Clinical Case Conference

1. Clinical Case Conference Eli Lancaster, MD October 5th, 2010

2. Case #1 • Reason for consult: ARF • HPI: 51 y/o WM with h/o MM is sent to the hospital by his Oncologist for ARF and plasmaphoresis. • He denies any symptoms but states that he has really lost his appetite and has not been eating much at home after last dose of chemo

3. ROS • Stable weight • No fever/chills • No rash or joint pains • Has had increasing LE swelling over the past 6 weeks • No diarrhea

4. Past medical history • No medical problems or kidney disease until 7 month prior to this presentation • 7 months ago he went to the ER with back pain and was found to have a lytic lesion with burst fracture on L4 • Work up found MM with IgG lambda and started on chemo and IV zoledronic acid

5. Medications • Valium 5 mg tid • Omeprazole 20 mg po daily • Allopurinol 300 mg po daily • Vit D • Ferrous sulfate • Dexamethasone 40 mg with chemo • Lasix 40 mg started 1 month prior for edema • Valcade/Doxil * finished cycle #6 on 6/1, 6/4, and 6/8

6. Social and Family Hx • Worked in coal mines until diagnosis • 40 PYH of smoking • No Alcohol • No h/o Drugs • Currently living in NH getting PT for spine • No family history

7. PE

8. Labs

9. Ddx? • Treatment?

10. Questions • Pt had overall decreasing level of paraproteinemia, why would pt now develop myeloma kidney • Is lasix toxic in the setting of MM? • Can Zometa cause ATN? • The role of plasmaphoresis?

11. Can lasix contribute to “myeloma kidney?” JCI, 1992

12. Background • Light chains have been shown to cause renal failure • The tubulotoxic proteins either collect in the endolysosomal system of the proximal tubule and damage these cells directly, or precipitate in the tubule lumen to form casts • The renal lesion associated with “myeloma kidney” is characterized morphologically by the presence of multiple intraluminalproteinaceous casts that contain the light chain and THP.

13. Background • Coaggregation of these proteins depends upon the ionic environment in that increasing concentrations of calcium, sodium, and chloride augment this interaction. So the ionic composition of tubule fluid appears to play a large role in cast formation as well as the intrinsic properties of the light chains • The aim of this study was to characterize the factors that modulate this phenomenon

14. Methods • 4 human Bence Jones proteins were used • BJP1 was a kappa light chain obtained from a patient who had no clinical evidence of renal dysfunction • BJP2 was kappa light chain • BJP3 was a lambda light chain • BJP4 was a kappa light chain

15. Methods • Animal preparation • Rats were used with mean weight of 228 gram • Surgery was done to expose the left kidney • Single-nephron perfusion technique • Used artificial tubular fluid to identify a nephron that had multiple surface proximal convolutions • Once identified a micropressure monitoring system was then inserted into a late surface proximal convolution to continuously monitor the proximal tubular pressure • Cast nephropathy was thought to be present if proximal tubule pressure rose to 20 mm Hg

16. Dose-response study • In this group, rats were infused ringer-bicarbonate at 1.2 ml/100 g BW/hr after a 1 ml bolus • To establish the dependence of intraluminal obstruction on the concentration of light chain • BJP3 was infused at increasing concentrations • Control was Albumin infused at 1 mg/ml

17. Dose-response study - Results

18. Dose-response study - Conclusions • The duration of perfusion needed to induce intraluminal obstruction decreased as concentration increased • Therefore, higher concentration means more likely to precipitate and cause cast nephropathy • The patient in this case that decreasing light chain concentration in response to Chemo

19. Effect of ECF volume • BJP1 which was not associated with ARF • BJP3 was used • Both infused at standard rate • One group was infused with 1.2 ml/100 g BW/hr • One group was infused with 2.0 ml/100 g BW/hr

20. Effect of ECF volume - Results

21. Effect of ECF volume - Results • Volume expansion decreased the rate of precipitation

22. Effect of loop diuretic • BJP3 was used at 1 mg/ml infusion • used alone • with furosemide at 2 concentrations

23. Effect of loop diuretic - Results

24. Effect of loop diuretic - Conclusions • Lasix increased the rate of precipitation causing luminal obstruction • The authors concluded that increase luminal concentration of Na+ and Cl- likely enhances binding of light chain and THP (also shown in Lab Invest 1995; 73:810-817) • Volume depletion may promote binding in the setting where the physical properties of the light chain may not be tubulotoxic

25. Should we avoid lasix in MM • I would say yes • Especially in setting of high light chain concentration, dehydration, and hypercalcemia or acidosis • Maybe for volume management we should only use more distal agents