Sensitized renal transplant recipients with high levels of donor-specific alloantibody (DSA) commonly develop antibody-mediated rejection (AMR), which may cause acute graft loss or shorten allograft survival. We examined the efficacy of terminal complement inhibition with the humanized anti-C5 antibody, eculizumab, in the prevention AMR in renal transplant recipients with a positive crossmatch against their living donor. The incidence of biopsy-proven AMR in the first 3 months posttransplant in 26 highly sensitized recipients of living donor renal transplants who received eculizumab posttransplant was compared to a historical control group of 51 sensitized patients treated with a similar plasma exchange (PE)-based protocol without eculizumab. The incidence of AMR was 7.7% (2/26) in the eculizumab group compared to 41.2% (21/51) in the control group (p = 0.0031). Eculizumab also decreased AMR in patients who developed high levels of DSA early after transplantation that caused proximal complement activation. With eculizumab, AMR episodes were easily treated with PE reducing the need for splenectomy. On 1-year protocol biopsy, transplant glomerulopathy was found to be present in 6.7% (1/15) eculizumab-treated recipients and in 35.7% (15/42) of control patients (p = 0.044). Inhibition of terminal complement activation with eculizumab decreases the incidence of early AMR in sensitized renal transplant recipients (ClincalTrials.gov number NCT006707).

The use of sirolimus-based immunosuppressive regimens leads to a higher incidence of wound-healing complications and will require new approaches to patient selection and management to decrease their incidence.

Calcineurin inhibitors have decreased acute rejection and improved early renal allograft survival, but their use has been implicated in the development of chronic nephrotoxicity. We performed a prospective, randomized trial in kidney transplantation comparing sirolimus-MMF-prednisone to tacrolimus-MMFprednisone. Eighty-one patients in the sirolimus group and 84 patients in the tacrolimus group were enrolled (mean follow-up = 33 months; range 13-47 months). At 1 year, patient survival was similar in the groups (98% with sirolimus, 96% with tacrolimus; p = 0.42) as was graft survival (94% sirolimus vs. 92% tacrolimus, p = 0.95). The incidence of clinical acute rejection was 10% in the tacrolimus group and 13% in the sirolimus group (p = 0.58). There was no difference in mean GFR measured by iothalamate clearance between the tacrolimus and sirolimus groups at 1 year (61 ± 19 mL/min vs. 63 ± 18 mL/min, p = 0.57) or 2 years (61 ± 17 mL/min vs. 61 ± 19 mL/min, p = 0.84). At 1 year, chronicity using the Banff schema showed no difference in interstitial, tubular or glomerular changes, but fewer chronic vascular changes in the sirolimus group. This study shows that a CNI-free regimen using sirolimus-MMF-prednisone produces similar acute rejection rates, graft survival and renal function 1-2 years after transplantation compared to tacrolimus-MMF-prednisone.

Multiple endocrine neoplasia type I (MEN-I) is an autosomal dominant disorder characterized by endocrinopathies involving the anterior pituitary gland, parathyroid glands, and pancreas. The long-term prognosis for patients affected with this disorder is uncertain. To better characterize this prognosis, we performed a retrospective review of all patients with MEN-I treated at a single institution during the period 1951-1997. A group of 233 patients served as the study population. Their records were analyzed for confirmation of diagnosis, treatments received, long-term survival, and cause of death. Altogether, 108 eight male patients (46%) and 125 female patients (54%) were identified. At the conclusion of the study, 164 (70%) were alive and 69 (30%) were deceased, with a median follow-up for patients alive at last contact of 13.4 years (range < 1 month to 54.3 years). The cause of death was reliably obtained in 60 patients. Of these patients, 17 (28%) died of causes related to MEN-I, most commonly metastatic islet cell tumors (10 patients). The remaining patients died of causes unrelated to MEN-I, most commonly coronary artery disease and nonendocrine malignancies (14% each). The overall 20-year survival of MEN-I patients was 64% (95% CI was 56-72%), and that of an age- and gender-matched upper Midwest population was 81% (p < 0.001). Patients with MEN-I appear to be at increased risk of premature death. Earlier diagnosis and treatment of potentially malignant pancreatic islet cell neoplasms may result in a decrease of this premature mortality.

Peanut allergy is characterized by more severe symptoms than other food allergies and by high rates of symptoms on minimal contact. Skin-prick testing and peanut-specific IgE levels do not predict clinical severity. Avoidance of peanut is difficult. Many people suffering severe relations are inadequately treated. Sufferers need education and training in the use of rescue medication.

No abstract

Renal transplant candidates with high levels of donorspecific anti-HLA antibodies have low transplantation rates and high mortality rates on dialysis. Using desensitization protocols, good short-term outcomes are possible in "positive crossmatch kidney transplants (+XMKTx)" , but long-term outcome data are lacking. The aim of the current study was to determine actual 5-year graft outcomes of +XMKTx. We compared graft survival and the functional and histologic status of 102 +XMKTx to 204 −XMKTx matched for age and sex. Actual 5-year death-censored graft survival was lower in the +XMKTx group (70.7% vs. 88.0%, p < 0.01) and chronic injury (glomerulopathy) was present in 54.5% of surviving grafts. Graft survival was higher in recipients with antibody against donor class I only compared with antibody against class II (either alone or in combination with class I) (85.3% vs. 62.6%, p = 0.05) and was similar to −XMKTx (85.3 vs. 88.0%, p = 0.64). Renal function and proteinuria ranged across a wide spectrum in all groups reflecting the different histological findings at 5 years. We conclude that when compared to −XMKTx, +XMKTx have inferior outcomes at 5 years, however, almost half of the surviving grafts do not have glomerulopathy and avoiding antibodies against donor class II may improve outcomes.

The immunosuppressive agent sirolimus exerts an antiproliferative effect by inhibiting mammalian target of rapamycin (mTOR). Because excessive proliferation of the biliary epithelium is a prominent feature of the polycystic liver that accompanies autosomal dominant polycystic kidney disease (ADPKD), we hypothesized that sirolimus may benefit patients with this disorder. We retrospectively measured the volumes of polycystic livers and kidneys in ADPKD patients who had received kidney transplants and had participated in a prospective randomized trial that compared a sirolimus-containing immunosuppression regimen to a tacrolimus-containing regimen. Sixteen subjects (seven with sirolimus, nine with tacrolimus) had received abdominal imaging studies within 11 mo before and at least 7 mo after transplantation, making them suitable for our analysis. Treatment with the sirolimus regimen for an average of 19.4 mo was associated with an 11.9 Ϯ 0.03% reduction in polycystic liver volume, whereas treatment with tacrolimus for a comparable duration was associated with a 14.1 Ϯ 0.09% increase. A trend toward a greater reduction in native kidney volume was also noted in the sirolimus group compared with the nonsirolimus group. Regarding mechanism, the epithelium that lines hepatic cysts exhibited markedly higher levels of phospho-AKT, phospho-ERK, phospho-mTOR, and the downstream effector phosphoS6rp compared with control biliary epithelium. In summary, treatment with sirolimus was associated with decreased polycystic liver volume, perhaps by preventing aberrant activation of mTOR in epithelial cells lining the cysts.