The aim of the study was to evaluate the predictive value of cell population data (CPD) parameters in comparison with procalcitonin (PCT) and C-reactive protein (CRP) for an early diagnosis of sepsis in intensive care unit (ICU). The effect of renal function on CPD, PCT and CRP, in septic and non-septic patients was also investigated.

This is a retrospective, observational and single-center study, performed with data collected from patients consecutively admitted to the ICU of the Edoardo Bassini Hospital in Milan. Patients were divided in septic and non-septic according to Sepsis-III criteria. The control group was formed by critically ill patients without sepsis. Patients with sepsis were further divided in patients with sepsis and patients with septic shock.

A significant difference between septic and non-septic patients was found for neutrophils complexity (NE-SSC), neutrophils fluorescence intensity (NE-SFL), width of dispersion of neutrophils fluorescence (NE-WY), monocytes complexity (MO-X), monocytes fluorescence intensity (MO-Y), PCT and CRP parameters. PCT, neutrophils sixe (NE-FSC), NE-WY, width of dispersion of neutrophils size (NE-WZ) and MO-X discriminated sepsis and septic-shock patients. CPD parameters were not influenced by renal function. CPD, PCT and CRP had a heterogeneous diagnostic performance efficiency in the prediction of sepsis. Overall, NE-SSC, NE-SFL, width of dispersion of neutrophils complexity (NE-WX), MO-X, MO-Y, PCT and CRP displayed the best diagnostic performance for sepsis.

This study suggested that some CPD parameters (i.e., NE-SFL and MO-X) might provide useful information for diagnosis and management of sepsis.

Metabolic diseases have exponentially increased in recent years, which has led to an increased prevalence of metabolic dysfunction-associated steatotic liver disease and concomitant kidney diseases. Ascites are a common presentation of cirrhosis, and renal impairment in cirrhosis is well described. However, patients with end-stage renal disease (ESRD) may also present with ascites even in the absence of cirrhosis. The literature on the management of patients with ESRD with ascites with or without concomitant cirrhosis is limited. Massive ascites in this population are often refractory to medical therapy and are associated with dismal prognosis. Pathophysiologically, increased hepatic vein hydrostatic pressure, fluid retention, increased peritoneal membrane permeability, and impaired peritoneal lymphatic drainage are proposed mechanisms for ascites in ESRD without cirrhosis. Identifying underlying cirrhosis and portal hypertension (PH) has therapeutic implications in such patients. However, diagnostic tools such as serum ascites albumin gradient and noninvasive tests to identify cirrhosis have limited utility in ESRD. Hemodialysis and continuous ambulatory peritoneal dialysis are effective but can be associated with hemodynamic compromise and peritonitis, especially in those with PH. TIPS for ascites has a limited role in the presence of ESRD due to the increased risk of HE. Kidney transplant is the treatment of choice in ESRD with ascites without PH. Simultaneous liver-kidney transplant remains the definitive treatment in the presence of PH, but is less commonly feasible, and kidney transplant alone in the presence of PH can be associated with the risk of decompensations. This review discusses the approach and management of ascites in chronic kidney disease and ESRD specifically.

An 8-week regimen of glecaprevir/pibrentasvir is recommended for treatment-naïve patients with chronic hepatitis C (CHC). In alignment with the Taiwanese government's objective to eliminate hepatitis C by 2025, this study aimed to provide real-world evidence on the use of this regimen in treatment-naïve patients with chronic kidney disease (CKD) by using data from the Taiwan Association for the Study of the Liver HCV Registry (TACR). CKD was defined by an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 or higher with proteinuria persisting for over 3 months. Patients were categorized as having early CKD (eGFR ≥45 mL/min/1.73 m2) or pre-end-stage renal disease (pre-ESRD) (eGFR <45 mL/min/1.73 m2). Among 1072 patients who received at least one dose of the regimen, 1054 had available data for assessing sustained virologic response at 12 weeks posttreatment (SVR12). The overall SVR12 rate was 99.6%, with rates of 99.7% for pre-ESRD patients and 99.6% for early CKD patients. Subgroup analysis showed 100% efficacy for genotype 3 and dyslipidemia, 99.5% for diabetes, 99.4% for cardiovascular disease, 96.9% for a history of cerebral vascular accident, and 95.5% for patients with a history of drug injection or HIV co-infection. Adverse events were reported in 16.8% of patients, with 0.8% experiencing serious events, and only two cases were treatment-related. Renal function significantly improved, with overall eGFR increasing from 39.2 to 41.9 mL/min/1.73 m2. Early CKD patients showed an eGFR rise from 53.5 to 57.1, while pre-ESRD patients improved from 27.1 to 29.2 at SVR12. The study concluded that the 8-week regimen is highly effective, well-tolerated, and associated with significant renal function improvement in treatment-naïve CHC patients with both early CKD and pre-ESRD.

Due to the multifaceted aspects of kidney function, the management of CKD not only requires knowledge of kidney physiology and pathophysiology but also a keen understanding of how to diagnose, treat, and monitor the metabolic derangements and complications of reduced kidney function. In this article, we provide questions that cover a broad range of clinical scenarios that may test the clinical acumen of a kidney health professional. Each question starts with a brief clinical scenario to guide the reader. Questions are followed by a selection of answers. As in most clinical situations, a variety of tests and/or interventions may be appropriate. As knowledge on the management of kidney diseases and associated complications evolve, the optimal choice for these questions may also evolve.

Background/Objectives: Glecaprevir/pibrentasvir (G/P) and elbasvir/grazoprevir (EBR/GZR) are effective treatments for chronic hepatitis C (CHC), especially in patients with chronic kidney disease (CKD). However, both regimens carry a risk of drug-induced liver injury (DILI). This study investigates the association between renal failure and DILI, using real-world data, and assesses the effectiveness of these treatments in peritoneal dialysis patients. Methods: A retrospective cohort study was conducted using data from the Ditmanson Research Database, including patients with CHC treated with G/P or EBR/GZR from 1 August 2017 to 31 December 2020. Patients were categorized into CKD and normal kidney function (NKF) groups. Two sensitivity analyses were performed to assess DILI risk. The study was approved by the DMF-CYCH Institutional Review Board (CYCH IRB No.: 2021010). Results: In 837 patients, DILI risk, expressed as incidence rate ratios (IRR), was 0.64 (95% CI 0.25-1.63) in the NKF group and 1.29 (95% CI 0.12-14.23) in the CKD group. Sensitivity analyses showed consistent results. A case-time-control analysis suggested liver instability despite treatment, with comorbid liver tumors (aOR 18.89; 95% CI 5.4-66.12) and hypertension (aOR 4.25; 95% CI 1.49-12.15) linked to higher DILI risk. All peritoneal dialysis patients (n = 10) achieved a 100% SVR12 rate. Conclusions: This real-world study supports the effectiveness of G/P and EBR/GZR in peritoneal dialysis patients. Comorbidities that impair liver function are key predictors of abnormal liver parameters, highlighting the need for careful monitoring during CHC treatment.

More than 3.5 million people worldwide and 540 000 individuals in the US receive maintenance hemodialysis or peritoneal dialysis for the treatment of chronic kidney failure. The 5-year survival rate is approximately 40% after initiation of maintenance dialysis.

Hemodialysis and peritoneal dialysis remove metabolic waste and excess body water and rebalance electrolytes to sustain life. There is no recommended estimated glomerular filtration rate (eGFR) threshold for initiating dialysis, and patient-clinician shared decision-making should help determine when to initiate dialysis. Persistent signs and symptoms of uremia (eg, nausea, fatigue) and volume overload (eg, dyspnea, peripheral edema), worsening eGFR, metabolic acidosis, and hyperkalemia inform the timing of therapy initiation. A randomized clinical trial reported no mortality benefit to starting dialysis at higher eGFR (10-14 mL/min/1.73 m2) vs lower eGFR (5-7 mL/min/1.73 m2) levels. Observational data suggested no differences in 5-year mortality with use of hemodialysis vs peritoneal dialysis. Cardiovascular (eg, arrhythmias, cardiac arrest) and infection-related complications of maintenance dialysis are common. In the US, hemodialysis catheter-related bloodstream infections occur at a rate of 1.1 to 5.5 episodes per 1000 catheter-days and affect approximately 50% of patients within 6 months of catheter placement. Peritonitis occurs at a rate of 0.26 episodes per patient-year and affects about 30% of individuals in the first year of peritoneal dialysis therapy. Chronic kidney failure-related systemic complications, such as anemia, hyperphosphatemia, hypocalcemia, and hypertension, often require pharmacologic treatment. Hypotension during dialysis, refractory symptoms (eg, muscle cramps, itching), and malfunction of dialysis access can interfere with delivery of dialysis.

In 2021, more than 540 000 patients in the US received maintenance hemodialysis or peritoneal dialysis for treatment of chronic kidney failure. Five-year survival rate after initiation of maintenance dialysis is approximately 40%, and the mortality rate is similar with hemodialysis and peritoneal dialysis. Decisions about dialysis initiation timing and modality are influenced by patient symptoms, laboratory trajectories, patient preferences, and therapy cost and availability and should include shared decision-making.

The coronavirus disease 2019 (COVID-19) has a significant impact on the global population, particularly on individuals with chronic kidney disease (CKD). COVID-19 patients with CKD will face a considerably higher risk of mortality than the general population. This study developed a predictive model for assessing mortality in COVID-19-affected CKD patients, providing personalized risk prediction to optimize clinical management and reduce mortality rates. We developed machine learning algorithms to analyze 219 patients' clinical laboratory test data retrospectively. The performance of each model was assessed using a calibration curve, decision curve analysis, and receiver operating characteristic (ROC) curve. It was found that the LightGBM model showed the most satisfied performance, with an area under the ROC curve of 0.833, sensitivity of 0.952, and specificity of 0.714. Prealbumin, neutrophil percent, respiratory index in arterial blood, half-saturated pressure of oxygen, carbon dioxide in serum, glucose, neutrophil count, and uric acid were the top 8 significant variables in the prediction model. Validation by 46 patients demonstrated acceptable accuracy. This model can serve as a powerful tool for screening CKD patients at high risk of COVID-19-related mortality and providing decision support for clinical staff, enabling efficient allocation of resources, and facilitating timely and targeted management for those who need the relevant interference urgently.

Immunoglobulin (Ig)A nephropathy, also known as Berger's disease, is characterized by IgA deposits in the kidney's mesangium and can lead to serious outcomes, including rapidly progressive glomerulonephritis. While Hepatitis C virus (HCV) infection is commonly associated with liver involvement, it is also linked to various renal pathologies, including membranous nephropathy and membranoproliferative glomerulonephritis. However, IgA nephropathy secondary to HCV is rare. This case study involves a 24-year-old male with a known history of untreated Hepatitis C, who presented with hematuria and foamy urine. Laboratory findings revealed increased levels of serum creatinine and urea, significant proteinuria, and a high HCV RNA viral load. A renal biopsy confirmed the diagnosis of IgA nephropathy with strong IgA and C3 deposits observed on immunofluorescence. Treatment with angiotensin receptor blockers and antiviral therapy led to substantial symptomatic improvement and stabilization of renal function. This case underscores the critical importance of considering IgA nephropathy in the differential diagnosis of renal complications in HCV-infected patients. Early detection and treatment of Hepatitis C are vital, as timely intervention can markedly enhance patient outcomes and mitigate the risk of serious complications. A heightened awareness of the potential renal implications of HCV emphasizes the urgency of proactive monitoring and swift management to safeguard kidney function and overall health.

Following the advent of direct-acting antivirals (DAAs), hepatitis C virus (HCV) infection can be cured in almost all infected patients. This has led to a number of clinical questions regarding the optimal management of the millions of patients cured of HCV. This position statement provides specific guidance on the appropriate follow-up after a sustained virological response in patients without advanced fibrosis, those with compensated advanced chronic liver disease, and those with decompensated cirrhosis. Guidance on hepatocellular carcinoma risk assessment and the management of extrahepatic manifestations of HCV is also provided. Finally, guidance is provided on the monitoring and treatment of reinfection in at-risk patients. The recommendations are based on the best available evidence and are intended to help healthcare professionals involved in the management of patients after treatment for HCV.

Sofosbuvir/Velpatasvir (SOF/VEL) is a combination drug used for chronic hepatitis C (HCV) infection. However, limited information exists regarding the pharmacokinetics of SOF/VEL and its metabolites in hemodialysis patients. We conducted a prospective investigation of the pharmacokinetic parameters of SOF/VEL after a single dose of SOF/VEL (400/100 mg) on days with and without dialysis in 12 Thai hemodialysis patients with chronic HCV infection, who had been undergoing hemodialysis for a duration of 0.5-20 years. Blood samples were collected before dose (0) and 0.5, 1.0, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, and 12.0 h after dose. Dialysate samples were also collected before dose (0) and 1.0, 2.0, 3.0, and 4.0 h after dose. Plasma and dialysate samples were quantified for SOF and its metabolite, GS-331007, and VEL concentrations using a fully validated LCMS technique. In addition, a preliminary efficacy study was conducted using the proposed SOF/VEL dose reduction regimen in all patients. No differences in SOF/VEL PK parameters between on- and off-dialysis studies. On the contrary, GS-331007 exhibited a 30% reduction in the area under the plasma concentration-time curve from time 0 to 24 h (AUC0-24h) on dialysis days compared with non-dialysis days (AUC0-24h ratio 0.68 vs. 1.04, respectively). The dialysis clearance of SOF and GS-331007 was 9.35 (8.72-15.11) and 8.89 (8.52-14.07) mL/min, respectively. Subsequently, an alternate-day regimen of SOF/VEL (400/100 mg) was administered for 12 weeks, resulting in an undetectable plasma HCV viral load without side effects. Further clinical studies are warranted to validate the efficacy and safety of our proposed dose reduction regimen.

Hepatitis C virus (HCV) can cause a range of kidney diseases. HCV is the primary cause of mixed cryoglobulinaemia, which leads to cryoglobulinaemic vasculitis and cryoglobulinaemic glomerulonephritis (GN). Patients with acute cryoglobulinaemic vasculitis often exhibit acute kidney disease due to HCV infection, which typically progresses to acute kidney injury (AKI). HCV also increases the risk of chronic kidney disease (CKD) and the likelihood of developing end-stage renal disease (ESRD). Currently, direct-acting antiviral agents (DAAs) can be used to treat kidney disease at different stages. This review focuses on key findings regarding HCV and kidney disease, discusses the impact of DAAs, and highlights the need for further research and treatment.

Viral hepatitis represents a major danger to public health, and is a globally leading cause of death. The five liver-specific viruses: Hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, and hepatitis E virus, each have their own unique epidemiology, structural biology, transmission, endemic patterns, risk of liver complications, and response to antiviral therapies. There remain few options for treatment, in spite of the increasing prevalence of viral-hepatitis-caused liver disease. Furthermore, chronic viral hepatitis is a leading worldwide cause of both liver-related morbidity and mortality, even though effective treatments are available that could reduce or prevent most patients' complications. In 2016, the World Health Organization released its plan to eliminate viral hepatitis as a public health threat by the year 2030, along with a discussion of current gaps and prospects for both regional and global eradication of viral hepatitis. Today, treatment is sufficiently able to prevent the disease from reaching advanced phases. However, future therapies must be extremely safe, and should ideally limit the period of treatment necessary. A better understanding of pathogenesis will prove beneficial in the development of potential treatment strategies targeting infections by viral hepatitis. This review aims to summarize the current state of knowledge on each type of viral hepatitis, together with major innovations.

Chronic kidney diseases (CKD) present a formidable global health challenge, characterized by a deficiency of effective treatment options. Extracellular vesicles (EVs), recognized as multifunctional drug delivery systems in biomedicine, have gained accumulative interest. Specifically, engineered EVs have emerged as a promising therapeutic approach for targeted drug delivery, potentially addressing the complexities of CKD management. In this review, we systematically dissect EVs, elucidating their classification, biogenesis, composition, and cargo molecules. Furthermore, we explore techniques for EV engineering and strategies for their precise renal delivery, focusing on cargo loading and transportation, providing a comprehensive perspective. Moreover, this review also discusses and summarizes the diverse therapeutic applications of engineered EVs in CKD, emphasizing their anti-inflammatory, immunomodulatory, renoprotective, and tissue-regenerating effects. It critically evaluates the challenges and limitations in translating EV therapies from laboratory settings to clinical applications, while outlining future prospects and emerging trends.

Background Hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections are more prevalent in hemodialysis patients compared to the general population. The objective of this study was to evaluate the prevalence of HBV, HCV, and HIV infections in hemodialysis patients dialyzing regularly at Kano Kidney Center (KKC) in the Eastern Health Cluster of Saudi Arabia in 2022. Methods This retrospective study included all hemodialysis patients who were dialyzed regularly at KKC during 2022. Their electronic medical records were reviewed for the results of HBV, HCV, and HIV along with the patient's demographics, comorbid conditions, and dialysis history. The study was approved and monitored by the Institutional Review Board of Dammam Medical Complex. Results A total of 239 regular hemodialysis patients were included, consisting of 142 males and 97 females (59.41% and 40.59%, respectively), with a mean age of 52.71±15.83 years. Most of the patients were Saudis (156 patients, 65.27%) with the non-Saudi patients being composed mostly of Arabian patients. Nine patients (3.77%) tested positive for hepatitis B surface antigen (HBsAg), the serologic hallmark of HBV infection. Two patients (0.84%) had resolved HBV infections as evidenced by positive hepatitis B core antibody (anti-HBc) and hepatitis B surface antibody (anti-HBs). However, the majority (226 patients, 94.56%) were never tested for anti-HBc. Anti-HBs, which can imply long-term immunity against HBV from prior immunizations or infections, were positive in 165 patients (69.04%). A protective anti-HBs level of ≥ 10 IU/L was detected in 158 patients (66.11%) including 104 patients (43.51%) having ≥ 100 IU/L. Eighteen patients (7.53%) had reactive HCV antibodies. Four patients (1.67%) had chronic HCV infection as they had detectable HCV RNA. The remaining 14 patients (5.86%) cleared HCV either spontaneously (seven patients, 2.93%) or by medications (seven patients, 2.93%). HIV screening tests were negative in all 239 patients (100%). HBsAg-positive patients did not have any statistically significant differences from HBsAg-negative patients. On the other hand, the patients who were positive for HCV antibodies were older than the patients who were negative for HCV antibodies (60.66 vs 52.05 years on average, p-value <0.05). They also contained a statistically larger proportion of non-Saudi patients than the patients with no evidence of prior infections (61.11% vs 32.13%, p-value <0.05). Conclusions The study found that the prevalence of HBV and HCV infections among hemodialysis patients in KKC at 3.77% and 1.67%, respectively, is higher than that reported in the general population in Saudi Arabia, with non-Saudis having a higher prevalence rate of HCV infection than Saudis. However, the current prevalence rate is lower compared to the previous studies that were conducted in Saudi Arabia in the first decade of the 21st century, and there were no cases of HIV infections. Nevertheless, a significant proportion of patients had unprotective or negative anti-HBs antibody titers, indicating the need for strict vaccination protocols and monitoring of antibody titers to ensure optimal protection.

Treatment of chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection poses unique challenges in patients with kidney disease. Direct-acting antivirals have been a major breakthrough in eradicating HCV infection, and several pangenotypic regimens are available for patients with chronic kidney disease or end-stage kidney disease requiring dialysis with high cure rates and no need for dose adjustment. Direct-acting antiviral therapy alone can treat HCV-associated cryoglobulinemic glomerulonephritis; concurrent antiviral and immunosuppressive therapy is needed for cases of severe, organ-threatening manifestations of cryoglobulinemia. Immunosuppression may be needed for HBV-associated kidney disease (polyarteritis nodosa or membranous nephropathy) when there is evidence of severe immune-mediated injury while weighing the risk of potential viral activation. Most HBV antiviral agents need to be dose-adjusted in patients with chronic kidney disease or end-stage kidney disease requiring dialysis, and drug-drug interactions need to be carefully evaluated in patients with kidney transplants. Considerations for accepting HCV- and HBV-infected donors for kidney transplantation are discussed.

The diagnosis of sepsis is often difficult and belated, substantially increasing mortality in affected patients. Its early identification allows for us to choose the most appropriate therapies in the shortest time, improving patients' outcomes and eventually their survival. Since neutrophil activation is an indicator of an early innate immune response, the aim of the study was to evaluate the role of Neutrophil-Reactive Intensity (NEUT-RI), which is an indicator of their metabolic activity, in the diagnosis of sepsis. Data from 96 patients consecutively admitted to the Intensive Care Unit (ICU) were retrospectively analyzed (46 patients with and 50 without sepsis). Patients with sepsis were further divided between sepsis and septic shock according to the severity of the illness. Patients were subsequently classified according to renal function. For the diagnosis of sepsis, NEUT-RI showed an AUC of >0.80 and a better negative predictive value than Procalcitonin (PCT) and C-reactive protein (CRP) (87.4% vs. 83.9% and 86.6%, p = 0.038). Unlike PCT and CRP, NEUT-RI did not show a significant difference within the "septic" group between patients with normal renal function and those with renal failure (p = 0.739). Similar results were observed among the "non-septic" group (p = 0.182). The increase in NEUT-RI values could be useful in the early ruling-out of sepsis, and it does not appear to be influenced by renal failure. However, NEUT-RI has not proved to be efficient in discriminating the severity of sepsis at the time of admission. Larger, prospective studies are needed to confirm these results.

Treatment of hepatitis C (HCV) has been revolutionized with the introduction of direct-acting antivirals (DAAs). Patients can be treated at more advanced stages of liver disease, with a growing number of cirrhotic patients achieving sustained virological response (SVR). Long-term outcomes for cured patients and the optimal follow-up care of patients after SVR are yet to be defined, because most studies on cirrhotic patients cured with DAAs have a short follow-up period. There are many open questions related to patient management after viral eradication with DAAs, such as which could be the most reliable non-invasive tool to predict liver-related complications, or to what extent viral eradication reduces the risk of liver disease progression in the long term. Growing evidence supports the personalization of follow-up care based on individual risk. The aim of this narrative review is to analyze the impact of viral eradication with DAAs on clinically significant portal hypertension, hepatocellular carcinoma, and extrahepatic manifestations, as well as to summarize indications for optimal follow-up care of HCV patients treated with DAAs.