The extent of tubulointerstitial inflammation is an independent predictor of renal survival in lupus nephritis

Gomes, Manuel Ferreira; Mardones, Claudia; Xipell, Marc; Blasco, Miquel; Solé, Manel; Espinosa, Gerard; García‐Herrera, Adriana; Cervera, Ricard; Quintana, Luís F.

doi:10.1007/s40620-021-01007-z

Cited by 26 publications

(24 citation statements)

References 29 publications

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“…In our study, tubulointerstitial lesions (TII and/or IFTA) in LN were present in 215 (75.4%) biopsies, which is within the range previously reported in other studies (39%–100%). 8,9,12,13,23–26 The 100% prevalence of TII (72.1% severe and 27.9% mild TII) was reported by Hsieh et al who measured TII by CD45 staining, a more sensitive method, but not readily available in clinical practice. 8…”

Section: Discussionmentioning

confidence: 99%

Predicting kidney outcomes among Latin American patients with lupus nephritis: The prognostic value of interstitial fibrosis and tubular atrophy and tubulointerstitial inflammation

Rodelo

Aguirre

Ortegón

et al. 2023

Lupus

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Objective To assess the effect of tubulointerstitial inflammation (TII) and interstitial fibrosis and tubular atrophy (IFTA) on kidney survival in lupus nephritis (LN). Methods Two hundred eighty five patients with biopsy-proven LN were retrospectively studied. Kidney survival was defined as the time from initial biopsy to end-stage kidney disease (ESKD), dialysis, or transplant. Kidney survival analysis was performed by the Kaplan–Meier method and the statistical difference between survival curves compared by the log-rank test. Cumulative incidence functions with competing risk of death for kidney survival were also graphed. Multivariable Cox proportional hazards regression and competing-risk analyses were performed to identify independent predictors of ESKD. Results Fifty-seven patients (20%) progressed to ESKD during a median time of 4.2 (2.0–55.2) months after biopsy. TII was present in 206 (72.3%) biopsies, while IFTA in 99 (34.7%) biopsies. Patients with moderate-to-severe IFTA had worse kidney survival than those with none or mild IFTA in both the Kaplan–Meier ( p = 0.018) and the competing-risk analyses ( p = 0.017). Patients with class IV ± V LN had worse kidney survival than those with non-class IV LN by the Kaplan–Meier method ( p = 0.050), but not in the competing-risk analysis ( p = 0.154). Worse kidney survival was also found among those with fibrous crescents than those without, in both the Kaplan–Meier ( p = 0.010) and the competing-risk ( p = 0.011) analyses. By multivariable Cox regression analysis, older age (HR 1.04, 95% CI 1.01–1.07) and class IV ± V LN (HR 5.06, 95% CI 1.82–14.09) were associated with higher risk of ESKD after adjusting for sex, ethnicity, TII, and IFTA. By competing-risk analyses, class IV ± V LN (SHR 3.32, 95% CI 1.25–8.83) and no response to immunosuppressive therapy (SHR 4.55, 95% CI 1.54–13.41) were associated with a higher risk of ESKD, while eGFR >90 mL/min/1.73 m2 (SHR 0.98 for each ml/min/1.73 m 2 , 95% 0.97–0.99) with a lower risk. Conclusions Patients with moderate-to-severe IFTA had worse kidney survival than those with none or mild IFTA. Worse kidney survival was also found among those with class IV LN and fibrous crescents versus those without IV LN and fibrous crescents, respectively.

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Section: Discussionmentioning

confidence: 99%

Predicting kidney outcomes among Latin American patients with lupus nephritis: The prognostic value of interstitial fibrosis and tubular atrophy and tubulointerstitial inflammation

Rodelo

Aguirre

Ortegón

et al. 2023

Lupus

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“…Recent evidence showed that tubulointerstitial injury can serve as an independent risk factor for LN prognostics. 35,36 Tubular cells also play an important role in renal microenvironmental regulation of LN, 37 which is necessary for maintaining the renal function. As the main executor of reabsorption and re-secretion, the applications of tubular cell-derived exosomes in acute kidney injury and diabetic nephropathy have been reported in few studies.…”

Section: Discussionmentioning

confidence: 99%

Identification and analysis of the predictive urinary exosomal miR-195-5p in lupus nephritis based on renal miRNA-mRNA co-expression network

Chen

Guo

Yang

et al. 2022

Lupus

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Objective Lupus nephritis (LN) is the main complication of systemic lupus erythematosus (SLE), causing huge financial burden and poor quality of life. Due to the low compliance of renal biopsy, we aim to find a non-invasive biomarker of LN to optimize its predictive, preventive, and personalized medical service or management. Method Herein, we provided a bioinformatic screen combined clinical validation strategy for rapidly mining exosomal miRNAs for LN diagnosis and management. We screened out differentially expressed miRNAs (DEMs) and differentially expressed mRNAs (DEGs) in LN database and performed a miRNA-mRNA integrated analysis to select out reliable changed miRNAs in LN tissues by using R and Cytoscape. Urinary exosomes were collected by ultracentrifugation and analyzed by nano-tracking analysis and western blotting. Detection of aquaporin-2 showed the tubular source of urinary exosomes. Urinary exosomal miRNAs were detected by RT-qPCR and the target of miR-195-5p was verified by using bioinformatic, dual-luciferase, and western blotting. Result 15 miRNAs and their 60 target mRNAs were contained in miRNA-mRNA integrated map. Bioinformatic analysis showed these miRNAs were involved in various cellular biological process. Exosomal miR-195-5p, miR-25-3p, miR-429, and miR-218-5p were verified in a small clinical group (n = 47). Urinary exosomal miR-195-5p, miR-25-3p, and miR-429 were downregulated in patients and miR-195-5p could recognize LN patients from SLE with good sensitivity and specificity, showing good potential in LN disease monitoring and diagnosis. Conclusion We analyzed and obtained a series of differential miRNAs in LN kidney tissues and suggested that urinary exosomal miR-195-5p could serve as a novel biomarker in LN. Further, miR-195-5p-CXCL10 axis could be a therapeutic target of LN.

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“…Furthermore, the Oxford paper included a limited sample size of participants and excluded severe cases. Some previous little sample size studies found that the presence of interstitial inflammation still to be a high-risk factor for kidney disease progression in IgAN [11, 12, 14, 15, 33] and lupus nephritis [34]. In the present two-center study with a larger sample size and a longer follow-up period, despite the correlation relationship between interstitial inflammation in the total cortex and T lesion, the variance inflation factor value of 1.71 did not suggest a collinearity between them.…”

Section: Discussionmentioning

confidence: 99%

Renal Interstitial Inflammation Predicts Nephropathy Progression in IgA Nephropathy: A Two-Center Cohort Study

et al. 2022

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Introduction: Renal interstitial inflammation often presents in immunoglobulin A nephropathy (IgAN), but its predictive role in kidney disease progression remains controversial. Methods: This retrospective two-center cohort study included 1,420 adult IgAN patients between January 2003 and May 2018 followed for a median of approximately 7 years at two Chinese hospitals. The predictor was renal interstitial inflammation within the total cortical interstitium (none/mild [0–25%], moderate [26–50%], or severe [>50%]). For the further propensity score matching analyses, the participants with moderate and severe level of interstitial inflammation were pooled to match those with none/mild level of interstitial inflammation. The outcomes included the rate of kidney function decline, and the composite kidney endpoint event defined as a >40% reduction in the estimated glomerular filtration rate, end-stage kidney disease. Linear regression and Cox proportional hazards regression analyses were used to examine the association between interstitial inflammation and the outcomes. The predictive performance of the model also assessed using multivariate logistic regression analyses with the receiver operating characteristic curve analysis. Reclassification was assessed using the continuous net reclassification improvement and integrated discrimination improvement adapted for censoring for the assessment of the model with or without interstitial inflammation. Results: For the check of reproducibility, the kappa statistic was 0.71, and intraclass correlation coefficient was 0.77. After adjustment for relating covariates, a higher level of interstitial inflammation was associated with a faster rate of kidney function decline (eGFR slope [mL/min/1.73 m2] of 1.34 [95% CI: −2.56 to 5.23], 3.50 [95% CI: −0.40 to 7.40], and 7.52 [95% CI: 3.02 to 12.01]) in the patients with none/mild, moderate, and severe interstitial inflammation, respectively, in the multivariable linear regression models and with an increased risk of kidney disease progression (HR for moderate vs. none/mild, 1.85; 95% CI: 1.10–3.13; HR for severe vs. none/mild, 2.95; 95% CI: 1.52–5.73) in the multivariable Cox proportional hazards models. Analyses in the propensity score-matched cohort, subgroups, and the sensitive analyses yielded consistent results. The receiver operating curves indicated a higher area under the curve of 0.83 in the model with interstitial inflammation compared with 0.81 in that without interstitial inflammation. In addition, incorporating interstitial inflammation into the International IgAN Risk Prediction Tool improved the diagnostic power of the algorithm to predict risk of progression. Conclusion: Interstitial inflammation is a reproducible pathologic parameter that may be adopted as a predictor for kidney disease progression in patients with IgAN.

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The extent of tubulointerstitial inflammation is an independent predictor of renal survival in lupus nephritis

Cited by 26 publications

References 29 publications

Predicting kidney outcomes among Latin American patients with lupus nephritis: The prognostic value of interstitial fibrosis and tubular atrophy and tubulointerstitial inflammation

Predicting kidney outcomes among Latin American patients with lupus nephritis: The prognostic value of interstitial fibrosis and tubular atrophy and tubulointerstitial inflammation

Identification and analysis of the predictive urinary exosomal miR-195-5p in lupus nephritis based on renal miRNA-mRNA co-expression network

Renal Interstitial Inflammation Predicts Nephropathy Progression in IgA Nephropathy: A Two-Center Cohort Study

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