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Background: Transplant glomerulitis, characterized by mononuclear cell infiltration of glomeruli, is likely to occur during clinical or subclinical antibody-mediated rejection., Methods: To determine whether T-cell phenotype influences the clinical presentation of this pathologic condition, we used reverse transcription quantitative polymerase chain reaction to analyze expression of Treg cells (Foxp3), cytotoxic CD8 T cells (Granzyme B), Th1 cells (INF-γ,T Bet), Th2 cells (GATA3, IL-4), and Th17 pathway (IL-17). Our study included 20 renal transplant recipients exhibiting subclinical glomerulitis (SG) diagnosed after a routine 3-month posttransplant biopsy. Results were compared with those observed in 22 patients with normal routine biopsies at 3 months (N) and 17 patients with clinical glomerulitis occurring during early acute renal dysfunction within the first year after transplantation in a context of acute antibody-mediated rejection., Results: Our results show that expression of IL-4 mRNA was significantly higher in SG patients than in N patients (P = 0.02). Expression of IFN-γ was significantly higher in patients with clinical glomerulitis than in patients with SG (P<0.001) and was associated with a clinical expression of glomerulitis., Conclusion: Our results suggest that the balance of Th1/Th2 is likely to differentiate clinical expression of transplant glomerulopathy. They also indicate that therapeutic approaches in cases of SG should be defined with caution and take into account transcriptional criteria.

Immunosuppressive drugs are used in the treatment of inflammatory and autoimmune diseases, as well as in transplantation. Frequently prescribed in young people, these treatments may have deleterious effects on fertility, pregnancy outcomes and the unborn child. This review aims to summarize the main gonadal side effects of immunosuppressants, to detail the effects on fertility and pregnancy of each class of drug, and to provide recommendations on the management of patients who are seen prior to starting or who are already receiving immunosuppressive treatment, allowing them in due course to bear children. The recommendations for use are established with a rather low level of proof, which needs to be taken into account in the patient management. Methotrexate, mycophenolate, and le- and teri-flunomide, cyclophosphamide, mitoxanthrone are contraindicated if pregnancy is desired due to their teratogenic effects, as well as gonadotoxic effects in the case of cyclophosphamide. Anti-TNF-alpha and mTOR-inhibitors are to be used cautiously if pregnancy is desired, since experience using these drugs is still relatively scarce. Azathioprine, glucocorticoids, mesalazine, anticalcineurins such as cyclosporine and tacrolimus, ß-interferon, glatiramer-acetate and chloroquine can be used during pregnancy, bearing in mind however that side effects may still occur. Experience is limited concerning natalizumab, fingolimod, dimethyl-fumarate and induction treatments. Conclusion: At the time of prescription, patients must be informed of the possible consequences of immunosuppressants on fertility and of the need for contraception. Pregnancy must be planned and the treatment modified if necessary in a pre-conception time period adapted to the half-life of the drug, imperatively in relation with the prescriber of the immunosuppressive drugs. [ABSTRACT FROM AUTHOR]

Summary The diabetes and renal phenotype of patients with maturity-onset diabetes of the young (MODY) on a transplantation waiting list is not known; neither is their outcome after pancreas (PT) and/or kidney transplantation (KT). Between 2002 and 2009, we screened 50 of 150 patients referred for kidney and pancreas transplantation to the Kremlin-Bicêtre center for HNF1B and HNF1A mutations if one or more of the following criteria was present (i) an atypical history of diabetes (ii) diabetes with at least one affected parent or two affected relatives, (iii) an absence of auto-antibodies at diagnosis (iv) a persistent secretion of fasting C peptide (v) a personal or a family history of renal cysts or dysplasia. Their phenotype and their outcome were analyzed. Four HNF1A (MODY3) and eight HNF1B mutations [renal cysts and diabetes (RCAD)] were identified. All MODY3 patients had diabetic nephropathy, but only 50% of RCAD patients. Four patients underwent a kidney and pancreas transplantation and two a kidney transplant alone. After 4.1 ± 1.1 years of follow-up, 83% of patients still have a functioning kidney and 75% a functioning pancreas. PT can be proposed with good results for MODY3 and RCAD patients. [ABSTRACT FROM AUTHOR]

Tubulo-interstitial microcalcifications in renal transplant are described with a wide difference of incidence (4–78%) according to time and goal of biopsies. Currently, staining procedures are used to deduce the composition of crystals and speculate about their aetiologies. Here we test the contribution of infrared microspectroscopy (IR-MS) in understanding kidney transplant crystal deposits. First, microcalcifications observed in 118 allograft biopsies are studied by IR-MS. The Fourier transform infrared signal shows that a major proportion (92%) of calcium phosphate crystals is in the pure or mixed form. Next, we compare 50 patients with calcifications to 100 without calcifications and show persistent hyperparathyroidism and tubular cell vacuolization as circumstances of crystal deposition. Finally, the graduation level of calcification by IR-MS appears to be correlated with the graft outcome. Graft survival seems to be worse in case of high microcalcification detection by IR-MS. These preliminary data suggest IR-MS as a great tool for clinicians to diagnose, characterize, and quantify microcalcifications in kidney allografts. [ABSTRACT FROM AUTHOR]