1. DE’s Deficient Kidneys Oct 7, 2009 Renal Rotation Sandra Katalinic Pharmacy Resident

2. Overview Objectives Patient Profile – Presentation – Medications – Review of Systems – Lab Values Disease States –Signs and Symptoms –Risk Factors –Pathophysiology –Treatment Options

3. Overview Pharmacy Assessment – Drug Related Problems – Goals of Therapy – Clinical Question Literature Review –K/DOQI –1˚ article –Therapeutic Options Outcome –Monitoring

4. Objectives Understand how kidney disease can cause anemia of chronic disease and iron deficiency anemia Understand the difference of lab value presentation of both types of anemia List the various pharmacological treatments for both types of anemia Be familiar with the K/DOQI recommendations for treatment of iron deficiency anemia

5. Patient Profile ID 76 y/o female hemo patient Allergy IV iron preps (dextran, sucrose, gluconate) chest pain,  BP C/C Weakness, and fatigue 2˚ anemia PMH Previous PD patient 2˚ to polycystic kidney disease. Intestinal perf. 2˚ colonoscopy, MI 2004, recurrent afib FH Son: polycystic kidney disease SH Non-smoker/drinker, eats well, 3 tea / day yearly flu shot and pneumococcal vaccine (‘08)

6. Patient Profile - Medications Renevite 1 tablet O.D. Metoprolol 50mg BID Ramipril 2.5mg O.D. Midodrine 2.5mg pre HD ASA 81mg O.D. Ferrous fumarate 300 TID Aranesp 150mcg IV q5 days Ranitidine 150mg BID Seroquel 6.25mg qhs Zopiclone 7.5mg qhs Quinine 300mg BID Gentamicin 0.1% ointment to exit site (at HD) Ø herbals / OTC’s

7. Review of Systems VITALSAVSS; T=36, HR=95, BP=160’s/80’s CNSOccasional headaches, Ø dizziness RESPOccasional SOB on exertion (i.e. walking) CVSØ chest pain Hgb:107(78), Hct:0.34(0.25), 87.3(88.5) TG: 1.54 (Aug 28) Fe:4, sats:18%, TIBC:22% GI/GUOccasional GERD, recovering bowel perf

8. Review of Systems cont’d LIVER/KIDNEYPolycystic liver / kidney disease SCr=301(399), GFR=13 (9) ENDOCRINEØ thyroid disorders, Ø diabetes, ? Parathyroid adenoma iPTH= 241.60 (Aug 22) MSK/EXTR/SKINArthritis in knees, occasional leg cramps, itch (full body, occurs on and off), Ca= 2.45(2.74) FLUID STATUSNo complaints or concerns; K=3.6 (4.5), Na=140 (138), Cl=101(98)

9. Anemia Inability for RBC’s to carry adequate oxygen to meet body’s demands Symptoms: fatigue, SOB, tachypnea, tachyarrhythmia, pallor, dry skin Usually due to an improperly formed RBC or inadequate production

10. Anemia in Kidney Disease RBC’s made in bone marrow in response to erythropoietin  made by kidneys  Kidney function =  erythropoietin production Also decreased RBC life span 2 uremic products in blood faster turnover  depletion of iron  iron deficiency anemia

11. Iron Deficiency Anemia Risk Factors: –Children younger <2 years –Adolescent girls –Pregnant females, –Elderly >65 years –Blood loss –Inadequate intake –Malabsorption

12. Iron Deficiency Anemia Presentation –Microcytic, hypochromic RBC’s –Low serum iron –High TIBC. –Transferrin saturation of 15% or lower is common Ferritin levels may be falsely increased with renal or hepatic disease, malignancies, infection or inflammation and may not correlate with iron stores in the bone marrow

13. Tx iron deficiency anemia Focus is on replenishing iron stores Best absorbed in the Fe2+ form Max absorption in the duodenum (acidity of the stomach) All Fe2+ salts (sulfate, fumarate, glutamate) absorbed similarly (approx 10-30%) The dose of iron depends on the patient’s tolerability Tolerance improves with a small initial dose and gradual escalation Recommended dose is 200 mg elemental iron daily

14. Anemia of Chronic Disease Risk factors: –infection –malignancy –inflammation –liver disease –uremia (all lasting >1-2 months)

15. Anemia of Chronic Disease A hypoproliferative anemia Can coexist with anemia of chronic kidney disease Presentation –Decreased TIBC and a –Decreased serum iron level –Normal or increased serum ferritin –Normocytic / normochromic –low reticulocyte count  underproduction of red cells

16. Anemia of Chronic Disease Multifactorial pathogenesis –blunted EPO response –impaired proliferation of progenitor cells –disturbance of iron homeostasis –Increased iron uptake and retention within cells –Shortened RBC life span Cause is uncertain; may involve blocked release of iron from cells in the bone marrow.  limited Iron availability to progenitor cells

17. Anemia of Chronic Disease May coexist with IDA and folic acid deficiency (many patients have poor dietary intake or GI blood loss) Examination of bone marrow  abundance of iron Release mechanism for iron is the central defect Erythrocyte survival may be reduced in patients with ACD A compensatory erythropoietic response usually does not occur

18. Diagnosis Anemia of Chronic Disease ParameterIDAACD Hgb  MCV  Iron  Sats (ferritin)   OR  TIBC (transferrin)  Reticulocytes       

19. Treatment Options EPO (Eprex) Darbopoietin (Aranesp) IV iron Oral Iron –Salts –Heme Iron

20. Drug Related Problems DE is experiencing iron deficiency anemia secondary to inadequate iron stores and hemoglobin production DE is at risk of decreased iron absorption secondary to concomitant use of H 2 RA DE is experiencing elevated calcium levels secondary to elevated PTH levels DE is not receiving adequate secondary prevention post MI DE is at risk of unintentional non-compliance secondary to confusion re: meds

21. Goals of Therapy Prevent symptoms –Return iron sats to 20-50% –Return serum iron to >7 –Return hemoglobin to 110-120 Prevent recurrence of disease –Ensure maintenance of iron levels Manage medication side effects

22. Clinical Question In a 76 year old female with iron deficiency anemia who is allergic to IV iron preparations, how does oral iron compare to IV iron in hematologic response?

23. The Evidence… K\DOQI guidelines: Strongly recommends the use of IV iron preparations in HD patients Serum ferritin>200 mg/L TSAT >20% Iron status tests q1mo IV iron preps produce a greater Hb level with lower ESA doses

24. The Evidence… A Randomized Study of Oral vs. Intravenous Iron Supplementation in Patients with Progressive Renal Insufficiency Treated with Erythropoietin John stoves, Helen Inglis Charles G. Newstead Nephrol Dial Transplant (2001)16: 967-974

25. The Evidence Population –45 anemic patients with progressive renal insufficiency Intervention –Randomized to oral ferrous sulfate 200mg TID or IV iron sucrose 300mg over 2 hours every month –Eprex 2000 units twice weekly

26. The Evidence Results –No statistically significant difference in Hgb response –122(106-128)g/L PO vs. 125(116-133)g/L IV –Hgb of 120g/L achieved in 3 mo –70% of PO iron, 59% of IV iron –Serum ferritin in 6 mo –95ug/L (63-149) vs. 330ug/L (186 – 423)

27. Therapeutic Options Ferrous Gluconate Ferrous Sulphate Ferrous Fumarate Heme iron polypeptide (Proferrin ® ) Covered Tolerated Pt already has supply Highest % of elem iron

28. The Outcome 2 Units of blood given at start of my involvement 5 Days later: Increased ferrous fumarate to 600mg TID Patient tolerates iron well Darbopoietin kept at 150mcg IV q5 days until iron stores are rebuilt

29. Monitoring Parameters Side effects of iron –Constipation, nausea, stomach cramping, vomiting Labs –Hgb, Hct, sats, Serum ferritin Pre EPO therapy q1mo until target Hgb  q3mo

30. Monitoring Parameters Response –Increase in blood reticulocyte count  first few days –Hb levels  4 weeks after therapy initiation, then q2 to 4 weeks. Target 110 – 120  Hb during EPO therapy generally indicates a need for (additional) iron –Patients who do not respond to 8 weeks of optimal dosage should not continue taking EPO

31. References DiPiro JT. Et al. Pharmacotherapy: A Pathophysiologic Approach 7 th Ed. McGraw Hill. New York. 2008; p. 1639-1663. Micromedex [Online] Feb 2009. [Accessed Oct 2, 2009] Available at URL: http://www.thomsonhc.com/hcs/librarian/ND_T/HCS/ND_PR/Main/CS/ 6F530E/DUPLICATIONSHIELDSYNC/9F6C8E/ND_PG/PRIH/ND_B/H CS/SBK/2/ND_P/Main/PFActionId/hcs.common.RetrieveDocumentCo mmon/DocId/CP2019C/ContentSetId/87/SearchTerm/anemia%20/Sea rchOption/BeginWith MD Consult [Online] Aug 2007. [Accessed Oct 2, 2009] Available at URL: http://www.mdconsult.com/das/pdxmd/body/163979092- 3/898967812?type=med&eid=9-u1.0-_1_mt_1014692 KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in Chronic Kidney Disease. American Journal of Kidney Diseases. 2006; Vol 47(5) Suppl 3: p. S1-S132. Stoves J, Inglis H, Newstead CG. A Randomized Study of Oral vs. Intravenous Iron Supplementation in Patients with Progressive Renal Insufficiency Treated with Erythropoietin. Nephrology Dial Transplant. 200l; Vol 16: p. 967-974.