Circulating Factor Associated with Increased Glomerular Permeability to Albumin in Recurrent Focal Segmental Glomerulosclerosis

Savin, Virginia J.; Sharma, Ram; Sharma, Mukut; McCarthy, Ellen T.; Swan, Suzanne K.; Ellis, Eileen N.; Lovell, Helen B.; Warady, Bradley A.; Gunwar, Sripad; Chonko, Arnold M.; Artero, Mary; Vincenti, Flavio

doi:10.1056/nejm199604043341402

Cited by 656 publications

(537 citation statements)

References 31 publications

Supporting

Mentioning

508

Contrasting

Unclassified

Order By: Relevance

“…The pathologic variants and percentage of sclerotic glomeruli were also comparable between the two groups. These findings indicated that IgM deposition is not likely the initiation of FSGS lesion, which has been identified as several genes mutations or variants (9-13), circulating permeability factors (14)(15)(16), and others (17)(18)(19)(20)(21)(22)(23). However, IgM and complement-mediated injury may be secondary phenomena that occur after the primary renal insult.…”

Section: Discussionmentioning

confidence: 97%

Clinical Significance of IgM and C3 Glomerular Deposition in Primary Focal Segmental Glomerulosclerosis

Zhang

Huang

et al. 2016

CJASN

View full text Add to dashboard Cite

Background and objectives Glomerular IgM deposition is commonly shown in primary FSGS and sometimes accompanied by C3 deposition. Clinical presentation and treatment outcomes of these patients are not investigated in detail.Design, setting, participants, &measurements One hundred six consecutive patients with biopsy-proven primary FSGS from 2004 to 2014 were enrolled retrospectively. Clinical features and treatment outcomes were compared between patients with and without IgM/C3 deposition.Results Fifty-eight (54.7%) patients presented with IgM glomerular deposition on sclerotic segments. C3 and C1q depositions were shown exclusively in patients with IgM deposition (34.5% versus 0.0%; P,0.001 and 8.6% versus 0.0%; P=0.04, respectively). Patients with IgM deposition were younger (median; range: 24.5; 18.8-39.0 versus 46.5; 26.0-64.0 years old; P=0.001), had higher level of serum IgM (142.5;.0 versus 107.0; 71.0-140.0 mg/dl; P=0.01), and had higher level of eGFR (median; range 97.7; 48.0-135.8 versus 62.1; 33.7-93.9 ml/min per 1.73 m 2 ; P=0.01) at the time of kidney biopsy. The percentage of sclerosis lesions was significantly higher in patients with C3 deposition (median; range: 21.7%; 15.3%-31.1% versus 9.2%; 6.6%-20.0%; P=0.002). Although patients received comparable immunosuppressive treatments during 58.9 (29.5-81.1) months of follow-up, a significantly higher prevalence of refractory cases (no response or steroid dependent) occurred in patients with combined IgM and C3 deposition compared with patients with IgM deposition alone or without IgM deposition (58.8% versus 22.2% versus 15.6%, respectively; P=0.004). Multivariate analysis identified combined IgM and C3 deposition (odds ratio, 11.32; 95% confidence interval, 2.26 to 56.65; P=0.003) as an independent risk factor for refractory patients; 19 of 98 patients developed renal dysfunction when their serum creatinine levels increased .30% from baseline and reached .1.5 mg/dl. Combined IgM and C3 deposition (hazard ratio, 5.67; 95% confidence interval, 1.34 to 23.84; P=0.02) was identified as an independent risk factor for renal dysfunction.Conclusions Patients with primary FSGS and IgM and C3 deposition showed unfavorable therapeutic responses and worse renal outcomes, which indicate that IgM and C3 deposition might involve disease progression via complement activation.

show abstract

Section: Discussionmentioning

confidence: 97%

Clinical Significance of IgM and C3 Glomerular Deposition in Primary Focal Segmental Glomerulosclerosis

Zhang

Huang

et al. 2016

CJASN

View full text Add to dashboard Cite

show abstract

“…The pathogenesis of FSGS remains unclear but has been attributed to a 'circulating factor' present in the serum of patients with FSGS (2). Recurrence of FSGS after transplantation is not unusual and is most likely to occur in those recipients who have progressed rapidly to end-stage renal disease (ESRD) from the time of diagnosis (3).…”

Section: Introductionmentioning

confidence: 99%

Renal Allograft Survival in Transplant Recipients with Focal Segmental Glomerulosclerosis

Cibrik¹,

Kaplan

Campbell

et al. 2003

American Journal of Transplantation

View full text Add to dashboard Cite

“…Indeed, the risk of recurrence when there has been a previous allograft failure due to recurrent FSGS may be as high as 80% (274,282,286,291). It has been shown by some investigators that the presence of an abnormal serum protein correlates with FSGS recurrence (286,292,293). However, standardized assays are not available for clinical use.…”

Section: The Evaluation Of Renal Transplant Candidates: Clinical Pracmentioning

confidence: 99%

The Evaluation of the Renal Transplant Candidates: Clinical Practice Guidelines

2001

American Journal of Transplantation

View full text Add to dashboard Cite

Circulating Factor Associated with Increased Glomerular Permeability to Albumin in Recurrent Focal Segmental Glomerulosclerosis

Abstract: A circulating factor found in some patients with focal segmental glomerulosclerosis is associated with recurrent disease after renal transplantation and may be responsible for initiating the renal injury.

Cited by 656 publications

References 31 publications

Clinical Significance of IgM and C3 Glomerular Deposition in Primary Focal Segmental Glomerulosclerosis

Clinical Significance of IgM and C3 Glomerular Deposition in Primary Focal Segmental Glomerulosclerosis

Renal Allograft Survival in Transplant Recipients with Focal Segmental Glomerulosclerosis

The Evaluation of the Renal Transplant Candidates: Clinical Practice Guidelines

Contact Info

Product

Resources

About