Nephrogenic Systemic Fibrosis (NSF): Analysis of Tissue Gadolinium Levels

Study Overview
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Brief Summary
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The primary objective of this study is to determine any causative or associated factors for the development of Nephrogenic Systemic Fibrosis (NSF), Nephrogenic Fibrosing Dermopathy (NFD), or related diagnosis. Our primary focus will be on the previous administration of gadolinium to these patients, but we will also look at other postulated causes and risk factors. The secondary objective of this study is to assess tissue gadolinium (Gd) levels in five groups of subjects: Those affected by NSF. Those with normal kidney function who have undergone a medical imaging procedure using Gd-based contrast agent (GBCA) in the 2 years prior to a skin biopsy. Those with normal kidney function who have never been exposed to GBCA and have had a skin biopsy. Those on dialysis or with eGFR ≤ 30 ml/min/1.73 m2 who have had a medical imaging procedure using GBCA in the 2 years prior to skin biopsy. Those on dialysis or with eGFR ≤ 30 ml/min/1.73 m2 who have never been exposed to GBCA and have had skin biopsy. We hypothesize that there is a correlation between the administration of Gd-containing agents usually associated with MRI procedures and the development of NSF in those with renal failure and some other predisposing condition. We also hypothesize that tissue Gd levels in those with NSF will be higher than in those who have been exposed to GBCA but do not have NSF. Of the two groups without NSF but with exposure to GBCA, we hypothesize that those with kidney dysfunction will have higher tissue Gd levels than those with normal kidney function. We hypothesize that in the two groups of subjects without exposure to GBCA, there will be no detectable levels of Gd, regardless of kidney function status.

Official Title
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Nephrogenic Systemic Fibrosis and Gadolinium-A Medical Record Review With Analysis of Existing Skin and Other Tissue Specimens to Assess Potential Causative or Associated Factors

Conditions
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Nephrogenic Systemic Fibrosis, Nephrogenic Fibrosing Dermopathy

Participation Criteria
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Eligibility Criteria
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NSF group Inclusion Criteria: Biopsy-confirmed diagnosis of NSF Exclusion Criteria: Does not have NSF Normal renal plus gadolinium exposure Inclusion Criteria: eGFR >30 Existing skin tissue sample Gadolinium exposure in 2 years preceding skin biopsy Exclusion Criteria: Does not fit inclusion criteria Abnormal renal plus gadolinium exposure Inclusion Criteria: eGFR <30 or on dialysis Existing skin tissue sample Gadolinium exposure in 2 years preceding skin biopsy Exclusion Criteria: Does not fit inclusion criteria Abnormal renal without gadolinium exposure Inclusion Criteria: eGFR <30 or on dialysis Existing skin tissue sample No gadolinium exposure ever Exclusion Criteria: Does not fit inclusion criteria Normal renal without gadolinium exposure Inclusion Criteria: eGFR >30 Existing skin tissue sample No gadolinium exposure ever Exclusion Criteria: Does not fit inclusion criteria Controls (neonatal) Inclusion Criteria: Existing skin biopsy tissue that was performed within the first 6 months of life Exclusion criteria: Does not fit inclusion criteria
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| NSF<br>Biopsy-proven diagnosis of NSF | |
| Kidney dysfunction plus gadolinium exposure<br>Those on dialysis or with eGFR ≤ 30 ml/min/1.73 m2 who have had a medical imaging procedure using GBCA in the 2 years prior to skin biopsy. | |
| Kidney dysfunction without gadolinium exposure<br>Those on dialysis or with eGFR ≤ 30 ml/min/1.73 m2 who have never been exposed to GBCA and have had skin biopsy. | |
| Normal kidney function with gadolinium exposure<br>Those with normal kidney function who have undergone a medical imaging procedure using Gd-based contrast agent (GBCA) in the 2 years prior to a skin biopsy. | |
| Normal kidneys without gadolinium exposure<br>Those with normal kidney function who have never been exposed to GBCA and have had a skin biopsy. | |
| Controls<br>Existing skin tissue from neonatal skin (<6 months) will be used as controls, as they presumably have never been exposed to gadolinium | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine causative or associated factors for the development of Nephrogenic Systemic Fibrosis (NSF), Nephrogenic Fibrosing Dermopathy (NFD), or related diagnosis. |  | 1988 to present | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tissue Gadolinium Level in 5 groups of patients, with and without NSF | Those affected by NSF. Those with normal kidney function who have undergone a medical imaging procedure using Gd-based contrast agent (GBCA) in the 2 years prior to a skin biopsy. Those with normal kidney function who have never been exposed to GBCA and have had a skin biopsy. Those on dialysis or with eGFR ≤ 30 ml/min/1.73 m2 who have had a medical imaging procedure using GBCA in the 2 years prior to skin biopsy. Those on dialysis or with eGFR ≤ 30 ml/min/1.73 m2 who have never been exposed to GBCA and have had skin biopsy. | 1988 to present |