Kidney Disease

This randomized clinical study evaluates two diuretic strategies for fluid overload in adult critically ill patients: furosemide monotherapy versus combined therapy with furosemide plus albumin. Albumin may enhance diuretic effectiveness by increasing intravascular oncotic pressure, improving renal perfusion, and facilitating drug delivery to the nephron. The protocol includes standardized dosing, measurement of urine output at 2 hours, and analysis of serum and urine biochemical parameters. Bedside ultrasound will be used to assess markers of fluid overload, including evaluation of the inferior vena cava and venous congestion patterns. Hemodynamic variables, electrolyte changes, and estimated glomerular filtration rate will also be monitored. The study aims to determine whether the co-administration of albumin provides a clinically meaningful improvement in diuretic response and renal function compared with furosemide monotherapy in critically ill patients with fluid overload.

Over 90% of adult males develop lower urinary tract symptoms (LUTS) secondary to bladder outlet obstruction by age 80, rendering benign prostatic hyperplasia (BPH) the most common proliferative abnormality in humans. LUTS secondary to BPH negatively impact the quality of life of 210 million men globally, accounting for significant life years lost, in addition to costing the US healthcare system over $4 billion per year. Medical therapy for the management of BPH, which includes α-adrenergic blockers (e.g., doxazosin, terazosin, tamsulosin or alfuzosin) and 5α reductase inhibitors (5ARI, i.e., finasteride or dutasteride) targets both stromal and epithelial cells in the prostate gland. Utilization of 5ARI remains ineffective in many patients, leading to invasive therapies in many patients. 5ARI's are the only class of BPH-related drugs that reduce prostate size for the alleviation of LUTS. However, the Medical Therapy of Prostatic Symptoms (MTOPS) trial, which randomized 3047 men, showed that 34% of BPH patients did not respond to individualized treatment with finasteride or doxazosin, while combining the 5ARI and α-blocker relieved LUTS in 66% of BPH patients. Resistance to 5ARI therapy is a major factor limiting the effectiveness of these agents in the management of BPH. Therefore, understanding the molecular pathogenesis of 5ARI resistance is a High-Priority Recommendation of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Prostate Research Strategic Plan. However, it is not yet possible to predict responders vs. non-responders to 5ARI therapy, which creates a significant gap in our ability to effectively manage patients with BPH. 5α reductase (5-AR) plays a critical role in the normal development of the human prostate and in the pathogenesis and progression of prostatic diseases. There are three types of 5-AR isozymes, Steroid 5 Alpha-Reductase 1, 2 3 (SRD5A1, SRD5A2 and SRD5A3), which are encoded by three distinct corresponding genes, SRD5A1, SRD5A2 and SRD5A3. Many studies suggest that all three 5-AR enzymes are expressed in prostate tissues; however, SRD5A2 is the predominant enzyme responsible for prostate development and growth. In addition, since the most commonly prescribed 5ARI, finasteride, is an inhibitor of SRD5A2, regulation of SRD5A2 will remain the focus of this study. It was previously shown that the mechanism of somatic suppression of SRD5A2 during adulthood is dependent on epigenetic changes in the promoter region of the SRD5A2 gene. DNA methylation is one of the most common epigenetic mechanisms affecting gene expression. Methylation of Cytosine-Phosphate-Guanine (CpG) islands has been associated with the regulation of genes during development, cancer initiation, and metastasis. Since the prostate is the only solid organ that grows during adulthood as a result of androgen exposure, it can be considered a benign tumor growth throughout adulthood. Therefore, similar to the neoplastic initiation and progression of many cancers, including prostate cancer, epigenetic changes and variable expression of SRD5A2 in benign prostate tissue is a plausible molecular mechanism. Finasteride, the most commonly prescribed 5ARI, is an inhibitor of SRD5A2. Finasteride has been shown in several large clinical trials to reduce prostate size by 20%, improve urinary flow rate, and improve urinary bothersome symptom scores in men suffering from bladder outlet obstruction caused by BPH. Despite their widespread use and clinical effectiveness, 25% to 30% of patients are resistant to the therapeutic effects of 5ARIs and another 5% to 7% of patients develop worsening symptoms and ultimately may require surgery. Given their age and comorbidities, these patients are often not ideal candidates for surgery. Therefore, understanding the mechanisms of 5ARI treatment failure may pave the way for the development of new medical therapies appropriately targeted to these specific patient groups and is a desirable way to move forward with precision medicine. This proposed work is based on the premise that epigenetic changes to SRD5A2 account for the significant number of patients who are unresponsive to 5ARI therapy. The goal is to assess SRD5A2 methylation and expression as a gene signature to predict which patients will respond to 5ARI therapy. The information gained from this proposal will pave the way toward the development of predictive biomarker assays that can be used to evaluate resistance to BPH-related therapies and allow clinicians to select alternate therapies for managing the most common proliferative disorder affecting men worldwide.

The LINKED- HEARTS Program is a multi-level project that intervenes at the practice level by linking home blood pressure monitoring (HBPM) with a telemonitoring platform (Sphygmo). The program incorporates team-based care by including community health workers (CHWs) and pharmacists to improve the outcomes of multiple chronic conditions (reduced blood pressure (BP), lower blood sugar, and improved kidney function). The LINKED-HEARTS Program will recruit a total of 600 adults with uncontrolled hypertension (BP ≥ 140/90 mm Hg) AND either type 2 diabetes or chronic kidney disease (CKD) across 16 community health centers or primary care practices serving high-risk adults. This cluster-randomized trial consists of two arms: (1) enhanced "usual care arm," wherein patients will be provided with Omron 10 series home BP monitors and will be managed by the patients' primary care clinicians as usual; and (2) the "intervention arm" which will integrate HBPM telemonitoring, a CHW intervention and provider-level interventions into the usual clinical care to improve BP control and provide support for self-management of chronic conditions. The study pharmacist will conduct telehealth, use the Sphygmo app and the Pharmacist Patient Care Process to collaborate with other providers to optimize pharmacologic therapy to improve hypertension outcomes and with payors to ensure consistent access to drug therapy.

The GENESIS study is a multicenter, prospective, non-interventional, clinical study with a target of 12,000 subjects and an anticipated total duration of 36 months. The aim of study GENESIS is to provide a pilot map of HLA genetic variation in the Greek population in order to be used in medical research and for possible clinical applications (evaluation of possible correlations with selected underlying diseases). During the study, each subject will conduct one visit to the participating cite, in which they will provide: 1. Demographic information \[i.e. date of birth, gender, race, ancestry (including information about the subject's grandparents' birthplace), height, weight\], 2. Other information about smoking/vaping, alcohol consumption, arterial blood pressure, diagnosed diseases (if any), current treatments (if any), and 3. Recent (up to 12 months prior to sample collection) results if/when are available from clinical lab tests such as blood count (Hct, Hb, RBC, WBC, PLT count), including a metabolic panel, liver enzymes and biochemical parameters (Glu, HbA1c, TC, TG, LDL-C, HDL-C, ALT, AST, ALP, γGT, bilirubin, LDH, insulin, C-peptide). Upon completion of the data registry, two buccal swabs will be collected per subject and they will be stored at ALTP premises until their shipment to Galatea.Bio. All buccal swab samples will be subjected to genetic material (DNA) extraction. The DNA samples will be further proceeded for HLA genotyping analysis. A follow up analysis will be performed in selected DNA samples via full low-pass whole genome sequencing (LP-WGS), which aims to further investigate the association between the HLA region and autoimmune diseases. Upon completion of the analysis, an individualized ancestry report will be securely made available to all study subjects which they can access, as and if they elect to.

The goal of this trial is to measure what happens to 1 or 2 doses of MK-2828 in a person's body over time (pharmacokinetic or PK trial). Researchers want to learn if the PK of people with certain types of kidney disease is similar to the PK of healthy people.

This is a randomized clinical trial, multicentre, parallel group, open label, to evaluate the use of sodium zirconium cyclosilicate (SZC) to optimize RAASi therapy in patients with heart failure and chronic kidney disease, through up-titration of ACEi, ARB, ARNI or MRA therapy according to clinical guidelines (1), without inducing clinically significant hyperkalemia. Eligible subjects will have been admitted to hospital because of an HF (NYHA I- III) decompensation, will have required intravenous diuretics and will have had mild hyperkalaemic values that needed stabilization or be at risk of developing hyperkalaemia. Subjects will be randomised in a 1:1 ratio to receive SZC or none (standard of care treatment without potassium binders) for 3 months while optimizing RAASi therapies according to the European Society of Cardiology (ESC) guidelines.

Establish a cohort of diabetic kidney disease(DKD) patients with intensive weight loss treatment to evaluate the impact of intensive weight loss treatment on the renal prognosis of DKD and construct a prediction model for the improvement of renal outcomes after weight loss.

To enhance the communication on shared decision-making between older adults with advanced kidney disease and clinicians, the investigator's research team developed the "CKD Jumpstart- Tips" communication-priming intervention. This study aims to conduct a cluster-randomized controlled trial to assess the effects of the 'CKD Jumpstart- Tips' communication-priming intervention on shared decision-making between older adults with advanced kidney disease and their clinicians. The primary objective of the study is to evaluate the effects of the intervention on observer-based shared decision-making in the target consultation. The secondary objective is to evaluate the effects of intervention on patient-reported shared decision-making, quality of communication, patient involvement in decision-making, decisional conflict, decision regret, timing of and adherence to treatment choice, and health-related quality of life. Consultation length will also be captured as a process measure.

This randomized controlled trial aims to compare the effectiveness of two different timings of physical therapy for individuals undergoing hemodialysis: intradialytic (during dialysis) and pre-dialysis (before dialysis). The study seeks to determine which approach provides better improvements in physical function, quality of life, and biochemical outcomes such as hemoglobin and electrolyte levels. A total of 72 adult participants with end-stage renal disease (ESRD) receiving hemodialysis will be randomly assigned to one of two groups. Both groups will receive standardized educational sessions on the benefits and safety of exercise before beginning the intervention. Participants in the intradialytic group will perform supervised exercises during their dialysis sessions, while those in the pre-dialysis group will complete similar exercises before their dialysis sessions. Each participant will undergo the intervention twice per week for 12 weeks. Primary outcomes include physical function, assessed using the Six-Minute Walk Test and the Five Times Sit-to-Stand Test. Secondary outcomes include hemoglobin levels, electrolyte balance, and health-related quality of life measured by the KDQOL questionnaire. The study will be conducted at Mubarak Al-Abdullah Al-Jaber Al-Sabah Dialysis Center, Kuwait, following ethical approval from the Ministry of Health Research Ethics Committee. The results are expected to inform best practices for integrating physical therapy into dialysis care to enhance the health, safety, and well-being of individuals undergoing hemodialysis.

Acute kidney injury (AKI) is a common complication of cardiac surgery occurring in up to 40% of patients.1, 2 This is more than 10 times the rate of other serious post-surgical complications in cardiac surgery such as stroke or deep sternal infection and is even greater than the incidence of prolonged ventilation.3, 4 Severe AKI requiring new onset dialysis after cardiac surgery occurs in 1-6% of cardiac surgery patients.3, 5 AKI increases length of hospital stay from 5 to 11 days and increases hospital costs from $18,463 to $37,674 per patient.6 The severity of AKI is strongly associated with in-hospital mortality with even the mildest forms of AKI having more than double the mortality and the more severe forms having 10-30 times higher mortality rates (depending on the definition of severe AKI and the patient population).6, 7 AKI contributes to 300,000 annual deaths in the U.S. and 2 million deaths globally each year.8, 9 Considering only the most relevant patient populations (major aortic and spinal surgery, relevant cardiovascular procedures, intensive care patients on mechanical ventilation, severe trauma patients), in the US alone more than 3.1 million patients per year are at risk of AKI.10-14 Of those, 30.6%12, 13, 15 will suffer AKI - adding annual hospital costs of $19 billion.6 It is for these reasons that the Society of Thoracic Surgeons lists renal failure as one of the 5 major complications of cardiac surgery. The pathophysiology of AKI after cardiac surgery is multifactorial but the profound hemodynamic changes that occur in cardiac surgery likely play an important role. The renal medulla has the highest metabolic activity and least oxygen reserve in the kidney and medullary hypoxia is thought to be a major determinant of AKI.16, 17 One major limitation in the effort to reduce the incidence of AKI is the lack of a real-time monitor of renal hypoxia. As there is no current therapy for AKI once the disease has occurred, prevention is the mainstay of treatment and an important step in preventing AKI is its timely recognition. Current diagnostic methods based on serum creatinine, oliguria, or even novel biomarkers, however, take hours to days to become diagnostic. The investigators have no accepted standard for diagnosing kidney hypoxia in real-time before the injury becomes irreversible. Most clinicians base intraoperative hemodynamic goals for the kidney on "educated guesses" of adequate renal perfusion, since the exact cardiac output or mean arterial pressure targets for preventing AKI are unknown. Even the practice of monitoring urine output is uncertain because of its non-specific relationship to kidney function.18-20 Near infrared spectroscopy (NIRS) is a promising technology for monitoring tissue hypoxia because it is noninvasive and has a long history of clinical use as a monitor of cerebral oximetry in both cardiac and vascular surgery. Because NIRS measures a mixture of arterial and venous capillary oxygenation, it is particularly well-suited to monitor the balance between oxygen consumption and delivery. A large body of literature describes the use of NIRS both as a systemic perfusion monitor and a regional monitor of kidney perfusion in neonates and small children.21-26 In adult cardiac surgery patients, two studies using ultrasound guided placement of NIRS sensors over the kidney found that intraoperative regional tissue oxygen desaturations were associated with the subsequent development of AKI.27, 28 A third study found a correlation between NIRS oxygen saturation measurements over the kidney and renal venous oxygen saturation in adult cardiac surgery patients.29 The problem with these studies, however, is that they excluded patients for body mass index (BMI) greater than 30kg/m2 or if the surface of their kidney was greater than 4cm from the skin. According to the Center for Disease Control, the incidence of obesity (BMI greater than 30kg/m2) is over 40% in the United States and obese patients having cardiac surgery are at increased risk for AKI.30, 31 Thus, if NIRS placed over the kidney in adult patients is to be an effective tool in monitoring kidney hypoxia in adults in the United States, then the technology must be effective in all adult patients. The major limitation to the use of NIRS for renal hypoxia monitoring in adults is the depth of penetration of the signal. Manufacturers guidelines suggest that the maximum depth of penetration of NIRS is 2.5 cm. The actual depth of penetration of NIRS measurements depends on the source-detector separation, the specific algorithm used, and the optical properties of the tissue being measured. When NIRS is modeled experimentally, there is a nonlinear relationship between source-detector separation and depth of penetration such that a source-detector separation of 20 mm resulted in a depth of penetration of 10 mm but a source-detector separation of 40mm resulted in a depth of penetration of 15mm.32 While in very thin adults, the surface of the kidney may be within 2 cm from the skin, the renal medulla (where most AKI is thought to occur) is several centimeters deeper and thus unlikely to be monitored accurately. The question then arises as to how these adult cardiac surgery studies showed a relationship between NIRS placed over the kidney, AKI outcome, and even renal venous oxygen saturation.27-29 The lab developed a porcine model in which the investigators directly compared kidney medullary oxygen concentration to NIRS measurements placed over the kidney and the thigh during hemorrhagic shock and aortic occlusion.33 The investigators found during extreme hemodynamic changes such as aortic occlusion, there was a moderate correlation between NIRS and invasive kidney tissue oxygen concentration, but this was true irrespective of whether the NIRS sensors were placed over the kidney or over the thigh. The relationship between kidney NIRS and thigh NIRS was stronger than that with kidney oxygen concentration. This was in animals with kidney surface to skin distances of less than 2 cm. Taken together, these data suggest that renal NIRS in adults may be measuring subcutaneous tissue oxygenation but that it is still a global perfusion monitor that may predict poor global perfusion and AKI risk. Indeed, a study in adult cardiac surgery patients showed that NIRS sensors placed over the thigh predicted subsequent AKI with receiver operator characteristic analysis suggesting an optimal cut-off of 67% and an area under the curve of 0.84.34 The purpose of the current study proposal is to directly compare NIRS placed over the kidney to NIRS placed over the arm or the thigh in adult patients having cardiac surgery at risk for AKI. The hypothesis is that limb NIRS and kidney NIRS will both predict AKI and that the ability of NIRS to predict AKI in adult cardiac surgery patients will be independent of BMI and kidney surface to skin distance.