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      Clinical significance of IgM deposition in pediatric minimal change disease

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          Abstract

          Background

          Idiopathic nephrotic syndrome (INS) is a common pediatric disease. Minimal change disease (MCD) is the most common histopathological subtype and usually has good prognosis. However, in less common presentations, INS may have an unusual course that makes renal biopsy a necessity to identify its etiology. Immunoglobulin M (IgM) occasionally deposits in the mesangium and can be seen under immunofluorescence (IF). The role of IgM is controversial in MCD. It is likely associated with less favorable outcomes for MCD. This study aims to investigate the clinical significance of mesangial IgM deposits on the outcome of MCD in a pediatric population.

          Methods

          In this retrospective cohort study, we obtained native kidney biopsy samples from 192 children who were diagnosed with MCD from 2003 to 2014. The samples were divided into groups according to the histopathological deposition of IgM in biopsies under IF. The group for which biopsies showed IgM was labeled as IgM + IF (n = 77), and the group for which biopsies were without IgM was labeled as IgM-IF (n = 115). We reviewed hypertension, hematuria, and estimated glomerular filtration rate (eGFR) at the time of presentation to our institute; response to steroid therapy (remission, dependence, frequent relapses, and resistance) and response after adjuvant immunosuppressive therapy (complete remission, partial remission, frequent relapses, and no response) when indicated; development of chronic kidney disease (CKD) and end-stage renal disease during the course of the disease (ESRD).

          Results

          Our results showed that mesangial IgM deposition in MCD showed significant statistical association with hypertension at the time of presentation ( P = .05). There was statistically significant association between the presence of IgM deposition and the development of steroid dependence ( P = .05) and CKD during the course of the disease ( P = .05).

          Conclusions

          Our study showed that IgM deposition in MCD showed statistical association with hypertension by the time the patient presented to our institute, development of steroid dependence, and CKD. IgM may play a role in MCD. However, we recommend a prospective study to verify the role of IgM in MCD outcomes.

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          Most cited references12

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          Primary nephrotic syndrome in children: clinical significance of histopathologic variants of minimal change and of diffuse mesangial hypercellularity. A Report of the International Study of Kidney Disease in Children.

          (1981)
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            Complications of nephrotic syndrome

            Nephrotic syndrome (NS) is one of the most common glomerular diseases that affect children. Renal histology reveals the presence of minimal change nephrotic syndrome (MCNS) in more than 80% of these patients. Most patients with MCNS have favorable outcomes without complications. However, a few of these children have lesions of focal segmental glomerulosclerosis, suffer from severe and prolonged proteinuria, and are at high risk for complications. Complications of NS are divided into two categories: disease-associated and drug-related complications. Disease-associated complications include infections (e.g., peritonitis, sepsis, cellulitis, and chicken pox), thromboembolism (e.g., venous thromboembolism and pulmonary embolism), hypovolemic crisis (e.g., abdominal pain, tachycardia, and hypotension), cardiovascular problems (e.g., hyperlipidemia), acute renal failure, anemia, and others (e.g., hypothyroidism, hypocalcemia, bone disease, and intussusception). The main pathomechanism of disease-associated complications originates from the large loss of plasma proteins in the urine of nephrotic children. The majority of children with MCNS who respond to treatment with corticosteroids or cytotoxic agents have smaller and milder complications than those with steroid-resistant NS. Corticosteroids, alkylating agents, cyclosporin A, and mycophenolate mofetil have often been used to treat NS, and these drugs have treatment-related complications. Early detection and appropriate treatment of these complications will improve outcomes for patients with NS.
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              Immunopathological findings in idiopathic nephrosis: clinical significance of glomerular "immune deposits".

              Idiopathic nephrosis (IN), which includes minimal change (MCD), diffuse mesangial proliferation (DMP) and focal segmental glomerular sclerosis (FSGS), is classically characterized by the absence of significant deposits by immunofluorescence microscopy (IF), except for the focal lesions of segmental sclerosis and/or hyalinosis of FSGS, which fix IgM and C3 antiserums. Since IF is available in most centres, an increasing number of unexpected findings has been reported. In order to evaluate the clinical significance of the glomerular deposits revealed by IF in some instances, we reviewed the renal biopsy findings of 222 consecutive children presenting with IN and in whom IF microscopy was available. By light microscopy, 122 patients showed MCD, 10 DMP, and 90 FSGS with DMP (11 cases) or without (79 cases). By IF, 125 specimens were negative and served as controls; 54 showed mesangial IgM deposits, 24 mesangial IgG deposits (associated with Clq deposits in 16), 15 scattered granules of C3 and 4 predominant deposits of mesangial IgA. We correlated these findings with initial response to steroid therapy and outcome and could find no significant difference between the various categories defined by IF and the control group. Repeat biopsies, performed in 21 cases, showed the persistence of deposits in 11 and their transformation in 10. The particular problem raised by the patients who present with IN and mesangial IgA deposits is discussed. Our results demonstrate that patients presenting with IN and "positive IF", whether showing IgM, IgG and Clq, C3 or IgA, do not represent distinct clinicopathological entities.
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                Author and article information

                Contributors
                Journal
                Int J Pediatr Adolesc Med
                Int J Pediatr Adolesc Med
                International Journal of Pediatrics & Adolescent Medicine
                King Faisal Specialist Hospital and Research Centre
                2352-6467
                12 September 2019
                December 2019
                12 September 2019
                : 6
                : 4
                : 146-150
                Affiliations
                [a ]Department of Pediatric Nephrology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
                [b ]Department of Pathology and Laboratory Medicine- Anatomic Pathology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
                Author notes
                []Corresponding author. Section of Pediatric Nephrology, Department of Pediatrics, King Faisal Specialist Hospital and Research Center, P.O. Box 3357 MBC: 58, Riyadh, 11211, Saudi Arabia. tshareef@ 123456kfshrc.edu.sa
                Article
                S2352-6467(19)30089-4
                10.1016/j.ijpam.2019.09.001
                6926217
                31890840
                5afbc03b-074c-452e-b0c6-cc76e60fc4ab
                © 2019 Publishing services provided by Elsevier B.V. on behalf of King Faisal Specialist Hospital & Research Centre (General Organization), Saudi Arabia.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 21 March 2019
                : 19 July 2019
                : 3 September 2019
                Categories
                Review Article

                nephrotic syndrome,minimal change disease,igm,igm nephropathy

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