DE’s Deficient KidneysOct 7, 2009Renal RotationSandra Katalinic Pharmacy Resident

Overview

• Objectives• Patient Profile

– Presentation – Medications – Review of Systems – Lab Values

• Disease States– Signs and Symptoms– Risk Factors– Pathophysiology– Treatment Options

Overview

• Pharmacy Assessment– Drug Related Problems – Goals of Therapy – Clinical Question

• Literature Review– K/DOQI – 1˚ article– Therapeutic Options

• Outcome– Monitoring

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

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)

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

Review of Systems

VITALS AVSS; T=36, HR=95, BP=160’s/80’s

CNS Occasional headaches, Ø dizziness

RESP Occasional SOB on exertion (i.e. walking)

CVS Ø chest painHgb:107(78), Hct:0.34(0.25), 87.3(88.5)TG: 1.54 (Aug 28) Fe:4, sats:18%, TIBC:22%

GI/GU Occasional GERD, recovering bowel perf

Review of Systems cont’d

LIVER/KIDNEY Polycystic liver / kidney disease SCr=301(399), GFR=13 (9)

ENDOCRINE Ø thyroid disorders, Ø diabetes, ? Parathyroid adenoma iPTH= 241.60 (Aug 22)

MSK/EXTR/SKIN Arthritis in knees, occasional leg cramps, itch (full body, occurs on and off), Ca= 2.45(2.74)

FLUID STATUS No complaints or concerns; K=3.6 (4.5), Na=140 (138), Cl=101(98)

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

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

Iron Deficiency Anemia

• Risk Factors:– Children younger <2 years– Adolescent girls– Pregnant females, – Elderly >65 years– Blood loss– Inadequate intake– Malabsorption

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

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

Anemia of Chronic Disease

• Risk factors:– infection– malignancy– inflammation – liver disease– uremia (all lasting >1-2 months)

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

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

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

Diagnosis

• Anemia of Chronic Disease

Parameter IDA ACDHgb MCV Iron Sats (ferritin) OR TIBC (transferrin) Reticulocytes

Treatment Options

• EPO (Eprex)• Darbopoietin (Aranesp)

• IV iron• Oral Iron

– Salts– Heme Iron

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 H2RA

• 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

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

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?

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

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. NewsteadNephrol Dial Transplant (2001)16: 967-974

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

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)

Therapeutic Options

• Ferrous Gluconate

• Ferrous Sulphate

• Ferrous Fumarate

• Heme iron polypeptide (Proferrin®)

Covered

Tolerated

Pt already has supply

Highest % of elem iron

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

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

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

References

• DiPiro JT. Et al. Pharmacotherapy: A Pathophysiologic Approach 7th 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/HCS/SBK/2/ND_P/Main/PFActionId/hcs.common.RetrieveDocumentCommon/DocId/CP2019C/ContentSetId/87/SearchTerm/anemia%20/SearchOption/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.