Thrombotic microangiopathy following pancreas after kidney transplants

Abstract:  Advances in immunosuppressive therapy and refinement in surgical techniques have allowed pancreas after kidney (PAK) transplantation to become a viable therapeutic option for patients with brittle type I diabetic recipients of a living donor or previous deceased kidney alone transplant. Although maintenance immunosuppressive therapy is not significantly changed after the addition of a pancreas, a temporary booster in immunosuppressive therapy and an increase in the dose of calcineurin inhibitor (CNI) are required after PAK transplantation. The latter has been implicated in the observed variable decline in kidney allograft function. We herein report two cases of kidney allograft dysfunction following PAK transplant due to biopsy-proven transplant, thrombotic microangiopathy (TMA). Whether PAK transplantation pre-disposes a subset of patients to the development of post-transplant TMA is not known. Diagnostic kidney biopsies should be considered in PAK transplant recipients with worsening kidney allograft function.     

Appropriateness and timing of kidney and/or pancreas transplants in type 1 and type 2 diabetes

Cure of diabetes through cell or organ transplantation remains an unattained but highly desirable goal. For now, prevention of end organ complications of diabetes is the most appropriate application of transplantation for patients with enough evidence of progressive disease to justify the substantial surgical and immunosuppression-based risks of pancreas transplantation. Uremic diabetics should, if possible, be offered renal transplantation, alone or in combination with pancreas transplantation, to obviate the excessive mortality associated with prolonged maintenance dialysis. Islet transplantation has been widely clinically unsuccessful but holds new promise as the therapy of choice for the future. This report reviews the history, state of the art, and selection process for timing and application of currently available transplantation modalities for diabetic patients.     

Kidney allograft and patient survival in type I diabetic recipients of cadaveric kidney alone versus simultaneous pancreas kidney transplants: a multivariate analysis of the UNOS database

Simultaneous pancreas-kidney transplant (SPK) is now a common treatment for insulin-dependent diabetic patients with end-stage renal disease. Renal graft survival rates after SPK have been less well studied. This study compared the kidney survival results for 3642 SPK and 2374 cadaveric renal transplants (CRT) in type I diabetic patients at 112 US transplant centers reported to UNOS during 1994 through 1997. The analysis included follow-up information through September 2000. The kidney graft survival rates were significantly lower among recipients of CRT compared with SPK recipients (P < 0.001). Patients who received SPK were younger, less often sensitized, transplanted after shorter periods on dialysis, and less often black. The donors of SPK organs were younger, more often died from head trauma, were less often female, and more often black. SPK renal grafts were transplanted with a shorter cold ischemia time to more poorly HLA-matched recipients. After adjustment of these and other factors, whether a patient was recipient of CRT or SPK was not associated with increased risk of kidney graft failure or patient death. SPK recipients experienced half the rate of delayed kidney function (11% versus 23%) but nearly double the rate of rejections during the initial hospitalization (15% versus 9%) compared with CRT recipients. SPK was associated with better renal allograft survival compared with CRT, despite a higher rate of renal allograft rejection. This observation was explained by favorable donor and recipient factors in the SPK group. After controlling for these factors, SPK provided no protective or detrimental effect on short-term renal allograft or patient survival.     

Pancreas after kidney transplants

BACKGROUND: For certain uremic diabetic patients, a sequential transplant of a kidney (usually from a living donor) followed by a cadaver pancreas has become an attractive alternative to a simultaneous transplant of both organs. The purpose of this study was to compare outcomes with simultaneous pancreas-kidney (SPK) versus pancreas after kidney (PAK) transplants to determine advantages and disadvantages of the two procedures. METHODS: Between January 1, 1994, and June 30, 2000, we performed 398 cadaver pancreas transplants at our center. Of these, 193 were SPK transplants and 205 were PAK transplants. We compared these two groups with regard to several endpoints, including patient and graft survival rates, surgical complications, acute rejection rates, waiting times, length of hospital stay, and quality of life. RESULTS: Overall, surgical complications were more common for SPK recipients. The total relaparotomy rate was 25.9% for SPK recipients versus 15.1% for PAK recipients (P = 0.006). Leaks, intraabdominal infections, and wound infections were all significantly more common in SPK recipients (P = 0.009, P = 0.05, and P = 0.01, respectively, versus PAK recipients). Short-term pancreas graft survival rates were similar between the two groups: at 1 year posttransplant, 78.0% for SPK recipients and 77.9% for PAK recipients (P = not significant). By 3 years, however, pancreas graft survival differed between the two groups (74.1% for SPK and 61.7% for PAK recipients), although this did not quite reach statistical significance (P = 0.15). This difference in graft survival seemed to be due to increased immunologic losses for PAK recipients: at 3 years posttransplant, the incidence of immunologic graft loss was 16.2% for PAK versus 5.2% for SPK recipients (P = 0.01). Kidney graft survival rates were, however, better for PAK recipients. At 3 years after their kidney transplant, kidney graft survival rates were 83.6% for SPK and 94.6% for PAK recipients (P = 0.001). The mean waiting time to receive the pancreas transplant was 244 days for SPK and 167 days for PAK recipients (P = 0.001). CONCLUSIONS: PAK transplants are a viable option for uremic diabetics. While long-term pancreas graft results are slightly inferior to SPK transplants, the advantages of PAK transplants include the possibility of a preemptive living donor kidney transplant, better long-term kidney graft survival, significantly decreased waiting times, and decreased surgical complication rates. Use of a living donor for the kidney transplant expands the donor pool. Improvements in immunosuppressive regimens will hopefully eliminate some of the difference in long-term pancreas graft survival between SPK and PAK transplants.     

Complications of kidney transplants]

Increasingly more publications are reported on reassuring results after kidney transplantation. After some initial difficulties promising results were achieved on three patients who now live with a transplanted kidney. The importance of improving diagnostic possibilities and the reduction of damages caused by immunosuppressive drugs is stressed and the possibility of altering if necessary the combination of drugs is suggested.     

Percutaneous biopsy of bladder-drained pancreas transplants.

Percutaneous biopsy is a valuable investigation in the management of allograft rejection for all solid organs. Pancreas transplants have not been biopsed percutaneously, though open and percystoscopic biopsies have proved useful. We have compared percutaneous needle core biopsy with fine-needle aspiration cytology for the diagnosis of rejection in 18 patients receiving combined kidney and pancreas transplants and in one who was transplanted with the pancreas alone. Percutaneous needle core biopsy was successful in 37 of 40 attempts (93%), while fine-needle aspiration yielded diagnostic material on 33 of 47 attempts (70%). Transient hyperamylasemia occurred in 29%, returning to baseline in three days. One patient twice developed transient macroscopic hematuria. There was agreement between needle core biopsy and fine-needle aspiration on the diagnosis of rejection on six occasions and for the absence of rejection on 16. There was an 8% false-positive rate for fine-needle aspiration. In 13 instances of histologically proved renal rejection, concurrent pancreas biopsy revealed rejection in 69%. Pancreas rejection was not, however, seen in the absence of renal rejection. In this pilot study, percutaneous biopsy of the bladder-drained pancreas allograft was shown to be a practicable and valuable investigation without major complications.     

Outcomes of shipped live donor kidney transplants compared with traditional living donor kidney transplants

The disparity between kidney transplant candidates and donors necessitates innovations to increase organ availability. Transporting kidneys allows for living donors and recipients to undergo surgery with a familiar transplant team, city, friends, and family. The effect of shipping kidneys and prolonged cold ischemia time (CIT) with living donor transplantation outcomes is not clearly known. This retrospective matched (age, gender, race, and year of procedure) cohort study compared allograft outcomes for shipped live donor kidney transplants and nonshipped living donor kidney transplants. Fifty‐seven shipped live donor kidneys were transplanted from 31 institutions in 26 cities. The mean shipping distance was 1634 miles (range 123–2811) with mean CIT of 12.1 ± 2.8 h. The incidence of delayed graft function in the shipped cohort was 1.8% (1/57) compared to 0% (0/57) in the nonshipped cohort. The 1‐year allograft survival was 98% in both cohorts. There were no significant differences between the mean serum creatinine values or the rates of serum creatinine decline in the immediate postoperative period even after adjusted for gender and differences in recipient and donor BMI. Despite prolonged CITs, outcomes for shipped live donor kidney transplants were similar when compared to matched nonshipped living donor kidney transplants.