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Elahi T, Ahmed S, Mubarak M. Short-term renal and patient outcomes of primary immunoglobulin-associated mesangiocapillary glomerulonephritis: Insights from a developing country. World J Nephrol 2024; 13:98969. [PMID: 39723356 PMCID: PMC11572649 DOI: 10.5527/wjn.v13.i4.98969] [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: 07/10/2024] [Revised: 09/09/2024] [Accepted: 09/19/2024] [Indexed: 11/07/2024] Open
Abstract
BACKGROUND Primary immunoglobulin (Ig)-associated mesangiocapillary glomerulonephritis (Ig-MCGN) is an immune complex glomerulonephritis of unknown etiology. It is a common cause of chronic kidney disease in developing countries. There is limited data available on renal and patient outcomes of this disease from developing countries. AIM To determine the short-term renal and patient outcomes of adults with a tissue-confirmed diagnosis of primary Ig-MCGN at a single center in Pakistan. METHODS A retrospective cohort study of adult patients was conducted on biopsy-proven Ig-MCGN cases diagnosed between 1998 and 2019 at the Sindh Institute of Urology and Transplantation, Karachi, Pakistan. Secondary causes were excluded. The primary endpoint was renal survival without end-stage kidney disease (ESKD) or mortality. The secondary endpoint was the rate of remission during the 2-year follow-up period. Survival curves were made with the use of Kaplan-Meier estimates. RESULTS A total of 163 patients were included in the study and their mean follow-up duration was 29.45 months ± 21.28 months. Among baseline characteristics, young age, lower estimated glomerular filtration rate, requirement of kidney replacement therapy, presence of crescents, and severity of interstitial fibrosis and tubular atrophy were found to have a significant association with renal outcomes. The renal outcomes were negatively correlated with the presence of hypertension, level of complements, and degree of proteinuria. In all, 63 (37.4%) patients were treated with steroids and 21 (13%) received combination therapy (cyclophosphamide with steroids). At 2 years, 124 (76.07%) patients were in complete remission or partial remission [56 (34.3%) and 68 (41.71%), respectively], while 32 (19.63%) patients progressed to ESKD and 7 (4.29%) patients died. CONCLUSION The outcomes of primary Ig-MCGN are guarded in Pakistan and require further prospective studies to improve our understanding of this relatively common disease so that more personalized treatment approaches can be developed.
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Affiliation(s)
- Tabassum Elahi
- Department of Nephrology, Sindh Institute of Urology and Transplantation, Karachi 74200, Pakistan
| | - Saima Ahmed
- Department of Nephrology, Sindh Institute of Urology and Transplantation, Karachi 74200, Pakistan
| | - Muhammed Mubarak
- Department of Histopathology, Sindh Institute of Urology and Transplantation, Karachi 74200, Pakistan
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Elahi T, Ahmed S, Ahmed E, Mubarak M. Clinicopathological characteristics and outcomes of adult patients with idiopathic membranoproliferative glomerulonephritis according to an immunofluorescence-based classification. J Nephrol 2024; 37:2255-2265. [PMID: 39400860 DOI: 10.1007/s40620-024-02083-7] [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: 02/09/2024] [Accepted: 08/16/2024] [Indexed: 10/15/2024]
Abstract
BACKGROUND The classification of membranoproliferative glomerulonephritis (MPGN) into immune complex-mediated MPGN and complement-mediated MPGN on immunofluorescence has provided insights into two distinct disease processes. There are limited data available on renal outcomes of MPGN from developing countries. METHODS A retrospective analysis was conducted on biopsy-proven MPGN cases diagnosed between 1998 and 2018 at the Sindh Institute of Urology and Transplantation (SIUT). Secondary causes were excluded. Patients were reclassified as immune complex-mediated-MPGN and complement-mediated-MPGN based on immunofluorescence results. The clinicopathological findings and outcomes of the two groups were compared. RESULTS In total, 213 patients with idiopathic MPGN were identified. Among these, 163 (76.5%) were reclassified as immune complex-mediated-MPGN and 50 (23.4%) as complement-mediated-MPGN. No significant differences were found between the two groups regarding age, gender, clinical characteristics, biopsy indications, biopsy findings, and renal function at presentation. Overall, 63 subjects (38.7%) with immune complex-mediated-MPGN and 27 (54%) with complement-mediated-MPGN received immunosuppressive agents (p = 0.08). Complete and partial remission rates were higher in immune complex-mediated-MPGN than in complement-mediated-MPGN (76% vs 58%, p < 0.05). At two years, median estimated glomerualr filtration rate (eGFR) tended to be higher in patients with immune complex-mediated-MPGN 91.2 (45.4-113.7) vs 83.45(34.6-102.50) ml/min/1.73 m2, p = 0.22) with significantly better renal survival (76% vs 58%, p = 0.03). Comparatively, more patients progressed to end-stage kidney disease (ESKD) in the complement-mediated-MPGN group (32% vs 19.6%, p = 0.06), with increased overall mortality (5 (10%) vs 7 (4.3%), p = 0.12). CONCLUSION The clinicopathological features at presentation of complement-mediated-MPGN are similar to those of immune complex-mediated-MPGN. However, it is less frequent and overall prognosis is less favorable.
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Affiliation(s)
- Tabassum Elahi
- Department of Nephrology, Sindh Institute of Urology and Transplantation, Chand Bibi Road Near Civil Hospital Karachi, Karachi, 74200, Pakistan.
| | - Saima Ahmed
- Department of Nephrology, Sindh Institute of Urology and Transplantation, Chand Bibi Road Near Civil Hospital Karachi, Karachi, 74200, Pakistan
| | - Ejaz Ahmed
- Department of Nephrology, Sindh Institute of Urology and Transplantation, Chand Bibi Road Near Civil Hospital Karachi, Karachi, 74200, Pakistan
| | - Muhammed Mubarak
- Department of Histopathology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan
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Xu L, Wei F, Feng J, Liu J, Liu J, Tang X, Fang X, Chen J, Zhai Y, Liu H, Sun L, Qian Y, Wu B, Wang H, Shen Q, Rao J, Xu H. Characteristics and outcomes of glomerulonephritis with membranoproliferative pattern in children. Transl Pediatr 2021; 10:2985-2996. [PMID: 34976764 PMCID: PMC8649586 DOI: 10.21037/tp-21-286] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Accepted: 08/16/2021] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND Membranoproliferative glomerulonephritis (MPGN) is a rare histopathologic pattern of glomerular injury with limited studies in pediatric patients. Characteristics and outcomes of children with MPGN have also remained to be further explored. METHODS We retrospectively reviewed the clinicopathological features, genetic findings, treatments and outcomes in 17 pediatric patients pathologically diagnosed with MPGN from 2007 to 2020 in the Children's National Medical Center in China. RESULTS Median age at disease onset was 9.9 years (IQR, 5.6-11.9 years). Most of the patients (12/17) had nephrotic range of proteinuria, and nephritic-nephrotic syndrome was the most common clinical presentation (35.2%). Secondary causes were identified in eight patients including hepatitis B virus (HBV) infection (n=4), methylmalonic acidemia (MMA, n=2), rheumatoid arthritis (RA, n=1) and Aymé-Gripp Syndrome (n=1). The nine patients with primary MPGN were further identified as immune-complex mediated MPGN (n=8), and unclassifiable MPGN (U-MGPN, n=1). Genetic analyses identified pathogenic variants of MMACHC gene in two cases of MMA and established the diagnosis for Aymé-Gripp syndrome in one case with a de novo variant of MAF gene. Comparing study between the complete or partial remission group (n=8) and non-response group (n=9) showed a significant difference in the timing of renal biopsy (P<0.05). Normal renal function was preserved in ten patients at the last follow-up. Two patients developed into end-stage renal disease (ESRD). CONCLUSIONS Children with MPGN pattern present heterogenous clinical features. Genetic detection helps to explore underlying causes of MPGN. Early identification of the primary or secondary causes of MPGN in children is vital.
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Affiliation(s)
- Linan Xu
- Department of Nephrology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.,Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, China.,Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
| | - Fengfang Wei
- Affiliated Hospital of Putian University, Fujian, China
| | - Jiayan Feng
- Department of Pathology, Children's Hospital of Fudan University, Shanghai, China
| | - Jiaojiao Liu
- Department of Nephrology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.,Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, China.,Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
| | - Jialu Liu
- Department of Nephrology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.,Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, China.,Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
| | - Xiaoshan Tang
- Department of Nephrology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.,Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, China.,Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
| | - Xiaoyan Fang
- Department of Nephrology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.,Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, China.,Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
| | - Jing Chen
- Department of Nephrology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.,Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, China.,Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
| | - Yihui Zhai
- Department of Nephrology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.,Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, China.,Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
| | - Haimei Liu
- Department of Rheumatology, Children's Hospital of Fudan University, Shanghai, China
| | - Li Sun
- Department of Rheumatology, Children's Hospital of Fudan University, Shanghai, China
| | - Yanyan Qian
- Clinical Genetic Center, Children's Hospital of Fudan University, Shanghai, China
| | - Bingbing Wu
- Clinical Genetic Center, Children's Hospital of Fudan University, Shanghai, China
| | - Huijun Wang
- Clinical Genetic Center, Children's Hospital of Fudan University, Shanghai, China
| | - Qian Shen
- Department of Nephrology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.,Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, China.,Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
| | - Jia Rao
- Department of Nephrology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.,Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, China.,Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
| | - Hong Xu
- Department of Nephrology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.,Shanghai Kidney Development and Pediatric Kidney Disease Research Center, Shanghai, China.,Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai, China
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Nakagawa N, Mizuno M, Kato S, Maruyama S, Sato H, Nakaya I, Sugiyama H, Fujimoto S, Miura K, Matsumura C, Gotoh Y, Suzuki H, Kuroki A, Yoshino A, Nakatani S, Hiromura K, Yamamoto R, Yokoyama H, Narita I, Isaka Y. Demographic, clinical characteristics and treatment outcomes of immune-complex membranoproliferative glomerulonephritis and C3 glomerulonephritis in Japan: A retrospective analysis of data from the Japan Renal Biopsy Registry. PLoS One 2021; 16:e0257397. [PMID: 34520493 PMCID: PMC8439563 DOI: 10.1371/journal.pone.0257397] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Accepted: 09/01/2021] [Indexed: 12/14/2022] Open
Abstract
The reclassification of membranoproliferative glomerulonephritis (MPGN) into immune-complex MPGN (IC-MPGN) and C3 glomerulopathy (C3G) based on immunofluorescence findings in kidney biopsies has provided insights into these two distinct diseases. C3G is further classified into dense deposit disease and C3 glomerulonephritis (C3GN) based on electron micrographic findings. Although these diseases have poor outcomes, limited Japanese literature confined to small, single-center cohorts exist on these diseases. We retrospectively analyzed 81 patients with MPGN type I and III from 15 hospitals in the Japan Renal Biopsy Registry to compare demographic, clinical characteristics and treatment outcomes of patients with IC-MPGN to those with C3GN. Of the 81 patients reviewed by immunofluorescence findings in kidney biopsies, 67 patients had IC-MPGN and 14 patients had C3GN. Age at diagnosis and systolic and diastolic pressure were higher and proteinuria and impaired renal function were significantly more prevalent in patients with IC-MPGN than those with C3GN. About 80% of the patients in both groups were treated with immunosuppressive therapy. At last follow-up (median 4.8 years), complete remission rate of proteinuria was significantly higher in patients with C3GN (64.3%) than in those with IC-MPGN (29.9%; P = 0.015). The renal survival rate was lower in patients with IC-MPGN when compared to C3GN (73.1% vs. 100%; log-rank, P = 0.031). Systolic blood pressure and renal function at baseline were independent predictors of progression to end-stage kidney disease. The overall prognosis of patients with C3GN is more favorable than for patients with IC-MPGN.
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Affiliation(s)
- Naoki Nakagawa
- Division of Cardiology, Nephrology, Pulmonology and Neurology, Department of Internal Medicine, Asahikawa Medical University, Asahikawa, Japan
- * E-mail:
| | - Masashi Mizuno
- Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Renal Replacement Therapy, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Sawako Kato
- Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shoichi Maruyama
- Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hiroshi Sato
- Clinical Pharmacology and Therapeutics, Tohoku University, Graduate School of Pharmaceutical Sciences, Sendai, Japan
| | - Izaya Nakaya
- Department of Nephrology and Rheumatology, Iwate Prefectural Central Hospital, Morioka, Japan
| | - Hitoshi Sugiyama
- Department of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Shouichi Fujimoto
- Faculty of Medicine, Department of Hemovascular Medicine and Artificial Organs, University of Miyazaki, Miyazaki, Japan
| | - Kenichiro Miura
- Department of Pediatric Nephrology, Tokyo Women’s Medical University, Tokyo, Japan
| | - Chieko Matsumura
- Department of Pediatrics, National Hospital Organization Chibahigashi National Hospital, Chiba, Japan
| | - Yoshimitsu Gotoh
- Department of Pediatric Nephrology, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan
| | - Hitoshi Suzuki
- Faculty of Medicine, Department of Nephrology, Juntendo University, Tokyo, Japan
| | - Aki Kuroki
- Division of Nephrology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan
| | - Atsunori Yoshino
- Department of Nephrology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan
| | - Shinya Nakatani
- Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Keiju Hiromura
- Department of Nephrology and Rheumatology, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Ryohei Yamamoto
- Health and Counseling Center, Osaka University, Toyonaka, Japan
| | - Hitoshi Yokoyama
- Department of Nephrology, Kanazawa Medical University School of Medicine, Uchinada, Japan
| | - Ichiei Narita
- Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Yoshitaka Isaka
- Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Japan
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