Referring to the International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2018 pathological classification, we aim to reveal the significance of cellular/fibrocellular crescents in lupus nephritis (LN) patients. Patients with LN proven by renal biopsy at the First Affiliated Hospital of Wenzhou Medical University from December 2001 to November 2017 were identified, and eligible cases were divided into two groups according to the presence or absence of cellular/fibrocellular crescents in renal biopsy tissues. A total of 401 LN patients were identified from our follow-up database, and 296 eligible LN patients were enrolled in the study. Of these patients, 146 patients in the group without cellular/fibrocellular crescents (non-crescent group) and 150 patients in the group with cellular/fibrocellular crescents (Crescent group). The median follow-up time of patients was 47 months, and a total of 54 patients progressed to the composite endpoint. Crescent group had higher serum creatinine, lower serum albumin, higher systemic lupus erythematosus (SLE) disease activity index, and higher activity index of renal tissue. The interaction between cellular/fibrocellular crescents and proteinuria at baseline was associated with the prognostic risk of LN (P = 0.006). In the group with proteinuria < 3.5 g/24 h, the prognosis of crescent group was significantly worse than of non-crescent group (P < 0.001), while in the group with proteinuria ≥ 3.5 g/24 h, there was no significant relationship between crescents and prognosis (p = 0.452). By multivariable Cox hazard analysis, positive anti-dsDNA, chronic index of renal biopsy tissue, cellular/fibrocellular crescents and its interaction with 24 h proteinuria were independent risk factors for poor prognosis of LN. LN patients with cellular/fibrocellular crescents had more severe and active disease features, and cellular/fibrocellular crescents is a risk factor for poor prognosis of LN. There was an interaction between cellular/fibrocellular crescents and proteinuria in predicting poor prognosis, and among patients with low levels of proteinuria at the time of renal biopsy, those with crescents had a worse long-term prognosis than those without crescents.

Background: Both primary IgA nephropathy (IgAN) with and without nephrotic syndrome (NS) can present massive proteinuria (24-h urinary protein >= 3.5 g/d). The clinical significance of massive proteinuria may be different in the two entities and needs further research.Methods: Data of 1870 patients with biopsy-proven IgAN in our hospital from January 2011 to December 2022 was retrospectively reviewed. A total of 242 IgAN patients with massive proteinuria were enrolled. Patients who presented with nephrotic syndrome at renal biopsy were included in the IgAN with NS cohort (IgAN-NS). The IgAN with nephrotic-range proteinuria cohort (IgAN-NR) consisted of 1:1 matched cases from the remaining according to age, gender, estimated glomerular filtration rate (eGFR) at baseline, and follow-up time. The clinical and pathological characteristics between the two cohorts were analyzed.Results: The IgAN-NS had a significantly higher proteinuria level than the IgAN-NR (p < .001). Cluster analysis revealed that proteinuria was associated with lipids in IgAN-NS, while it was associated with inflammatory indicators in IgAN-NR. When the complete remission of proteinuria (CR) was not achieved, the Kaplan-Meier analysis showed the prognosis of IgAN-NS was significantly worse than that of IgAN-NR (p = .04). Then, our GLMM model and line chart showed that the serum albumin level of the IgAN-NR was always evidently higher than that of the IgAN-NS while the significant difference in urinary albumin/creatinine ratio between the two cohorts gradually disappeared during the short-term follow-up (1 year). Moreover, the Cox regression analysis showed that the increased serum albumin was an independent protective factor for the poor outcomes (eGFR decreased from the baseline >= 30% continuously or reached end-stage renal disease [ESRD]).Conclusion: The IgAN-NS had poorer clinicopathologic manifestation than IgAN-NR, including severer massive proteinuria. When the CR was not achieved, the prognosis of IgAN-NS was inferior to that of the IgAN-NR.

Introduction:Primary IgA nephropathy (IgAN) with light chain λ restriction in the mesangial deposits (IgAN-λ) has unique immunofluorescence (IF) features. Nevertheless, its clinicopathology and prognosis are still ambiguous. Methods:From January 2002 to December 2020, the clinical and pathologic data of 3872 patients who were diagnosed with having primary IgAN by renal biopsy in our hospital were reviewed. A total of 187 patients who met the selection criteria for IgAN-λ were enrolled to conduct a retrospective single-center study. The selection criteria were that IF features conform to light chain λ restriction in the mesangial deposits. According to age, sex, renal function (estimated glomerular filtration rate [eGFR]), and follow-up time, the control group was constructed with 1:3 matched cases of IgAN. The clinicopathologic and prognostic differences between the 2 groups were analyzed. Results:Compared with that in the IgAN group, the serum fibrinogen level in the IgAN-λ group was significantly higher (P < 0.001). Furthermore, cluster analysis indicated the different clusters involved in fibrinogen between the IgAN-λ and IgAN groups and that fibrinogen is associated with factors reflecting renal function in IgAN-λ but proteinuria levels in IgAN. The light chain λ deposit in the mesangium is associated with the formation of crescents in those with IgAN-λ, but complement C3 deposition in those with IgAN. Our Kaplan-Meier analysis revealed that the prognosis of the IgAN-λ group was significantly worse than that of the IgAN group within >6 years of follow-up (P = 0.02). The multi-Cox analysis revealed that the light chain λ restriction in the mesangial deposits was an independent risk factor for poor outcomes (eGFR decreased from the baseline ≥ 30% continuously or reached end-stage renal disease [ESRD] or died). Conclusion:The prognosis of those with IgAN-λ was worse than that of those with IgAN, which may be attributed to the light chain λ restriction in the mesangial deposits inducing a significant systemic inflammation manifested as severe clinical features and frequent crescent.

OBJECTIVE:Enhancer RNAs (eRNAs), a class of non-coding RNAs, play indispensable roles in regulating target gene transcription and maintaining cell identity in cooperation with promoters. In this study, we investigated the transcriptional landscape and potential functions of eRNAs in peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE).METHODS:PBMCs from five patients with stable SLE, five patients with active SLE, and ten healthy individuals (HCs) were subjected to RNA-sequencing. Putative regulators, differential expression, and pathways were analyzed. eRNAs that were significantly upregulated were first validated by RT-qPCR in 12 samples. Then, candidate eRNAs were confirmed in a validation cohort of 45 samples. We conducted comprehensive pathway analyses to explore the correlations between the candidate eRNAs and SLE pathology.RESULTS:By analyzing eRNA transcript data from PBMCs from SLE patients and HCs, we identified various eRNAs and functional super-enhancers potentially related with SLE. The SLE-specificity of eRNAs seemed to be largely driven by SLE-specific transcription factors (TFs). A Venn diagram of eRNAs differentially expressed in stable, active, and total SLE vs HCs revealed that 13 and 23 eRNAs were commonly upregulated and downregulated, respectively, in patients with stable SLE and those with active SLE. The commonly upregulated eRNAs participate in regulating SLE-related pathways. Only eRNA TCONS_00034326 was significantly (P < 0.05) upregulated in PBMCs of patients with SLE when compared with those of HCs as indicated by RT-qPCR. The area under the receiver-operating curve of TCONS_00034326 for distinguishing SLE patients from HCs was 0.691. Through its putative SLE-related master TF, TCONS_00034326 is involved in multiple SLE-relevant signaling pathways, especially tumor necrosis factor signaling.CONCLUSION:This study unraveled the transcriptional landscape of eRNAs, eRNA-related TFs, and super-enhancers in PBMCs from SLE patients and HCs. We identified a panel of SLE-relevant eRNAs, providing potential targets in SLE pathogenesis.

The clinical significance of intrarenal vascular lesions has not been elucidated in primary IgA nephropathy (IgAN), especially in non-hypertensive subjects. From January 2003 to December 2020, data of 3435 patients with biopsy-proven IgAN were reviewed. Two hundred-forty non-hypertensive patients who met the criteria for IgAN and had intrarenal vascular lesions (IgAN-vas) were selected. The control cohort was constructed with 1:1 matched cases of non-hypertensive IgAN patients without vascular lesions according to age, gender, estimated glomerular filtration rate (eGFR) and follow-up time. The IgAN-vas cohort had significantly higher serum uric acid levels than the control IgAN cohort (P < 0.05); glomerulosclerosis was more common in IgAN-vas patients. Moreover, cluster analysis indicated that the serum uric acid level was associated with serum creatinine (s-Cr) levels in IgAN-vas while it was associated with serum lactate dehydrogenase (LDH) levels in control cases with IgAN. Both Kaplan–Meier analysis and generalized linear mixed-effects models revealed that the prognosis of the IgAN-vas cohort was significantly worse than that of the IgAN cohort after > 5 years of follow-up. Intimal thickening was an independent risk factor associated with reaching the endpoint (eGFR decrease ≥ 30% from the baseline or reaching end-stage renal disease [ESRD] or death). The prognosis of non-hypertensive patients with IgAN-vas was worse than that of matched individuals with IgAN. The clinicopathologic manifestation of IgAN-vas was more severe, and included a higher proportion of glomerulosclerosis, and a higher serum uric acid level correlated with renal function impairment.