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      Renal Tubular Complement 3 Deposition in Children with Primary Nephrotic Syndrome

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          Abstract

          Background

          This study aimed to investigate the clinical significance of complement 3 (C3) deposition in renal tubules of children with primary nephrotic syndrome (PNS).

          Methods

          The clinical and pathological characteristics of PNS were retrospectively reviewed in 99 PNS pediatric patients, who were divided into the C3 deposition and the non-C3 deposition groups.

          Results

          A total of 39 patients (39.39%) had renal tubule C3 deposition. In the C3 deposition group, the ratios of urine N-acetylglucosaminidase/creatinine (UNAG/Cr), urine β2 microglobulin/creatinine (U β2MG/Cr), and urine transferrin/creatinine (UTRF/Cr) were significantly higher than those of the non-C3 deposition group. The patients of the C3 deposition group had lower serum total protein and albumin, higher cholesterol and D-dimer (DD), lower proportion of CD3+CD8+ cells, and higher proportion of CD19+CD23+ cells. The number of the patients with interstitial fibrosis, renal cell vacuolar degeneration, renal tubular immunoglobulin deposition, and severe tubulointerstitial injury in the C3 deposition group was higher than that of the non-C3 deposition group. The C3 deposition intensity was positively correlated with the number of recurrences.

          Conclusion

          PNS pediatric patients with C3 deposition in renal tubules have more severe disease condition, tubulointerstitial injury, and recurrence suggesting a worse long-term prognosis.

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          Predicting renal outcome in IgA nephropathy.

          M G Radford, J V Donadio, E J Bergstralh … (1997)
          Immunoglobulin A (IgA) nephropathy, the most common form of glomerulonephritis worldwide, is characterized by a heterogeneous clinical course. In this study, multivariate analysis was performed to identify histopathologic and clinical features that most accurately predict adverse outcome from a dataset of 148 individuals with IgA nephropathy who underwent renal biopsy at our institution between 1973 and 1995. A semiquantitative scoring system was developed for assessment of six glomerular, eight interstitial, and six vascular histopathologic features of IgA nephropathy. Glomerular and interstitial proliferative activity was evaluated by immunostaining archival biopsy specimens with Mib-1, an antibody directed against the Ki-67 antigen. Kaplan-Meier survival analysis was performed, with renal failure being defined as onset of dialysis or transplantation. A number of clinicopathologic factors were univariately associated with adverse outcome, including elevated serum creatinine levels; the presence of hypertension; proteinuria; component and total histopathologic scores; and positive glomerular or interstitial Mib-1 scores. The total glomerular score, consisting of the arithmetic sum of each of the six component scores, was the strongest histopathologic predictor of adverse outcome. Total interstitial and vascular scores also provided more prognostic information than did individual component scores. By multivariate analysis, high total glomerular scores, increased serum creatinine levels at diagnosis, and younger age were significant (P < 0.01) independent predictors of renal failure. Our studies provide a rational basis for the inclusion of composite histopathologic scores in clinical intervention studies of patients with IgA nephropathy and other glomerular disorders.
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            Decreased Circulating C3 Levels and Mesangial C3 Deposition Predict Renal Outcome in Patients with IgA Nephropathy

            Seung Kim, Hyang Mo Koo, Beom Jin Lim … (2012)
            Background and Aims Mesangial C3 deposition is frequently observed in patients with IgA nephropathy (IgAN). However, the role of complement in the pathogenesis or progression of IgAN is uncertain. In this observational cohort study, we aimed to identify the clinical implications of circulating C3 levels and mesangial C3 deposition and to investigate their utility as predictors of renal outcomes in patients with IgAN. Methods A total of 343 patients with biopsy-proven IgAN were enrolled between January 2000 and December 2008. Decreased serum C3 level (hypoC3) was defined as C3 <90 mg/dl. The study endpoint was end-stage renal disease (ESRD) and a doubling of the baseline serum creatinine (D-SCr). Results Of the patients, there were 66 patients (19.2%) with hypoC3. During a mean follow-up of 53.7 months, ESRD occurred in 5 patients (7.6%) with hypoC3 compared with 9 patients (3.2%) with normal C3 levels (P = 0.11). However, 12 patients (18.2%) with hypoC3 reached D-SCr compared with 17 patients (6.1%) with normal C3 levels [Hazard ratio (HR), 3.59; 95% confidence interval (CI), 1.33–10.36; P = 0.018]. In a multivariable model in which serum C3 levels were treated as a continuous variable, hypoC3 significantly predicted renal outcome of D-SCr (per 1 mg/dl increase of C3; HR, 0.95; 95% CI, 0.92–0.99; P = 0.011). The risk of reaching renal outcome was significantly higher in patients with mesangial C3 deposition 2+ to 3+ than in patients without deposition (HR 9.37; 95% CI, 1.10–80.26; P = 0.04). Conclusions This study showed that hypoC3 and mesangial C3 deposition were independent risk factors for progression, suggesting that complement activation may play a pathogenic role in patients with IgAN.
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              Nephrotic syndrome in infants and children: pathophysiology and management.

              Claire Gallibois, Rulan Parekh, Damien G. Noone … (2017)
              Nephrotic syndrome is defined by nephrotic-range proteinuria (≥40 mg/m2/hour or urine protein/creatinine ratio ≥200 mg/mL or 3+ protein on urine dipstick), hypoalbuminaemia (<25 g/L) and oedema. This review focuses on the classification, epidemiology, pathophysiology, management strategies and prognosis of idiopathic nephrotic syndrome of childhood, and includes a brief overview of the congenital forms.
              Article 0 comments Cited 43 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Xiaozhong Li:
                ORCID: http://orcid.org/0000-0002-2911-7814
                Journal
                Journal ID (nlm-ta): Biomed Res Int
                Journal ID (iso-abbrev): Biomed Res Int
                Journal ID (publisher-id): BMRI
                Title: BioMed Research International
                Publisher: Hindawi
                ISSN (Print): 2314-6133
                ISSN (Electronic): 2314-6141
                Publication date Collection: 2018
                Publication date (Electronic): 30 May 2018
                Volume: 2018
                Electronic Location Identifier: 4386438
                Affiliations
                1Department of Nephrology, Children's Hospital of Soochow University, Suzhou, China
                2Department of Pediatrics, Taixing Hospital Affiliated to Yangzhou University, Taixing, Jiangsu, China
                3Department of Pathology, Children's Hospital of Soochow University, Suzhou, China
                Author notes

                Academic Editor: Maria Stangou

                Author information
                http://orcid.org/0000-0002-2911-7814
                Article
                DOI: 10.1155/2018/4386438
                PMC ID: 5998187
                SO-VID: acab7438-c340-44ca-a18c-268754cdf43e
                Copyright © Copyright © 2018 Fengying Wang et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 25 February 2018
                Date accepted : 29 March 2018
                Categories
                Subject: Research Article

                Data availability:

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