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Vivarelli M, Samuel S, Coppo R, Barratt J, Bonilla-Felix M, Haffner D, Gibson K, Haas M, Abdel-Hafez MA, Adragna M, Brogan P, Kim S, Liu I, Liu ZH, Mantan M, Shima Y, Shimuzu M, Shen Q, Trimarchi H, Hahn D, Hodson E, Pfister K, Alladin A, Boyer O, Nakanishi K. IPNA clinical practice recommendations for the diagnosis and management of children with IgA nephropathy and IgA vasculitis nephritis. Pediatr Nephrol 2025; 40:533-569. [PMID: 39331079 PMCID: PMC11666671 DOI: 10.1007/s00467-024-06502-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 08/08/2024] [Accepted: 08/08/2024] [Indexed: 09/28/2024]
Abstract
IgA nephropathy and IgA vasculitis with nephritis, albeit rare, represent two relatively frequent glomerular conditions in childhood. Compared to adults, pediatric IgA nephropathy has a more acute presentation, most frequently with synpharyngitic macrohematuria and histologically with more intense inflammation and less intense chronic damage. Management of these conditions is controversial and supported by little high-quality evidence. The paucity of evidence is due to the disease heterogeneity, its inter-ethnic variability, and the difficulty of extrapolating data from adult studies due to the peculiarities of the condition in children. IgA vasculitis with nephritis is a kidney manifestation of a systemic disorder, typical of the pediatric age, in which both the diagnosis of kidney involvement and its management are poorly defined, and an interdisciplinary approach is crucial. Both conditions can have a profound and long-lasting impact on kidney function and the global health of affected children. The International Pediatric Nephrology Association has therefore convened a diverse international group of experts from different disciplines to provide guidance on the recommended management of these conditions in children and to establish common definitions and define priorities for future high-quality, evidence-based collaborative studies for the benefit of children.
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Affiliation(s)
- Marina Vivarelli
- Laboratory of Nephrology, Bambino Gesù Children's Hospital, IRCCS, Piazza S. Onofrio 4 00165, Rome, Italy.
| | - Susan Samuel
- Section of Nephrology, Department of Pediatrics, University of Calgary, Calgary, Canada
| | - Rosanna Coppo
- Fondazione Ricerca Molinette, Regina Margherita Hospital, Turin, Italy
| | | | - Melvin Bonilla-Felix
- Department of Pediatrics, University of Puerto Rico-Medical Sciences Campus, San Juan, , Puerto Rico
| | - Dieter Haffner
- Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany
| | - Keisha Gibson
- University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Mark Haas
- Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | | | - Marta Adragna
- Hospital de Pediatría Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina
| | - Paul Brogan
- University College London Great Ormond Street Institute of Child Health, London, England, UK
| | - Siah Kim
- Children's Hospital at Westmead, Westmead, Australia
| | - Isaac Liu
- Duke-NUS Medical School and YLLSOM, National University of Singapore, Singapore, Singapore
| | - Zhi-Hong Liu
- Nanjing University School of Medicine, Nanjing, China
| | - Mukta Mantan
- Maulana Azad Medical College, University of Delhi, Delhi, India
| | - Yuko Shima
- Wakayama Medical University, Wakayama, Japan
| | - Masaki Shimuzu
- Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo, Japan
| | - Qian Shen
- Children's Hospital of Fudan University, Shanghai, China
| | | | - Deirdre Hahn
- Children's Hospital at Westmead, Westmead, Australia
| | | | - Ken Pfister
- Department of Pediatrics, University of Calgary, Calgary, Canada
| | - Areefa Alladin
- Department of Pediatrics, University of Calgary, Calgary, Canada
- University of Guyana, Georgetown, Guyana
| | - Olivia Boyer
- Pediatric Nephrology, MARHEA Reference Center, Imagine Institute, Paris Cité University, Necker Children's Hospital, APHP, Paris, France
| | - Koichi Nakanishi
- Department of Child Health and Welfare (Pediatrics), Graduate School of Medicine, University of Ryukyus, Nishihara, Okinawa, Japan
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Ambarsari CG, Palupi-Baroto R, Sinuraya FAG, Suryati E, Widyastuti E, Widhiati S. Nephropathy in a Child with Severe Recessive Dystrophic Epidermolysis Bullosa Treated with Cyclophosphamide: A Case Report. Case Rep Nephrol Dial 2023; 13:75-83. [PMID: 37484797 PMCID: PMC10359707 DOI: 10.1159/000530875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Accepted: 04/20/2023] [Indexed: 07/25/2023] Open
Abstract
Long-term inflammation and recurrent skin infection in recessive dystrophic epidermolysis bullosa (RDEB) are associated with the presence of immunoglobulin A (IgA)-containing immune complexes in the glomerulus. Only eight pediatric RDEB cases with IgA nephropathy (IgAN) have been documented in English-language literature. Most RDEB patients with IgAN progress to kidney failure within 5 years of diagnosis, indicating that these patients may require more intensive early treatment compared to those with primary IgAN. However, diagnosing IgAN in RDEB cases with severe cutaneous manifestations can be challenging. Herein, we report a rare case of nephropathy in an 11-year-old boy with severe RDEB and a frameshift mutation on the COL7A1 gene, which may manifest as kidney disorders. He presented with persistent hematuria and progressing proteinuria. A presumptive IgAN diagnosis was based on clinical features and increased IgA serum levels, as kidney biopsy was refused by his parents. Nephrotic-range proteinuria persisted despite initial steroid and lisinopril treatment. Monthly intravenous cyclophosphamide (IV CPA; 500 mg/m2) led to proteinuria remission and preservation of kidney function for 2 years posttreatment. We conclude that COL7A1 mutations may result in extracutaneous manifestations, including kidney disorders. The association between IgA-containing immune complex deposits in the glomerulus and recurrent skin infection in RDEB may indicate IgAN, particularly when kidney biopsy is infeasible due to severe skin manifestations. In our case, positive results with IV CPA suggest further investigation is needed to explore its potential role in non-rapidly progressing IgAN in children with RDEB.
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Affiliation(s)
- Cahyani Gita Ambarsari
- Department of Child Health, Faculty of Medicine Universitas Indonesia - Cipto Mangunkusumo Hospital, Jakarta, Indonesia
- School of Medicine, University of Nottingham, Nottingham, UK
- Medical Technology Cluster, Indonesian Medical Education and Research Institute (IMERI), Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
| | - Retno Palupi-Baroto
- Department of Child Health, Faculty of Medicine, Public Health and Nursing Universitas Gadjah Mada/Dr. Sardjito General Hospital, Yogyakarta, Indonesia
| | | | - Elvi Suryati
- Department of Child Health, Faculty of Medicine Universitas Indonesia - Cipto Mangunkusumo Hospital, Jakarta, Indonesia
- Department of Child Health, Faculty of Medicine Universitas Lampung - Abdoel Moeloek General Hospital, Bandar Lampung, Indonesia
| | - Etty Widyastuti
- Puri Betik Hati Women and Children Hospital, Bandar Lampung, Indonesia
| | - Suci Widhiati
- Department of Dermatology and Venereology, Faculty of Medicine, Universitas Sebelas Maret, Dr. Moewardi Hospital, Surakarta, Indonesia
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Han SY, Jung CY, Lee SH, Lee DW, Lee S, Kim CD, Choi BS, Kim BS. A multicenter, randomized, open-label, comparative, phase IV study to evaluate the efficacy and safety of combined treatment with mycophenolate mofetil and corticosteroids in advanced immunoglobulin A nephropathy. Kidney Res Clin Pract 2022; 41:452-461. [PMID: 35545228 PMCID: PMC9346400 DOI: 10.23876/j.krcp.21.146] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 12/07/2021] [Indexed: 11/19/2022] Open
Abstract
Background It remains unclear whether immunosuppressive agents are effective in patients with immunoglobulin A nephropathy (IgAN). We investigated the efficacy of a mycophenolate mofetil (MMF) and corticosteroid combination therapy in patients with advanced IgAN. Methods We conducted a multicenter, randomized, placebo-controlled, parallel-group study of 48 weeks administration of MMF and corticosteroids in biopsy-proven advanced IgAN patients with estimated glomerular filtration rate (eGFR) of 20–50 mL/min/1.73 m2 and urine protein-to-creatinine ratio (UPCR) of >0.75 g/day. The primary outcome was complete (UPCR < 0.3 g/day) or partial (>50% reduction of UPCR compared to baseline) remission at 48 weeks. Results Among the 48 randomized patients, the percentage that achieved complete or partial remission was greater in thecombination therapy group than in the control group (4.2% vs. 0% and 29.1% vs. 5.0%, respectively). Compared with the combination therapy group, eGFR in the control group decreased significantly from week 36 onward, resulting in a final adjusted mean change of –4.39 ± 1.22 mL/min/1.73 m2 (p = 0.002). The adjusted mean changes after 48 weeks were 0.62 ± 1.30 and –5.11 ± 1.30 mL/min/1.73 m2 (p = 0.005) in the treatment and control groups, respectively. The UPCR was significantly different between the two groups; the adjusted mean difference was –0.47 ± 0.17 mg/mgCr and 0.07 ± 0.17 mg/mgCr in the treatment and control group, respectively (p = 0.04). Overall adverse events did not differ between the groups. Conclusion In advanced IgAN patients with a high risk for disease progression, combined MMF and corticosteroid therapy appears to be beneficial in reducing proteinuria and preserving renal function.
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Affiliation(s)
- Sang Youb Han
- Department of Internal Medicine, Inje University College of Medicine, Goyang, Republic of Korea
| | - Chan-Young Jung
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sang Ho Lee
- Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, Republic of Korea
| | - Dong Won Lee
- Department of Internal Medicine, Pusan National University School of Medicine, Yangsan, Republic of Korea
| | - Sik Lee
- Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea
| | - Chan-Duck Kim
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Bum Soon Choi
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Bum Soon Choi Department of Internal Medicine, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea. E-mail:
| | - Beom Seok Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Correspondence: Beom Seok Kim Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03772, Republic of Korea. E-mail:
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Treatment of IgA nephropathy in children: a land without KDIGO guidance. Pediatr Nephrol 2021; 36:491-496. [PMID: 32060820 DOI: 10.1007/s00467-020-04486-7] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 09/25/2019] [Accepted: 01/20/2020] [Indexed: 10/25/2022]
Abstract
IgA nephropathy (IgAN) in children is no longer considered a rare and benign disease but a nephritis with different presentations and various outcomes. The decision to initiate a treatment and the therapeutic choice depend on the individual risk of progression. The Kidney Disease: Improving Global Outcomes (KDIGO) clinical guidelines in 2012 considered that the risk factors for progression of IgAN were similar in both children and adults and suggested in some conditions to follow the adult schedules. In 2017 a KDIGO Controversies Conference on management and treatment of glomerular diseases decided not to include an update in children with IgAN since the level of evidence of treatments in children was too scarce. Children can follow the indications for adults as far as the disease is similar in the various ages. This review is aimed at discussing why the KDIGO guidelines are poorly suitable to treat children with IgAN, and there is a need to develop new prediction models for progression of IgAN in children to guide selection of the cases to be treated. The identification of different risk levels in children with IgAN may personalize the choice of available drugs and support the use of new targeted therapies.
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Cambier A, Boyer O, Deschenes G, Gleeson J, Couderc A, Hogan J, Robert T. Steroid therapy in children with IgA nephropathy. Pediatr Nephrol 2020; 35:359-366. [PMID: 30778826 DOI: 10.1007/s00467-018-4189-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2018] [Revised: 12/20/2018] [Accepted: 12/21/2018] [Indexed: 01/14/2023]
Abstract
IgA nephropathy (IgAN) is one the most common primary glomerulonephritis in children and adolescents worldwide, with 20% of children developing end-stage kidney disease (ESKD) within 20 years of diagnosis. There is a need for treatment guidelines, especially for steroids in children with primary IgAN, since the STOP-IgA trial casts doubts on the use of steroids in adults with intermediate risk. Pediatricians are prone to prescribe steroids in addition to renin-angiotensin system blockade (RASB) when proteinuria is > 0.5 g/l, eGFR deteriorates < 70 ml/min/1.73 m2, or when a biopsy sample shows glomerular inflammation. Lack of randomized controlled trials (RCTs) in children with IgAN has led to an absence of consensus on the use of immunosuppressive agents in the treatment of progressive IgAN. This literature review evaluates the available evidence on steroid treatment in children with IgAN.
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Affiliation(s)
- Alexandra Cambier
- Pediatric Department of Nephrology and Transplantation, Assistance Publique-Hôpitaux de Paris, Hôpital Robert-Debré, Paris, France.
| | - Olivia Boyer
- Pediatric Department of Nephrology and Transplantation, Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Paris, France
| | - Georges Deschenes
- Pediatric Department of Nephrology and Transplantation, Assistance Publique-Hôpitaux de Paris, Hôpital Robert-Debré, Paris, France
| | - James Gleeson
- Université Paris Diderot, Faculté de Médecine, Site Xavier Bichat, INSERM U1149 & CNRS ERL8252, Centre de Recherche sur l'Inflammation, Paris, France
| | - Anne Couderc
- Pediatric Department of Nephrology and Transplantation, Assistance Publique-Hôpitaux de Paris, Hôpital Robert-Debré, Paris, France
| | - Julien Hogan
- Pediatric Department of Nephrology and Transplantation, Assistance Publique-Hôpitaux de Paris, Hôpital Robert-Debré, Paris, France
| | - Thomas Robert
- Department of Nephrology, Transplantation and Emergency, Assistance Publique-Hôpitaux de Marseille, Hôpital de la Conception, Marseille, France.
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Liu N, Ma ZZ, Yan HF, Li Q, Lyu XQ, Kang WL, Yin ZR. [Clinical effect of double filtration plasmapheresis combined with glucocorticoid and immunosuppressant in treatment of children with severe Henoch-Schönlein purpura nephritis]. ZHONGGUO DANG DAI ER KE ZA ZHI = CHINESE JOURNAL OF CONTEMPORARY PEDIATRICS 2019; 21:955-959. [PMID: 31642426 PMCID: PMC7389723] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Accepted: 07/30/2019] [Indexed: 11/12/2023]
Abstract
OBJECTIVE To study the clinical effect and safety of double filtration plasmapheresis (DFPP) combined with double pulse therapy with methylprednisolone (MP) and cyclophosphamide (CTX) in the treatment of children with severe Henoch-Schönlein purpura nephritis (HSPN). METHODS A total of 60 children with severe HSPN who were admitted to the hospital from January 2014 to March 2018 were enrolled and were randomly divided into an observation group and a control group (n=30 each). In addition to routine treatment, the children in the control group were given MP+CTX pulse therapy. Those in the observation group were given DFPP treatment in addition to the treatment in the control group, with three courses of treatment in total. After three courses of treatment, the two groups were compared in terms of 24-hour urinary protein, urinary microproteins, renal function parameters, adverse reactions, and clinical outcome. RESULTS After three courses of treatment, the observation group had significantly greater reductions in 24-hour urinary protein, urinary albumin, urinary immunoglobulin G, urinary β2-microglobulin, serum creatinine, and blood urea nitrogen than the control group (P<0.05). After the treatment ended, the observation group had a significantly shorter time to achieve remission than the control group (P<0.05). No serious adverse reactions, such as hemorrhagic cystitis, thrombocytopenia, and hemolysis, were observed, and there was no significant difference in the overall incidence rate of adverse reactions between the two groups (P>0.05). CONCLUSIONS Compared with MP+CTX pulse therapy alone in the treatment of severe HSPN in children, DFPP combined with MP+CTX pulse therapy can further alleviate renal injury and improve clinical outcome and does not increase the incidence rate of adverse reactions.
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Affiliation(s)
- Na Liu
- Department of Pediatrics, Harrison International Peace Hospital, Hengshui, Hebei 053000, China.
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7
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Liu N, Ma ZZ, Yan HF, Li Q, Lyu XQ, Kang WL, Yin ZR. [Clinical effect of double filtration plasmapheresis combined with glucocorticoid and immunosuppressant in treatment of children with severe Henoch-Schönlein purpura nephritis]. ZHONGGUO DANG DAI ER KE ZA ZHI = CHINESE JOURNAL OF CONTEMPORARY PEDIATRICS 2019; 21:955-959. [PMID: 31642426 PMCID: PMC7389723 DOI: 10.7499/j.issn.1008-8830.2019.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 04/01/2019] [Accepted: 07/30/2019] [Indexed: 06/10/2023]
Abstract
OBJECTIVE To study the clinical effect and safety of double filtration plasmapheresis (DFPP) combined with double pulse therapy with methylprednisolone (MP) and cyclophosphamide (CTX) in the treatment of children with severe Henoch-Schönlein purpura nephritis (HSPN). METHODS A total of 60 children with severe HSPN who were admitted to the hospital from January 2014 to March 2018 were enrolled and were randomly divided into an observation group and a control group (n=30 each). In addition to routine treatment, the children in the control group were given MP+CTX pulse therapy. Those in the observation group were given DFPP treatment in addition to the treatment in the control group, with three courses of treatment in total. After three courses of treatment, the two groups were compared in terms of 24-hour urinary protein, urinary microproteins, renal function parameters, adverse reactions, and clinical outcome. RESULTS After three courses of treatment, the observation group had significantly greater reductions in 24-hour urinary protein, urinary albumin, urinary immunoglobulin G, urinary β2-microglobulin, serum creatinine, and blood urea nitrogen than the control group (P<0.05). After the treatment ended, the observation group had a significantly shorter time to achieve remission than the control group (P<0.05). No serious adverse reactions, such as hemorrhagic cystitis, thrombocytopenia, and hemolysis, were observed, and there was no significant difference in the overall incidence rate of adverse reactions between the two groups (P>0.05). CONCLUSIONS Compared with MP+CTX pulse therapy alone in the treatment of severe HSPN in children, DFPP combined with MP+CTX pulse therapy can further alleviate renal injury and improve clinical outcome and does not increase the incidence rate of adverse reactions.
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Affiliation(s)
- Na Liu
- Department of Pediatrics, Harrison International Peace Hospital, Hengshui, Hebei 053000, China.
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Serum IgG Level and IgG/IgM Ratio on Admission Predict Steroid-Resistant Response in Vietnamese Children with Idiopathic Nephrotic Syndrome. Nephrourol Mon 2019. [DOI: 10.5812/numonthly.93248] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
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Identification of a novel COL4A5 mutation in the proband initially diagnosed as IgAN from a Chinese family with X-linked Alport syndrome. SCIENCE CHINA-LIFE SCIENCES 2019; 62:1572-1579. [PMID: 31209800 DOI: 10.1007/s11427-018-9545-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/22/2018] [Accepted: 02/16/2019] [Indexed: 01/20/2023]
Abstract
Alport syndrome (AS) is a hereditary progressive nephropathy characterized by hematuria, ultrastructural lesions of the glomerular basement membrane, ocular lesions and sensorineural hearing loss. Germline mutations of COL4A5 are associated with X-linked AS with an extreme phenotypic heterogeneity. Here, we investigated a Chinese family with Alport syndrome. The proband was a 9-year-old boy with hematuria and proteinuria. Based on the test results of renal biopsy and immunofluorescence, the proband was initially diagnosed as IgA nephropathy and the treatment was recommended accordingly. Meanwhile, we found that the treatment outcome was poor. Therefore, for proper clinical diagnosis and appropriate treatment, targeted exome-based next-generation sequencing has been undertaken. We identified a novel hemizygous single nucleotide deletion c.1902delA in COL4A5 gene. Segregation analysis identified that this novel mutation is co-segregated among the affected family members but absent in unaffected family members. The clinical diagnosis of the proband was revised as AS accompanied by IgA nephropathy, which has been rarely reported. Our findings demonstrated the significance of the application of Genetic screening, expanded the mutation spectrum of COL4A5 associated AS patients with atypical renal phenotypes and provided a good lesson to be learned from our detour during the diagnosis.
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Tang SCW, Wong AKM, Mak SK. Clinical practice guidelines for the provision of renal service in Hong Kong: General Nephrology. Nephrology (Carlton) 2019; 24 Suppl 1:9-26. [PMID: 30900340 DOI: 10.1111/nep.13500] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Affiliation(s)
- Sydney Chi-Wai Tang
- Division of Nephrology, Department of Medicine, The University of Hong Kong, Hong Kong
| | | | - Siu-Ka Mak
- Department of Medicine and Geriatrics, Kwong Wah Hospital, Hong Kong
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Wu MY, Chen CS, Yiang GT, Cheng PW, Chen YL, Chiu HC, Liu KH, Lee WC, Li CJ. The Emerging Role of Pathogenesis of IgA Nephropathy. J Clin Med 2018; 7:225. [PMID: 30127305 PMCID: PMC6112037 DOI: 10.3390/jcm7080225] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2018] [Revised: 08/12/2018] [Accepted: 08/16/2018] [Indexed: 12/20/2022] Open
Abstract
IgA nephropathy is an autoimmune disease induced by fthe ormation of galactose-deficient IgA1 and anti-glycans autoantibody. A multi-hit hypothesis was promoted to explain full expression of IgA nephropathy. The deposition of immune complex resulted in activation of the complement, increasing oxidative stress, promoting inflammatory cascade, and inducing cell apoptosis via mesangio-podocytic-tubular crosstalk. The interlinked signaling pathways of immune-complex-mediated inflammation can offer a novel target for therapeutic approaches. Treatments of IgA nephropathy are also summarized in our review article. In this article, we provide an overview of the recent basic and clinical studies in cell molecular regulation of IgAN for further treatment interventions.
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Affiliation(s)
- Meng-Yu Wu
- Department of Emergency Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan.
- Department of Emergency Medicine, School of Medicine, Tzu Chi University, Hualien 970, Taiwan.
| | - Chien-Sheng Chen
- Department of Emergency Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan.
- Department of Emergency Medicine, School of Medicine, Tzu Chi University, Hualien 970, Taiwan.
| | - Giou-Teng Yiang
- Department of Emergency Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan.
- Department of Emergency Medicine, School of Medicine, Tzu Chi University, Hualien 970, Taiwan.
| | - Pei-Wen Cheng
- Yuh-Ing Junior College of Health Care & Management, Kaohsiung 807, Taiwan.
- Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.
| | - Yu-Long Chen
- Department of Emergency Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan.
- Department of Emergency Medicine, School of Medicine, Tzu Chi University, Hualien 970, Taiwan.
| | - Hsiao-Chen Chiu
- Department of Obstetrics and Gynecology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan.
- Department of Obstetrics and Gynecology, School of Medicine, Tzu Chi University, Hualien 970, Taiwan.
| | - Kuan-Hung Liu
- Division of Nephrology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine National Cheng Kung University, Tainan 704, Taiwan.
| | - Wen-Chin Lee
- Division of Nephrology, Department of Internal Medicine, Chang Bing Show Chwan Memorial Hospital, Changhua 505, Taiwan.
| | - Chia-Jung Li
- Research Assistant Center, Show Chwan Memorial Hospital, Changhua 500, Taiwan.
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12
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Fujinaga S, Nishino T. Favorable Renal Outcome of Japanese Children with Severe IgA Nephropathy With Nephrotic Syndrome. Indian Pediatr 2018. [DOI: 10.1007/s13312-018-1307-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Yang P, Chen X, Zeng L, Hao H, Xu G. The response of the Oxford classification to steroid in IgA nephropathy: a systematic review and meta-analysis. Oncotarget 2017; 8:59748-59756. [PMID: 28938678 PMCID: PMC5601774 DOI: 10.18632/oncotarget.19574] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2017] [Accepted: 06/02/2017] [Indexed: 11/25/2022] Open
Abstract
Background The present review is aimed to evaluate the correlation between pathological features and the response to steroid in the patients with IgA nephropathy according to the Oxford classification, mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), tubular atrophy and interstitial fibrosis (T). Methods We searched Chinese Biomedical Database, EMBASE, Cochrane Library, PubMed and MEDLINE with all spellings of “IgA nephropathy”, “Oxford Classification”, and “steroid”. Results 5 studies with 637 patients were eligible for inclusion. The analysis showed that M1, S1, and T1/2 was strongly associated with the prediction to steroid resistance when compared with M0 [odds ratio (OR) 1.89, 95% confidence interval (CI) 1.01 - 3.56, P < 0.05], S0 (OR 2.24, 95% CI 0.99 - 5.08, P = 0.05) and T0 (OR 2.16, 95% CI 1.29 - 3.63, P = 0.004) respectively. There is no difference in steroid sensitivity between E0 and E1 (P = 0.55). The pooled OR of steroid resistance for E1 versus T1/2 is 0.50 (P = 0.04). Conclusion IgA nephropathy patients with serious pathological changes (M1, S1, and T1/2) were more resistant to steroid than slight ones (M0, S0, and T0), and E1 is better response to steroid therapy than T1/2.
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Affiliation(s)
- Pingping Yang
- Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Xi Chen
- Grade 2013, The Second Clinical Medical College of Nanchang University, Nanchang, China
| | - Lei Zeng
- Department of Pathology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Hua Hao
- Department of Pathology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Gaosi Xu
- Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
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Du B, Jia Y, Zhou W, Min X, Miao L, Cui W. Efficacy and safety of mycophenolate mofetil in patients with IgA nephropathy: an update meta-analysis. BMC Nephrol 2017; 18:245. [PMID: 28724421 PMCID: PMC5517790 DOI: 10.1186/s12882-017-0647-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Accepted: 06/28/2017] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND The application of mycophenolate mofetil (MMF) in treating patients with immunoglobulin A nephropathy (IgAN) remains uncertain. This update meta-analysis was performed to re-evaluate the therapeutic potential of MMF in IgAN. METHODS Articles were obtained by searching the electronic databases without language restriction. Randomized controlled trials studying the role of MMF in treating IgAN were collected. The quality of included studies was critically evaluated. Data analyses were performed by using RevMan 5.3 software. RESULTS A total of 297 articles were screened and eight articles were finally included. Among the eight randomized controlled trials, five and three were high quality and low quality, respectively. Both fixed-effect and random-effect model were used. Pooled results by combining all the eight studies suggested that IgAN patients in MMF group had a higher remission rate than that in control group. Compared to placebo or corticosteroid monotherapy, MMF monotherapy exerted a higher remission rate and side effect rate in both main analysis and subgroup analysis by human race. Compared to corticosteroid plus other immunosuppressive agent therapy, corticosteroid plus MMF therapy had a higher remission rate, lower serum creatinine doubling rate, progression to end-stage renal disease rate and side effects rate. Subgroup analysis by therapeutic regimen further confirmed these results between corticosteroid plus MMF therapy and corticosteroid plus cyclophosphamide therapy. Funnel-plot displayed a symmetrical figure, indicating no publication bias existed. CONCLUSIONS MMF has the potential in treatment of IgAN, especially for Asians. The evidence currently available shows that MMF monotherapy has a more efficacy but higher side effects when compared to placebo or corticosteroid monotherapy in treatment of Asians with IgAN. While MMF combined with corticosteroid regimen has a more efficacy and lower side effects when compared with corticosteroid plus cyclophosphamide regimen.
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Affiliation(s)
- Bing Du
- Department of Cardiology, the Second Part of First Hospital, Jilin University, Changchun, 130031 China
| | - Ye Jia
- Department of Nephrology, Second Hospital, Jilin University, 218 Ziqiang Street, Changchun, Jilin, 130041 China
| | - Wenhua Zhou
- Department of Nephrology, Second Hospital, Jilin University, 218 Ziqiang Street, Changchun, Jilin, 130041 China
| | - Xu Min
- Department of Nephrology, Second Hospital, Jilin University, 218 Ziqiang Street, Changchun, Jilin, 130041 China
| | - Lining Miao
- Department of Nephrology, Second Hospital, Jilin University, 218 Ziqiang Street, Changchun, Jilin, 130041 China
| | - Wenpeng Cui
- Department of Nephrology, Second Hospital, Jilin University, 218 Ziqiang Street, Changchun, Jilin, 130041 China
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Lu Z, Song J, Mao J, Xia Y, Wang C. Evaluation of Mycophenolate Mofetil and Low-Dose Steroid Combined Therapy in Moderately Severe Henoch-Schönlein Purpura Nephritis. Med Sci Monit 2017; 23:2333-2339. [PMID: 28515415 PMCID: PMC5444683 DOI: 10.12659/msm.904206] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
Background The most appropriate management of Henoch-Schönlein Purpura (HSP) nephritis with nephrotic-range proteinuria remains uncertain. The aim of this study was to evaluate the clinical therapeutic effects of mycophenolate mofetil and low-dose steroid in Henoch-Schönlein purpura nephritis (HSPN) with nephrotic-range proteinuria and pathological classification less than IV in children. Material/Methods The clinical effects of MMF and low-dose steroid therapy were studied in children with Henoch-Schönlein purpura nephritis manifested with nephrotic-range proteinuria, normal kidney function, and <50% crescents or sclerosing lesions on renal biopsy. We enrolled 32 boys and 29 girls with nephrotic-range proteinuria, normal kidney function, and pathological classification less than IV on renal biopsy. We treated 41 cases (67.2%) with mycophenolate mofetil and low-dose prednisone combined therapy and 20 cases (32.8%) were treated with full-dose prednisone alone. Results Short-term response was significantly different between 2 groups (χ2=4.371, P=0.037), while no significant difference was found in long-term prognosis (χ2=0.419, P=0.522) after follow-up. The ROC curve showed that the most appropriate cutoff value was 30.67 μg·h/ml for MPA-AUC and the area under the ROC curve was 0.731, with 85.2% sensitivity and 64.3% specificity. Conclusions Mycophenolate mofetil and low-dose prednisone combined therapy is a reasonable treatment choice which can promote the remission of proteinuria without increasing obvious adverse reactions in pediatric HSPN with nephrotic state and pathological classification less than grade IV. MPA-AUC more than 30 μg·h/ml was an appropriate value for MMF in the combined therapy with MMF and steroid for treating children with HSPN.
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Affiliation(s)
- Zhihong Lu
- Department of Nephrology, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China (mainland)
| | - Junfeng Song
- Department of Pediatrics, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, Zhejiang, China (mainland)
| | - Jianhua Mao
- Department of Nephrology, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China (mainland)
| | - Yonghui Xia
- Department of Nephrology, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China (mainland)
| | - Caiyun Wang
- Department of Nephrology, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China (mainland)
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16
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IgA nephropathy with presentation of nephrotic syndrome at onset in children. Pediatr Nephrol 2017; 32:457-465. [PMID: 27714465 DOI: 10.1007/s00467-016-3502-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2016] [Revised: 09/02/2016] [Accepted: 09/06/2016] [Indexed: 10/20/2022]
Abstract
BACKGROUND Despite a low incidence, nephrotic syndrome (NS) can present with IgA nephropathy (IgAN). The clinical characteristics and long-term outcomes of pediatric patients with IgAN presenting with NS (NS-IgAN) at onset have not been fully elucidated. METHODS We retrospectively analyzed 426 patients, and compared clinical and pathological (Oxford) findings between those with NS-IgAN and those with non-NS-IgAN. RESULTS Among 426 patients, 30 (7.0 %) had NS-IgAN. Logistic analyses showed that male sex (OR: 7.6, p = 0.0002), M1 (OR: 10.3, p = 0.002), and E1 (OR: 15.2, p = 0.0001) were significantly related to NS. The mean observation period was 6.2 ± 3.2 years. Although NS-IgAN was associated with significantly lower renal survival than non-NS-IgAN according to Kaplan-Meier analysis (p = 0.02), renal survival of NS-IgAN was good (92.4 % at 10 years). The most significant prognostic factor for renal survival was remission of proteinuria after treatment, and NS at onset is also a significant prognostic factor for renal survival after adjusting for remission of proteinuria. Twenty children with NS-IgAN were treated with prednisolone alone, or prednisolone and immunosuppressant. Remission of proteinuria occurred in 21 patients. Three cases of NS-IgAN progressed to stage III-V chronic kidney disease at the most recent observation. They all demonstrated heavy proteinuria after the 2-year initial treatment. The significant factor for persistent proteinuria at 5 years was S1 in NS-IgAN. CONCLUSIONS The most significant factor for renal survival was responsiveness to treatment, not NS itself. As modifiable acute lesions are the dominant pathological findings in NS-IgAN, histological improvements achieved by appropriate treatments can result in a favorable prognosis.
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Rasche FM, Keller F, Rasche WG, Schiekofer S, Boldt A, Sack U, Fahnert J. Why, when and how should immunosuppressive therapy considered in patients with immunoglobulin A nephropathy? Clin Exp Immunol 2016; 186:115-133. [PMID: 27283488 PMCID: PMC5054563 DOI: 10.1111/cei.12823] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2016] [Revised: 05/20/2016] [Accepted: 05/20/2016] [Indexed: 12/13/2022] Open
Abstract
IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Lifelong mesangial deposition of IgA1 complexes subsist inflammation and nephron loss, but the complex pathogenesis in detail remains unclear. In regard to the heterogeneous course, classical immunosuppressive and specific therapeutic regimens adapted to the loss of renal function will here be discussed in addition to the essential common renal supportive therapy. Renal supportive therapy alleviates secondary, surrogate effects or sequelae on renal function and proteinuria of high intraglomerular pressure and subsequent nephrosclerosis by inhibition of the renin angiotensin system (RAASB). In patients with physiological (ΔGFR < 1·5 ml/min/year) or mild (ΔGFR 1·5-5 ml/min/year) decrease of renal function and proteinuric forms (> 1 g/day after RAASB), corticosteroids have shown a reduction of proteinuria and might protect further loss of renal function. In patients with progressive loss of renal function (ΔGFR > 3 ml/min within 3 months) or a rapidly progressive course with or without crescents in renal biopsy, cyclophosphamide with high-dose corticosteroids as induction therapy and azathioprine maintenance has proved effective in one randomized controlled study of a homogeneous cohort in loss of renal function (ΔGFR). Mycophenolic acid provided further maintenance in non-randomized trials. Differentiated, precise, larger, randomized, placebo-controlled studies focused on the loss of renal function in the heterogeneous forms of IgAN are still lacking. Prospectively, fewer toxic agents will be necessary in the treatment of IgAN.
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Affiliation(s)
- F M Rasche
- Department of Internal Medicine, Neurology, Dermatology, Clinic for Endocrinology, Nephrology, Section of Nephrology, University Leipzig, Leipzig, Germany
| | - F Keller
- Department of Internal Medicine I, Division of Nephrology, University Hospital of Ulm, Ulm, Germany.
| | - W G Rasche
- Department of Head Medicine and Oral Health, Department of Ophthalmology, University Leipzig, Leipzig, Germany
| | - S Schiekofer
- Center for Geriatric Medicine at Bezirksklinikum Regensburg, Department of Psychiatry and Psychotherapy, University Regensburg, Regensburg, Germany
| | - A Boldt
- Institute of Clinical Immunology, Medical Faculty, Leipzig, Germany
| | - U Sack
- Institute of Clinical Immunology, Medical Faculty, Leipzig, Germany
| | - J Fahnert
- Department of Diagnostic and Interventional Radiology, University Leipzig, Leipzig, Germany
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Alshomar AA. Nephrotic syndrome is a rare manifestation of IGA nephropathy. Int J Health Sci (Qassim) 2016; 10:455-458. [PMID: 27610069 PMCID: PMC5003589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/06/2023] Open
Abstract
Nephrotic syndrome is a rare presentation of IgA nephropathy. The degree of proteinuria in IgA nephropathy predicts poor prognosis. We herein report a teenager with IGA nephropathy, the nephrotic syndrome and segmental glomerular scars who after developing complications from high dose corticosteroid therapy was successfully treated with tacrolimus and low dose prednisone.
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Affiliation(s)
- Ahmad A Alshomar
- Correspondence: Ahmad A Alshomar, Demonstrator, Medicine Department, College of Medicine, Qassim University, Kingdom of Saudi Arabia. Mobile: +966566534423,
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Salvadori M, Rosso G. Update on immunoglobulin a nephropathy. Part II: Clinical, diagnostic and therapeutical aspects. World J Nephrol 2016; 5:6-19. [PMID: 26788460 PMCID: PMC4707169 DOI: 10.5527/wjn.v5.i1.6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2015] [Revised: 11/13/2015] [Accepted: 12/03/2015] [Indexed: 02/06/2023] Open
Abstract
Immunoglobulin A nephropathy (IgAN) is characterized by different clinical manifestations and by long-term different outcomes. Major problem for the physicians is to understanding which patients are at risk of a disease evolution and to prescribe the right therapy to the right patients. Indeed, in addition to patients with a stable disease with no trend to evolution or even with a spontaneous recovery, patients with an active disease and patients with a rapidly evolving glomerulonephritis are described. Several histopathological, biological and clinical markers have been described and are currently used to a better understanding of patients at risk, to suggest the right therapy and to monitor the therapy effect and the IgAN evolution over time. The clinical markers are the most reliable and allow to divide the IgAN patients into three categories: The low risk patients, the intermediate risk patients and the high risk patients. Accordingly, the therapeutic measures range from no therapy with the only need of repeated controls, to supportive therapy eventually associated with low dose immunosuppression, to immunosuppressive treatment in the attempt to avoid the evolution to end stage renal disease. However the current evidence about the different therapies is still matter of discussion. New drugs are in the pipeline and are described. They are object of randomized controlled trials, but studies with a number of patients adequately powered and with a long follow up are needed to evaluate efficacy and safety of these new drugs.
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