Bone Marrow-Derived Multipotent Stromal Cells Attenuate Inflammation in Obliterative Airway Disease in Mouse Tracheal Allografts

Obliterative bronchiolitis (OB) remains the most significant cause of death in long-term survival of lung transplantation. Using an established murine heterotopic tracheal allograft model, the effects of different routes of administration of bone marrow-derived multipotent stromal cells (MSCs) on the development of OB were evaluated. Tracheas from BALB/c mice were implanted into the subcutaneous tissue of major histocompatibility complex- (MHC-) disparate C57BL/6 mice. At the time of transplant, bone marrow-derived MSCs were administered either systemically or locally or via a combination of the two routes. The allografts were explanted at various time points after transplantation and were evaluated for epithelial integrity, inflammatory cell infiltration, fibrosis, and luminal obliteration. We found that the most effective route of bone marrow-derived MSC administration is the combination of systemic and local delivery. Treatment of recipient mice with MSCs suppressed neutrophil, macrophage, and T-cell infiltration and reduced fibrosis. These beneficial effects were observed despite lack of significant MSC epithelial engraftment or new epithelial cell generation. Our study suggests that optimal combination of systemic and local delivery of MSCs may ameliorate the development of obliterative airway disease through modulation of immune response

Increased renal function decline in fast metabolizers using extended-release tacrolimus after kidney transplantation

Y Fast metabolism of immediate-release tacrolimus (IR-Tac) is associated with decreased kidney function after renal transplantation (RTx) compared to slow metabolizers. We hypothesized, by analogy, that fast metabolism of extended-release tacrolimus (ER-Tac) is associated with worse renal function. We analyzed data from patients who underwent RTx at three different transplant centers between 2007 and 2016 and received an initial immunosuppressive regimen with ER-Tac, mycophenolate, and a corticosteroid. Three months after RTx, a Tac concentration to dose ratio (C/D ratio)= 1.0 ng/ml . 1/mL slow metabolism. Renal function (estimated glomerular filtration rate, eGFR), first acute rejection (AR), conversion from ER-Tac, graft and patient survival were observed up to 60-months. 610 RTx patients were divided into 192 fast and 418 slow ER-Tac metabolizers. Fast metabolizers showed a decreased eGFR at all time points compared to slow metabolizers. The fast metabolizer group included more patients who were switched from ER-Tac (p<0.001). First AR occurred more frequently (p=0.008) in fast metabolizers, while graft and patient survival rates did not differ between groups (p=0.529 and p=0.366, respectively). Calculation of the ER-Tac C/D ratio early after RTx may facilitate individualization of immunosuppression and help identify patients at risk for an unfavorable outcome

Male kidney allograft recipients at risk for urinary tract infection?

Urinary tract infection (UTI) is the most common infection after renal transplantation (RTx). Although female sex is a well-known risk factor for the development of UTI after RTx, the role of the donor sex in this context remains unclear.In this case control study 6,763 RTx cases were screened for UTI when presenting at our transplant outpatient clinics. 102 different RTx patients fulfilled the inclusion criteria and were compared to 102 controls. Data on renal function was prospectively followed for 12 months. Results were compared to a previous RTx cohort from our transplant center. Additionally, we assessed the immunological response of leukocytes from 58 kidney recipients and 16 controls to lipopolysaccharide stimulation.After identification by univariate analysis, multivariate logistic regression analysis indicated female sex, minor height, advanced age and male kidney allograft sex to be associated with the occurrence of UTI after RTx. Female recipients who received male grafts had the best renal function 12 months after presentation. However, leukocyte response of recipients to lipopolysaccharide was impaired irrespective of donor and recipient sex to the same extend.We conclude from our data that male kidney allografts are associated with the occurrence of UTI after RTx but did not influence the response of leukocytes to lipopolysaccharide. Further prospective studies are needed to identify the underlying mechanisms of higher male kidney donor dependent UTI

Complications.

<p>Chi²-test; DGF, delayed graft function; CMV, cytomegalovirus</p><p>Complications.</p

Biopsy results.

<p>^a Chi²-test;</p><p>^b t-test; ABMR, antibody-mediated rejection; HLA, human leucocyte antigen; DSA, donor specific antibodies; TCMR, T cell-mediated rejection; CNI calcineurin inhibitor</p><p>Biopsy results.</p

Costs for immunoadsorption.

<p>All prices are shown in Euro. Expenses do not include replacement fluids and labor costs.</p><p>Costs for immunoadsorption.</p

Patients`characteristics.

<p>^a t-test;</p><p>^b Chi2-test;</p><p>^c Mann-Whitney-U-Test. All patients were Western European descent. ESRD, end stage renal disease; BMI, body mass index; ADPKD, autosomal dominant polycystic kidney disease; FSGS, focal segmental glomerulosclerosis; GN, glomerulonephritis; GBM, glomerular basement membrane; HLA, human leukocyte antigen; PRA, panel reactive antibodies, vPRA, virtual panel reactive antibodies; CIT, cold ischemia time; WIT, warm ischemia time.</p><p>Patients`characteristics.</p

Immunoadsorption (IA).

<p>^a Mann-Whitney-U test;</p><p>^b t-test;</p><p>^c Chi² test;</p><p>^d paired t-test of the platelet count before and after IA in the Glycosorb group;</p><p>^e paired t-test of the platelet count in the Immunosorba group; PPh, plasmapheresis; RTx, renal transplantation; BW, bodyweight.</p><p>Immunoadsorption (IA).</p