Anemia and iron management with ckd the challenge
Download
1 / 68

Anemia and Iron Management With CKD: The Challenge - PowerPoint PPT Presentation


  • 72 Views
  • Uploaded on

Anemia and Iron Management With CKD: The Challenge. Connie Gilet, ANP UNC Healthcare/Kidney Center May 23, 2012. Outline. Brief history of anemia management Guidelines: what they are and what they are not Research about anemia management Research about iron administration

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about ' Anemia and Iron Management With CKD: The Challenge ' - jana-townsend


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
Anemia and iron management with ckd the challenge

Anemia and Iron Management With CKD: The Challenge

Connie Gilet, ANP

UNC Healthcare/Kidney Center

May 23, 2012


Outline
Outline

  • Brief history of anemia management

  • Guidelines: what they are and what they are not

  • Research about anemia management

  • Research about iron administration

  • Gaps in the research anemia & iron research

  • Information about ESA and Iron medications

  • Using the new guidelines: case studies


Brief history
Brief History

  • Epogen approved for treatment of anemia of CKD, June 1989

  • Prior to 1989, blood transfusions used to treat anemia (about 15% received blood)

    >Blood transfusions increased the likelihood

    of developing antibodies that could make a

    kidney donor transplant difficult/impossible

    >Adverse effects, including vol. & iron overload



Peginesatide new esa
Peginesatide: New ESA

  • Studied in USA/Europe. Mean f/u 67.4 weeks

  • Studies funded by Affymax and Takeda

  • Drug was approved by FDA 3/2012

    >Greater than 25,000 received medication

  • Pulled from the market 2/2013

    >0.2% dialysis pts have severe allergic rx

    >0.02% fatal rx with first dose, 30 mins after

    administration (N = 3)

    >Reasons for reactions are unclear


Definitions kdoqi and kdigo
Definitions: KDOQI and KDIGO

  • KDOQI

    >Kidney Disease Outcomes Quality Initiatives

    >Created 1995 by National Kidney Foundation

    >Publish practice guidelines

  • KDIGO

    >Kidney Disease Improving Global Outcomes

    >Created 2003

    >Independent, non profit organization governed

    by multi-discipline international board and

    managed by the National Kidney Foundation




Consequences of using treatment guidelines
Consequences Of Using Treatment Guidelines

  • Guidelines supported increasing Epogen

    doses >>> Hgbvalues increased…

    >Hgb 9.6 in 1991 >>>>>

    >Hgb 12.0 in 2006

    (90% of those receiving epogen on dialysis)

    >Hypothesis: higher Hgb would decrease

    cardiovascular complications (e.g. LVH)

    >Improved quality of life (e.g. functional

    status)

  • How did the research support the guidelines?


Evolution of guidelines is more better
Evolution of Guidelines: Is More Better?

  • Since Epogen successful to increase Hgb, why not treat anemia to targeted “normal” levels?

    >Women ~ 12 g/dl and men ~13 g/dl or

    Hct 30% vs 42%

  • Larger doses of Epogen given to achieve these higher Hgb (without much research to support)



How does one interpret research data
How Does One Interpret Research Data?

  • Few important facts about research studies….

  • Randomized control trial (RCT) done prospectively with a large number of subjects followed for a long time produces the most reliable data. May want to base therapy on results.

    VS

  • Observational study done retrospectively with a

    few subjects, may provide ‘food for thought’ but

    don’t want to base therapy on results

  • Can not generalize research results to groups other than the one(s) studied


Normal hematocrit trial
Normal Hematocrit Trial

  • RCT, prospective study (1998) of 1233 people on

    HD with cardiac disease compared “low” Hct

    (30%) vs “normal” Hct (42%)

    >Average age 65

    >Many with diabetes

    >Followed for average 14 months

    >Epogen doses 160u/kg/week for “low” group vs

    “normal” group 460u/kg/week

    Besarab, et al, 1998


Normal hematocrit trial1
Normal Hematocrit Trial

  • Although difference did not meet statistical

    significance, greater mortality, MI and

    vascular clots in group with “normal” Hct

    values, trial was stopped before all enrolled

  • No improvement in QOL with higher Hct levels

    Besarab, et al, 1998


Choir study correction of hemoglobin and outcomes in renal insufficiency
“CHOIR” StudyCorrection of Hemoglobin and Outcomes in Renal Insufficiency

  • RCT study (2006) looked at 1432 patients with CKD, stage 3 and 4

    >Compared Hgb >= 13 to 11.3 gm/d: Group

    with Hgb >= 13 had increased risk of MI,

    hospitalization, stroke, and death.

    >Terminated early

    >Similar improvements in quality of life

  • After the study, goal Hgb reverted 11-12 g/dl

    Singh, et al 2006


Create study cv risk reduction by early anemia treatment with epoetin beta
“CREATE” StudyCV Risk Reduction by Early Anemia Treatment with Epoetin Beta

  • RCT (2006) of 603 CKD-ND (c/s diabetes) people

    >Compared Hgb 13-15 to 10.5 to 11.5: risk of

    CV events not lowered by correcting the anemia

    >Epogen doses 5,000 VS 2,000 units per week

    >After about 3 years, Hgb 13-15 group 22%

    greaterfirst CV event (not statistically

    significant)

    >Renal function declined faster

    >Higher QOL scores

    Drueke, et al, 2006


Treat study trial to reduce cv events with aranesp therapy
“Treat” StudyTrial to Reduce CV Events with Aranesp Therapy

  • RCT study (2009) of 4, 038 CKD 3 & 4 with diabetes. Compared treatment with placebo with Aranesp to achieve a Hgb of 13 gm/d

    >No difference death or progression to ESRD

    >Greater doses increased risk for stroke, venous clots

    and possibly, malignancy.

    >Reported a small improvement in fatigue and QOL

    >54% of those had Hgb of 13

    >49% of those receiving placebo also reported

    improvements in fatigue and QOL

    Pfeffer, et al, 2009



Research about anemia management and transplant
Research About Anemia Management And Transplant?

  • Retrospective study (2009), non randomized.

    >1794 transplant recipients

    >Hgb > 12.5 g/dl associated with increased

    mortality


What are the o utcomes if hgb is high without esa
What Are The Outcomes If Hgb Is High Without ESA?

  • DOPPS study

    >DOPPS = Dialysis Outcomes and Practice

    Patterns Study

    >Prospective, observational with 20 counties

    >545 of 29,796 (1.8%) folks on HD maintained

    a Hgb >12.0 g/dl for 4 months without ESA

    >No increase in mortality noted

    Goodwin, et al, 2009


Anemia management with esa resistance
Anemia Management With ESA Resistance?

  • About 15% of ESRD are ESA resistance

  • “Choir” Study

    >High dose Epogen associated with 57%

    increased risk death, MI, HF and stroke

  • “Treat” Study

    >Poor response to Aranesp >>increase risk of

    CV adverse events


Summary of research findings for anemia management
Summary Of Research Findings For Anemia Management

  • Most research done on adults with CKD-ND and some with those receiving HD

  • “Reasonable” dose of ESA probably has some benefits

  • Do not want Hgb >= 13 with ESA dosing

  • Individualize epogen therapy balancing

    the pros(feeling better/dec blood transfusions)

    vs

    the cons (inc chance MI, stroke and death)


Summary of research findings
Summary Of Research Findings

  • Those who are ESA resistant and treated

    with high ESA doses may have more

    adverse outcomes (e.g CV and death).

  • Naturally occurring high Hgb probably less risky than a high Hgb achieved with ESA


Gaps in research data
Gaps In Research Data

  • Most of the research done on those with CKD, not on dialysis, older than 60 years with many comorbitities (e.g. DM, HTN)

    >Apply findings to groups not studied with

    caution. For example,how much Epogen do you

    give to a 25 year old who was started on HD due

    to IgA nephropathy and has no comorbidities?

  • Little info on PD, children or those transplanted


Gaps in research data1
Gaps In Research Data

  • What is the optimal Epogen dose frequency; one a week, twice a week, three times per week?

  • While research demonstrates Hgb > 13.0 are associated with adverse outcomes, no data on the benefits vs. adverse outcomes of Hgb between 11.5 and 13.0 g/dl


Gaps in research data2
Gaps In Research Data

  • Doses of Epogen varied widely to obtain Hgb

    values greater than 13.

    >ESA resistant patients received the highest

    Epogen doses? How do we better ID those

    who are resistant? How much Epogen is

    too much? How does one decide how much

    Epogen to administer in this group?


Most recent kdigo guidelines ckd nd
Most Recent KDIGO Guidelines: CKD-ND

  • Individualize dose; use the lowest dose that reduces need for blood transfusion

    >Target Hgb range not provided

    >Consider starting ESA when Hgb below 10

    and reduce or stop ESA when Hgb above 10


Most recent fda guidelines ckd nd
Most Recent FDA Guidelines: CKD-ND

  • Consider ESA when Hgb < 10 g/dl.

    If Hgb > 10, reduce or interrupt dose


Unc ckd nd anemia guidelines
UNC CKD-ND Anemia Guidelines

  • Outpatient anemia clinic guidelines for CKD III to V

    >Start Aranesp at 50mg/kg

    >Goal Hgb between 9.5 and 10.4

    >If Hgb >= 11.0 hold Ananesp


Most recent kdigo guidelines ckd hd
Most Recent KDIGO Guidelines: CKD-HD

  • Use ESA therapy to avoid Hgb below 9.0

    Start ESA between 9 & 10.

  • Initiate therapy less than 10 and reduce

    or interrupt if Hgb exceeds 11.5


Most recent fda guidelines ckd hd
Most Recent FDA Guidelines: CKD-HD

  • CKD-D: start ESA when Hgb < 10.

    >Reduce or interrupt when Hbg > 11.0


Recent kdigo guidelines for both ckd nd and ckd hd
Recent KDIGO GuidelinesFor Both CKD-ND and CKD-HD

  • Base dosing decision/initiation of ESA

    >How rapidly Hgbdecreasing

    >Response to Iron administration

    >Risks of transfusion and ESA therapy

    >Symptoms due to anemia

  • Don’t use ESA to maintain Hgb > 11.5, unless willing to take the risk

  • Don’t use ESA to incHgb > 13 g/dl


Recent kdigo guidelines for both ckd nd and ckd hd1
Recent KDIGO GuidelinesFor Both CKD-ND and CKD-HD

  • Prefer decreasing dose vs holding dose ESA

  • Use ESA’s with GREAT caution in people with CKD if malignancy, past or current, or history of stroke

  • Blood transfusions may be preferred if

    > Hemoglobinopathies, ESA resistance,

    Malignancy, Stroke

  • Address all correctable causes of anemia before starting ESA


Guidelines for anemia management with esa resistance
Guidelines For Anemia Management With ESA Resistance

  • FDA-inadequate response to ESA over 12

    week escalation period, no further dose

    increases

  • Per KDOQI: Evaluate “for specific causes of hyporesponse whenever the Hb level is inappropriately low for the ESA dose administered.”


Kdigo guidelines for esa hyporesponsiveness
KDIGO Guidelines For ESA Hyporesponsiveness

  • Initial

    >No incHgb from baseline after 1 month of

    weight-based dosing = hyporesponsive

    > If hyporesponsive, suggest no inc dose beyond

    doubling initial weight-based dose (50 to 100 u/kg)

  • Subsequent (acquired)

    >If previously stable Hgb, may inc50% beyond

    dose at which stable (no data to support)

    >Avoid inc dose beyond 2 x dose at which Hgb had

    been stable


Kdigo guidelines for esa hyporesponsiveness1
KDIGO GuidelinesFor ESA Hyporesponsiveness

  • Management

    >Treat cause of poor ESA response

    >If poor response remains, balance benefits/

    burden of

    >Decrease in Hgb

    >Continuing ESA

    >Blood transfusions

    (All 2D = Suggest and very low quality evidence)


Correctable vs not correctable causes of anemia
Correctable Vs Not Correctable Causes of Anemia




Anemia management and iron
Anemia Management and Iron

  • FDA Black Box warning is 2007 >> decreased Epogen doses

    >As Epogen doses decreased, IV iron usage

    increased

    >% dialysis patients receiving IV iron

    increased from 57% to 71% between

    8/2010 to 8/2011.*

    *Pisoni, et al 2011


Iron where it s found and how it s measured
Iron: Where It’s Found And How It’s Measured

  • Most iron found in liver and red blood cells. Also present in bone marrow, spleen and in all cells

    >Body hoards and recycles iron

  • Two tests used to estimate iron stores, ferritin and transferrin saturation (TSAT)

    >Ferritin: measures protein inside cells that

    store iron

    > TSAT: % serum iron and total iron binding

    capacity. 20% sats = 20% of the binding sites of

    transferrin occupied by iron


Why we care about how to measure iron stores
Why We Care About How to Measure Iron Stores

  • Can have too much of a good thing >>>

    iron toxicity

  • Iron toxicity >> organ damage

    >Lungs - fluid

    >Liver failure - n/v and bleeding

    >CV - hypotension

    >Neuro - drowiness, seizures and coma

    >Death


What do iron tests tell you
What Do Iron Tests Tell You?

  • If sats <30% and ferritin <500 = iron deficiency

  • If sats 25% and ferritin 650 ???

    >Increase in ferritin can be due neoplasm,

    inflammatory (including autoimmune dx) or

    infectious state

    OR

    >Iron overload

  • Should iron be given if sats low and ferritin high?


Research about iron and ckd
Research About Iron and CKD

  • Observational study (2004)

    >No relationship between IV iron & mortality

    >Subjects had depleted iron stores and no

    systemic inflammation *

  • Several studies claim people on dialysis have iron overload per labs, yet no clinical symptoms of iron overload **

    *Feldman, et al, 2004

    **Conavese, et al, 2004. Ferrari, et al, 2001. Rostocker, et al, 2012


More research about iron and ckd drive i 2007
More Research About Iron and CKD: Drive I (2007)

  • RCT, prospective study of CKD-hemodialysis

    >Low sats (<=25%) and high ferritin (500-

    1200)

    >Hgb <= 11 and Epogen >= 225u/kg/week


Drive i and ii
DRIVE I and II

  • Drive I

    >Showed no adverse effect when ferritin levels

    high (up to 1200) and sats low

    >Only followed 134 people for 6 wks

  • Drive II

    >Observational study: Those who received

    iron maintained Hgb for 12 weeks despite

    lower Epogen doses


Other iron studies
Other Iron Studies

  • Study (2011), prospective study with 25 people

    with CKD III to VI found, after infusion of IV iron,

    increases of iron in liver don’t correlate with

    increases in serum ferritin or TSATs

  • Little data on long-term clinical benefit of iron administration other than increasing Hgb

    Ferrari 2011


Summary of iron research data
Summary of Iron Research Data

  • If the sats are low (< = 30) and ferritin

    < = 500, ok to give oral or IV iron

  • If the sats are low and ferritin > 500, unclear status of iron stores >>> dosing???

    >Individualize care: balance pros and cons of

    giving IV iron


Kdigo guidelines for iron administration
KDIGO Guidelines For Iron Administration

  • Balance potential benefits with risks of harm

  • For adults with CKD-ND, trial of iron if TSAT is <=30% & ferritin is <=500 ng/ml

  • CKD-HD: If Hb increase or Epogen dose decrease desired, try iron.

  • Avoid administering IV iron to patients with active systemic infections. (Not Graded)


Kdigo guidelines for iron administration1
KDIGO Guidelines For Iron Administration

  • For CKD ND patients who require iron supplementation, select

    route of iron administration based on severity of iron deficiency,

    availability of venous access, response to prior oral iron, side effects

    with prior oral or IV iron therapy, patient compliance, and cost.

    (Not Graded)

  • Guide subsequent iron administration in CKD patients based on

    Hbresponses to recent iron therapy, as well as ongoing blood losses,

    iron status tests (TSAT and ferritin), Hb concentration, ESA

    responsiveness and ESA dose in ESA treated patients, trends in each

    parameter, and the patient’s clinical status. (Not Graded)


Iron management and children
Iron Management And Children

  • For all pediatric CKD patients with anemia not on

    iron or ESA therapy, we recommend oral iron (or IV

    iron in CKD HD patients) administration when

    TSAT is <=20% and ferritin is <=100 ng/ml 100 ug/l).

    (1D)

  • For all pediatric CKD patients on ESA therapy who are not receiving iron supplementation, we recommend oral iron (or IV iron in CKD HD patients) administration to maintain TSAT >20% and ferritin >100 ng/ml. (1D)

    (1D = Recommended but very low quality of evidence)


Anemia management and children
Anemia Management And Children

  • Data lacking for adults/very little data, if any, for children. KDIGO = Hgb between 11 & 12

  • UNC Kidney Center: Goal = Hgb 10-12


Case study 1
Case Study #1

  • Mr. C.C. is a 70 year old male with

    >Hx: CKD IV, IDDM, CAD with two stents, TIA

    >Meds = 3 HTN, Zocor, oral iron bid, ASA, insulin

    >VS/Labs: BP 135/82, Creatinine 2.6, GFR 25 ml

    Hgb 9.4, Ferritin 110 ng, Saturation 19%

    Weight = 70 kg

  • Should Mr. C.C. receive an ESA? IV iron?


Case study 11
Case Study #1

  • Mr. C.C. receives IV iron, repeat labs are…

    >Ferritin 350, Sats 35%, Hgb 9.5

  • Should Mr. C.C. receive epogen ?

    >When Hgb below 10, consider…

    >Rate of Hgb decrease

    >Prior response to iron

    >Risk of needing transfusion

    >Symptoms 2/2 anemia


Case study 12
Case Study #1

  • Mr. C.C. was started on Aranesp 40 mcg. Labs drawn 2 weeks after dose given:

    >Hgbinc from 9.5 to 9.6

    >Ferritin inc from 350 to 500 ,

    >Satsdec from 35 to 31%

    >No c/o SOB or change in energy level

    >With a history of TIA, CAD, do you want to

    increase the Aranesp dose?


Case study 2
Case Study #2

  • Ms. A.A. is a 52 year old on HD with

    >Hx: DM, HTN, CAD, PVD and SVC syndrome

    >Meds: 4 HTN, ASA, Warfarin, Lantus

    >VS/Labs: BP 150/90, Weight 60 kg

    Hgb 9.6, Ferritin 750, Sats 29%

    >Receiving Epogen 3,000 units 3 x per wk

    Just completed 1000 mg of ferrlecit IV


Case study 21
Case Study #2

  • Ms. A.A. is a 52 year old on HD with

    >Hx: DM, HTN, CAD, PVD and SVC syndrome

    >Hgb 9.6, Ferritin 750, Sats 29%

  • Do the guidelines support giving additional iron?

  • Do the guidelines support increasing the Epogen dose?


Unanswered questions
Unanswered Questions

  • Is there a maximum or toxic dose of ESA?

  • What makes someone ESA resistant?

  • How does one manage ESA resistance?

  • Does dosing frequency matter?

    >Is it better to give 2,000 units 3 x per week or

    6,000 units once per week?

  • How does Hgb variability due to ESA dosing changes affect outcomes?


What is the optimal hgb goal
What Is The Optimal Hgb Goal?

  • Is this the question we should be asking?

  • Our patients are all different; different genes,

    comorbidities, functional abilities, needs and

    expectations

    >Should the question not be ?….

    >For each individual, at what Hgb level are

    the risks minimized (e.g. CV) and the

    benefits maximized (less fatigue, feel “better”)

    >Intern’ltask force examining this question



References
References

  • Bailie, G.R. (2012). Comparison of rates of reported adverse events associated with I.V. iron products in the United States. American Journal of Health-System Pharmacy, 69,(4), 310-320.

  • Besarab, A., Bolton, W.K., Browne, J.K., Egrie, J.C., Nissenson, A.R., Okamoto, D.M., Schwab, S.J., & Goodkin, D.A. (1998). The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin(Normalized Hct). New England Journal of Medicine, 339, (9), 584-590.


References1
References

  • Cavanese, C., et al. (2004). Validation of serum ferritin values by magnetic susceptometry in predicting iron overload in dialysis patients. Kidney International, 65, 1091-1098.

  • Coyne, D.W. et al. (2007). Ferric gluconate is highly efficacious in anemic hemodialysis patients with high serum ferritin and low transferrin saturation: results from the dialysis patients’ response to IV iron with elevated ferrin (DRIVE) study. Journal of American Society of Nephrology, 18, 975-984.


References2
References

  • Drueke, T.B., Locatelli, F., & Clyne, N. (2006). Normalization of hemoglobin level in patients with chronic kidney disease and anemia(CREATE). New England Journal of Medicine, 355, 2071-2084.

  • Drueke, T.B., Parfrey, P.S. (2012). Summary of the KDIGO guideline on anemia and comment: reading between the guideline(s). Kidney International, 82, 952-960.

  • Dutka, P. (2012). Erythorpoiesis-stimulating agents for the management of anemia of chronic kidney disease: Past Advancements and Current Innovations. Nephrology Nursing Journal, 39 (6), 447-457.


References3
References

  • Feldman, H., et al. (2004). Administration of parenteral iron and mortality among hemodialysis patients. Journal of American Society of Nephrology, 15, 1623-1632.

  • Ferrari, P, et al. (2011). Serum iron markers are inadequate for guiding iron depletion in chronic kidney disease. Clinical Journal of American Society of Nephrology, 6, 77-83.

  • Goodkin, D.A. et al. (2011). Naturally occurring

    higher hemoglobin concentration does not increase

    mortality among hemodialysis patients. Journal of

    American Society of Nephrology, 20, 358-365.


References4
References

  • Heinz, G., Kainz, A., Horl, W., & Oberbauer, R.

    (2009). Mortality in renal transplant

    recipients given erythropoietins to increase

    haemoglobin concentration: cohort study.

    British Medical Journal, 339, 4081.

  • Kalantar-Zadeh, K. et al (2006). The fascinating but deceptive ferritin: to measure of not to measure it in chronic kidney disease. Clinical Journal of American Society of Nephrology, 1 (Supple 1), S9-S18.


References5
References

  • Kapalon, T. et al (2008). Ferric gluconate reduces epoetin requirements in hemodialysis patients with elevated ferritin. Journal of American Society of Nephrology, 19, 372-379.

  • Pisoni, R.L. et al (2011). The DOPPS practice monitor for US dialysis care: trends throught August 2011. The American Journal of Kidney Diseases, 60, 160-165,


References6
References

  • Pfeffer, M. A., Burdmann,E.A., Chen, C.Y., Cooper, M.E., de Zeeuw, D.,Eckardt, K., Ivanovich, P., Kewalramani, R., Levey, A.S., Lewis, E.F., McGill, J., McMurray, J., Parfrey, P., Parving, H., Remuzzi, G., Singh, A.K., Solomon, S.D., Toto, R., Uno, H. (2009). Baseline characteristics in the trial to reduce cardiovascular events with aranesp therapy (TREAT). American Journal of Kidney Diseases, 54 (1), 59-69.


References7
References

  • Rostocker, G. et al. (2012). Hemodialysis-associated hemosiderosis in the era of erythropoisis-stimulating agents. American Journal of Medicine, 125, 991-999.

  • Singh, A.K., Szczech, L., Tang, K.L., Burnhart, H., Sapp, S., Wolfson, M., Reddan, D. (2006). Correction of anemia with epoetinalfa in chronic kidney disease, New England Journal of Medicine, 355, 2085-2098.


ad