KIDNEY DISEASE AND GADOLINIUM: IS THERE A LINK?

1. KIDNEY DISEASE AND GADOLINIUM: IS THERE A LINK?

2. Nephrogenic Systemic Fibrosis New Disease. All Should Know.

3. Nephrogenic Systemic Fibrosis • Nephrogenic systemic fibrosis (NSF) is a recently identified fibrosing disorder seen only in patient with kidney failure. • It is characterized by two primary features • Thickening and hardening of the skin overlying the extermities and trunk. • Marked expansion and fibrosis of the dermis in association with CD34-positive fibrocytes.

4. Terminology • Nephrogenic fibrosing dermopath (NFD) 2. Dialysis – associated systemic fibrosis

5. Epidemiology • NSF occurs exclusively in patients with kidney failure. • The first cases were noted between 1997 and 2000.

6. No Predilection to NSF by gender, race, or age, etiology of kidney disease or duration of renal failure. • Peritoneal dialysis, May be at Higher risk than hemodialysis.

7. Etiology • A retrospective analysis of two large tissue repositories failed to identify any cases presenting before 1997. • A case matched study undertaken by the centers for disease control failed to isolate a single mediator (drug, medical technique, chemical or infectious agent) that could explain every case of NSF. • Increasing epidemlologic evidence has implicated gadolinium-containing contrast agents.

8. Gadolinium • Gadolinium chelaes are excreted unchanged exclusively by the kidney. • Its half-life is 1.3hours in healthy. • 10 hours at an estimated. (GFR) of 20 to 40 ML/min. • 34 hours in patients with end-stage renal disease. • 1.9 to 2.6 hours if hemodialysis follows the administration of gadolinium

9. Risk • Dose-response relationship exists. • Erythropoietin therapy

10. Clinical Manifestations • The latent period between exposure and disease onset is usually two to four weeks. • The range is as short as two days and as long as 18 moths

11. Skin involvement • Skin disease in NSF symmetrical. • Bilateral fibrotic indurated papules, plaques. • Subcutaneous nodules may be erythematous.

12. The lesions first develop on the lower legs, ankles, feet, wrist, hand. • Common distribution patterns involve the ankles up to mid-thighs. • Skin between the wrists and mid-upper arms, bilaterally. • Unusual distribution patterns overlying the mid and lower abdomen.

13. The head is spared. • The lesion preceded by edema and may initially be misdiagnosed as cellulitis. • The edema usually resolves and skin retains a thickened and firm texture.

14. The skin may have a cobblestone woody or peau d’ orange appearance. • The lesions may be pruritic and sharp pain or a burning sensation. • Movement of the joints may be so limited and flexibility is lost.

15. Systemic involvement • Movement of the joints may be so limited and flexibility is lost. • Muscle induration but strength is normal joint contractures. • Fibrosis of internal organs, diaphragm , myocardium, pericardium and pleura and dura mater. • Yellow asymptoatic scleral plaques similar to pinguicula.

20. Diagnosis • Marked ESR and CRP • Histopathologic examination of a biopsy.

21. Biopsy • Light microscopy varies with disease severity, ranging from proliferation of dermal fibrocytes in early lesions, to marked thickening of the dermis with florid proliferation of fibrocytes with long dendritic processes in fully developed cases. • Associated with histiocytes and factor XIIIa+drmal dendritic cells

22. 3. Thick collagen bundles with surrounding clefts are a prominent finding. 4. Immunohistochemical staining reveals. CD34+dermal cells, with the dendritic processes. 5. Elastic fibers and around collagen bundles in a dense network

23. 6. Increased number of CD68+and factor XIII+dendritic cells 7. Special tasting may reveal gadolinium.

28. Laboratory tests • Elevations in serum C-reactive protein, serum ferritin, reduction in serum albumin • Normal or absent are the eosinophil count, serum and urine protein electrophoresis, thyroid function tests are normal.

29. Pulmonary function tests reveal reductions in total lung capacity and volume and diffusing capacity. • Echocardiography is suggested possible cardiomyopathy. • Muscle biopsy

30. Differential Diagnosis • Scleroderma • Scleromyxedema • Eosinophilic • Calciphylaxis

31. In a review of the published literature, • 28% of patients had no improvement • 28% of patients died • 20% had modest improvement

32. Improvement in or remission of NSF has been described, primarlly in patients who recovered renal funtion.

33. Prevention • Avoidance of gadolinium

34. Gadolinium at high doses should be used only if clearly necessary • Should be avoided in patients with a diagnosis or clinical suspicion of NSF. • Institute prompt hemodialysis after the imaging study if gadolinium is given

35. 4. the average rates of gadolinium removal were 78, 96, and 99 percent in the first, second, and third every –other-day dialysis sessions respectively 5. No evidence that hemodialysis immediately after exposure lowers the risk or severity of NSF. 6. Gadolinium is cleared much more slowly with peritoneal dialysis hemodialysis after the procedure is advisable.

36. Treatment • No proven therapy for NSF other than recovery of renal function. • Intensive physical therapy is recommended in all patients to prevent or reverse disability • Renal transplantation

37. 3. Extracorporeal photopheresis 4. Ultraviolet A phototherapy 5. Plasmapheresis 6. Other modalities photodynamic therapy, pentoxifylline, sodium thiosulfate, intravenous immune globulin.