Although heat shock protein 72 (HSP72) ameliorates renal tubulointerstitial fibrosis by inhibiting epithelial-to-mesenchymal transition (EMT), the underlying mechanism is unknown. Because Smad proteins transduce TGF-beta signaling from the cytosol to the nucleus and HSP72 assists in protein folding and facilitates nuclear translocation, we investigated whether HSP72 inhibits TGF-beta-induced EMT by modulating Smad expression, activation, and nuclear translocation. To evaluate the roles of distinct HSP72 structural domains in these processes, we constructed vectors that expressed wild-type HSP72 or mutants lacking either the peptide-binding domain (HSP72-DeltaPBD), which is responsible for substrate binding and refolding, or the nuclear localization signal (HSP72-DeltaNLS). Overexpression of wild-type HSP72 or HSP72-DeltaNLS inhibited TGF-beta1-induced EMT, but HSP72-DeltaPBD did not, suggesting a critical role for the PBD in this inhibition. HSP72 overexpression inhibited TGF-beta1-induced phosphorylation and nuclear translocation of Smad3 and p-Smad3, but not Smad2; these inhibitory effects required the PBD but not the NLS. Coimmunoprecipitation assays suggested a physical interaction between Smad3 and the PBD. siRNA knockdown of endogenous HSP72 enhanced both TGF-beta1-induced Smad3 phosphorylation and EMT and confirmed the interaction of HSP72 with both Smad3 and p-Smad3. In vivo, induction of HSP72 by geranylgeranylacetone suppressed Smad3 phosphorylation in renal tubular cells after unilateral ureteral obstruction. In conclusion, HSP72 inhibits EMT in renal epithelial cells primarily by exerting domain-specific effects on Smad3 activation and nuclear translocation.

Immunoglobulin G4 (IgG4)-related disease is a fibroinflammatory condition characterized by tumefactive lesions, dense lymphoplasmacytic infiltrates rich in IgG4-positive plasma cells. We report the case of a 67-year-old man with a history of transient jaundice and recurrent steatorrhea, initially diagnosed at 62 years. Abdominal magnetic resonance imaging raised suspicion of pancreatic cancer owing to a pancreatic head mass. The patient opted for conservative management, and jaundice resolved spontaneously. Diabetes was diagnosed concurrently. The patient was referred to our department for generalized edema of 3 months’ duration and an elevated serum IgG4 level at age 67. Kidney biopsy confirmed IgG4-related kidney disease and diabetic nephropathy. Gastrointestinal endoscopy revealed multiple polyps, with IgG4-positive plasma cell infiltration in gastric and colonic tissues. Follow-up computed tomography excluded pancreatic mass. After excluding systemic lupus erythematosus and plasma cell/lymphocytic proliferative disorders, the patient was treated with glucocorticoids and rituximab. Steatorrhea and edema improved, and serum IgG4 levels decreased. Urinary protein resolved, but hypoalbuminemia persisted. Technetium-99m--labeled human serum albumin scintigraphy indicated intestinal protein loss. This case illustrates a significant treatment response in IgG4-related disease involving the kidney, pancreas, and gastrointestinal tract, complicated by protein-losing enteropathy. Routine IgG4 testing should be considered in patients with unexplained kidney disease or tumefactive lesions.

RNA therapies hold tremendous promise for treating genetic eye diseases. However, their development is limited by the lack of non-viral delivery platforms that can target specific ocular cell types. Here, we describe a charge-altering releasable transporter (CART) that delivers RNA selectively to the corneal endothelium, a non-regenerative cell layer whose dysfunction underlies several blinding conditions. We characterize the safety of CART-RNA nanoparticles in mice and show that they facilitate delivery of diverse RNA cargoes to the corneal endothelium, including circular RNA and CRISPR/Cas9. We verify that these nanoparticles can be redosed and apply them to achieve corneal gene editing. We further demonstrate CART transfection of corneal endothelial cells from a human donor in vitro and in a non-human primate in vivo, supporting the feasibility of clinical translation. Our findings establish CARTs as a platform for non-viral gene delivery to the eye, with the potential to treat corneal dystrophies and other vision disorders.

Introduction:Tubular epithelial cells (TECs) under adaptive state (aTECs) have been frequently reported in the injured kidney closely associated with disease progression. However, whether aTECs is present in the urine of patients with diabetic kidney disease (DKD) and its clinical implication have not been assessed. Methods:Urine samples from patients with early and advanced DKD were collected and subjected to single-cell RNA sequencing (scRNA-seq). Kidney single nucleus RNA-seq, spatial scRNA-seq, and bulk RNA-seq datasets were employed to reconstruct their local environment and to delineate differences between shed cells and local residence. Results:Most urinary TEC in patients with DKD are under adaptive states. Whereas the composition of urinary TEC is consistent in early and advanced DKD, a higher ratio of aTECs under progenitor and fibrosis state is defined in early DKD. Trajectory inference reveals that some aTECs are early derivatives of injured proximal tubule (PT). Spatial mapping reveals that proliferative and fibrosis aTECs reside close to the glomerulus region. Systemic evaluation of different states of urinary aTECs in patients of diverse-cause kidney injury suggests that the ratio of progenitor or proliferative aTECs to fibrosis aTECs is of diagnostic value. Conclusion:Urine is an underestimated source of aTECs providing us noninvasive manner to interrogate the injured state of tubule. The ratio of fibrosis aTECs and progenitor or proliferative aTECs in urine features tubular injury state and may help improve DKD diagnosis.

BACKGROUND:IgA nephropathy (IgAN), a major cause of primary glomerulonephritis, is closely associated with malignant hypertension (MHT). This study aimed to explore the clinicopathological characteristics and renal prognosis of patients with IgAN combined with malignant hypertension kidney injury (IgAN-MHT) and investigate the associations of clinicopathological indicators with prognosis. METHODS:In this single-center retrospective cohort study, patients diagnosed with IgAN-MHT through kidney biopsy between January 1, 2008, and June 30, 2023, in our hospital were enrolled. Cox regression models were used to assess the associations between clinical indicators and renal prognosis in IgAN-MHT patients. RESULTS:A total of 70 patients were included in the analysis of renal function improvement. During a median follow-up time of 9.4 months, 26 patients (37.1%) achieved renal function improvement. Patients in the improved renal function group had higher hemoglobin levels (p = 0.003), lower serum creatinine levels (p = 0.006), a higher proportion of patients using sulodexide (p = 0.018), and a lower proportion of glomerulosclerosis (p < 0.001). Multivariable Cox regression analysis indicated that a higher proportion of glomerulosclerosis was independently associated with a lower likelihood of renal function improvement (HR = 0.97, 95% CI = 0.96-0.99, p = 0.003), while sulodexide administration was independently associated with a higher likelihood of improvement (HR = 2.75, 95% CI = 1.18-6.41, p = 0.019). CONCLUSION:This study revealed that in IgAN-MHT patients, a higher proportion of glomerulosclerosis was independently associated with poorer renal outcomes, while the use of sulodexide showed a significant independent association with improved renal function.

Background Cardiovascular‐kidney‐metabolic (CKM) syndrome is an emerging clinical entity emphasizing the need for a holistic approach to patient care. The relationship between CKM syndrome and cognitive decline or dementia remains undetermined. Methods A total of 10 426 participants in the ARIC (Atherosclerosis Risk in Communities) study, classified into 4 CKM risk categories at baseline (visit 2: 1990–1992): low risk (≤5%), borderline risk (5%–7.4%), intermediate risk (7.5%–19.9%), and high risk (≥20%), were used to investigate the associations between CKM risk and cognitive decline or dementia using regression analysis. Results Elevated CKM risk level is significantly associated with increased risks of cognitive decline and dementia incidence. Each 1‐unit increase in CKM risk level is linked to a 6% higher risk of dementia progression in the fully adjusted model. Conclusions These findings highlight a strong association between CKM syndrome and cognitive decline or incident dementia, underscoring the importance of early interventions.

RNA medicine is an emerging groundbreaking technology for the prevention and treatment of disease. However, tools to deliver messenger RNA (mRNA) and other polyanions (circRNA, saRNA, pDNA, CRISPR-Cas, reprogramming factors) are required to advance current RNA therapies and address next generation challenges. Existing delivery systems often suffer from laborious syntheses, limited organ selectivity, formulation complexity, and undesired inflammatory responses. Here, we report novel mRNA delivery systems termed Discrete Immolative Guanidinium Transporters (DIGITs), which are synthesized convergently in as few as 4 steps. Unlike most cationic (ammonium) delivery systems, DIGITs are based on cationic guanidinium moieties, which complex mRNA at acidic pH and undergo irreversible neutralization at physiological pH to enable efficient RNA release. Systematic evaluation of structural variations and formulations have led to DIGIT/mRNA complexes that selectively target lung, spleen, and immature red blood cells in peripheral blood in female mice model. DIGIT/mRNA delivery systems show minimal toxicity based on cell viability and biochemical assays, supporting their future utility in biomedical applications.

Background: Fibroblast growth factor 23 (FGF23) is a phosphate-regulating hormone that is secreted in large amounts early in chronic kidney disease. In this cohort, we aimed to investigate the association between serum FGF23 concentration and mortality in patients undergoing peritoneal dialysis (PD).Methods: Serum FGF23 level was determined by enzyme-linked immunosorbent assay (ELISA) in a large 15-year prospective cohort study of PD patients with stored serum samples at baseline. Kaplan-Meier survival curves and Cox proportional hazards models were performed to characterise the relationship of FGF23 with mortality.Results: A total of 737 incident PD patients were analysed. The baseline median FGF23 concentration was 683.2 (518.5-896.2) pg/mL. Age, serum phosphorus, high-density lipoprotein cholesterol and high-sensitivity C-reactive protein were independently correlated with serum FGF23 concentration. During a median follow-up of 66.7 (41.1-95.4) months, 171 of the 737 participants (23.2%) died, including 84 (49.1%) cardiovascular disease-related and 50 (29.2%) infection-related deaths. Multivariable Cox regression analysis showed that the adjusted hazard ratios of the highest tertile of serum FGF23 compared with those in the lowest tertile were 1.36 (95% confidence interval (CI): 0.89-2.07; p = 0.154), 0.75 (95% CI: 0.40-1.38; p = 0.353) and 2.66 (95% CI: 1.15-6.15; p = 0.022) for all-cause, cardiovascular disease-related and infection-related mortality, respectively.Conclusion: High serum FGF23 concentration is associated with a higher risk of infection-related death for incident PD patients.

Primary membranous nephropathy (PMN) is one of the prevalent pathological types of adult primary nephrotic syndrome. Pathogenic autoantibodies targeting podocyte antigens such as phospholipase A2 receptor (PLA2R) lead to the disease. Patients frequently experience notable adverse effects when treated with conventional immunosuppressive therapies. Rituximab (RTX), a mouse/human monoclonal antibody, selectively depletes B cells and leads to a decrease in the antibody levels in the circulation, which helps to alleviate membranous nephropathy. Various RTX dosage regimens have been applied globally in the PMN treatment with satisfactory effects. Nevertheless, the optimal dosage of RTX has yet to be determined. This article reviews the application of different doses of RTX in the management of PMN so far.

BACKGROUND:Vascular calcification (VC), especially coronary artery calcification (CAC), serves as a robust predictor of cardiovascular mortality in chronic kidney disease (CKD) patients. Recent studies have revealed that the presence of extra-coronary calcifications (ECCs) contributes to cardiovascular disease (CVD). Elevated myocardial injury markers predict mortality risk in CKD patients and are associated with CVD. Nevertheless, the relationship between VC, including CAC and ECCs, and myocardial injury markers remain unexplored in non-dialysis CKD patients. METHODS:In 278 non-dialysis CKD patients of stage G3 to G5, we assessed calcified scores in CAC (Agatston score) and ECCs including thoracic aortic calcification (TAC), abdominal aortic calcification (AAC), carotid artery calcification, and valvular calcification. We analyzed the relationships between VC and myocardial injury markers of cardiac troponin T (cTnT) and creatine kinase-MB (CK-MB). RESULTS:A total of 278 non-dialysis CKD patients (median age 52.4 ± 13.2; male 65.1%; diabetes 33.5%) were enrolled. A total of 71.8% (227) of patients had cTnT levels above the upper limit of normal (> 0.014 ng/mL). Moderate to severe (calcified score ≥100 vs. <100), CAC (OR 6.39; 95% CI 1.03-39.61) and TAC (OR 6.16; 95% CI 1.76-21.55) were significantly associated with higher cTnT concentrations after adjustment for confounders. Additionally, male sex and a lower eGFR were also associated with cTnT elevation. However, when we included CAC and TAC in one model, only moderate to severe TAC (OR 4.85; 95% CI 1.38-16.96) was a risk factor for cTnT elevation, but not CAC. Furthermore, patients with severer TAC presented lower diastolic blood pressure (DBP), wider pulse pressure (p < 0.001) and higher prevalence of left ventricular hypertrophy (LVH). CONCLUSION:Moderate to severe thoracic aortic calcification (TAC score ≥ 100) is significantly associated with elevated cTnT concentrations in non-dialysis CKD patients of stage G3 to G5. The linkage may result from decreased coronary perfusion and relative myocardial ischemia.

Objectives To investigate PET/CT registration and quantification accuracy of thoracic lesions of a single 30-second deep-inspiration breath-hold (DIBH) technique with a total-body PET (TB-PET) scanner, and compared with free-breathing (FB) PET/CT. Methods 137 of the 145 prospectively enrolled patients finished a routine FB-300 s PET/CT exam and a 30-second DIBH TB-PET with chest to pelvis low dose CT. The total-body FB-300 s, FB-30 s, and DIBH-30 s PET images were reconstructed. Quantitative assessment (SUVmax and SUVmean of lung and other organs), PET/CT registration assessment and lesion analysis (SUVmax, SUVpeak, SUVmean and tumor-background ratio) were compared with Wilcoxon signed-rank tests. Results The SUVmax and SUVmean of the lung with DIBH-30 s were significantly lower than those with FB. The distances of the liver dome between PET and CT were significantly smaller with DIBH-30 s than with FB. 195 assessable lesions in 106 patients were included, and the detection sensitivity was 97.9 % and 99.0 % in FB-300 s, and DIBH-30 s, respectively. For both small co-identified lesions (n = 86) and larger co-identified lesions with a diameter ≥ 1 cm (n = 91), the lesion SUVs were significantly greater with DIBH-30 s than with FB-300 s. Regarding lesion location, the differences of the SUVs for the lesions in the lower thorax area (n = 97, p < 0.001) were significant between DIBH-30 s and FB-300 s, while these differences were not statistically significant in the upper thorax (n = 80, p > 0.05). The lesion tumor-to-surrounding-background ratio (TsBR) was significantly increased, both in the upper and lower thorax. Conclusion The TB DIBH PET/CT technique is feasible in clinical practice. It reduces the background lung uptake and achieves better registration and lesion quantification, especially in the lower thorax.

Journal Article Corrected proof Initial rituximab monotherapy for adult indiopathic nephrotic syndrome with minimal change lesion pattern Get access Ricong Xu, Ricong Xu Department of Nephrology, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Haofei Hu, Haofei Hu Department of Nephrology, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Hengchang Xu, Hengchang Xu Department of Nephrology, Longgang Orthopedics Hospital of Shenzhen, Shenzhen, Guangdong, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Zhijian Li, Zhijian Li Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Jianying Guo, Jianying Guo Department of Nephrology, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Tao Cao, Tao Cao Department of Nephrology, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Yi Yu, Yi Yu Department of Nephrology, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Xiaojie Chen, Xiaojie Chen Department of Nephrology, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Yi Xu, Yi Xu Department of Nephrology, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Qijun Wan Qijun Wan Department of Nephrology, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China Correspondence to: Qijun Wan; E-mail: yiyuan2224@sina.com https://orcid.org/0009-0008-0273-1364 Search for other works by this author on: Oxford Academic PubMed Google Scholar Nephrology Dialysis Transplantation, gfae012, https://doi.org/10.1093/ndt/gfae012 Published: 13 January 2024 Article history Received: 15 October 2023 Published: 13 January 2024 Corrected and typeset: 24 January 2024

Selective RNA delivery is required for the broad implementation of RNA clinical applications, including prophylactic and therapeutic vaccinations, immunotherapies for cancer, and genome editing. Current polyanion delivery relies heavily on cationic amines, while cationic guanidinium systems have received limited attention due in part to their strong polyanion association, which impedes intracellular polyanion release. Here, we disclose a general solution to this problem in which cationic guanidinium groups are used to form stable RNA complexes upon formulation but at physiological pH undergo a novel charge-neutralization process, resulting in RNA release. This new delivery system consists of guanidinylated serinol moieties incorporated into a charge-altering releasable transporter (GSer-CARTs). Significantly, systematic variations in structure and formulation resulted in GSer-CARTs that exhibit highly selective mRNA delivery to the lung (∼97%) and spleen (∼98%) without targeting ligands. Illustrative of their breadth and translational potential, GSer-CARTs deliver circRNA, providing the basis for a cancer vaccination strategy, which in a murine model resulted in antigen-specific immune responses and effective suppression of established tumors.

The delivery of oligonucleotides across biological barriers is a challenge of unsurpassed significance at the interface of materials science and medicine, with emerging clinical utility in prophylactic and therapeutic vaccinations, immunotherapies, genome editing, and cell rejuvenation. Here, we address the role of readily available branched lipids in the design, synthesis, and evaluation of isoprenoid charge-altering releasable transporters (CARTs), a pH-responsive oligomeric nanoparticle delivery system for RNA. Systematic variation of the lipid block reveals an emergent relationship between the lipid block and the neutralization kinetics of the polycationic block. Unexpectedly, iA21A11, a CART with the smallest lipid side chain, isoamyl-, was identified as the lead isoprenoid CART for the in vitro transfection of immortalized lymphoblastic cell lines. When administered intramuscularly in a murine model, iA21A11-mRNA complexes induce higher protein expression levels than our previous lead CART, ONA. Isoprenoid CARTs represent a new delivery platform for RNA vaccines and other polyanion-based therapeutics.

Aristolochic acid (AA)-induced acute kidney injury (AKI) presents with progressive decline in renal function and rapid progression to end-stage renal disease. Among the multiple mechanisms identified in AKI, ferroptosis has been shown to be involved in various forms of AKI. But few studies have elucidated the role of ferroptosis in AA-induced AKI. In this study, we investigated the role of ferroptosis in AA-induced acute renal tubular injury in vivo and in vitro. Mice with acute aristolochic acid nephropathy showed increased malondialdehyde levels, aggravated lipid peroxidation, decreased superoxide dismutase activity, and glutathione depletion. The expression of glutathione peroxidase 4 was decreased and the expression of acyl-CoA synthetase long-chain family member 4 was increased. Inhibition of ferroptosis by ferrostatin-1 significantly improved the renal function, reduced histopathological lesions, partially alleviated lipid peroxidation, and restored the antioxidant capacity. In vitro studies also revealed that AA significantly reduced cell viability, induced reactive oxygen species production, increased intracellular iron level and decreased ferroptosis-related protein expression. Inhibition of ferroptosis significantly increased cell viability and attenuated AA-induced renal tubular epithelial cell injury. It is suggested that ferroptosis plays an important role in AA-induced acute tubular injury. And inhibition of ferroptosis may exert renoprotective effects possibly by preventing lipid peroxidation, restoring the antioxidant activity or regulating iron metabolism.

In recent decades, researchers worldwide have directed their efforts toward enhancing the quality of PET imaging. The detection sensitivity and image resolution of conventional PET scanners with a short axial field of view have been constrained, leading to a suboptimal signal-to-noise ratio. The advent of long-axial-field-of-view PET scanners, exemplified by the uEXPLORER system, marked a significant advancement. Total-body PET imaging possesses an extensive scan range of 194 cm and an ultrahigh detection sensitivity, and it has emerged as a promising avenue for improving image quality while reducing the administered radioactivity dose and shortening acquisition times. In this review, we elucidate the application of the uEXPLORER system at the Sun Yat-sen University Cancer Center, including the disease distribution, patient selection workflow, scanning protocol, and several enhanced clinical applications, along with encountered challenges. We anticipate that this review will provide insights into routine clinical practice and ultimately improve patient care.

Objectives To compare the diagnostic and staging efficacy of PET/diagnostic-level CT (PET/DxCT) and PET/low-dose CT (PET/LDCT) in pretreatment pediatric lymphoma patients and to estimate the reduction of the CT effective dose in the PET/CT scan. Methods One hundred and five pediatric patients who underwent total-body PET/CT examination were enrolled and divided into the DxCT group ( n = 47) and LDCT group ( n = 58) according to their dose levels. The sensitivity, specificity, PPV, and NPV of PET/DxCT and PET/LDCT for detecting the involvement of lymph node, spleen, bone marrow, and other extranodal organs in pretreatment lymphoma were compared. ROC analysis was performed to evaluate the integral efficiency. The staging accuracies based on PET/DxCT and PET/LDCT were also evaluated. Dosimetry was calculated for DxCT and LDCT, and the reduction in the effective dose was estimated. Results In the diagnosis of nodal, splenic, bone marrow, and other extranodal involvement, the differences in sensitivity, specificity, PPV, and NPV between PET/LDCT and PET/DxCT were not significant (all p values ∈ [0.332, 1.000]). Both modalities had accuracies above 90% and the ROC analysis indicated good or high efficiency in diagnosing all patterns of lymphoma involvement. PET/LDCT and PET/DxCT each had a staging accuracy of 89.7% and 89.4%, respectively. LDCT had a comparable image quality score with DxCT, with a significant increase in noise ( p < 0.001) and a 66.1% reduction in effective dose. Conclusions PET/LDCT allowed for a 66.1% CT effective dose reduction compared to PET/DxCT in pediatric lymphoma patients without compromising the diagnostic and staging efficacy. Key Points • Pediatric lymphoma patients can benefit from a reduced effective dose of PET/CT. • This retrospective study showed that the diagnostic and staging efficacies of PET/low-dose CT are comparable to those of PET/diagnostic-level CT, both with satisfactory efficiency in diagnosing all patterns of lymphoma involvement. • PET/low-dose CT allowed for a 66.1% CT effective dose reduction compared to PET/diagnostic-level CT.

Introduction: The aim of this study was to evaluate the association of peripheral eosinophil (EOS) count with disease activity and kidney outcomes in lupus nephritis (LN) patients. Methods: A total of 453 hospitalized and biopsy-proven LN patients at our hospital from 2006 to 2013 were enrolled, of which 388 patients had repeated measurements of EOS. Relationships were explored between average EOS and disease activity at baseline, using the systemic lupus erythematosus disease activity (SLEDAI) and activity index (AI) on kidney biopsy. Follow-up data were available through December 2016. The primary outcome measure was a composite of doubling of serum creatinine and end-stage kidney disease after a median follow-up of 51 months. Results: The mean age of the enrolled 388 LN patients was 33.1 ± 10.8 years old, and 335 (86%) were female. The median average peripheral EOS count was 0.033 (0.015–0.057) ×109/L. Mean AI and SLEDAI score were 6.8 ± 2.5 and 14.9 ± 5.4, respectively. Logistic regression models showed that decreased average EOS was independently associated with higher AI (≥6) and higher SLEDAI (≥15) (odds ratio [OR] 0.93, 95% confidence interval [CI] 0.90–0.97; and OR 0.96, 95% CI: 0.93–0.99, respectively). There was a parabolic relationship between average EOS and the primary outcome, with hazard ratio (HR) > 1 for both levels ≤0.033 and >0.16 × 109/L. Conclusion: Lower EOS count was independently associated with severe disease activity and kidney progression in LN.