Histological reappraisal of IgA nephropathy: the role of glomerular pattern of injury and mesangial complement deposition.
Complement
Glomerular pattern
Histology
IgA nephropathy
Renal outcome
Journal
BMC nephrology
ISSN: 1471-2369
Titre abrégé: BMC Nephrol
Pays: England
ID NLM: 100967793
Informations de publication
Date de publication:
24 Apr 2024
24 Apr 2024
Historique:
received:
19
01
2024
accepted:
11
04
2024
medline:
25
4
2024
pubmed:
25
4
2024
entrez:
24
4
2024
Statut:
epublish
Résumé
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. 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. 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/1.73m 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.
Sections du résumé
BACKGROUND
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
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
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/1.73m
CONCLUSIONS
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.
Identifiants
pubmed: 38658875
doi: 10.1186/s12882-024-03577-z
pii: 10.1186/s12882-024-03577-z
doi:
Substances chimiques
Complement C3
0
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
145Informations de copyright
© 2024. The Author(s).
Références
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(10):1584.
doi: 10.3390/jcm8101584
pubmed: 31581654
pmcid: 6833025
Pitcher D, Braddon F, Hendry B, Mercer A, Osmaston K, Saleem MA, Steenkamp R, Wong K, Turner AN, Wang K, Gale DP, Barratt J. Long-term outcomes in IgA nephropathy. Clin J Am Soc Nephrol. 2023;18(6):727–38.
doi: 10.2215/CJN.0000000000000135
pubmed: 37055195
Rauen T, Eitner F, Fitzner C, Sommerer C, Zeier M, Otte B, Panzer U, Peters H, Benck U, Mertens PR, Kuhlmann U, Witzke O, Gross O, Vielhauer V, Mann JF, Hilgers RD, Floege J. STOP-IgAN investigators. Intensive supportive care plus immunosuppression in IgA nephropathy. N Engl J Med. 2015;373(23):2225–36.
doi: 10.1056/NEJMoa1415463
pubmed: 26630142
Lv J, Wong MG, Hladunewich MA, Jha V, Hooi LS, Monaghan H, Zhao M, Barbour S, Jardine MJ, Reich HN, Cattran D, Glassock R, Levin A, Wheeler DC, Woodward M, Billot L, Stepien S, Rogers K, Chan TM, Liu ZH, Johnson DW, Cass A, Feehally J, Floege J, Remuzzi G, Wu Y, Agarwal R, Zhang H, Perkovic V, Testing Study Group. Effect of oral methylprednisolone on decline in kidney function or kidney failure in patients with IgA nephropathy: the testing randomized clinical trial. JAMA. 2022;327(19):1888–98.
doi: 10.1001/jama.2022.5368
pubmed: 35579642
pmcid: 9115617
Wheeler DC, Toto RD, Stefánsson BV, Jongs N, Chertow GM, Greene T, et al. A pre-specified analysis of the DAPA-CKD trial demonstrates the effects of dapagliflozin on major adverse kidney events in patients with IgA nephropathy. Kidney Int. 2021;100(1):215–24.
doi: 10.1016/j.kint.2021.03.033
pubmed: 33878338
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(1):20119.
doi: 10.1038/s41598-023-47393-1
pubmed: 37978255
pmcid: 10656480
Barbour SJ, Canney M, Coppo R, Zhang H, Liu ZH, Suzuki Y, et al. Improving treatment decisions using personalized risk assessment from the international IgA nephropathy prediction tool. Kidney Int. 2020;98(4):1009–19.
doi: 10.1016/j.kint.2020.04.042
pubmed: 32464215
Bellur SS, Roberts ISD, Troyanov S, Royal V, Coppo R, Cook HT, Cattran D, Arce Terroba Y, Asunis AM, Bajema I, Bertoni E, Bruijn JA, Cannata-Ortiz P, Casartelli D, Di Maria A, Ferrario F, Fortunato M, Furci L, Gakiopoulou H, Galesic Ljubanovic D, Giannakakis K, Gomà M, Gröne HJ, Gutiérrez E, Asma Haider S, Honsova E, Ioachim E, Karkoszka H, Kipgen D, Maldyk J, Mazzucco G, Orhan D, Ozluk Y, Pantzaki A, Perkowska-Ptasinska A, Riispere Z, Soderberg MP, Steenbergen E, Stoppacciaro A, Von Sundelin B, Tardanico R. Reproducibility of the Oxford classification of immunoglobulin a nephropathy, impact of biopsy scoring on treatment allocation and clinical relevance of disagreements: evidence from the validation of IGA study cohort. Nephrol Dial Transpl. 2019;34(10):1681–90.
doi: 10.1093/ndt/gfy337
Bajema IM, Wilhelmus S, Alpers CE, Bruijn JA, Colvin RB, Cook HT, D’Agati VD, Ferrario F, Haas M, Jennette JC, Joh K, Nast CC, Noël LH, Rijnink EC, Roberts ISD, Seshan SV, Sethi S, Fogo AB. Revision of the international society of nephrology/renal pathology society classification for lupus nephritis: clarification of definitions, and modified national institutes of health activity and chronicity indices. Kidney Int. 2018;93(4):789–96.
doi: 10.1016/j.kint.2017.11.023
pubmed: 29459092
Brix SR, Noriega M, Tennstedt P, Vettorazzi E, Busch M, Nitschke M, et al. Development and validation of a renal risk score in ANCA-associated glomerulonephritis. Kidney Int. 2018;94(6):1177–88.
doi: 10.1016/j.kint.2018.07.020
pubmed: 30385041
Kidney Disease. Improving global outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 clinical practice guideline for the management of glomerular diseases. Kidney Int. 2021;100(4S):S1–276.
Zhang H, Rizk DV, Perkovic V, Maes B, Kashihara N, Rovin B, et al. Results of a randomized double-blind placebo-controlled phase 2 study propose iptacopan as an alternative complement pathway inhibitor for IgA nephropathy. Kidney Int. 2024;105(1):189–99.
doi: 10.1016/j.kint.2023.09.027
pubmed: 37914086
Rovin BH, Barratt J, Heerspink HJL, Alpers CE, Bieler S, Chae DW, Diva UA, Floege J, Gesualdo L, Inrig JK, Kohan DE, Komers R, Kooienga LA, Lafayette R, Maes B, Małecki R, Mercer A, Noronha IL, Oh SW, Peh CA, Praga M, Preciado P, Radhakrishnan J, Rheault MN, Rote WE, Tang SCW, Tesar V, Trachtman H, Trimarchi H, Tumlin JA, Wong MG, Perkovic V. DUPRO steering committee and PROTECT investigators. Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial. Lancet. 2023;402(10417):2077–90.
doi: 10.1016/S0140-6736(23)02302-4
pubmed: 37931634
Caster DJ, Lafayette RA. The treatment of primary IgA nephropathy: change, change, change. Am J Kidney Dis. 2024;83(2):229–40.
doi: 10.1053/j.ajkd.2023.08.007
pubmed: 37742867
Mathur M, Barratt J, Chacko B, Chan TM, Kooienga L, Oh KH, Sahay M, Suzuki Y, Wong MG, Yarbrough J, Xia J, Pereira BJG, ENVISION Trial Investigators Group. A phase 2 trial of Sibeprenlimab in patients with IgA nephropathy. N Engl J Med. 2024;390(1):20–31.
doi: 10.1056/NEJMoa2305635
pubmed: 37916620
Barratt J, Lafayette R, Kristensen J, Stone A, Cattran D, Floege J, et al. Results from part A of the multi-center, double-blind, randomized, placebo-controlled NefIgArd trial, which evaluated targeted-release formulation of budesonide for the treatment of primary immunoglobulin a nephropathy. Kidney Int. 2023;103(2):391–402.
doi: 10.1016/j.kint.2022.09.017
pubmed: 36270561
Obrișcă B, Vornicu A, Procop A, Herlea V, Terinte-Balcan G, Gherghiceanu M, Ismail G. A histology-guided approach to the management of patients with Lupus Nephritis. Are We There Yet? Biomedicines. 2022;10(6):1409.
pubmed: 35740431
Rodrigues JC, Haas M, Reich HN. IgA nephropathy. Clin J Am Soc Nephrol. 2017;12(4):677–86.
doi: 10.2215/CJN.07420716
pubmed: 28159829
pmcid: 5383386
Obrișcă B, Ștefan G, Gherghiceanu M, Mandache E, Ismail G, Stancu S, Boitan B, Ion O, Mircescu G. Associated or secondary IgA nephropathy? An outcome analysis. PLoS ONE. 2019;14(8):e0221014.
doi: 10.1371/journal.pone.0221014
pubmed: 31398224
pmcid: 6688810
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J. CKD-EPI (chronic kidney disease epidemiology collaboration). A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604–12.
doi: 10.7326/0003-4819-150-9-200905050-00006
pubmed: 19414839
pmcid: 2763564
Histologic Subclassification of. IgA Nephropathy: A Clinicopathologic Study of 244 Cases.
Trimarchi H, Barratt J, Cattran DC, Cook HT, Coppo R, Haas M, et al. Oxford classification of IgA nephropathy 2016: an update from the IgA nephropathy classification working group. Kidney Int. 2017;91(5):1014–21.
doi: 10.1016/j.kint.2017.02.003
pubmed: 28341274
Working Group of the International IgA Nephropathy Network and the Renal Pathology Society, Roberts IS, Cook HT, Troyanov S, Alpers CE, Amore A, Barratt J, Berthoux F, Bonsib S, Bruijn JA, Cattran DC, Coppo R, D’Agati V, D’Amico G, Emancipator S, Emma F, Feehally J, Ferrario F, Fervenza FC, Florquin S, Fogo A, Geddes CC, Groene HJ, Haas M, Herzenberg AM, Hill PA, Hogg RJ, Hsu SI, Jennette JC, Joh K, Julian BA, Kawamura T, Lai FM, Li LS, Li PK, Liu ZH, Mackinnon B, Mezzano S, Schena FP, Tomino Y, Walker PD, Wang H, Weening JJ, Yoshikawa N, Zhang H. The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility. Kidney Int. 2009;76(5):546–56.
doi: 10.1038/ki.2009.168
Barratt J, Liew A, Yeo SC, Fernström A, Barbour SJ, Sperati CJ, Villanueva R, Wu MJ, Wang D, Borodovsky A, Badri P, Yureneva E, Bhan I, Cattran D. Cemdisiran phase 2 study investigators and collaborators. Phase 2 trial of Cemdisiran in adult patients with IgA nephropathy: a randomized controlled trial. Clin J Am Soc Nephrol. 2024 Jan;15. https://doi.org/10.2215/CJN.0000000000000384
Lv J, Liu L, Hao C, Li G, Fu P, Xing G, et al. Randomized phase 2 trial of telitacicept in patients with IgA nephropathy with persistent proteinuria. Kidney Int Rep. 2023;8(3):499–506.
doi: 10.1016/j.ekir.2022.12.014
pubmed: 36938094
Obrișcă B, Jurubiță R, Andronesi A, Sorohan B, Achim C, Bobeica R, Gherghiceanu M, Mandache E, Ismail G. Histological predictors of renal outcome in lupus nephritis: the importance of tubulointerstitial lesions and scoring of glomerular lesions. Lupus. 2018;27(9):1455–63.
doi: 10.1177/0961203318776109
pubmed: 29759047
Coppo R. Towards a personalized treatment for IgA nephropathy considering pathology and pathogenesis. Nephrol Dial Transpl. 2019;34(11):1832–8.
doi: 10.1093/ndt/gfy338
Lafayette R, Kristensen J, Stone A, Floege J, Tesař V, Trimarchi H, Zhang H, Eren N, Paliege A, Reich HN, Rovin BH, Barratt J. NefIgArd trial investigators. Efficacy and safety of a targeted-release formulation of budesonide in patients with primary IgA nephropathy (NefIgArd): 2-year results from a randomised phase 3 trial. Lancet. 2023;402(10405):859–70.
doi: 10.1016/S0140-6736(23)01554-4
pubmed: 37591292
Hou FF, Xie D, Wang J, Xu X, Yang X, Ai J, et al. Effectiveness of mycophenolate mofetil among patients with progressive IgA nephropathy: a randomized clinical trial. JAMA Netw Open. 2023;6(2):e2254054.
doi: 10.1001/jamanetworkopen.2022.54054
pubmed: 36745456
Hou JH, Le WB, Chen N, Wang WM, Liu ZS, Liu D, et al. Mycophenolate mofetil combined with prednisone versus full-dose prednisone in IgA nephropathy with active proliferative lesions: a randomized controlled trial. Am J Kidney Dis. 2017;69(6):788–95.
doi: 10.1053/j.ajkd.2016.11.027
pubmed: 28215945
Tesar V, Troyanov S, Bellur S, Verhave JC, Cook HT, Feehally J, et al. Corticosteroids in IgA nephropathy: a retrospective analysis from the VALIGA study. J Am Soc Nephrol. 2015;26:2248–58.
doi: 10.1681/ASN.2014070697
pubmed: 25677392
pmcid: 4552116
Maillard N, Wyatt RJ, Julian BA, Kiryluk K, Gharavi A, Fremeaux-Bacchi V, et al. Current understanding of the role of complement in IgA nephropathy. J Am Soc Nephrol. 2015;26(7):1503–12.
doi: 10.1681/ASN.2014101000
pubmed: 25694468
pmcid: 4483595
Ștefan G, Alamartine E, Mariat C, Maillard N. Systematic review of the Link between Oxford MEST-C classification and complement activation in IgA nephropathy. Kidney Int Rep. 2023;9(2):356–69.
doi: 10.1016/j.ekir.2023.11.005
pubmed: 38344730
pmcid: 10851005