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1.
J Clin Med ; 13(13)2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38999366

ABSTRACT

Backgrounds and Aims: Patients with cirrhosis are susceptible to sepsis and septic shock. Cirrhotic patients also have increased capillary permeability and are prone to developing volume overload. Patients with septic shock may have an enhanced pulmonary vascular permeability index (PVPI) and extravascular lung water index (EVLWI), both of which are associated with an unfavorable prognosis. It is plausible that pre-existing hyperpermeability may deteriorate when cirrhotic patients develop septic shock. However, it remains unknown whether PVPI and EVLWI can predict the prognosis of cirrhotic patients with septic shock. Pulse Indicator Continuous Cardiac Output (PiCCO) is an established tool to measure PVPI and EVLWI. Therefore, we conducted this retrospective study to investigate the prognostic significance of PVPI and EVLWI in cirrhotic patients with septic shock using PiCCO monitoring. Methods: We included 83 patients with liver cirrhosis and septic shock. EVLW indexed to actual body weight (aEVLWI), EVLW indexed to predicted body weight (pEVLWI), PVPI, disease severity scores, and other biomarkers were analyzed. We collected the PiCCO data on the first 2 days. Results: The overall 28-day mortality was 43.4%. The values of PVPI, aEVLWI, and pEVLWI on day 2 (PVPID2, aEVLWID2, EVLWID2) were significantly higher in non-survivors. The discriminating power of PVPID2 and EVLWID2 to predict 28-day mortality was tested using the area under a ROC curve. The areas under ROC curves (mean ± SEM) were 0.713 ± 0.061 and 0.650 ± 0.063 for PVPID2 and pEVLWID2. In the multivariate analysis, PVPID2, bilirubin, and lactate were independent factors which predicted 28-day mortality. Conclusions: Higher levels of PVPID2 and pEVLWID2 are associated with higher 28-day mortality rates in cirrhotic patients with septic shock. PVPI and pEVLWI may be useful to guide fluid management in this clinical setting.

2.
Ther Clin Risk Manag ; 20: 437-447, 2024.
Article in English | MEDLINE | ID: mdl-39040852

ABSTRACT

Background: Listeriosis is caused by the facultative anaerobic bacterium Listeria monocytogenes. Infection from Listeria-contaminated food or water is the main etiology. If Listeria travels outside the intestines, it can cause invasive listeriosis, such as sepsis, meningitis, and meningoencephalitis. Invasive illness is especially dangerous for pregnant women and their newborns, elderly people, and people with compromised immune systems or medical conditions such as end-stage kidney disease (ESKD) patients receiving long-term dialysis. Purpose: Describe the manifestations and hospital outcomes of invasive listeriosis and identify the risk factors for in-hospital and one-year mortality in ESKD patients receiving long-term dialysis. Patients and Methods: This retrospective observational study examined hospitalized patient records at a Taiwanese tertiary medical center from August 1, 2000, to August 31, 2021. ESKD patients on chronic dialysis were identified with invasive listeriosis by blood culture and discharge diagnosis. Over 21 years, we accurately recorded 26 cases. Results: ESKD patients on chronic dialysis with invasive listeriosis have a poor prognosis. Only 53.8% of chronic dialysis patients with invasive listeriosis survived their first hospital episode. 42.3% of hospitalized ESKD patients with invasive listeriosis survived one year later. In univariate analysis, shock, tachypnea (RR ≥ 22), respiratory failure, qSOFA score ≥ 2, and lower initial platelet count were linked to greater in-hospital mortality rates. Conclusion: ESKD patients with invasive listeriosis have a grave prognosis. Our research reveals that an early blood sample for a bacterial culture may identify invasive listeriosis in chronic dialysis patients with fever, nausea or vomiting, confusion, and respiratory distress. This study is the first to identify a lower platelet count and qSOFA score ≥ 2 as markers of high-risk invasive listeriosis in ESKD patients.

3.
J Formos Med Assoc ; 2024 May 21.
Article in English | MEDLINE | ID: mdl-38777672

ABSTRACT

Kidney transplant recipients have an increased risk of cytomegalovirus (CMV) infection and disease. A strategy for mitigating the risk of CMV infection in kidney transplant recipients has not yet been established in Taiwan. The Transplantation Society of Taiwan aimed to develop a consensus by expert opinion on the prevention and management of CMV infection. Based on the results of Consensus Conference, we suggested low-dose valganciclovir prophylaxis (450 mg once daily) for kidney transplant recipients. The prophylaxis duration was ≥6 months for high-risk (D+/R-) patients and 3 months for moderate-risk (R+) patients. Even for low-risk (D-/R-) patients, prophylaxis for at least 3 months is recommended because of the high seroprevalence of CMV in Taiwan. CMV prophylaxis was suggested after anti-thymocyte globulin treatment but not after methylprednisolone pulse therapy. Routine surveillance after prophylaxis, secondary prophylaxis after CMV disease treatment, and mTOR inhibitors for primary CMV prophylaxis were not recommended. Letermovir and marabavir are emerging CMV agents used for prophylaxis and refractory CMV disease. CMV immunoglobulins have been used to treat refractory CMV disease in Taiwan. We hope this consensus will help professionals manage patients with CMV in Taiwan to improve the quality of care.

4.
Transplant Proc ; 56(3): 742-745, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38519267

ABSTRACT

BACKGROUND: Numerous successful pregnancy outcomes have been reported after kidney transplantation, but until now, there have been no reports of healthy twin deliveries through in vitro fertilization treatment in high-gestation aged women with a long post-transplant duration. In our report, we present a case of a high-gestation aged kidney transplant recipient who successfully delivered healthy twins with the aid of in vitro fertilization. CASE PRESENTATION: At the age of 29, a woman with end-stage kidney disease caused by immunoglobin A nephropathy underwent kidney transplantation. She had a history of premature ovarian failure and had been on continuous ambulatory peritoneal dialysis since the age of 18. Eleven years after starting dialysis, she received a cadaveric kidney transplant. Despite being infertile for 7 years after transplantation, she wished to have children. In vitro fertilization embryo transfer was conducted after failure of ovarian stimulation, considering her age and premature ovarian failure. The patient successfully delivered twins at 29 weeks gestation via cesarean section, as the first fetus presented in breech position. The first newborn weighed 945 g and the second weighed 855 g, with no other congenital abnormalities found. One year after childbirth, neither the recipient nor her babies experienced any fatal complications. CONCLUSIONS: A woman who underwent kidney transplantation and has stage 3 CKD may successfully deliver healthy twins through in vitro fertilization embryo transfer, even if she is of advanced maternal age and has a long post-transplant period. However, there is a risk of preterm premature rupture of membrane in such cases.


Subject(s)
Fertilization in Vitro , Kidney Transplantation , Humans , Female , Pregnancy , Adult , Pregnancy, Twin , Pregnancy Outcome , Kidney Failure, Chronic/surgery , Embryo Transfer
5.
Aging (Albany NY) ; 16(5): 4236-4249, 2024 02 21.
Article in English | MEDLINE | ID: mdl-38385990

ABSTRACT

BACKGROUND AND HYPOTHESIS: Pruritus is a common and distressing symptom that affects patients with chronic kidney disease. The concentration of protein bounded uremic toxin was associated with the uremic pruritus. The aim is to assess the efficacy of AST-120 for uremic pruritus in hemodialysis patients. MATERIALS AND METHODS: The participants were enrolled and then divided into the AST-120 treatment group and control group with a ratio of 2:1. All participants underwent pre-observation screenings two weeks before the study with three visits. In the treatment phase (week 1 to week 4), the treatment group added 6g/day of AST-120 along with routine anti-pruritic treatment. Visual analog scale (VAS) and biochemical parameters were measured. RESULTS: The VAS score began to be lower in the AST-120 treatment group after the 5th visiting (p < 0.05). The reduction in indoxyl sulfate (IS) at 5th week along with TNF-alpha. The reduction ratio of indoxyl sulfate correlated with reduction of parathyroid hormone. CONCLUSION: This study has demonstrated that the four-week treatment of AST-120 decreased the severity of uremic pruritus in patients with ESRD. The concentration of IS and TNF-alpha decreased in the AST-120 treatment group. The reduction of iPTH correlated with the reduction of IS in the AST-120 treatment.


Subject(s)
Carbon , Indican , Oxides , Uremia , Humans , Uremia/complications , Uremia/metabolism , Cytokines , Tumor Necrosis Factor-alpha , Renal Dialysis/adverse effects , Pruritus/drug therapy , Pruritus/etiology
6.
Microbes Infect ; 26(4): 105299, 2024.
Article in English | MEDLINE | ID: mdl-38224944

ABSTRACT

This study aimed to develop aptamers targeting LipL32, a most abundant lipoprotein in pathogenic Leptospira, to hinder bacterial invasion. The objectives were to identify high-affinity aptamers through SELEX and evaluate their specificity and inhibitory effects. SELEX was employed to generate LipL32 aptamers (L32APs) over 15 rounds of selection. L32APs' binding affinity and specificity for pathogenic Leptospira were assessed. Their ability to inhibit LipL32-ECM interaction and Leptospira invasion was investigated. Animal studies were conducted to evaluate the impact of L32AP treatment on survival rates, Leptospira colonization, and kidney damage. Three L32APs with strong binding affinity were identified. They selectively detected pathogenic Leptospira, sparing non-pathogenic strains. L32APs inhibited LipL32-ECM interaction and Leptospira invasion. In animal studies, L32AP administration significantly improved survival rates, reduced Leptospira colonies, and mitigated kidney damage compared to infection alone. This pioneering research developed functional aptamers targeting pathogenic Leptospira. The identified L32APs exhibited high affinity, pathogen selectivity, and inhibition of invasion and ECM interaction. L32AP treatment showed promising results, enhancing survival rates and reducing Leptospira colonization and kidney damage. These findings demonstrate the potential of aptamers to impede pathogenic Leptospira invasion and aid in recovery from Leptospira-induced kidney injury (190 words).


Subject(s)
Aptamers, Nucleotide , Bacterial Outer Membrane Proteins , Leptospira , Leptospirosis , Lipoproteins , SELEX Aptamer Technique , Animals , Mice , Aptamers, Nucleotide/pharmacology , Bacterial Outer Membrane Proteins/metabolism , Bacterial Outer Membrane Proteins/genetics , Disease Models, Animal , Kidney/microbiology , Kidney/pathology , Leptospira/drug effects , Leptospira/pathogenicity , Leptospira/metabolism , Leptospirosis/microbiology , Leptospirosis/drug therapy , Lipoproteins/antagonists & inhibitors , Lipoproteins/metabolism
7.
Perit Dial Int ; 44(2): 141-144, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37905306

ABSTRACT

Encapsulating peritoneal sclerosis (EPS) is a rare and potentially fatal complication of long-term peritoneal dialysis (PD). EPS-induced large volume and recurrent ascites represents a challenging condition. We report a 51-year-old man with kidney failure treated with PD for 13 years who eventually developed early stage of EPS accompanied with poor intake and recurrent ascites. After management including discontinuing PD and switching to haemodialysis, as well as oral steroids and tamoxifen administration, the patient had refractory ascites. An intervention of weekly intraperitoneal steroid infusion with methylprednisolone was implemented for a year. Gradually, we observed a reduction in ascites drainage, an improvement of clinical symptoms and the patient's nutritional status. The PD catheter was successfully removed as there was no recurrence of ascites. Intraperitoneal corticosteroid administration represents a new intervention for patients with early stage of EPS and recurrent ascites after PD cessation.


Subject(s)
Peritoneal Dialysis , Peritoneal Fibrosis , Male , Humans , Middle Aged , Peritoneal Dialysis/adverse effects , Peritoneal Fibrosis/diagnosis , Peritoneal Fibrosis/drug therapy , Peritoneal Fibrosis/etiology , Ascites/drug therapy , Ascites/etiology , Renal Dialysis/adverse effects , Steroids , Sclerosis/complications
8.
Biomed J ; : 100682, 2023 Dec 06.
Article in English | MEDLINE | ID: mdl-38065365

ABSTRACT

INTRODUCTION: BK Polyomavirus (BKPyV) infection is a common complication in kidney transplant recipients and can result in poor outcome and graft failure. Currently, there is no known effective antiviral agent. This study investigated the possible antiviral effects of Interferon alpha (IFNα) and its induced protein, MxA, against BKPyV. METHODS: In vitro cell culture experiments were conducted using human primary renal proximal tubular epithelial cells (HRPTECs). We also did animal studies using Balb/c mice with unilateral kidney ischemic reperfusion injury. RESULTS: Our results demonstrated that IFNα effectively inhibited BKPyV in vitro and murine polyomavirus in animal models. Additionally, IFNα and MxA were found to suppress BKPyV TAg and VP1 production. Silencing MxA attenuated the antiviral efficacy of IFNα.We observed that MxA interacted with BKPyV TAg, causing it to remain in the cytosol and preventing its nuclear translocation. To determine MxA's essential domain for its antiviral activities, different mutant MxA constructs were generated. The MxA mutant K83A retained its interaction with BKPyV TAg, and its antiviral effects were intact. The MxA T103A mutant, on the other hand, abolished GTPase activity and lost its protein-protein interaction with BKPyV TAg, and lost its antiviral effect. CONCLUSION: IFNα and its downstream protein, MxA, have potent antiviral properties against BKPyV. Furthermore, our findings indicate that the interaction between MxA and BKVPyV TAg plays a crucial role in determining the anti-BKPyV effects of MxA.

9.
Virus Res ; 336: 199220, 2023 Oct 15.
Article in English | MEDLINE | ID: mdl-37689160

ABSTRACT

Recent studies have suggested that BK polyomavirus (BKPyV) may be associated with the development of urothelial carcinoma. In Merkel cell carcinoma, TAg and tAg are the major viral proteins of Merkel cell polyomavirus with oncogenic potential. In this study, we aimed to distinguish the role of TAg and tAg in cell migration. Our result demonstrated that ERK was phosphorylated in human renal tubular cells expressing its TAg and tAg after BKPyV infection. Treatment with the ERK inhibitor U0126 suppressed BKPyV gene expression and reduced BKPyV replication. Both TAg and tAg induced cell migration via ERK-dependent signaling. Furthermore, the expression of TAg and tAg had a significant regulatory effect on focal adhesion molecules in renal proximal tubular cells, which strongly suggests that alterations in the focal adhesion complexes are critically involved in TAg and tAg-induced cell migration. Gelatin zymography profiling revealed that TAg regulates the expression and activity of MMP-2 and MMP-9, but not tAg. Interestingly, TAg regulates the expression and activity of MMP-9 through ERK signaling, whereas MMP-2 is regulated through an ERK-independent pathway. Unbalanced ERK pathway activity is frequently observed in many cancers, while MMP proteins are usually overexpressed in aggressive tumors. These findings support the view that BKPyV is an oncogenic virus.

10.
Medicina (Kaunas) ; 59(6)2023 May 24.
Article in English | MEDLINE | ID: mdl-37374218

ABSTRACT

Background and Objectives: In peritoneal dialysis (PD) therapy, intra-abdominal adhesions (IAAs) can cause catheter insertion failure, poor dialysis function, and decreased PD adequacy. Unfortunately, IAAs are not readily visible to currently available imaging methods. The laparoscopic approach for inserting PD catheters enables direct visualization of IAAs and simultaneously performs adhesiolysis. However, a limited number of studies have investigated the benefit/risk profile of laparoscopic adhesiolysis in patients receiving PD catheter placement. This retrospective study aimed to address this issue. Materials and Methods: This study enrolled 440 patients who received laparoscopic PD catheter insertion at our hospital between January 2013 and May 2020. Adhesiolysis was performed in all cases with IAA identified via laparoscopy. We retrospectively reviewed data, including clinical characteristics, operative details, and PD-related clinical outcomes. Results: These patients were classified into the adhesiolysis group (n = 47) and the non-IAA group (n = 393). The clinical characteristics and operative details had no remarkable between-group differences, except the percentage of prior abdominal operation history was higher and the median operative time was longer in the adhesiolysis group. PD-related clinical outcomes, including incidence rate of mechanical obstruction, PD adequacy (Kt/V urea and weekly creatinine clearance), and overall catheter survival, were all comparable between the adhesiolysis and non-IAA groups. None of the patients in the adhesiolysis group suffered adhesiolysis-related complications. Conclusions: Laparoscopic adhesiolysis in patients with IAA confers clinical benefits in achieving PD-related outcomes comparable to those without IAA. It is a safe and reasonable approach. Our findings provide new evidence to support the benefits of this laparoscopic approach, especially in patients with a risk of IAAs.


Subject(s)
Laparoscopy , Peritoneal Dialysis , Humans , Retrospective Studies , Catheters, Indwelling , Renal Dialysis , Peritoneal Dialysis/adverse effects , Laparoscopy/adverse effects , Laparoscopy/methods , Peritoneum
11.
Biomed J ; 46(4): 100595, 2023 08.
Article in English | MEDLINE | ID: mdl-37142093

ABSTRACT

Leptospirosis is a neglected bacterial disease caused by leptospiral infection that carries a substantial mortality risk in severe cases. Research has shown that acute, chronic, and asymptomatic leptospiral infections are closely linked to acute and chronic kidney disease (CKD) and renal fibrosis. Leptospires affect renal function by infiltrating kidney cells via the renal tubules and interstitium and surviving in the kidney by circumventing the immune system. The most well-known pathogenic molecular mechanism of renal tubular damage caused by leptospiral infection is the direct binding of the bacterial outer membrane protein LipL32 to toll-like receptor-2 expressed in renal tubular epithelial cells (TECs) to induce intracellular inflammatory signaling pathways. These pathways include the production of tumor necrosis factor (TNF)-α and nuclear factor kappa activation, resulting in acute and chronic leptospirosis-related kidney injury. Few studies have investigated the relationship between acute and chronic renal diseases and leptospirosis and further evidence is necessary. In this review, we intend to discuss the roles of acute kidney injury (AKI) to/on CKD in leptospirosis. This study reviews the molecular pathways underlying the pathogenesis of leptospirosis kidney disease, which will assist in concentrating on potential future research directions.


Subject(s)
Acute Kidney Injury , Leptospira , Leptospirosis , Renal Insufficiency, Chronic , Humans , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/pathology , Kidney/microbiology , Kidney/pathology , Leptospira/metabolism
12.
Genomics ; 115(3): 110624, 2023 05.
Article in English | MEDLINE | ID: mdl-37062365

ABSTRACT

Leptospirosis can cause chronic kidney damage, putting patients at risk of additional kidney injury due to other factors that can lead to renal failure. To understand the combined effect, the transcriptome profiles of kidneys of mice with adenine-induced and chronically Leptospira-infected kidneys were analysed. Chronic inflammation and T-helper 17 immune responses were activated and a high-level expression of Indoleamine 2,3-dioxygenase 1 protein was found. The results indicate that the combination may predispose patients to chronic inflammation, kidney function disruption, and symptoms seen in progressive chronic kidney disease (CKD). Furthermore, immunometabolic regulation may contribute to renal injury caused by chronic leptospirosis with secondary nephrotoxic injury. This study identified several significantly disrupted genes that could serve as potential targets for the diagnosis or treatment of CKD. Our work provides insight into the combined effect of leptospirosis and secondary kidney damage and the molecular basis for rapid progression of CKD.


Subject(s)
Anti-Infective Agents , Leptospirosis , Renal Insufficiency, Chronic , Animals , Mice , Transcriptome , Leptospirosis/complications , Kidney , Renal Insufficiency, Chronic/complications , Inflammation
13.
Biosensors (Basel) ; 13(1)2023 Jan 03.
Article in English | MEDLINE | ID: mdl-36671916

ABSTRACT

Developing ultraflexible sensors using metal oxides is challenging due to the high-temperature annealing step in the fabrication process. Here, we demonstrate the ultraflexible relative humidity (RH) sensor on food plastic wrap by using 808 nm near-infrared (NIR) laser annealing for 1 min at a low temperature (26.2-40.8 °C). The wettability of plastic wraps coated with sol-gel solution is modulated to obtain uniform films. The surface morphology, local temperature, and electrical properties of the SnO2 resistor under NIR laser irradiation with a power of 16, 33, and 84 W/cm2 are investigated. The optimal device can detect wide-range RH from 15% to 70% with small incremental changes (0.1-2.2%). X-ray photoelectron spectroscopy reveals the relation between the surface binding condition and sensing response. Finally, the proposed sensor is attached onto the face mask to analyze the real-time human breath pattern in slow, normal, and fast modes, showing potential in wearable electronics or respiration monitoring.


Subject(s)
Electronics , Oxides , Humans , Humidity , Monitoring, Physiologic , Plastics
14.
Ren Fail ; 45(1): 2153064, 2023 Dec.
Article in English | MEDLINE | ID: mdl-36632795

ABSTRACT

INTRODUCTION: Tuberculous peritonitis (TBP) is a rare but fatal complication in patients on peritoneal dialysis (PD). In this study, we aimed to determine the demographic features, clinical features, laboratory parameters, and clinical outcomes of PD patients with TBP and to clarify possible risk factors for mortality. MATERIALS AND METHODS: We retrospectively reviewed 2084 PD patients from January 1985 to December 2019. The diagnosis of TBP was established by positive peritoneal fluid culture for Mycobacterium tuberculosis. RESULTS: 18 patients were diagnosed with TBP. The incidence was 2.029 episodes per 1000 patient-years. The most common symptom was fever (94.4%), followed by cloudy effluent (83.3%) and abdominal pain (83.3%). The average peritoneal dialysis effluent (PDE) white blood cell (WBC) count was 172.7 cells/µL. Nine patients (50%) had WBC counts lower than 100 cells/µL and 13 patients (72.2%) had neutrophilic predominant WBC counts. Acid fast stain (AFS) was positive in 7 patients (38.9%). Only 2 patients (11.1%) continued with PD after TB infection, while 10 patients (55.6%) changed to hemodialysis. Seven patients (38.9%) died within 1 year. Significant differences were observed in sex (p = 0.040), the presence of diabetes mellitus (p = 0.024), and PD catheter removal (p < 0.001) between TBP patients with and without mortality. However, none of them was a significant factor for 1-year mortality in multivariate Cox regression model. CONCLUSION: Physicians should pay attention to the unusual presentations of peritonitis, especially if symptoms include fever or an initial low PDE WBC count. Catheter removal is not mandatory if early diagnosis and appropriate therapy are available.


Subject(s)
Peritoneal Dialysis , Peritonitis, Tuberculous , Peritonitis , Humans , Retrospective Studies , Taiwan/epidemiology , Peritoneal Dialysis/adverse effects , Peritonitis/etiology , Peritonitis/microbiology , Peritoneum , Peritonitis, Tuberculous/diagnosis , Peritonitis, Tuberculous/epidemiology , Peritonitis, Tuberculous/etiology
15.
Infection ; 51(4): 967-980, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36512270

ABSTRACT

PURPOSE: BK Polyomavirus (BKPyV) infection manifests as renal inflammation and can cause kidney damage. Tumor necrosis factor-α (TNF-α) is increased in renal inflammation and injury. The aim of this study was to investigate the effect of TNF-α blockade on BKPyV infection. METHODS: Urine specimens from 22 patients with BKPyV-associated nephropathy (BKPyVN) and 35 non-BKPyVN kidney transplant recipients were analyzed. RESULTS: We demonstrated increased urinary levels of TNF-α and its receptors, TNFR1 and TNFR2, in BKPyVN patients. Treating BKPyV-infected human proximal tubular cells (HRPTECs) with TNF-α stimulated the expression of large T antigen and viral capsid protein-1 mRNA and proteins and BKPyV promoter activity. Knockdown of TNFR1 or TNFR2 expression caused a reduction in TNF-α-stimulated viral replication. NF-κB activation induced by overexpression of constitutively active IKK2 significantly increased viral replication and the activity of the BKPyV promoter containing an NF-κB binding site. The addition of a NF-κB inhibitor on BKPyV-infected cells suppressed viral replication. Blockade of TNF-α functionality by etanercept reduced BKPyV-stimulated expression of TNF-α, interleukin-1ß (IL-1ß), IL-6 and IL-8 and suppressed TNF-α-stimulated viral replication. In cultured HRPTECs and THP-1 cells, BKPyV infection led to increased expression of TNF-α, interleukin-1 ß (IL-1ß), IL-6 and TNFR1 and TNFR2 but the stimulated magnitude was far less than that induced by poly(I:C). This may suggest that BKPyV-mediated autocrine effect is not a major source of TNFα. CONCLUSION: TNF-α stimulates BKPyV replication and inhibition of its signal cascade or functionality attenuates its stimulatory effect. Our study provides a therapeutic anti-BKPyV target.


Subject(s)
BK Virus , Polyomavirus Infections , Humans , BK Virus/genetics , Tumor Necrosis Factor-alpha , Receptors, Tumor Necrosis Factor, Type I , Receptors, Tumor Necrosis Factor, Type II/genetics , NF-kappa B , Interleukin-6 , Polyomavirus Infections/metabolism , Polyomavirus Infections/pathology , Inflammation
16.
Am J Kidney Dis ; 81(6): 665-674.e1, 2023 06.
Article in English | MEDLINE | ID: mdl-36252882

ABSTRACT

RATIONALE & OBJECTIVE: Dialysis-treated acute kidney injury (AKI) is increasingly common in intensive care units (ICUs) and is associated with poor outcomes. Few studies have explored the temporal trends in severity of acute illness at dialysis initiation, indications for dialysis, and their association with patient outcomes. STUDY DESIGN: Multicenter retrospective cohort study. SETTING & PARTICIPANTS: 9,535 adult patients admitted to the ICU who received their first dialysis treatment from Chang Gung Memorial Hospital system in Taiwan from 2009 through 2018. EXPOSURE: Calendar year. OUTCOMES: ICU mortality and dialysis treatment at discharge among hospital survivors. ANALYTICAL APPROACH: The temporal trends during the study period were investigated using test statistics suited for continuous or categorical data. The association between the study year and the risk of mortality was analyzed using multivariable Cox regression with adjustment for relevant clinical variables, including the severity of acute illness, defined by Sequential Organ Failure Assessment (SOFA) score. RESULTS: The mean SOFA score at dialysis initiation decreased slightly from 14.0 in 2009 to 13.6 in 2018. There was no significant trend in the number of indications for dialysis initiation that were fulfilled over time. Observed ICU mortality decreased over time, and the curve appeared to be reverse J-shaped, with a substantial decrease from 56.1% in 2009 to 46.3% in 2015 and a slight increase afterward. The risk of mortality was significantly reduced from 2013 to 2018 compared with 2009 in adjusted models. The decreasing trend in ICU mortality over time remained significant. There was an increase in dialysis treatment at discharge among survivors, mainly in patients with estimated glomerular filtration rate<60mL/min/1.73m2, from 36.8% in 2009 to 43.9% in 2018. LIMITATIONS: Residual confounding from unmeasured factors over time such as severity of comorbidities, detailed medication interventions, and delivered dialysis dose. CONCLUSIONS: We observed reductions in mortality among ICU patients with dialysis-treated acute kidney injury between 2009 and 2018, even after adjusting for dialysis indication and severity of illness at dialysis initiation. However, dialysis treatment at discharge among survivors has increased over time, mainly in patients with preexisting kidney disease. PLAIN-LANGUAGE SUMMARY: The current medical management of severe acute kidney injury (AKI) is primarily limited to supportive care and kidney replacement therapy if indicated, leading to perceptions that outcomes among intensive care unit (ICU) patients with dialysis-treated AKI have not improved. In this multicenter retrospective study of ICU patients with dialysis-treated AKI between 2009 and 2018 in Taiwan, patient mortality decreased over time despite increasing comorbidities. Moreover, the decreasing linear trends remained significant even when considering severity of acute illness at dialysis initiation, which was based on physiologic and laboratory measurements seldom evaluated in previous studies. Further research should explore the basis for these improvements.


Subject(s)
Acute Kidney Injury , Renal Dialysis , Adult , Humans , Retrospective Studies , Acute Disease , Intensive Care Units , Renal Replacement Therapy , Acute Kidney Injury/epidemiology , Acute Kidney Injury/therapy , Critical Illness
17.
Clin Nephrol ; 98(6): 274-279, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36331016

ABSTRACT

INTRODUCTION: Fluid overload is an unavoidable problem in patients on peritoneal dialysis (PD) and is associated with poor outcomes. The aim of our study was to estimate ultrafiltration (UF) under different dextrose concentrations (DCs) and four peritoneal transport levels. MATERIALS AND METHODS: 70 patients, with a total of 1,848 daily treatment records and 8,266 single dwells on automated PD (APD) through Homechoice Claria with Sharesource were followed in October 2020 and categorized into two groups according to the DC (D1.5% and D2.5% groups). Baseline characteristics, peritoneal membrane characteristics, and daily PD treatment records from Sharesource were obtained. We compared UF under the different conditions. RESULTS: The mean night UF per cycle, the mean night UF corrected by fill volume (FV) per cycle, and the mean night UF corrected by FV and dwelling time (DT) per cycle were all significantly higher in the D2.5% group than in the D1.5% group (95.8 vs. 220.3 mL, 5.5 vs. 12.0%, and 5.0 vs. 11.6 0/000/minutes, all p < 0.001). However, there was no significant difference among the four transport categories in any group. CONCLUSION: This retrospective study presents precise UF measurements with two solutions at different DCs and four peritoneal transport levels. With a 2-L indwell (DT ranging from ~ 1 to 3 hours), the mean net UF rate was 1.0 mL/min in the D1.5% group and 2.3 mL/min in the D2.5% group.


Subject(s)
Peritoneal Dialysis , Ultrafiltration , Humans , Icodextrin , Pilot Projects , Retrospective Studies , Glucans , Glucose , Peritoneum , Dialysis Solutions
18.
World J Gastrointest Surg ; 14(8): 809-820, 2022 Aug 27.
Article in English | MEDLINE | ID: mdl-36157361

ABSTRACT

BACKGROUND: Mesenteric ischemia is significantly more common in end-stage kidney disease patients undergoing chronic dialysis than in the general population and is associated with high morbidity and mortality. However, reports on prognostic factors in this population are limited. AIM: To elucidate the in-hospital outcomes of acute mesenteric ischemia in chronic dialysis patients and to analyze protective factors for survival. METHODS: The case data of 426 chronic dialysis patients who were hospitalized in a tertiary medical center for acute mesenteric ischemia over a 14-year period were retrospectively reviewed. Of these cases, 103 were surgically confirmed, and the patients were enrolled in this study. A Cox regression analysis was used to evaluate the protective factors for survival. RESULTS: The in-hospital mortality rate among the 103 enrolled patients was 46.6%. Univariate analysis was performed to compare factors in survivors and nonsurvivors, with better in-hospital outcomes associated with a surgery delay (defined as the time from onset of signs and symptoms to operation) < 4.5 d, no shock, a higher potassium level on day 1 of hospitalization, no resection of the colon, and a total bowel resection length < 110 cm. After 1 wk of hospitalization, patients with lower white blood cell count and neutrophil counts, higher lymphocyte counts, and lower C-reactive protein levels had better in-hospital outcomes. Following multivariate adjustment, a higher potassium level on day 1 of hospitalization (HR 1.71, 95%CI 1.19 to 2.46; P = 0.004), a lower neutrophil count (HR 0.91, 95%CI 0.84 to 0.99; P = 0.037) at 1 wk after admission, resection not involving the colon (HR 2.70, 95%CI 1.05 to 7.14; P = 0.039), and a total bowel resection length < 110 cm (HR 4.55, 95%CI 1.43 to 14.29; P = 0.010) were significantly associated with survival. CONCLUSION: A surgery delay < 4.5 d, no shock, no resection of the colon, and a total bowel resection length < 110 cm predicted better outcomes in chronic dialysis patients with acute mesenteric ischemia.

19.
J Am Heart Assoc ; 11(19): e027516, 2022 10 04.
Article in English | MEDLINE | ID: mdl-36172933

ABSTRACT

Background The benefit of low-density lipoprotein cholesterol (LDL-C) levels in chronic kidney disease populations remains unclear. This study evaluated the cardiovascular and renal outcomes in patients with stage 3 chronic kidney disease with different LDL-C levels during statin treatment. Methods and Results There were 8500 patients newly diagnosed as having stage 3 chronic kidney disease under statin treatment who were identified from the Chang Gung Research Database and divided into 3 groups according to their first LDL-C level after the index date: <70 mg/dL, 70 to 100 mg/dL, and >100 mg/dL. Inverse probability of treatment weighting was performed to balance baseline characteristics. Compared with the LDL-C ≥100 mg/dL group, the 70≤LDL-C<100 mg/dL group exhibited significantly lower risks of major adverse cardiac and cerebrovascular events (6.8% versus 8.8%; subdistribution hazard ratio [SHR], 0.76 [95% CI, 0.64-0.91]), intracerebral hemorrhage (0.23% versus 0.51%; SHR, 0.44 [95% CI, 0.25-0.77]), and new-onset end-stage renal disease requiring chronic dialysis (7.6% versus 9.1%; SHR, 0.82 [95% CI, 0.73-0.91]). By contrast, the LDL-C <70 mg/dL group exhibited a marginally lower risk of major adverse cardiac and cerebrovascular events (7.3% versus 8.8%; SHR, 0.82 [95% CI, 0.65-1.02]) and a significantly lower risk of new-onset end-stage renal disease requiring chronic dialysis (7.1% versus 9.1%; SHR, 0.76 [95% CI, 0.67-0.85]). Conclusions Among patients with stage 3 chronic kidney disease, statin users with 70≤LDL-C<100 mg/dL and with LDL-C <70 mg/dL had similar beneficial effect in the reduction of risks of major adverse cardiac and cerebrovascular events and new-onset end-stage renal disease compared with those with LDL-C >100 mg/dL. Moreover, the 70≤LDL-C<100 mg/dL group seemed to have a lowest risk of intracerebral hemorrhage, although the incidence was low.


Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors , Kidney Failure, Chronic , Renal Insufficiency, Chronic , Cerebral Hemorrhage/chemically induced , Cholesterol, LDL , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/epidemiology , Treatment Outcome
20.
Int J Mol Sci ; 23(15)2022 Jul 31.
Article in English | MEDLINE | ID: mdl-35955634

ABSTRACT

The aberrant activation of the purinergic signaling pathway has been shown to promote cyst growth and fluid secretion in autosomal dominant polycystic kidney disease (ADPKD). Suramin is an anti-parasitic drug that has strong anti-purinergic properties. Whether suramin could have a therapeutic effect on ADPKD has not been fully investigated. We examined the effect of suramin on cyst progression in a Pkd1 microRNAs transgenic mouse model that presented stable Pkd1 knockdown and moderate disease progression. The Pkd1-deficient mice were treated with suramin (60 mg/kg) by intraperitoneal injection twice a week from postnatal days 35 to 90. Kidney-to-body weight ratios, cyst indices, and blood urea nitrogen (BUN) levels were measured. Cell proliferation and macrophage infiltration were determined by immunohistochemistry. The suramin-treated group had significantly lower renal cyst densities, cell proliferation, and macrophage infiltration compared with saline-treated controls. Suramin significantly inhibited ERK phosphorylation and the expression of Il1b, Il6, Nlrp3, Tgfb, Fn1, P2rx7, and P2ry2 mRNAs in the kidneys. However, BUN levels remained high despite the reduction in cyst growth. Furthermore, plasma cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) levels were significantly higher in the suramin-treated group compared with the control group. Periodic acid-Schiff staining revealed degenerative changes and epithelial cell vacuolation in the non-cystic renal tubules, which indicated phospholipidosis following suramin treatment. These results suggest that suramin may reduce renal cyst growth and inflammation, but the associated tubular cell injuries could limit its therapeutic potential. Other purinergic receptor antagonists with less nephrotoxicity may deserve further investigation for the treatment of ADPKD.


Subject(s)
Cysts , Polycystic Kidney Diseases , Polycystic Kidney, Autosomal Dominant , TRPP Cation Channels/metabolism , Animals , Cell Proliferation , Cysts/drug therapy , Disease Models, Animal , Kidney/metabolism , Mice , Mice, Transgenic , Polycystic Kidney Diseases/metabolism , Polycystic Kidney, Autosomal Dominant/drug therapy , Polycystic Kidney, Autosomal Dominant/genetics , Polycystic Kidney, Autosomal Dominant/metabolism , Suramin/pharmacology , Suramin/therapeutic use , TRPP Cation Channels/genetics
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