Bulk and single-cell transcriptome profiling identify potential cellular targets of the long noncoding RNA Gas5 in renal fibrosis.

The long noncoding RNA growth arrest-specific 5 (lncRNA Gas5) is implicated in various kidney diseases. In this study, we investigated the lncRNA Gas5 expression profile and its critical role as a potential biomarker in the progression of chronic kidney disease. Subsequently, we assessed the effect of lncRNA Gas5 deletion on renal fibrosis induced by unilateral ureteral obstruction (UUO). The results indicated that loss of lncRNA Gas5 exacerbates UUO-induced renal injury and extracellular matrix deposition. Notably, the deletion of lncRNA Gas5 had a similar effect on control mice. The fibrogenic phenotype observed in mice lacking lncRNA Gas5 correlates with peroxisome proliferator-activated receptor (PPAR) signaling pathway activation and aberrant cytokine and chemokine reprogramming. Single-cell RNA sequencing analysis revealed key transcriptomic features of fibroblasts after Gas5 deletion, revealing heterogeneous cellular states suggestive of a propensity for renal fibrosis. Our findings indicate that lncRNA Gas5 regulates the differentiation and activation of immune cells and the transcription of key genes in the PPAR signaling pathway. These data offer novel insights into the involvement of lncRNA Gas5 in renal fibrosis, potentially paving the way for innovative diagnostic and therapeutic targets.

In-center Automated Peritoneal Dialysis: Clinical Features, Practice Patterns, and Patient Survival From a 6-year Cohort Study in China.

INTRODUCTION: In-center automated peritoneal dialysis (APD) has been more frequently adopted in clinical practice for maintenance PD patients in China. For a better understanding of its clinical uptake, this retrospective study reviewed incident PD patients for a period of 6 years, investigating the practice pattern of in-center APD, factors associated with the use of in-center APD, and report on the patient survival compared to the non-users of APD among hospitalised PD patients. METHODS: This was a cohort study of all incident PD patients who met the inclusion criteria from 2013/01/01 to 2018/09/30, and were followed until death, cessation of PD, loss to follow-up, or 2018/12/31. Clinical characteristics, patient outcomes, and detailed data on APD sessions were recorded. We used time-dependent Cox model to estimate the variables associated with the initiation of in-center APD, and marginal structural model through inverse probability weighting to adjust for time-varying APD use on the causal pathway to all-cause mortality. RESULTS: A total of 651 subjects over 17501 patient-months were enrolled. Of these, 633 (97.2%) PD patients were hospitalised at least once during follow-up, and 369 (56.7%) received in-center APD at a certain point, and the timing of APD use during the first 3 months, first year and first 2 years since PD inception were 14.8%, 45.4% and 74.8%, respectively. A total of 12553 in-center APD sessions were recorded, where 85.9% used 4 bags of 5L-exchanges per prescription. Time-dependent Cox model showed that diabetes (hazard ratio [HR], 1.39, 95% confidence interval [CI], 1.09-1.76), urine output (HR 0.80, 95% CI 0.70-0.92), serum albumin (HR 0.84, 95%CI 0.72-0.99), hemoglobin (HR 0.88, 95%CI 0.77-0.99), and Ca×P (HR 1.19, 95%CI 1.06-1.35) were significantly associated with in-center APD use. Among all hospitalised PD patients, the estimated hazard ratio corresponding to the marginal causal effect of in-center APD use on all-cause mortality is 0.13 (95% CI 0.05-0.31, P<0.001). Significant survival benefit (adjusted-HR 0.56, 95%CI 0.33-0.95) associated with starting APD after the first PD year was observed among in-center APD users. CONCLUSIONS: In-center APD is used intensively during the first 2 years of PD and is associated with certain clinical features. Over all a significant survival benefit of in-center APD use was observed.

Urokinase-based lock solutions for catheter salvage: A case of an upcoming kidney transplant recipient.

Catheter-related bloodstream infection (CRBSI) is a significant complication among patients on haemodialysis (HD) who are dependent on a central venous catheter (CVC) for an extended period. Catheter removal as first-line treatment can induce accelerated venous access site depletion in patients on HD who rely on it to survive. It is possible to retain the catheter in stable patients without septic syndrome while administering systemic antibiotics and antibiotic lock therapy. Herein, we report the case of a patient on HD with CRBSI who was successfully treated with intravenous levofloxacin- and urokinase-based antibiotic lock, without catheter removal prior to kidney transplantation. The use of urokinase in combination with antibiotics in lock solutions for treating catheter infections is rare. We verified the physical compatibility of levofloxacin and urokinase by visual inspection, turbidimetric measurements, and particle count. To our knowledge, this was a rare case demonstrating the effective use of urokinase and levofloxacin in a catheter lock for CRBSI in a patient on HD. Considering the need for highly concentrated antimicrobials and the availability of various antibiotics, the compatibility and stability of the lock solution is a matter of concern. Further studies are warranted to assess the stability and compatibility of various antibiotics in combination with urokinase.

The impact of long-term exposure to ambient air pollution in patients undergoing peritoneal dialysis: A cohort study in China.

There is increasing evidence for an association of air pollutants and the incidence of chronic kidney disease, and the progression to end stage kidney disease (ESKD). Despite the global expansion of peritoneal dialysis (PD), the impact of environmental and climatic factors in PD patients has not been studied in detail. We aimed to assess the association of long-term residential exposure to air pollutants, with patient survival and incidence of hospitalizations. This was a cohort study of all prevalent ESKD patients who were stable on PD therapy for more than 90 days in our PD center from 2013/01/01 to 2018/12/31. The enrolled patients were followed until death, cessation of PD, loss to follow-up, or 2018/12/31. Time-varying pollutant exposures were modeled as the key time-dependent variables. We used time-dependent Cox model to evaluate the risk of mortality and hospitalizations associated with air pollutant exposures adjusted for potential confounders. A total of 886 subjects who meets inclusion criteria with 27,024 patient-months were modeled. Over a mean follow-up of 30.5 ± 21.3 months, we ascertained 246 cases of death and 2611 cases of hospital admission. Significant hazard ratios (HRs) were observed for all four air pollutants including PM2.5 (hazard ratio [HR] 1.27, 95% confidence interval [95%CI] 1.05-1.54), PM10 (HR 1.31, 95%CI 1.04-1.65), NO2 (HR 1.45, 95%CI 1.02-2.06), and SO2 (HR 1.20, 95%CI 1.10-1.32) in fully adjusted model, corresponding to per interquartile range µg/m3 increase of air pollutant concentrations for mortality, and non-significant HRs for incidence of hospitalization. Non-linear associations with respect to different air pollutants were observed in models for all-cause mortality and recurrent hospitalization. The estimates for mortality were significantly higher in certain groups of patients. Our findings suggest long-term exposure to ambient air pollution was associated with higher risk of all-cause mortality in PD patients, but the association with incidence of hospitalizations was less clear.

Coexistence of primary biliary cirrhosis-autoimmune hepatitis overlap syndrome and membranous nephropathy: A case report.

Overlap syndrome is the combination of autoimmune liver diseases, and this term usually describes the coexistence of autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) in the same patient. Membranous nephropathy (MN) is the most common pattern of idiopathic nephrotic syndrome in patients without diabetes. The coexistence of PBC-AIH overlap syndrome and MN is very rare. Herein, the patient we describe exhibited large amounts of proteinuria and hepatic dysfunction nearly at the same time. We administered azathioprine to our patient. Fortunately, the patient demonstrated a good response to azathioprine, including a partial reduction in proteinuria from ~ 12.5 g/D to 2.62 g/D after 21 months of observation and the improvement of liver function. Our findings suggest that azathioprine may be a suitable treatment option for patients presenting with coexisting PBC-AIH overlap syndrome and MN.

Large vessel vasculitis with rare presentation of acute rhabdomyolysis: A case report and review of literature.

BACKGROUND: Musculoskeletal involvement in primary large vessel vasculitis (LVV), including giant cell arteritis and Takayasu's arteritis (TAK), tends to be subacute. With the progression of arterial disease, patients may develop polyarthralgia and myalgias, mainly involving muscle stiffness, limb/jaw claudication, cold/swelling extremities, etc. Acute development of rhabdomyolysis in addition to aortic aneurysm is uncommon in LVV. Herein, we report a rare case of LVV with the first presentation of acute rhabdomyolysis. CASE SUMMARY: A 70-year-old Asian woman suffering from long-term low back pain was hospitalized due to limb claudication, dark urine and an elevated creatine kinase (CK) level. After treatment with fluid resuscitation and antibiotics, the patient remained febrile. Her workup showed persistent elevated levels of inflammatory markers, and imaging studies revealed an aortic aneurysm. A decreasing CK was evidently combined with elevated inflammatory markers and negativity for anti-neutrophilic cytoplasmic antibodies. LVV was suspected and confirmed by magnetic resonance angiography and positron emission tomography with 18F-fluorodeoxyglucose/computed tomography. With a favourable response to immunosuppressive treatment, her symptoms resolved, and clinical remission was achieved one month later. However, after failing to follow the tapering schedule, the patient was readministered 25 mg/d prednisolone due to disease relapse. Follow-up examinations showed decreased inflammatory markers and substantial improvement in artery lesions after 6 mo of treatment. At the twelve-month follow-up, she was clinically stable and maintained on corticosteroid therapy. CONCLUSION: An exceptional presentation of LVV with acute rhabdomyolysis is described in this case, which exhibited a good response to immunosuppressive therapy, suggesting consideration for a differential diagnosis when evaluating febrile patients with myalgia and elevated CK. Timely use of high-dose steroids until a diagnosis is established may yield a favourable outcome.

Reversal of hepatorenal syndrome and kidney recovery: When renal has more to offer.

Hepatorenal syndrome (HRS) is one of the most severe complications in advanced cirrhosis. Type-1 HRS is relatively uncommon, yet carries considerably higher mortality rate. Effective treatment for HRS, especially therapy towards survival benefits, is still limited. However, the role for dialysis in HRS has been questioned over the years. The initiation of dialysis remains controversial for those who aren't transplant candidates. Meanwhile, there's a growing attention towards the successful use of peritoneal dialysis (PD) in cirrhotic patients. Herein, we report a case of HRS-1 in a 76-year-old male patient with decompensated cirrhosis. Through a series of adjustments of hemodialysis regimens and pharmacological prescriptions, patient stabilized and the opportunity for transjugular intrahepatic portosystemic shunt (TIPS) insertion was gained. PD was initiated after TIPS placement. With a gradual decrease of dialysis dose, patient successfully weaned off PD and achieved both reversal of HRS and kidney recovery. Markedly improved nutritional status and quality of life were reported. The potential role of dialysis and TIPS in HRS may be worth revisiting. Further studies regarding the optimal timing of dialysis initiation, choices of dialysis modality, and efficacy of dialysis therapy in combination with TIPS in HRS patients are warranted.

Xiaoyu Xiezhuo Drink Protects against Ischemia-Reperfusion Acute Kidney Injury in Aged Mice through Inhibiting the TGF-ß1/Smad3 and HIF1 Signaling Pathways.

Acute kidney injury (AKI) is responsible for significant mortality among hospitalized patients that is especially troubling aged people. An effective self-made Chinese medicine formula, Xiaoyu Xiezhuo Drink (XXD), displayed therapeutic effects on AKI. However, the compositions and underlying mechanisms of XXD remain to be elucidated. In this study, we used the ultra-high-performance liquid chromatography method coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) to investigate the chemical components in XXD. Then, the absorbable components of XXD were identified based on the five principles and inputted into the SwissTargetPrediction and STITCH databases to identify the drug targets. AKI-related targets were collected from the GenCLiP 3, GeneCards, and DisGeNET databases. The crossover genes of XXD and AKI were identified for functional enrichment analysis. The protein-protein interaction (PPI) network of crossover genes was constructed, followed by the identification of hub genes. Subsequently, the effects and potential mechanisms of XXD on AKI predicted by the network pharmacology and bioinformatics analyses were experimentally validated in ischemia-reperfusion (I/R) injury-induced AKI aged mouse models. A total of 122 components in XXD were obtained; among them, 58 components were found that could be absorbed in the blood. There were 800 potential drug targets predicted from the 58 absorbable components in AKI which shared 36 crossover genes with AKI-related targets. The results of functional enrichment analysis indicated that crossover genes mostly associated with the response to oxidative stress and the HIF1 signaling pathway. In the PPI network analysis, 12 hub genes were identified, including ALB, IL-6, TNF, TP53, VEGFA, PTGS2, TLR4, NOS3, EGFR, PPARG, HIF1A, and HMOX1. In AKI aged mice, XXD prominently alleviated I/R injury-induced renal dysfunction, abnormal renal pathological changes, and cellular senescence, inflammation, and oxidative damage with a reduction in the expression level of the inflammatory mediator, α-SMA, collagen-1, F4/80, TP53, VEGFA, PTGS2, TLR4, NOS3, EGFR, PPARG, HIF1A, ICAM-1, TGF-ß1, Smad3, and p-Smad3 and an increase of nephridial tissue p-H3, Ki67, HMOX1, MMP-9, and Smad7 levels. In summary, our findings suggest that XXD has renoprotective effects against AKI in aged mice via inhibiting the TGF-ß1/Smad3 and HIF1 signaling pathways.

Yi-Qi-Jian-Pi-Xiao-Yu-Xie-Zhuo Formula Improves Muscle Atrophy via Modulating the IGF-1/PI3K/Akt Signaling Pathway in 5/6 Nephrectomized Rats.

The Yi-Qi-Jian-Pi-Xiao-Yu-Xie-Zhuo (YQJPXYXZ) formula has been used for treating chronic kidney disease (CKD) for many years with good efficiency based on the cumulative empirical experience of previous practitioners. Impairment of the IGF-1/PI3K/Akt signaling pathway plays an important role in mediating muscle wasting. This study aimed to observe effects of the YQJPXYXZ formula on muscle atrophy in CKD rats and investigate its possible mechanism on regulation of the IGF-1/PI3K/Akt signaling pathway. The 5/6 nephrectomized rats were randomly allocated into 3 groups: the CKD group, the KT (compound α-ketoacid tablets) group, and the YQJPXYXZ group. Besides, sham-operated rats were included as the sham group. All rats were treated for 12 weeks. Results showed that administration of the YQJPXYXZ formula prevented body weight loss and muscle fiber size decrease. Moreover, the YQJPXYXZ formula increased the IGF-1 level of serum and skeletal muscle in CKD rats and enhanced the phosphorylation level of Akt. Furthermore, the YQJPXYXZ formula decreased the Atrogin1 and MuRF1 mRNA and MuRF1 proteins. In conclusion, our data demonstrated that the YQJPXYXZ formula improves muscle wasting in CKD rats, which might be associated with the modulation of the IGF-1/PI3K/Akt signaling pathway and inhibition of the ubiquitin-proteasome system (UPS).

Infection Control Precautions and Care Delivery in Hemodialysis Unit during Coronavirus Disease 2019 Outbreak: A Case Series.

BACKGROUND: With an estimated basic reproductive number of 3.77, the Coronavirus Disease 2019 (COVID-19) continues to spread. It is urgent to exert adequate efforts for the management of dialysis patients, caregivers, and healthcare personnel (HCP). This study aimed at reporting practical workflow, identification of high-risk or suspected cases of CO-VID-19, and subsequent response measures. METHODS: At the time of the COVID-19 outbreak, precautions and practice protocols were applied in our dialysis units (DUs). This single-center study retrospectively reviewed all high-risk/suspected cases from January 23, 2020, to February 10, 2020. Epidemiological, clinical feature, and detailed data on all cases were recorded. RESULTS: Practical workflow for the clinical management of dialysis patients, caregivers, and HCP was initiated. A total of 6 high-risk/suspected cases were identified. Female gender, older age, presence of cardiovascular disease, diabetes, anuresis, immunocompromised status, hypoalbuminemia, and underweight were noticeable features in these cases. Direct evidence of infection or epidemiological risk was detected in five cases. Close monitoring for temperature and oxygen saturation during hemodialysis sessions may be reasonable. No confirmed COVID-19 cases were reported in our DU, but certain cases showed rapid deterioration due to other critically severe condition needing hospitalization. Portable dialysis machines are of great need to ensure dialysis care provision. CONCLUSIONS: Our study described a practical workflow for patient-centered management during COVID-19 outbreak. Potential risk factors and underlying clinical patterns were reported. Further studies regarding the efficacy of infection control precautions and practice protocols tailored for dialysis settings are warranted.

Efficacy and safety of anti-viral therapy for Hepatitis B virus-associated glomerulonephritis: A meta-analysis.

OBJECTIVES: To assess the potency of anti-viral treatment for hepatitis B virus-associated glomerulonephritis (HBV-GN). Method: We searched for controlled clinical trials on anti-viral therapy for HBV-GN in MEDLINE, Embase, the Cochrane Library, and PubMed from inception to March 11th 2019. Seven trials, including 182 patients met the criteria for evaluating. The primary outcome measures were proteinuria and changes in the estimated glomerular filtration rate, and the secondary outcome measure was hepatitis B e-antigen clearance. A fixed or random effect model was established to analyze the data. Subgroup analyses were performed to explore the effects of clinical trial type, anti-viral drug type, age, and follow-up duration. RESULTS: The total remission rate of proteinuria (OR = 10.48, 95% CI: 4.60-23.89, I2 = 0%), complete remission rate of proteinuria (OR = 11.64, 95% CI: 5.17-26.21, I2 = 23%) and clearance rate of Hepatitis Be Antigen (HBeAg) were significantly higher in the anti-viral treatment group than in the control group (OR = 27.08, 95% CI: 3.71-197.88, I2 = 63%). However, antiviral therapy was not as effective regarding the eGFR (MD = 5.74, 95% CI: -4.24-15.73). In the subgroup analysis, age and drug type had significant impacts on proteinuria remission, and study type and follow-up duration only slightly affected the heterogeneity. CONCLUSION: Antiviral therapy induced remission of proteinuria and increased HBeAg clearance but failed to improve the eGFR. Pediatric patients were more sensitive to antiviral therapy than adults. IFNs seem more effective but are accompanied by more adverse reactions than NAs.

Fungal peritonitis in peritoneal dialysis: 5-year review from a North China center.

PURPOSE: Fungal peritonitis (FP) is a rare but devastating complication in peritoneal dialysis (PD), accounting for high rates of technique failure, morbidity and mortality. This study was conducted to investigate FPs with regard to peritonitis rate, microbiology testing, patient characteristics, clinical features, antifungal treatments, and clinical outcomes in patients on PD. METHODS: This single-center study retrospectively reviewed all FP episodes diagnosed from June 1, 2012 to June, 2017. All FPs were matched in a 1:5 ratio with PD patients diagnosed with bacterial peritonitis. Clinical, biochemical characteristics and detailed data on peritonitis episodes were recorded. RESULTS: Eleven fungal peritonitis episodes (rate of 0.0067 episodes per patient-year on dialysis) were identified. All FPs were caused by Candida species (identification and antifungal susceptibility testing were performed with VITEK 2® compact system), including C. albicans (6/11), C. parapsilosis (4/11) and C. krusei (1/11). Except C. krusei, no Candida resistance to fluconazole was detected. Compared to bacterial peritonitis (matched cases, n = 55), FP group showed higher rate of previous antibiotic use (p = 0.002), higher total effluent cell count (p = 0.007), and lower serum albumin (p = 0.01), higher rate of infection-related surgery (p < 0.001), HD transfer (p = 0.001), and all-cause death (p = 0.006). High prevalence (≥ 50%) of female gender, anuria, CCI ≥ 4, hypoalbuminemia, anemia, and hypokalemia were also observed in FP patients. More than half of the FP patients presented gastrointestinal symptoms (7/11) and extraperitoneal infection (6/11). Eight (72.7%) patients had catheter surgically removed with a median 5.5 lag days, four (36.4%) patients died within 3 months and six (54.5%) cases led to technique failure. CONCLUSIONS: FP results in high rates of catheter loss and all-cause mortality in 3 months of follow-up, candida species were the commonest pathogens in our center. Variations of clinical features and susceptibility patterns were observed. Gastrointestinal disorders maybe a potential risk factor for FP.

Peritonitis: Episode Sequence, Microbiological Variation, Risk Factors and Clinical Outcomes in a North China Peritoneal Dialysis Center.

BACKGROUND/AIMS: This study investigated peritonitis episodes with regard to time sequence, microbiological variation, factors associated with peritonitis and clinical outcomes in peritoneal dialysis (PD) patients. METHODS: This single-center cohort study enrolled all incident patients who met the inclusion criteria at our center from June 1, 2012 to June 30, 2015 and who were followed until June, 2017. Clinical, biochemical characteristics and detailed data on peritonitis episodes, and hospitalizations were recorded. RESULTS: A total of 218 episodes of peritonitis corresponding to a rate of 0.27 episode per patient-year were recorded. Gram positive bacteria, identified in 115 (52.8%) episodes, were the most common pathogens. The occurrence of enterococcus peritonitis increased from 15.1% of the first to 27.3% of the later episodes. Multivariate logistic regression showed that the presence of cardiovascular disease (CVD, odds ratio [OR] 2.177, 95% confidence interval [95%CI] 1.214-3.903, P=0.009), age≤ 55 (OR 2.282, 95%CI 1.062-4.906, P=0.035), non-independent operator (OR 0.440, 95%CI 0.206-0.938, P=0.034), lower values of potassium (OR=0.671,95%CI 0.472-0.954, P=0.026) and higher values of calcium-phosphate product (OR 1.410, 95%CI 1.065-1.868, P=0.017) were associated with peritonitis. Besides CVD (risk ratio [RR] 2.591, 95%CI 1.893-3.543, P< 0.001) and non-independent operator (RR 0.583, 95%CI 0.439-0.776, P< 0.001), a lower level of education (RR 0.641, 95%CI 0.487-0.842, P=0.001) was associated with higher peritonitis rates in log-linear analysis. Spearman analyses indicated that the time to the 1st episode was negatively related to the peritonitis rate (r=-0.291, P=0.001). Time-dependent Cox regression showed no association between the time to the 1st episode and patient survival (P=0.151). Patients with a high peritonitis rate (HPR) demonstrated worse technique survival (P< 0.001). CONCLUSION: The present study has revealed several center-based features and modifiable risk factors for peritonitis. The presence of CVD and the need for assistance with PD operation not only increased the odds of peritonitis but were also associated with more peritonitis episodes. Time to first peritonitis was related to the peritonitis rate but not associated with patient survival. Patients with HPR had worse technique survival.

Probiotics, prebiotics and synbiotics for chronic kidney disease: protocol for a systematic review and meta-analysis.

INTRODUCTION: There is a growing interest in probiotic, prebiotic and synbiotic supplements for patients with chronic kidney disease (CKD). However, a systematic review and evaluation is lacking. The purpose of the present study is to assess the efficacy and safety of probiotics, prebiotics and synbiotics for non-dialysis or non-renal transplant patients with CKD. METHODS AND ANALYSIS: An extensive literature search will be undertaken to identify potentially eligible studies from electronic databases including PubMed (1946 to present), EMBASE (1974 to present), Web of Science (1900 to present) and the Cochrane Central Register of Controlled Trials (CENTRAL, all years). No language restriction will be applied to the search. Both parallel and crossover randomised controlled trials will be included. The risk of bias of each included study will be assessed using the Cochrane Risk of Bias Tool. The primary outcome measures are uraemic toxins. Secondary outcomes include kidney function, adverse cardiovascular events, all-cause mortality, cause-specific death, progression to end-stage kidney disease, quality of life, gastrointestinal function and adverse events. Data will be synthesised using appropriate statistical methods. The quality of evidence for each outcome will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: No ethical approval is required as no primary data will be collected. We will publish findings from this systematic review in a peer-reviewed scientific journal, and the data set will be made freely available. PROSPERO REGISTRATION NUMBER: CRD42017079177.