The presence of extraglomerular deposits correlated with higher serum creatinine, a high number of urinary erythrocytes, and low C3 and hematocrit. An abnormal urinalysis with or without an elevated plasma creatinine concentration is present in a large proportion of patients at the time of diagnosis of lupus nephritis (LN). (A)Free survival curve (A) and KFI and death-free survival curve (B) of the study population during the entire follow-up period. Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, 10400, Thailand, Kornwipa Krassanairawiwong,Mongkon Charoenpitakchai,Ouppatham Supasyndh&Bancha Satirapoj, You can also search for this author in A new classification for lupus nephritis was recently proposed, namely, the revised ISN/RPS 2018 classification. 2023 Jan 26;11(2):365. doi: 10.3390/biomedicines11020365. Data supporting this study are available upon request. Int Urol Nephrol 53, 13911398 (2021). However, when we evaluated separately interstitial infiltration in patients with or without interstitial chronic lesions, the correlation with KFI was only maintained when tubular atrophy/interstitial fibrosis were present (P<0.001), whereas the correlation was lost in the presence of normal cortex (P=0.68). Moroni G, Gatto M, Tamborini F, Quaglini S, Radice F, Saccon F, Frontini G, Alberici F, Sacchi L, Binda V, Trezzi B, Vaglio A, Messa P, Sinico RA, Doria A: Lack of EULAR/ERA-EDTA response at 1 year predicts poor long-term renal outcome in patients with lupus nephritis. We retrospectively evaluated the immunofluorescence data and classified extraglomerular immune deposits as present or absent. Thus, serum creatinine was significantly and directly correlated with both activity and chronicity indices. An official website of the United States government. Mesangial proliferative LN. Clin Rheumatol. All of the histologic variables were evaluated as 0 if absent; 1+ if mild (in <25% of glomeruli and/or in tubulointerstitial area); 2+ if moderate (between 25% and <50% of glomeruli and/or in tubulointerstitial area); and 3+ if severe (in >50% of glomeruli and/or in tubulointerstitial area). Moreover, adding activity and chronicity index to the ISN/RPS LN classification improves the prognostic value of kidney biopsy. Over the last decades, advances in the therapeutic approach have improved the outcome of LN and mitigated the prognostic differences among histologic classes. No significant association was found between demographic parameters and activity index. Received 2021 Aug 20; Accepted 2021 Nov 1. We also specified if the deposits were localized in the tubular basement membrane, interstitial capillary wall, and/or small arteries. 2023 May 16. doi: 10.1007/s10067-023-06629-1. Adding the histologic characteristic to the clinical data, in multivariate analysis, serum creatinine (for any milligram per deciliter increase in serum creatinine, OR, 1.68; 95% CI, 1.31 to 2.15; P<0.001), arterial hypertension (OR, 4.64; 95% CI, 1.90 to 11.32; P<0.001), glomerulosclerosis (OR, 2.12; 95% CI, 1.00 to 4.50; P=0.05), fibrous crescents (OR, 5.18; 95% CI, 2.43 to 11.04; P<0.001), and months from LN onset to kidney biopsy (OR, 1.01; 95% CI, 1.00 to 1.01; P=0.03) were found to be independent predictors of KFI. At the same time, a renewed interest has arisen in the activity and chronicity indices, which were proposed years ago by Austin et al. Google Scholar, Chen YE, Korbet SM, Katz RS, Schwartz MM, Lewis EJ, Collaborative Study G (2008) Value of a complete or partial remission in severe lupus nephritis. Class VI: No changes have been made but it is recognized that a more precise distinction from advanced stages of chronic class IV lupus nephritis is needed. Objective: As observed in kidney transplantation, interstitial inflammation in normal tubulointerstitial areas may be considered as an expression of active rejection, which can potentially respond to therapy. doi: 10.3346/jkms.2009.24.S1.S7. PubMed An overview of the epidemiology, pathogenesis, diagnosis, and classification of LN will be presented here. Glomerular mTORC1 activation was associated with podocytes to endothelial cells communication in lupus nephritis. The .gov means its official. A total number of 41 patients with proliferative lupus nephritis on adequate renal biopsy specimen between 2017 and 2018 were included. Kidney Int 82(8):840856. After induction therapy, 56.1% of patients reached complete and partial remission and 43.9% reached no remission. However, tubulointerstitial damage may lead to KFI through different mechanisms. In univariate analyses, baseline glomerular filtration rate (GFR), presence of anti-DNA titer, cellular crescents, interstitial inflammation, glomerulosclerosis, interstitial fibrosis, tubular atrophy and total chronicity index strongly impacted renal response. The site is secure. An abnormal urinalysis with or without an elevated plasma creatinine concentration is present in a large proportion of patients at the time of diagnosis of lupus nephritis (LN). eCollection 2023 Apr. G. Banfi, M. Calatroni, C. Ponticelli, G. Porata, and F. Reggiani were responsible for visualization; G. Banfi, G. Moroni, and C. Ponticelli provided supervision; G. Banfi, G. Moroni, C. Ponticelli, G. Porata, S. Quaglini, and L. Sacchi were responsible for validation; G. Banfi, G. Moroni, G. Porata, and C. Ponticelli reviewed and edited the manuscript; V. Binda, G. Frontini, G. Moroni, G. Porata, S. Quaglini, F. Raffiotta, and L. Sacchi were responsible for data curation and formal analysis; V. Binda, G. Frontini, G. Moroni, G. Porata, and F. Raffiotta were responsible for investigation; G. Moroni and C. Ponticelli conceptualized the study; G. Moroni and G. Porata were responsible for methodology and resources; and G. Moroni, C. Ponticelli, and G. Porata wrote the original draft. Value of chronicity index and extraglomerular deposits in predicting clinical features at time of renal biopsy. Helps you get and maintain an erection when you need it. Epub 2013 May 28. The chronicity index was correlated with serum creatinine. 8600 Rockville Pike https://doi.org/10.1097/mnh.0b013e328327b379, Yokoyama H, Wada T, Hara A, Yamahana J, Nakaya I, Kobayashi M, Kitagawa K, Kokubo S, Iwata Y, Yoshimoto K, Shimizu K, Sakai N, Furuichi K, Kanazawa Study Group for Renal D, Hypertension (2004) The outcome and a new ISN/RPS 2003 classification of lupus nephritis in Japanese. Comparison of the 2018 and 2003 International Society of Nephrology/Renal Pathology Society classification in terms of renal prognosis in patients of lupus nephritis: a retrospective cohort study. Introduction The kidney is often affected in SLE and the impairment of renal function results from glomerular, tubule-interstitial and vascular lesions [ 1 ]. Introduction. Before 1Department of Biomedical Sciences, Humanitas University, Milan, Italy, 2Nephrology and Dialysis Unit, San Paolo Hospital, Milan, Italy, 3Nephrology and Dialysis Unit, Fatebenefratelli Hospital, Milan, Italy, 4Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy, 5Nephrology Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca Granda Ospedale Maggiore Policlinico, Milan, Italy, 6SantAgostino Medical Center, Milano, Italy, 7Nephrology, IRCCS Ospedale Maggiore Policlinico, Milano, Italy. Methods: Kidney Int 59(6):21562163. and transmitted securely. The 2018 revised International Society of Nephrology/Renal Pathology Society classification for lupus nephritis adopted the most recent NIH indices to replace subclasses A, C, and A/C. https://doi.org/10.4103/0366-6999.232809, Rush PJ, Baumal R, Shore A, Balfe JW, Schreiber M (1986) Correlation of renal histology with outcome in children with lupus nephritis. government site. A new classification for lupus nephritis was recently proposed, namely, the revised ISN/RPS 2018 classification. Before A new classification for lupus nephritis was recently proposed, namely, the revised ISN/RPS 2018 classification. This article contains the following supplemental material online at http://kidney360.asnjournals.org/lookup/suppl/doi:10.34067/KID.0005512021/-/DCSupplemental. HHS Vulnerability Disclosure, Help https://doi.org/10.1177/0961203317706558, Mavragani CP, Fragoulis GE, Somarakis G, Drosos A, Tzioufas AG, Moutsopoulos HM (2015) Clinical and laboratory predictors of distinct histopathogical features of lupus nephritis. PubMed Central Lupus nephritis (LN) occurs in ~50% of patients with SLE and is the most common, but not the only, cause of kidney injury in SLE. The clinical characteristics of the whole group at kidney biopsy are reported in Table 2. Treatment of Class V and VI remains controversial. Nephrotic syndrome was defined as proteinuria >3.5 g/24 h, with hypoalbuminemia and hypercholesterolemia. Activity and chronicity indices were dichotomized according to their median values. Epub 2022 Mar 28. The study identified baseline GFR, anti-DNA titer, cellular crescent, and high chronicity index according to revised ISN/RPS 2018 classification as important predictors of renal response after induction therapy in proliferative lupus nephritis. KFI, kidney function impairment; LN, lupus nephritis. For the aims of the study, KFI was defined by a decrease in creatinine clearance (14) of 30% over the baseline, confirmed by at least three determinations for at least 3 months. https://doi.org/10.1038/sj.ki.5002118, Yu F, Wu LH, Tan Y, Li LH, Wang CL, Wang WK, Qu Z, Chen MH, Gao JJ, Li ZY, Zheng X, Ao J, Zhu SN, Wang SX, Zhao MH, Zou WZ, Liu G (2010) Tubulointerstitial lesions of patients with lupus nephritis classified by the 2003 International Society of Nephrology and Renal Pathology Society system. This site needs JavaScript to work properly. 2020;51(6):483-492. doi: 10.1159/000507213. Thirteen patients (6%) who did not develop KFI died after a median (IQR) of 11.43 (3.9120.87) years; their causes of death were infections (three patients), cardiovascular accidents (five patients), and neoplasia (five patients). Clinical and histological variables were tested for their association with renal remission. This is not surprising if one considers that LN is probably initiated by glomerular deposition of immune complexes containing nucleic acids (18). Lupus Nephritis Classification Kidney Int 76(3):307317. Several studies pointed out the importance of assessing activity and chronicity changes in all kidney compartments (710), and the Working Group for LN proposed to add the activity and chronicity indices to all classes of the ISN/RPS classification to improve the prognostic value of kidney biopsy (11). After multivariate logistic regression analysis, we identified aging, presence of cellular crescents, and high total renal chronicity index as independent predictors of renal remission. A new classification for lupus nephritis was recently proposed, namely, the revised ISN/RPS 2018 classification. Before biopsy, all participants signed an informed consent for the scientific use of their anonymized records. doi: 10.1136/lupus-2023-000896. A Validation of the 2018 Revision of International Society of Nephrology/Renal Pathology Society Classification for Lupus Nephritis: A Cohort Study from China. Values indicate significant differences between the two compared groups (P<0.05), unless otherwise indicated by a footnote symbol. In addition, hyaline deposits were also significantly associated with higher proteinuria and lower serum albumin levels. Fanouriakis A, Kostopoulou M, Cheema K, Anders HJ, Aringer M, Bajema I, Boletis J, Frangou E, Houssiau FA, Hollis J, Karras A, Marchiori F, Marks SD, Moroni G, Mosca M, Parodis I, Praga M, Schneider M, Smolen JS, Tesar V, Trachana M, van Vollenhoven RF, Voskuyl AE, Teng YKO, van Leew B, Bertsias G, Jayne D, Boumpas DT: 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Broder A, Mowrey WB, Khan HN, Jovanovic B, Londono-Jimenez A, Izmirly P, Putterman C: Tubulointerstitial damage predicts end stage renal disease in lupus nephritis with preserved to moderately impaired renal function: A retrospective cohort study. The .gov means its official. volume53,pages 13911398 (2021)Cite this article. The term "endocapillary proliferation" is eliminated and the definition of endocapillary hypercellularity considered in some detail. Careers. https://doi.org/10.2215/CJN.03280807, Radhakrishnan J, Cattran DC (2012) The KDIGO practice guideline on glomerulonephritis: reading between the (guide) linesapplication to the individual patient. Google Scholar, Satirapoj B, Tasanavipas P, Supasyndh O (2015) Clinicopathological correlation in Asian patients with biopsy-proven lupus nephritis. Immunological and translational key challenges in systemic lupus erythematosus: A symposium update. Lupus nephritis is a specific type of inflammation in the kidneys known as a glomerulonephritis. 4 UNI | 4.95 per 1UNI. These data and our results, obtained in a larger cohort and with a longer follow-up, can support the thesis that glomerulosclerosis and interstitial fibrosis are linked pathogenetically. Epub 2013 May 28. The Revisited Classification of GN in SLE at 10 Years: Time to Re-Evaluate Histopathologic Lesions. Exclusion criteria comprised patients needing RRT at presentation or patients with inadequate kidney biopsy. After kidney biopsy, all patients received an induction therapy, which consisted of methylprednisolone pulses in 84% of patients, and the remaining patients were given oral prednisone. The aims of this study were (1) to detect the histologic features associated with the development of kidney function impairment (KFI), and (2) to identify the best clinical-histologic model to predict KFI at time of kidney biopsy. In a multicenter Chinese study, interstitial inflammation, tubular atrophy, and interstitial fibrosis were the only independent risk factors of kidney outcome (24). Clinical and histologic characteristics of 203 patients with lupus nephritis at kidney biopsy. Univariate and multivariate logistic regression and Cox proportional hazards models were used to investigate whether activity and chronicity indices could predict KFI development. Before The https:// ensures that you are connecting to the Lupus 27(9):14551463. The KaplanMeier estimate was used for survival. Would you like email updates of new search results? lupus nephritis; renal biopsy; systemic lupus erythematosus. If not otherwise specified, data are expressed as medians with interquartile ranges. 8600 Rockville Pike Austin HA 3rd, Muenz LR, Joyce KM, Antonovych TA, Kullick ME, Klippel JH, Decker JL, Balow JE: Prognostic factors in lupus nephritis. https://doi.org/10.1093/ndt/gft272, Tesar V, Hruskova Z (2017) Understanding histolopathologic characteristics to predict renal outcomes in lupus nephritis. The study identified baseline GFR, anti-DNA titer, cellular crescent, and high chronicity index according to revised ISN/RPS 2018 classification as important predictors of renal response after induction therapy in proliferative lupus nephritis. Clipboard, Search History, and several other advanced features are temporarily unavailable. Several studies evaluated, separately or together, the effect of interstitial inflammation (20,2326), chronic tubulointerstitial lesions (19,20,23,24), and extraglomerular deposits (21,22,25,27) in predicting kidney outcome, but with conflicting results. In addition, serum C3 and C4 levels were directly correlated with chronicity index. Hill GS, Delahousse M, Nochy D, Mandet C, Barity J: Proteinuria and tubulointerstitial lesions in lupus nephritis. Combining all factors achieved a perfect score predicting renal response (AUC 0.924; 95% CI 0.840-1.000). This suggests that, in the presence of high serum creatinine, without a kidney biopsy, it is difficult to establish if the renal impairment is due to active or chronic lesions. In univariate analysis, there was a strong correlation between laboratory signs of LN and the activity index and most of its components (Tables 3 and and4).4). Curr Opin Nephrol Hypertens 18(3):220225. Clin J Am Soc Nephrol 12(5):734743. CAS The https:// ensures that you are connecting to the Among the clinical variables, serum creatinine (for any milligram per deciliter increase in serum creatinine, OR, 1.79; 95% CI, 1.45 to 2.22; P<0.001); arterial hypertension (OR, 6.15; 95% CI, 2.60 to 14.58; P<0.001); and, among the possible confounders, months from clinical LN onset to kidney biopsy (for each month delay in performing renal biopsy, OR, 1.01; 95% CI, 1.00 to 1.01; P=0.02) were independent predictors of KFI in multivariate analysis (Table 6). No significant correlation was found between interstitial inflammation and extraglomerular immune deposits (data not shown), disproving the pathogenetic interdependence between the two lesions. The authors declare that they have no competing interests. official website and that any information you provide is encrypted Int J Rheum Dis. sharing sensitive information, make sure youre on a federal PubMed Central (21), and in contrast to Hill et al. - 185.216.179.244. 2015 Dec;26(12):2938-46. doi: 10.1681/ASN.2015040384. Leatherwood C, Speyer CB, Feldman CH, DSilva K, Gmez-Puerta JA, Hoover PJ, Waikar SS, McMahon GM, Rennke HG, Costenbader KH: Clinical characteristics and renal prognosis associated with interstitial fibrosis and tubular atrophy (IFTA) and vascular injury in lupus nephritis biopsies. Conclusion: https://doi.org/10.1097/MD.0000000000000829, Wernick RM, Smith DL, Houghton DC, Phillips DS, Booth JL, Runckel DN, Johnson DS, Brown KK, Gaboury CL (1993) Reliability of histologic scoring for lupus nephritis: a community-based evaluation. Interstitial inflammation was the only element of the activity index that was associated with KFI in univariate analysis, but this association was not found during multivariate analysis. The divergent isotypes of antibodies deposited in the glomeruli and in the interstitium may validate this hypothesis (31). CAS Lupus nephritis is histologically evident in most patients with SLE, even those without cl. Regardless of the relationship between glomerular and tubulointerstitial damage, our data show that chronic glomerular and tubulointerstitial damage are both the determinants of kidney prognosis. Renaudineau Y, Muller S, Hedrich CM, Chauveau D, Bellire J, De Almeida S, Damoiseaux J, Scherlinger M, Guery JC, Sailler L, Bost C. J Transl Autoimmun. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). https://doi.org/10.2215/CJN.10601016, Bajema IM, Wilhelmus S, Alpers CE, Bruijn JA, Colvin RB, Cook HT, DAgati VD, Ferrario F, Haas M, Jennette JC, Joh K, Nast CC, Noel LH, Rijnink EC, Roberts ISD, Seshan SV, Sethi S, Fogo AB (2018) 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. FOIA Am J Med 83(5):877885, Chen DN, Fan L, Wu YX, Zhou Q, Chen W, Yu XQ (2018) A predictive model for estimation risk of proliferative lupus nephritis. Bethesda, MD 20894, Web Policies Int J Mol Sci. https://doi.org/10.1093/rheumatology/ken019, Article Among the demographic variables, only the calendar year of biopsy (P=0.05) was weakly correlated with an activity index of more than six. Bookshelf In the activity index, we include fibrinoid necrosis as a specific descriptor. International Urology and Nephrology This content does not have an English version. We also make recommendations on issues for which there are limited data at present and that can best be addressed in future studies (phase 2). Cyclophosphamide or mycophenolate were added in 87% of patients. After induction therapy, 56.1% of patients reached complete and partial remission and 43.9% reached no remission. As a library, NLM provides access to scientific literature. Class II. https://doi.org/10.5114/pjp.2014.45786, Markowitz GS, DAgati VD (2007) The ISN/RPS 2003 classification of lupus nephritis: an assessment at 3 years. Mannon RB, Matas AJ, Grande J, Leduc R, Connett J, Kasiske B, Cecka JM, Gaston RS, Cosio F, Gourishankar S, Halloran PF, Hunsicker L, Rush D; DeKAF Investigators : Inflammation in areas of tubular atrophy in kidney allograft biopsies: A potent predictor of allograft failure. The excessive deposition of extracellular matrix can replace functional parenchyma, release inflammatory mediators and reactive oxygen species, and induce epithelial-mesenchymal transition, eventually leading to interstitial fibrosis and chronic kidney failure (3740). (19) and Broder et al. A precise description of renal histological lesions and an appropriate classification of lupus nephritis are both essential for nephrologists to guide treatment and predict prognosis among patients. In this study, we evaluated whether the demographic characteristics of the population had an effect on the severity of activity and chronicity index scores at baseline kidney biopsy. When kidney biopsy was performed 3 or <3 months after the clinical LN onset, the respective mean chronicity index scores were 2.9 (2.8) and 1.8 (2; P=0.001). Not surprising if one considers that LN is probably initiated by glomerular deposition of immune complexes containing acids! 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