Les vascularites pauci-immunes avec atteinte rénale (comparaison de deux populations de patients âgés et très âgés)

TOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Design agroécologique: Définition

National audienceLe design agroécologique est une démarche de conception d’un agroécosystème durable qui s’appuie sur les interactions bénéfiques entre les éléments qui le constituent. Cette démarche repose sur une approche systémique permettant de répondre aux exigences de résilience et d’autonomie des exploitations et des territoires..

Hnf-1β transcription factor is an early hif-1α-independent marker of epithelial hypoxia and controls renal repair.

International audienceEpithelial repair following acute kidney injury (AKI) requires epithelial-mesenchyme-epithelial cycling associated with transient re-expression of genes normally expressed during kidney development as well as activation of growth factors and cytokine-induced signaling. In normal kidney, the Hnf-1β transcription factor drives nephrogenesis, tubulogenesis and epithelial homeostasis through the regulation of epithelial planar cell polarity and expression of developmental or tubular segment-specific genes. In a mouse model of ischemic AKI induced by a 2-hours hemorrhagic shock, we show that expression of this factor is tightly regulated in the early phase of renal repair with a biphasic expression profile (early down-regulation followed by transient over-expression). These changes are associated to tubular epithelial differentiation as assessed by KSP-cadherin and megalin-cubilin endocytic complex expression analysis. In addition, early decrease in Hnf1b expression is associated with the transient over-expression of one of its main target genes, the suppressor of cytokine signaling Socs3, which has been shown essential for renal repair. In vitro, hypoxia induced early up-regulation of Hnf-1β from 1 to 24 hours, independently of the hypoxia-inducible factor Hif-1α. When prolonged, hypoxia induced Hnf-1β down-regulation while normoxia led to Hnf-1β normalization. Last, Hnf-1β down-regulation using RNA interference in HK-2 cells led to phenotype switch from an epithelial to a mesenchyme state. Taken together, we showed that Hnf-1β may drive recovery from ischemic AKI by regulating both the expression of genes important for homeostasis control during organ repair and the state of epithelial cell differentiation

Innate-Like and Conventional T Cell Populations from Hemodialyzed and Kidney Transplanted Patients Are Equally Compromised

International audienceClinicians are well aware of existing pharmacologically-induced immune deficient status in kidney-transplanted patients that will favor their susceptibility to bacterial or viral infections. Previous studies indicated that advanced Stage 4–5 Chronic Kidney Disease might also be regarded as an immune deficiency-like status as well, even though the mechanisms are not fully understood. Here, we analyzed the ex vivo frequency and the functional properties of both conventional and innate-like T (ILT) lymphocyte subsets in the peripheral blood of 35 patients on hemodialysis, 29 kidney transplanted patients and 38 healthy donors. We found that peripheral blood cell count of ILT cells, as iNKT (invariant Natural Killer T) and MAIT (mucosal-associated invariant T), were significantly decreased in hemodialyzed patients compared to healthy controls. This deficiency was also observed regarding conventional T cells, including the IL-17-producing CD4 + Th17 cells. Pertaining to regulatory T cells, we also noticed major modifications in the global frequency of CD4 + CD25 + Foxp3 + T lymphocytes, including the resting suppressive CD45RA + Foxp3 lo and activated suppressive CD45RA 2 Foxp3 hi T cell subpopulations. We found no significant differences between the immune status of hemodialyzed and kidney-transplanted subjects. In conclusion, we demonstrated that both ILT and conventional T cell numbers are equally impaired in hemodialyzed and kidney-transplanted patients

Patient demographic characteristics.

<p>Two hemodialysed patients had glomerulonephritis and vascular nephropathy at the same time.</p

Global Foxp3⁺ T cell numbers are reduced in HD patients.

<p>(A) Representative FACS analysis of CD4⁺CD25⁺Foxp3⁺T cells and their distinct subsets on PBMC from control (top) and HD patients (bottom). (B) CD4⁺CD25⁺Foxp3⁺T cell numbers are reduced in HD patients. (C to E) Among these gated cells, cytokine-secreting CD45RA⁻Foxp3^lo nonsuppressive (C), resting suppressive CD45RA⁺Foxp3^lo (D) and activated suppressive CD45RA⁻Foxp3^hi (E) cells, all these subsets are reduced in HD patients compared to controls. Bars represent the median. *, P<0.01; ****, P<0.0001.</p

CD4⁺ and CD8⁺ T cell numbers are reduced in HD patients.

<p>(A) CD4⁺ and CD8⁺T cell numbers are significant decreased in the peripheral blood of HD patients compared to healthy donors. Bars represent the median. (B) The percentage of IFN<b>γ</b>⁺ cells among gated CD8⁺ or CD4⁺ T lymphocytes or (C) the percentage of IL-4⁺ and IL-17⁺ cells among gated CD4⁺ T lymphocytes was assessed after 6 h stimulation with PMA and ionomycin. Box-and-whisker plots are used to represent the distributions. The bottom and the top of a box represent the 5th and 95th percentiles, and the bar in the box shows the median. *, P<0.01; **, P<0.001; ***, P<0.0005 versus controls. Representative FACS analysis of IL-4, IL-17 and IFN<b>γ</b> production by gated CD4⁺ (E) or CD8⁺ (F) T cells from health donor controls (top) or HD patients (bottom) are represented.</p

iNKT cell deficit in HD patients.

<p>(A) iNKT cells were double stained by anti-CD3 and the PBS57-loaded CD1d-tetramer. Representative FACS profile showing the percentage of iNKT and MAIT cells in control versus HD patients. (B and C) HD patients had significant low numbers (B) and percentage (C) of peripheral blood iNKT and MAIT cells when compared to healthy donors. Bars represent the median. (D) The frequency of CD4⁺ and CD8⁻ subsets respectively among gated iNKT and MAIT cells in control versus HD patients is represented. (E) The percentage of IL-4⁺ or IFN<b>γ</b>⁺ cells among gated iNKT lymphocytes was assessed after 5 h stimulation with PMA and ionomycin. Box-and-whisker plots are used to represent the distributions. The bottom and the top of a box represent the 5th and 95th percentiles, and the bar in the box shows the median. **, P<0.001; ***, P<0.0005; ****, P<0.0001 versus controls.</p

Both ILT and conventional T cells are equally deficient in HD and KD patients.

<p>(A) HD patients had no significant differences in their number of iNKT, MAIT, CD4⁺ and CD8⁺ T cells when compared to kidney transplanted (KT) patients. Bars represent the median. (B) CD4⁺CD25⁺Foxp3⁺T cell numbers are similarly reduced in HD as in KD patients. Among these gated cells, cytokine-secreting CD45RA⁻Foxp3^lo nonsuppressive, resting suppressive CD45RA⁺Foxp3^lo and activated suppressive CD45RA⁻Foxp3^hi cell levels, are also similar in HD and KD patients. (C and D) The percentage of IFN<b>γ</b>⁺, IL-4⁺ or IL-17⁺ cells among gated CD4⁺ (C) or CD8⁺ (D) T lymphocytes was assessed after 6 h stimulation with PMA and ionomycin. Box-and-whisker plots are used to represent the distributions. The bottom and the top of a box represent the 5th and 95th percentiles, and the bar in the box shows the median. (A and B) Bars represent the median. *, P<0.01.</p

Short- and long-term renal outcomes following severe rhabdomyolysis: a French multicenter retrospective study of 387 patients

International audienceBACKGROUND:Rhabdomyolysis is a life-threatening disease that can lead to severe hyperkalemia, acute kidney injury (AKI) and hypovolemic shock. The predictive factors of AKI and acute to chronic kidney disease (CKD) transition remain poorly described.METHODS:This multicenter retrospective study enrolled 387 patients with severe rhabdomyolysis (CPK > 5000 U/L). Primary end-point was the development of severe AKI, defined as stage 2 or 3 of KDIGO classification. Secondary end-points included the incidence of AKI to CKD transition.RESULTS:Among the 387 patients, 315 (81.4%) developed AKI, including 171 (44.1%) with stage 3 AKI and 103 (26.6%) requiring RRT. Stage 2-3 AKI was strongly correlated with serum phosphate, potassium and bicarbonate at admission, as well as myoglobin over 8000 U/L and the need for mechanical ventilation. 42 patients (10.8%) died before day 28. In the 80 patients with available eGFR values both before and 3 months after the rhabdomyolysis, the decrease in eGFR (greater than 20 mL/min/1.73 m2 in 23 patients; 28.8%) was correlated to the severity of the AKI and serum myoglobin levels > 8000 U/L at admission.CONCLUSIONS:Severe rhabdomyolysis leads to AKI in most patients admitted to an ICU. Mechanical ventilation and severity of the rhabdomyolysis, including myoglobin level, are associated with the risk of stage 2-3 AKI. The long-term renal decline is correlated to serum myoglobin at admission