A survey: the prevalence of laparoscopic donor nephrectomy at large U.S. transplant centers.

BACKGROUND: There is controversy whether laparoscopic donor nephrectomy (LDN) is the procedure of choice for live kidney donors. The purpose of this survey therefore was to determine the current practices, attitudes, and plans regarding LDN in high-volume renal transplant centers. METHODS: Medical directors of the 31 highest volume kidney transplant centers were surveyed via telephone. Kidney transplant data for 1998 and 1999 were collected. RESULTS: The surveyed centers performed 5213 transplantations in 1998, representing 43% of all kidney transplantations done nationally. Twelve (39%) of the 31 centers performed LDN in 1998, increasing to 20 (65%) of 31 in 1999. Of 1174 live donor operations performed by the 20 centers in 1999, 365 (31%) were LDNs. Among the surveyed centers, four had no plans to begin an LDN program. The most commonly cited incentive for LDN was "shorter recovery time," whereas the most common disincentive was "concern about graft quality." A combination of observation and animate laboratory was the most commonly reported method of learning the LDN procedure. Six-month follow-up interviews found that 26 (84%) of 31 centers had performed LDN; only 1 of the 31 centers had no plans to perform LDNs. CONCLUSIONS: LDN may be the de facto procedure of choice for live donors within the next year. Efforts should now focus on improving techniques for performing and teaching this procedure.

Successful long-term kidney-pancreas transplants regardless of C-peptide status or race.

BACKGROUND: We have previously shown that our patient population of 60% minority races has end-stage renal disease primarily as a result of diabetes mellitus and hypertension. It therefore was logical to explore the restoration of normal insulin production and renal function by simultaneous pancreas-kidney (SPK) transplantation, without regard to race. This study represents new analyses integrating race with C-peptide status and reports the outcome of 136 SPK transplantations performed over the last 10 years. RESULTS: Of the 49 African-Americans with diabetes mellitus and end-stage renal disease, 60% were type I and 40% were type II, based on C-peptide levels. In comparison, only 16% of Caucasians were type II. The average age at onset of diabetes mellitus was 15.7 years for type I compared with 20.7 years for type II (P>0.05). The actuarial 10-year survival rates for the 136 SPKs were 91.79% (patient), 85.07% (pancreas), and 83.58% (kidney). The type I and type II survival rates were similar in the two diabetic groups. CONCLUSIONS: The data strongly suggest that pretransplant C-peptide status does not influence the outcome of SPK transplantation in patients with renal failure from diabetes mellitus. SPK transplants should be offered to all suitable diabetic patients with renal failure regardless of C-peptide status or race.

A comparison of daclizumab to ATGAM induction in simultaneous pancreas-kidney transplant recipients on triple maintenance immunosuppression.

Daclizumab (DAC) is a molecularly engineered humanized IgGa monoclonal Ab directed against the alpha chain of the interleukin-2 receptor (IL2R). Inhibiting the amplification of the immune response by blocking IL2R can reduce the frequency of acute rejection without the attendant risk of infection. The purpose of this retrospective study was to compare DAC to antithymocyte (ATGAM) induction in 24 simultaneous pancreas-kidney (SPK) transplants performed between September 1995 and September 1998. The primary endpoints were the incidence within 6 months posttransplant of: 1) biopsy-proven acute rejection; and 2) infection. The two groups (DAC, n = 12; ATGAM, n = 12) were matched on age, race, ESRD, number of HLA mismatches, PRA level, and cold ischemia time. DAC (1 mg/kg) was given on the day of transplant, then every other week (a total of five doses); ATGAM (15 mg/kg) was given on post-transplant day 1, then daily for 7-10 d. Immunosuppressive therapy consisted of cyclosporine (Neoral 8-10 mg/kg/d) or Prograf (0.16-0.2 mg/kg/d), mycophenolate mofetil (Cell- 2-3 g/d) and steroids. Of the 12 DAC patients, 3 patients (25%) had biopsy-proven acute rejection versus 8/12 (67%) of the ATGAM patients. The time to acute rejection was significantly different by group (DAC = 110 d; AT-GAM = 26 d). There was a reduction in the number of patients receiving antilymphocyte drugs for moderate to severe rejection (DAC = 2/12; ATGAM = 4/12), with 2 of the 4 ATGAM patients experiencing more than two episodes of biopsy-proven rejection. There was an increase in infection by group (DAC = 4/12; ATGAM = 7/12): total of three septic infections occurred in the ATGAM group opposed to none in the DAC group. Patient, pancreas, kidney 6-month survival rates were 100% for both groups. We conclude that DAC induction coupled with triple immunosuppressive therapy reduces the incidence of rejection in SPK transplant patients. The time to acute rejection was prolonged in the DAC group compared with the ATGAM group without the attendant risks of rejection.

Is laparoscopic donor nephrectomy the new criterion standard?

HYPOTHESIS: The posttransplantation renal function outcomes between consecutive open donor and laparoscopic donor nephrectomies (LDNs) are similar and affect living donation. DESIGN: Using the medical records of renal living donor-recipient pairs, 36 consecutive open donor nephrectomies were compared with the subsequent 100 LDNs. Data collected on donor characteristics included demographics (age, race, sex, weight, and height), renal vascular and ureteral anatomical features, surgical information (blood loss, number of blood transfusions, operating time, warm ischemia time, and renal injury), complications, and length of hospital stay. Recipients' data also included renal function information (serum creatinine level on postoperative days 7 and 30) and ureteral complications during the initial hospital stay. SETTING: A not-for-profit tertiary care teaching hospital in a metropolitan area. PATIENTS: Adults who had end-stage renal disease and received a living donation kidney. MAIN OUTCOME MEASURES: Operative time, warm ischemia time, blood loss, and posttransplantation serum creatinine level. RESULTS: Patient characteristics were not significantly different between the open donor nephrectomy and LDN groups. No right kidney LDNs were done because of the shortness of the right renal vein; and, after the initial experience, left kidneys with more than 2 arteries were excluded. Warm ischemia time was recorded only for LDN, and it was found that a warm ischemia time of 10 minutes or longer was associated with difficulty in extraction and was uniformly associated with elevated mean serum creatinine levels on postoperative day 7. CONCLUSIONS: The length of hospital stay was decreased and cosmetic result enhanced. The number of living donors has increased from 28 in 1997 to 53 in 1998 and to 63 in 1999 at our institution. The length of hospital stay, incidence of complications, and comparable kidney quality indicate that LDN should be the initiating procedure for most patients.

Tacrolimus vs Neoral in renal and renal/pancreas transplantation.

In a retrospective analysis we compared the outcome of a group of 63 kidney or kidney/pancreas transplant recipients who were transplanted between June 1994 and February 1997 and received either tacrolimus (FK, n = 22) or Neoral (NEO, n = 41) as part of a triple immunosuppressive protocol. Ten patients in the NEO group has recurrent rejection episodes between 1 and 8 months post-transplant and were converted to FK. CellCept was the secondary immunosuppressive agent in about half the FK, three-quarters of the NEO, and in all but one in the conversion (CON) groups. Patients in all groups were on prednisone in equal amounts. Mean duration of follow-up for FK, NEO and CON groups was 32, 19 and 13 months, respectively. One-yr patient and graft survival was 100% in all groups. At 2 yr, graft survival was 95, 96 and 100% in FK, NEO and CON groups, respectively. Acute rejection at 1 yr was twice as high in the NEO group as the FK group. There were no rejection episodes among the FK patients who also received CellCept. The mean current serum creatinines (mg%) were: FK = 1.6, NEO = 1.8, CON = 1.9. Recurrent infection was more common with FK (8/22) than NEO (1/31) (p = 0.023). Our experience suggests there is less rejection but more infection in recipients treated with FK compared to NEO. In patients with recurrent rejection, conversion from NEO to FK stabilizes renal function and minimizes subsequent rejection episodes.

Long-term graft survival after transplantation with kidneys from uncontrolled nonheartbeating donors.

BACKGROUND: Notwithstanding the widely acknowledged organ-donor shortage coupled with the expanded waiting list for organs, many transplant programs have been reluctant to use kidneys from nonheartbeating donors. Some reasons expressed by those programs include a higher rate of delayed graft function, additional dialysis requirements, more medication usage, and inferior graft survival rates. To refute the common misperceptions, we reviewed our 4-year experience with 31 nonheartbeating donor kidneys recovered from uncontrolled donors (Maashticht classification) at our institution. METHODS: After cardiac arrest and declaration of death, all donors underwent intravascular and intraperitoneal cooling. Immediately after bilateral en bloc nephrectomy, kidneys were placed on the Waters MOX pulsatile preservation machine. Preservation parameters were monitored hourly, using pharmacologic agents (Stelazine, dexamethasone, Humulin R) as indicated by those parameters. RESULTS: The nonheartbeating donors ranged in age from 15 to 53 years, 83% were males, and 60% of deaths were caused by trauma. For the 21 recovered and transplanted at our center, delayed graft function occurred with 16 kidneys; there was no primary nonfunction. There was no obvious correlation between functional status and donor age. It was noted that the immediate-function kidneys had shorter warm ischemia and total preservation times compared with the delayed graft function group. Nineteen of the 21 grafts continue to function. All patients are surviving. CONCLUSIONS: This series suggests that to obtain excellent results with nonheartbeating donor kidneys certain principles should be followed: use machine preservation to resuscitate and evaluate viability, choose immunologically low-risk recipients, avoid immediate exposure to immunophilin antagonists, and perform biopsy frequently for allograft dysfunction to exclude low-grade rejection.

Successful long-term kidney-pancreas transplants in diabetic patients with high C-peptide levels.

BACKGROUND: Pancreas transplants are rarely done in type 2 (noninsulin dependent) diabetic patients. Most researchers believe that in type 2 diabetic patients, peripheral insulin resistance plays a central role and also is associated with relative insulin deficiency or an insulin secretory defect. This suggests that in patients receiving transplants, the new beta cells will be overstimulated, leading to beta cell "exhaustion" and graft failure. METHODS: Early in our experience, simultaneous pancreas-kidney transplant candidates were selected using only clinical criteria for type 1 diabetes, i.e., early onset of diabetes and rapid onset of insulin use. Pretransplant sera were available for C-peptide analysis in 70 of 94 of those patients. Forty-four percent (31/70) were African American (AA). RESULTS: Thirteen patients (12 AA) with a nonfasting C-peptide level >1.37 ng/ml were identified. In these patients with high C-peptide levels, pancreas and kidney survival rates were 10O%. The results did not differ statistically from the low C-peptide group (< or =1.37 ng/ ml). There were no differences between patient and pancreas-kidney survival rates when the patients were separated into AA and non-AA groups. The follow-up was 1-89 months, with a mean of 45.5 months. CONCLUSIONS: Long-term pancreas graft function is attainable and beta cell "exhaustion" does not occur in patients with high preoperative C-peptide (>1.37 ng/ ml) levels. AA and non-AA patients have equivalent long-term patient, kidney, and pancreas-kidney graft survival rates.

Donor hepatitis C virus status does not adversely affect short-term outcomes in HCV+ recipients in renal transplantation.

BACKGROUND: Recipient hepatitis C virus (HCV) seropositivity has been associated with inferior outcomes in renal transplantation (RTx). We sought to determine whether donor HCV+ status influenced the incidence of rejection, liver dysfunction, and graft survival in HCV+ recipients. METHODS: We reviewed 44 HCV+ recipients (R+) receiving RTx from HCV+ (D+) and HCV- (D-) donors between February 1991 and September 1996. All patients were followed to the end of the study period (mean=36 months, range=12-60 months). We compared the R+ group with a demographically matched cohort of 44 HCV- recipients (R-). RESULTS: Of the 44 R+, 25 (57%) had a total of 48 rejection episodes. Among the 44 R-, 32 (73%) had 58 rejection episodes (P>0.1). Within the R+ group, 28 were D+/R+; of these 14 (50%) had 27 rejection episodes, whereas among the 16 D-/R+, 11 (68%) had 21 rejection episodes (P>0.3). Graft and patient survival was similar in both the groups (86.4% and 91%, respectively). Liver dysfunction was slightly increased in the R+ group (4/44 vs. 0/44, P>0.1), with one death due to liver failure in this group. CONCLUSION: Donor HCV+ status had no influence on outcomes in HCV+ recipients after kidney transplantation in the short term. The incidence of rejection, graft loss, and mortality was comparable between the D+/R+ and D-/R+ groups. Furthermore, rejection, graft loss, and death were identical in R+ and R-groups throughout the 5-year study period. We therefore conclude that HCV+ recipients can safely receive kidney transplants without concern about donor HCV status or fear of adverse events from their own HCV+ status.

Increased beta 2-microglobulin (B2M) is useful in the detection of post-transplant lymphoproliferative disease (PTLD).

This study examines whether changes in beta 2-microglobulin (B2M) serum levels are useful in the early detection of post-transplant lymphoproliferative disease (PTLD). Serum B2M is monitored daily post-transplant at our center as a marker of change in lymphocyte activation. We identified 16 cases (16/1359; 1.2%) of PTLD from among 1359 kidney and kidney-pancreas transplants. Those with CNS lymphoma (two patients) and titer change only (one) were not included in this review. Thirteen patients had serum titer and clinical evidence of EBV activity; 12 of these patients had histological evidence of PTLD (lymph node 6, kidney 3, and generalized disease 3). Three patients died with disseminated PTLD infection. Nine are alive but only two have the original transplant kidney. All patients received quadruple immunosuppression for induction, and 11 were subsequently treated with OKT3 or ALG for rejection. The mean number of days of induction ALG therapy was 14.8 d (20 mg/kg/d). The mean number of days of OKT3 therapy for rejection was 14.4 d (5 mg/d). During rejection the highest mean creatinine level was 6.8 mg/dL, and the highest mean B2M level was 16.4. With PTLD, the highest mean creatinine level was 7.0 mg/dL and the highest mean B2M level was 32.3 mg/L. The difference in creatinine levels was not significant, but the difference in B2M levels was significant (p < 0.01). We conclude that B2M levels are useful markers in differentiating rejection from PTLD.

A rapid organ recovery program for non-heart-beating donors.

We report a successful method for rapid organ recovery from the non-heart-beating donor, which can open a new resource of organs for transplantation. The RORP is not controversial, is simple in design and execution, and results in kidneys that are viable for transplantation. Special personnel and equipment are needed but are easily incorporated in the overall budget of an OPO or donor hospital. Clearly more research is needed to rebuild ischemically damaged cells ex vivo and to develop new agents/methods to minimize the reperfusion response. When these processes are better understood and managed, the full potential of the NHBD as a donor resource will be fully achieved. We agree with others that the donor shortage could be entirely relieved by routine organ recovery from NHBD trauma victims.

Acute respiratory failure and pulmonary fibrosis secondary to administration of mycophenolate mofetil.

BACKGROUND: We report the first documented case of pulmonary toxicity to mycophenolate mofetil in this article. METHODS: A 51-year-old woman experienced systemic reactions beginning 10 days after cadaveric renal transplantation. RESULTS: Recurrent respiratory failure and documented progressive pulmonary fibrosis ensued. Cultures were negative and other agents were discontinued. It was not until the mycophenolate was stopped did the patient improve. CONCLUSIONS: Mycophenolate mofetil can cause acute respiratory failure simulating opportunistic infection or pulmonary edema. If not recognized, this may lead to the rapid development of severe pulmonary fibrosis, some of which may not be reversible.

A new approach for increasing the organ supply.

The donation of organs and tissues for the benefit of another person is an altruistic act and one that is a guaranteed option for the next-of-kin through various national Required Request legislations. At the Washington Hospital Center we have developed an approach that permits organ recovery from non-heart beating donors. The focus is on victims of fatal trauma and assures that each family is empowered with the right to make a donation decision. In October 1993 a consensus conference was held on implementing a program to recover organs from fatal trauma victims. The participants recommended that safeguards be incorporated to assure ethical treatment of both the trauma victim and the next-of-kin. An Office of Decedent Affairs (ODA) was then established and implemented in September 1994. The ODA is staffed by Family Advocates who are on duty continuously and respond to all trauma and death events. Their mission is to consolidate all death events, provide support to decedent families, assure that required request mandates are fulfilled, interact with the local Organ Procurement Organization (OPO) in the consent process, and facilitate the implementation of the Rapid Organ Recovery Program (RORP). The RORP consists of two specific procedures: cannulation of the femoral arterial-venous system for flushing the kidneys with a preservative solution, and intubation of the peritoneum for in situ cooling using an ice/lavage process. In the 1-yr period since the ODA was established, organ and tissue donation has increased by more than 300%.

Immediate function and cost comparison between static and pulsatile preservation in kidney recipients.

During a 1-yr period between September 1993 and September 1994, 74 patients received cadaveric kidney transplants at our institution. Thirty nine (39) kidneys were cold stored (CS), while 35 received pulsatile preservation (PP) on the Water's Mox system using U.W. Machine Preservation Solution. A perfusionist maintained pressure, flows, pH, and osmolality, within accepted ranges. Vasodilators (Regitine, Stelazine, Verapamil) were routinely added to the machine preservation solution. Most kidneys on PP were from marginal donors, or were imported and had associated long ice storage times. The CS kidneys, however, were from "ideal donors" where immediate function (IF) was expected. The kidneys were transplanted using a common protocol by a variety of surgeons. PP was associated with higher IF rates, shorter hospital stay and decreased overall costs. The function of those kidneys was also compared with the mate kidneys, obtained through a telephone survey of the various transplant centers throughout the country. PP was again associated with higher immediate function rates.

New profile of cadaveric donors: what are the kidney donor limits?

The need for donor organs is increasing more rapidly than the number of organs available from present resources using today's techniques. While efforts to improve consent rates through education and various incentives should continue, and while recovery and utilization of kidneys from donors at the extremes of age can further improve, we believe that the greatest potential for future expansion of the donor resource lies in the non-heart-beating donor. The combination of effective in situ preservation and ex vivo pulsatile preservation allows donation to occur from uncontrolled asystolic donors and provides a mechanism for both evaluation and resuscitation of the recovered kidneys. This approach, if fully utilized, can double the number of kidneys available for transplantation.