1. Renal Complications in Hematologic Malignancies Julie M. Vose, M.D. University of Nebraska Medical Center jmvose@unmc.edu

2. Renal Complications in Hematologic Malignancies Causes of Renal Insufficiency Direct infiltration (NHL, AML, MM) Hydronephrosis (NHL, HD) Thrombosis, HUS/TTP (rare cause) Hypercalcemia (MM, NHL) Hyperuricemia (NHL, AML, MM) Nephrotoxic agents Tumor lysis syndrome

5. Ultrasound of the right (A) and left (B) kidney showing hypoechogenic massively enlarged kidneys. Sellin L et al. Nephrol. Dial. Transplant. 2004;19:2657-2660 Nephrol Dial Transplant Vol. 19 No. 10 © ERA-EDTA 2004; all rights reserved

6. Kidney biopsy. NHL CD 20+ Sellin L et al. Nephrol. Dial. Transplant. 2004;19:2657-2660 Nephrol Dial Transplant Vol. 19 No. 10 © ERA-EDTA 2004; all rights reserved

7. Treatment of NHL with Renal Failure Nephrostomy if necessary IV Hydration Alkalinization Treat Hyperuricemia If due to direct infiltration – treatment of NHL most important Need reduced doses of some medications – Methotrexate, Cytarabine

8. The graph shows the rapid increase of the serum creatinine during the development of ARF. Sellin L et al. Nephrol. Dial. Transplant. 2004;19:2657-2660 Nephrol Dial Transplant Vol. 19 No. 10 © ERA-EDTA 2004; all rights reserved

10. Excessive numbers of abnormal plasma cells in the bone marrow

11. Overproduction of intact monoclonal immunoglobulins (IgG, IgA, IgD, or IgE) or Bence-Jones protein (free antibody light chains)Reproduced with permission from the Multiple Myeloma Research Foundation Web site. Available at: http://www.multiplemyeloma.org/about_myeloma/index.html Ig=immunoglobulin. Kufe. Cancer Medicine. 6th ed. 2003:2219.

12. Hallmarks of MM Plasma cell Lytic lesions, Pathologic fractures, Hypercalcemia Anemia Bone destruction Marrow infiltration MULTIPLE MYELOMA Reduced globulins Monoclonal globulins Urine: Renal failure Blood: Hyperviscosity, Cryoglobulins, Neuropathy Tissue: Amyloidosis Infection Carr et al, 1999.

13. Renal Complications of Multiple Myeloma Serum creatinine > 2 in 25-40% of patients Causes “myeloma kidney” – light chain deposition Dehydration Hypercalcemia Hyperuricemia Amyloidosis (10-15% of cases) Medications (NSAIDs, diuretics, etc)

14. Renal Complications of Multiple Myeloma Light chain production higher than ability to filter the protein Heavy and light chain deposition cause tubular damage – cast formation Serum free light chain assay is more helpful than urine

15. Treatment of Renal Failure and Multiple Myeloma Treatment of renal insufficiency IV Hydration Remove contraindicated medications Treat hypercalcemia - Aredia (not Zometa) Treat hyperuricemia Plasmapheresis? Dialysis if needed – may reverse renal insufficiency in some cases Treat the MM – bortezomib containing combination (lenalidamide reduced dosing)

17. IgG Multiple Myeloma

18. Waldenstrom’s Macroglobulinemia

19. Indolent lymphomas

21. Tumor Lysis Syndrome – Diagnosis and Treatment

22. Lysis of Tumor Cells and the Release of DNA, Phosphate, Potassium, and Cytokines. Howard SC et al. N Engl J Med 2011;364:1844-1854

23. Crystals of Uric Acid, Calcium Phosphate, and Calcium Oxalate. Howard SC et al. N Engl J Med 2011;364:1844-1854

24. Definitions of Laboratory and Clinical Tumor Lysis Syndrome. Howard SC et al. N Engl J Med 2011;364:1844-1854

25. Assessment and Initial Management of the Tumor Lysis Syndrome. Howard SC et al. N Engl J Med 2011;364:1844-1854

26. Increased Risk of Tumor Lysis Syndrome Large volume, bulky mass, high blast count or a large number of circulating cells High proliferative tumor – high LDH, high KI-67, etc Renal involvement by tumor Highly chemosensitive tumor Dehydration, Hyperuricemia

27. Increased Risk of Tumor Lysis Syndrome Acidic urine Exogenous potassium or phosphates Delayed uric acid removal Exposure to nephrotoxins Nephropathy before diagnosis

28. Renal Failure and Hematologic Malignancies Multiple causes – direct or indirect Need to check at diagnosis and as treatment starts Remove contributory drugs or toxins Continue to monitor during therapy Modifications of therapy as needed