Therapy and outcomes of C3 glomerulopathy and immune-complex membranoproliferative glomerulonephritis

Khandelwal, Priyanka; Bhardwaj, Swati; Singh, Geetika; Sinha, Aditi; Hari, Pankaj; Bagga, Arvind

doi:10.1007/s00467-020-04736-8

Cited by 27 publications

(18 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A previous study had reported lupus nephritis was the most common cause among adult patients with secondary MPGN (12), and our results presented HBV infection as the most common cause for secondary MPGN in pediatric patients. A heterogenous clinical presentation of our patients displayed as nephriticnephrotic syndrome, nephrotic syndrome with hematuria or abnormal renal function, nephritic syndrome and asymptomatic hematuria or proteinuria, in line with the previous reports (22,23). Genetic detection helps to explore the underlying causes of MPGN.…”

Section: Discussionsupporting

confidence: 89%

“…It seems that current diagnostic criteria of IF labeling for C3G may be strict on pediatric patients with MPGN. Previous studies had shown the prognosis of patients with C3G is worse than patients with IC-MPGN, particularly in DDD patients(23,27). Therefore, we must take a close look at the clinical course for the patients with C3 dominant deposit in the glomerulus.…”

mentioning

confidence: 98%

See 1 more Smart Citation

Characteristics and outcomes of glomerulonephritis with membranoproliferative pattern in children

Xu¹,

Wei²,

Feng³

et al. 2021

Transl Pediatr

View full text Add to dashboard Cite

Background: Membranoproliferative glomerulonephritis (MPGN) is a rare histopathologic pattern of glomerular injury with limited studies in pediatric patients. Characteristics and outcomes of children with MPGN have also remained to be further explored. Methods:We retrospectively reviewed the clinicopathological features, genetic findings, treatments and outcomes in 17 pediatric patients pathologically diagnosed with MPGN from 2007 to 2020 in the Children's National Medical Center in China.Results: Median age at disease onset was 9.9 years (IQR, 5.6-11.9 years). Most of the patients (12/17) had nephrotic range of proteinuria, and nephritic-nephrotic syndrome was the most common clinical presentation (35.2%). Secondary causes were identified in eight patients including hepatitis B virus (HBV) infection (n=4), methylmalonic acidemia (MMA, n=2), rheumatoid arthritis (RA, n=1) and Aymé-Gripp Syndrome (n=1). The nine patients with primary MPGN were further identified as immune-complex mediated MPGN (n=8), and unclassifiable MPGN (U-MGPN, n=1). Genetic analyses identified pathogenic variants of MMACHC gene in two cases of MMA and established the diagnosis for Aymé-Gripp syndrome in one case with a de novo variant of MAF gene. Comparing study between the complete or partial remission group (n=8) and non-response group (n=9) showed a significant difference in the timing of renal biopsy (P<0.05). Normal renal function was preserved in ten patients at the last follow-up. Two patients developed into end-stage renal disease (ESRD). Conclusions:Children with MPGN pattern present heterogenous clinical features. Genetic detection helps to explore underlying causes of MPGN. Early identification of the primary or secondary causes of MPGN in children is vital.

show abstract

Section: Discussionsupporting

confidence: 89%

mentioning

confidence: 98%

Characteristics and outcomes of glomerulonephritis with membranoproliferative pattern in children

Xu¹,

Wei²,

Feng³

et al. 2021

Transl Pediatr

View full text Add to dashboard Cite

show abstract

“…4. We also did not screen diacylglycerol kinase epsilon (DGKE) gene mutations, in which MPGN pattern of injury and C3 dominant staining were reported on repeated kidney biopsy specimens in children [29]. Despite all these limitations, we still think that this study might present valuable information for the guidance of C3G management in clinical practice for pediatric nephrologists.…”

Section: Discussionmentioning

confidence: 98%

Complement gene mutations in children with C3 glomerulopathy: Do they affect clinical outcome?

Günay,

Dursun,

Gökce

et al. 2023

Preprint

View full text Add to dashboard Cite

Background C3 glomerulopathy(C3G) is a complement-mediated disease caused by abnormalities in the alternative complement pathway. Although genetic studies are not required for diagnosis, they are valuable for treatment planning and prognosis prediction. The aim of this study is to investigate the clinical phenotypes, kidney survival, and response to MMF treatment in pediatric C3G patients with and without mutations in complement related genes.Methods Sixty pediatric C3G patients were included, divided into two groups based on complement related gene mutations. Demographic and clinical-pathological findings, treatment modalities, and outcome data were compared, and Kaplan-Meier analysis was performed for kidney survival.Results Out of the 60 patients, 17 had mutations, with the most common mutation in the CH gene (47%). The mean age at diagnosis was significantly higher in the group with mutation (12.9 ± 3.6 vs 11.2 ± 4.1 years p = 0.039). While the patients without mutation were most frequently presented with the nephritic syndrome (44.2%), patients with the mutation were most likely to have asymptomatic urinary abnormalities (%47.1, p = 0.043). Serum parameters and histopathological characteristics were similar between the groups, but hypoalbuminemia was more common in patients without mutation. During a 45-month follow-up,10 patients progressed to CKD5, with four having a genetic mutation. The time to develop CKD5 was longer in the mutation group but not significantly different. MMF treatment had no effect on C3G progression in either group.Conclusions This study is the largest pediatric study examining the relationship between genotype and phenotype in C3G. We showed that in the mutation group often presented with asymptomatic urinary abnormalities, were diagnosed relatively late, but were not different from the mutation group in terms of MMF treatment response and kidney survival.

show abstract

“…Moreover, there has been no improvement in patient outcomes over the last several decades [17,18]. The multiple small cohort pediatric research studies in children with IC-MPGN/C3G, conducted post reclassification, have demonstrated either a worse renal prognosis in C3G [6,7], or no differences in treatment outcomes between the groups [8,[19][20][21]. Bomback et al previously found a 40% rate of progression rate to advanced chronic kidney disease (CKD), ESKD, or death in a large American cohort study of 111 C3G patients; approximately onethird of the 111 patients were children [22].…”

Section: Plos Onementioning

confidence: 99%

Demographic, clinical characteristics and treatment outcomes of immune-complex membranoproliferative glomerulonephritis and C3 glomerulonephritis in Japan: A retrospective analysis of data from the Japan Renal Biopsy Registry

et al. 2021

View full text Add to dashboard Cite

The reclassification of membranoproliferative glomerulonephritis (MPGN) into immune-complex MPGN (IC-MPGN) and C3 glomerulopathy (C3G) based on immunofluorescence findings in kidney biopsies has provided insights into these two distinct diseases. C3G is further classified into dense deposit disease and C3 glomerulonephritis (C3GN) based on electron micrographic findings. Although these diseases have poor outcomes, limited Japanese literature confined to small, single-center cohorts exist on these diseases. We retrospectively analyzed 81 patients with MPGN type I and III from 15 hospitals in the Japan Renal Biopsy Registry to compare demographic, clinical characteristics and treatment outcomes of patients with IC-MPGN to those with C3GN. Of the 81 patients reviewed by immunofluorescence findings in kidney biopsies, 67 patients had IC-MPGN and 14 patients had C3GN. Age at diagnosis and systolic and diastolic pressure were higher and proteinuria and impaired renal function were significantly more prevalent in patients with IC-MPGN than those with C3GN. About 80% of the patients in both groups were treated with immunosuppressive therapy. At last follow-up (median 4.8 years), complete remission rate of proteinuria was significantly higher in patients with C3GN (64.3%) than in those with IC-MPGN (29.9%; P = 0.015). The renal survival rate was lower in patients with IC-MPGN when compared to C3GN (73.1% vs. 100%; log-rank, P = 0.031). Systolic blood pressure and renal function at baseline were independent predictors of progression to end-stage kidney disease. The overall prognosis of patients with C3GN is more favorable than for patients with IC-MPGN.

show abstract

Therapy and outcomes of C3 glomerulopathy and immune-complex membranoproliferative glomerulonephritis

Cited by 27 publications

References 32 publications

Characteristics and outcomes of glomerulonephritis with membranoproliferative pattern in children

Characteristics and outcomes of glomerulonephritis with membranoproliferative pattern in children

Complement gene mutations in children with C3 glomerulopathy: Do they affect clinical outcome?

Demographic, clinical characteristics and treatment outcomes of immune-complex membranoproliferative glomerulonephritis and C3 glomerulonephritis in Japan: A retrospective analysis of data from the Japan Renal Biopsy Registry

Contact Info

Product

Resources

About