 12, 24, and 36 months. RESULTS Patient survival at month 36 was 91.18% in the Tac/Aza/S group and 97.56% in the Tac/MMF/S group. Graft survival at month 36 was 82.35% and 85.37%, respectively. During the study period, 22 cases of biopsy-proven AR were diagnosed in 17 patients (22.6%). After 36 months the total number of AR was 11 in the Aza-treated group (32.4%) and 11 in the MMF-treated group (26.8%). DM was diagnosed de novo in 17 individuals (22.6%). During 36 months, 10 patients from Aza-treated group (29.4%) and seven from MMF-treated group developed DM (17.1%). Serum creatinine values were not significantly different in both arms of the study. Comparison of arterial blood pressure and total cholesterol revealed no significant changes in any of the studied groups. CONCLUSIONS We conclude that combinations of steroids, tacrolimus, and azathioprine or MMF provide good results with regard to renal function.

In situ perfusion and UW solution used for storage did not decrease the incidence of ATN in kidneys harvested from hemodynamically unstable donors.

Abstract The incidence of acute tubular necrosis ATN after cadaveric kidney transplantation in our centre has been in the range of 50%. A prospective study was carried out in 1991 and 1992 to assess the effect of in situ perfusion and hypothermic storage of kidneys harvested from brain‐dead haemodynamically stable and unstable donors. Three litres of Ringers solution were used for in situ perfusion. In 40 cases, the kidneys were stored in Euro‐Collins (EC) solution and in the other 78 cases, in University of Wisconsin (UW) solution. Among the factors that could contribute to ATN, we analysed warm ischaemia time, anastomosis time and cold storage time. Function was considered to be delayed if the patient required posttransplantation dialysis. The donors were considered haemodynamically unstable when hypotension before harvesting was present (BP < 70 mm Hg over 2 h) despite high doses (> 15 μg/kg per minute) of dopamine or when cardiac arrest occurred at the time of harvesting and oliguria had been present for at least 2 h. Haemodynamically stable donors with a BP greater than 80 mm Hg had a normal diuresis. In all donors in this group the dose of dopamine was lower than 10 μg/kg per minute. The study showed that storage in UW solution did not influence the incidence of ATN in kidneys harvested from haemodynamically unstable donors. Differences observed in our study were due to haemodynamic status preceding donor nephrectomy and length of cold storage time.

Can the immunosupressive effect of perioperative single high-dose antithymocyte globulin administration in kidney allograft recipients be due to apoptosis of activated lymphocytes?

DESPITE that the new, potent immunosuppressive medications (tacrolimus, mycophenolate mofetil, sirolimus) have been widely used, the monoclonal or polyclonal antilymphocytic antibodies are still being used in organ transplant recipients. Antibodies are more often used as induction therapy, particularly in high-risk patient populations. Until recently the induction therapy consisted of the use of antibodies for 7 to 12 days after transplantation and withdrawal of calcineurin inhibitors for the first week. Antithymocyte globulin (ATG) treatment induces a profound depletion of peripheral blood lymphocytes. The precise mechanism of action of ATG remains largely unknown. Various mechanisms have been proposed to explain lymphocyte depletion, including complement-mediated cytolysis or clearance of lymphocytes by opsonization and phagocytosis by macrophages. Apoptosis has also been suggested as a possible mechanism of lymphocyte depletion by ATG. This biologic agent has been the mixture of polyclonal antibodies with various lymphocyte surface antigens. It contain antibodies to CD2 and CD3, which accounts for the mitogenic properties. Published results of in vivo and in vitro tests indicate that the effect of ATG can be due to binding to CD2 , CD3 , CD4 , CD4 /CD28 , CD5 , CD7 , LFA-1 , and ICAM-1 lymphocytes. The rationale for the perioperative use of monoclonal or polyclonal antibodies is based on the fact that sensitization of the recipient’s immune system begins immediately after revascularization of the graft. ATG in that respect seems to have wider specificity than new anti-IL2 receptor antibodies. Kaden et al were the first to propose the perioperative administration of a single, high dose of ATG in patients receiving cadaveric kidney transplantation. Their positive results prompted other investigators to use the same protocol. In these studies the basic immunosuppressive protocol consisted of Neoral (cyclosporine), steroids, and azathioprine. Our preliminary results of a prospective randomized study of in vivo immunosuppressive activity of high, single dose (9 mg/kg) of ATG administered immediately before revascularization to kidney allograft recipients receiving triple-drug immunosupression (Neoral, steroids, mycophenolate mofetil) showed that this protocol is effective and allowed good patient and graft 2-year survival (Table 1). The follow-up ranged from 24 months up to 3 years. There were no side effects or differences in serious adverse events reported during observation period. The incidence of delayed graft function occurred, although not significantly, more often in the control group (16 of 39 vs 20 of 40 patients). There was no difference in 2-year patients and graft survival between groups. Two-year graft survival in ATG-treated patients with and without acute tubular necrosis (ATN) was 80% vs 90%. In the control group, the graft survival in patients with and without ATN was 75% and 95%, respectively. The onset of acute rejection was delayed and the number of rejection episodes were lower in ATG-treated patients. The difference between groups in that respect was statistically significant. A higher number of lost grafts in the control group correlated with delayed graft function.

Geography of the Referred Potential Liver Recipients and Donors in Poland in 2004

Our aim was to assess the accessibility of potential liver recipients to cadaveric organs and the ability of transplant teams to realize recipients needs in Poland in 2004. Our calculations revealed that in Poland the number of cadaveric liver transplants was two to three times lower than in other countries and is insufficient to meet the needs, also the number of referred potential liver recipients is two to three times lower than expected.