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CASE REPORT |
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| Year : 2010 | Volume
: 64
| Issue : 1 | Page : 33-36 |
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Nephrogenic systemic fibrosis following acute kidney injury and exposure to gadolinium
Archana Bhaskaran1, Purna Kashyap2, Brent Kelly3, Princy Ghera4
1 Department of Infectious Diseases, Cleveland Clinic, Cleveland, Ohio, USA
2 Department of Gastroenetrology, Mayo Clinic, Rochester, USA
3 Department of Dermatology, University of Texas Medical Branch, Galveston, Texas, USA
4 Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas, USA
| Date of Web Publication | 31-Jan-2012 |
Correspondence Address:
Archana Bhaskaran
35 Severance Circle, #822, Cleveland Heights, Cleveland, OH 44118
USA
DOI: 10.4103/0019-5359.92485 PMID: 22301807
Nephrogenic systemic fibrosis (NSF) is a scleroderma-like systemic fibrosing condition of unknown etiology described in patients with renal insufficiency. Gadolinium exposure has been strongly associated with the development of NSF though the mechanism of such injury is not known. There are only few reported cases of NSF in the setting of acute renal failure and fewer reported cases where skin lesions developed after kidney function had returned to normal. We report a case of NSF in a young Hispanic woman with lupus nephritis but normal creatinine, who received gadolinium during a brief episode of prerenal acute kidney injury not requiring dialysis, secondary to sepsis.
Keywords: Acute renal failure, gadolinium, nephrogenic systemic fibrosis, normal creatinine, normal kidney function, prerenal acute renal failure
How to cite this article:
Bhaskaran A, Kashyap P, Kelly B, Ghera P. Nephrogenic systemic fibrosis following acute kidney injury and exposure to gadolinium. Indian J Med Sci 2010;64:33-6 |
How to cite this URL:
Bhaskaran A, Kashyap P, Kelly B, Ghera P. Nephrogenic systemic fibrosis following acute kidney injury and exposure to gadolinium. Indian J Med Sci [serial online] 2010 [cited 2013 May 23];64:33-6. Available from: http://www.indianjmedsci.org/text.asp?2010/64/1/33/92485 |
| ¤ Introduction | |  |
Nephrogenic systemic fibrosis (NSF) is a relatively new disease characterized by scleroderma-like systemic fibrosis. It has been predominantly reported in patients on dialysis or with advanced kidney disease. Recently, gadolinium exposure has been strongly associated with the development of NSF. Therefore, there are restrictions on the use of gadolinium in patients with renal failure.
| ¤ Case Report | | |
The patient was a 37-year-old Latin American woman, recently diagnosed with lupus nephritis, diffuse proliferative type 4. She was initiated on prednisone 60 mg tid and mycophenolate 1500 mg tid. Her serum creatinine was mildly increased at 0.87 mg/dl. An estimated glomerular filtration rate (eGFR), calculated from serum creatinine using the Modification of Diet in Renal Disease (MDRD) Study equation, was 78 ml/min at this point. One month after initiation of therapy, she developed bilateral lower extremity cellulitis and sepsis with hemodynamic instability. During the hospital stay, she developed acute renal failure and metabolic acidosis secondary to sepsis. Renal failure was likely pre-renal as she had an FE Na of <1, a benign urine sediment, and responded to volume resuscitation. The patient had significant lower extremity edema and underwent magnetic resonance angiography (MRA) with gadolinium of the abdomen, pelvis and lower extremities to assess for an inferior vena cava thrombus. The MRA results did not support this entity. The serum creatinine at the time of this investigation was 1.82 mg/dl (eGFR 33 ml/min) and continued to increase to a maximum of 2.42 mg/dl (eGFR 24 ml/min) over the next 3 days. It normalized to her baseline, <1.0 mg/dl, after 10 days with fluid and pressor support. Anti-cardiolipin antibodies were positive 1 month prior to the above admission but negative during this period. She had had a central line placed during the ICU admission.
The patient presented 3 months after recovery from acute renal failure with a 2-week history of a skin rash, which initially was noted on both arms and eventually involved the back and abdominal area. She reported pruritus but denied any fever or jaundice. Her medications included Glipizide, Mycophenolate (250 mg daily), Prednisone (20 mg daily), Vitamin C and Zinc sulfate. She denied recent intake of new medications like erythropoietin or angiotensin-converting enzyme inhibitors. On examination, large, indurated, hyperpigmented, slightly erythematous, and well-demarcated plaques were seen on the back [Figure 1] and abdomen. There were erythematous and edematous plaques on the forearms. The serum creatinine at this point was 0.42 mg/dl (eGFR > 90 ml/min). | Figure 1: Well-demarcated erythematous, hyperpigmented and indurated plaque on the back
Click here to view |
A punch biopsy of the lesion on the abdomen revealed dermal proliferation of spindle-shaped fibroblasts and slightly thickened collagen bundles with only minimal inflammation [Figure 2]. A mucin stain (colloidal iron) revealed a mild increase of dermal mucin. The fibroblasts were positive for CD-34 by immunohistochemistry (IHC) [Figure 3]. These features were consistent with a diagnosis of NSF. Uninvolved skin of the right shoulder did not reveal any abnormal histologic findings. Interestingly, in both involved and uninvolved skin, gadolinium was detected in the paraffin-embedded samples by energy dispersive X-ray spectroscopy. | Figure 2: Dermal proliferation of spindle-shaped fibroblasts and slightly thickened collagen bundles with minimal inflammation (H and E, ×200)
Click here to view |
 | Figure 3: Immunohistochemistry with CD34 showing strong positive staining in the dermal fibroblasts (IHC - streptavidin biotin, ×200)
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| ¤ Discussion | | |
In summary, our patient was a young Hispanic female recently diagnosed with lupus nephritis and had a relatively normal serum creatinine, who was initiated on steroids and immunosuppressive therapy. She presented with normal creatinine and NSF, 3 months after exposure to gadolinium, which occured at the time of prerenal acute kidney injury. Based on Naranjo's algorithm for adverse drug reaction, the skin lesions were probably (score = 5) secondary to gadolinium. [1]
The first case series of NSF was reported in 2000 by Cowper et al. as skin lesions in patients on dialysis, but subsequently was shown to involve other organs. NSF has been associated with severe edema, venous thrombosis, anti-phospholipid antibody, vascular intervention, erythropoietin therapy and gadolinium exposure. [2],[3],[4],[5] Metabolic acidosis may predispose patients exposed to gadolinium to develop NSF. [4] Of the above-mentioned conditions, our patient had edema, vascular intervention, gadolinium exposure, metabolic acidosis and history of a hypercoagulable state. The course of the disease is variable but regression of skin lesions has been observed with improvement of renal failure and renal transplantation. [6]
The exact pathogenesis of NSF is not completely understood. Normal renal elimination of gadolinium is prolonged in renal insufficiency. [7] Gadolinium is complexed with a ligand which dissociates over a prolonged period of time at a low pH to a free ion which can deposit in tissues. [4],[7] Gadolinium, rather than the chelator, seems to be the culprit in the development of NSF. [8] An in vitro study demonstrated macrophages exposed to gadolinium release proinflammatory and profibrotic cytokines including TGF-β which stimulate dermal fibroblasts to secrete collagen. [5] Fibrosis has been demonstrated in skin, subcutaneous tissue, fascia and visceral organs along with increased expression of TGF-β . [9]
NSF has been predominantly reported in patients on dialysis or with advanced kidney disease. There are only few reported cases of NSF in the setting of acute renal failure and fewer reported cases where skin lesions developed after kidney function had returned to normal. [2],[10],[11] Our case is also unique in that NSF developed in the setting of prerenal azotemia. In our patient, renal insufficiency in addition to edema, vascular intervention and acidic milieu at the time of gadolinium administration probably led to deposition of gadolinium in the skin, which was not mobilized after recovery of renal function, and thus the development of NSF. Our case reinforces that acute kidney injury is a risk factor for the development of NSF when exposed to gadolinium.
| ¤ References | | |
| 1. | Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45. 
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| 2. | Cassis TB, Jackson JM, Sonnier GB, Callen JP. Nephrogenic fibrosing dermopathy in a patient with acute renal failure never requiring dialysis. Int J Dermatol 2006;45:56-9.
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| 3. | Cowper SE. Nephrogenic fibrosing dermopathy: The first 6 years. Curr Opin Rheumatol 2003;15:785-90.
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| 4. | Grobner T. Gadolinium--a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant 2006;21:1104-8.
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| 5. | Wermuth PJ, Del Galdo F, Jiménez SA. Induction of the expression of profibrotic cytokines and growth factors in normal human peripheral blood monocytes by gadolinium contrast agents. Arthritis Rheum 2009;60:1508-18.
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| 6. | Panesar M, Banerjee S, Barone GW. Clinical improvement of nephrogenic systemic fibrosis after kidney transplantation. Clin Transplant 2008;22:803-8.
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| 7. | Bongartz G. Imaging in the time of NFD/NSF: Do we have to change our routines concerning renal insufficiency? MAGMA 2007;20:57-62.
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| 8. | Sieber MA, Lengsfeld P, Walter J, Schirmer H, Frenzel T, Siegmund F, et al. Gadolinium-based contrast agents and their potential role in the pathogenesis of nephrogenic systemic fibrosis: The role of excess ligand. J Magn Reson Imaging 2008;27:955-62.
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| 9. | Jiménez SA, Artlett CM, Sandorfi N, Derk C, Latinis K, Sawaya H, et al. Dialysis-associated systemic fibrosis (nephrogenic fibrosing dermopathy): Study of inflammatory cells and transforming growth factor beta1 expression in affected skin. Arthritis Rheum 2004;50:2660-6.
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| 10. | Kalb RE, Helm TN, Sperry H, Thakral C, Abraham JL, Kanal E. Gadolinium-induced nephrogenic systemic fibrosis in a patient with an acute and transient kidney injury. Br J Dermatol 2008;158:607-10.
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| 11. | Lu CF, Hsiao CH, Tjiu JW. Nephrogenic systemic fibrosis developed after recovery from acute renal failure: Gadolinium as a possible aetiological factor. J Eur Acad Dermatol Venereol 2009;23:339-40.
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[Figure 1], [Figure 2], [Figure 3]
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