Author Interview: Jerrold L. Abraham, MD
Co-Authors: Sanyal S, Marckmann P, Scherer
Multiorgan gadolinium (Gd) deposition and fibrosis in a patient with nephrogenic systemic fibrosis--an autopsy-based review.

Sanyal S, Marckmann P, Scherer S, Abraham JL.
Nephrol Dial Transplant. 2011 Mar 25.

What are the main findings of the study?

The distribution of deposits of insoluble Gadolinium (Gd) phosphates resulting from the release of Gd from the chelated form in MRI contrast agents had not been previously studied at the histologic scale other than in skin. This extensive examination of many tissues from an autopsy case of Nephrogenic Systemic Fibrosis (NSF) documents the widespread distribution of such deposits. Most deposits were seemingly related to blood vessels, but intraparenchymal deposits in cells of some organs such as liver were also noted.

Were any of the findings unexpected?

The most surprising finding was the deposition of Gd within cells in the central nervous system (cerebellum). The deposition of Gd has been shown in abnormal brain tissue (i.e., brain tumors) even with normal renal function, but apparently in some cases of NSF the Gd (either in chelated form and/or after release of free Gd from the chelate) is able to cross the Blood Brain Barrier (BBB) in otherwise normal brain tissue. Although we have detected Gd in myocardium in many other NSF cases, none was detected in this case (most likely a result of solubilization of Gd-phosphate deposits during acidic fixation of the heart).

What should clinicians and patients take away from this study?

The widespread distribution of Gd in tissues of NSF patients highlights the need to prevent this disease and also the need for further studies of the mechanisms involved in the reactions to Gd and the complex problem of calcium and phosphate regulation and sequelae in patients with chronic renal failure (CRF) or end stage renal disease (ESRD). For example, the role of Gd itself in promoting calcium phosphate deposition is in need of further study.
Remember that each single standard dose of Gd contrast agent contains approximately 1.5 GRAMS of the element Gadolinium, of which approximately 1% (15 mg) may be retained in the body (mostly in bones) even in persons with normal renal function.

What recommendations do you have for nephrology health care providers as a result of your study?

First, this study reminds the clinician of systemic involvement by this predominantly dermatologic clinical condition. And the systemic involvement (fibrosis in many organs) is associated with widespread gadolinium deposition. Systemic pathologic involvement when present may be subtle and overlap with findings of chronic renal failure. Since this is a rare and disappearing disease, clinicians should keep NSF in the differential diagnosis of systemic clinical findings in a patient with NSF.

Clinicians should become aware of the potential for release of Gd from various MRI contrast agents (both existing and newer ones) and possible long term consequences of accumulation of a body burden of Gd in millions of patients. This will require long term follow up and investigations by many medical scientists.

Multiorgan gadolinium (Gd) deposition and fibrosis in a patient with nephrogenic systemic fibrosis--an autopsy-based review.
Sanyal S, Marckmann P, Scherer S, Abraham JL.
Nephrol Dial Transplant. 2011 Mar 25.
Department of Pathology, SUNY Upstate Medical University, Syracuse, NY.


Abstract

BACKGROUND:
Nephrogenic systemic fibrosis (NSF) is a systemic disorder of patients with severe renal insufficiency who have received gadolinium (Gd)-based magnetic resonance contrast agents (GBCAs). The causative association with Gd exposure was strengthened by the demonstration of Gd in various tissues of NSF patients, predominantly at the bulk chemical level. The distribution of Gd at the histologic level of organs other than skin has not been reported previously.

METHODS:

We analysed tissues from an autopsy case with verified advanced NSF by light microscopy and scanning electron microscopy/energy-dispersive X-ray spectroscopy. Furthermore, we reviewed published literature to compare the histological and histochemical findings in NSF patients and chronic renal failure (CRF) patients without NSF.

RESULTS:

Insoluble Gd-phosphate deposits were detected in the skin, liver, lungs, intestinal wall (ileum), kidney, lymph node, skeletal muscle, dura mater and cerebellum of the NSF autopsy case, primarily in vascular walls. Some, but not all, Gd deposits were seen in fibrotic areas. Literature review highlighted that non-specific tissue fibrosis and calcification are frequent findings in tissues of patients with CRF with and without NSF.

CONCLUSIONS:

Vascular and extracellular Gd deposits are found in multiple organs of NSF patients, associated with calcification, and often in fibrotic areas. Gd deposits are not seen in patients with CRF unexposed to GBCAs but rarely may be seen in GBCA-exposed patients without clinical signs of NSF. Apart from diagnostic findings in skin, fibrosis of muscle and dura may be more prominent in NSF patients. Our findings should stimulate further investigation of mechanisms of fibrosis and pathologic calcification.

More on Nephrogenic Systemic Sclerosis - NSF

 


 
 
 
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