Kidney Disease Biomarkers

Kidney Disease Clinical Trial

Official title: Kidney Disease Biomarkers

Status Completed

Clinical Trial Summary

Kidney Disease Biomarkers

Summary: This study will identify biomarkers (proteins and other molecules in the blood or urine) that may help scientists predict what kidney disease a patient has and whether a given patient would respond to particular therapies. The study will look for biomarkers in the blood and urine of patients with various kidney diseases and study of the effects of angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARB) on biomarkers. Blood and urine from healthy volunteers will be studied for comparison.

Healthy people and the following patients may be eligible for this study: adults with diabetic nephropathy 18 years of age and older; children with newly diagnosed clinical idiopathic nephrotic syndrome between 2 and 18 year of age; children and adults with glomerular disease (minimal change disease, focal segmental glomerulosclerosis, or collapsing glomerulopathy).

Participants undergo tests and procedures as follows:

Glomerular Disease: Adults with glomerular disease provide about four to six blood and urine samples over the course of 6 to 12 months. The samples are collected at the time of regularly scheduled visits for the NIH treatment protocol in which they are participating. Children provide only blood samples.

Chronic Kidney Disease: Patients with chronic kidney disease provide a blood and urine sample every 6 months for 3 years or more.

Angiotensin Antagonism: Patients with chronic kidney disease who are taking ACE inhibitors or ARBs stop their medicines for 4 weeks, while those who are not taking ACE inhibitors or ARBs begin one of the medicines. In general, patients just starting on the medications continue them after the study is completed, since they are beneficial for chronic kidney disease.

• Medication withdrawal group: Patients come to NIH for 2 successive days at the beginning of the study for blood and urine tests (including one 24-hour urine collection) and to receive iothalamate (a chemical used to measure kidney function). Iothalamate is delivered over 24 hours through a needle placed in the abdomen (or elsewhere) via a pump similar to pumps that some diabetics use to deliver insulin. Patients then stop taking their ACE inhibitor or ARB medication. They monitor their blood pressure every day and return to NIH after 1, 2 and 4 weeks for blood tests. During week 4, the iothalamate infusion is repeated, and blood and urine samples are collected as at the beginning of the study. Patients then resume taking their ACE inhibitor or ARB once a day with the dose being increased at 2-week intervals. They come to NIH weekly after 1 week and then every other week for blood tests. Four weeks after reaching the highest FDA-recommended dose of medication tolerated, the iothalamate infusion and blood and urine collections are repeated.

• Medication induction group: At the beginning of the study, patients have the iothalamate infusion and blood and urine collections described above and then begin to take either an ACE inhibitor or ARB. The dose is increased after 2 weeks. Patients monitor their blood pressure every day. After being on the highest dose for 4 weeks, patients repeat the iothalamate infusion and blood and urine collections. The study is then complete and they are provided a 2-month supply of medicine to take home.

Information is gathered on symptoms, treatments, and results of past laboratory tests of all patients. Healthy volunteers provide blood and urine sample collections every month or every other month for up to four collections to be used for biomarker studies and the screen for common chronic diseases.

Clinical Trial Description

There is a pressing need to develop biomarkers for renal disease, which might assist in diagnosis and prognosis and might provide endpoints for clinical trials of drugs designed to slow progression of renal insufficiency. We propose to study potential biomarkers in five populations. First, we will study remittive therapy for glomerular disease (sample size up to 40), enrolling children with idiopathic nephrotic syndrome (N=20) and adults with minimal change, focal segmental glomerulosclerosis, and collapsing glomerulopathy (N=20). We will collect periodic urine samples as these patients receive remittive therapy with glucocorticoids or other agents. We will also study up to 10 healthy adult volunteers. We will carry out targeted urine proteomic studies, measuring levels of glomerular cell markers and cytokines, and we will profile urine proteins using mass spectrometry. Our goals are to identify markers of particular disease entities and of steroid responsiveness and to explore whether biomarkers contribute to the histologic sub-classification of these diseases. Second, we will study up to 40 adults with progressive chronic kidney disease of various etiologies and glomerular filtration rate <60 ml/min/1.73m2. We will study blood and urine samples, using both targeted and profiling approaches. Our goal is to identify biomarkers that correlate with progressive loss of glomerular filtration function, which is a functional correlate of progressive renal fibrosis. Third, we will study up to 40 adults, primarily with diabetic nephropathy, who start or stop angiotensin antagonist therapy (angiotensin converting enzyme inhibitors or angiotensin receptor blockers) and compare urine proteomic profiles on therapy and off therapy (4 week interval). Our goal is to identify potential biomarkers that correlate with the beneficial anti-fibrotic effects of these agents. Fourth, we wish to define possible sex differences in urine exosome proteins, obtained from healthy volunteers, who are hospitalized for six days for administration of a standard diet and collection of research urine samples. Fifth, we wish to determine whether salt intake influences urine exosome proteins, obtained from healthy volunteers. These subjects will be hospitalized for 12 days during which time they will be placed sequentially on a high salt diet and a low salt diet, with collection of research urine samples and blood pressure monitoring. Proteomic analysis in these studies will take several approaches, including mass spectrometry of urinary peptides, analysis of urinary exosomes, and immunologic detection and quantification of candidate proteins in urine and blood. ;

Related Conditions & MeSH terms

• Collapsing Glomerulopathy
• Focal Segmental Glomerulosclerosis
• Glomerular Disease
• Glomerulosclerosis, Focal Segmental
• Idiopathic Nephrotic Syndrome
• Kidney Disease
• Kidney Diseases
• Nephrosis
• Nephrotic Syndrome

• NCT number: NCT00255398
• Study type: Observational
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Start date: November 10, 2005
• Completion date: December 3, 2014