Nephrectomy after transplant failure: current practice and outcomes.

The role of transplant nephrectomy after transplant failure is uncertain. We report the use and consequences of transplant nephrectomy among 19 107 transplant failure patients between 1995 and 2003 in the United States. Among 3707 patients with early transplant failure (graft survival <12 m), nephrectomy was performed in 56%, and was associated with an increased risk of death (HR 1.13, 95% CI 1.01-1.26). In contrast, among 15,400 patients with late transplant failure (graft survival > or =12 m), nephrectomy was performed in 27%, and was associated with a decreased risk of death (HR 0.89, 95% CI 0.83-0.95). In early transplant failure patients, nephrectomy was associated with a lower risk of repeat transplant failure (HR 0.72, 95% CI 0.56-0.94), while among late transplant failure patients; nephrectomy was associated with a higher risk of repeat transplant failure (HR 1.20, 95% CI 1.02-1.41). Definitive conclusions are not possible from this observational study. The role of nephrectomy in the management of dialysis treated transplant failure patients, and the implications of nephrectomy for repeat transplantation should be further studied in prospective studies.

Renal transplantation in children 15 Kg or less: the British Columbia Children's Hospital experience.

PURPOSE: Small infants are the most challenging group of patients to undergo renal transplantation. PURPOSE: We reviewed the transplantation experience at our institution with children less than 15 kg at transplantation. MATERIALS AND METHODS: We retrospectively reviewed the records of 24 recipients in a 20-year period. Technical and allograft outcomes were compared to those in the North American Pediatric Renal Transplant Cooperative Study database. RESULTS: Since the inception of our program 24 recipients weighing 15 kg or less who were 6 years or younger have undergone transplantation. Seven grafts (29%) were from living donors. At transplantation mean age was 3.1 years (range 1.8 to 5.7) and mean weight was 13.4 kg (range 9.0 to 15.7). Average cold and warm ischemic times were 14.1 hours (range 3.4 to 37.2) and 23.1 minutes (range 21 to 41), respectively. Early complications were ureteral stricture requiring pyeloureterostomy in 1 case, reversible acute tubular necrosis in 2 and early arterial thrombosis salvaged by immediate thrombectomy in 1. Delayed complications were arterial stenosis requiring angioplasty in 2 cases, and 3 delayed deaths related to malignant hypertension in 2 and sepsis in 1. No grafts were lost due to thrombosis. Mean serum creatinine at years 1 to 3 and 5 were 48.5, 67.5, 79.1 and 84.4 mumol/l, respectively. Graft survival was 92% (22 patients after censoring 1 who died with a functioning graft) at 2 and 5 years. Overall results compare favorably to those in the North American Pediatric Renal Transplant Cooperative Study. CONCLUSIONS: With a multidisciplinary team effort successful results can be achieved in this challenging group of patients.

Resistance of established porcine islet xenografts to humoral rejection by hyperimmune sera.

BACKGROUND: Although preformed natural antibodies cause hyperacute rejection of primarily vascularized xenografts, tissue grafts such as skin or islets are revascularized by in-growth of host capillaries and therefore might be resistant to circulating antibodies. We examined the effect of hyperimmune serum and primed T cells on the survival of long-term porcine islet xenografts in diabetic nude mice. METHODS: Porcine islets were transplanted beneath the kidney capsule of streptozotocin-induced diabetic BALB/c athymic mice. Hyperimmune serum and sensitized splenocytes were prepared by repeated immunization of BALB/c mice with porcine lymph node cells. Splenic T cells were enriched by nylon wool column separation. Tissues were examined by immunohistology using murine- and porcine-specific monoclonal antibodies. RESULTS: Porcine islets survived in nude mice for > 100 days with high levels of circulating porcine C-peptide and maintenance of normoglycemia. Injection of the hyperimmune sera (IgG) into normoglycemic nude mice bearing porcine islets for > 70 days failed to induce rejection despite the continued presence of circulating anti-porcine cytotoxic antibody. Injection of sensitized T cells caused acute rejection of long-term (>140 days) porcine islets, whereas injection of naive T cells had no effect. Histologically, porcine islets removed from mice treated with hyperimmune serum showed no staining for IgG. Long-surviving porcine islet grafts showed strong staining for interleukin (IL)-10 and a lesser amount of IL-4 but no staining for IL-2 or interferon-gamma. Although fresh porcine islets were positive for swine leukocyte antigen class 1 antigen and intercellular adhesion molecule (ICAM)-1 but negative for mouse platelet endothelial cell adhesion molecule and ICAM-2, long-surviving porcine islets showed positive endothelial staining for mouse platelet endothelial cell adhesion molecule and ICAM-2. CONCLUSIONS: Established islet xenografts are resistant to hyperimmune serum as a result of a lack of target endothelial antigens, whereas they remain susceptible to rejection caused by primed T cells. Local production of Th2 cytokines may explain the inability of long-surviving islet xenografts to activate injected naive T cells.

Successful renal transplantation with ipsilateral femoral arteriovenous grafts.

BACKGROUND: The choice of location for revascularization of a renal allograft is frequently influenced by the presence of previous pelvic surgery or failed allografts that remain in situ. The presence of polytetrafluoroethylene (PTFE) loop grafts in the femoral vessels may potentially result in iliac venous hypertension, thereby compromising the function of a renal allograft placed nearby. The purpose of this study is to report the hemodynamic changes within the iliac veins as a result of PTFE femoral grafts and report the outcome of renal allografts placed ipsilateral to such grafts. METHODS: THREE patients with a failed renal allograft in the right iliac fossa and functioning left groin PTFE loop grafts underwent left iliac venography and hemodynamic measurements of the iliac venous system. All three patients underwent renal transplantation in the left iliac fossa without ligation or alteration of the loop graft. Standard clinical data were collected after transplantation. RESULTS: All three patients demonstrated widely patent external iliac and common iliac veins ipsilateral to the loop graft. Elevated pressures measured within the venous limb of the loop graft dissipated rapidly within the common femoral and external iliac veins. All three kidneys were well perfused, as documented by posttransplant technetium 99m-diethylenetriaminepentaacetic acid nuclear renography. All three patients have normal renal function past 7 months after transplant, and all three femoral loop grafts are still functioning. CONCLUSIONS: PTFE loop grafts to the femoral vessels are not associated with local venous hypertension in the ipsilateral external iliac veins. Revascularization of a renal allograft may be performed ipsilateral to a femoral loop graft provided other venous diseases, such as strictures, have been excluded.

Importance of natural killer cells in the rejection of hamster skin xenografts.

BACKGROUND: In the hamster to rat xenogeneic combination, antibodies, T cells, and natural killer (NK) cells have all been implicated in the process of rejection. 3.2.3 is a mouse IgG1kappa monoclonal antibody (mAb) directed against NKR-P1A on rat NK cells. The purpose of this study was to evaluate the effect of this mAb independently and in combination with other immunosuppressive agents in a hamster to rat skin graft model in order to elucidate the mechanisms involved in xenograft rejection. METHODS: Lewis rats were recipients of hamster skin grafts. Various groups received antilymphocyte serum (ALS) (days -1, 0, and +2), rapamycin (3 mg/kg; alternate days from day +1 through day +13), and 3.2.3 mAb (days 0, +1, and +2). Anti-hamster antibody production was determined serially with a complement-dependent cytotoxicity assay. Lewis anti-hamster mixed lymphocyte reaction and cell-mediated lympholysis assays were performed within 7 days after rejection of the skin graft. NK cell function was tested using a cytotoxicity assay versus YAC-1 target cells on day 14 or day 15 after skin grafting. RESULTS: Median graft survival in untreated animals was 7 days. There was only modest prolongation in rats treated with rapamycin alone (median survival time [MST]=9 days) or ALS alone (MST=10 days). The use of 3.2.3 mAb in untreated rats (3.2.3 alone MST=7 days) and in ALS-treated rats (ALS+3.2.3 MST=9.5 days) did not improve graft survival. The combination of ALS+rapamycin substantially improved graft survival (MST=13 days), and even greater prolongation was seen with the addition of 3.2.3 mAb (ALS+rapamycin+3.2.3 MST=18.5 days). Cytotoxic antibodies, secondary mixed lymphocyte reaction responses, cytotoxic T cells, and normal NK activity were seen at the time of rejection in untreated rats as well as those treated with 3.2.3 mAb alone, ALS alone, ALS+3.2.3 mAb, and rapamycin alone. ALS+rapamycin completely blocked the formation of anti-hamster antibodies and cytotoxic T cells but did not suppress NK activity. The use of 3.2.3 mAb produced a marked but transient suppression of NK activity in all groups. CONCLUSION: Hamster skin xenografts can be rejected by Lewis rats in the absence of cytotoxic antibodies and cytotoxic T cells. ALS, rapamycin, and ALS+rapamycin do not suppress NK activity in Lewis rats, although their use produces a modest prolongation of hamster skin graft survival. The administration of 3.2.3 mAb to Lewis rats results in a marked but transient suppression of NK cell function, which substantially prolongs hamster skin graft survival only when antibody and cytotoxic T-cell production have also been suppressed.

Magnetic resonance angiography in the evaluation of living-related renal donors.

Live-donor kidney donation requires an accurate determination of renal arterial anatomy. Traditionally, conventional angiography has supplied this information. The present study was undertaken to determine the accuracy of magnetic resonance angiography (MRA) compared with conventional angiography (CA) in the evaluation of potential living renal donors. Fifteen potential living renal donors underwent both conventional angiography (midstream aortic injection) and three-dimensional phase contrast MRA. Two overlapping volumes of 64 slices (slice thickness 1.5 mm) were obtained in the axial plane to allow coverage from the celiac trunk to the aortic bifurcation. Conventional angiography demonstrated single renal arteries in 24 kidneys and multiple renal arteries in 6 kidneys. Magnetic resonance angiography demonstrated multiple renal arteries in 5 of the 6 kidneys. The sensitivity of MRA in determining kidneys with multiple renal arteries was 83% (5/6). One kidney with an accessory 2-mm polar artery was incorrectly identified as having a single renal artery by MRA. The overall accuracy of MRA in identifying the number of renal arteries was 97% (29/30). Fibromuscular dysplasia was demonstrated in 2 patients by CA, but was not visualized prospectively by MRA. Based on standard physician and hospital fees for each procedure, use of MRA alone would represent a cost savings of approximately $1900 over CA. Despite its minimally invasive and economic attractions, MRA does not achieve the level of accuracy required to replace CA in the evaluation of potential living kidney donors.

Gonadal tumors in disorders of sexual differentiation.

OBJECTIVE: To study the prevalence and distribution of gonadal tumors in patients with disorders of sexual differentiation. METHODS: Retrospective review of pathologic materials and clinical data on all patients diagnosed with mixed gonadal dysgenesis, pure gonadal dysgenesis, androgen insensitivity, and true hermaphroditism between 1982 and 1990. RESULTS: Twenty-one patients were identified and all underwent bilateral gonadectomy at the time of diagnosis. Nine of 21 patients had a gonadal tumor for a prevalence of 44 percent. Those at greatest risk for tumor were patients with mixed gonadal dysgenesis (6 of 11 patients) and pure gonadal dysgenesis (2 of 3 patients). There were four gonadoblastomas, two dysgerminomas, and one each of teratocarcinoma, seminoma, cystadenofibroma, and juvenile granulosa cell tumor. CONCLUSIONS: The high prevalence of gonadal tumors in children with mixed and pure gonadal dysgenesis warrants consideration of early, bilateral, prophylactic gonadectomy once the diagnosis is established with certainty.