Recurrence of Focal Segmental Glomerulosclerosis in Renal Allografts

J, Pinto; G, Lacerda; Js, Cameron; Dr, Turner; Bewick, M.; Cs, Ogg

doi:10.1097/00007890-198108000-00001

Cited by 99 publications

(60 citation statements)

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“…In 90% of these patients, nephrotic syndrome recurs within the first hours after transplantation, suggesting the intervention of a circulating albuminuric factor. The beneficial effect of plasmapheresis also supports this hypothesis [3][4][5][6] . Several attempts have been made in order to determine the nature of this putative albuminuric factor, but its molecular characterization has remained elusive.…”

supporting

confidence: 59%

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Potential Role of Soluble ST2 Protein in Idiopathic Nephrotic Syndrome Recurrence Following Kidney Transplantation

Bruneau

Berre

Hervé

et al. 2009

American Journal of Kidney Diseases

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France.DS and JD contributed equally to this work. No differences were detected in these sera before transplantation. Moreover, recurrent patients displayed the same sST2 isoform as the two control groups. In vitro, a mouse podocyte cell line was profoundly altered by incubation with sera of recurrent patients. However, purified sST2 from these patients was not able to reproduce these damages. In addition, induction of high sST2 levels in rats did not trigger proteinuria. Collectively, these data suggest that sST2 is a marker of INS recurrence that could be of interest for its diagnosis in ambiguous clinical situations. Nonetheless, sST2 does not seem to be directly implicated in INS development. This work was supported in part by

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supporting

confidence: 59%

“…After transplantation, 30-50% of these patients develop a recurrence of their initial disease, leading to roughly 50% of graft lost 3,4 . In 90% of these patients, nephrotic syndrome recurs within the first hours after transplantation, suggesting the intervention of a circulating albuminuric factor.…”

mentioning

confidence: 99%

Potential Role of Soluble ST2 Protein in Idiopathic Nephrotic Syndrome Recurrence Following Kidney Transplantation

Bruneau

Berre

Hervé

et al. 2009

American Journal of Kidney Diseases

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“…As the prevalence of FSGS in the Western world has increased steadily (15), it now represents the leading cause of chronic renal failure in North America. Treatment of FSGS is limited, and the disease frequently recurs in the renal transplant with massive proteinuria (16). As treatment and prognosis of MCD and FSGS are fundamentally different, a clear diagnostic distinction between these entities is of central importance.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiles of Podocyte-Associated Molecules as Diagnostic Markers in Acquired Proteinuric Diseases

Schmid¹,

Henger²,

Cohen³

et al. 2003

Journal of the American Society of Nephrology

120

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Abstract. For identifying potential diagnostic markers of proteinuric glomerulopathies, glomerular mRNA levels of molecules relevant for podocyte function (␣-actinin-4, glomerular epithelial protein 1, Wilms tumor antigen 1, synaptopodin, dystroglycan, nephrin, podoplanin, and podocin) were determined by quantitative real-time RT-PCR from microdissected glomeruli. Biopsies from 83 patients with acquired proteinuric diseases were analyzed (minimal change disease [MCD; n ϭ 13], benign nephrosclerosis [n ϭ 16], membranous glomerulopathy [n ϭ 31], focal and segmental glomerulosclerosis [FSGS; n ϭ 9], and controls [n ϭ 14]). Gene expression levels normalized to two different housekeeping transcripts (glyceraldehyde-3-phosphate-dehydrogenase and 18 S rRNA) did not allow a separation between proteinuric disease categories. However, a significant positive correlation between ␣-actinin-4, glomerular epithelial protein 1, synaptopodin, dystroglycan, Wilms tumor antigen 1, and nephrin was found in all analyzed glomeruli, whereas podocin mRNA expression did not correlate. Because varying amounts of housekeeper cDNA per glomerulus can confound expression ratios relevant for a subpopulation of cells, an "in silico" microdissection was performed using a podocyte-specific cDNA as a reference gene. Expression ratio of podocin to synaptopodin, the two genes with the most disparate expression, allowed a robust separation of FSGS from MCD and nephrosclerosis. Segregation of FSGS from MCD via this ratio was confirmed in an independent population of formaldehyde-fixed archival biopsies (MCD, n ϭ 5; FSGS, n ϭ 4) after glomerular laser capture microdissection. In addition, the expression marker was able to predict steroid responsiveness in diagnostically challenging cases of MCD versus FSGS (n ϭ 6). As the above approach can be performed as an add-on diagnostic tool, these molecular diagnostic parameters could give novel information for the management of proteinuric diseases.Proteinuric glomerular diseases still pose a formidable challenge to nephrology. Recent studies have highlighted the importance of proteinuria both as a clinical prognostic marker and as a factor predicting progressive loss of renal function (1-3). Alteration of the glomerular filtration barrier leads via damage of the glomerular podocyte to leakage of proteins into the ultrafiltrate (4). The filtration barrier consists of a specialized fenestrated endothelium, the fibrillar, hydrated meshwork of the glomerular basement membrane (GBM), and interdigitating podocyte foot processes with intervening filtration slits as the final filtration barrier (5). Identification of mutations in podocyte-associated molecules in various hereditary nephrotic disorders has highlighted the key role of the podocyte for the pathophysiology of proteinuria. The gene product of NPHS1, nephrin, mutated in congenital nephrotic syndrome of the Finnish type, has been localized to the podocyte slit diaphragm (6). Mutations in a gene termed NPHS2, encoding the novel protein podocin, are associate...

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“…Recurrence of FSGS after kidney transplantation is frequent (20-40%) and associated with poor graft survival (7)(8)(9)(10)(11)(12)(13) (14)(15)(16). Immunosuppressive drug therapy with cyclosporine (CsA), cyclophosphamide, mycophenolate mofetil or tacrolimus, either as monotherapy or in combination, has also produced inconsistent results (7,8,12,(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). In a pediatric series, however, intravenous CsA induced sustained remission in 70% of patients who received PE and in 30% of patients without PE (21).…”

Section: Primary Focal Segmental Glomerulosclerosis (Fsgs) Leads To Ementioning

confidence: 99%

Intensive and Prolonged Treatment of Focal and Segmental Glomerulosclerosis Recurrence in Adult Kidney Transplant Recipients: A Pilot Study

Canaud

Zuber

Sberro

et al. 2009

American Journal of Transplantation

114

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No treatment has consistently induced long-term remission of proteinuria in adult patients with focal segmental glomerulosclerosis (FSGS) recurrence after kidney transplantation. We undertook an open-label, nonrandomized pilot trial of intensive and prolonged treatment of FSGS recurrence. Over an 18-month period, 10 adult kidney transplant recipients with FSGS recurrence received concomitantly high-dose steroids, intravenous cyclosporine for 14 days followed by oral cyclosporine therapy, and an intensive and prolonged course of plasma exchanges (PE). We compared this treatment with those of a control group of 19 patients with a FSGS recurrence transplanted between 1997 and 2005. Complete, rapid (mean 23 ± 7 days) and sustained remission was obtained in 9/10 patients (90%) as opposed to 27% in the control group. At month 3 and month 12, proteinuria was 0.16 g/day (range 0.05-0.3 g/day) and 0.19 g/day (range 0.05-1 g/day) respectively. Only one patient remained in partial remission at month 12 but he had already lost two previous grafts due to FSGS recurrence. PEs were stopped at month 9 in all patients except for the patient with a partial remission who remains PE-dependent. This small pilot study provides very encouraging results demonstrating that this treatment rapidly achieves complete and sustained remission in a high proportion of patients.

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Recurrence of Focal Segmental Glomerulosclerosis in Renal Allografts

Cited by 99 publications

References 0 publications

Potential Role of Soluble ST2 Protein in Idiopathic Nephrotic Syndrome Recurrence Following Kidney Transplantation

Potential Role of Soluble ST2 Protein in Idiopathic Nephrotic Syndrome Recurrence Following Kidney Transplantation

Gene Expression Profiles of Podocyte-Associated Molecules as Diagnostic Markers in Acquired Proteinuric Diseases

Intensive and Prolonged Treatment of Focal and Segmental Glomerulosclerosis Recurrence in Adult Kidney Transplant Recipients: A Pilot Study

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