Fabry: Renal Function During Long-term ERT by 51Cr-EDTA Clearance

Fabry Disease: Renal Function During Long-term Enzyme Replacement Therapy Evaluated by Gold Standard GFR 51Cr-EDTA Clearance

The aim of this study was to investigate renal function decline by measured glomerular filtration rate (mGFR) in patients with FD during enzyme replacement therapy, and to explore the influence of age on renal function in FD.

Study Overview

• Status: Completed
• Conditions: Fabry Disease
• Intervention / Treatment: Drug: Enzyme replacement therapy

Detailed Description

Nephropathy is common in Fabry disease (FD). Renal function decline is often the first sign of major organ involvement, sometimes progressing to end-stage renal failure. Available studies of renal function during enzyme replacement therapy have shown inconsistent results, and are based on different composition of patient materials and follow-up time.

Most investigations have used estimated glomerular filtration rate (eGFR) for evaluating renal function. GFR is an important indicator of renal function. eGFR based on a serum creatinine measurement is most commonly used in FD. However, this method has been shown to be unreliable, as serum creatinine levels are influenced by other factors than renal function such as ethnic group, muscle mass, age, hydration and diet. Performance of eGFR in detecting minor changes in renal function is poor. A 10 year old review on renal function evaluation in patients with FD recommended the use of GFR based on an exogenous marker, e.g. Cr-EDTA. Nevertheless, only few studies have used mGFR for evaluation of renal function and to our knowledge, the present study is the first to describe the rate of renal function decline with consecutive mGFR values in a nationwide population of patients with FD.

Renal function declines with age in renal healthy individuals. To our knowledge, the present study is the first to age-standardize renal function in patients with FD to adjust for age-dependent renal deterioration.

• Study Type: Observational
• Enrollment (Actual): 52

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, DK-2100
    • National University Hospital, Department of Medical Endocrinology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with Fabry disease

Description

Inclusion Criteria:

• Genetically and/or enzymatically verified Fabry disease

Exclusion Criteria:

• End-stage renal disease prior to baseline (GFR <15 ml/min/1.73m2, dialysis or renal transplant)
• Patient has not received enzyme replacement therapy during follow-up
• Patient has had less than 3 measurement of GFR during follow-up

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
measured glomerular filtration rate	GFR was measured at least once a year by the one sample 51Cr-ethylenendiaminetetra acetic acid (EDTA) clearance technique using two (for duplicate determination) plasma samples 200 min after the injection of 4 (3.8-4.2) MBq 51Cr-EDTA. In children (< 15y) the injected 51Cr-activity was 3 MBq, and the blood-samples were collected 120 min after radiotracer injection. (< 5y: 2 MBq).	Assessed every 6-12 months; from baseline and up to 15 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
urinary protein excretion	Repeated twenty-four hour urine samples were collected by patients at home, the last 24 hours before coming to the hospital. These samples were analysed for albumin, creatinine and protein. Furthermore spot urine samples were applied and analysed for albumin, creatinine and protein. Albumin-creatinine-ratio was calculated and abnormal values were defined as > 30 mg/g. Urine protein- and albumin values below detection limit (< 0.04 g/L and < 3 mg/L, respectively) were converted to zero for statistical analyses.	Assessed every 6-12 months; from baseline and up to 15 years

Collaborators and Investigators

• Sponsor: Ulla Feldt-Rasmussen
• Investigators: Principal Investigator: Ulla V Feldt-Rasmussen, MD, DMSc, Department of Medical Endocrinology, Copenhagen University Hospital, Rigshospitalet

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): December 9, 2016

Study Registration Dates

• First Submitted: November 2, 2016
• First Submitted That Met QC Criteria: November 16, 2016
• First Posted (Estimate): November 21, 2016

Study Record Updates

• Last Update Posted (Actual): October 16, 2018
• Last Update Submitted That Met QC Criteria: October 15, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Enzyme replacement therapy; Nephropathy; Fabry Disease; Measured GFR
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Fabry Disease
• Other Study ID Numbers: FAB-KIDNEY

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO