Association of podocyte ultrastructural changes with proteinuria and pathological classification in type 2 diabetic nephropathy.

AIMS: Podocyte injury plays an essential role in the progression of diabetic nephropathy (DN). The associations between the ultrastructural changes of podocyte with proteinuria and the pathological classification of DN proposed by Renal Pathology Society (RPS) have not been clarified in patients with type 2 diabetic nephropathy (T2DN). METHODS: We collected 110 patients with kidney biopsy-confirmed T2DN at Peking University First Hospital from 2017 to 2022. The morphometric analysis on the podocyte foot process width (FPW) and podocyte detachment (PD) as markers of podocyte injury was performed, and the correlations between the ultrastructural changes of podocytes with severity of proteinuria and the RPS pathological classification of DN were analyzed. RESULTS: Mean FPW was significantly broader in the group of T2DN patients with nephrotic proteinuria (565.1 nm) than those with microalbuminuria (437.4 nm) or overt proteinuria (494.6 nm). The cut-off value of FPW (> 506 nm) could differentiate nephrotic proteinuria from non-nephrotic proteinuria with a sensitivity of 75.3% and a specificity of 75.8%. Percentage of PD was significantly higher in group of nephrotic proteinuria (3.2%) than that in microalbuminuria (0%) or overt proteinuria (0.2%). FPW and PD significantly correlated with proteinuria in T2DN (r = 0.473, p < 0.001 and r = 0.656, P < 0.001). FPW and PD correlated with RPS pathological classification of T2DN (r = 0.179, P = 0.014 and r = 0.250, P = 0.001). FPW value was increased significantly with more severe DN classification (P for trend =0.007). The percentage of PD tended to increase with more severe DN classification (P for trend = 0.017). CONCLUSIONS: Podocyte injury, characterized by FPW broadening and PD, was associated with the severity of proteinuria and the pathological classification of DN.

COVID-19 increases extracorporeal coagulation during hemodialysis associated with upregulation of vWF/FBLN5 signaling in patients with severe/critical symptoms.

BACKGROUND: COVID-19 has been shown to increase the risk of extracorporeal coagulation during hemodialysis in patients, but the underlying mechanism remains unclear. This study aimed to investigate the effect and mechanism of COVID-19 on the risk of extracorporeal coagulation in patients with chronic kidney disease undergoing hemodialysis. METHODS: A retrospective analysis of the extracorporeal coagulation status of 339 hemodialysis patients at our center before and after COVID-19 infection was performed, including subgroup analyses. Post-infection blood composition was analyzed by protein spectrometry and ELISA. RESULTS: Compared to the pre-COVID-19 infection period, COVID-19-induced extracorporeal coagulation predominantly occurred in patients with severe/critical symptoms. Further proteomic analysis demonstrated that in patients with severe/critical symptoms, the coagulation cascade reaction, platelet activation, inflammation, and oxidative stress-related pathways were significantly amplified compared to those in patients with no/mild symptoms. Notably, the vWF/FBLN5 pathway, which is associated with inflammation, vascular injury, and coagulation, was significantly upregulated. CONCLUSIONS: Patients with severe/critical COVID-19 symptoms are at a higher risk of extracorporeal coagulation during hemodialysis, which is associated with the upregulation of the vWF/FBLN5 signaling pathway. These findings highlight the importance of early anticoagulant therapy initiation in COVID-19 patients with severe/critical symptoms, particularly those undergoing hemodialysis. Additionally, vWF/FBLN5 upregulation may be a novel mechanism for virus-associated thrombosis/coagulation.

Evolution of Peritoneal Dialysis-Associated Peritonitis: Pathogen, Antibiotic Resistance, and the Impact of Lymphocyte Count on Treatment Outcomes.

Purpose: Antibiotic administration leads to alterations in pathogenic organisms and antibiotic resistance, posing a significant risk to peritoneal dialysis patients' health. This study aimed to investigate changes in the cause-specific peritonitis, pathogen profiles, antibiotic resistance, and the prognostic factors among patients with peritoneal dialysis-associated peritonitis (PDAP) at our center. Patients and Methods: We included 463 PDAP patients who attended Peking University Shenzhen Hospital between 2002 and 2023. We analyzed the effects of empirical treatment regimens with cefazolin and ceftazidime or gentamicin. Results: From 2002 to 2023, we observed that gram-positive staphylococci emerged as the primary causative agents, while the proportion of gram-negative bacillary, enteric peritonitis, and catheter-associated peritonitis decreased significantly. However, the overall cure rate for PDAP and gram-negative bacillary peritonitis declined significantly from 2014 to 2023. Notably, we observed no increase in antibiotic resistance associated with antibiotic drugs use. In addition, reduced lymphocyte counts due to the prevalence of 2019 coronavirus disease (COVID-19) emerged as an independent risk factor for treatment failure in cases of gram-negative bacillary peritonitis. Conclusion: We did not observe elevated antibiotic resistance in our center when employing empirical dosing strategies involving cefazolin, ceftazidime, or gentamicin. Additionally, we found that a decrease in lymphocyte count due to the COVID-19 epidemic was a significant risk factor for treatment failure in cases of gram-negative bacillary peritonitis at our center. This study provides a foundation for developing clinical treatment strategies for PDAP.

Risk factors and prognosis for latent tuberculosis infection in dialysis patients: A retrospective cohort study at a single tertiary care center.

INTRODUCTION: Recent studies report that latent tuberculosis infection (LTBI) may lead to an increased risk of cardiovascular disease (CVD) that led us to hypothesize that LTBI may play an important role in major adverse cardiovascular events (MACE) in dialysis patients. METHODS: A single-center retrospective cohort study was conducted. A total of 270 patients undergoing hemodialysis or peritoneal dialysis more than 3 months were included. The interferon enzyme-linked immunospot (IFN-γ ELISPOT) assay was used for the diagnosis of LTBI. Primary endpoints were MACE, including all-cause death and acute coronary syndrome (ACS). The association between LTBI and MACE was examined using multivariate Cox proportional hazards regression after adjusting for covariates and Kaplan-Meier survival analysis. RESULTS: In our study, the patients were classified into LTBI (n = 47) or non-LTBI (n = 223) groups. Independent risk factors for LTBI in dialysis population were prior tuberculosis (TB) history (odds ratio [OR] 4.817 [1.064-22.306]), tobacco use (OR 2.903 [1.155-7.299]), and older age (OR 1.027 [1.002-1.053]). After a median follow-up of 39 months, the incidence of active TB was 6.4% versus 0% in dialysis patients with and without LTBI, respectively (p = 0.005). Multivariate Cox analysis showed that LTBI was significantly associated with MACE (hazard ratio [HR] 2.540 [1.490-4.350]) after adjustment for potential confounders. CONCLUSIONS: Prior TB history, tobacco use, and the elderly can be used to select cost-effective LTBI screening target groups in dialysis patients. LTBI is not only closely related to active TB but also an independent risk factor for higher incidence of MACE in dialysis population.

Phosphorylated vimentin at Ser72 is associated with epithelial-mesenchymal transition in lupus nephritis.

OBJECTIVES: To measure the expression of vimentin and its phosphorylated forms in lupus nephritis (LN) and explore their potential role in LN development. METHODS: Lupus renal biopsies from LN patients and normal renal biopsies from kidney transplant donors were collected. The expression of vimentin and its phosphorylated forms (p-vimentin (Ser39, Ser56, Ser72, Ser83, and Tyr117)) were measured by Western blots and immunohistochemistry. To construct stable cell line that overexpress vimentin and its phosphorylated forms, an immortalized proximal tubule epithelial cell line (HK-2 cells) was utilized. The roles of vimentin and its phosphorylated forms on the migration of HK-2 cells were examined by transwell migration assay and wound healing analysis. RESULTS: We first observed a significant upregulation of vimentin protein in TGFß1-induced HK-2 cells. This finding was further confirmed in renal tissues obtained from LN patients and animal model. Interestingly, among the five phosphorylated forms of vimentin, only vimentin phosphorylated at Ser72 was upregulated in LN. Through the establishment of stable vimentin and its phosphorylated forms overexpression in HK-2 cells, we found that the overexpression of vimentin and its phosphorylated forms at Ser72 significantly enhances the cell migration. CONCLUSIONS: Vimentin phosphorylated on Ser72 is important for renal epithelial cell migration, which would enhance the progression of vimentin-induced epithelial-mesenchymal transition during LN development.

Kidney Function Measures and Mortality: A Mendelian Randomization Study.

RATIONALE & OBJECTIVE: Individuals with a low estimated glomerular filtration rate (eGFR) are at a high risk of death. However, the causes underpinning this association are largely uncertain. This study aimed to assess the causal relationship of low eGFR with all-cause and cause-specific mortality. STUDY DESIGN: Retrospective cohort study incorporating Mendelian randomization (MR). SETTING & PARTICIPANTS: Individual-level data from 436,214 White participants (54.3% female; aged 56.8±8.0 years) included in the UK Biobank. EXPOSURES: eGFR estimated using cystatin C (eGFRcyst). OUTCOMES: The outcomes of interest included all-cause mortality, cardiovascular mortality, cancer mortality, infection mortality, and other-cause mortality. ANALYTICAL APPROACH: Cox proportional hazards analysis for the conventional observational analyses; linear and nonlinear MR analyses implemented using genetic allele scores as instrumental variables representing kidney function to estimate the effect of kidney function on the survival outcomes. RESULTS: During a median follow-up of 12.1 years, there were 30,489 deaths, 6,098 of which were attributed to cardiovascular events, 15,538 to cancer, 1,516 to infection, and 7,227 to other events. In the conventional observational analysis, eGFRcyst exhibited a nonlinear association with all the outcomes. MR analysis suggested that a genetically predicted lower eGFRcyst was linearly associated with a higher rate of cardiovascular mortality (HR, 1.43; 95% CI, 1.18-1.75) across the entire measurement range (every 10-mL/min/1.73m2 decrement). Nonetheless, no causal associations between eGFRcyst and all-cause mortality (HR, 1.07; 95% CI, 0.98-1.17) or any types of noncardiovascular mortality were detected. LIMITATIONS: Potential misclassification of the actual cause of death, a nonrepresentative sample, and potential error in the interpretation of the magnitude of associations generated in MR analyses. CONCLUSIONS: These findings suggest a potential causal association between low eGFR and cardiovascular mortality in the general population, but no causal relationship with all-cause mortality or noncardiovascular mortality was observed. Further studies in other populations are warranted to confirm these findings. PLAIN-LANGUAGE SUMMARY: This study investigated the existence of a causal relationship between lower kidney function and death of different causes. Using data from 436,214 people in the United Kingdom, we applied conventional statistical analyses and those incorporating genetic data to implement Mendelian randomization, an approach that estimates causal associations. The observational analysis showed a nonlinear association between kidney function and various types of mortality outcomes. However, Mendelian randomization analysis suggested a linear increase in the risk of cardiovascular mortality with lower kidney function, but no causal link between the level of kidney function and all-cause or noncardiovascular mortality was identified. Managing kidney health may help reduce cardiovascular mortality, but caution is needed in interpreting the magnitudes of these results. Further validation in other populations and in those with advanced kidney failure is needed.

Cystatin C-based estimated glomerular filtration rate and risk of stroke in the general population: a prospective cohort study.

Background: Previous results on the association between the estimated glomerular filtration rate (eGFR) and stroke are mixed. Most studies derived the eGFR from serum creatinine, which is affected by non-kidney determinants and thus has possibly biased the association with stroke risk. Methods: In this cohort study, we included 429 566 UK Biobank participants (94.5% white, 54% women, age 56 ± 8 years) free of stroke at enrollment. The eGFRcys and eGFRcr were calculated with serum cystatin C and creatinine, respectively. Outcomes of interest were risk of total stroke and subtypes. We investigated the linear and nonlinear associations using Cox proportional hazards models and restricted cubic splines, corrected for regression dilution bias. Results: During an average follow-up of 10.11 years, 4427 incident strokes occurred, among which 3447 were ischemic and 1163 were hemorrhagic. After adjustment for confounders, the regression dilution-corrected hazard ratios (95% confidence intervals) for every 10 mL/min/1.73 m2 decrement in eGFRcys were 1.10 (1.05-1.14) for total stroke and 1.11 (1.08-1.15) for ischemic stroke. A similar pattern was observed with eGFRcr, although the association was weaker. When either type of eGFR was below 75 mL/min/1.73 m2, the risks of total and ischemic stroke increased exponentially as eGFR decreased. A U-shaped relationship was witnessed if eGFRcr was used instead. There was a null association between eGFR and hemorrhagic stroke. Conclusions: The risks of total stroke and ischemic stroke increased exponentially when the eGFRcys fell below 75 mL/min/1.73 m2.

Retinopathy is associated with impaired cognition in patients undergoing peritoneal dialysis.

Objective: Previous studies have shown a relationship between retinopathy and cognition including population with and without chronic kidney disease (CKD) but data regarding peritoneal dialysis (PD) are limited. This study aims to investigate the relationship between retinopathy and cognitive impairment in patients undergoing peritoneal dialysis (PD). Methods: In this observational study, we recruited a total of 107 participants undergoing PD, consisting of 48 men and 59 women, ages ranging from 21 to 78 years. The study followed a cross-sectional design. Retinal microvascular characteristics, such as geometric changes in retinal vascular including tortuosity, fractal dimension (FD), and calibers, were assessed. Retinopathy (such as retinal hemorrhage or microaneurysms) was evaluated using digitized photographs. The Modified Mini-Mental State Examination (3MS) was performed to assess global cognitive function. Results: The prevalence rates of retinal hemorrhage, microaneurysms, and retinopathy were 25%, 30%, and 43%, respectively. The mean arteriolar and venular calibers were 63.2 and 78.5 µm, respectively, and the corresponding mean tortuosity was 37.7 ± 3.6 and 37.2 ± 3.0 mm-1. The mean FD was 1.49. After adjusting for age, sex, education, mean arterial pressure, and Charlson index, a negative association was revealed between retinopathy and 3MS scores (regression coefficient: -3.71, 95% confidence interval: -7.09 to -0.33, p = 0.03). Conclusions: Retinopathy, a condition common in patients undergoing PD, was associated with global cognitive impairment. These findings highlight retinopathy, can serve as a valuable primary screening tool for assessing the risk of cognitive decline.

Spatial proteomics landscape and immune signature analysis of renal sample of lupus nephritis based on laser-captured microsection.

OBJECTIVE: We aimed to reveal a spatial proteomic and immune signature of kidney function regions in lupus nephritis (LN). MATERIAL AND METHODS: The laser capture microdissection (LCM) was used to isolate the glomerulus, tubules, and interstitial of the kidney from paraffin samples. The data-independent acquisition (DIA) method was used to collect proteomics data. The bioinformatic analysis was performed. RESULTS: A total of 49,658 peptides and 4056 proteins were quantitated. Our results first showed that a high proportion of activated NK cells, naive B cells, and neutrophils in the glomerulus, activated NK cells in interstitial, and resting NK cells were accumulated in tubules in LN. The immune-related function analysis of differential expression proteins in different regions indicated that the glomerulus and interstitial were major sites of immune disturbance and regulation connected with immune response activation. Furthermore, we identified 7, 8, and 9 hub genes in LN's glomerulus, renal interstitial, and tubules. These hub genes were significantly correlated with the infiltration of immune cell subsets. We screened out ALB, CTSB, LCN2, A2M, CDC42, VIM, LTF, and CD14, which show higher performance as candidate biomarkers after correlation analysis with clinical indexes. The function within three regions of the kidney was analyzed. The differential expression proteins (DEGs) between interstitial and glomerulus were significantly enriched in the immune-related biological processes, and myeloid leukocyte-mediated immunity and cellular response to hormone stimulus. The DEGs between tubules and glomerulus were significantly enriched in cell activation and leukocyte-mediated immunity. While the DEGs between tubules and interstitial were enriched in response to lipid, antigen processing, and presentation of peptide antigen response to oxygen-containing compound, the results indicated a different function within kidney regions. CONCLUSIONS: Collectively, we revealed spatial proteomics and immune signature of LN kidney regions by combined using LCM and DIA.

Association between long-term exposure to low level air pollutants and incident end-stage kidney disease in the UK Biobank: A prospective cohort.

BACKGROUND: Previous studies suggest that air pollution can increase the risk of incident chronic kidney disease (CKD). However, the association between end-stage kidney disease (ESKD) and co-exposure to relatively low-level air pollutants remains unclear. METHODS: A prospective cohort was designed based on UK Biobank. From 1 January 2010 to 12 November 2021, 453,347 participants were followed up over a median of 11.87 years. Principal component analysis was used to identify major patterns of five air pollutants, including PM2.5, PM2.5-10, PM10, NO2, and NOx. Sub-distribution hazards models were used to estimate the associations between air pollution, individually or jointly, and incident ESKD, CKD, and all-cause death, respectively. RESULTS: Principal component analysis identified two principal components, namely RC1 (PM2.5, NO2, and NOx) and RC2 (PM2.5-10 and PM10). An elevated risk of incident ESKD was associated with an interquartile range (IQR) increase in PM2.5 (hazard ratio: 1.11, 95% confidence interval: 1.02-1.22), NO2 (1.16, 1.04-1.30), NOx (1.08, 1.00-1.17), and RC1 (1.12, 1.02-1.23). An elevated risk of incident CKD was associated with an IQR increase in PM2.5 (1.05, 1.03-1.07), NO2 (1.04, 1.02-1.06), NOx (1.03, 1.02-1.05), and RC1 (1.04, 1.02-1.06). An increased risk of all-cause mortality was associated with an IQR increase in PM2.5 (1.02, 1.00-1.04). Restricted cubic spline analyses indicated a monotonic elevating association of PM2.5, NO2, NOx, and RC1 with ESKD incidence. CONCLUSIONS: Long-term exposure to PM2.5, NO2, NOx, and their complex was associated with elevated ESKD incidence, even at relatively lower levels of air pollution.

Long-Term Effects of Severe Burns on the Kidneys: Research Advances and Potential Therapeutic Approaches.

Burns are a seriously underestimated form of trauma that not only damage the skin system but also cause various complications, such as acute kidney injury (AKI). Recent clinical studies have shown that the proportion of chronic kidney diseases (CKD) in burn patients after discharge is significantly higher than that in the general population, but the mechanism behind this is controversial. The traditional view is that CKD is associated with hypoperfusion, AKI, sepsis, and drugs administered in the early stages of burns. However, recent studies have shown that burns can cause long-term immune dysfunction, which is a high-risk factor for CKD. This suggests that burns affect the kidneys more than previously recognized. In other words, severe burns are not only an acute injury but also a chronic disease. Neglecting to study long-term kidney function in burn patients also results in a lack of preventive and therapeutic methods being developed. Furthermore, stem cells and their exosomes have shown excellent comprehensive therapeutic properties in the prevention and treatment of CKD, making them increasingly the focus of research attention. Their engineering strategy further improved the therapeutic performance. This review will focus on the research advances in burns on the development of CKD, illustrating the possible mechanism of burn-induced CKD and introducing potential biological treatment options and their engineering strategies.

Estimated 24-h urinary sodium excretion and risk of end-stage kidney disease.

The association between sodium intake and long-term kidney disease endpoints is debated and yet to be proven. We aimed to investigate the associations of estimated 24-h urinary sodium excretion, reflecting daily sodium intake, with the incidence of end-stage kidney disease (ESKD). In this prospective cohort study including 444,375 UK Biobank participant, 865 (0.2%) ESKD events occurred after median follow-up of 12.7 years. For every 1 g increment in estimated 24-h urinary sodium excretion, multivariable-adjusted hazard ratio for incident ESKD was 1.09 (95% confidence interval 0.94-1.26). Nonlinear associations were not detected with restricted cubic splines. The null findings were confirmed by a series of sensitivity analyses, which attenuated potential bias from measurement errors of the exposure, regression dilution, reverse causality, and competing risks. In conclusion, there is insufficient evidence that estimated 24-h urinary sodium excretion is associated with the incidence of ESKD.

The circRNA-miRNA-mRNA regulatory network in plasma and peripheral blood mononuclear cells and the potential associations with the pathogenesis of systemic lupus erythematosus.

OBJECTIVES: This study aimed to explore the possible role of plasma and peripheral blood mononuclear cells (PBMCs) circular RNA (circRNA) in systemic lupus erythematosus (SLE). METHOD: Total RNA was extracted from blood plasma samples obtained from 10 patients with SLE and 10 healthy controls and subjected to microarray analysis to define the profile of circRNA expression. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) amplification was conducted. The overlapped circRNA between PBMCs and plasma was performed, the interactions with microRNAs were predicted, the miRNA target mRNA was predicted, and the GEO database was used. The Gene ontology and pathway analysis was performed. RESULTS: One hundred thirty-one upregulated and 314 significantly downregulated circRNAs were identified in the plasma of patients with SLE by the Fold change criteria (≥ 2.0) and P < 0.05. The qRT-PCR results showed that the expression of has-circRNA-102531, has-circRNA-103984, and has-circRNA-104262 was increased in plasma of SLE, and the expression of has-circRNA-102972, has-circRNA-102006, has-circRNA-104313 was decreased in plasma of SLE. Twenty-eight upregulated circRNAs and 119 downregulated circRNAs were overlapped from PBMCs and plasma, and ubiquitination was enriched. Furthermore, the circRNA-miRNA-mRNA network was constructed in SLE after analyzing dataset GSE61635 from GEO. The circRNA-miRNA-mRNA network comprises 54 circRNAs, 41 miRNAs, and 580 mRNAs. In addition, the TNF signaling pathway and the MAPK pathway were enriched from the mRNA of the miRNA target. CONCLUSION: We first revealed the differentially expressed circRNAs in plasma and PBMCs, and then the circRNA-miRNA-mRNA network was constructed. The network's circRNAs could be a potential diagnostic biomarker and potentially play an important role in the pathogenesis and development of SLE. Key Points • This study analyzed the circRNAs expression profiles combined with the plasma and PBMCs, which provided a comprehensive overview of circRNAs expression patterns in SLE. • The network of the circRNA-miRNA-mRNA in SLE was constructed, which contributes to a better understanding of the pathogenesis and development of SLE.

Sex-specific equations to estimate body composition: Derivation and validation of diagnostic prediction models using UK Biobank.

BACKGROUND & AIMS: Body mass index and waist circumference are simple measures of obesity. However, they do not distinguish between visceral and subcutaneous fat, or muscle, potentially leading to biased relationships between individual body composition parameters and adverse health outcomes. The purpose of this study was to develop and validate prediction models for volumetric adipose and muscle. METHODS: Based on cross-sectional data of 18,457, 18,260, and 17,052 White adults from the UK Biobank, we developed sex-specific equations to estimate visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (ASAT), and total thigh fat-free muscle (FFM) volumes, respectively. Volumetric magnetic resonance imaging served as the reference. We used the least absolute shrinkage and selection operator and the extreme gradient boosting methods separately to fit three sequential models, the inputs of which included demographics and anthropometrics and, in some, bioelectrical impedance analysis parameters. We applied comprehensive metrics to assess model performance in the temporal validation set. RESULTS: The equations that included more predictors generally performed better. Accuracy of the equations was moderate for VAT (percentage of estimates that differed <30% from the measured values, 70 to 78 in males, 64 to 69 in females) and good for ASAT (85 to 91 in males, 90 to 95 in females) and FFM (99 to 100 in both sexes). All the equations appeared precise (interquartile range of the difference, 0.89 to 1.76 L for VAT, 1.16 to 1.61 L for ASAT, 0.81 to 1.39 L for FFM). Bias of all the equations was negligible (-0.17 to 0.05 L for VAT, -0.10 to 0.12 L for ASAT, -0.07 to 0.09 L for FFM). The equations achieved superior cardiometabolic correlations compared with body mass index and waist circumference. CONCLUSIONS: The developed equations to estimate VAT, ASAT, and FFM volumes achieved moderate to good performance. They may be cost-effective tools to revisit the implications of diverse body components.

A modified renal risk score for Chinese patients with antineutrophil cytoplasmic antibody-associated vasculitis.

BACKGROUND: The renal risk score (RRS) is a useful tool to predict end-stage renal disease (ESRD) in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The current study aimed to validate the predictive performance of RRS and to further modify this model in Chinese AAV patients. METHODS: Two hundred and seventy-two patients diagnosed with AAV confirmed by renal biopsies were retrospectively enrolled from a single center. The RRS was calculated based on 3 categorical variables, i.e., the proportion of normal glomeruli, the proportion of interstitial fibrosis and tubular atrophy (IF/TA), and eGFR at biopsy, classifying these patients into low-, medium-, and high-risk groups. In addition, a modified model was developed based on the RRS and was further validated in another independent cohort of 117 AAV patients. The predictive performance of each model was evaluated according to discrimination and calibration. RESULTS: Patients were classified by the RRS into low- (26.5%), medium- (46.7%), and high-risk (26.8%) groups, with 120-month renal survival rates of 93.3%, 57.2%, and 18.4%, respectively (P < 0.001). The RRS showed good discrimination but less satisfactory calibration. Therefore, a modified model with improved discrimination and calibration was developed in Chinese AAV patients, with eGFR, proportion of normal glomeruli (both as continuous variables), and IF/TA (< 25%, 25-50%, > 50%) included. Internal and external validation of the modified model were performed. Finally, an online risk prediction tool was developed based on the modified model. CONCLUSIONS: The RRS was an independent predictor of ESRD of AAV patients. The modified model could predict the probability of ESRD for AAV patients with improved performance in Chinese AAV patients.

The role of Kimmelstiel-Wilson nodule in the kidney outcome in patients with diabetic kidney disease: A two-center retrospective cohort study.

AIMS: In the current study, we aimed to investigate the predictive value of the Kimmelstiel-Wilson (K-W) nodule for the risk of ESKD in patients with type 2 diabetes mellitus (T2DM). METHODS: In the two-center retrospective study, clinical and pathological parameters were compared between DKD patients with and without K-W nodules. Furthermore, we used Cox regression analysis to explore the predictive value of the K-W nodule for the risk of ESKD. RESULTS: Compared with DKD patients without K-W nodules, patients with K-W nodules had a significantly higher level of proteinuria [5.1(3.1, 8.0) g/24 hr vs. 2.4(1.1, 4.4) g/24 hr, p < 0.001]. Patients with K-W nodules had significantly higher interstitial fibrosis and tubular atrophy (IFTA) and arteriosclerosis scores than those without (p = 0.001 and p = 0.006). Kaplan-Meier analysis showed that the probability of developing ESKD was significantly higher in patients with K-W nodules than in those without (log-rank test, p < 0.001). However, after adjusting closer variables, the K-W nodule was not an independent predictor for the risk of ESKD (p > 0.05). CONCLUSIONS: In T2DM patients with DKD, the K-W nodule was associated with a more severe phenotype, and to some extent, associated with poorer renal outcome, but might not be an independent risk factor for the progression of ESKD.

The therapeutic effects of human embryonic stem cells-derived immunity-and-matrix regulatory cells on membranous nephropathy.

BACKGROUND: Primary membranous nephropathy (MN) is a kidney-specific autoimmune disease. Human embryonic stem cells-derived immunity-and-matrix regulatory cells (hESC-IMRCs) have immunoregulatory functions. We hypothesized that hESC-IMRCs might have therapeutic effects on MN and be a potential treatment in clinical practice. METHODS: Rats of Heymann nephritis were injected with sheep anti-rat Fx1A serum. hESC-IMRCs were intravenously administrated upon the detection of proteinuria, with 6 × 106 cells (high-dose) or 3 × 106 cells (low-dose) in 1 ml every other day. Splenocytes and IMRCs were co-cultured at different times and ratios. Cell types and cytokines were detected by flow cytometry and enzyme-linked immunosorbent assay. RESULTS: The urinary protein of rats with Heymann nephritis was reduced remarkably to a level comparable to negative controls, in both low-dose (45.6 vs. 282.3 mg/d, P < 0.001) and high-dose (35.2 vs. 282.3 mg/d, P < 0.001) hESC-IMRC treatment groups. IgG and C3 deposit, glomerular basement membrane thickness and foot process effacement were alleviated and the reduced podocin was recovered in the kidneys. The proportions of CD4 + CD25 + T cells in circulation and spleen were increased, and the circulating level of IL-10 was increased, after IMRC interventions. IL-17 and TNF-α were reduced after IMRCs treatments. IL-10 increased remarkably in the co-culture supernatant of lymphocytes and IMRCs at 48 h with ratio 10:1. CONCLUSIONS: The intravenously delivered hESC-IMRCs alleviated proteinuria and kidney injuries of Heymann nephritis, by their immunosuppressive functions through regulatory T cells and IL-10. These pre-clinical results indicate that IMRCs worth careful consideration for human trials in the treatment of MN.

A 28-Year-Old Woman Presenting with a Clinical Flare of Systematic Lupus Erythematosus and Abdominal Pain Due to Rectus Sheath Hematoma.

BACKGROUND A flare, or flare-up, of systematic lupus erythematosus (SLE) is diagnosed by an increase in disease activity in one or more organs, new symptoms, or changes in laboratory measurements. A hematoma can occur in the sheath of the rectus abdominis following muscle trauma or rupture of an epigastric vessel, or it can occur spontaneously. This report is of a 28-year-old woman who presented with a clinical flare of SLE and abdominal pain due to rectus sheath hematoma. CASE REPORT A 28-year-old woman had been suspected of having SLE 9 years ago and had received glucocorticoid therapy combined with hydroxychloroquine. However, lupus flared after she discontinued glucocorticoids, and she was admitted with a 1-month history of marked generalized edema, abdominal distension, frothy urine, and massive ascites. During hospitalization, she abruptly developed a continuous, stabbing abdominal pain and a bulge over the right abdomen as a result of straining during a bowel movement. On examination, a well-demarcated round mass that measured 121 mm × 96 mm was detected in the right quadrant. Abdominal emergency computed tomography revealed a right rectus sheath hematoma (21.4×4.7 cm). After her condition improved, the patient underwent an ultrasound-guided renal biopsy and was diagnosed with class III (A/C) and class V lupus nephritis. CONCLUSIONS This case has shown that spontaneous rectus sheath hematoma can occur without a history of trauma in a patient with an exacerbation of SLE. This association appears to be rare, and the cause is unknown.

Value of gamma interferon enzyme-linked immunospot assay in the diagnosis of peritoneal dialysis-associated tuberculous peritonitis.

BACKGROUND: Tuberculous peritonitis is the most common form of extrapulmonary tuberculosis infection in peritoneal dialysis patients. However, diagnosing tuberculous peritonitis quickly and early has always been a challenge for nephrologists. Mycobacterium tuberculosis antigen-specific gamma interferon enzyme-linked immunospot (IFN-γ ELISPOT) assay has been widely used in the clinical diagnosis of tuberculous pleurisy and peritonitis, but its use has not been reported for uremia. METHODS: This study mainly verified the feasibility of using the M. tuberculosis antigen-specific IFN-γ ELISPOT assay in the diagnosis of continuous ambulatory peritoneal dialysis (CAPD) patients with tuberculous peritonitis. Taking M. tuberculosis culture as the gold standard, the IFN-γ ELISPOT assay was used to analyze peripheral blood and peritoneal dialysis fluid of patients, and the receiver operating characteristic (ROC) curves in patients with tuberculous peritonitis (TBP) or non-tuberculous peritonitis (NTBP) were analyzed. RESULTS: The area under the receiver operating characteristic curve (AUC) was 0.927 (95% CI 0.816-1.000, P = 0.001) for the ELISPOT assay with peritoneal fluid mononuclear cells (PFMC), which was higher than that for the ELISPOT assay with peripheral blood mononuclear cells (PBMC) (0.825, 95% CI 0.6490-1.000, P = 0.011). The cutoff value for the diagnosis of TBP was 40 spot-forming cells (SFCs)/2 × 105 for the ELISPOT with PBMC, with a sensitivity of 55.6%, a specificity of 92.3%, and a diagnostic efficiency of 77.3%. The cutoff value for the diagnosis of TBP was 100 SFCs/2 × 105 for the ELISPOT on PFMC, with a sensitivity, specificity, and diagnostic efficiency 77.8%, 84.6%, and 81.8%, respectively. Parallel and serial testing algorithms appeared more accurate than single ELISPOT assays with PBMC, but ELISPOT assays with PFMC. CONCLUSIONS: The IFN-γ release test can be used for the early diagnosis of CAPD-related TBP; compared with peripheral blood, peritoneal fluid may be a more effective and accurate medium to diagnose CAPD complicated with tuberculous peritonitis.

Immune cell and TCR/BCR repertoire profiling in systemic lupus erythematosus patients by single-cell sequencing.

The immune cells and the repertoire of T cells and B cells play an important role in the pathogenesis of systemic lupus erythematosus (SLE). Exploring their expression and distribution in SLE can help us better understand this lethal autoimmune disease. In this study, we used a single-cell 5' RNA sequence and single-cell T cell receptor (TCR)/B cell receptor (BCR) to study the immune cells and the repertoire from ten SLE patients and the paired normal controls (NC). The results showed that 9732 cells correspondence to 12 cluster immune cell types were identified in NC, whereas 11042 cells correspondence to 16 cluster immune cell types were identified in SLE. The results demonstrated that neutrophil, macrophage, and dendritic cells were accumulated in SLE by annotating the immune cell types. Besides, the bioinformatics analysis of differentially expressed genes (DEGs) in these cell types indicates their role in inflammation response. In addition, patients with SLE showed increased TCR and BCR clonotypes compared with the healthy controls. Furthermore, patients with SLE showed biased usage of TCR and BCR V(D)J genes. Taken together, we characterized the transcriptome and TCR/BCR immune repertoire profiles of SLE patients, which may provide a new avenue for the diagnosis and treatment of SLE.