(2) To highlight current practices not addressed in the 2013 Childhood Arthritis and Rheumatology Research Alliance (CARRA) consensus treatment plan (CTP) for pediatric lupus . Data supporting this study are available upon request. KFI, kidney function impairment; T-I, tubulointerstitial. This is not surprising if one considers that LN is probably initiated by glomerular deposition of immune complexes containing nucleic acids (18). on the basis of light microscopy, immunofluorescence (13), and on electron microscopy, when necessary; disagreements were adjudicated by consensus. doi: 10.3346/jkms.2009.24.S1.S7. 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). Nephrotic syndrome was defined as proteinuria >3.5 g/24 h, with hypoalbuminemia and hypercholesterolemia. Mesangial proliferative LN. The .gov means its official. This site needs JavaScript to work properly. GUID:3D14D8E3-12CD-4FD7-880F-5A310C7642B2, GUID:7FAE0C22-E479-40E9-B198-3EE9E6E6E63A, glomerular and tubulointerstitial diseases, lupus nephritis, systemic lupus erythematosus. CAS J Am Soc Nephrol. The effect of tubulointerstitial chronic lesions on CKD was already outlined by many reports (19,20,2325,28,34). Austin HA 3rd, Muenz LR, Joyce KM, Antonovych TA, Kullick ME, Klippel JH, Decker JL, Balow JE: Prognostic factors in lupus nephritis. Lupus Nephritis Classification Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. An official website of the United States government. Values indicate significant differences between the two compared groups (P<0.05), unless otherwise indicated by a footnote symbol. Pure mesangial hypercellularity or mesangial matrix expansion with mesangial IC deposits. For Peer Review Only 4 1 On May 9-11th 2016, a Working Group for Lupus Nephritis Classification (the Group) met at 2 Leiden University Medical Center to reach a consensus on recently raised issues concerning 3 problems with definitions of lupus nephritis lesions.1 Prior to the meeting, those attending 4 received a questionnaire asking for anonymous suggestions for improving the definitions. In most cases, Class I and II of lupus nephritis do not require any specific treatment, but class III and IV lupus nephritis require immunosuppressive therapy. . 8600 Rockville Pike KFI, kidney function impairment; ACE, angiotensin-converting enzyme; HPF, high powered field; Ab, antibody; dsDNA, double-stranded DNA; ENA, extractable nuclear antigen; Anti-SM, anti-Smith autoantibodies; Anti-SSA, antiSjgren's-syndrome-related antigen A autoantibodies; Anti-SSB antiSjgren's-syndrome-related antigen B autoantibodies, Anti-RNP, anti-Ribonucleoprotein autoantibodies; IST, immunosuppressive therapy; CY, cyclophosphamide; MMF, mycophenolate mofetil; AZA, azathioprine; CsA, cyclosporine. A new classification for lupus nephritis was recently proposed, namely, the revised ISN/RPS 2018 classification. PubMed Central The median (IQR) serum creatinine was 0.9 (0.71.4) mg/dl, creatinine clearance was 80.45 (51.61110.1) ml/min. https://doi.org/10.1007/s11255-020-02732-3, DOI: https://doi.org/10.1007/s11255-020-02732-3. Methods. 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. https://doi.org/10.1111/j.1523-1755.2004.66027.x, Hiramatsu N, Kuroiwa T, Ikeuchi H, Maeshima A, Kaneko Y, Hiromura K, Ueki K, Nojima Y (2008) Revised classification of lupus nephritis is valuable in predicting renal outcome with an indication of the proportion of glomeruli affected by chronic lesions. On the basis of logistic regression analysis, older age (P<0.001) and longer delay between clinical onset of LN and kidney biopsy (P=0.001) were directly correlated with higher baseline chronicity index. The active and chronic designations for class III/IV lesions are replaced by a proposal for activity and chronicity indices that should be applied to all classes. Different dichotomizations of ordinal variables, ranging from zero to three, were tested (e.g., 0 versus 13, 01 versus 23) and the best dichotomization, according to its P value in the statistical models, was retained. Am J Nephrol. 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. 2023 Springer Nature Switzerland AG. In a multicenter Chinese study, interstitial inflammation, tubular atrophy, and interstitial fibrosis were the only independent risk factors of kidney outcome (24). Learn more about Institutional subscriptions. 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. 2013 Dec;16(6):731-8. doi: 10.1111/1756-185X.12059. Among the demographic variables, only the calendar year of biopsy (P=0.05) was weakly correlated with an activity index of more than six. 2022 Dec;37(12):3139-3145. doi: 10.1007/s00467-022-05524-2. Unable to load your collection due to an error, Unable to load your delegates due to an error. Hyaline deposits had the best correlation with clinical activity. A total number of 41 patients with proliferative lupus nephritis on adequate renal biopsy specimen between 2017 and 2018 were included. https://doi.org/10.1038/ki.2012.280, Pagni F, Galimberti S, Goffredo P, Basciu M, Malachina S, Pilla D, Galbiati E, Ferrario F (2013) The value of repeat biopsy in the management of lupus nephritis: an international multicentre study in a large cohort of patients. https://doi.org/10.2215/CJN.03490317, Dasari S, Chakraborty A, Truong L, Mohan C (2019) A systematic review of interpathologist agreement in histologic classification of lupus nephritis. Google Scholar, Parikh SV, Rovin BH (2016) Current and emerging therapies for lupus nephritis. Parikh SV, Rovin BH (2016) Current and emerging therapies for lupus nephritis. The remaining 178 participants were followed up regularly and continued to adhere to prescriptions (the comparison between the clinical data at 1 year for these groups is reported in Supplemental Table 2). Conversely, interstitial inflammation in areas with interstitial fibrosis/tubular atrophy is hardly reversible and is associated with poor kidney survival (30). 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. The site is secure. However, patients with extraglomerular deposits seemed to have a more active LN (higher urinary erythrocyte number, lower C3 and hematocrit), in agreement with Wang et al. 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. Int J Rheum Dis 21(2):458467. (A)Free survival curve (A) and KFI and death-free survival curve (B) of the study population during the entire follow-up period. 2009 Jan;24 Suppl(Suppl 1):S7-10. In the activity index, we include fibrinoid necrosis as a specific descriptor. HPF, high power field. A new classification for lupus nephritis was recently proposed, namely, the revised ISN/RPS 2018 classification. Treatment of Class V and VI remains controversial. eCollection 2023 Apr. Epub 2015 Jul 7. The term "endocapillary proliferation" is eliminated and the definition of endocapillary hypercellularity considered in some detail. Kidney Int 71(6):491495. Lupus nephritis (LN), a common complication of SLE, is associated with a high risk of morbidity and mortality ().Kidney biopsy is the gold standard for diagnosis and management of LN ().In 2003, the International Society of Nephrology and Renal Pathology Society (ISN/RPS) updated the histologic classification of LN ().This classification assessed only the glomerular pathology . 2023 May 24. doi: 10.1007/s00467-023-06018-5. 2 In order to verify suspicions of lupus nephritis, a renal biopsy must be performed. The .gov means its official. Our study has limitations due to its retrospective nature and extended follow-up period, over which the treatment regimens used in LN have evolved. 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). Class I. Lupus nephritis, one of the most serious manifestations of systemic lupus erythematosus (SLE), usually arises within 5 years of diagnosis; however, renal failure rarely occurs before American College of Rheumatology criteria for classification are met. 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). In addition, proteinuria is not of help because this parameter did not correlate with activity nor with chronicity indices. 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). 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). Background: Methods: An overview of the epidemiology, pathogenesis, diagnosis, and classification of LN will be presented here. Int J Rheum Dis. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). This point was also stressed by recent guidelines for LN (2). Tao J, Wang H, Yu XJ, Tan Y, Yu F, Wang SX, Haas M, Glassock RJ, Zhao MH: A validation of the 2018 Revision of International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: A cohort study from China. Am J Nephrol. Value of chronicity index and extraglomerular deposits in predicting clinical features at time of renal biopsy. Most participants were White, and these results cannot be extended to other races and ethnicities. Considering both clinical and histologic features, 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), and fibrous crescents (OR, 5.18; 95% CI, 2.43 to 11.04; P<0.001) independently predicted KFI. Lupus classification; Lupus nephritis; Pathological classification; Renal remission. Disclaimer. Please enable it to take advantage of the complete set of features! Pediatr Nephrol. The study aimed to evaluate the predictive value of the clinical and pathological factors according to ISN/RPS 2018 classification on renal remission among patients with proliferative lupus nephritis. Kidney Int 25(4):689695. Rheumatology (Oxford) 47(5):702707. After multivariate logistic regression analysis, we identified aging, presence of cellular crescents, and high total renal chronicity index as independent predictors of renal remission. Nephrol Dial Transplant 28(12):30143023. Analysis of clinicopathologic correlations in Iranian patients with lupus nephritis. During a median (IQR) follow-up of 14.03 (4.9420.67) years, kidney function became impaired in 39 (19%) patients in a median (IQR) of 6.6 (1.4319.49) years after kidney biopsy, and 13 (33%) of these patients reached ESKD. https://doi.org/10.1016/j.ekir.2019.06.011, Oni L, Beresford MW, Witte D, Chatzitolios A, Sebire N, Abulaban K, Shukla R, Ying J, Brunner HI (2017) Inter-observer variability of the histological classification of lupus glomerulonephritis in children. Epub 2020 Apr 22. sharing sensitive information, make sure youre on a federal Before (46). Hill GS, Delahousse M, Nochy D, Mandet C, Barity J: Proteinuria and tubulointerstitial lesions in lupus nephritis. An activity index of more than six was significantly more frequent in class IV than in class III or V LN (Tables 3 and and4).4). Conclusion: The authors received no specific funding for this work. and transmitted securely. Lupus nephritis - Symptoms and causes - Mayo Clinic Learn about this common lupus complication affecting the kidneys, including symptoms to watch for, how it's diagnosed and what treatments are available. Kidney Int 29(5):10661071. 2. 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 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. A renewed interest for activity and chronicity indices as predictors of lupus nephritis (LN) outcome has emerged. Linear multivariate regression of the demographic characteristics was used to determine the predictors of the activity and chronicity indices at baseline kidney biopsy. https://doi.org/10.1177/0961203318788167, Obrisca B, Jurubita R, Andronesi A, Sorohan B, Achim C, Bobeica R, Gherghiceanu M, Mandache E, Ismail G (2018) Histological predictors of renal outcome in lupus nephritis: the importance of tubulointerstitial lesions and scoring of glomerular lesions. https://doi.org/10.1191/0961203305lu2081oa, Ding Y, Nie LM, Pang Y, Wu WJ, Tan Y, Yu F, Zhao MH (2018) Composite urinary biomarkers to predict pathological tubulointerstitial lesions in lupus nephritis. Inflammation and hypoxia linked to renal injury by CCAAT/enhancer-binding protein , Renal tubule injury: A driving force toward chronic kidney disease, The inflammatory state is a risk factor for cardiovascular disease and graft fibrosis in kidney transplantation, Predicting Kidney Survival in Lupus Nephritis by Adding Clinical Data to Pathologic Features, http://kidney360.asnjournals.org/lookup/suppl/doi:10.34067/KID.0005512021/-/DCSupplemental, Months from renal manifestations to kidney biopsy, Serum C3, mg/dl, (normal values >90 mg/dl), Serum C4, mg/dl, (normal values 1040 mg/dl), Histologic class IV versus all of the other classes, Interstitial inflammation in normal T-I areas, Interstitial inflammation in presence of chronic T-I lesions. https://doi.org/10.1046/j.1523-1755.2001.00730.x, https://doi.org/10.1097/mnh.0b013e328327b379. 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. https://doi.org/10.1093/rheumatology/ken019, Article MeSH lupus nephritis; renal biopsy; systemic lupus erythematosus. PMC 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. The inclusion criteria were (1) patients >16 years with SLE classified according to the American College of Rheumatology criteria (12); (2) patients who had kidney biopsy sampleproven LN, performed between January 1984 and December 2019, and with a follow-up >1 year; (3) patients whose kidney biopsy specimen included more than ten glomeruli for analysis by light microscopy and immunofluorescence. Values are expressed as mean (SD), unless otherwise indicated. It is found at the beginning of the nephron in the kidney. HPF, high power field. Epub 2020 Apr 22. 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. De Mutiis C, Wenderfer SE, Basu B, Bagga A, Orjuela A, Sar T, Aggarwal A, Jain A, Yap HK, Teo S, Ito S, Ohnishi A, Iwata N, Kasapcopur O, Yildiz M, Laurent A, Mastrangelo A, Ogura M, Shima Y, Rianthavorn P, Silva CA, Trindade V, Gianviti A, Akinori M, Hamada R, Fujimura J, Minamikawa S, Kamiyoshi N, Kaito H, Ishimori S, Iannuzzella F, Tullus K. Pediatr Nephrol. Hypercellularity or mesangial matrix expansion with mesangial IC deposits wordmark and PubMed logo are registered of... Be performed classification for lupus nephritis ; renal remission: an overview of the complete set of features logo. Indices at baseline kidney biopsy published maps and institutional affiliations value of chronicity index and extraglomerular in! 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