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The ISN/RPS 2016 classification predicts renal prognosis in patients with first-onset class III/IV lupus nephritis.

ABSTRACT: Lupus nephritis (LN) is a life-threatening complication of systemic lupus erythematosus. The 2003 pathological classification of LN was revised in 2016; it quantitatively evaluates the interstitium in addition to the glomeruli. We performed a retrospective multi-centre cohort study and investigated the utility of the 2016 classification-including the activity index (AI), chronicity index (CI), and each pathological component to predict complete remission or renal function decline, defined as 1.5-fold increase in serum creatinine levels-and compare with that of the 2003 classification. Ninety-one consecutive adult patients with first-onset class III/IV LN who were newly prescribed any immunosuppressants were enrolled and followed up for a median of 51 months from January 2004. Cox regression analysis demonstrated the subclasses based on the 2003 classification, which mainly evaluate glomerular lesions, were not associated with clinical outcomes. After adjustments for estimated glomerular filtration rate and urinary protein levels, higher CI and higher interstitial fibrosis and lower hyaline deposit scores were associated with renal functional decline. Similarly, higher CI and interstitial inflammation scores were associated with failure to achieve complete remission. Therefore, the 2016 classification can predict the clinical outcomes more precisely than the 2003 classification.

SUBMITTER: Hachiya A

PROVIDER: S-EPMC7810677 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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The ISN/RPS 2016 classification predicts renal prognosis in patients with first-onset class III/IV lupus nephritis.

Hachiya Asaka A Karasawa Munetoshi M Imaizumi Takahiro T Kato Noritoshi N Katsuno Takayuki T Ishimoto Takuji T Kosugi Tomoki T Tsuboi Naotake N Maruyama Shoichi S

Scientific reports 20210115 1

Lupus nephritis (LN) is a life-threatening complication of systemic lupus erythematosus. The 2003 pathological classification of LN was revised in 2016; it quantitatively evaluates the interstitium in addition to the glomeruli. We performed a retrospective multi-centre cohort study and investigated the utility of the 2016 classification-including the activity index (AI), chronicity index (CI), and each pathological component to predict complete remission or renal function decline, defined as 1.5 ...[more]

PMID: 33452282

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Project description:To treat lupus nephritis effectively, proper identification of the histologic class is essential. Although the classification system for lupus nephritis is nearly 40 years old, remarkably few studies have investigated interobserver agreement. Interobserver agreement among nephropathologists was studied, particularly with respect to the recognition of class III/IV lupus nephritis lesions, and possible causes of disagreement were determined.A link to a survey containing pictures of 30 glomeruli was provided to all 360 members of the Renal Pathology Society; 34 responses were received from 12 countries (a response rate of 9.4%). The nephropathologist was asked whether glomerular lesions were present that would categorize the biopsy as class III/IV. If so, additional parameters were scored. To determine the interobserver agreement among the participants, ? or intraclass correlation values were calculated. The intraclass correlation or ?-value was also calculated for two separate levels of experience (specifically, nephropathologists who were new to the field or moderately experienced [less experienced] and nephropathologists who were highly experienced).Intraclass correlation for the presence of a class III/IV lesion was 0.39 (poor). The ?/intraclass correlation values for the additional parameters were as follows: active, chronic, or both: 0.36; segmental versus global: 0.39; endocapillary proliferation: 0.46; influx of inflammatory cells: 0.32; swelling of endothelial cells: 0.46; extracapillary proliferation: 0.57; type of crescent: 0.46; and wire loops: 0.35. The highly experienced nephropathologists had significantly less interobserver variability compared with the less experienced nephropathologists (P=0.004).There is generally poor agreement in terms of recognizing class III/IV lesions. Because experience clearly increases interobserver agreement, this agreement may be improved by training nephropathologists. These results also underscore the importance of a central review by experienced nephropathologists in clinical trials.

Project description:Renal involvement in Systemic Lupus Erythematous (SLE) patients is one of the leading causes of morbidity and a significant contributor to mortality. It's estimated that nearly 50% of SLE individuals develop kidney disease in the first year of the diagnosis. Class IV lupus nephritis (LN-IV) is the class of lupus nephritis most common in Colombian patients with SLE. Altered miRNAs expression levels have been reported in human autoimmune diseases including lupus. Variations in the expression pattern of peripheral blood circulating miRNAs specific for this class of lupus nephritis could be correlated with the pathophysiological status of this group of individuals. The aim of this study was to evaluate the relative abundance of circulating microRNAs in peripheral blood from Colombian patients with LN-IV. Circulating miRNAs in plasma of patients with diagnosis of LN-IV were compared with individuals without renal involvement (LNN group) and healthy individuals (CTL group). Total RNA was extracted from 10 ml of venous blood and subsequently sequenced using Illumina. The sequences were processed and these were analyzed using miRBase and Ensembl databases. Differential gene expression analysis was carried out with edgeR and functional analysis were done with DIANA-miRPath. Analysis was carried out using as variables of selection fold change (?2 o ?-2) and false discovery rate (0.05). We identified 24 circulating microRNAs with differential abundance between LN-IV and CTL groups, fourteen of these microRNAs are described for the first time to lupus nephritis (hsa-miR-589-3p, hsa-miR-1260b, hsa-miR-4511, hsa-miR-485-5p, hsa-miR-584-5p, hsa-miR-543, hsa-miR-153-3p, hsa-miR-6087, hsa-miR-3942-5p, hsa-miR-7977, hsa-miR-323b-3p, hsa-miR-4732-3p and hsa-miR-6741-3p). These changes in the abundance of miRNAs could be interpreted as alterations in the miRNAs-mRNA regulatory network in the pathogenesis of LN, preceding the clinical onset of the disease. The findings thus contribute to understanding the disease process and are likely to pave the way towards identifying disease biomarkers for early diagnosis of LN.

Project description:BackgroundArguments still exist on prognosis of late-onset SLE, especially their kidney function. The purpose of this study was to investigate long-term kidney outcomes in patients with late-onset lupus nephritis (LN).MethodsA retrospective long-term cohort study was conducted in adult Chinese patients with LN. The patients were divided into late- (>50 years) and early-onset (<50 years) LN groups. The baseline characteristics, especially the kidney pathological characteristics, were compared. The cohort was followed-up for kidney outcome defined as doubling of serum creatinine or ESRD. Cox regression analysis was used to examine the association between late onset LN and its outcomes.ResultsA total of 1,264 patients were recruited, who were assigned to late-onset LN with 102 patients and early-onset LN with 1,162 patients. The late-onset LN group showed a worse baseline kidney function and more chronic pathological lesions than the early-onset LN group. During a follow-up time of 55 (3, 207) months, 114 (13.1%) deaths occurred, 107 (12.2%) had doubling of creatinine, and 80 (9.1%) developed end-stage kidney disease. The 5- and 10-year survival rates of the late-onset LN group were 67.6 and 50.5%, respectively, which were much worse than those of the early-onset LN group (89.8 and 84.6%, respectively). However, no significant difference was found on kidney survival (log-rank chi-square = 3.55, p = 0.06). Cox regression analysis showed that late-onset LN was an independent risk factor for patient survival (hazard ratio = 3.03, 95% CI (1.39, 6.58), p = 0.005). Increased baseline serum creatinine was an independent risk factor for kidney survival of patients with late-onset LN.ConclusionsPatients with late-onset LN had milder active lesions but severer chronic lesions in kidney pathology. They have poorer overall outcome but relatively favorable kidney outcome.Trial registrationClinicalTrials.gov Identifier: NCT03001973, 22 December 2016 retrospectively registered.

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The ISN/RPS 2016 classification predicts renal prognosis in patients with first-onset class III/IV lupus nephritis.

Publications

The ISN/RPS 2016 classification predicts renal prognosis in patients with first-onset class III/IV lupus nephritis.

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