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Abstract Background The prevalence of vascular calcification (VC) in chronic kidney disease (CKD) patients remains substantial, but currently, there are no effective pharmaceutical therapies available. BRCA1/BRCA2-containing complex subunit 36 (BRCC36) has been implicated in osteoblast osteogenic conversion; however, its specific role in VC remains to be fully elucidated. The aim of this study was to investigate the role and underlying mechanisms of BRCC36 in VC. Methods The association between BRCC36 expression and VC was examined in radial arteries from patients with CKD, high-adenine-induced CKD mice, and vascular smooth muscle cells (VSMCs). Western blotting, real-time polymerase chain reaction, immunofluorescence, and immunohistochemistry were used to analyse gene expression. Gain- and loss-of-function experiments were performed to comprehensively investigate the effects of BRCC36 on VC. Coimmunoprecipitation and TOPFlash luciferase assays were utilized to further investigate the regulatory effects of BRCC36 on the Wnt/β-catenin pathway. Results BRCC36 expression was downregulated in human calcified radial arteries, calcified aortas from CKD mice, and calcified VSMCs. VSMC-specific BRCC36 overexpression alleviated calcium deposition in the vasculature, whereas BRCC36 depletion aggravated VC progression. Furthermore, BRCC36 inhibited the osteogenic differentiation of VSMCs in vitro. Rescue experiments revealed that BRCC36 exerts the protective effects on VC partly by regulating the Wnt/β-catenin signalling pathway. Mechanistically, BRCC36 inhibited the Wnt/β-catenin pathway by decreasing the K63-linked ubiquitination of β-catenin. Additionally, pioglitazone attenuated VC partly through upregulating BRCC36 expression. Conclusions Our research results emphasize the critical role of the BRCC36-β-catenin axis in VC, suggesting that BRCC36 or β-catenin may be promising therapeutic targets to prevent the progression of VC in CKD patients. Graphical Abstract

Abstract Background Bromadiolone is a wide-use long-acting anticoagulant rodenticide known to cause severe coagulation dysfunction. At present, there have been no detailed reports of acute kidney injury (AKI) resulting from bromadiolone poisoning. Case presentation A 27-year-old woman was admitted to the hospital due to severe coagulopathy and severe AKI. Coagulation test revealed a prothrombin time exceeding 120 s and an international normalized ratio (INR) greater than 10. Further examination for coagulation factors showed significantly reduced level of factors II, VII, IX and X, indicating a vitamin K deficiency. The AKI was non-oliguric and characterized by gross dysmorphic hematuria. Following the onset of the disease, the patient’s serum creatinine rose from 0.86 to 6.96 mg/dL. Suspecting anticoagulant rodenticide poisoning, plasma bromadiolone was identified at a concentration of 117 ng/mL via gas chromatography/mass spectrometry. All other potential causes of AKI were excluded, except for the presence of a horseshoe kidney. The patient’s kidney function fully recovered after the coagulopathy was corrected with high doses of vitamin K and plasma transfusion. At a follow-up 160 days post-discharge, the coagulation function had normalized, and the serum creatinine had returned to 0.51 mg/dL. Conclusion Bromadiolone can induce AKI through a severe and prolonged coagulation disorder. Kidney function can be restored within days following treatment with high-dose vitamin K1.

Background The M-type phospholipase A2 receptor (PLA2R)-associated primary membranous nephropathy (PMN) is an immune-related disease in adults with increasing morbidity and variable treatment response, in which inflammation may contribute to the multifactorial immunopathogenesis. The relationship between fibrinogen-albumin ratio (FAR), serving as a novel inflammatory biomarker, and PMN is still unclear. Therefore, this study aims to clarify the association between FAR and disease activity and therapy response of PMN.Methods 110 biopsy-proven phospholipase A2 receptor (PLA2R) -associated PMN participants with nephrotic syndrome from January 2017 to December 2021 were recruited in the First Affiliated Hospital of Nanjing Medical University. The independent risk factors of non-remission (NR) and the predictive ability of FAR were explored by Cox regression and receiver-operating characteristic (ROC) curve analysis. According to the optimal cutoff value, study patients were categorized into the low-FAR group (≤the cutoff value) and the high-FAR group (>the cutoff value). Spearman’s correlations were used to examine the associations between FAR and baseline clinicopathological characteristics. Kaplan-Meier method was used to assess the effects of FAR on remission.Results In the entire study cohort, 78 (70.9%) patients reached complete or partial remission (CR or PR). The optimal cutoff value of FAR for predicting the remission outcome (CR + PR) was 0.233. The Kaplan-Meier survival analysis demonstrated that the high-FAR group (>0.233) had a significantly lower probability to achieve CR or PR compared to the low-FAR group (≤0.233) (Log Rank test, p = 0.021). Higher levels of FAR were identified as an independent risk factor for NR, and the high-FAR group was associated with a 2.27 times higher likelihood of NR than the low-FAR group (HR 2.27, 95% CI 1.01, 5.13, p = 0.048). These relationships remained robust with further analysis among calcineurin inhibitors (CNIs)-receivers. In the multivariate Cox regression model, the incidence of NR was 4.00 times higher in the high-FAR group than in the low-FAR group (HR 4.00, 95% CI 1.41, 11.31, p = 0.009). Moreover, ROC analysis revealed the predictive value of FAR for CR or PR with a 0.738 area under curve (AUC), and the AUC of anti-PLA2R Ab was 0.675. When combining FAR and anti-PLA2R Ab, the AUC was boosted to 0.766.Conclusions FAR was significantly correlated with proteinuria and anti-PLA2R Ab in PMN. As an independent risk factor for NR, FAR might serve as a potential inflammation-based prognostic tool for identifying cases with poor treatment response, and the best predictive cutoff value for outcomes was 0.233.

BackgroundSeveral heart rate variability (HRV) parameters were reported to be associated with residual renal function (RRF) in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). However, it is unclear whether using HRV or other autonomic nervous system (ANS) activity indexes can predict RRF decline in CAPD patients.MethodsPatients undergoing CAPD in 2022 from the First Affiliated Hospital of Nanjing Medical University were enrolled in this study. Their clinical characteristics, 5-min HRV parameters and average voltage of 5-min skin sympathetic nerve activity (aSKNA) were collected. According to the 12-month glomerular filtration rate (GFR) decline rate compared with the upper quartile, these patients were categorized into two groups: RRF decline (RRF-D) group and RRF stable (RRF-S) group. Clinical factors and ANS activity indexes for predicting 1-year RRF decline were analyzed using logistic regression, and a nomogram model was further established. The relationships between volume load related indexes and aSKNA were displayed by Spearman's correlation graphs.ResultsNinety-eight patients (53 women, average age of 46.7 ± 13.0 years old) with a median dialysis vintage of 24.5 months were enrolled in this study. Seventy-three patients were categorized into the RRF-S group and 25 patients into the RRF-D group. Compared with RRF-S group, patients in the RRF-D group had higher systolic blood pressure (BP; p = 0.019), higher GFR (p = 0.016), higher serum phosphorous level (p = 0.030), lower total Kt/V (p = 0.001), and lower levels of hemoglobin (p = 0.007) and albumin (p = 0.010). The RRF-D group generally exhibited lower HRV parameters and aSKNA compared with the RRF-S group. A nomogram model included clinical factors (sex, systolic BP, hemoglobin, GFR, and total Kt/V) and aSKNA showed the largest AUC of 0.940 (95% CI: 0.890–0.990) for predicting 1-year RRF decline.ConclusionThe nomogram model included clinical factors (sex, systolic BP, hemoglobin, GFR and total Kt/V) and ANS activity index (aSKNA) might be a promising tool for predicting 1-year RRF decline in CAPD patients.

Abstract Background Cancer-related fatigue (CRF) is a pervasive, persistent, and distressing symptom experienced by cancer patients, for which few treatments are available. We investigated the efficacy and safety of infrared laser moxibustion (ILM) for improving fatigue in breast cancer survivors. Methods A three-arm, randomized, sham-controlled clinical trial (6-week intervention plus 12-week observational follow-up) was conducted at a tertiary hospital in Shanghai, China. The female breast cancer survivors with moderate to severe fatigue were randomized 2:2:1 to ILM (n = 56) sham ILM (n = 56), and Waitlist control (WLC)(n = 28) groups. Patients in the ILM and sham ILM (SILM) groups received real or sham ILM treatment, 2 sessions per week for 6 weeks, for a total of 12 sessions. The primary outcome was change in the Brief Fatigue Inventory (BFI) score from baseline to week 6 with follow-up until week 18 assessed in the intention-to-treat population. Results Between June 2018 and July 2021, 273 patients were assessed for eligibility, and 140 patients were finally enrolled and included in the intention-to-treat analysis. Compared with WLC, ILM reduced the average BFI score by 0.9 points (95% CI, 0.3 to 1.6, P = .007) from baseline to week 6, with a difference between the groups of 1.1 points (95% CI, 0.4 to 1.8, P = .002) at week 18. Compared with SILM, ILM treatment resulted in a non-significant reduction in the BFI score (0.4; 95% CI, -0.2 to 0.9, P = .206) from baseline to week 6, while the between-group difference was significant at week 18 (0.7; 95% CI, 0.2 to 1.3, P = .014). No serious adverse events were reported. Conclusion While ILM was found to be safe and to significantly reduce fatigue compared with WLC, its promising efficacy against the sham control needs to be verified in future adequately powered trials. Trial registration Clinicaltrials.gov: NCT04144309. Registered 12 June 2018.

Membranous nephropathy (MN) is an antibody-mediated autoimmune glomerular disease in which PLA2R1 is the main autoantibody. It has become the most common cause of adult nephrotic syndrome, and about one-third of patients can progress to end-stage kidney disease, but its pathogenesis is still unclear. Animal models can be used as suitable tools to study the pathogenesis and treatment of MN. The previous Heymann nephritis rat model and C-BSA animal model are widely used to study the pathogenesis of MN. However, the lack of target antigen expression in podocytes of model animals (especially rodents) restricts the application. In recent years, researchers constructed animal models of antigen-specific MN, such as THSD7A, PLA2R1, which more truly simulate the pathogenesis and pathological features of MN and provide more choices for the follow-up researchers. When selecting these MN models, we need to consider many aspects, including cost, difficulty of model preparation, labor force, and whether the final model can answer the research questions. This review is to comprehensively evaluate the mechanism, advantages and disadvantages and feasibility of existing animal models, and provide new reference for the pathogenesis and treatment of MN.

BackgroundFew studies have investigated the relationship between sarcopenia and the incidence of major adverse cardiovascular events (MACE), which are common complications in maintenance hemodialysis (MHD) patients. This study thus explored the association between sarcopenia and MACE in a prospective cohort with mediation analysis.MethodsAdult MHD patients in Jiangdu People’s Hospital in December 2019 were screened. The exposure was sarcopenia, as defined by the 2019 Asian Working Group. The primary endpoint was the occurrence of MACE, defined as the composite of all-cause mortality or hospital admission with a primary diagnosis of acute myocardial infarction, stroke, or heart failure during a 3-year follow-up period. Multivariate Cox regression analyses were used to test the association between sarcopenia and subsequent MACE incidence. Mediation analyses were used to investigate whether potential mediators influenced the association between sarcopenia and MACE.ResultsOf the 230 patients enrolled, 57% were male, with a median age of 57 years (interquartile range [IQR]: 50 to 66), and a median dialysis vintage of 67 months (IQR: 32 to 119). The prevalence of sarcopenia was 45.2%. The presence of sarcopenia was significantly correlated with age (Spearman’s r = 0.47, p

BackgroundHigh sodium intake and fluid overhydration are common factors of and strongly associated with adverse outcomes in chronic kidney disease (CKD) patients. Yet, their effects on cardiac dysfunction remain unclear.AimsThe study aimed to explore the impact of salt and volume overload on cardiac alterations in non-dialysis CKD.MethodsIn all, 409 patients with CKD stages 1–4 (G1–G4) were enrolled. Daily salt intake (DSI) was estimated by 24-h urinary sodium excretion. Volume status was evaluated by the ratio of extracellular water (ECW) to total body water (TBW) measured by body composition monitor. Recruited patients were categorized into four groups according to DSI (6 g/day) and median ECW/TBW (0.439). Echocardiographic and body composition parameters and clinical indicators were compared. Associations between echocardiographic findings and basic characteristics were performed by Spearman’s correlations. Univariate and multivariate binary logistic regression analysis were used to determine the associations between DSI and ECW/TBW in the study groups and the incidence of left ventricular hypertrophy (LVH) and elevated left ventricular filling pressure (ELVFP). In addition, the subgroup effects of DSI and ECW/TBW on cardiac abnormalities were estimated using Cox regression.ResultsOf the enrolled patients with CKD, the median urinary protein was 0.94 (0.28–3.14) g/d and estimated glomerular filtration rate (eGFR) was 92.05 (IQR: 64.52–110.99) mL/min/1.73 m2. The distributions of CKD stages G1–G4 in the four groups was significantly different (p = 0.020). Furthermore, compared to group 1 (low DSI and low ECW/TBW), group 4 (high DSI and high ECW/TBW) showed a 2.396-fold (95%CI: 1.171–4.902; p = 0.017) excess risk of LVH and/or ELVFP incidence after adjusting for important CKD and cardiovascular disease risk factors. Moreover, combined with eGFR, DSI and ECW/TBW could identify patients with higher cardiac dysfunction risk estimates with an AUC of 0.704 (sensitivity: 75.2%, specificity: 61.0%). The specificity increased to 85.7% in those with nephrotic proteinuria (AUC = 0.713). The magnitude of these associations was consistent across subgroups analyses.ConclusionThe combination of high DSI (>6 g/d) and high ECW/TBW (>0.439) independently predicted a greater risk of LVH or ELVFP incidence in non-dialysis CKD patients. Moreover, the inclusion of eGFR and proteinuria improved the risk stratification ability of DSI and ECW/TBW in cardiac impairments in CKD.

Abstract Background Urinary ascites represents a scarcely observed pseudo-acute kidney injury in clinical settings. Protracted or missed diagnosis may hold grave ramifications for patient outcomes. Case presentation We reported a case involving an elderly female patient experiencing pseudo-acute kidney injury accompanied by ascites, wherein her renal dysfunction persisted despite medical intervention and hemodialysis. Urinary ascites was identified via a methylene blue test and by contrasting creatinine levels in serum and ascites. This patient’s kidney function was multiple typified by a marked elevation in serum creatinine/Cystatin C ratio (> 2 L/dL), potentially serving as a clue for the clinical diagnosis of pseudo-acute kidney injury engendered by urinary ascites. Conclusions This case suggested the potential diagnostic value of an asynchronous increase in serum creatinine and serum CysC (or an increased ratio of blood creatinine to blood CysC) in patients with pseudo-acute kidney injury.

Background: Oxidative stress (OS) is involved in the development of diabetes, but the genetic mechanisms are not completely understood. We integrated multi-omics data in order to explore the genetic relations between OS-related genes, diabetes mellitus, and microvascular complications using Mendelian randomization and colocalization analysis. Methods: Summary-level data related to OS were acquired from respective studies of methylation, expression, and protein abundance quantitative trait loci. Genetic associations concerning diabetes, diabetic nephropathy (DN), and diabetic retinopathy (DR) were derived from the FinnGen study. Summary-data-based Mendelian randomization (SMR) analysis was conducted to evaluate the correlations between molecular features concerned with OS-related genes and diabetes mellitus, along with its microvascular complications. Additionally, we performed colocalization analysis to determine if the detected signal pairs shared a causal genetic variant. Results: At the genetic level, we identified ten potential causal associations of oxidative stress genes with diabetes, along with microvascular complications, through SMR and colocalization analysis. After integrating the DNA methylation quantitative trait loci (mQTL) and expression QTL (eQTL) data, our analyses revealed a correlation between the methylation site cg26343298 and reduced expression of TP53INP1, supporting the protective role of cg26343298 methylation on type 2 diabetes (T2D) and diabetic nephropathy. Similarly, an inverse association was observed between gene methylation and expression in CHEK1 (cg07110182), confirming the beneficial effect of modification of CHEK1 by cg07110182 in diabetic retinopathy. In addition, upregulation of SUOX expression by cg22580629 was linked to a reduced risk of diabetic retinopathy. At circulating protein levels, genetically predicted a higher level of ICAM1 (OR 1.05, 95%CI 1.03–1.08) was positively connected with the risk of diabetic retinopathy. Conclusions: This SMR study elucidated that the TP53INP1 gene was putatively associated with T2D and DN risk, while the SUOX and CHEK1 genes were associated with DR risk through oxidative stress mechanisms. Additionally, our study showed a positive correlation between the ICAM-1 protein and DR. These findings may enhance our understanding of their pathogenesis and suggest new therapeutic targets for clinical practice.

Objective Glomerular basement membrane (GBM) thickening is a typical and essential histopathological characteristic for the diagnosis of primary membranous nephropathy (PMN). The present study aimed to explore the relationship between GBM thickness and treatment response in PMN patients.Methods A total of 128 patients with nephrotic syndrome concurrent with PMN were studied. The highest GBM thickness was measured from at least five glomerular capillary loops using an electron microscope, and the mean value was obtained. Patients were categorized into three groups according to the tertiles of GBM thickness as follows: Group 1 (GBM thickness ≤ 1100 nm, n = 48), Group 2 (1100 nm 1300 nm, n = 40). Clinicopathological features and treatment response were compared among the three groups. The associations of GBM thickness with complete remission (CR) were assessed by Cox proportional hazard analyses and a cubic spline curve.Results During a median follow-up period of 25.80 months, 69 (53.9%) patients achieved CR. Kaplan–Meier analysis showed that the non-CR probability was significantly higher in the highest tertile of GBM thickness (p˂0.001). Univariate Cox proportional hazard analysis indicated that GBM thickness was associated with CR (HR per SD 0.617, 95% CI [0.471–0.809], p˂0.001). After adjusting for age, duration of PMN, estimated glomerular filtration rate (eGFR), urinary protein excretion, grade of C3 deposition, and titer of serum anti-phospholipase A2 receptor (PLA2R) antibody, GBM thickness remained an independent predictor of CR (HR per SD 0.580, 95% CI [0.436–0.772], p˂0.001). Further multivariable-adjusted restricted cubic spline analysis confirmed a significant reverse linear association between GBM thickness and CR (p for nonlinear = 0.1261).Conclusions GBM thickness is an independent risk factor of CR. PMN patients with an increased level of GBM thickening at diagnosis have a lower probability of achieving CR.

Objective To explore the clinicopathological features of anti-glomerular basement membrane (anti-GBM) glomerulonephritis (anti-GBM-GN) and the prognostic values of clinical and laboratory indicators at diagnosis on renal and patient survival.Methods A total of 76 patients (34 males and 42 females) with anti-GBM-GN who were hospitalized in the First Affiliated Hospital of Nanjing Medical University between January 2010 and June 2021 were included in this study. The baseline clinical features, histopathological data from renal biopsies, and predictors of renal and patient survival were retrospectively analyzed.Results Among the 76 patients, the median serum creatinine at diagnosis was 618.0 (350.98, 888.25) μmol/L and the median estimated glomerular filtration rate (eGFR) was 6.62 (4.39, 14.41) mL/min. Of these 76 patients, 55 (72.4%) received initial kidney replacement therapy (KRT) and 39 (51.3%) received plasma exchange or double-filtered plasmapheresis (DFPP). During a median follow-up duration of 28.5 (6.0, 71.8) months, 53 (69.7%) patients progressed to kidney failure with replacement therapy (KFRT) and received maintenance dialysis. Initial KRT (HR = 3.48, 95% CI = 1.22–9.97, p = 0.020) was a significant risk factor for renal survival. During the follow-up, 49 (64.5%) of 76 patients survived. Age (≥60 years, HR = 4.13, 95% CI = 1.65–10.38, p = 0.003) and initial KRT (HR = 2.87, 95% CI = 1.01–8.14, p = 0.047) were predictive of patient survival.Conclusions Among patients with anti-GBM-GN, initial KRT at presentation was predictive of KFRT while older age and initial KRT were associated with higher all-cause mortality.

Purpose The mean perfusion pressure (MPP) was recently proposed to personalized management tissue perfusion pressure in critically ill patients. Increased MPP variability (MPPV) may be associated with organ injuries. Our objective was to determine if increased MPPV was associated with subsequent deterioration of renal function in critically ill patients.Methods We analyzed data stored in the eICU-CRD and MIMIC-IV databases. The exposure was MPPV, measured as the coefficient of variation (CV) using the MPP data of the first 24 h after first ICU admission. The primary endpoint was deterioration of renal function, defined as new-onset or progress of acute kidney injury between 24 and 72 h after ICU admission.Results The study population consisted of 8,590 patients from eICU-CRD and 6,723 patients from MIMIC-IV database. A total of 28.4% and 30.2% of the study population experienced deteriorated renal function, respectively. Patients with deteriorated renal function had significantly higher median MPP-CV compared with those without (12.2% vs 11.5% and 12.8% vs 12.5%, p

The lateral hypothalamus' orexinergic system has been associated with anxiety-related behaviors, and electroacupuncture (EA) modifies orexin neurons to control the anti-anxiety process. However, in a rat model of post-traumatic stress disorder (PTSD), the important role of LH orexin neurons (OXNs) in the anxiolytic effects induced by EA has not been explored. In this study, rats underwent modified single prolonged stress (MSPS) for seven days before developing EA. The rats were then subjected to elevated plus maze (EPM) and open field (OFT) tests, and western blot and c-Fos/orexin double labeling investigations were carried out to determine the functional activation of LH orexinergic neurons. Compared to MSPS model rats, it has been demonstrated that EA stimulation enhanced the amount of time spent in the central zone (TSCZ) in OFT and the amount of time spent in the open arm (TSOA) in EPM in MSPS model rats (P

Purpose: This study was developed to evaluate the effects of moxibustion on tumor microenvironmental hypoxia in a murine model of Lewis lung carcinoma (LLC). Methods: Twenty-four tumor-bearing mice were randomized into tumor group (T), tumor + cisplatin group (TC), tumor + moxibustion group (TM), and tumor + cisplatin + moxibustion group (TMC) (n = 6/group). Six age-matched C57BL/6 mice were employed as control group (Ctrl). A tumor model was established by implanting LLC cells into the right flank of each mouse. Animals in the TM group received moxibustion treatment at the ST36 (bilateral) and GV4 acupoints on the day of visible tumor formation. Moxibustion treatment was performed every other day for a total of 7 sessions. Animals in the TC group were intraperitoneally injected with cisplatin (3 mg/kg) on day 3 after visible tumor formation, and this treatment was performed every 3 days for 4 times. Animals in the TMC group underwent combined moxibustion and chemotherapy treatment, following the same conditions as outlined above. Following treatment, the concentrations of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), CD31, and Ki67 were measured using ELISA, Western blot, and immunohistochemical staining. Results: Compared to the tumor group, treatment in the TM, TC, and TCM groups resulted in varying reductions in tumor growth ( P

BackgroundPrimary membranous nephropathy (PMN) is an immune-related disease with increased morbidity and the most common cause of adult nephrotic syndrome (NS). The serum 25-hydroxyvitamin D [25(OH)D)], a biomarker of vitamin D (VD) status, tends to decline in patients with kidney disease. However, the relationship between 25(OH)D and PMN is still unclear. Therefore, this study aims to clarify the association between 25(OH)D and disease severity and therapy response of PMN.MethodsA total of 490 participants diagnosed with PMN by biopsy from January 2017 to April 2022 were recruited at the First Affiliated Hospital of Nanjing Medical University. The correlations between baseline 25(OH)D and manifestations of nephrotic syndrome (NS) or seropositivity of anti-PLA2R Ab were confirmed by univariate and multivariate logistic analyses. Spearman’s correlations were used to examine the associations between baseline 25(OH)D and other clinical parameters. In the follow-up cohort, Kaplan-Meier analysis was used to assess remission outcomes among groups with low, medium, and high levels of 25(OH)D. Furthermore, the independent risk factors for non-remission (NR) were explored by COX regression analysis.ResultsAt baseline, 25(OH)D was negatively related to 24-h urinary protein and serum anti-PLA2R Ab. The lower level of baseline 25(OH)D was associated with an increased risk for the incidence of NS in PMN (model 2, OR 6.8, 95% CI 4.4, 10.7, P < 0.001) and seropositivity of anti-PLA2R Ab (model 2, OR 2.4, 95% CI 1.6, 3.7, P < 0.001). Furthermore, the lower level of 25(OH)D during follow-up was demonstrated as an independent risk factor for NR even after adjusting age, gender, MBP, 24 h UP, serum anti-PLA2R Ab, serum albumin, and serum C3 [25(OH)D (39.2–62.3 nmol/L): HR 4.90, 95% CI 1.02, 23.53 P = 0.047; 25(OH)D < 39.2 nmol/L: HR 17.52, 95% CI 4.04, 76.03 P < 0.001); vs. 25(OH)D ≥ 62.3 nmol/L]. The Kaplan-Meier survival analysis also demonstrated that the higher level of follow-up 25(OH)D had a higher possibility of remission than the lower one (log-rank test, P < 0.001).ConclusionBaseline 25(OH)D was significantly correlated with nephrotic proteinuria and seropositivity of anti-PLA2R Ab in PMN. As an independent risk factor for NR, a low level of 25(OH)D during follow-up might serve as a prognostic tool for sensitively identifying cases with a high probability of poor treatment response.

BackgroundThe mean perfusion pressure (MPP) was recently proposed to personalize tissue perfusion pressure management in critically ill patients. Severe fluctuation in MPP may be associated with adverse outcomes. We sought to determine if higher MPP variability was correlated with increased mortality in critically ill patients with CVP monitoring.MethodsWe designed a retrospective observational study and analyzed data stored in the eICU Collaborative Research Database. Validation test was conducted in MIMIC-III database. The exposure was the coefficient of variation (CV) of MPP in the primary analyses, using the first 24 hours MPP data recorded within 72 hours in the first ICU stay. Primary endpoint was in-hospital mortality.ResultsA total of 6,111 patients were included. The in-hospital mortality of 17.6% and the median MPP-CV was 12.3%. Non-survivors had significantly higher MPP-CV than survivors (13.0% vs 12.2%, p 19.2%) were associated with increased risk of hospital mortality compared with those in the fifth and sixth decile (adjusted OR: 1.38, 95% Cl: 1.07-1.78). These relationships remained remarkable in the multiple sensitivity analyses. The validation test with 4,153 individuals also confirmed the results when MPP-CV > 21.3% (adjusted OR: 1.46, 95% Cl: 1.05-2.03).ConclusionsSevere fluctuation in MPP was associated with increased short-term mortality in critically ill patients with CVP monitoring.

Lupus Nephritis (LN) is the most common manifestation of severe organ damage for systemic lupus erythematosus (SLE) patients. Severe active LN could result in acute kidney injury (AKI), which could even require Kidney Replacement Therapy (KRT). Therefore, there needs to be a more proactive and safe induction therapy to quickly and effectively control renal immune inflammation, maintain kidney function or reverse kidney damage. While multiple clinical studies have proven the efficacy and safety of Belimumab in treating SLE and LN, these studies have not included cases of severe LN requiring KRT. We observed the effectiveness and safety of Belimumab in treating four severe active LN patients undergoing KRT. With Belimumab administered at a dosage of 10mg/kg, all four patients were able to discontinue KRT with no adverse events (AEs) to date ultimately. These cases provided an excellent basis for the application of Belimumab combined with standard therapy to LN patients with a medium to severe kidney injury.

BackgroundDue to the various clinical and pathological manifestations of kidney involvement in lymphoproliferative disorder (LPD), the whole spectrum of kidney disease in LPD is still unclear, and data on kidney prognosis is scarce.MethodsWe retrospectively reviewed the renal pathology profiles from January 2010 to December 2021, and 28 patients with B-cell LPD combined with intact renal biopsy data were included.ResultsThere were 20 men and eight women aging 41 to 79 years at the time of renal biopsy (median age 62 years). According to hematological diagnosis, patients were classified into four groups: chronic lymphocytic leukemia (CLL) (group1, n=7), Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) (group 2, n=8; WM, n=6; LPL, n=2), Other non-Hodgkin’s lymphomas (NHL) (group3, n=7; diffuse large B-cell lymphoma (DLBCL), n=2; mucosa-associated lymphoid tissue (MALT) lymphoma, n=4; Low grade B-cell lymphoma, n=1), and monoclonal gammopathy of undetermined significance/monoclonal gammopathy of renal significance (MGUS/MGRS) (group 4, n=6). Median serum creatinine (Scr) level was 129 (range,59-956) umol/L. Eight patients (29%) were presented with acute kidney injury (AKI), and five patients (18%) required hemodialysis upon admission. Twenty-three patients (82%) presented with proteinuria (median protein excretion, 2.14 g/d), 11(39%) of whom had the nephrotic syndrome. Interstitial malignant infiltration was the most frequent renal lesion (n=6). Eight patients underwent immunohistochemistry of renal tissues, of which three patients (CLL, n=1; LPL, n=1; WM, n=1) had confirmed lymphoma infiltrates, and the infiltrating cells in the remaining five patients (CLL, n=1; MALT lymphoma, n=2; MGUS, n=2) were considered unrelated to lymphoma. The most common glomerular diseases were renal amyloidosis (n=4) and membranous nephropathy (n=4). Only 20 patients were treated, 13 of whom were treated with rituximab separately or in combination. The median follow-up time was 11 months. Of these, six had achieved hematological response, complete response in five cases. Eight had achieved renal response. At the end-of-study visit, four patients died and two progressed to end stage kidney disease (ESKD).ConclusionIn conclusion, the clinicopathological spectrum of renal involvement in BLPD is diverse. Renal biopsy and immunohistochemistry are required for early diagnosis and prognostic assessment.

Abstract The current study aimed to assess the dietary salt intake in patients with CKD in Jiangsu province and investigate the relationship of urinary sodium excretion with blood pressure. A total of 800 patients with CKD stages 1–4 were recruited. All enrolled patients were asked to collect complete 24‐h urine specimen. At the same time, patient's demographic and laboratory data were recorded. The mean age was 47.45 ± 15.25 years old, including 423 men and 377 women. There was no significant difference in urinary sodium excretion among different stages of CKD (p = .748). This study revealed that the median urinary sodium excretion of all patients was 127.20 mmol/d (IQR 91.03–172.06), corresponding to a salt intake of 7.4 g/d. Among them, only 167 (20.9%) cases had salt intake

Chronic kidney disease (CKD) is a global public health problem, and cardiovascular disease is the most common cause of death in patients with CKD. The incidence and prevalence of cardiovascular events during the early stages of CKD increases significantly with a decline in renal function. More than 50% of dialysis patients die from cardiovascular disease, including coronary heart disease, heart failure, arrhythmia, and sudden cardiac death. Therefore, developing effective methods to control risk factors and improve prognosis is the primary focus during the diagnosis and treatment of CKD. For example, the SPRINT study demonstrated that CKD drugs are effective in reducing cardiovascular and cerebrovascular events by controlling blood pressure. Uncontrolled blood pressure not only increases the risk of these events but also accelerates the progression of CKD. A co-crystal complex of sacubitril, which is a neprilysin inhibitor, and valsartan, which is an angiotensin receptor blockade, has the potential to be widely used against CKD. Sacubitril inhibits neprilysin, which further reduces the degradation of natriuretic peptides and enhances the beneficial effects of the natriuretic peptide system. In contrast, valsartan alone can block the angiotensin II-1 (AT1) receptor and therefore inhibit the renin–angiotensin–aldosterone system. These two components can act synergistically to relax blood vessels, prevent and reverse cardiovascular remodeling, and promote natriuresis. Recent studies have repeatedly confirmed that the first and so far the only angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan can reduce blood pressure more effectively than renin–angiotensin system inhibitors and improve the prognosis of heart failure in patients with CKD. Here, we propose clinical recommendations based on an expert consensus to guide ARNI-based therapeutics and reduce the occurrence of cardiovascular events in patients with CKD.

Conventional homeopathy and traditional Chinese medicine (TCM) are two popular alternative systems of medicine, which are practiced also in many countries outsidethe countries of origin. Homeopathy originated in Germany in the 19th century and spread throughout the world in spite of antagonism by theorthodox practitioners. It is a holistic medicine based on the principles of treatment where the remedy and the disease have similar symptoms,applies a single potentized medicine at a time, in minimum dose. TCM, also a holistic medicine originating in ancient China about 3000 years ago, has been developed and practiced through centuries till today as one of the most popular alternative medicines in the world. Both the systems ofmedicine have many differences in theories, principles and practices, but they have some important aspects in common. Both are holistic in approach,treating the whole patient, not the affected organs only; focusing on stimulating the intrinsic life principle to bring order, and on homeostasis and balance in the organism. In therapeutics, they may advantageously be applied as adjuvant to each other, producing synergistic effects.

ObjectiveVolume overload is a frequent feature related to left ventricular hypertrophy (LVH) in dialysis patients, but its influence on patients with chronic kidney disease (CKD) not on dialysis has not been accurately uncovered. This article was to examine the relationship between overhydration (OH) and LVH in patients with CKD not yet on dialysis.MethodsA total of 302 patients with CKD stages 1–4 were included. Participants were divided into different subgroups according to occurring LVH or not, and OH tertiles. Clinical and laboratory parameters were compared among groups. Spearman correlation analyses were adopted to explore the relationships of echocardiographic findings with the clinical and laboratory characteristics. Binary logistic regression models were performed to estimate the odds ratios (ORs) for the associations between OH and LVH. Restricted cubic splines were implemented to assess the possible non-linear relationship between OH and LVH. LVH was defined as left ventricular mass index (LVMI) >115 g/m2 in men and >95 g/m2 in women.ResultsOf the enrolled patients with CKD, the mean age was 45.03 ± 15.14 years old, 165 (54.6%) cases were men, and 65 (21.5%) cases had LVH. Spearman correlation analyses revealed that OH was positively correlated with LVMI (r = 0.263, P < 0.001). After adjustment for age, gender, diabetes, body mass index (BMI), systolic blood pressure (SBP), hemoglobin, serum albumin, estimated glomerular filtration rate (eGFR), and logarithmic transformation of urinary sodium and urinary protein, multivariate logistic regression analyses demonstrated that both the middle and highest tertile of OH was associated with increased odds of LVH [OR: 3.082 (1.170–8.114), P = 0.023; OR: 4.481 (1.332–15.078), P = 0.015, respectively], in comparison to the lowest tierce. Restricted cubic spline analyses were employed to investigate the relationship between OH and LVH, which unfolded a significant non-linear association (P for non-linear = 0.0363). Furthermore, patients were divided into two groups according to CKD stages. The multivariate logistic regression analyses uncovered that increased odds of LVH were observed in the middle and the highest tertile of OH [OR: 3.908 (0.975–15.670), P = 0.054; OR: 6.347 (1.257–32.054), P = 0.025, respectively] in patients with stages 1–2.ConclusionThese findings suggest that a higher level of OH was associated with a higher occurrence of LVH in patients with CKD not on dialysis, especially in patients with CKD stages 1–2.

Background: An early net ultrafiltration (NUF) rate may be associated with prognosis in patients receiving continuous kidney replacement therapy (CKRT). In this study, we tested whether high or low early NUF rates in patients treated with CKRT were associated with increased mortality.Methods: We conducted a retrospective, observational study among all patients in the Medical Information Mart for Intensive Care IV database who received CKRT for more than 24 h within 14 days after intensive care unit admission. We defined the early (initial 48 h) NUF rate as the amount of fluid removal per hour adjusted by the patients' weight and took it as a classified variable (low rate: 3.1 ml/kg/h). The association between 28-day mortality and the NUF rate was analyzed by logistic regression and mediation analyses.Results: A total of 911 patients were included in our study. The median NUF rate was 2.71 (interquartile range 1.90–3.86) ml/kg/h and the 28-day mortality was 40.1%. Compared with the moderate NUF rate, the low NUF rate (adjusted odds ratio 1.56, 95% CI 1.04–2.35, p = 0.032) and high NUF rate (adjusted odds ratio 1.43, 95% CI 1.02–2.01, p = 0.040) were associated with higher 28-day mortality. The putative effect of high or low NUF rates on 28 day mortality was not direct [adjusted average direct effects (ADE) for a low NUF rate = 0.92, p = 0.064; adjusted ADE for a high NUF rate = 1.03, p = 0.096], but mediated by effects of the NUF rate on fluid balance during the same period [adjusted average causal mediation effects (ACME) 0.96, p = 0.010 for a low NUF rate; adjusted ACME 0.99, p = 0.042 for a high NUF rate]. Moreover, we found an increase trend in the NUF rate corresponding to the lowest mortality when fluid input increased.Conclusion: Compared with NUF rates between 1.6–3.1 ml/kg/h in the first 48 h of CKRT, NUF rates > 3.1 and

Uraemic cardiomyopathy (UCM) is one of the most common complications in chronic kidney disease (CKD). Our aim was to compare characteristics of various UCM mouse models. Mice were assigned to the following groups: the pole ligation group, 5/6 nephrectomy group (5/6Nx), uninephrectomy plus contralateral ischemia followed by reperfusion group (IR), adenine group, and sham group. Mice were sacrificed at 4, 8, and 16 weeks after surgery in the pole ligation, 5/6Nx, and IR groups, respectively. In the adenine group, mice were sacrificed at 16 weeks after the adenine diet. The structure and function of the heart and the expression of fibroblast growth factor 23 (FGF-23) and growth differentiation factor 15 (GDF-15) in hearts were assessed. The mortality in the 5/6 Nx group was significantly higher than that in the pole ligation, IR, and adenine groups. Echocardiogram and histological examination showed cardiac hypertrophy in the adenine,5/6Nx, ligation group, and IR group. In addition, cardiac fibrosis occurred in all CKD modeling groups. Interestingly, cardiac fibrosis was more serious in the IR and adenine groups. FGF-23 expression in sham mice was similar to that in modeling groups; however, the GDF-15 level was decreased in modeling groups. Our results suggest that the four models of UCM show different phenotypical features, molding time and mortality. GDF-15 expression in the hearts of UCM mice was downregulated compared with sham group mice.

BackgroundImmune checkpoint inhibitors (ICIs) have brought a paradigm shift to cancer treatment. However, little is known about the risk of renal adverse events (RAEs) of ICI-based regimens, especially ICI combination therapy.MethodsWe carried out a network meta-analysis of randomized controlled trials (RCTs) to compare the risk of RAEs between ICI-based regimens and traditional cancer therapy, including chemotherapy and targeted therapy. Subgroup analysis was conducted based on tumor types.ResultsNinety-five eligible RCTs involving 40,552 participants were included. The overall incidence of RAEs, grade 3–5 RAEs, acute kidney injury (AKI), and grade 3–5 AKI was 4.3%, 1.2%, 1.3%, and 0.8%, respectively. Both ICI-based treatment regimens and traditional cancer therapy showed significantly higher risk of RAEs and AKI than the placebo. Among ICI monotherapy, anti-PD-1 (RR: 0.51, 95%CI: 0.29–0.91) was significantly safer than anti-CTLA-4 in terms of RAEs. Anti-CTLA-4 showed significantly higher toxicity than anti-PD-1 (RR: 0.33, 95%CI: 0.14-0.77), anti-PD-L1 (RR: 0.38, 95%CI:0.16-0.91), and anti-PD-1 plus anti-CTLA-4 (RR: 0.32, 95%CI: 0.12-0.87) in terms of grade 3-5 RAEs. The difference was not significant between ICI monotherapy and traditional cancer therapy, except that targeted therapy seemed the least toxic therapy in terms of the incidence of AKI. Anti-CTLA-4 plus anti-PD-1 were associated with higher risk of RAEs than anti-PD-1 (RR: 1.61, 95%CI: 1.02–2.56). The difference was not significant between other dual ICI regimens and ICI monotherapy in terms of RAEs and AKI. ICI plus chemotherapy showed increased risk of both RAEs and AKI compared with ICI monotherapy, chemotherapy, and targeted therapy. The overall results remained robust in the meta-regression and sensitivity analyses.ConclusionsAmong ICI monotherapy, anti-CTLA-4 appeared to be associated with increased toxicity, especially in terms of grade 3–5 RAEs. Anti-CTLA-4 plus anti-PD-1 were associated with higher risk of RAEs than anti-PD-1. However, the difference was not significant between other dual ICI regimens and ICI monotherapy in terms of RAEs and AKI. ICIs plus chemotherapy seemed to be the most toxic treatment regimen in terms of RAEs, AKI, and grade 3–5 AKI.Systematic Review RegistrationPROSPERO, identifier CRD42020197039.

Electroacupuncture (EA) is a promising clinical approach to treating posttraumatic stress disorder (PTSD), yet the mechanisms whereby EA can alleviate anxiety and other PTSD symptoms have yet to be clarified. In the present report, rats underwent EA for 14 consecutive days following modified single prolonged stress (MSPS) exposure. These animals were then evaluated in open field and elevated plus maze tests (OFT and EPM), while Fos immunohistochemical staining was performed to assess ventromedial prefrontal cortex (vmPFC) functional activation. In addition, an extracellular recording and stimulation system was used to analyze vmPFC inputs into the ventral tegmental area (VTA) in these rats. Temporary vmPFC inactivation was further performed to assess whether this was sufficient to reverse the anxiolytic effects of EA. Overall, rats that underwent EA treatment spent more time in the central region (OFT) and the open arm (EPM) relative to MSPS model animals (P < 0.05). These MSPS model animals also exhibited significantly fewer activated Fos-positive nuclei in the vmPFC following behavioral testing, while EA was associated with a significant relative increase in c-Fos expression in this region. The transient inactivation of the vmPFC was sufficient to reverse the effects of EA treatment on anxiety-like behaviors in MSPS model rats. MSPS and SEA rats exhibiting no differences in bursting activity between baseline and vmPFC stimulation, whereas bursting activity rose relative to baseline upon ventral mPFC stimulation in EA treated and control rats. Together, these findings indicate that the vmPFC and its inputs into the VTA are functionally linked to the anxiolytic activity of EA, implicating this pathway in the EA-mediated treatment of PTSD.

Introduction: Acute kidney injury has been identified as a common complication of cardiac surgery. To date, the effect of the time interval from coronary angiography to cardiac surgery on postoperative acute kidney injury is still controversial. The aim of this study was to investigate the relationship between the timing of coronary angiography and cardiac surgery associated acute kidney injury.Methods: Eight hundred thirteen patients who underwent coronary angiography and cardiac surgery successively from January 2017 to December 2018 were included in this retrospective cohort study. We applied multivariate logistic regression, propensity score analysis, and subgroup analysis to evaluate the association between the time interval and postoperative acute kidney injury incidence and prognosis. Meta-analysis was conducted to verify the results.Results: The overall incidence of the cardiac surgery associated acute kidney injury was 28.8%. Age (OR = 1.046, 95%CI: 1.017–1.075), cardiopulmonary bypass (OR = 3.439, 95%CI: 1.316–8.986) and diabetes (OR = 2.522, 95%CI: 1.439–4.417) were found to be independent risk factors of postoperative acute kidney injury in multivariate logistic regression and propensity score analysis. Undergoing cardiac surgery within 7 days after coronary angiography was not associated with increased incidence of postoperative acute kidney injury or worse prognosis. Meta-analysis obtained consistent results.Conclusions: The time interval shorter than 7 days had no influence on cardiac surgery associated acute kidney injury incidence and prognosis. The decision of delaying the surgery should be made after comprehensive evaluation of the patient.

ObjectiveTo determine the prognostic values of histopathologic classification of myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis and other clinical and laboratory features at the time of presentation on renal and patient survival associated with myeloperoxidase-ANCA-associated glomerulonephritis (MPO-ANCA-GN).MethodsA total of 112 patients diagnosed with MPO-ANCA-GN from October 2005 to December 2018 were enrolled. The baseline clinical characteristics, renal histopathological data, and risk factors predictive of renal and patient survival were retrospectively analyzed.ResultsAll 112 patients underwent renal biopsy. Disease in 32 patients was classified as focal, 26 as mixed, 29 as crescentic, and 25 as sclerotic. Over a median follow-up period of 41.5 months, there were 44 patients dialysis-dependent. The renal survival rate was significantly higher in the focal group than the other groups (p < 0.001) and significantly lower in the sclerotic group (p < 0.05). In addition, disease histopathologically classified as sclerotic (p = 0.044), high serum creatinine level (≥320 μmol/L, p < 0.001), low albumin (

ObjectiveTo determine the relationship between obesity and the risk of AKI after cardiac surgery (CS-AKI) in a cohort study.MethodsA total of 1,601 patients undergoing cardiac surgery were collected and their incidence of CS-AKI was recorded. They were divided into underweight, normal weight, overweight, and obese groups. Logistic regression was used to estimate the association between BMI (body mass index) and CS-AKI risk. Then, a meta-analysis of published cohort studies was conducted to confirm this result using PubMed and Embase databases.ResultsA significant association was observed in this independent cohort after adjusting age, gender, hypertension and New York Heart Association classification (NYHA) class. Compared with normal BMI group (18.5 ≤ BMI < 24.0), the individuals with aberrant BMI level had an increased AKI risk (OR: 1.68, 95% CI: 1.01–2.78) for BMI < 18.5 group and (OR: 1.43, 95% CI: 0.96–2.15) for BMI ≥ 28.0. Interestingly, the U-shape curve showed the CS-AKI risk reduced with the increasing of BMI when BMI ≤ 24.0. As BMI increases with BMI > 24.0, the risk of developing CS-AKI increased significantly. In the confirmed meta-analysis, compared with normal weight, overweight group with cardiac surgery had higher AKI risk (OR: 1.28, 95% CI: 1.16–1.41, Pheterogeneity = 0.49). The similar association was found in obesity subgroup (OR: 1.79, 95% CI: 1.57–2.03, Pheterogeneity = 0.42).ConclusionIn conclusion, the results suggested that abnormal BMI was a risk factor for CS-AKI independently.

Purpose: Accurate preoperative parathyroid localization is important for successful parathyroidectomy (PTX). The aim of our study was to investigate whether SPECT/CT has enhanced effect in preoperative localization of parathyroids. Methods: In our retrospective cohort study, we evaluated the effects of technetium-99m methoxyisobutylisonitrile-single-photon emission computed tomography/computed tomography (99mTc-MIBI SPECT/CT) on preoperative parathyroid localization for 645 secondary hyperparathyroidism (SHPT) patients. Among them, 569 successful PTX patients were divided into group A (received 99mTc-MIBI scintigraphy, n = 175) and group B (received 99mTc-MIBI scintigraphy and SPECT/CT imaging, n = 394). Sensitivity, specificity, and consistency of two imaging methods in preoperative localization of parathyroids were compared. Results: Overall sensitivity and consistency were higher in group B, while there was no difference in specificity between the two groups. In group A, the sensitivity of 99mTc-MIBI was 50.00%, 77.11%, 61.76%, and 76.54% in the right upper gland (RU), right lower gland (RL), left upper gland (LU), and left lower gland (LL) subgroups, while the consistency was 52.00%, 76.57%, 61.71%, and 75.43%, respectively. In group B, the sensitivity of 99mTc-MIBI with SPECT/CT was 69.39%, 90.03%, 78.07%, and 84.27%, and the consistency was 69.54%, 88.32%, 78.43%, and 84.26%, respectively. The sensitivity and consistency in lower glands were higher than in upper glands in both groups. Sensitivity for eutopic parathyroid was higher in group B, while there was no difference for ectopic parathyroid. Conclusions: 99mTc-MIBI SPECT/CT can increase the sensitivity and consistency of preoperative localization of eutopic parathyroid glands, and it can accurately locate ectopic parathyroid without sensitivity improvement.

Traditional Indian medicine or Ayurveda (阿育吠陀) and Traditional Chinese Medicine remain the most ancient yet living traditions. These are the two great traditional medicines with rich philosophical, experiential, and experimental basis. Both the systems have been developed and enriched by thousands of years of practices, observations, and experiences. As India and China are neighbors, some exchange of medical ideas and practices might have occurred between the two nations since ancient times. Therefore, when the two traditional medicines are examined closely, many similarities become apparent in the theories and practices along with individual differences.

Abstract Background Renal replacement therapy (RRT) with regional citrate anticoagulation (RCA) is an important therapeutic approach for refractory hypercalcemia complicated with renal failure. However, RCA has the potential to induce arrhythmia caused by rapid calcium loss. We report a case of arrhythmia associated with rapid calcium loss during RCA-RRT. Case presentation A 51-year-old man with hypercalcemia, primary hyperparathyroidism, and acute kidney injury was treated by predilutional-RCA-hemofiltration at a rate of 4.3 L/h. The effect of lowering serum calcium was unsatisfactory despite reducing calcium substitution gradually from 5.3 to 2.2 mmol/h in the first 8-h session of RCA-hemofiltration. New-onset sinus tachycardia with a prolonged QT interval occurred when calcium substitution was infused at rate of 1.1 mmol/h after 15 min of starting the second RCA-hemofiltration session (estimated net calcium loss was 7.54 mmol/h). When the calcium substitution was increased to usual rate of 5.6 mmol/h, the arrhythmia disappeared after 2 min. Arrhythmia did not recur when the calcium substitution rate was 2.2 mmol/h during the third session (estimated net calcium loss was 6.44 mmol/L). After the third RCA-hemofiltration session, the patient underwent parathyroidectomy and serum calcium returned to normal. Conclusions This case indicated that rapid calcium loss may cause arrhythmia in RCA-hemofiltration, and the rate of net calcium loss should be limited below a threshold value to prevent similar adverse effect during RCA-RRT.

Nocardiosis manifests as an opportunistic infection, primarily affecting individuals who are immunocompromised and susceptible to the infection. We present a case study of one patient with nephrotic syndrome and membranous nephropathy, who underwent treatment with prednisone and cyclosporine in 2016. In early 2017, the patient was diagnosed with a "fungal infection" and discontinued the use of cyclosporine. After one month of anti-infection therapy, a cranial magnetic resonance imaging scan showed multiple abscesses in the right temporal region. The diagnosis of nocardiosis was confirmed based on the presence of metastatic abscess masses, multiple lung and brain lesions, and a positive culture of Nocardia in the drainage. We changed the antiinfection therapy to a combination of trimethoprim-sulfamethoxazole (TMP-SMX), minocycline, and voriconazole. However, the patient experienced a sudden cardiac arrest and subsequently recovered after cardiopulmonary resuscitation. During the five-month follow-up period following the discharge, the patient displayed an enhanced nutritional status and stable renal function. The focal infection ultimately resolved during the subsequent three years. Neuro-infection caused by Nocardia should be considered in immunocompromised patients, and TMP-SMX is the preferred initial therapy; however, because of the high mortality rate, a long-term combination therapy with imipenem, cefotaxime, amikacin, and TMP-SMX is suggested. [ABSTRACT FROM AUTHOR]

Background/Aims: Risk factor studies for acute kidney injury (AKI) in China are lacking, especially those regarding non-traditional risk factors, such as laboratory indicators. Methods: All adult patients admitted to 38 tertiary and 22 secondary hospitals in China in any one month between July and December 2014 were surveyed. AKI patients were screened according to the Kidney Disease: Improving Global Outcomes’ definition of AKI. Logistic regression was used to analyze the risk factors for AKI, and Cox regression was used to analyze the risk of in-hospital mortality for AKI patients; additionally, a propensity score analysis was used to reconfirm the risk factors among laboratory indicators for mortality. Results: The morbidity of AKI was 0.97%. Independent risk factors for AKI were advancing age, male gender, hypertension, and chronic kidney disease. All-cause mortality was 16.5%. The predictors of mortality in AKI patients were advancing age, tumor, higher uric acid level and increases in Acute Physiologic Assessment and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores. The hazard ratio (HR) for mortality with uric acid levels > 9.1 mg/dl compared with ≤ 5.2 mg/dl was 1.78 (95% CI: 1.23 to 2.58) for the AKI patients as a group, and was 1.73 (95% CI: 1.24 to 2.42) for a propensity score-matched set. Conclusion: In addition to traditional risk factors, uric acid level is an independent predictor of all-cause mortality after AKI.

Abstract Background Acute kidney injury (AKI) places a heavy burden on the healthcare system in China and is usually misdiagnosed. However, there are limited studies that have described the epidemiology and diagnosis of AKI in China. The aim of this study was to describe the incidence and diagnosis of AKI in hospitalized adult patients in a tertiary teaching hospital in southeast China. Methods All adult patients hospitalized from October 1, 2013 to September 30, 2014 in the First Affiliated Hospital of Nanjing Medical University were screened using the Lab Administration Network. AKI definition and staging were based on the KDIGO AKI criteria. Demographic characteristics, laboratory examination, clinical data, and clinical outcomes of AKI patients were recorded and analyzed. Results The incidence of AKI was 1.6% (1401/87196). The 30-day mortality was 35.3%. AKI stage 1, 2, 3 and RRT accounted for 38.0% (532/1401), 22.0% (309/1401), 40.0% (560/1401), and 16.3% (228/1401) of patients, respectively. The Renal, other Internal Medicine, Surgery, and ICU Departments accounted for 7.4%, 37.1%, 30.1%, and 25.4% of AKI patients, respectively. The timely diagnosis rate, delayed diagnosis rate, and missed diagnosis rate were 44% (616/1401), 3.3% (46/1401), and 52.7% (739/1401), respectively. Patients hospitalized in the Renal Department had the highest AKI diagnosis rate (89.3%, 88/103), while missed diagnosis rate of the surgical patients was as high as 75.1% (317/422). Multivariable logistic regression analysis indicated that presence of tumors, higher serum albumin, and AKI stage 1 were associated with failure to timely diagnose AKI, whereas presence of chronic kidney disease, oliguria, higher blood urea nitrogen, and greater number of organ failures correlated with earlier diagnosis. Conclusions AKI was characterized by a high incidence, high short-term mortality, and high missed diagnosis rate in hospitalized adult patients in our hospital. Interventions for improving diagnosis of AKI are urgently needed.

Objective. Coronary slow/no reflow is not rare after successfully undergoing primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI), and shock index (SI) is an important factor for adverse cardiovascular prognosis. In this study, we are to explore whether SI is associated with coronary slow/no reflow in patients with AMI following primary PCI. Methods. A total of 153 consecutive AMI patients undergoing primary PCI within 24 hours of symptom onset were included in this study. The participants were divided into normal flow group (n=124) and slow/no reflow group (n=29) according to cineangiograms recorded during the period of PCI. Cardiovascular risk factors, hematologic parameters, preoperative management of antithrombotic therapy, and baseline angiography were collected. Results. SI, plasma glucose, white blood cells (WBC) and neutrophil count, neutrophil to lymphocyte ratio (PLR), high sensitivity C-reactive protein (hs-CRP), probrain natriuretic peptide (pro-BNP), and Killip classification on admission and thrombus burden on initial angiography were significantly different between patients with and without slow/no reflow. Multivariate analysis revealed that SI≥0.66, thrombus burden, and plasma glucose on admission were independent predictors for coronary slow/no reflow. Preoperative management of tirofiban therapy improves initial thrombolysis in myocardial infarction (TIMI). However, it has no effect on prognosis of slow/no reflow. Conclusion. Our findings demonstrated that slow/no reflow in patients with AMI following primary PCI was more likely associated with SI≥0.66, thrombus burden, and plasma glucose on admission. SI as a predictor for coronary slow/no reflow should be further confirmed in the following more large-scale and prospective studies. The clinical registration number is ChiCTR1900024447.

Objective This study was performed to explore the risk factors for hungry bone syndrome (HBS) and establish prediction equations for calcium supplementation after parathyroidectomy in hemodialysis patients with secondary hyperparathyroidism. Methods We retrospectively analyzed data from 252 hemodialysis patients undergoing successful total parathyroidectomy with autotransplantation. HBS was defined according to a minimum postoperative serum corrected calcium (PcCa) concentration of

Background/Aims: Cisplatin is widely used to treat malignancies. However, its major limitation is the development of dose-dependent nephrotoxicity. The precise mechanisms of cisplatin-induced kidney damage remain unclear. Previous study demonstrated the central role of mitochondrial ROS (mtROS) in the pathogenesis of cisplatin nephrotoxicity. The purpose of this study was to explore the mechanism of mtROS regulation in cisplatin nephrotoxicity. Methods: p53, MnSOD and p66shc were detected at mRNA and protein levels by qPCR and western blot in HK2 cells. mtROS levels were determined by DCFDA and MitoSOX staining. Cell viability and cell apoptosis were accessed by CCK-8 assay, TUNEL assay and flow cytometry, respectivesly. siRNAs were used to knock down p53 and p66shc expression and subsequent changes were observed. In vivo assays using a mouse model of cisplatin-induced acute kidney injury were used to validate the in vitro results. Results: In HK2 cells, cisplatin exposure decreased the MnSOD and increased the expression of p53 and p66shc. MnTBAP, a MnSOD mimic, blocked cisplatin-induced the generation of mtROS and cell injury. P66shc and p53 siRNAs rendered renal cells resistant to cisplatin-induced mtROS production and cell death. Furthermore, knockdown of p53 restored MnSOD and inhibiting p66shc. Consistent with these results, we revealed that p53 inhibitor reduced cisplatin-induced oxidative stress and apoptosis by regulating MnSOD and p66shc in the kidney of cisplatin-treated mice. Conclusion: Our study identifies activation of p53 signalling as a potential strategy for reducing the nephrotoxicity associated with cisplatin treatments and, as a result, broadens the therapeutic window of this chemotherapeutic agent.