Nephrogenic Systemic Fibrosis

高雄長庚腎臟科 Fellow 2 王奕淳

VS 莊峰榮 & Chief 李建德2009.10.14

Kidney forum

Question

什麼是 NSF?

Gadolinium 會導致 NSF 嗎 ?

腎功能多差時要避免Gadolinium?

Gadolinium 需要預防性洗腎 ?

Q: 什麼是 NSF?

NSF: Clinical

Patients with renal insufficiency

Swelling of distal parts of the extremities

Subsequent thickening, indurations and hardening of the skin

Distinct nodules

Kidney International (2007) 72, 260–264

NSF: Clinical

The distal extremities are the most common area of involvement

Followed by the trunk.

The face is almost never involved.

Kidney International (2007) 72, 260–264

Diffuse thickening, induration, and hyperpigmentation of lower legs with inhibition ofjoint flexion.

Diffuse swelling of the skin, erythematous papules andnodules

NSF :Skin biopsy

Thickened dermis

Bundles of collagen

Surrounding clefts

Mucin deposition

Proliferation of fibroblasts

Proliferation of elastic fibers

No inflammation

Kidney International (2007) 72, 260–264

The dermis is thickened and demonstrates swollen collagenbundles with surrounding clefts and spindle cell proliferation. Interstitial mucin deposition is frequently present

Fibrocytes (yellow arrow) and swollen collagen bundles(green arrow) with surrounding clefts are shown.Interstitial mucin (red arrows) is increasedThe light blue arrow indicates degenerated collagen fibers

Q: Gadolinium會導致 NSF 嗎 ?

NSF: History

1997: Recognition NSF

2000: First description in literature

2006: (NDT) 5 patients received MRI and subsequently developed NSF within 2–4 weeks.

2006 (JASN) 13 patients acquire NSF when exposed to gadodiamide (OR 32.5)

2007 FDA Warning

Kidney International (2007) 72, 260–264

FDA Warning

[Posted 05/23/2007]

Risk for NSF following exposure to GBCA

Acute or chronic severe renal insufficiency (GFR <30 mL/min/1.73m2)

Acute renal insufficiency of any severityHepato-renal syndrome

Peri-operative liver transplantation period.

FDA Warning

Healthcare professionals should avoid the use of a GBCA in these patients

Unless diagnostic information is essential and not available with non-contrast enhanced MRI

Radiology: Volume 245: Number 1—October 2007

A retrospective analysis was performed of all adult patients undergoing dialysis in the west of Scotland between January1, 2000, and July 1, 2006

Patient

All patients who underwent renal replacement therapy (RRT) for established chronic renal failure (stage 5 chronic kidney disease, estimated GFR <15 mL/min)

Results

14 of 1826 patients had NSF13/14 (93%) undergone gadolinium enhanced MRI

408/1812 (22.5%) unaffected

(P <001)

Conclusion

The data support a positive association between gadolinium based contrast agent administration and development of nephrogenic systemic fibrosis in the established renal failure population

The odds of developing NSF were 27 times greater in patients exposed to gadolinium

The odds of developing NSF were 20 times greater in patients exposed to gadodiamide

Conclusion

The current state of evidence suggests an association and potentially causal link between the use of GBCAs and the development of NSF among patients with advanced kidney disease

Q: 腎功能多差時要避免Gadolinium?

Gadolinium

Patient Half life

Healthy volunteers 1.3 hr

Chronic renal failure 30–120 hr

Hemodialysis 2.6 hr

Peritoneal dialysis 52.7 hr

Kidney International (2007) 72, 260–264

NSF in CKD

Prevalence of NSFStage 1–4 CKD: 0%

Stage 5 CKD of 18%

Invest Radiol 2008; 43: 141–144

NSF in CKD

NSF has been observed in up to 18% of patients receiving chronic haemodialysis

May occur in individuals with stages 3 and 4 chronic kidney disease

Occasionally in individuals who had experienced acute renal failure

Ann Rheum Dis 2008;67(Suppl III):iii66–iii69.

American College of Radiology (ACR)

In patients with stage 3 or moderate CKD, the ACR noted that there were insufficient data to make any recommendations

Cleve ClinJ Med 2008; 75: 95–97

FDA & ACR

FDA and the ACR both recommend

Withholding all GBCAs in CKD stage 4–5 (GFR<30 mL/min/1.73m2)

Kidney International (2007) 72, 260–264

The journal of urology 180, 830-835, September 2008

Kidney International (2009) 75, 465–474

Safety studies, including USPIO administration (ferumoxytol) as iron supplement therapy in CKD patients on and not on dialysis, suggest that decreased kidney functiondoes not alter the safety profile.

Q: Gadolinium 需要預防性洗腎 ?

Prophylactic HD for NSF

Three patients have been described who developed NSF developed despite daily hemodialysis for 3 days immediately following gadodiamide exposure

Am J Roentgenol 2007;188(2):586–592.

Prophylactic HD for NSF

Patients who received hemodialysis within 24 hours still developed NSF.

Absence of controls, investigators could not ascertain whether the risk and severity of the NSF was reduced.

Hemodialysis was not started until at least 9 hours postexposure.

Fundam Clin Pharmacol. 2006;20:563-576.

Radiologist’s view

If there is no alternative to the use of gadodiamide

The lowest diagnostic dose should be used

Prompt dialysis after imaging may facilitate removal of gadodiamide

Radiology: Volume 245: Number 1—October 2007

FDA’s view

If patients with severe CKD need GBCAs

Prompt haemodialysis following contrast administration should be considered

http://www.fda.gov/CDER/drug/InfoSheets/HCP/gcca 00612HCP.htm

ACR’s view

Prophylactic use of dialysis be warranted only in patients who were already on dialysis.

For patients not already on haemodialysis (e.g. stage 3 or 4 CKD) =>The risks of initiating haemodialysis should be weighed against that of developing NSF

Am J Roentgenol 2007; 188: 1447–1474

Question

Gadolinium 會導致 NSF 嗎 ? =>Yes!腎功能多差時要避免 Gadolinium?

=>Stage 4-5 (FDA)Gadolinium 需要預防性洗腎 ?

=>Stage 5!, Stage 3-4?(ACR)

Conclusion

Potentially causal link between GBCAs and development of NSF among patients with advanced kidney diseaseWithholding all GBCAs in CKD stage 4–5 (GFR<30 mL/min/1.73m2)USPIOs such as ferumoxytol as an alternative to GBCA in patients at risk for NSFProphylactic use of dialysis after GBCAs in patients who were already on dialysis

Thanks for your attention!