Prevention of renal allograft rejection without immune suppression: a model to revisit.

Spectacular success in preventing renal allograft rejection in rats was obtained over 40 yr ago using only the reactants of the response: donor-type antigen and homologous antiserum directed against donor-type antigen. Tolerance was antigen specific and sustained by persistent antigen of the graft. The model has never been tested rigorously in a large species, though the rationale for why the procedures should work applies across species including humans. Confirming the results in a large species would have profound impact on research for treating multiple immune mediated diseases, in addition to providing a way for treating some transplant recipients. This is a propitious time to confirm the applicability to larger species. If successful, only the lack of imagination limits the potential impact.

Proposed classification of complications after live donor nephrectomy.

OBJECTIVES: A standardized classification for the potential complications of living donor nephrectomy is an essential step in establishing a construct for monitoring and reporting the outcomes of this procedure. It is also helpful in informing potential donors about the inherent risks of the donor operation as part of the informed choice process. METHODS: We reviewed 600 laparoscopic live donor nephrectomies performed at our center. A modification of the Clavien classification system describing procedure-related complications was developed and used to grade the severity of all complications. RESULTS: We observed 43 complications (7.2%) in our series of 600 patients. Grade 1 defines all events that, if left untreated, would have a spontaneous resolution or needed a simple bedside procedure (39.5%). Grade 2 complications differ from grade 1 in that they are potentially life-threatening and usually require some form of intervention, but do not result in ongoing disability. We subdivided grade 2 complications (55.8% in our study) into 2a, 2b, and 2c. The latter describes complications requiring open conversion of laparoscopic donor nephrectomy for patient treatment. Grade 3 complications are events with residual or lasting disability (4.7% in our review). Grade 4 events are those resulting in renal failure or death because of any complication (none occurred in our series). CONCLUSIONS: A graded classification scheme for reporting the complications of donor nephrectomy may be useful for maintaining registry information on donor outcomes and when informing potential donors about the risks and benefits of this procedure.

Alemtuzumab induction and prednisone-free maintenance immunotherapy in kidney transplantation: comparison with basiliximab induction--long-term results.

This study examined alemtuzumab (anti-CD 52, Campath-1H) and basiliximab (anti-CD 25, Simulect) as induction immunosuppression in kidney transplantation. We used a single-center, nonrandomized, retrospective, sequential study design to evaluate outcomes in kidney transplant recipients given either alemtuzumab (n = 123) or basiliximab (n = 155) induction in combination with a prednisone-free maintenance protocol using tacrolimus and mycophenolate mofetil. Kaplan-Meier analyses of long-term patient and graft survivals and rejection rates were determined according to induction agent, donor source and recipient ethnicity. Secondary endpoints included the quality of renal allograft function and the etiology of infectious complications. Overall long-term patient and graft survival rates did not significantly differ between patients treated with alemtuzumab and basiliximab. A lower rate of early (<3 months) rejection was observed in the alemtuzumab (4.1%) versus the basiliximab (11.6%) group, but the rates for both groups were equivalent at 1 year. Patient and kidney survival and rejection rates were nearly identical between Caucasians and African Americans that received alemtuzumab. Quality of renal function and incidence of infectious complications were similar in the two groups. Alemtuzumab induction therapy was similar in efficacy to basiliximab in a prednisone-free maintenance immunosuppressive protocol for an ethnically diverse population of kidney transplant recipients.

Laparoscopic donor nephrectomy 1997 to 2003: lessons learned with 500 cases at a single institution.

BACKGROUND: Laparoscopic live donor nephrectomy (LDN) is a less invasive alternative to traditional open nephrectomy that has several potential advantages. However, there have been few large series reports describing the complications of LDN and the details of their management. METHODS: We performed a retrospective review of 500 LDNs performed at our center between October 1997 and September 2003. We evaluated preoperative donor characteristics, intraoperative parameters and complications, and postoperative recovery and complications. A modification of the Clavien classification was developed and used to grade the severity of all complications. RESULTS: The overall rate of intraoperative complications was 2.8%. There were 9 open conversions (1.8%), of which 6 were in the first 100 cases. Six of the 9 open conversions were for management of complications; 3 were elective. Seven renovascular incidents (1.4%) all required open conversion except one. The overall rate of postoperative complications was 3.4%. Thirty of 500 patients in our LDN series experienced an intraoperative or procedure-related complication (6.0%). When graded by severity, 18 of 31 (58.1%) of all complications were grade 1, 11 of 31 (35.4%) grade 2, and 2 of 31 (6.5%) grade 3. Only 1 recipient experienced delayed graft function, and only 1 recipient had a urologic complication. CONCLUSIONS: Our series supports the safety and efficacy of LDN with very low intraoperative complication and conversion rates. Most of the intraoperative complications can be managed laparoscopically. Readmissions are extremely rare (1.5%). Aberrant vascular anatomy and obesity are not contraindications to LDN, but they require experience. With careful surgical technique, delayed graft function and urologic complications in recipients can be avoided. A graded classification scheme for reporting complications of donor nephrectomy might be useful for maintaining registry information on donor outcomes and when informing potential donors about the risks and benefits of this procedure.

Technical and immunologic progress in simultaneous pancreas-kidney transplantation.

BACKGROUND: During the past few years the use of new immunosuppressants and refinements in surgical technique of simultaneous pancreas-kidney (SPK) transplantation have resulted in markedly improved outcomes. This is a retrospective study of 208 SPK transplants performed at Northwestern University, demonstrating the advances made at a single center that are reflective of the field at large. METHODS: An 8.5-year time span was split into 4 distinct eras marking sequential changes in immunosuppression and surgical technique that ensued. SPK transplant outcomes of patient and graft survival and rejection rates were compared. Also examined were end points related to the changing risk profile of the recipients, as well as quality of allograft function and rates of rehospitalizations. RESULTS: Recipients receiving tacrolimus/mycophenolate mofetil-based immunosuppression had patient, kidney, and pancreas survival rates significantly higher than those of earlier cohorts. The elimination of corticosteroids did not reduce survival rates or increase rejection risk. The use of pancreatic exocrine enteric drainage technique over bladder drainage reduced rehospitalizations. CONCLUSIONS: Advances in immunosuppression management combined with technical refinements have made SPK transplantation a safer and more effective treatment option for the diabetic, uremic patient.

Sequential kidney/islet transplantation using prednisone-free immunosuppression.

Islet transplantation is becoming established as a treatment option for type I diabetes in select patients. Individuals with type I diabetes who have previously received a successful kidney allograft may be good candidates for islet transplantation. They have already assumed the risks of chronic immunosuppression, so the added procedural risk of a subsequent islet transplant would be minimal. Furthermore, because of the preimmunosuppressed state it is possible that islet-after-kidney transplantation may result in a more efficient early islet engraftment. Consequently, insulin independence might be achieved with significantly fewer islets than the approximately 8-10,000 islet equivalents/kg/b.w. currently required. A mass that usually demands two or more cadaveric donors. A case of successful islet-after-kidney transplantation is described using the steroid-free Edmonton immunosuppression protocol. Characteristics of the final islet product are: a) islet equivalents: 265,888 (4100 islet equivalents/kg/b.w.); b) islet purity: 75-80%; c) viability: >95% (trypan blue exclusion); and d) mean islet potency (static low-high glucose challenge): 4.16 +/- 1.91-fold increase. Post-transplant the patient's hypoglycemic episodes abated. Exogenous insulin requirements were eliminated at week 12 post-transplant as basal and Ensure (Abbott Laboratories, Abbott Park, IL, USA) oral glucose stimulated C-peptide levels peaked and stabilized. Twenty-four-hour continuous glucose monitoring confirmed moment-to-moment glycemic control, and periodic nonfasting finger stick glucose determinations over the next month confirmed glycemia was controlled. Hemoglobin A1c levels declined from a pretransplant level of 6.9% to 5.3%. Renal allograft function remained changed.

A prospective study of rapid corticosteroid elimination in simultaneous pancreas-kidney transplantation: comparison of two maintenance immunosuppression protocols: tacrolimus/mycophenolate mofetil versus tacrolimus/sirolimus.

BACKGROUND: We examined the feasibility of rapid corticosteroid elimination in simultaneous pancreas kidney transplantation. METHODS: Forty consecutive simultaneous pancreas-kidney (SPK) transplant recipients were enrolled in a prospective study in which antithymocyte globulin induction and 6 days of corticosteroids were administered along with tacrolimus and MMF (n=20) or tacrolimus and sirolimus (n=20). Mean+/-SD follow-up for recipients receiving tacrolimus/MMF and tacrolimus/sirolimus were 12.7+/-3.9 and 13.4+/-2.9 months, respectively. Patient and graft survival, and rejection rates were compared to an historical control group (n=86; mean follow-up 41.5+/-15.4 months) of SPK recipients that received induction and tacrolimus, MMF, and corticosteroids. RESULTS: Demographic characteristics of recipient and donor variables were similar among all groups. The 1-year actuarial patient, kidney, and pancreas survival rates in the 40 SPK transplant recipients with rapid corticosteroid elimination were 100, 100, and 100%, respectively. In the historical control group the 1-year actual patient, kidney, and pancreas survival rates were 96.5, 93.0, and 91.9%, respectively. The 1-year rejection-free survival rate recipients in the rapid steroid elimination group collectively was 97.5 vs 80.2% in the historical control group (P=0.034). At 6 and 12 months posttransplant the serum creatinine values remained stable in all groups. CONCLUSIONS: We conclude that chronic corticosteroid exposure is not required in SPK transplant recipients receiving antithymocyte globulin induction and maintenance immuno-suppression consisting of either tacrolimus and mycophenolate mofetil or tacrolimus and sirolimus.