1. AKI in a patient with known multiple myeloma James Alva PGY-1

2. Learning objectives To understand the various causes of AKI, and how to identify pre-renal vs intrinsic renal. To identify the possible sources of AKI in patients with Multiple myeloma, and their pathogenesis.

3. HPI 76 y/o F with PMH of IgG multiple myeloma on velcade/decadron, CHF (EF 30%), CAD, MI s/p PCI P/w Diarrhea x 2 months. Non-bloody Vomiting x 1 day. Non-bloody, non-bilious. Generalized malaise x 2 days Abnormal clinic results BUN/Cr: 15/2.25 Baseline Cr: 1.08

4. History PMH: IgG MM NSTEMI s/p PCI CHF 30% HLD Medications Coreg: 6.25 mg BID Lipitor: 40 mg once daily Plavix 75 mg once daily ASA 81 mg once daily Lisinopril 5 mg once daily Nitroglycerin PRN chest pain Allergies: NKA Social: Denies smoking. Social drinking (rare), no recreational drugs ROS: Negative

5. Physical exam Vitals: T: 36.5 HR: 125 BP: 98/67 RR: 16 O2 sat: 98 General: Well appearing, NAD Neuro: AOx3 Neck: Supple, no JVD, trachea midline Cardio: Tachycardic. Normal S1, S2, no m/r/g Lungs: CTAB, no r/w/r Abdomen: Obese, soft, non-tender, non-distended Extremities: Full ROM, 5/5 UE, LE, trace edema

6. Labs/Imaging CBC WBC:5.83, H/H: 10.6/32.3, Plt:337 Chem Na:142, K:3.3, Cl:106, Bicarb:22, BUN/Cr: 17/2.38 GFR: 24, Ca: 9.4 U/A: Neg. Urine chem: Na: 28, K: 13.1, Cl: 45, Cr: 60.5 Osm: 202 Renal ultrasound: Unremarkable. No obstruction

7. AKI Definition RIFLE: Increase in serum Cr > 50% over < 7 days AKIN: Increase in Cr: > 50% OR increase in serum Cr: 0.3 mg/dl in < 48 hrs. KDIGO: Increase in Cr > 0.3 mg/dl over 48 hours OR > 50% increase over 7 days Various staging within each criteria

8. Types of AKI

9. Calculations FENA: (Una)/(Pna)/(Ucr)/(Pcr) x 100 0.78%  Pre-renal BUN/Cr ratio 7.14  Intrinsic

10. Causes of AKI Prerenal Hypovolemia, CHF, medications, hypotension, Renal artery obstruction, cirrhosis Intrinsic renal Tubular disease (ATN), glomerular disease, vascular disease, malignancy, interstitial disease Postrenal Urethral obstruction, obstruction of solitary kidney, obstructing neoplasm, retroperitoneal fibrosis, ureteral obstruction*

11. Multiple myeloma Common findings African American IgG, IgA Anemia Renal failure* Recurrent infections Decreased normal immunoglobulins Cord compression Plasmacytoma or spinal fractures

12. Multiple myeloma renal disease Renal failure may be initial manifestation >2.0 mg/dl in 20% Causes: Light chain cast nephropathy (myeloma kidney) Direct damage and occlusion in ascending loop of henle Tamm-Horsfall mucoprotein Amyloidosis Light chains taken up and metabolized by macrophages, secreted, and precipitate: Congo red-positive B-pleated fibrils. Monoclonal immunoglobulin deposition disease Light chain/heavy chain fragments. Congo red negative. Renal tubular dysfunction Reabsorption and accumulation of light chains in proximal tubular cells. Fanconi syndrome. Exacerbates light chain cast nephropathy. Other causes

13. Hypercalcemia 15% of patients >11.0 mg/dl at diagnosis Renal vasoconstriction via intratubular calcium deposition. Nephrogenic diabetes insipidus Reversible IV radiocontrast Rare. 1.5% of pts Due to Hypovolemia and light chain deposition Interaction between contrast and light chains Drugs NSAIDs Bisphosphonates Assd. With ATN and focal/segmental glomerulosclerosis Bortezomib Treatment for myeloma kidney, but may be assd. With other causes of renal failure RARE. Bilateral hydronephrosis, nephrolithiasis, renal failure. Lenalidomide Renal failure 4-10% of pts. Lisinopril Elevated BUN/Cr common. AKI rare.

14. Labs cont. Immunoglobulins: IgA: 70 IgM: 60 IgG: 807 Free light chains Kappa: 12.4 Lambda: 16.6 C. Dif: Neg.

15. Intervention Patient given 2 L IV fluids in ER, 1 L as inpatient Lisinopril d/c Loperamide started Creatinine (1.08 baseline) Cr: 2.38  1.71  1.68 AKI 2/2 to hypovolemia Prolonged hypovolemia, hypotension, CHF  ischemic injury  pre-renal, intrinsic renal failure findings

16. References Agabegi, Steven S., Elizabeth D. Agabegi, and Adam C. Ring. Step-up to Medicine. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins, 2013. Print. Cline, David. Tintinalli's Emergency Medicine: Just the Facts. New York: McGraw-Hill, 2013. Print. Leung, Nelson. "Types of Renal Disease in Multiple Myeloma." Types of Renal Disease in Multiple Myeloma. N.p., n.d. Web. 13 Sept. 2015..