Circulating soluble CD30 is associated with renal tertiary lymphoid structures and the progression of IgA nephropathy.

BACKGROUND: Renal tertiary lymphoid structures (TLSs) are involved in renal pathology and prognosis of IgA nephropathy (IgAN). CD30 and its ligands participate in the formation of renal TLSs. However, the relationship between circulating CD30 and renal prognosis is unclear. The objective of this study was to evaluate the relationship between circulating CD30 and prognosis in patients with IgAN. METHODS: We conducted a retrospective study including 351 patients with biopsy proved IgAN. We collected clinical and pathologic features at the time of biopsy and recorded renal follow-up outcomes. Circulating CD30 levels in IgAN patients at the time of biopsy were measured via enzyme-linked immunosorbent assay (ELISA). The association between elevated CD30 levels and the composite endpoint (defined as a ≥ 50 % decline in eGFR from baseline, end-stage renal disease, or death) was investigated using Cox regression analysis. RESULTS: During a median follow-up period of 5.12 years, 44 (12.5 %) patients in the cohort reached the composite endpoint. Kaplan-Meier survival curve analysis revealed a significant association between higher circulating CD30 levels and a poorer renal prognosis (log-rank P < 0.001). Cox regression analysis showed that high CD30 was an independent factor for the composite endpoints in multivariable-adjusted models (HR 3.397, 95 % CI: 1.230-9.384, P = 0.018). These associations were also observed in a subgroup of patients with concomitant renal TLSs formation (10.443, 95 % CI: 1.680-65.545, P = 0.012), proteinuria > 1 g/d (HR 12.287, 95 % CI: 1.499-100.711, P = 0.019), and female patients (HR 22.372, 95 % CI: 1.797-278.520, P = 0.016). CONCLUSION: Elevated level of circulating CD30 is an independent risk factor for renal disease progression in patients with IgAN.

Incidence, risk factors and outcome of postoperative acute kidney injury in China.

BACKGROUND: Postoperative acute kidney injury (AKI) is a common condition after surgery, however, the available data about nationwide epidemiology of postoperative AKI in China from large and high-quality studies are limited. This study aimed to determine the incidence, risk factors and outcomes of postoperative AKI among patients undergoing surgery in China. METHODS: This was a large, multicentre, retrospective study performed in 16 tertiary medical centres in China. Adult patients (≥18 years of age) who underwent surgical procedures from 1 January 2013 to 31 December 2019 were included. Postoperative AKI was defined by the Kidney Disease: Improving Global Outcomes creatinine criteria. The associations of AKI and in-hospital outcomes were investigated using logistic regression models adjusted for potential confounders. RESULTS: Among 520 707 patients included in our study, 25 830 (5.0%) patients developed postoperative AKI. The incidence of postoperative AKI varied by surgery type, which was highest in cardiac (34.6%), urologic (8.7%) and general (4.2%) surgeries. A total of 89.2% of postoperative AKI cases were detected in the first 2 postoperative days. However, only 584 (2.3%) patients with postoperative AKI were diagnosed with AKI on discharge. Risk factors for postoperative AKI included older age, male sex, lower baseline kidney function, pre-surgery hospital stay ≤3 days or >7 days, hypertension, diabetes mellitus and use of proton pump inhibitors or diuretics. The risk of in-hospital death increased with the stage of AKI. In addition, patients with postoperative AKI had longer lengths of hospital stay (12 versus 19 days) and were more likely to require intensive care unit care (13.1% versus 45.0%) and renal replacement therapy (0.4% versus 7.7%). CONCLUSIONS: Postoperative AKI was common across surgery type in China, particularly for patients undergoing cardiac surgery. Implementation and evaluation of an alarm system is important for the battle against postoperative AKI.

Light activates Ube3a, an Angelman syndrome-associated gene, by mediating the chromatin structures during postnatal development of mouse retina.

Angelman syndrome, a severe neurodevelopmental disorder, is primarily caused by mutations or deletions of maternally inherited ubiquitin protein ligase E3A (UBE3A). Activation of the silenced paternal copy of UBE3A can occur with pharmacological perturbation; however, an environmental approach has not been examined. Here, we found Ube3a is highly expressed in embryonic and early neonatal mouse retina and is maternally-, but not paternally-, expressed in ganglion cells, amacrine cells, and horizontal cells. Moreover, we analyzed UBE3A expression in the retina and visual cortex of postnatal day 28 mice (P28) following exposure to light emissions from white compact-fluorescent bulbs or blue light-emitting diodes from postnatal day 0 (P0) to 28 (P28), encompassing a crucial phase of visual system development. We found higher levels of Ube3a RNA and protein in the retina, but not visual cortex compared with tissues from P28 mice exposure to typical lighting (controls). Levels of both paternal- and maternal-UBE3A protein in mouse retina were higher than controls in P28 mice exposed to white or blue light. Moreover, levels of open and repressive chromatin structures, indicated by histone H3 lysine 4 trimethylation (H3K4me3) and histone H3 lysine 27 trimethylation (H3K27me3), respectively, were increased in the Ube3a promoter from mouse retina exposed to white or blue light. Our findings strongly suggest that extended exposure to white or blue light constitutes a substantial environmental factor that can effectively promote UBE3A expression within the central nervous system.

Development of a new prognostic index PNPI for prognosis prediction of CKD patients with pneumonia at hospital admission.

Background: The aim of this study was to investigate the relationship between pneumonia and chronic kidney disease (CKD), to elucidate potential risk factors, and to develop a new predictive model for the poor prognosis of pneumonia in CKD patients. Method: We conducted a retrospective observational study of CKD patients admitted to Tongji Hospital between June 2012 and June 2022. Demographic information, comorbidities or laboratory tests were collected. Applying univariate and multivariate logistic regression analyses, independent risk factors associated with a poor prognosis (i.e., respiratory failure, shock, combined other organ failure, and/or death during hospitalization) for pneumonia in CKD patients were discovered, with nomogram model subsequently developed. Predictive model was compared with other commonly used pneumonia severity scores. Result: Of 3,193 CKD patients with pneumonia, 1,013 (31.7%) met the primary endpoint during hospitalization. Risk factors predicting poor prognosis of pneumonia in CKD patients were selected on the result of multivariate logistic regression models, including chronic cardiac disease; CKD stage; elevated neutrophil to lymphocyte ratio (NLR) and D-dimer; decreased platelets, PTA, and chloride iron; and significant symptom presence and GGO presentation on CT. The nomogram model outperformed other pneumonia severity indices with AUC of 0.82 (95% CI: 0.80, 0.84) in training set and 0.83 (95% CI: 0.80, 0.86) in testing set. In addition, calibration curve and decision curve analysis (DCA) proved its efficiency and adaptability. Conclusion: We designed a clinical prediction model PNPI (pneumonia in nephropathy patients prognostic index) to assess the risk of poor prognosis in CKD patients with pneumonia, which may be generalized after more external validation.

T Follicular Helper Cells in Tertiary Lymphoid Structure Contribute to Renal Fibrosis by IL-21.

Tertiary lymphoid structure (TLS) represents lymphocyte clusters in non-lymphoid organs. The formation and maintenance of TLS are dependent on follicular helper T (TFH) cells. However, the role of TFH cells during renal TLS formation and the renal fibrotic process has not been comprehensively elucidated in chronic kidney disease. Here, we detected the circulating TFH cells from 57 IgAN patients and found that the frequency of TFH cells was increased in IgA nephropathy patients with renal TLS and also increased in renal tissues from the ischemic-reperfusion-injury (IRI)-induced TLS model. The inducible T-cell co-stimulator (ICOS) is one of the surface marker molecules of TFH. Remarkably, the application of an ICOS-neutralizing antibody effectively prevented the upregulation of TFH cells and expression of its canonical functional mediator IL-21, and also reduced renal TLS formation and renal fibrosis in IRI mice in vivo. In the study of this mechanism, we found that recombinant IL-21 could directly promote renal fibrosis and the expression of p65. Furthermore, BAY 11-7085, a p65 selective inhibitor, could effectively alleviate the profibrotic effect induced by IL-21 stimulation. Our results together suggested that TFH cells contribute to TLS formation and renal fibrosis by IL-21. Targeting the ICOS-signaling pathway network could reduce TFH cell infiltration and alleviate renal fibrosis.

Perception of transitional care quality associated with functional outcomes among patients with fractures and stroke in Taiwan.

This study aimed to examine the relationship between self-perceived quality of transitional care and functional outcome among patients with stroke and fractures. The Care Transition Measure (CTM-15) was used to survey patient's self-perceived transitional care quality before discharge. General estimating equations were used to investigate the influences of transitional care quality on patient's functional outcomes at before, 1 week after, and 1 or 3 months after discharge. Among stroke patients, higher CTM-15 scores were positively associated with greater outcome in Instrumental Activities of Daily Living (IADL) following discharge. Higher scores for "reader-friendly written care plan," "consideration of patient's preferences," and "understanding of health management" had significantly positive effects on functional recovery in IADL among both patient groups following discharge. These findings suggest that heterogeneity in transitional care needs between medical and surgical patients shall not be overlooked. A one-size-fits-all strategy may be insufficient for ensuring patient care continuity following discharge.

Proliferative ability of circulating tumor cells is a prognostic factor in Early-Stage lung adenocarcinoma.

INTRODUCTION: Circulating tumor cells (CTCs) and their proliferative ability in lung adenocarcinoma (LUAD) were not well-investigated. We developed a protocol combining an efficient viable CTC isolation and in-vitro cultivation for the CTC enumeration and proliferation to evaluate their clinical significance. METHOD: The peripheral blood of 124 treatment-naïve LUAD patients were processed by a CTC isolation microfluidics, DS platform, followed by in-vitro cultivation. LUAD-specific CTCs were defined by immunostaining of DAPI+/CD45-/(TTF1/CK7)+ and were enumerated upon isolation and after 7-day cultivation. The CTC proliferative ability was evaluated by both the cultured number and the culture index, a ratio of cultured CTC number to the initial CTC number in 2 mL of blood. RESULT: All but two LUAD patients (98.4%) were detected with at least one CTC per 2 mL of blood. Initial CTC numbers did not correlate with metastasis (75 ± 126 for non-metastatic, 87 ± 113 for metastatic groups; P = 0.203). In contrast, both the cultured CTC number (mean: 28, 104, and 185 in stage 0/I, II/III, and IV; P < 0.001), and the culture index (mean: 1.1, 1.7 and 9.3 in stage 0/I, II/III, and IV; P = 0.043) were significantly correlated with the stages. Overall survival analysis within the non-metastatic group (N = 53) showed poor prognosis for patients with elevated cultured counts (cutoff ≥ 30; P = 0.027). CONCLUSION: We implemented a CTC assay in clinical LUAD patients with a high detection rate and cultivation capability. Cultured CTC count and proliferative ability, rather than the crude CTC numbers, highly associated with cancer prognosis.

Clinical characteristics and risk factor analysis of Pneumocystis jirovecii pneumonia in patients with CKD: a machine learning-based approach.

Patients with chronic kidney disease (CKD) who are being treated with immunosuppressive medications are at risk for developing Pneumocystis jirovecii pneumonia (PCP). We attempted to characterize the clinical aspects of PCP in CKD patients in order to alert high-risk patients with bad prognosis. A retrospective study of CKD patients was conducted from June 2018 to June 2022. Based on PCP diagnostic criteria, these patients were divided into PCP and non-PCP groups. Using univariate and multivariate logistic regression analysis, risk indicators were evaluated, and nomogram and decision tree were developed. Of the CKD patients screened for Pneumocystis carinii nucleic acid, 1512 were included. Two-hundred forty four (16.14%) were diagnosed with PCP. Of the PCP, 88.5% was receiving glucocorticoid (GC) therapy, of which 66.3% received more than 0.5 mg/kg GC. Multivariate analysis showed that membranous nephropathy (OR 2.35, 95% CI 1.45-3.80), immunosuppressive therapy (OR 1.94, 95% CI 1.06-3.69), and ground glass opacity of CT scanning (OR 1.71, 95% CI 1.10-2.65) were associated with increased risk of Pneumocystis carinii infection. The AUC of nomogram based on logistics regression was 0.78 (0.75-0.81). The mortality in patients with PCP was 32.40%. Univariate analysis and decision tree showed that pulmonary insufficiency (PO2: OR 0.98, 95% CI 0.96-1.00), elevated APTT (OR 1.07, 95% CI 1.04-1.11), and reduced hemoglobin (OR 0.97, 95% CI 0.96-0.98) were associated with poor prognosis. PCP is not rare in CKD patients, particularly in those treated with immunosuppressive therapy. Considering the high mortality of the cases, further studies on the prevention and management of these patients are needed.

Nut Consumption and Effects on Chronic Kidney Disease and Mortality in the United States.

BACKGROUND: Nuts have been found to have beneficial effects on some diseases, including cardiovascular disease and cancer, in several studies. However, there are few studies to show the effects of nuts on chronic kidney disease (CKD). Thus, we conducted this study to examine the association between the consumption frequency of nuts and the prevalence and mortality of CKD among adults in the USA. METHODS: We analyzed data from 6,072 individuals (aged ≥20 years) who participated in the NHANES 2003-2006 following the scheduled procedure. Data on death were provided by the CDC. A logistic regression model was used to evaluate the association between nut consumption frequency and the prevalence of CKD. A Cox proportional hazards regression model was performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between nut consumption frequency and all-cause mortality and cardiovascular mortality in the CKD and non-CKD populations. RESULTS: Consuming nuts 1-6 times per week was associated with a lower prevalence of CKD (model 3: OR: 0.67; 95% CI: 0.49-0.91). In addition, higher nut consumption was significantly associated with lower all-cause and cardiovascular mortality in the non-CKD population. For the CKD population, a consistently significant inverse association could be seen between consuming nuts 1-6 per week and all-cause mortality (model 3: HR: 0.63; 95% CI: 0.47-0.86). No groups showed a significant difference in cardiovascular mortality compared with the reference in the full model. CONCLUSION: We recommend the CKD population to have an adequate intake of nuts 1-6 times per week, while the consumption frequency can be more flexible for the non-CKD. Further prospective studies should be conducted to confirm this conclusion.

Association between chronic kidney disease and cancer including the mortality of cancer patients: national health and nutrition examination survey 1999-2014.

PURPOSE: This study aimed to investigate the association between chronic kidney disease (CKD) and different types of cancer and the effect of CKD on mortality among types of cancer. METHODS: 30559 participants from NHANES 1999-2014 were included in our analysis, which had 2824 participants with cancer. Subgroups were grouped by cancer location. The association of different types of cancer with CKD was assessed using logistic regression models. Kaplan-Meier estimates and Cox proportional hazards models were used to evaluate the correlation between CKD and all-cause mortality in different cancer groups. RESULTS: Age, gender, race, education level, income level, hypertension, diabetes, smoking status, alcohol consumption, TG, HDL-C, UA and eGFR were significantly different between the cancer and non-cancer group. The three cancers with highest prevalence of CKD were kidney cancer (72.3%), bladder cancer (54.7%), and colon cancer (43.0%) in this study. The prevalence of CKD was higher in cancer patients compared to non-cancer ones. Only genitourinary cancer showed a positive association with CKD (OR=1.23, 95% CI: 1.05-1.44) after adjusting for confounding factors. However, CKD was an independent risk factor for mortality from cancer regardless of the type of cancer. CONCLUSION: CKD is significantly associated only with genitourinary cancer among different types of cancer. CKD is an independent risk factor for survival in cancer patients, regardless of the type of cancer. Monitoring and maintaining the renal function of cancer patients is essential for prolonging their life.

Sugar-sweetened beverage consumption and mortality of chronic kidney disease: results from the US National Health and Nutrition Examination Survey, 1999-2014.

Background: The relationship between intake of sugar-sweetened beverages (SSBs) and the risk of death in patients with chronic kidney disease (CKD) is unclear. We evaluated the association between SSB intake and subsequent overall mortality in CKD patients. Methods: We included data from 3996 CKD patients who participated in the 1999-2014 National Health and Nutrition Examination Survey (NHANES). SSB intake was assessed by a 24-h dietary recall, grouped as none, >0 to <1 serving/day, 1 to <2 servings/day and ≥2 servings/day. After adjusting for demographic variables, lifestyle, diet and comorbidities, Cox proportional risk regressions were applied to analyze the associations between the daily intake of SSBs as well as added sugar from beverages and all-cause mortality. Results: In the whole research population, the median age at baseline was 67 years, 22% were Black and 54% were female. A total of 42% had stage 3 CKD. During an average follow-up period of 8.3 years, a sum of 1137 (28%) deaths from all causes was recorded. The confounder-adjusted risk of mortality was associated with an increase of 1 serving/day of SSBs, with all-cause mortality of 1.18 [95% confidence interval (95% CI)1.08-1.28], and intakes of increased 20-g added sugar/1000 kcal of total energy per day were associated with all-cause mortality of 1.14 (1.05-1.24). Equivalently substituting 1 serving/day of SSBs with unsweetened coffee [HR (95% CI) 0.82 (0.74-0.91)], unsweetened tea [HR (95% CI) 0.86 (0.76-0.98)], plain water [HR (95% CI) 0.79 (0.71-0.88)], or non- or low-fat milk [HR (95% CI) 0.75 (0.60-0.93)] were related to a 14-25% reduced risk of all-cause mortality. Conclusion: Findings suggest that in the CKD population, increased SSB intake was associated with a higher risk of mortality and indicated a stratified association with dose. Plain water and unsweetened coffee/tea might be possible alternatives for SSBs to avert untimely deaths.

Early Menopause May Associate With a Higher Risk of CKD and All-Cause Mortality in Postmenopausal Women: An Analysis of NHANES, 1999-2014.

Background: Chronic kidney disease (CKD) in women is often accompanied by hormone disorders such as sex hormones, and most women with CKD are in the post-menopausal age group. Due to the close relationship between menopause and sex hormones, we aimed to explore the association between early menopause and CKD in post-menopausal women, and the influence of early menopause on longevity in the CKD population. Methods: Information regarding 4,945 post-menopausal women was extracted from the database of the National Health and Nutrition Examination Survey (NHANES) 1999-2014, and then divided into 4 groups according to the type of menopause (natural or surgical) and early menopause (menopause at age <45) or not. The association between early menopause and CKD prevalence was examined using multivariable logistic regression, while we used multivariable Cox proportional hazards models to investigate the possible relationship between early menopause and all-cause mortality in CKD and non-CKD populations. The differences in the levels of sex hormones between women with and without CKD were also explored. Results: Compared with women with natural menopause at age ≥45, women experiencing early natural menopause had a higher risk of CKD [OR = 1.26 (1.01-1.56)]. Similarly, as compared to women with surgical menopause at age ≥ 45, women in the early surgical menopause group were more likely to have CKD [OR = 1.38 (1.05-1.81)]. In addition, early surgical menopause was associated with higher mortality in the non-CKD group [HR = 1.62 (1.06-2.49)], but not in the CKD group. Women with CKD had a higher level of luteinizing hormone and follicle-stimulating hormone, combined with a lower level of testosterone and estradiol than the non-CKD women. Conclusion: Both early natural and surgical menopause were associated with a higher risk of CKD. Early surgical menopause was a hazard factor for survival in the non-CKD group, but not in the CKD group. Further research is required to understand the mechanisms.

Low-Carbohydrate-Diet Score and Mortality in Adults With and Without Chronic Kidney Disease: Results From the Third National Health and Nutrition Examination Survey.

OBJECTIVE: The long-term safety of consuming low-carbohydrate diets (LCDs) remains controversial. As high protein and high fat might accelerate chronic kidney disease (CKD) progression, the impact of LCD on mortality might be different in subjects with CKD and subjects without CKD. Therefore, the objective of this study was to assess the association of LCD with mortality among individuals with and without CKD. METHODS: Data from 1158 subjects with CKD and 9523 subjects without CKD in the Third National Health and Nutrition Examination Survey were analyzed. The LCD score was calculated based on a 24-hour dietary recall interview. Mortality was from baseline until 31 December 2015. Cox proportional hazards regression models were fitted to estimate multivariable-adjusted hazard ratios and 95% confidence intervals. RESULTS: During the median follow-up of 24 years, 751 (65%) deaths and 2624 (28%) deaths were recorded in the CKD group and the non-CKD group, respectively. The multivariable-adjusted hazard ratio for all-cause mortality comparing the highest versus lowest quarters of LCD score was 1.51 (95% confidence interval, 1.01-2.25, P for trend = 0.045) in the CKD group. However, there were no association between the LCD score and all-cause mortality in the non-CKD group. CONCLUSIONS: The LCD scores were found significantly positively associated with all-cause mortality in adults with CKD, but not in adults without CKD.

Effect of Marital Status on Depression and Mortality among Patients with Chronic Kidney Disease from National Health and Nutrition Examination Survey 2005-2014.

BACKGROUND: The relationship between marital status and CKD is rarely studied. We aimed to explore the effect of marital status on the depression and mortality of patients with CKD. METHODS: The data sources came from the NHANES database during 2005-2014 and 3,865 participants were included in this study. We used logistic regression models to examine the relationship between marital status and depression of CKD patients. The Cox proportional hazard models were used to evaluate the association between marital status and mortality of CKD patients. RESULTS: In terms of depression in CKD patients, unmarried patients had a worse situation than married patients. Meanwhile, after adjusting the covariables, unmarried patients had increased risk of depression (OR = 1.26, 95% CI: 1.01-1.57) compared with married CKD patients, especially in males (OR = 1.45, 95% CI: 1.02-2.06) and patients with more than college education level (OR = 12.4, 95% CI: 3.75-41.02). There was a significant relationship between marital status and mortality of general CKD patients (HR = 1.36, 95% CI: 1.17-1.58). Moreover, marriage showed a protective effect against death among male patients, patients with school graduate or less and more than college educational level, patients with high income, and patients in different estimated glomerular filtration rate groups. CONCLUSIONS: The use of large numbers of participants has revealed the effect of marital status on CKD patients. Unmarried ones had a higher risk of depression than married ones among CKD patients. Meanwhile, the risk of death was higher in unmarried ones than married ones among CKD patients in this study.

Regulatory Mechanisms and Functional Roles of Hypoxia-Induced Long Non-Coding RNA MTORT1 in Breast Cancer Cells.

Long non-coding RNAs (lncRNAs) have been found to participate in multiple genetic pathways in cancer. Also, mitochondria-associated lncRNAs have been discovered to modulate mitochondrial function and metabolism. Previously, we identified oxygen-responsive lncRNAs in MCF-7 breast cancer cells under different oxygen concentrations. Among them, a novel mitochondria-encoded lncRNA, mitochondrial oxygen-responsive transcript 1 (MTORT1), was chosen for further investigation. Nuclear, cytoplasmic, and mitochondrial fractionation assays were performed to evaluate the endogenous expression levels of MTORT1 in breast cancer cells. In vitro proliferation and migration assays were conducted to investigate the functions of MTORT1 in breast cancer cells by knockdown of MTORT1. RNA immunoprecipitation and luciferase reporter assays were used to examine the physical binding between MTORT1 and microRNAs. Our results showed that MTORT1 had low endogenous expression levels in breast cancer cells and was mainly located in the mitochondria. Knockdown of MTORT1 enhanced cell proliferation and migration, implying a tumor suppressor role of this novel mitochondrial lncRNA. MTORT1 served as sponge of miR-26a-5p to up-regulate its target genes, CREB1 and STK4. Our findings shed some light on the characterization, function, and regulatory mechanism of the novel hypoxia-induced mitochondrial lncRNA MTORT1, which functions as a microRNA sponge and may inhibit breast cancer progression. These data suggest that MTORT1 may be a candidate for therapeutic targeting of breast cancer progression.

Risk Factors and Outcomes of Acute Kidney Injury in Critically Ill Patients with Coronavirus Disease 2019.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has emerged as a major global health threat with a great number of deaths worldwide. Acute kidney injury (AKI) is a common complication in patients admitted to the intensive care unit. We aimed to assess the incidence, risk factors and in-hospital outcomes of AKI in COVID-19 patients admitted to the intensive care unit. METHODS: We conducted a retrospective observational study in the intensive care unit of Tongji Hospital, which was assigned responsibility for the treatments of severe COVID-19 patients by the Wuhan government. AKI was defined and staged based on Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Mild AKI was defined as stage 1, and severe AKI was defined as stage 2 or stage 3. Logistic regression analysis was used to evaluate AKI risk factors, and Cox proportional hazards model was used to assess the association between AKI and in-hospital mortality. RESULTS: A total of 119 patients with COVID-19 were included in our study. The median patient age was 70 years (interquartile range, 59-77) and 61.3% were male. Fifty-one (42.8%) patients developed AKI during hospitalization, corresponding to 14.3% in stage 1, 28.6% in stage 2 and 18.5% in stage 3, respectively. Compared to patients without AKI, patients with AKI had a higher proportion of mechanical ventilation mortality and higher in-hospital mortality. A total of 97.1% of patients with severe AKI received mechanical ventilation and in-hospital mortality was up to 79.4%. Severe AKI was independently associated with high in-hospital mortality (OR: 1.82; 95% CI: 1.06-3.13). Logistic regression analysis demonstrated that high serum interleukin-8 (OR: 4.21; 95% CI: 1.23-14.38), interleukin-10 (OR: 3.32; 95% CI: 1.04-10.59) and interleukin-2 receptor (OR: 4.50; 95% CI: 0.73-6.78) were risk factors for severe AKI development. CONCLUSIONS: Severe AKI was associated with high in-hospital mortality, and inflammatory response may play a role in AKI development in critically ill patients with COVID-19.

Recovery of new-onset kidney disease in COVID-19 patients discharged from hospital.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has emerged as a major global health threat with a great number of deaths worldwide. Despite abundant data on that many COVID-19 patients also displayed kidney disease, there is limited information available about the recovery of kidney disease after discharge. METHODS: Retrospective and prospective cohort study to patients with new-onset kidney disease during the COVID-19 hospitalization, admitted between January 28 to February 26, 2020. The median follow-up was 4 months after discharge. The follow-up patients were divided into the recovery group and non-recovery group. Descriptive statistics and between-groups comparison were used. RESULTS: In total, 143 discharged patients with new-onset kidney disease during the COVID-19 hospitalization were included. Patients had a median age was 64 (IQR, 51-70) years, and 59.4% of patients were men. During 4-months median follow-up, 91% (130 of 143) patients recovered from kidney disease, and 9% (13 of 143) patients haven't recovered. The median age of patients in the non-recovery group was 72 years, which was significantly higher than the median age of 62 years in the recovery group. Discharge serum creatinine was significantly higher in the non-recovery group than in the recovery group. CONCLUSIONS: Most of the new-onset kidney diseases during hospitalization of COVID-19 patients recovered 4 months after discharge. We recommend that COVID-19 patients with new-onset kidney disease be followed after discharge to assess kidney recovery, especially elderly patients or patients with high discharge creatinine.

LRG1 Mitigates Renal Interstitial Fibrosis through Alleviating Capillary Rarefaction and Inhibiting Inflammatory and Pro-Fibrotic Cytokines.

INTRODUCTION: Increasing evidence has demonstrated that loss of peritubular capillaries plays a critical role in renal interstitial fibrosis. Leucine-rich α2-glycoprotein-1 (LRG1) has been observed promoting angiogenesis in the ocular disease mouse model and myocardial infarction model. We aimed to explore the role of LRG1 in renal interstitial fibrosis. METHODS: We analyzed the expression of LRG1 in the plasma and kidney of CKD patients by ELISA and immunohistochemistry. Relationships between the expression of LRG1 in plasma and kidney and renal fibrosis and inflammation were analyzed. Tube formation assay was used to detect the angiogenesis in the human umbilical vein endothelial cell lines (HUVECs). And real-time PCR was used to detect the mRNA expression of LRG1, inflammatory factors, renal tubular injury indicators, pro-fibrotic cytokines, and CD31. We examined the effects of genetic ablation of LRG1 on renal fibrosis induced by unilateral ureteral obstruction (UUO) mice model at day 7. RESULTS: We demonstrated that the expression of LRG1 in renal tissues and plasma samples was upregulated in CKD patients. And the expression of LRG1 was elevated in human renal tubular epithelial cell line (HK-2) cells in response to the stimulation of TNF-α in vitro, and in kidney after UUO in vivo. The deficiency of the LRG1 gene aggravated renal fibrosis, inflammatory cells infiltration, and capillary rarefaction after UUO. In vitro, LRG1 promoted the tube formation of HUVEC cells. LRG1 inhibits fibronectin secretion induced by TGF-ß1 in HK-2 and overexpression of LRG1 in HK-2 cells decreased fibronectin secretion. CONCLUSION: LRG1 may prevent renal fibrosis by inhibiting the secretion of inflammatory and pro-fibrotic cytokines and promoting angiogenesis.

Tertiary lymphoid organs are associated with the progression of kidney damage and regulated by interleukin-17A.

Background: Tertiary lymphoid organs (TLOs) occur after multiple chronic kidney injuries. interleukin-17A (IL-17A) has been reported to associate with the development of TLOs in inflammatory diseases. However, regulation of the renal TLOs and its clinical significance to the pathogenesis of chronic kidney injury are unknown. Methods: To evaluate the clinical significance and regulation of renal TLOs, we analyzed the progression of patients with kidney damage based on the existence and absence of TLOs in a larger multicenter cohort. We also blocked the recruitment of lymphocyte cells into the kidney by FTY720 (fingolimod) in vivo. Besides, we used aged IL-17A genetic knocked out mice and IL-17A-neutralizing antibody to explore the role of IL-17A in renal TLOs formation. Results: We demonstrated that renal TLOs of IgA nephropathy patients were associated with disease severity and were independent risk factors for renal progression after adjustment for age, sex, mean arterial pressure, proteinuria and, baseline eGFR and MEST-C score, especially in the early stage. Plasma levels of TLO-related chemokines CXCL13, CCL19, and CCL21 were higher in patients with renal TLOs. Inhibiting the formation of renal TLOs by FTY720 could reduce the intrarenal inflammation and fibrosis, and early intervention was found to be more effective. IL-17A was increased in renal TLOs models, and genetic depletion of IL-17A or treatment with anti-IL-17A antibody resulted in a marked reduction of the TLOs formation as well as alleviation of renal inflammation and fibrosis. Conclusion: These results indicate that TLOs are associated with the progression of kidney damage and regulated by IL-17A and may be effective targets for the treatment of kidney damage.

Characteristics and Prognostic Value of Tertiary Lymphoid Organs in Membranous Nephropathy: A Retrospective Study.

BACKGROUND: Tertiary lymphoid organs play an essential role in the inflammation of the kidney. The clinical association between TLOs and membranous nephropathy (MN) is not clear yet. METHODS: Consecutive patients with the histologically confirmed membranous nephropathy in Tongji Hospital from July 19, 2012, to September 26, 2019, were included in this study. TLOs in renal biopsy tissues were detected by periodic acid-Schiff-stained and immunohistochemistry. Logistic regression was performed to evaluate the correlations of TLOs and clinical features of patients with MN. Kaplan-Meier analysis was utilized to examine the relationship between TLOs and remission of proteinuria. RESULTS: A total of 442 patients with MN were included in this study, of which the average age was 46.4 years old, and 58.8% were male. Moreover, 33% of patients with MN had TLOs in this study. The median value of proteinuria among patients with MN with TLOs was 4.9 g/24 h, which was much greater than no-TLOs ones (3.2 g/24 h, p < 0.001). Moreover, the patients with TLOs had higher serum creatinine and lower serum albumin. The severity of clinical features among the patients with MN aggravated with the increase in the grade of TLOs. In addition, the patients who had TLOs were more likely to be positive of anti-phospholipase A2 receptor autoantibodies. Meanwhile, the patients without TLOs showed significantly higher complete remission and total remission of proteinuria. CONCLUSION: In this study, we demonstrated that TLOs were common among patients with MN. Moreover, the patients with MN with TLOs showed a worse clinical manifestation and an outcome compared with the patients without TLOs.