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Maslyennikov Y, Claudia Rusu C, Moldovan D, Potra A, Tirinescu D, Ticala M, Barar A, Alexandra U, Ioana Bondor C, Kacso I. Epidemiology of kidney biopsy from regional referral center in Romania: 10-year review. ROMANIAN JOURNAL OF INTERNAL MEDICINE = REVUE ROUMAINE DE MEDECINE INTERNE 2025; 63:79-92. [PMID: 39722204 DOI: 10.2478/rjim-2024-0032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/28/2024]
Abstract
PURPOSE To provide epidemiologic data on kidney biopsy from Romania. METHODS Retrospective observational study of kidney biopsy records for adult patients from a referral center in the north-western part of Romania, reported for 2014-2023. RESULTS 556 biopsies were performed, corresponding to an incidence of 12 biopsies/m person-year with over 50% increase over the last reported year. Optimal core for optic microscopy was available in 81.4%, immunofluorescence was performed in 86.3%, and electron microscopy in 35.2% of patients. The mean age at biopsy was 47.12 years, and 53.8% were males. Indications for kidney biopsy were nephrotic syndrome in 63.1% of patients, nephritic in 25.9% of patients, asymptomatic urinary abnormalities in 2.9%, acute kidney injury/ rapid progressive renal failure in 3.6%, and chronic kidney disease in 1.4%. The most frequent diagnostic categories were membranous nephritis (14.7%), IgA nephropathy (13.9%), focal segmental glomerulosclerosis (11,1%), minimal change disease (12,2%), lupus nephritis (10,9%), vasculitis (7.6%), and membranoproliferative glomerulonephritis (8%). The age of diagnosis increased for IgA Nephropathy over time while it decreased for membranous nephritis. CONCLUSIONS Our study adds data for the completion of the kidney biopsy map in our region.
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Affiliation(s)
- Yuriy Maslyennikov
- Department of Nephrology, University of Medicine, and Pharmacy "Iuliu Hatieganu" Cluj-Napoca, 8 Victor Babeș Street, 400012 Cluj-Napoca, Romania
- Department of Nephrology, Emergency County Clinical Hospital Cluj-Napoca, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania
| | - Crina Claudia Rusu
- Department of Nephrology, University of Medicine, and Pharmacy "Iuliu Hatieganu" Cluj-Napoca, 8 Victor Babeș Street, 400012 Cluj-Napoca, Romania
- Department of Nephrology, Emergency County Clinical Hospital Cluj-Napoca, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania
| | - Diana Moldovan
- Department of Nephrology, University of Medicine, and Pharmacy "Iuliu Hatieganu" Cluj-Napoca, 8 Victor Babeș Street, 400012 Cluj-Napoca, Romania
- Department of Nephrology, Emergency County Clinical Hospital Cluj-Napoca, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania
| | - Alina Potra
- Department of Nephrology, University of Medicine, and Pharmacy "Iuliu Hatieganu" Cluj-Napoca, 8 Victor Babeș Street, 400012 Cluj-Napoca, Romania
- Department of Nephrology, Emergency County Clinical Hospital Cluj-Napoca, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania
| | - Dacian Tirinescu
- Department of Nephrology, University of Medicine, and Pharmacy "Iuliu Hatieganu" Cluj-Napoca, 8 Victor Babeș Street, 400012 Cluj-Napoca, Romania
- Department of Nephrology, Emergency County Clinical Hospital Cluj-Napoca, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania
| | - Maria Ticala
- Department of Nephrology, University of Medicine, and Pharmacy "Iuliu Hatieganu" Cluj-Napoca, 8 Victor Babeș Street, 400012 Cluj-Napoca, Romania
- Department of Nephrology, Emergency County Clinical Hospital Cluj-Napoca, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania
| | - Andrada Barar
- Department of Nephrology, University of Medicine, and Pharmacy "Iuliu Hatieganu" Cluj-Napoca, 8 Victor Babeș Street, 400012 Cluj-Napoca, Romania
- Department of Nephrology, Emergency County Clinical Hospital Cluj-Napoca, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania
| | - Urs Alexandra
- Department of Nephrology, University of Medicine, and Pharmacy "Iuliu Hatieganu" Cluj-Napoca, 8 Victor Babeș Street, 400012 Cluj-Napoca, Romania
- Department of Nephrology, Emergency County Clinical Hospital Cluj-Napoca, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania
| | - Cosmina Ioana Bondor
- Department of Medical Informatics, and Biostatistics, University of Medicine, and Pharmacy "Iuliu Hatieganu" Cluj-Napoca, 6 Pasteur Street, 400349 Cluj-Napoca, Romania
| | - Ina Kacso
- Department of Nephrology, University of Medicine, and Pharmacy "Iuliu Hatieganu" Cluj-Napoca, 8 Victor Babeș Street, 400012 Cluj-Napoca, Romania
- Department of Nephrology, Emergency County Clinical Hospital Cluj-Napoca, 3-5 Clinicilor Street, 400006 Cluj-Napoca, Romania
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Stefan G, Stancu S, Zugravu A, Terinte-Balcan G. Prognostic role of mesangial IgM deposition in IgA nephropathy: a long-term cohort study. Ren Fail 2024; 46:2313179. [PMID: 38357771 PMCID: PMC10877648 DOI: 10.1080/0886022x.2024.2313179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Accepted: 01/28/2024] [Indexed: 02/16/2024] Open
Abstract
BACKGROUND The clinical significance of mesangial immunoglobulin (Ig) M deposition in IgA nephropathy (IgAN) has been less explored and remains a topic of debate. Therefore, our study aimed to investigate the prognostic value of mesangial IgM deposition in a long-term follow-up cohort of IgAN patients. METHODS A unicentric retrospective study was conducted on 93 consecutive IgAN patients (median age 41 years, 68% male, eGFR 48.7 mL/min, proteinuria 1.1 g/g) from 2010 to 2015. They were followed until end-stage kidney disease (ESKD), death, or until the end of the study in January 2021, with a median follow-up of 7 years. An independent pathologist evaluated the IgM immunofluorescence pattern, Oxford MEST-C score, and transmission electron microscopy (TEM) lesions following a comprehensive protocol. RESULTS In our cohort, 70% had mesangial IgM-positive deposits, while 30% were IgM-negative. Both groups were similar in age, sex, prevalence of arterial hypertension, Charlson comorbidity scores, kidney function (eGFR and proteinuria), pathology findings (Oxford MEST-C score, IgG and C3 immune deposition), and TEM analysis. Treatment with RASI and immunosuppression, and death rates were also comparable. However, 37% of IgM-positive patients progressed to ESKD, significantly higher than the 11% in the IgM-negative group. Univariate and multivariate Cox proportional hazards regression analyses identified lower eGFR, higher Oxford MEST-C score, and mesangial IgM deposits as independent factors associated with shorter kidney survival. CONCLUSIONS Our study highlights mesangial IgM deposition as a potential risk factor for ESKD in patients with advanced IgAN, laying a foundation for further research in this area.
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Affiliation(s)
- Gabriel Stefan
- Department of Nephrology, University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
- Department of Nephrology, “Dr. Carol Davila” Teaching Hospital of Nephrology, Bucharest, Romania
| | - Simona Stancu
- Department of Nephrology, University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
- Department of Nephrology, “Dr. Carol Davila” Teaching Hospital of Nephrology, Bucharest, Romania
| | - Adrian Zugravu
- Department of Nephrology, University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
- Department of Nephrology, “Dr. Carol Davila” Teaching Hospital of Nephrology, Bucharest, Romania
| | - George Terinte-Balcan
- Department of Nephrology, University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
- Ultrastructural Pathology Laboratory, “Victor Babes” National Institute of Pathology, Bucharest, Romania
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Levett JJ, Alatassi R, Huk OL, Antoniou J. Immunoglobulin A Nephropathy in a Patient With Bilateral Metal-on-Metal Hip Arthroplasty. Arthroplast Today 2024; 27:101407. [PMID: 38946922 PMCID: PMC11214374 DOI: 10.1016/j.artd.2024.101407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 04/21/2024] [Accepted: 04/27/2024] [Indexed: 07/02/2024] Open
Abstract
Immunoglobulin A (IgA) nephropathy in the presence of a metal-on-metal (MoM) hip arthroplasty is a rare condition that requires close monitoring. A 61-year-old male with bilateral hip osteoarthritis underwent resurfacing hip arthroplasty with MoM articulating surfaces. Prior to his four-year postoperative visit, the patient was diagnosed with IgA nephropathy. During this visit, the patient reported clicking in the left resurfacing hip arthroplasty, and serum metal ions were significantly elevated. Consequently, the patient underwent conversion to bilateral ceramic-on-cross-linked polyethylene total hip arthroplasty, which resulted in the restoration of metal ion levels to normal. This case highlights that IgA nephropathy played a critical role in impeding the clearance of metal ions. Routine metal ion counts are warranted in patients with MoM articulating interfaces and a newly diagnosed nephropathy.
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Affiliation(s)
- Jordan J. Levett
- Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada
| | - Raheef Alatassi
- Department of Orthopaedic Surgery, London Health Sciences Centre, University Hospital, London, Ontario, Canada
- Division of Orthopedic Surgery, Department of Surgery, King Faisal Specialist Hospital & Research Centre, Jeddah, Saudi Arabia
| | - Olga L. Huk
- Department of Orthopaedic Surgery, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
| | - John Antoniou
- Department of Orthopaedic Surgery, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
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Obrișcă B, Mocanu V, Jurubiță R, Vrabie A, Berechet A, Lujinschi Ș, Sorohan B, Andronesi A, Achim C, Lupușoru G, Micu G, Caceaune N, Gherghiceanu M, Ismail G. Histological reappraisal of IgA nephropathy: the role of glomerular pattern of injury and mesangial complement deposition. BMC Nephrol 2024; 25:145. [PMID: 38658875 PMCID: PMC11040743 DOI: 10.1186/s12882-024-03577-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Accepted: 04/11/2024] [Indexed: 04/26/2024] Open
Abstract
BACKGROUND There is a clear need to refine the histological assessment in IgA Nephropathy (IgAN). We sought to investigate the clinical significance of the light microscopy (LM) pattern of glomerular injury and of the intensity of mesangial C3 staining in IgAN. METHODS We conducted a retrospective, observational study that included all patients with biopsy-proven primary IgAN that had at least 12 months of follow-up. The LM pattern of glomerular injury was reevaluated based on a modified HAAS classification. Mesangial C3 deposition by immunofluorescence (IF) staining was scored semi-quantitatively. The study primary composite endpoint was defined as doubling of serum creatinine or ESRD (dialysis, renal transplant or eGFR < 15 ml/min). The secondary study endpoint was eGFR decline per year. RESULTS This cohort included 214 patients with IgAN (mean age, 41.4 ± 12.6 years), with a mean eGFR and median 24-h proteinuria of 55.2 ± 31.5 ml/min/1.73m2 and 1.5 g/day (IQR:0.8-3.25), respectively. The most frequent LM pattern was the mesangioproliferative (37.4%), followed by the sclerotic (22.5%) and proliferative/necrotizing patterns (21.4%). Regarding the IF findings, mild-moderate and intense mesangial C3 staining was present in 30.6% and 61.1% of patients, respectively. Those with sclerosing and crescentic patterns had the worst renal survival (5-year renal survival of 48.8% and 42.9%) and the highest rate of eGFR change/year (-2.32 ml/min/y and - 2.16 ml/min/y, respectively) compared to those with other glomerular patterns of injury. In addition, those with intense C3 staining reached the composite endpoint more frequently compared to those without intense C3 staining (35.5% vs. 21.4%, p = 0.04). After multivariate adjustment, patients with crescentic and sclerosing patterns had a 3.6-fold and 2.1-fold higher risk for the composite endpoint compared to those with mesangioproliferative pattern, while an intense mesangial C3 deposition being also associated with a worse renal outcome (HR, 3.33; 95%CI, 1.21-9.2). CONCLUSIONS We have shown that the LM pattern of glomerular injury and the intensity of mesangial C3 deposition might stratify more accurately the renal outcome in patients with IgAN.
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Affiliation(s)
- Bogdan Obrișcă
- "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania.
| | - Valentin Mocanu
- "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania
| | - Roxana Jurubiță
- "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania
| | - Alexandra Vrabie
- "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania
| | - Andreea Berechet
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania
| | - Ștefan Lujinschi
- "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania
| | - Bogdan Sorohan
- "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania
| | - Andreea Andronesi
- "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania
| | - Camelia Achim
- "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania
| | - Gabriela Lupușoru
- "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania
| | - Georgia Micu
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania
| | - Nicu Caceaune
- Department of Internal Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Mihaela Gherghiceanu
- "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- "Victor Babes" National Institute of Pathology, Bucharest, Romania
| | - Gener Ismail
- "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania
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Ștefan G, Zugravu A, Stancu S. Mortality in IgA Nephropathy: A Long-Term Follow-Up of an Eastern European Cohort. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:247. [PMID: 38399535 PMCID: PMC10890558 DOI: 10.3390/medicina60020247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 01/28/2024] [Accepted: 01/29/2024] [Indexed: 02/25/2024]
Abstract
Background and Objectives: IgA nephropathy (IgAN), the most common primary glomerulonephritis, has been extensively studied for renal outcomes, with limited data on patient survival, particularly in Eastern Europe. We aimed to investigate the long-term survival rate of patients with IgAN and the associated risk factors in an Eastern European cohort. Materials and Methods: We conducted a retrospective analysis of 215 IgAN patients (median age 44, 71% male) diagnosed at a Romanian tertiary center between 2010 and 2017. We assessed clinical and pathological attributes, including the Charlson comorbidity index, the prevalence of diabetes, renal function, and treatment with renin-angiotensin-system inhibitors (RASIs). Results: Over a median 7.3-year follow-up, 20% of patients died, mostly due to cardiovascular diseases. Survival rates at 1, 5, and 10 years were 93%, 84%, and 77%, respectively. Deceased patients had higher Charlson comorbidity index scores, greater prevalence of diabetes, and poorer renal function. They were less frequently treated with RASIs and more frequently reached end-stage kidney disease (ESKD). Conclusions: We report a 20% mortality rate in our Eastern European IgAN cohort, primarily due to cardiovascular diseases. Death correlates with increased age, comorbidity burden, decreased renal function at diagnosis, and the absence of RASI use. RASI treatment may potentially improve survival, highlighting its importance in managing IgAN.
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Affiliation(s)
- Gabriel Ștefan
- Nephrology Department, University of Medicine and Pharmacy “Carol Davila”, 050474 Bucharest, Romania; (A.Z.); (S.S.)
- Nephrology Department, “Dr. Carol Davila” Teaching Hospital of Nephrology, 010731 Bucharest, Romania
| | - Adrian Zugravu
- Nephrology Department, University of Medicine and Pharmacy “Carol Davila”, 050474 Bucharest, Romania; (A.Z.); (S.S.)
- Nephrology Department, “Dr. Carol Davila” Teaching Hospital of Nephrology, 010731 Bucharest, Romania
| | - Simona Stancu
- Nephrology Department, University of Medicine and Pharmacy “Carol Davila”, 050474 Bucharest, Romania; (A.Z.); (S.S.)
- Nephrology Department, “Dr. Carol Davila” Teaching Hospital of Nephrology, 010731 Bucharest, Romania
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Obrișcă B, Vornicu A, Mocanu V, Dimofte G, Andronesi A, Bobeică R, Jurubiță R, Sorohan B, Caceaune N, Ismail G. An open-label study evaluating the safety and efficacy of budesonide in patients with IgA nephropathy at high risk of progression. Sci Rep 2023; 13:20119. [PMID: 37978255 PMCID: PMC10656480 DOI: 10.1038/s41598-023-47393-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Accepted: 11/13/2023] [Indexed: 11/19/2023] Open
Abstract
We sought to evaluate the efficacy and safety of budesonide (Budenofalk) in the treatment of patients with IgA Nephropathy. We conducted a prospective, interventional, open-label, single-arm, non-randomized study that enrolled 32 patients with IgAN at high risk of progression (BUDIGAN study, ISRCTN47722295, date of registration 14/02/2020). Patients were treated with Budesonide at a dose of 9 mg/day for 12 months, subsequently tapered to 3 mg/day for another 12 months. The primary endpoints were change of eGFR and proteinuria at 12, 24 and 36 months. The study cohort had a mean eGFR and 24-h proteinuria of 59 ± 24 ml/min/1.73m2 and 1.89 ± 1.5 g/day, respectively. Treatment with budesonide determined a reduction in proteinuria at 12-, 24- and 36-months by -32.9% (95% CI - 53.6 to - 12.2), - 49.7% (95% CI - 70.1 to - 29.4) and - 68.1% (95% CI - 80.6 to - 55.7). Budesonide determined an eGFR preservation corresponding to a 12-, 24- and 36-months change of + 7.68% (95% CI - 4.7 to 20.1), + 7.42% (95% CI - 7.23 to 22.1) and + 4.74% (95%CI - 13.5 to 23), respectively. The overall eGFR change/year was + 0.83 ml/min/y (95% CI - 0.54 to 4.46). Budesonide was well-tolerated, and treatment emergent adverse events were mostly mild in severity and reversible. Budesonide was effective in the treatment of patients with IgAN at high-risk of progression in terms of reducing proteinuria and preserving renal function over 36 months of therapy.
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Affiliation(s)
- Bogdan Obrișcă
- Department of Nephrology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania.
| | - Alexandra Vornicu
- Department of Nephrology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania
| | - Valentin Mocanu
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania
| | - George Dimofte
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania
| | - Andreea Andronesi
- Department of Nephrology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania
| | - Raluca Bobeică
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania
| | - Roxana Jurubiță
- Department of Nephrology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania
| | - Bogdan Sorohan
- Department of Nephrology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania
| | - Nicu Caceaune
- Department of Internal Medicine, Fundeni Clinical Institute, Bucharest, Romania
| | - Gener Ismail
- Department of Nephrology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- Department of Nephrology, Fundeni Clinical Institute, Bucharest, Romania
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Terinte-Balcan G, Stefan G. A closer look: ultrastructural evaluation of high-risk progression IgA nephropathy. Ultrastruct Pathol 2023; 47:461-469. [PMID: 37700534 DOI: 10.1080/01913123.2023.2256836] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 09/05/2023] [Indexed: 09/14/2023]
Abstract
This retrospective, cross-sectional study sought to examine the ultrastructural characteristics of glomerular lesions using Transmission Electron Microscopy (TEM) in IgA nephropathy (IgAN) and their relationship with the high risk of progression phenotype defined by KDIGO guideline as proteinuria ≥1 g/24 hours despite 3 months of optimized supportive care. We analyzed 81 IgAN patients (median age 41 years, 67% male, eGFR 43.8 mL/min, proteinuria 1.04 g/day); 42 (52%) of them had high risk of progression. There were no differences in terms of age, sex, comorbidities, eGFR, and hematuria between the two groups. High-risk patients more often had segmental glomerulosclerosis (29% vs 8%, p 0.01) in optical microscopy, while in TEM had more frequent podocyte hypertrophy (62% vs 26%, p 0.001) and podocyte foot process detachment from the glomerular basement membrane (19% vs 8%, p 0.05), more often thicker (19% vs 5%, p 0.05) and duplicated (26% vs 10%, p 0.05) glomerular basement membrane, and the presence of subendothelial and subepithelial deposits (31% vs 13%, p 0.05). However, in multivariate binary logistic regression analysis, only podocyte hypertrophy (OR 3.14; 95%CI 1.12, 8.79) was an independent risk factor for high-risk progression in IgAN. These findings highlight the importance of podocytopathy in IgAN progression.
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Affiliation(s)
- George Terinte-Balcan
- Department of Nephrology, University of Medicine and Pharmacy "Carol Davila", Bucharest, Romania
- Ultrastructural Pathology Laboratory, "Victor Babes" National Institute of Pathology, Bucharest, Romania
| | - Gabriel Stefan
- Department of Nephrology, University of Medicine and Pharmacy "Carol Davila", Bucharest, Romania
- Department of Nephrology, "Dr. Carol Davila" Teaching Hospital of Nephrology, Bucharest, Romania
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Tota M, Baron V, Musial K, Derrough B, Konieczny A, Krajewska M, Turkmen K, Kusztal M. Secondary IgA Nephropathy and IgA-Associated Nephropathy: A Systematic Review of Case Reports. J Clin Med 2023; 12:jcm12072726. [PMID: 37048809 PMCID: PMC10094848 DOI: 10.3390/jcm12072726] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 03/20/2023] [Accepted: 03/29/2023] [Indexed: 04/08/2023] Open
Abstract
Primary (pIgAN), secondary IgA nephropathy (sIgAN), and IgA-associated nephropathy can be distinguished. While pIgAN has been thoroughly studied, information about the etiology of sIgAN remains scarce. As concerns sIgAN, several studies suggest that different etiologic factors play a role and ultimately lead to a pathophysiologic process similar to that of pIgAN. In this article, we review a vast number of cases in order to determine the novel putative underlying diseases of sIgAN. Moreover, updates on the common pathophysiology of primary disorders and sIgAN are presented. We identified liver, gastrointestinal, oncological, dermatological, autoimmune, and respiratory diseases, as well as infectious, iatrogenic, and environmental factors, as triggers of sIgAN. As novel biological therapies for listed underlying diseases emerge, we suggest implementing drug-induced sIgAN as a new significant category. Clinicians should acknowledge the possibility of sIgAN progression in patients treated with TNF-α inhibitors, IL-12/IL-23-inhibitors, immune checkpoint inhibitors, CTLA-4, oral anticoagulants, thioureylene derivatives, and anti-vascular endothelial growth factor drugs.
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Affiliation(s)
- Maciej Tota
- Faculty of Medicine, Wroclaw Medical University, 50-367 Wrocław, Poland
| | - Vanessa Baron
- Faculty of Medicine, Wroclaw Medical University, 50-367 Wrocław, Poland
- Faculty of Dentistry, Wroclaw Medical University, 50-435 Wrocław, Poland
| | - Katie Musial
- Faculty of Medicine, Wroclaw Medical University, 50-367 Wrocław, Poland
| | - Bouchra Derrough
- Faculty of Medicine, Wroclaw Medical University, 50-367 Wrocław, Poland
| | - Andrzej Konieczny
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, 50-556 Wrocław, Poland
| | - Magdalena Krajewska
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, 50-556 Wrocław, Poland
| | - Kultigin Turkmen
- Division of Nephrology, Department of Internal Medicine, Meram Medical Faculty, Necmettin Erbakan University, Konya 42090, Turkey
| | - Mariusz Kusztal
- Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, 50-556 Wrocław, Poland
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The significance of galactose-deficient immunoglobulin A1 staining in kidney diseases with IgA deposition. Int Urol Nephrol 2023:10.1007/s11255-023-03512-5. [PMID: 36849627 DOI: 10.1007/s11255-023-03512-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Accepted: 01/09/2023] [Indexed: 03/01/2023]
Abstract
BACKGROUND This study investigated the significance of galactose-deficient immunoglobulin A1 staining in kidney diseases with IgA deposition. METHODS A total of 120 patients with IgA-dominant deposition in kidney tissues were enrolled and divided into four groups: primary IgA nephropathy (PIgAN), secondary IgA nephropathy (SIgAN), monotypic IgA nephropathy (MIgAN), and IgA variant monoclonal gammopathy of renal significance (IgA-MGRS). KM55 (the antibody of galactose-deficient immunoglobulin A1), IgA subtypes, and complement pathway factors (properdin, C4d, and C1q) were detected through immunofluorescence or immunohistochemistry analysis. RESULTS KM55 and IgA double staining showed colocalization within glomeruli in all cases except for IgA-MGRS, which showed negative or weak staining of KM55 but strong staining of IgA. The PIgAN group showed the highest intensity of KM55 and KM55/IgA ratio, while these values in the IgA-MGRS group were the lowest (P < 0.01). A KM55/IgA quantified ratio of 0.78 was the optimal cut-off value to distinguish PIgAN from SIgAN, whereas a cut-off value of 0.21 was optimal to distinguish between MIgAN and IgA-MGRS. The clinicopathological characteristics showed significant differences as the groups were divided by diseases with optimal cut-off values, and these differences corresponded to the pathogenesis of each disease entity. CONCLUSIONS PIgAN, SIgAN, and MIgAN are caused by the deposition of abnormally glycosylated IgA1 whereas IgA-MGRS is not. The KM55/IgA quantified ratio is valuable in distinguishing PIgAN from SIgAN, as well as MIgAN from IgA-MGRS.
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Zhang S, Chen YL, Liu CL, Xie JY, Sun BD, Liu DZ. Case Report: IgA Nephropathy in a Patient With Anti-Transcription Intermediary Factor-1γ Antibody-Positive Dermatomyositis. Front Immunol 2022; 13:757802. [PMID: 35185871 PMCID: PMC8852326 DOI: 10.3389/fimmu.2022.757802] [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: 08/12/2021] [Accepted: 01/12/2022] [Indexed: 11/25/2022] Open
Abstract
Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis characterized by IgA deposits in the mesangial area of glomeruli. Connective tissue disorders are some of the most frequent causes of secondary IgAN. Nevertheless, IgAN rarely occurs in systemic autoimmune myopathies (SAMs). The present case study reports on a 58-year-old patient with dermatomyositis with positive anti-transcription intermediary factor (TIF)-1γ antibodies who was diagnosed with IgAN during standard immunosuppressive therapy. Moreover, we have made a systematic review regarding the association of SAMs and IgAN. To the best of the authors’ knowledge, this is the first case study describing a patient with anti-TIF1γ antibody-positive dermatomyositis who developed IgAN, which demonstrates a potential relationship between anti-TIF1γ-positive dermatomyositis and IgAN. It is important for clinicians to be aware of the possibility of renal involvement in patients with SAMs, even in those with anti-TIF1γ-positive dermatomyositis.
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Affiliation(s)
- Suo Zhang
- Department of Rheumatology and Immunology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China.,Department of Rheumatology and Immunology, Shenzhen Second People's Hospital, Shenzhen, China
| | - Yu-Lan Chen
- Department of Rheumatology and Immunology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
| | - Cui-Lian Liu
- Department of Rheumatology and Immunology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
| | - Jing-Yi Xie
- Department of Rheumatology and Immunology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
| | - Bao-Dong Sun
- Department of Rheumatology and Immunology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
| | - Dong-Zhou Liu
- Department of Rheumatology and Immunology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
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11
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Huang Z, Chen B, Zhou Y, Liang Y, Qiu W, Lv Y, Ding X, Zhang J, Chen C. Clinicopathological and prognostic study of IgA-dominant postinfectious glomerulonephritis. BMC Nephrol 2021; 22:248. [PMID: 34225678 PMCID: PMC8256496 DOI: 10.1186/s12882-021-02462-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 06/23/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The clinicopathological and prognostic features of IgA-dominant postinfectious glomerulonephritis and its difference from the primary IgA nephropathy remains to be investigated. METHODS The clinical and pathological data of 6542 patients who underwent renal biopsy from 2009 to 2020 in our hospital were reviewed and 50 patients who met the selection criteria of IgA-dominant postinfectious glomerulonephritis were enrolled to conduct a retrospective and observational single-center study. The selection criteria were: meet the characteristics of IgA dominance or codominance in immunofluorescence, and conform to 3 of the following 5 criteria: 1.Clinical or laboratory evidence show that there is infection before or at the onset of glomerulonephritis; 2.The level of serum complement decreased; 3.Renal pathology is consistent with endocapillary proliferative glomerulonephritis; 4. Glomerular immunofluorescence staining showed complement C3 dominance or codominance; 5. Hump-like subepithelial immune complex deposition was observed under electron microscopy. According to age, sex, renal function (estimated glomerular filtration rate, eGFR) and follow-up time, the control group was constructed with 1:3 matched cases of primary IgA nephropathy. The clinicopathological and prognostic differences between the two groups were analyzed. RESULTS The most common histological pattern of IgA-dominant postinfectious glomerulonephritis was acute endocapillary proliferative glomerulonephritis and exudative glomerulonephritis. Immunofluorescence showed mainly IgA deposition or IgA deposition only, mainly deposited in the mesangial area (deposition rate 100 %), with typical C3 high-intensity staining (intensity++~+++), mainly deposited in the mesangial area (deposition rate 92.0 %). The fluorescence intensity of kappa is usually not weaker than lambda. The probability of the appearance of typical hump-like electron deposition under electron microscopy is low. Compared to primary IgA nephropathy, patients with IgA-dominant postinfectious glomerulonephritis had higher proportion of crescents (p = 0. 005) and endocapillary hypercellularity (p < 0.001) in pathological manifestations. Using serum creatinine level doubled of the baseline or reached end-stage renal disease as the endpoint, the prognosis of IgA-dominant postinfectious glomerulonephritis patients was worse than that of primary IgA nephropathy patients (p = 0.013). CONCLUSIONS The clinicopathological features of patients with IgA-dominant postinfectious glomerulonephritis was different from that of primary IgA nephropathy, and the prognosis was worse.
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Affiliation(s)
- Ziyuan Huang
- Department of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Ouhai District, Zhejiang, 325000, Wenzhou, People's Republic of China.,Institute of Chronic Kidney Disease, Wenzhou Medical University, Zhejiang, 325000, Wenzhou, People's Republic of China
| | - Bo Chen
- Department of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Ouhai District, Zhejiang, 325000, Wenzhou, People's Republic of China.,Institute of Chronic Kidney Disease, Wenzhou Medical University, Zhejiang, 325000, Wenzhou, People's Republic of China
| | - Ying Zhou
- Department of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Ouhai District, Zhejiang, 325000, Wenzhou, People's Republic of China.,Institute of Chronic Kidney Disease, Wenzhou Medical University, Zhejiang, 325000, Wenzhou, People's Republic of China
| | - Yan Liang
- Department of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Ouhai District, Zhejiang, 325000, Wenzhou, People's Republic of China.,Institute of Chronic Kidney Disease, Wenzhou Medical University, Zhejiang, 325000, Wenzhou, People's Republic of China
| | - Wenxian Qiu
- Department of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Ouhai District, Zhejiang, 325000, Wenzhou, People's Republic of China.,Institute of Chronic Kidney Disease, Wenzhou Medical University, Zhejiang, 325000, Wenzhou, People's Republic of China
| | - Yinqiu Lv
- Department of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Ouhai District, Zhejiang, 325000, Wenzhou, People's Republic of China.,Institute of Chronic Kidney Disease, Wenzhou Medical University, Zhejiang, 325000, Wenzhou, People's Republic of China
| | - Xiaokai Ding
- Department of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Ouhai District, Zhejiang, 325000, Wenzhou, People's Republic of China.,Institute of Chronic Kidney Disease, Wenzhou Medical University, Zhejiang, 325000, Wenzhou, People's Republic of China
| | - Ji Zhang
- Department of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Ouhai District, Zhejiang, 325000, Wenzhou, People's Republic of China. .,Institute of Chronic Kidney Disease, Wenzhou Medical University, Zhejiang, 325000, Wenzhou, People's Republic of China.
| | - Chaosheng Chen
- Department of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Ouhai District, Zhejiang, 325000, Wenzhou, People's Republic of China. .,Institute of Chronic Kidney Disease, Wenzhou Medical University, Zhejiang, 325000, Wenzhou, People's Republic of China.
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12
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Jeon YH, Kim DW, Lee SJ, Park YJ, Kim HJ, Han M, Kim IY, Lee DW, Song SH, Lee SB, Seong EY. Autoimmune hepatitis in a patient with immunoglobulin A nephropathy: A case report. World J Clin Cases 2020; 8:3828-3834. [PMID: 32953860 PMCID: PMC7479551 DOI: 10.12998/wjcc.v8.i17.3828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 08/05/2020] [Accepted: 08/19/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Immunoglobulin A nephropathy (IgAN) is the most commonly encountered glomerular disease in Asian countries. It has a broad clinical presentation, and it is frequently associated with other conditions. Chronic liver disease is well recognized as the leading cause of secondary IgAN. However, cases of IgAN associated with autoimmune hepatitis (AIH) have seldom been reported.
CASE SUMMARY A 63-year-old Korean woman was admitted to Pusan National University Hospital for an evaluation of abdominal pain and elevated liver enzymes. Two weeks prior, she had presented to our hospital with proteinuria of approximately 1350 mg/d and hematuria and was diagnosed with IgAN. Autoimmune profiles were highly positive for antinuclear antibodies, and symptoms related to portal hypertension including ascites and peripheral edema were present. A diagnosis of AIH was made according to the simplified scoring system of the International Autoimmune Hepatitis Group. Despite immunosuppression with prednisolone and azathioprine, rapid deterioration of liver function led to end-stage liver disease. After a living-donor liver transplantation, liver function gradually improved, and she had maintained stable liver and kidney function at the six months follow-up.
CONCLUSION Cases of secondary IgAN with chronic liver disease have been frequently reported in the literature but are rarely associated with AIH. We encountered an IgAN patient with concurrent progressive liver failure due to AIH.
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Affiliation(s)
- You Hyun Jeon
- Department of Internal Medicine, Pusan National University School of Medicine, Busan 49241, South Korea
| | - Da Woon Kim
- Department of Internal Medicine, Pusan National University School of Medicine, Busan 49241, South Korea
| | - So Jeong Lee
- Department of Pathology, Pusan National University Hospital, Busan 49241, South Korea
| | - Young Joo Park
- Division of Gastroenterology, Department of Internal Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan 49241, South Korea
| | - Hyo Jin Kim
- Division of Nephrology, Department of Internal Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan 49241, South Korea
| | - Miyeun Han
- Division of Nephrology, Department of Internal Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan 49241, South Korea
| | - Il Young Kim
- Division of Nephrology, Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan 626-770, South Korea
| | - Dong Won Lee
- Division of Nephrology, Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan 626-770, South Korea
| | - Sang Heon Song
- Division of Nephrology, Department of Internal Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan 49241, South Korea
| | - Soo Bong Lee
- Division of Nephrology, Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan 626-770, South Korea
| | - Eun Young Seong
- Division of Nephrology, Department of Internal Medicine, Biomedical Research Institute, Pusan National University Hospital, Busan 49241, South Korea
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Ismail G, Obrişcă B, Jurubiţă R, Andronesi A, Sorohan B, Vornicu A, Sinescu I, Hârza M. Budesonide versus systemic corticosteroids in IgA Nephropathy: A retrospective, propensity-matched comparison. Medicine (Baltimore) 2020; 99:e21000. [PMID: 32590815 PMCID: PMC7329020 DOI: 10.1097/md.0000000000021000] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
IgA Nephropathy (IgAN) is characterized by mesangial deposition of dominant, polymeric, galactose-deficient IgA1 molecules of gut-associated lymphoid tissue origin. We sought to evaluate the efficacy of targeting the mucosal immune system dysregulation underlying IgAN pathogenesis with a pH-modified formulation of budesonide with a maximum release of active compound in the distal ileum and proximal colon.We did a retrospective study evaluating the efficacy of budesonide (Budenofalk) in the treatment of IgAN. From a retrospective cohort of 143 patients with IgAN followed in our department we identified 21 patients that received treatment with budesonide. These patients received budesonide at a dose of 9 mg/d in the first 12 months, followed by a dose reduction to 3 mg/d for the subsequent period. Only patients that received a 24-month treatment with budesonide were included in the analysis (n = 18). We matched the budesonide-treated cohort to 18 patients with IgAN treated with systemic steroids from the same retrospective cohort. Efficacy was measured as change in proteinuria, hematuria and estimated glomerular filtration rate over a 24-month period.Treatment with budesonide was associated with a 24-month renal function decline of -0.22 (95%CI, -8.2 to 7.8) ml/min/1.73m, compared to -5.89 (95%CI, -12.2 to 0.4) ml/min/1.73m in the corticosteroid treatment group (p = 0.44, for between group difference). The median reduction in proteinuria at 24-month was 45% (interquartile range [IQR]: -79%; -22%) in the budesonide group and 11% (IQR: -39%; 43%) in the corticosteroid group, respectively (P = .009, for between group difference). The median reduction in hematuria at 24-month was 72% (IQR: -90%; -45%) in the budesonide group and 73% (IQR: -85%; 18%) in the corticosteroid group, respectively (P = .22, for between group difference). Treatment with budesonide was well tolerated with minimal side effects.Budesonide (Budenofalk) was effective in the treatment of patients with IgAN at high-risk of progression in terms of reducing proteinuria, hematuria and preserving renal function over 24 months of therapy.
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Affiliation(s)
- Gener Ismail
- Department of Nephrology, Fundeni Clinical Institute
- Department of Uronephrology, “Carol Davila” University of Medicine and Pharmacy
| | - Bogdan Obrişcă
- Department of Nephrology, Fundeni Clinical Institute
- Department of Uronephrology, “Carol Davila” University of Medicine and Pharmacy
| | - Roxana Jurubiţă
- Department of Nephrology, Fundeni Clinical Institute
- Department of Uronephrology, “Carol Davila” University of Medicine and Pharmacy
| | - Andreea Andronesi
- Department of Nephrology, Fundeni Clinical Institute
- Department of Uronephrology, “Carol Davila” University of Medicine and Pharmacy
| | - Bogdan Sorohan
- Department of Nephrology, Fundeni Clinical Institute
- Department of Uronephrology, “Carol Davila” University of Medicine and Pharmacy
| | | | - Ioanel Sinescu
- Department of Uronephrology, “Carol Davila” University of Medicine and Pharmacy
- Center of Uronephrology and Renal Transplantation, Fundeni Clinical Institute, Bucharest, Romania
| | - Mihai Hârza
- Department of Uronephrology, “Carol Davila” University of Medicine and Pharmacy
- Center of Uronephrology and Renal Transplantation, Fundeni Clinical Institute, Bucharest, Romania
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14
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Obrișcă B, Sinescu I, Ismail G, Mircescu G. Has The Time Arrived to Refine The Indications of Immunosuppressive Therapy and Prognosis in IgA Nephropathy? J Clin Med 2019; 8:E1584. [PMID: 31581654 PMCID: PMC6833025 DOI: 10.3390/jcm8101584] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Revised: 09/22/2019] [Accepted: 09/26/2019] [Indexed: 02/07/2023] Open
Abstract
Immunoglobulin A nephropathy (IgAN) is the most frequent glomerular disease worldwide and a leading cause of end-stage renal disease. Particularly challenging to the clinician is the early identification of patients at high risk of progression, an estimation of the decline in renal function, and the selection of only those that would benefit from additional immunosuppressive therapies. Nevertheless, the pathway to a better prognostication and to the development of targeted therapies in IgAN has been paved by recent understanding of the genetic and molecular basis of this disease. Merging the data from the Oxford Classification validation studies and prospective treatment studies has suggested that a disease-stratifying algorithm would be appropriate for disease management, although it awaits validation in a prospective setting. The emergence of potential noninvasive biomarkers may assist traditional markers (proteinuria, hematuria) in monitoring disease activity and treatment response. The recent landmark trials of IgAN treatment (STOP-IgAN and TESTING trials) have suggested that the risks associated with immunosuppressive therapy outweigh the benefits, which may shift the treatment paradigm of this disease. While awaiting the approval of the first therapies for IgAN, more targeted and less toxic immunotherapies are warranted. Accordingly, the targeting of complement activation, the modulation of mucosal immunity, the antagonism of B-cell activating factors, and proteasomal inhibition are currently being evaluated in pilot studies for IgAN treatment.
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Affiliation(s)
- Bogdan Obrișcă
- Department of Nephrology, Fundeni Clinical Institute, 022328 Bucharest, Romania;
- Department of Uronephrology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (I.S.); (G.M.)
| | - Ioanel Sinescu
- Department of Uronephrology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (I.S.); (G.M.)
- Center of Uronephrology and Renal Transplantation, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Gener Ismail
- Department of Nephrology, Fundeni Clinical Institute, 022328 Bucharest, Romania;
- Department of Uronephrology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (I.S.); (G.M.)
| | - Gabriel Mircescu
- Department of Uronephrology, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania; (I.S.); (G.M.)
- Department of Nephrology, “Dr. Carol Davila” Teaching Hospital of Nephrology, 010731 Bucharest, Romania
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