Clinical Research Directory

Dosimetry of Tc-99m-Tilmanocept

This proposal will use kidney SPECT/CT of Tc-99m-tilmanocept to evaluate the mesangial changes seen in diabetics across the spectrum of kidney disease as well as persons with hypertensive kidney disease, the next most common cause of kidney disease in patients with diabetes. We aim to demonstrate that these different disease types and stages can be differentiated with Tc-99m-tilmanocept SPECT/CT and can thus be used for future trials evaluating early diagnosis and treatment of diabetic nephropathy.

Mechanisms of Diabetic Kidney Disease in American Indians

Background: \- An ongoing study is looking at American Indians who have kidney problems caused by type 2 diabetes. Kidney disease due to type 2 diabetes is a major problem in American Indians. We previously found that early treatment of kidney disease with losartan was probably beneficial for reducing progression of the disease. Researchers now want to see if these benefits continue to be seen several years after the end of the treatment study. Objectives: \- To study long-term benefit of losartan treatment for diabetic kidney disease in American Indians with type 2 diabetes. Eligibility: \- Participants in the American Indian diabetic kidney disease study (OH95-DK-N037). Design: * Participants will have a physical exam and medical history before starting the study. Blood and urine samples will be collected. * Participants will have a set of tests as part of this study. Those who have severe kidney problems, such as kidney failure, will only have a basic kidney exam with scans. The remaining participants will have a full urine collection and analysis. They will also provide a kidney biopsy. * Treatment will not be provided as part of this study.

Family Investigation of Nephropathy and Diabetes (F.I.N.D.)

The Family Investigation of Nephropathy and Diabetes (FIND) is a multicenter study designed to identify genetic determinants of diabetic kidney disease. FIND will be conducted in eleven centers and in many ethnic groups throughout the United States. Two different strategies will be used to localize genes predisposing to kidney disease: a family-based genetic linkage study and a case-control study that utilizes admixture linkage disequilibrium. The center based at the Phoenix office of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK-Phoenix) will conduct family-based linkage studies among American Indian populations in the southwestern United States. Participants (index cases) with diabetes and kidney disease will initially be recruited, and their parents and siblings will also be invited to participate. Genetic material from these participants will be used to genotype markers throughout the genome. Linkage analysis will be conducted to identify particular chromosomal regions containing genes that influence susceptibility to diabetic kidney disease. Linkage analyses will also be used to identify genes influencing traits related to diabetic kidney disease, such as serum creatinine, urinary protein excretion, plasma glucose levels, blood pressure and blood lipid levels. Regions that show evidence for linkage will then be examined in more detail, with both genetic linkage and association studies, to attempt to identify the specific genes that influence diabetic kidney disease, or related traits. The identification of genes that influence susceptibility to diabetic kidney disease will lead to a better understanding of how kidney disease develops. In the long run, this may lead to improved treatment and prevention of diabetic kidney disease.

The Evaluation of the Drug R3R01 for the Excretion of Protein in the Urine in Patients With Diabetic Kidney Disease.

The goal of this clinical trial is to to investigate whether the drug R3R01 has a beneficial effect on the amount of protein excreted in the urine in adult patients (above 18 years of age) with type 2 diabetes and resulting kidney disease. The main questions it aims to answer are: 1. Does 3 months of treatment with 200mg of the drug R3R01 morning and evening have a beneficial effect on the amount of protein excreted in the urine in patients with type 2 diabetes and kidney disease? 2. Does R3R01 have an effect on kidney function and daily blood pressure? Researchers will compare the results of 40 people who take R3R01 to 20 people who receive an inactive substance (placebo). Participants will receive R3R01 or the placebo as an oral tablet and undergo a selection of medical examinations - such as: * blood samples * urine tests * kidney tests involving a radiolabelled marker which is injected into the bloodstream and monitored via blood samples * 24 hour blood pressure monitoring via a wearable device * urine pregnancy test (if applicable)

Development and Validation of a Machine Learning Model for Differentiating Diabetic Kidney Disease and Non-Diabetic Kidney Disease in Type 2 Diabetes

This multicenter retrospective observational study aims to develop and validate an interpretable machine learning model for differentiating diabetic kidney disease (DKD) from non-diabetic kidney disease (NDKD) in patients with type 2 diabetes mellitus. Clinical, laboratory, and pathological data from biopsy-confirmed patients were collected from 14 medical centers in China. Multiple machine learning algorithms were evaluated and externally validated. The final model was implemented as a web-based clinical decision support tool.

Evaluation of MTX-439 in Healthy Adults and Adults With Diabetic Kidney Disease

This is a phase 1 randomized, double-blind, single ascending dose (SAD) and multiple ascending dose (MAD) study to assess the safety, tolerability, and Pharmacokinetics (PK) of single and multiple ascending doses of MTX-439 administered in healthy adults and adults with diabetic kidney disease (DKD)

Effect of Chinese Herbal Medicine on Renal Function in Diabetic Kidney Disease

This study is a randomized controlled pilot trial designed to evaluate the effects and safety of a traditional Chinese medicine formula (DKD-1) as an add-on therapy to standard treatment in patients with Diabetic Kidney Disease (DKD). Eligible participants will be randomly assigned to receive either standard care alone or standard care combined with DKD-1 for 12 weeks. Kidney function, glycemic control, proteinuria, quality of life, and traditional Chinese medicine tongue features will be assessed before and after the intervention. The study aims to provide preliminary evidence on whether DKD-1 can improve renal function, glycemic control, and quality of life in this patient population.

Effect of Urinary Alkalinization on Urine Uric Acid Precipitation and Crystallization in Adults With Type 1 Diabetes

The purpose of this study is to determine whether alkalinization of urine uric acid by 2 doses of sodium bicarbonate (1950mg) over 24-hours reduces precipitation and crystallization of urine uric acid over in adults with type 1 diabetes.

Mechanism of SGLT2 Inhibition in the Kidney

The goal of this open-label, non-randomized clinical trial is to determine what effects, if any, an FDA-approved drug class known as SGLT2 inhibitors (Canagliflozin or INVOKANA) has any protective effects on kidney function in Type 2 diabetes. We are looking for participants 18-80 years of age, who have had a clinical diagnosis of Type 2 diabetes for ≥ 3 years. Participants will be asked to sign a consent and complete a screening visit prior to study entry including the following procedures for this study: Consent and Screening: * Laboratory tests to determine baseline health * Ultrasound to measure kidney size and ensure presence of 2 functioning kidneys Month 0: * Study entry kidney MRI (day 0) * Study entry kidney biopsy (within 30 days of MRI) * Study entry visit for dispensing 100 mg/daily Canagliflozin medication 3 month supply Month 3: * Study visit to dispense remaining 3 months of 100 mg/daily Canagliflozin medication * Review of systems Month 6: * Follow-up kidney MRI * Follow-up kidney biopsy Study participants will also be requested to provide blood and urine samples for biobanking purposes. They will also be provided the opportunity to provide a stool sample at two time points, as well as the option to participate in a related study collecting samples to create induced Pluripotent Stem Cells (iPSCs). Participants will be compensated for their time and loss of work time, additionally, a nominal additional compensation for optional stool and iPSC samples.

Trial of Semaglutide for Diabetic Kidney Disease in Type 1 Diabetes

The primary objective of this study is to determine the effects of semaglutide on change in albuminuria from baseline to 26 weeks in type 1 diabetes. The secondary objective is to determine the effects of semaglutide on change in kidney parameters (including kidney oxygenation and function) measured by MRI from baseline to 26 weeks in type 1 diabetes. Other objectives are to determine the glycemic effects and safety of semaglutide in type 1 diabetes.

Renal Mechanism of SGLT2 Inhibition

Canagliflozin is an oral drug which is currently approved for use in patients with type 2 diabetes by the US Food and Drug Administration (FDA). Canagliflozin acts by increasing salt and sugar loss in the urine, and has shown to protect heart, kidney, and blood vessel function in patients with type 2 diabetes. However, it is unknown how canagliflozin protects the kidneys from disease. Therefore, this study plans to learn more about how canagliflozin works to protect against diabetic kidney disease in adults with type 2 diabetes. This study will use state-of-the-art kidney imaging, kidney biopsies and detailed testing of kidney function to determine the mechanisms of protection afforded by canagliflozin.

Atrasentan in Patients With Proteinuric Glomerular Diseases

The AFFINITY Study is a phase 2, open-label, basket study to evaluate the efficacy and safety of atrasentan in patients with proteinuric glomerular disease who are at risk of progressive loss of renal function.

Pathogenesis of Kidney Disease in Type 1 Diabetes: a Modern Kidney Biopsy Cohort (The PANDA Study)

Diabetic kidney disease (DKD) occurs in up to 40% of people with type 1 diabetes (T1D), often leading to kidney failure and markedly magnifying risks of cardiovascular disease and premature death. Landmark T1D kidney biopsy studies identified the classic pathological lesions of DKD, which have been attributed largely to hyperglycemia. Recent advances in continuous glucose monitoring (CGM) and automated insulin delivery have facilitated improved glycemic control, but the residual risk of DKD continues to be high. In addition, obesity and insulin resistance (IR) have accompanied intensive glycemic therapy and may promote mitochondrial dysfunction and inflammation. Deciphering the molecular underpinnings of DKD in modern-day T1D and identifying modifiable risk factors could lead to more effective and targeted therapies to prevent DKD.

Spironolactone Alternate Dosing vs Finerenone in Elevated Potassium - K Safety Study

This study evaluates the safety of finerenone compared with alternate-day spironolactone in patients with heart failure and diabetic kidney disease at increased risk of hyperkalemia. Patients with chronic kidney disease and heart failure often benefit from mineralocorticoid receptor antagonists, but their use is frequently limited by elevated potassium levels. Finerenone has been associated with a lower risk of hyperkalemia in clinical trials, but direct comparisons with spironolactone in high-risk patients are limited. In this randomized study, eligible participants will be assigned to receive either finerenone once daily or spironolactone on alternate days, in addition to standard therapy. Patients will be closely monitored during hospitalization and followed for 4 weeks. The primary outcome is clinically relevant hyperkalemia, defined by elevated potassium levels or the need to adjust or discontinue treatment due to hyperkalemia. Secondary outcomes include changes in potassium levels, kidney function, and clinical events. This study aims to provide practical evidence to guide the safe use of mineralocorticoid receptor antagonists in patients at high risk for hyperkalemia.

DiEtary Sodium Intake Effects on Ertugliflozin-induced Changes in GFR, reNal Oxygenation and Systemic Hemodynamics: the DESIGN Study

SGLT2 inhibitors such as ertugliflozin improve blood pressure and kidney outcomes in people living with diabetes through incompletely understood mechanisms, however, not all patients treated with SGLT2 inhibition have improved outcomes. Changes in kidney sodium handling is among the mechanisms by which SGLT2 inhibition may reduce blood pressure and drive beneficial kidney outcomes. This process is heavily dependent on daily sodium intake by patients receiving SGLT2 inhibitor treatment. In this study, the effect of daily sodium intake on SGLT2-inhibitor induced physiological effect is studied, including blood pressure regulation and kidney physiology.

NAD Augmentation in Diabetes Kidney Disease

A phase 2a trial randomized, double-blind, placebo-controlled, parallel group trial to determine whether NMN administration improves DKD, as indicated by a significantly greater reduction in UACR compared with placebo administration. Eligible participants will be randomized to receive either 1000 mg NMN or placebo twice daily.

Pentoxifylline in Diabetic Kidney Disease

Pentoxifylline (PTX) is a medication that has been on the market since 1984 for use in disease in the blood vessels of the legs. There is some preliminary information that it may protect the kidneys from damage due to diabetes and other diseases. "Pentoxifylline in Diabetic Kidney Disease" is a study to bee conducted in 40 VA hospitals across the nation to determine definitively whether or not PTX can prevent worsening of kidney disease and delay death in patients with diabetic kidney disease.

Multimodal Magnetic Resonance Imaging in Evaluation of Diabetic Kidney Disease

The goal of this study is to investigate the value of noninvasive evaluation of multimodal magnetic resonance imaging in diagnosis and treatment of diabetic kidney disease (DKD). We aim to explore the feasibility of multimodal magnetic resonance imaging in the staging diagnosis of DKD, and establish a non-invasive method for evaluating the progression of DKD disease by combining imaging and biochemical indicators. Multimodal magnetic resonance examinations will be performed on diabetic patients with different stages as well as regular follow-up during treatment, in order to investigate the relationship between imaging findings and pathophysiological changes of the kidneys.

Improving Kidney Care in Type 2 Diabetes: A Study of Pharmacist Prescribing Versus Usual Care

Type 2 diabetes is the leading cause of chronic kidney disease, which can result in serious complications such as kidney failure and heart disease. Although effective medications exist to slow the progression of kidney damage, they are often underused in primary care, particularly for individuals without a regular family doctor. In response to this gap, 46 community pharmacy-led primary care clinics were launched across Nova Scotia in 2023 to serve under-resourced areas. Pharmacists at these clinics can prescribe for many chronic conditions, but currently not for diabetic kidney disease. To address this, the research team collaborated with kidney, diabetes, and primary care experts, patient partners and regulatory bodies to develop and validate step-by-step prescribing guide (called algorithms) that support pharmacists in identifying and managing diabetic kidney disease. All medications included are approved, publicly funded in Nova Scotia, target people with earlier categories of diabetic kidney disease and includebuilt-in safety monitoring, nurse practitioner consultation or referral to a kidney doctor. This study will evaluate whether these algorithms improve kidney protective medication use which have shown to be beneficial for people with diabetes and kidney disease. The investigators will recruit 120 adults with type 2 diabetes from a provincial diabetes registry who do not have a primary care provider and screen them at pharmacy clinics for diabetic kidney disease. Those eligible and who wish to participate will be randomly assigned to either an intervention group receiving pharmacist-led care using the algorithms or a control group receiving usual care through walk-in, mobile, or virtual clinics. The investigators will measure how many patients begin and continue recommended medications, as well as any medication-related side effects or hospitalizations. Pharmacist participants will also complete a survey to identify what helps or hinders implementation in real-world practice. This research is relevant because it aims to expand access to kidney-protective treatments for people with diabetes, especially those with early forms of diabetic kidney disease who do not have regular access to primary care provider, ultimately improving long-term health outcomes.

The Hong Kong Diabetes Biobank

Asia is in the midst of an epidemic of diabetes. Epidemiological figures suggest that there are more than 110 million people affected by diabetes in China, with a significant proportion of young adults already affected. With increasingly young age of onset, the financial implications due to productivity loss and health care expenditures are colossal. As a result, prevention of diabetes and diabetic complications has been identified as a top healthcare priority in China. In Chinese, diabetic kidney disease with albuminuria, which reflects widespread vascular damage, is a major predictor for end-stage renal failure, cardiovascular complications and death, and a major contributor to the increased healthcare burden associated with diabetes. There is an immense demand for effective tools which can accurately predict diabetes and diabetic complications. Only few genetic factors have been consistently shown to be associated with diabetic kidney disease or other diabetic complications. Identification of genetic factors or other biomarkers predicting these complications can facilitate early identification of high risk subjects for treatment, as well as provide novel targets for drug treatment. To address this, the investigators plan to utilize both hypothesis-generating whole-genome approach as well as candidate gene-based studies to identify novel genetic, epigenetic factors as well as other biomarkers associated with the development of diabetic cardiovascular and renal complications, as well as other diabetes-related outcomes. The Hong Kong Diabetes Biobank (HKDB) is being established in order to serve as a territory-wide diabetes register and biobank for epidemiological analyses, as well as large-scale discovery and replication of genetic and epigenetic markers, and other biomarkers relating to diabetes, diabetes complications or related outcomes. Subjects will be recruited from diabetes centres across Hong Kong, and will have detailed clinical information collected at the time of written consent and blood taking. Subjects will have detailed assessment of baseline diabetes complications through a structured clinical assessment, and will be prospectively followed up for development of different diabetes-related endpoints, as well as collection of clinical information and causes of hospitalization, along with information on medications and prescription records. This multi-centre cohort and biobank aims to improve our understanding of the epidemiology of diabetes and diabetes complications and related outcomes, as well as provide a unique resource for large-scale biomarker research to advance diabetes care and precision medicine in diabetes.

Immune System in Diabetic Kidney Disease

Diabetes is a chronic condition marked by long-term elevated blood glucose levels. There are more types of diabetes; the majority of patients have type 1 or type 2 diabetes. Over long period of time, high blood sugar damages blood vessels and organs. One of the most common complications is diabetic kidney disease, which can slowly lead to kidney failure. People with this condition also have a much higher risk of heart and blood vessel diseases. Newer research shows that the immune system, especially the complement system (a group of proteins that help defend the body), may also play a role in worsening kidney disease in diabetes. High blood sugar can activate these proteins, and they have been found in kidney tissue of patients with diabetic kidney disease. The goal of this study is to find out how much the complement system contributes to kidney damage in diabetes, whether it affects different groups of patients differently, and whether it is linked to blood vessel health or the stage of kidney disease. The study will also assess if improved diabetes control is linked to reduced complement system activity.

Formoterol in Diabetes

The purpose of the study is to evaluate if formoterol fumarate is effective in treating patients with diabetic kidney disease. Study participants will be randomly assigned to either receive formoterol fumarate (in addition to their current standard of care treatment) or standard of care treatment only. Study participants will have a 50% chance of receiving formoterol fumarate and a 50% chance of not receiving formoterol fumarate. Both groups will continue their standard of care treatment during the study. The primary goal is to gather data on feasibility and effect sizes to properly power a future clinical trial.

Gut Microbiota and Serum Metabolites as Predictors of Glycemic Variability and Outcomes in Diabetic Kidney Disease

Diabetic kidney disease (DKD) is one of the main complications of diabetes and a leading cause of end-stage kidney disease. Blood glucose variability is closely associated with disease progression in individuals with DKD. Recent evidence suggests that gut bacteria and their circulating metabolites may play important roles in regulating blood glucose variability and clinical outcomes. However, it remains unclear whether gut bacteria and blood metabolites influence DKD progression through effects on blood glucose variability. This study aims to (1) characterize gut bacteria and blood metabolites in individuals with DKD at different stages and levels of disease severity, and evaluate their value in predicting adverse outcomes; (2) assess the relationships among gut bacteria, blood metabolites, and blood glucose variability; and (3) determine whether gut bacteria and blood metabolites affect clinical outcomes by modulating blood glucose variability. A total of 270 individuals with DKD will be enrolled in a prospective observational cohort. The investigators will conduct continuous glucose monitoring and collect stool and blood samples for advanced analyses of gut microbiota and blood metabolites. The objective is to clarify how gut bacteria and circulating metabolites relate to blood glucose variability and disease prognosis, and to develop tools to identify high-risk individuals at an early stage. Ultimately, the findings may provide new insights and strategies to improve clinical care and quality of life for individuals with DKD.

"Residual Kidney Function and Oxidative Stress in Incremental vs Standard Peritoneal Dialysis (2 Mexican Centers)"

Title: Comparison of Oxidative Stress and Preservation of Residual Kidney Function Between Incremental and Standard Peritoneal Dialysis in Incident Patients at the Regional General Hospital No. 58 and HGZ/UMF 21 of the Mexican Institute of Social Security (IMSS) in León, Guanajuato BACKGROUND: Peritoneal dialysis (PD) employs hypertonic dextrose-based solutions to remove toxins and excess fluids. This exposure promotes mitochondrial overproduction of reactive oxygen species (ROS), triggers inflammation, and may accelerate the decline of residual kidney function (RKF), leading to complications such as peritonitis, peritoneal fibrosis, and technique failure. Although more biocompatible solutions are available, their high cost and limited accessibility restrict their use in our setting. Incremental peritoneal dialysis (IPD), in contrast to standard peritoneal dialysis (SPD)-which typically involves four daily exchanges with full-dose dialysis-uses reduced dialysis doses tailored to RKF, thereby decreasing glucose exposure. The primary aim of this study was to compare the effects of IPD versus SPD on oxidative stress, inflammation, and the preservation of residual kidney function in incident peritoneal dialysis patients at the Regional General Hospital No. 58 in León, Guanajuato. MATERIALS AND METHODS: A prospective, longitudinal, single-center, open-label, randomized clinical trial will be conducted. Incident peritoneal dialysis patients at the Regional General Hospital No. 58 and Gneral Hospital of Zone Numbre 21 of the Mexican Institute of Social Security (IMSS) who meet the inclusion criteria and provide informed consent will be randomly assigned to either the standard or incremental peritoneal dialysis group. Acute-phase reactants will be measured at baseline and at 3, 6, 9, and 12 months. Oxidative stress will be assessed via baseline and end-of-study malondialdehyde levels. Dialysis and urine Kt/V will be evaluated betwen 6 weeks and 3 moths and 6, 9, and 12 months. Appropriate statistical analyses will be performed thereafter.