Renal Function: MRI's, eGFR, and other 'New' News

1. Renal Function: MRI's, eGFR, and other 'New' News Keelyn Ericson, MD April 24th, 2008

2. Overview MRI Contrast Agents: Nephrogenic Systemic Fibrosis. Hypertension : New treatment options. Sodium Bicarbonate: Radiocontrast nephropathy made worse? eGFR : When and how to use it.

3. Warning

5. MRI

6. MRI Contrast Agents: Nephrogenic Systemic Fibrosis.

7. Nephrogenic fibrosing dermopathy • Probably more properly referred to as Nephrogenic Systemic Fibrosis: • From Galan, Cowper, et.al. • “Nephrogenic systemic fibrosis (NSF) is a recently identified fibrosing disorder seen only in patients with kidney failure. It is characterized by two primary features:” • “Thickening and hardening of the skin overlying the extremities and trunk” • “Marked expansion and fibrosis of the dermis in association with CD34-positive fibrocytes.”

8. Nephrogenic fibrosing dermopathy Huh? What the heck is this? How does it occur? Who is at risk? Is it serious? Who needs to know about it? Is there a treatment for it? What are the options? Review

9. Nephrogenic fibrosing dermopathyHuh? • Nephro- : Greek νεφρός (nephros) - “kidney” • -genic : Greek γενής (genēs) – “born” • Fibrosing : Latin fibrae (fiber)– “fiber[forming]” • Dermo- : Greek δέρμα (derma) – “skin, hide” • -pathy : Greek πάθος (pathos) – “passion, suffering, or (more commonly) disease”

10. Nephrogenic fibrosing dermopathyHuh? • Nephro- : Greek νεφρός (nephros) - “kidney” • -genic : Greek γενής (genēs) – “born” • Fibrosing : Latin fibrae (fiber)– “fiber[forming]” • Dermo- : Greek δέρμα (derma) - "skin, hide“ • -pathy : Greek πάθος (pathos) – “passion, suffering, or (more commonly) disease” • [Kidney-born Fiber-forming Skin-disease] • AKA : Nephrogenic Systemic Fibrosis [Kidney-born Systemic Fiber-forming-state]

12. Nephrogenic fibrosing dermopathy Huh? What the heck is this? How does it occur? Who is at risk? Is it serious? Who needs to know about it? Is there a treatment for it? What are the options? Review

13. What the heck is this? • It can make you look like this!

14. What the heck is this? • Seriously… “The typical course begins with subacute swelling of distal parts of the extremities and is followed in subsequent weeks by severe skin induration and sometimes anatomic extension to involve thighs, antebrachium, and lower abdomen. The skin induration may be aggressive and associated with constant pain, muscle restlessness, and loss of skin flexibility.” 6 (All photos: 10)

15. What the heck is this? “In some cases, NSF leads to serious physical disability, including wheelchair requirement. NSF initially was observed in and thought to affect solely the skin (thus the initial term nephrogenic fibrosing dermopathy), but more recent patient reports have demonstrated that several organs may be involved.” 6

16. What the heck is this? “Yellow asymptomatic scleral plaques are common.” (They don’t affect vision.)

17. What the heck is this? Fibrotic forearm skin.

19. Nephrogenic fibrosing dermopathy Huh? What the heck is this? How does it occur? Who is at risk? Is it serious? Who needs to know about it? Is there a treatment for it? What are the options? Review

20. How does it occur? • Etiology and Pathogenesis • The disease did not exist prior to 1997 • How do we know?

21. How does it occur? • Etiology and Pathogenesis • The disease did not exist prior to 1997 • How do we know? • Prior tissue samples (skin biopsies) have been reviewed; no cases were found similar to samples identified for NSF since 1997.

22. How does it occur? • Etiology and Pathogenesis • The disease did not exist prior to 1997 • The disease has only been found in patients with renal disease • How do we know?

23. How does it occur? • Etiology and Pathogenesis • The disease did not exist prior to 1997 • The disease has only been found in patients with renal disease • How do we know? • Of approximately 300+ cases identified through 2008, none have come from patients with normal renal function

24. How does it occur? • Etiology and Pathogenesis • The disease did not exist prior to 1997 • The disease has only been found in patients with renal disease • Multiple associations have been identified; the most common, by far, has been with the administration of Gadolinium “contrast” agents • But does that mean anything?

25. How does it occur? • Etiology and Pathogenesis • The disease did not exist prior to 1997 • The disease has only been found in patients with renal disease • Multiple associations have been identified; the most common, by far, has been with the administration of Gadolinium “contrast” agents • But does that mean anything? • We think so…

26. How does it occur? Gd deposited in vessel walls of the skin

27. How does it occur? • Sodium, Phosphate, and Calcium are found in vessel walls along with Gd – many ESRD (dialysis) patients and Chronic Kidney Disease patients already have Ca/Phos metabolism disease (known commonly as secondary hyperparathyroid disease).

28. How does it occur? • This is thought to lead to activation of some kind of “fibrotic” or “scarring” factor. • Abnormal activation of “fibrocytes” is consistent with one theory of the pathogenesis of NSF.

29. How does it occur? • I thought Gadolinium was fairly safe.

30. How does it occur? • I thought Gadolinium was fairly safe. • Gd-DTPA (Gd-Diethylene triamine pentaacetic acid or “gadodiamide”) was introduced in 1988 as a paramagnetic contrast agent for use in MRI scans and was believed to be safe for patients with impaired renal function. Free Gd ions can form precipitates with anions, such as phosphate, because of its poor solubility, and it is considered highly toxic in its ionic form. Marckmann et al have posited that NFD may result from liberated Gd ions deposited in the tissues. These molecules are known to be extremely toxic and to produce deposits of Gd with calcium phosphates in the tissues of rodents.

31. How does it occur? • English please…

32. How does it occur? • English please… Renal failure + Gadolinium + = NSF (High risk) Renal failure + + Other stuff = NSF (Perhaps) + Gadolinium + Other stuff = NSF (Never) Renal failure + Gadolinium + Other stuff = NSF (High risk)

33. (Other Stuff) • Vascular manipulation • High dose Epo/Aranesp • Clotting events • Underlying clotting abnormalities (hypercoagulable states)

35. Nephrogenic fibrosing dermopathy Huh? What the heck is this? How does it occur? Who is at risk? Is it serious? Who needs to know about it? Is there a treatment for it? What are the options? Review

36. Who is at risk? • Renal Failure patients • All cases so far are associated with subjects who have renal failure. • Not all subjects with Chronic Kidney Disease(CKD) are at risk. Those with lower kidney function (esp. those on dialysis) are at higher risk, it seems. • A cutoff of GFR <30mL/min (CKD Stage 4) is currently held by the FDA as a cutoff for high risk designation (or Cr>1.5) • ANY case of acute renal failure is a contraindication for use of Gd “contrast” agents (a transiently low or quickly worsening renal function, that is).

37. Who is at risk? • Additional Factors • Renal patients [read CKD] who have recently had a vascular manipulation (fistula placement for example) • Renal patients who have recently had a DVT, PE, thrombosis, or who are hypercoagulable (Factor V Leiden deficiency, etc.) • Renal patients who are on very high doses of Aranesp/Epo

39. Nephrogenic fibrosing dermopathy Huh? What the heck is this? How does it occur? Who is at risk? Is it serious? Who needs to know about it? Is there a treatment for it? What are the options? Review

40. Is it serious? In some cases, NSF leads to serious physical disability including wheelchair requirement. …it is now known that several organs such as liver, lungs, muscles and heart may be involved. Organ involvement may explain the suspected increased mortality of patients with NSF. There is no established treatment for NSF,… Severely affected patients may be unable to walk, or fully extend the joints of their arms, hands, legs, and feet. Complaints of muscle weakness are common. Approximately 5% of patients have a rapidly progressive (fulminant) course.

42. Nephrogenic fibrosing dermopathy Huh? What the heck is this? How does it occur? Who is at risk? Is it serious? Who needs to know about it? Is there a treatment for it? What are the options? Review

43. Who needs to know about it? • Radiologists * • Nephrologists *

44. Who needs to know about it? • Radiologists * • Nephrologists * • Nephrology staff members ** • Primary Care providers ** • Primary Care staff members **

45. Who needs to know about it? • Radiologists * • Radiology Technicians and staff • Nephrologists * • Nephrology staff members ** • Dialysis nursing staff • Primary Care providers ** • Primary Care staff members **

47. Nephrogenic fibrosing dermopathy Huh? What the heck is this? How does it occur? Who is at risk? Is it serious? Who needs to know about it? Is there a treatment for it? What are the options? Review

48. Is there a treatment for it?

49. Is there a treatment for it? • Immune globulin (IgG)

50. Is there a treatment for it? • Immune globulin (IgG) • Unproven – case series small