Global positioning system use in the community to evaluate improvements in walking after revascularization: a prospective multicenter study with 6-month follow-up in patients with peripheral arterial disease

International audienceRevascularization aims at improving walking ability in patients with arterial claudication. The highest measured distance between 2 stops (highest-MDCW), the average walking speed (average-WSCW), and the average stop duration (average-DSCW) can be measured by global positioning system, but their evolution after revascularization is unknown.We included 251 peripheral artery diseased patients with self-reported limiting claudication. The patients performed a 1-hour stroll, recorded by a global positioning system receiver. Patients (n = 172) with confirmed limitation (highest-MDCW \textless2000m) at inclusion were reevaluated after 6 months. Patients revascularized during the follow-up period were compared with reference patients (ie, with unchanged lifestyle medical or surgical status). Other patients (lost to follow-up or treatment change) were excluded (n = 89).We studied 44 revascularized and 39 reference patients. Changes in highest-MDCW (+442 vs. +13 m) and average-WSCW (+0.3 vs. -0.2 km h) were greater in revascularized than in reference patients (both P \textless 0.01). In contrast, no significant difference in average-DSCW changes was found between the groups. Among the revascularized patients, 13 (29.5%) had a change in average-WSCW, but not in highest-MDCW, greater than the mean + 1 standard deviation of the change observed for reference patients.Revascularization may improve highest-MDCW and/or average-WSCW. This first report of changes in community walking ability in revascularized patients suggests that, beyond measuring walking distances, average-WSCW measurement is essential to monitor these changes. Applicability to other surgical populations remains to be evaluated. REGISTRATION: http://www.clinicaltrials.gov/ct2/show/NCT01141361

APOL1 polymorphisms and development of CKD in an identical twin donor and recipient pair.: Kidney donation in twins with APOL1 variant

International audienceWe report an occurrence of progressive loss of transplant function and ultimately transplant failure after living related kidney transplantation involving monozygotic twin brothers of Afro-Caribbean origin who were both heterozygous for the G1 and G2 kidney disease risk alleles in the APOL1 gene, which encodes apolipoprotein L-I. A 21-year-old man with end-stage kidney disease of unknown cause received a kidney from his brother, who was confirmed as a monozygotic twin by microsatellite analysis. Thirty months after transplantation, the patient presented with proteinuria and decreased estimated glomerular filtration rate; a biopsy of the transplant showed typical focal segmental glomerulosclerosis lesions. He received steroid therapy, but progressed to kidney failure 5 years later. The twin brother had normal kidney function without proteinuria at the time of transplantation; however, 7 years later, he was found to have decreased estimated glomerular filtration rate (40mL/min/1.73m(2)) and proteinuria (protein excretion of 2.5g/d). APOL1 genotyping revealed that both donor and recipient were heterozygous for the G1 and G2 alleles. This case is in stark contrast to the expected course of kidney transplantation in identical twins and suggests a role for APOL1 polymorphisms in both the donor and recipient

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-γ, IL-23, and RORγt 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

A 59-kd renal antigen as a new target for rapidly progressive glomerulonephritis

Anti-glomerular basement membrane (anti-GBM) antibodies are the hallmark of anti-GBM disease, which is characterized by rapidly progressive glomerulonephritis. We describe the case of a 58-year-old woman who presented with rapidly progressive glomerulonephritis with typical anti-GBM staining found by means of direct immunofluorescence microscopy, associated with linear immunoglobin G deposits on tubules. Serum analysis showed circulating anti-tubular basement membrane antibodies, but failed to detect anti-GBM antibodies. Immunoblotting showed that serum antibodies reacted with a 59-kd antigen found along both the GBM and tubular basement membrane

Clinicopathological study of glomerular diseases associated with sarcoidosis : A multicenter study.

International audienceBACKGROUND: The association between sarcoidosis and glomerular diseases has not been extensively investigated in a large series and the potential features of this uncommon association remain to be determined. METHODS: We retrospectively identified 26 patients with biopsy-proven glomerular lesions that occurred in a sarcoidosis context. Potential remission of glomerular disease and sarcoidosis under specific treatment (steroid and/or immunosuppressive agents) was recorded for all patients. Demographic, clinical and biological characteristics were assessed at the time of kidney biopsy for each patient. Therapeutic data were analyzed for all patients. RESULTS: Glomerular disease occurred after the diagnosis of sarcoidosis in 11 of 26 cases (42%) (mean delay of 9.7 years). In six patients (23%), the glomerulopathy preceded the sarcoidosis diagnosis (mean delay 8 years). In the last nine patients (35%), both conditions occurred simultaneously. The most frequent glomerular disease occurring in sarcoidosis patients was membranous nephropathy in eleven cases. Other glomerular lesions included IgA nephropathy in six cases, focal segmental glomerulosclerosis in four patients, minimal change nephrotic syndrome for three patients and proliferative lupus nephritis in two patients. Granulomatous interstitial nephritis was associated with glomerular disease in six patients and was exclusively found in patients in whom the both disease occurred simultaneously. In nine patients with simultaneous glomerular and sarcoidosis diseases, we observed a strong dissociation between glomerular disease and sarcoidosis in terms of steroid responsiveness. At the end of the follow-up (mean of 8.4 years), six patients had reached end-stage renal disease and three patients had died. CONCLUSIONS: A wide spectrum of glomerular lesions is associated with sarcoidosis. The close temporal relationship observed in some patients suggests common causative molecular mechanisms of glomerular injury but complete remission of both diseases in response to exclusive steroid therapy is infrequent

c-mip down-regulates NF-κB activity and promotes apoptosis in podocytes.

International audienceThe mechanisms of podocyte disorders in cases of idiopathic nephrotic syndrome (INS) are complex and remain incompletely elucidated. The abnormal regulation of NF-κB may play a key role in the pathophysiology of these podocyte diseases, but at present, NF-κB has not been thoroughly investigated. In this study, we report that induction of c-mip in podocytes of patients with INS is associated with a down-regulation of RelA, a potent antiapoptotic factor that belongs to the NF-κB family. Overexpression of c-mip in differentiated podocytes promotes apoptosis by inducing caspase-3 activity and up-regulating the proapoptotic protein Bax, whereas the overall levels of the antiapoptotic protein Bcl-2 was concomitantly decreased. The associated overexpression of RelA prevented the proapoptotic effects of c-mip. In addition, the targeted induction of c-mip in podocytes in vivo inhibited the expression of the RelA protein and increased the Bax/Bcl-2 ratio. The expression of both c-mip and active caspase-3 increased in focal and segmental glomerulosclerosis biopsies, and both proteins displayed a close spatial relationship. These results suggest that alterations in NF-κB activity might result from the up-regulation of c-mip and are likely to contribute to podocyte disorders in cases of INS

Upregulation of c-mip is closely related to podocyte dysfunction in membranous nephropathy.

International audienceMembranous nephropathy is a glomerular disease typified by a nephrotic syndrome without infiltration of inflammatory cells or proliferation of resident cells. Although the cause of the disease is unknown, the primary pathology involves the generation of autoantibodies against antigen targets on the surface of podocytes. The mechanisms of nephrotic proteinuria, which reflect a profound podocyte dysfunction, remain unclear. We previously found a new gene, c-mip (c-maf-inducing protein), that was associated with the pathophysiology of idiopathic nephrotic syndrome. Here we found that c-mip was not detected in the glomeruli of rats with passive-type Heymann nephritis given a single dose of anti-megalin polyclonal antibody, yet immune complexes were readily present, but without triggering of proteinuria. Rats reinjected with anti-megalin develop heavy proteinuria a few days later, concomitant with c-mip overproduction in podocytes. This overexpression was associated with the downregulation of synaptopodin in patients with membranous nephropathy, rats with passive Heymann nephritis, and c-mip transgenic mice, while the abundance of death-associated protein kinase and integrin-linked kinase was increased. Cyclosporine treatment significantly reduced proteinuria in rats with passive Heymann nephritis, concomitant with downregulation of c-mip in podocytes. Thus, c-mip has an active role in the podocyte disorders of membranous nephropathy