Notes

Outline

Anemia Management Management of Patients with Sub-11 Hemoglobin Network 15 & Network 16 (a collaborative effort) Sponsored by an unrestricted educational grant from Amgen Patricia McCarley, RN, MSN,NP Diablo Nephrology Walnut Creek, CA bargo1@pacbell.net

Objectives: Describe the pathophysiologic basis for anemia in Chronic Kidney Disease (CKD). Identify factors effecting Hb variability. Discuss trending of Hbs, Iron indices and ESA doses. Identify opportunites to improve Hb variability and prevent sub-11 Hb. Improve outcomes for our patients.

"“Some is not a..." “Some is not a number ….           soon is not a time!” Robin Newhouse, 2006

RULES bargo1@pacbell.net HDCN.net Take Home Messages

Overview: Physiology Erythrokinetics ESAs Iron & RE blockade Anemia in CKD            Prevalence         Symptoms Clinical consequences Treatment of Anemia of CKD New K/DQOI Anemia Guidelines – May 2006 Cases

Erythropoiesis in CKD

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ESA: Erythropoiesis        Stimulating Agents IV ESA has 100% bioavailability – half-life varies among ESAs (8, 29, 130 hours) SQ ESA had decreased bioavailability         - administration results in slower increase in serum ESA levels, but maintenance of a stable serum level Epoietin - increased efficacy SQ– use                       20 – 40 % less to maintain a target Hb Aranesp – lower bioavailability SQ – IV/SQ dose the same

RBC Production

Anemia

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Patient Factors/Intercurrent Events

Patient Factors/Intercurrent Events

Patient Factors/Intercurrent Events

Practice Patterns  CMS- Erythropoietin Claims Monitoring Policy Effective April 1, 2006 Designed to promote the efficient use of ESAs May effect Hb variability Changing Oct 1, 2006

Explaining the numbers – CBC

Explaining the numbers – CBC

Trend the Numbers

Trend the Numbers

Trend the Numbers

Trend the Numbers

Trend the Numbers

Trend the Numbers

Summary – RBC Production Absence of Erythropoietin can lead to programmed cell death & ¯ Erythrocyte mass Remember RBC production is about 2 weeks behind dosing with the full cycle of RBC life taking 64 days ID Patient Factors and Intercurrent Events affecting the rate of production or the rate of destruction – Anticipate the effect on the Hb SQ EPO more efficacy Trend the numbers – Anticipate the  next Hb to avoid sub-11 Hb

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Iron Physiology

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IRON – Body Compartments 3000 - 4000 mg

Absolute Iron Deficiency

Change in Iron Balance during ESA Treatment

Functional Iron Deficiency

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RE Blockade

Acute Phase Response Body’s Defense Against Stress

Explaining the numbers – IRON

Explaining the numbers – IRON

Explaining the numbers – IRON

Explaining the numbers – IRON

Explaining the numbers – IRON

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Iron Deficiency

CASES – Trend the Numbers

CASES – Trend the Numbers

CASES – Trend the Numbers

Summary -  Iron Iron deficiency should be assessed by examining the whole patient - clinical setting (eg patient factors,    intercurrent events) - trends in ESA dose, Hb and serum   ferritin/TSAT in response to iron   administration    The goal of iron therapy is to maintain Hb in Target Range

Anemia Starts Early in CKD and Worsens With Disease Progression

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Should you care if your patient is Anemic? It can affect: Risk of death – Likely Morbidity - Likely Cardiovascular Disease - Likely Quality of Life - RCT Exercise Tolerance – Likely Cognition/ Development - Maybe Nutrition/ Growth – Not Clear, but Likely

Relative Risk of Hospitalization

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HB Variability Time spent < 11 g/dl 42,000 HD patients (US) followed to determine the % of time Hb levels were < 11 g/dl over a 6 month period Only 25% of patients did not drop below 11 g/dl 53% of patients < 11  – 20% of the time 29% of patients < 11 – 40% of the time

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Impact of Anemia in CKD on Outcomes

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Quality of Life Improves with Higher Hb Cognitive Function Energy/activity Sleep and eating behavior Satisfaction with health Well-being Satisfaction Exercise capacity Functional ability Health status Sex life Psychological effect Happiness

Summary Beneficial effects of anemia treatment CKD – 1-4 undertreated Risk associated with any time spent below target Patients at risk: new, post-hospitalization,

NKF-K/DOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia Chronic Kidney Disease 2006

Members of the Anemia Work Group David Van Wyck, MD Co-chair John Adamson, MD George Bailie,PharmD, PhD Jeffrey Berns, MD Steven Fishbane, MD Robert Foley, MD Sana Ghaddar, RD, PhD John Gill, MD Katy Jabs, MD Kai-Uwe Eckardt, MD Co-Chair Patricia McCarley, NP Hans Messner, MD Allen Nissenson, MD Gregorio Obrador, MD John Stivelman, MD Colin White, MD Consultants Iain Macdougall, MD Francesco Locatelli, MD

Evidence-based Guideline vs Clinical Practice Recommendation (CPR) Quality of evidence distinguishes two approaches If high or moderately high:  Guideline statement If low, very low, or missing:  CPR (opinion) High or moderately high evidence Randomized, controlled trials (RCTs) or Method without significant limitations Results consistent among available trials Applicable to target patient population Evidence of harm

"Number of" Number of   Clinical Practice   Recommendations:  32    Evidence-Based Guidelines:  3 We have a lot of work left to do!

Guideline and Clinical Practice Recommendations 2.1 Hemoglobin Range

Hb Range    2.1.1  Lower limit of Hb:    In patients with CKD, the Hb should be ≥11.0 g/dL (MODERATELY STRONG RECOMMENDATION)

Higher Hb Targets – END POINTS Studied -RCTs All-cause mortality* Non-fatal CV events* LVH Hospitalization Quality of Life ­ Access thrombosis ­ Other embolic events * Safety Issues Seizure BP change ­ Dialysis Adequacy in HD Transfusion Requirement ¯ Kidney Disease Progression in ND-CKD

Safety Issues Present Hb > 13 Of 19 available RCTs, only 1 had adequate power to examine safety and showed Besarab 1998 (Normal Hct Heart Trial) Terminated early for safety concerns, Increased risk of death or MI 14 Hb vs 10 Hb, 3.1% vs 2.3%, not significant An additional RCT also demonstrated harm risk Parfrey 2005 (Canada-Europe) Increased stroke in higher target (13.5 -14.5 g/dL) compared to lower target (9.5 to 11.5 g/dL), 4% vs 1%, significant .045 Two large unpublished trials:  CREATE, CHOIR

Guideline and Clinical Practice Recommendations 3.1 3.2 Using Iron Agents

Using Iron Agents 3.2.3 Targets of iron therapy:      In the opinion of the Work Group, sufficient iron should be administered to generally maintain the following indices of iron status during ESA treatment:    3.2.3.1  HD-CKD: Serum ferritin >200 ng/mL, and TSAT >20%, or CHr >29 pg/cell    3.2.3.2  ND-CKD and PD-CKD: Serum ferritin >100 ng/mL and TSAT >20%

Using Iron Agents: 3.2.4   Upper level of ferritin:    In the opinion of the Work Group, there is insufficient evidence to recommend routine administration of IV iron if serum ferritin is > 500 ng/ml.  When ferritin is                   > 500 ng/ml, decisions regarding IV iron administration should weigh ESA responsiveness, Hb level and the patient's clinical status.

Ferritin upper limits:  Key findings No information from interventional trials is available about the safety of ferritin targets > 500 ng/ml Sufficient evidence exists to suggest that tissue iron stores in patients with ferritin levels > 500 ng/ml are normal to above normal:-General Pop – bone marrow and liver iron adequate            -CKD patients – 2 studies – no patients with ferritin > 500              showed absent iron stores (N=88pt.)           - CKD patients with Ferritin > 500 – liver iron excess by              SQUID  (N=40)

IV Iron – Misc. Infection risk – important growth factor for bacteria growth- Recent trial – no increased incident of infection with IV iron administration Prudent to hold iron when treating an acute infection Studies show doses between 25-65mg/wk achieve neutral iron balance (Brimble, 2003; Tolman, 2005; Fishbane, 2005)

Guideline and Clinical Practice Recommendations 3.5 Evaluating and Correcting Persistent Failure To Reach or Maintain Hb Target

Hyporesponse MOST Common Persistent iron deficiency Freq hosp. Hosp. for infection Temp cath insertion Perm cath insertion Hypoalbuminemia ­ C-reactive protein Pancytopenia Hemolytic anemia Chronic blood loss Cancer, chemo,radiation Inflammatory disease HIV Infection

NKF-K/DOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia Chronic Kidney Disease 2006

Case 1 74 yo black male ESRD secondary to Hypertension Hx of CAD HD x 1 months PermCath Recent access placement

CASE 1

Case 1 ID patient factors and intercurrent events. What other information do you want to know? Identify Therapeutic Options.

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Case 1 ID patient factors and intercurrent events. What other information do you want to know? Identify Therapeutic Options.

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Case 1 ID patient factors and intercurrent events. What other information do you want to know? Identify Therapeutic Options.

Case 1 Options

Conclusions: ANEMIA AFFECTS PATIENTS          Even small amounts of time sub-11 can increase risk of morbidity and mortality. Focus on these groups of patients: New patients Patient after hospitalization Patients with co-morbidities

Conclusions TREND, TREND, TREND Together !!!! Hb, ESA dose, & Iron parameters  Important in determining next steps and helping you to identify patient factors and intercurrent events early and avoiding sub-11 Hb

Conclusions You are the ANEMIA CASE MANAGER – evaluate the patients entire clinical situation (patient factors and intercurrent events) for best results

"Be Patient Centered !!!!!" Be Patient Centered !!!!!