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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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Agrebi I, Kammoun K, Dammak N, Hachicha J, Boudawara T, Jarraya F, Hmida MB. Primary membranoproliferative glomerulonephritis in Sfax, Tunisia: epidemiologic profile and prognostic factors. Pan Afr Med J 2021; 38:218. [PMID: 34046124 PMCID: PMC8140733 DOI: 10.11604/pamj.2021.38.218.21059] [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: 11/22/2019] [Accepted: 02/01/2021] [Indexed: 11/26/2022] Open
Abstract
Introduction membranoproliferative glomerulo nephritis (MPGN) is a rare kidney disease with a poor prognosis as 50% of patients attend the end stage renal failure after 10 years of follow up. Several factors have been described associated with poor renal prognosis. The aim of our study is to determine the epidemiologic profile and to identify prognostic factors of MPGN. Methods our study is retrospective over a period of 16 years (January 1996 - December 2011) including all cases of primary MPGN aged more than 15 years, collected at the nephrology department of Hedi Chaker University Hospital, Sfax, Tunisia. Results we collected 118 cases of primary MPGN, with mean age of 45 (SD 19) years. The incidence of MPGN has decreased from 10 cases/year between 1996 and 1999 to 5 cases/year between 2008 and 2011. Seventy-nine percent of patients (n=93) had renal failure at the moment of diagnosis (e-GFR less than 60 ml/min/1.73m2;). After a mean follow-up of 51.9 (SD 44) months, progression to end stage renal failure was observed in 43.5% of followed cases (n=20). On univariate analysis, factors associated with death or progression to end stage renal failure were initial renal failure and sclerotic glomeruli (respectively p at 0.040 and 0.032). Multivariate analysis indicated that initial renal failure was significantly correlated with death or progression to end stage renal failure (HR: 0.14, 95% CI (0.033-0.593), p=0.008). Conclusion there has been a decline in the number of cases of MPGN diagnosed in our hospital. The presence of renal failure at diagnosis was associated with death or progression to end stage renal failure.
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Affiliation(s)
- Ikram Agrebi
- Nephrology Department, Hedi Chaker University Hospital, Faculty of Medicine of Sfax, Sfax, Tunisia
| | - Khawla Kammoun
- Nephrology Department, Hedi Chaker University Hospital, Faculty of Medicine of Sfax, Sfax, Tunisia.,Laboratory of Research of Renal Pathology LR 19ES11, Faculty of Medicine of Sfax, Sfax, Tunisia
| | - Najla Dammak
- Nephrology Department, Hedi Chaker University Hospital, Faculty of Medicine of Sfax, Sfax, Tunisia.,Laboratory of Research of Renal Pathology LR 19ES11, Faculty of Medicine of Sfax, Sfax, Tunisia
| | - Jamil Hachicha
- Nephrology Department, Hedi Chaker University Hospital, Faculty of Medicine of Sfax, Sfax, Tunisia
| | - Tahya Boudawara
- Laboratory of Anatomopathology, Habib Bourguiba University Hospital, Faculty of Medicine of Sfax, Sfax, Tunisia
| | - Faiçal Jarraya
- Nephrology Department, Hedi Chaker University Hospital, Faculty of Medicine of Sfax, Sfax, Tunisia.,Laboratory of Research of Renal Pathology LR 19ES11, Faculty of Medicine of Sfax, Sfax, Tunisia
| | - Mohamed Ben Hmida
- Nephrology Department, Hedi Chaker University Hospital, Faculty of Medicine of Sfax, Sfax, Tunisia.,Laboratory of Research of Renal Pathology LR 19ES11, Faculty of Medicine of Sfax, Sfax, Tunisia
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Chothia MY, Panday AS, Coetzee L, Bates W. Outcomes of immunoglobulin-associated mesangiocapillary glomerulonephritis: A South African experience. Nephrology (Carlton) 2020; 25:765-774. [PMID: 32463170 DOI: 10.1111/nep.13736] [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: 04/13/2020] [Revised: 05/16/2020] [Accepted: 05/20/2020] [Indexed: 11/28/2022]
Abstract
AIM Immunoglobulin-associated mesangiocapillary glomerulonephritis is currently the most common biopsy-confirmed glomerulonephritis in Cape Town, South Africa. We aimed to determine the outcome of patients with a biopsy-confirmed diagnosis of immunoglobulin-associated mesangiocapillary glomerulonephritis at our centre. METHODS A retrospective cohort study of adult patients was conducted from January 1, 2000 to December 31, 2016. The endpoint was a composite of doubling of creatinine and/or end-stage renal disease and/or death. Cox univariable and multivariable proportional hazards models were used to examine the association between the composite endpoint and predictor variables. Survival curves were made with the use of Kaplan-Meier estimates. RESULTS A total of 70 patients were included in the study and their median duration of follow-up was 30.4 months. Forty-eight (68.6%) patients reached the composite endpoint. The proportion reaching this endpoint at 1, 3 and 5 years were 37.5%, 64.6% and 81.3%, respectively. Cox multivariable proportional hazards model identified a serum creatinine concentration > 200 μmol/L at the time of biopsy, moderate to severe interstitial fibrosis, ≥50% crescents and cyclophosphamide therapy as predictors of the composite endpoint. CONCLUSION Immunoglobulin-associated mesangiocapillary glomerulonephritis remains a common glomerular pathological diagnosis in our setting and has poor outcomes. This may partially be explained by late presentation. Future research needs to focus on identifying the possible cause(s) of this common glomerular disease so that more targeted therapeutic approaches can be offered.
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Affiliation(s)
- Mogamat-Yazied Chothia
- Division of Nephrology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Amaan Shabeer Panday
- Division of Nephrology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Liezel Coetzee
- Department of Anatomical Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University and National Health Laboratory Service, Cape Town, South Africa
| | - William Bates
- Department of Anatomical Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University and National Health Laboratory Service, Cape Town, South Africa
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Kelleher C, Kocinsky H. Novel Complement Therapeutics in Development as Potential Treatment for Renal Disease. Adv Chronic Kidney Dis 2020; 27:95-103. [PMID: 32553251 DOI: 10.1053/j.ackd.2020.02.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 02/20/2020] [Accepted: 02/20/2020] [Indexed: 11/11/2022]
Abstract
The complement system is an evolutionarily ancient arm of the innate immune system. It remains, however, one of the last major pathways in immunology for which specific pharmaceutical antagonists have been developed. In recent years, a fundamental role for complement has been described in many different renal diseases, including both pauci-immune as well as immune-complex diseases. Since the 2011 FDA approval of eculizumab, the only marketed complement antagonist, no new therapeutics have entered clinical practice. There are now multiple new agents in clinical trials, from oral molecules to small inhibitory RNA, that target the classical, lectin, and alternative pathways. Herein we summarize several potential renal diseases in which complement inhibitors may provide a therapeutic benefit, as well as specific complement inhibitors in development.
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Wearne N, Swanepoel CR, Duffield MS, Davidson BJ, Manning K, Tiffin N, Boulle A, Rayner BL, Naidu P, Okpechi IG. The effects of add-on corticosteroids on renal outcomes in patients with biopsy proven HIV associated nephropathy: a single centre study from South Africa. BMC Nephrol 2019; 20:44. [PMID: 30728003 PMCID: PMC6366071 DOI: 10.1186/s12882-019-1208-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Accepted: 01/09/2019] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The aim of this study was to assess, the efficacy and safety of add-on corticosteroids to antiretroviral therapy [ART] in patients with biopsy proven HIV associated nephropathy. METHODS All included patients had histological evidence of either collapsing or non-collapsing focal segmental glomerulosclerosis (FSGS) or podocyte and/or parietal cell hypertrophy or hyperplasia. All patients had evidence of tubulointerstitial inflammation with microcysts. Patients were randomized to ART with the addition of 1 mg/kg of corticosteroids [ART+C] or remained in the group [ART Alone] and followed for 2 years. A repeat biopsy was performed at 6 months. RESULTS Twenty-one patients were randomized to [ART+C] and 17 to [ART Alone]. The baseline estimated glomerular filtration rate (eGFR) was significantly lower in the [ART+C] vs. [ART Alone] group [35mls/min/1.73m2 vs. 47 mls/min/1.73m2, p = 0.015]. The [ART+C] cohort had a statistically significant improvement in median (eGFR) from baseline to last follow up compared with [ART Alone] i.e. [Δ = 25mls/min (IQR: 15;51) vs 9 mls/min (IQR: 0-24), p = 0.008]. There were no statistically significant differences between the groups when proteinuria and histology were analyzed. There were 8 deaths during the trial period, 7 from [ART+C] (Log rank p = 0.071). CONCLUSIONS In the [ART+C] cohort there was a significant improvement in eGFR over 2-years with increased mortality. Routine corticosteroid use cannot currently be recommended. Further investigation to define which subgroup of this cohort would safely benefit from the positive effects is required. TRIAL REGISTRATION ISRCTN study ID ( 56112439 ] was retrospectively registered on the 5 September 2018.
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Affiliation(s)
- Nicola Wearne
- Division of Nephrology and Hypertension, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa
- Kidney and Hypertension Research Unit, University of Cape Town, Cape Town, South Africa
| | - Charles R. Swanepoel
- Division of Nephrology and Hypertension, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa
- Kidney and Hypertension Research Unit, University of Cape Town, Cape Town, South Africa
| | - Maureen S. Duffield
- Division of Pathology, Department of Clinical Laboratory Services, University of Cape Town, Cape Town, South Africa
| | - Bianca J. Davidson
- Division of Nephrology and Hypertension, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa
- Kidney and Hypertension Research Unit, University of Cape Town, Cape Town, South Africa
| | - Kathryn Manning
- Department of Medicine, Statistical Analyst, University of Cape Town, Cape Town, South Africa
| | - Nicki Tiffin
- CIDER: School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa
| | - Andrew Boulle
- CIDER: School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa
| | - Brian L. Rayner
- Division of Nephrology and Hypertension, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa
- Kidney and Hypertension Research Unit, University of Cape Town, Cape Town, South Africa
| | - Priyanka Naidu
- Department of Undergraduate Medicine, University of Cape Town, Cape Town, South Africa
| | - Ikechi G. Okpechi
- Division of Nephrology and Hypertension, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa
- Kidney and Hypertension Research Unit, University of Cape Town, Cape Town, South Africa
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Okpechi IG, Ameh OI, Bello AK, Ronco P, Swanepoel CR, Kengne AP. Epidemiology of Histologically Proven Glomerulonephritis in Africa: A Systematic Review and Meta-Analysis. PLoS One 2016; 11:e0152203. [PMID: 27011216 PMCID: PMC4806979 DOI: 10.1371/journal.pone.0152203] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2015] [Accepted: 03/10/2016] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND AND AIM Glomerulonephritis (GN) is a leading cause of end-stage renal disease (ESRD) in Africa. Data on epidemiology and outcomes of glomerular diseases from Africa is still limited. We conducted a systematic review on the epidemiology of histologically proven glomerular diseases in Africa between 1980 and 2014. MATERIALS AND METHODS We searched literature using PubMed, AfricaWide, the Cumulative Index to Nursing and Allied Health Literature on EBSCO Host, Scopus, African Journals online databases, and the African Index Medicus, for relevant studies. The review was conducted using standard methods and frameworks using only biopsy-confirmed data. RESULTS Twenty four (24) studies comprising 12,093 reported biopsies from 13 countries were included in this analysis. The median number of biopsies per study was 127.0 (50-4436), most of the studies (70.0%) originated from North Africa and the number of performed kidney biopsies varied from 5.2 to 617 biopsies/year. Nephrotic syndrome was the commonest indication of renal biopsy. The frequency of reported primary pathologic patterns included, minimal change disease (MCD); 16.5% (95%CI: 11.2-22.6), focal segmental glomerulosclerosis (FSGS); 15.9% (11.3-21.1), mesangiocapillary GN (MCGN); 11.8% (9.2-14.6), crescentic GN; 2.0% (0.9-3.5) and IgA nephropathy 2.8% (1.3-4.9). Glomerular diseases related to hepatitis B and systemic lupus erythematosus had the highest prevalence among assessed secondary diseases: 8.4% (2.0-18.4) and 7.7% (4.5-11.7) respectively. There was no evidence of publication bias and regional differences were seen mostly for secondary GNs. CONCLUSIONS Glomerular diseases remain poorly characterized in sub-Saharan Africa due to declining renal biopsy rates and consequent paucity of data on pathologic patterns of key renal diseases. Development of renal biopsy registries in Africa is likely to enable adequate characterization of the prevalence and patterns of glomerular diseases; this could have a positive impact on chronic kidney disease evaluation and treatment in the African continent since most glomerulopathies are amenable to treatment.
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Affiliation(s)
- Ikechi G. Okpechi
- E13 Renal Unit, Groote Schuur Hospital and Division of Nephrology and Hypertension, University of Cape, Observatory, Cape Town, South Africa
| | - Oluwatoyin I. Ameh
- E13 Renal Unit, Groote Schuur Hospital and Division of Nephrology and Hypertension, University of Cape, Observatory, Cape Town, South Africa
| | - Aminu K. Bello
- Department of Medicine, University of Alberta, Edmonton, Canada
| | - Pierre Ronco
- Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche Paris, France; Sorbonne Universités, Université Pierre and Marie Curie, Paris, France; and Assistance Publique-Hôpitaux de Paris, Department of Nephrology and Dialysis, Tenon Hospital, Paris, France
| | - Charles R. Swanepoel
- E13 Renal Unit, Groote Schuur Hospital and Division of Nephrology and Hypertension, University of Cape, Observatory, Cape Town, South Africa
| | - Andre P. Kengne
- Non-Communicable Diseases Research Unit, South African Medical Research Council & University of Cape Town, Cape Town, South Africa
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