We identified 5 risk factors for nocardiosis after SOT. Low-dose cotrimoxazole was not found to prevent Nocardia infection. These findings may help improve management of transplant recipients.

Sirolimus is very probably responsible for interstitial pneumonitis on the following grounds: (a) occurrence of pneumonitis during sirolimus therapy; (b) absence of any other causes; and (c) resolution within 3 months of sirolimus discontinuation or dose reduction. Sirolimus should now be added to the list of possible causes of pulmonary complications after renal transplantation. Discontinuation or dose reduction of sirolimus led to complete and lasting resolution of symptoms.

clinicaltrials.gov Identifier: NCT01208818.

Sirolimus has been associated with high-range proteinuria when used in replacement of calcineurin inhibitors in renal transplant recipients with chronic allograft nephropathy (CAN). Primary FSGS was demonstrated previously in some such patients, but the coexistence of CAN lesions made the interpretation uneasy. However, nephrotic syndrome and FSGS were observed recently in three patients who received sirolimus de novo, without medical history of primary FSGS or CAN. Markers of podocyte differentiation were studied in kidney biopsies of the three patients who received sirolimus de novo and of five patients who switched to sirolimus. All patients developed FSGS lesions of classic type (not otherwise specified), but only switched patients exhibited advanced sclerotic lesions. Immunohistochemistry showed that some podocytes in FSGS lesions had absent or diminished expression of the podocyte-specific epitopes synaptopodin and p57, reflecting dedifferentiation, and had acquired expression of cytokeratin and PAX2, reflecting a immature fetal phenotype. Such a pattern of epitope expression provides evidence for podocyte dysregulation. Moreover, a decrease in vascular endothelial growth factor expression was observed in some glomeruli. In conclusion, sirolimus induces FSGS that is responsible for proteinuria in some transplant patients.

Lymphocytic alveolitis and radiologic bronchiolitis obliterans-organizing pneumonia are the key findings in sirolimus-associated pneumonitis. Sirolimus withdrawal was associated with recovery within 6 months.

Our results suggest that cerebrovascular cause of death, history of hypertension, and elevated creatinine are significant independent donor risk factors for graft survival, whereas donor age is a statistically significant, but dependent, risk factor. This result is important for the design of allocation and transplantation strategies for kidneys procured in elderly donors.

Kidney transplantation is now considered as a reasonable option for HIV-infected patients with endstage renal disease. We describe here a retrospective study conducted in five transplantation centers in Paris. Twenty-seven patients were included. Immunosuppressive protocol associated an induction therapy and a long-term treatment combining mycophenolate mofetil, steroids and either tacrolimus or cyclosporine. All the patients had protocol biopsies at 3 months and 1 year. Patient's survival was 100% at 1 year and 98% at 2 years. Graft survival at 1 and 2 years is 98% and 96% at 1 and 2 years, respectively. The mean glomerular filteration rate values at 12 and 24 months were 60.6 mL/min/1.73 m 2 (range 23-98) and 65.4 mL/min/1.73m 2 (range 24-110), respectively. Acute cellular rejection was diagnosed in four cases (15%). Because of high trough levels of calcineurin inhibitor, protease-inhibitor therapies were withdrawn in 11 cases. HIV disease progression was not observed. One patient developed B-cell lymphoma.In conclusion, our study confirms the safety of renal transplantation in HIV-infected patients with few adverse events and a low incidence of acute rejection.

Patients with Type 2 diabetes (T2D) are highly susceptible to infection and have an increased incidence of some tumors, possibly due to immune system dysfunction. In the innate cellular immune system, Natural Killer (NK) lymphocytes are important effectors responsible for controlling infections and combating tumor development. We analyzed NK cell subsets in 51 patients with long-standing T2D. Compared with healthy blood donors, diabetic patients showed a profound decrease in both NKG2D-positive NK cells (44% vs. 55.5%, P<0.01) and NKp46-positive cells (26% vs. 50%, P<0.01). Decreased expression of these receptors was associated with functional defects, such as reduced NK degranulation capacity when challenged with the tumor target cell line K562 (10.3 vs. 15.8%, P<0.05). This defect could be restored in vitro by stimulating NK cells from T2D patients with IL-15 (P<0.05). NKG2D expression was found to be negatively correlated with HBA1c level (r = −0.50; P = 0.009), suggesting that sustained hyperglycemia could directly influence NK cell defects. We demonstrated that endoplasmic reticulum (ER) stress, an important mediator in diabetes-associated complications, was inducible in vitro in normal NK cells and that tunicamycin treatment resulted in a significant decrease in NKG2D expression (P<0.05). Furthermore, markers of the Unfolded Protein Response (UPR) BiP, PDI and sXBP1 mRNAs were significantly increased in NK cells from T2D patients (P<0.05, P<0.01, P<0.05, respectively), indicating that ER stress is activated in vivo through both PERK and IRE1 sensors. These results demonstate for the first time defects in NK cell-activating receptors NKG2D and NKp46 in T2D patients, and implicate the UPR pathway as a potential mechanism. These defects may contribute to susceptibility to infections and malignancies and could be targetted therapeutically.