Rituximab therapy prevents focal and segmental glomerulosclerosis recurrence after a second renal transplantation.

Preventive treatment of focal and segmental glomerulosclerosis (FSGS) allograft recurrence in high risk recipients having a prior history of graft loss caused by FSGS recurrence is still a challenging question. We retrospectively identified four patients who underwent a second renal transplantation because of recurrent FSGS and who received Rituximab therapy as a prophylactic treatment. Loss of their first allograft was directly related to an early (<3 months) recurrence of FSGS that was either resistant to plasmapheresis therapy in two cases or had escaped to this therapeutic management in the two others. After the second renal transplantation, all patients were free of FSGS recurrence during follow-ups that were between 12 and 54 months long. These preliminary results demonstrate for the first time that Rituximab therapy may constitute an attractive prophylactic option for patients being considered for a second renal transplantation because of recurrent FSGS in their first graft.

Intrarenal IFN-γ mRNA expression differentiates clinical and subclinical glomerulitis in renal transplant recipients.

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.

Acute kidney injury in sickle patients with painful crisis or acute chest syndrome and its relation to pulmonary hypertension.

BACKGROUND: The association between chronic kidney involvement and sickle cell disease (SCD) has been well characterized, but our knowledge on acute kidney injury (AKI) in relation to SCD remains limited. METHODS: We retrospectively assessed 254 episodes of vaso-occlusive complication in 161 SCD patients who were admitted to our hospital: these included 174 episodes of painful crisis (PC), 58 episodes of moderate acute chest syndrome (ACS) and 22 episodes of severe ACS. RESULTS: The overall incidence of AKI [defined according to Acute Kidney Injury Network (AKIN) criteria] during vaso-occlusive complications was low (4.3%) but seemed to be related to its severity: 2.3% for PC vs 6.9% for moderate ACS and 13.6% for severe ACS (P = 0.03). This finding led us prospectively to look at specific risk factors for AKI occurrence in SCD patients admitted to our intensive care unit for severe ACS and, in particular, the possible link between AKI and haemodynamic status (transthoracic echocardiography). Among patients with severe ACS, those with AKI displayed significantly greater aminotransferases, bilirubin and lactate dehydrogenase levels than patients without AKI. Echocardiography identified higher systolic pulmonary artery pressure in patients with AKI than in those without, whereas the cardiac index was similar between groups. CONCLUSIONS: AKI incidence during vaso-occlusive complications of SCD is relatively low (<5%) and appears to be confined to patients with ACS and pulmonary hypertension. These findings suggest a pathophysiological process involving right ventricular dysfunction and venous congestion.

Intragraft levels of Foxp3 mRNA predict progression in renal transplants with borderline change.

The optimal therapeutic management of borderline lymphocytic infiltrates in renal allografts, described by Banff criteria, is unknown, largely because of the inability to predict clinical outcome in these cases. For determination of molecular factors that may predict outcome in cases of borderline change histology, mRNA levels of Foxp3, Granzyme B, IFN-gamma, IL-23, and RORgammat were measured in renal tissue from 46 untreated patients. Twenty-five patients were considered "nonprogressive," defined by a serum creatinine that remained <110% of baseline during the 40 d after biopsy. Twenty-one patients were considered "progressive," defined by an increase in serum creatinine >110% from baseline and by repeat histologic examination within 40 d showing progression toward acute rejection. Only Foxp3 mRNA levels were significantly higher in nonprogressors than in progressors (P = 0.001). Analysis of receiver operating characteristic curves demonstrated that the outcome for patients with biopsies showing borderline change could be predicted with 90% sensitivity and 79.1% specificity using the optimal Foxp3 mRNA cutoff value. Our findings suggest that the measurement of Foxp3 mRNA offers a means of improving prediction of outcome of borderline change.