Background: Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis. The intestinal microbial ecosystem and metabolic network of IgAN have not been systematically analyzed. The present study aims to improve understanding of the gut microbiota and its metabolic capabilities to facilitate the development of diagnostic, therapeutic, and prognostic methods for IgAN. Methods: We characterized the gut microbiota and metabolic patterns of fecal and serum samples of IgAN patients and healthy controls from the south of China using 16s ribosomal RNA gene sequencing and liquid chromatography-tandem mass spectrometry, respectively, and bioinformatics approaches. Results: We found that the relative abundances of Streptococcus and Enterococcus were higher in IgAN patients, whereas Bacteroidetes and Bacteroides were lower. Changes in the gut microbiota of IgAN affected the metabolism and absorbance of microbiota-associated metabolites, in particular polyunsaturated fatty acids, free amino acid, and oligopeptides, and activated the phenylalanine metabolism pathway, thereby constructing a unique metabolic system of IgAN. We identified six pivotal metabolites, including bilirubin, trimethoprim, stearamide, phenylalanine, cis-9,10-epoxystearic acid, and phosphatidylethanolamine 17:0, that connected the metabolic networks of the gut and blood. Additionally, 5-hydroxyeicosatetraenoic acid and 5-hydroxy-6E,8Z,11Z-eicosatrienoic acid were shown to be associated with the classification of glomerular sclerosis. Conclusions: We establish a relational network between microbiota, fecal metabolites, and serum metabolites in IgAN. The core microbiota and metabolites identified have promising value in therapeutic applications.

Background: This experimental study was designed as a preclinical study for testing the hypothesis that intrarenal arterial (IRA) transfusion of human umbilical cord-derived mesenchymal stem cells (HUCDMSCs) therapy preserved the residual renal function of diabetic kidney disease (DKD) in rat [induction by 5/6 nephrectomy of left kidney and right nephrectomy, followed by intraperitoneal administration of aminoguanidine (180 mg/kg) and streptozotocin (30 mg/kg)]. Methods: Animals (n = 24) were categorized into group 1 (sham-operated control), group 2 (DKD), group 3 [DKD + HUCDMSCs (2.1 × 10⁵/IRA injection at day 28 after CKD induction)] and group 4 [(DKD + HUCDMSCs (6.3 × 10⁵/IRA injection)]. Results: By day 60 after DKD induction, the kidneys were harvested and the result showed that the creatinine level, ratio of urine protein/urine creatinine and kidney injury score were lowest in group 1, highest in group 2 and significantly lower in group 4 than in group 3 (all p < 0.0001). The protein expressions of apoptotic (cleaved caspase-3/cleaved PARP/mitochondrial Bax), fibrotic (TGF-ß/p-Smad3), autophagic (ratio of LC3B-II/LC3B-I, Atg5/Beclin-1), oxidative stress (NOX-1/NOX-2/oxidized protein/p22phox), mitochondrial/DNA-damaged (cytosolic-cytochrome-C/DRP1/γ-H2AX) and inflammatory (MMP-9/TNF-α/p-NF-κB) biomarkers exhibited an identical pattern, whereas the protein expressions of angiogenesis factors (CD31/vWF/vascularity) exhibited an opposite pattern of creatinine level among the groups (all p < 0.0001). Histopathological findings demonstrated the renal tubular-damaged (KIM-1)/kidney fibrosis area/oxidative stress (8-OHdG + cells) expressed an identical pattern, whereas the podocyte components (ZO-1/synaptopodin/podocin) exhibited an opposite pattern of creatinine level among the groups (all p < 0.0001). No tumorigenesis or immune rejection event was identified. Conclusion: IRA injection of xenogeneic MSCs was safe and effectively protected the residual renal function and architectural integrity in DKD rat.

The serum immunoglobulin A (IgA)/C3 ratio is considered to be an effective predictor of IgA nephropathy (IgAN). This study sought to explore the diagnostic value of the IgA/C3 ratio in IgAN among primary glomerular nephropathy patients in China. We recruited 1095 biopsy-diagnosed primary glomerular nephropathy patients, including 757 IgAN patients and 338 non-IgAN patients. Patient demographics, serum immunological indices, and other clinical examinations were measured. IgAN cases were propensity score matched (PSM) to non-IgAN cases on the logit of the propensity score using nearest neighbor matching in a 1:1 fashion, with a caliper of 0.02 with no replacements, according to age, gender, BMI, proteinuria level, and estimated glomerular filtration rate (eGFR). We found that in both the full cohort and PSM cohort, the IgA/C3 ratio in the IgAN group was significantly higher than that of the non-IgAN group. The same results were also obtained with stratification by different levels of proteinuria and renal function. In the PSM cohort, there was no difference in IgA/C3 ratio in patients with IgAN between different proteinuria groups and different chronic kidney disease (CKD) groups. The area under the ROC curve (AUROC) of the IgA/C3 ratio in distinguishing IgAN among primary glomerular disease was 0.767 in the full cohort, and 0.734 in the PSM cohort. The highest AUROC of the IgA/C3 ratio was in the ≤1 g/d proteinuria group (0.801 in the full cohort, and 0.803 in the PSM cohort); however, there was no difference between all CKD groups. Meanwhile, the diagnostic accordance rate for the diagnosis of IgAN among all patients with an IgA/C3 ratio > 3.5304 was as high as 92.02% in the full cohort. IgAN was independently correlated with IgA/C3 ratio in the full cohort by multivariate logistic regression analysis. The present study provides clear evidence that the IgA/C3 ratio is an effective predictor of IgA diagnosis, especially in patients with proteinuria ≤1 g/d. In order to study the effectiveness of this biomarker, and to determine a standardized cut-off value, additional multicenter large-scale studies are needed.

This study tested the hypothesis that empagliflozin (EMPA) therapy effectively protected renal and heart functions via downregulating reactive oxygen species (ROS) and activating AMPK signaling in cardiorenal syndrome (CRS) (induced by doxorubicin-5/6 nephrectomy) rats. In vitro result showed that underwent p-Cresol treatment, the H9C2/NRK-52E cell viabilities, were significantly suppressed, whereas cellular levels of ROS and early/late apoptosis of these cells were significantly increased that were significantly reversed by EMPA treatment (all p < 0.001). The protein levels of the cell-stress/oxidative signaling (p-PI3K/p-Akt/p-mTOR/NOXs/p-DRP1) were significantly activated, whereas the mitochondrial biogenesis signaling (p-AMPK/SIRT-1/TFAM/PGC-1α) was significantly repressed in these two cell lines treated by p-Cresol and all of these were significantly reversed by EMPA treatment (all p < 0.001). Male-adult-SD rats were categorized into groups 1 [sham-operated control (SC)]/2 [SC + high protein diet (H^PD) since day 1 after CKD induction]/3 (CRS + H^PD)/4 (CRS + H^PD+EMPA/20 mg/kg/day) and heart/kidney were harvested by day 60. By day 63, the renal function parameters (creatinine/BUN/proteinuria)/renal artery restrictive index/cellular levels of ROS/inflammation were significantly increased in group 3 than in groups 1/2, whereas heart function exhibited an opposite pattern of ROS among the groups, and all of these parameters were significantly reversed by EMPA treatment (all p < 0.0001). The protein levels of inflammation/ oxidative-stress/cell-stress signalings were highest in group 2, lowest in group 1 and significantly lower in group 4 than in group 2, whereas the AMPK-mitochondrial biogenesis displayed an opposite manner of oxidative-stress among the groups (all p < 0.0001). EMPA treatment effectively protected the heart/kidney against CRS damage via suppressing ROS signaling and upregulating AMPK-mediated mitochondrial biogenesis.

Objectives Frailty has been extensively studied in the general population. However, there is little information on frailty among patients undergoing haemodialysis (HD) in China. This study analysed the prevalence and associated factors of frailty among Southern Chinese Han patients on HD. Design Observational cross-sectional study. Setting Three HD centres in Southern China. Participants Three hundred patients who underwent regular HD between June 2019 and October 2019. Main outcomes and measures Frailty was assessed using the Tilburg indicator of frailty (TFI) questionnaire, and the psychological status of the respondents was evaluated by the Self-Rating Depression Scale (SDS) and the Self-Rating Anxiety Scale (SAS). Results Seventy-five per cent of participants were in the frailty group, and the TFI score of HD patients was 6.89±2.87, with 8.15±2.06 in the frailty group and 2.87±1.31 in the non-frailty group. Frailty patients had higher SDS and SAS scores, and were more likely to suffer depression and anxiety than non-frailty patients. Multivariate logistic regression analysis excluding depression and anxiety showed that age, Charlson Comorbidity Index (excluding end-stage renal disease), a nuclear family (compared with living alone), and albumin were independently associated with frailty (all p<0.05). In the model including depression and anxiety, age, diabetes mellitus, living as a couple (compared with living alone), a nuclear family (compared with living alone), an extended family (compared with living alone), low phosphorus, depression and anxiety were associated with frailty by multivariate logistic regression analysis (all p<0.05). Conclusions Approximately three-quarters of patients with HD in Southern China are frail, often accompanied with depression and anxiety. Age, diabetes mellitus, family structure, phosphorus, depression and anxiety were associated with frailty.

Background: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common and serious complication after cardiac surgery. The influence of statin use before surgery on the renal outcome of patients undergoing cardiac surgery is controversial. The purpose of this study was to evaluate the effect of statins on postoperative renal outcomes in patients undergoing cardiac surgery.Methods: We included CSA-AKI patients in the Medical Information Mart for Intensive Care (MIMIC)—IV database and were divided into statin group and non-statin group according to whether they used statins before entering intensive care units (ICU). The main outcomes were hospitalization and 30-day mortality, and the secondary outcomes were 60-day mortality and 90-day mortality. We used propensity score matching (PSM) to adjust for confounding factors. The 95% confidence interval (CI) and risk ratio (RO) were calculated by the COX proportional regression model. At the same time, stratified analysis was used to explore whether the relationship between the statins use before intensive care units and mortality was different in each subgroup and whether the relationship between different doses of Atorvastatin and mortality was different.Result: We identified 675 pre-ICU statin users and 2095 non-statin users. In the COX proportional regression model, pre-ICU statin use was associated with decreased in-hospital (HR = 0.407, 95%confidence interval 0.278–0.595, p < 0.001) and 30-day mortality (HR = 0.407, 95%CI 0.279–0.595, p < 0.001). The survival rate of patients who took statins before entering ICU was significantly higher than that of those who did not use statins at 30 days, 60 days and 90 days. There is a significant interaction between patients with aged>65 years (HR = 0.373, 95%CI 0.240–0.581, p < 0.001), Acute kidney injury grade I (HR = 0.244, 95%CI 0.118–0.428, p < 0.001), and without post-myocardial infarction syndrome (HR = 0.344, 95%CI 0.218–0.542, p < 0.001). The mortality in hospital and 60 days of CSA-AKI patients treated with ≥80 mg Atorvastatin before operation was significantly reduced (p < 0.05).Conclusion: The pre-ICU statin use was significantly associated with decreased risk in hospital and 30-day mortality. The preoperative use of ≥80 mg Atorvastatin may improve the prognosis of CSA-AKI.