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Anemia in Transplantation. Yvette Talusan- Tomacruz, M.D. HD. KT. PD. Is it prevalent? Etiology? Can we do something about it?. WHY SHOULD WE TALK ABOUT ANEMIA?. ?KT. Anemia- Definition. Mild: Males= Hgb>120 g/L and <130 g/L Female= Hgb >110 g/L and <120 g/L Moderate
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Anemia in Transplantation Yvette Talusan- Tomacruz, M.D.
HD KT PD
Is it prevalent? Etiology? Can we do something about it? WHY SHOULD WE TALK ABOUT ANEMIA?
Anemia- Definition • Mild: • Males= Hgb>120 g/L and <130 g/L • Female= Hgb >110 g/L and <120 g/L • Moderate • Males= Hgb>110 g/L and <120 g/L • Female= Hgb >100 g/L and <110 g/L • Severe • Males= Hgb <110 g/L • Female= Hgb <100 g/L Kasiske, JASN 2000: 11 (Suppl 15)
76% 21% 36% *Hct<30, 36% Iron profile 46% had iron supplements 40% EPO
At enrollment, 38.6% were anemic, 8.5% were severely anemic,17.8% were on epo. Vanrenterghem, AJT 2003; 3:835
Risk factors for AnemiaNon-Anemic vs Anemic Vanrenterghem, AJT 2003; 3:835
Risk factors for AnemiaNon-Anemic vs Severely Anemic Vanrenterghem, AJT 2003; 3:835
Etiology • Chronic Kidney Disease • Iron Deficiency • Drugs • Immunosuppressive agents- CNI, MMF, AZA, Sirolimus • ACE In vs. ARB • Malignancy • Infections • Active infections • Parvovirus B19
Chronic Kidney Disease in Renal Transplant Patients Karthikeyen, AJT 2003;4:262
Complications per CKD Stage Mean Number of complication Chronic Kidney Disease Stage Karthikeyan, AJT 2003;4:262-269
Hgb and Iron indices according to CKD Stage Karthikeyan, AJT 2003;4:262-269
Immunosuppressive agents • ACE In and ARB Use AR rates are down AR
ACE In and AII RB • Post transplant erythrocytosis • Direct inhibition of erythropoietin of insulin-like growth factor • Indirect mechanism that improves renal perfusion followed by a subsequent decrease in oxygen consumption • May have a negative effect on hematopoiesis at the bone marrow level since AII receptors on erythroid progenitors
Effect of ARB on KT without PTE P<0.05 P<0.01
Sirolimus-Related Anemia • Known adverse effect of sirolimus therapy • Sirolimus-related anemia is concentration dependent (>15 ng/mL) • Analysis of phase I/II data in 40 renal allograft recipients demonstrated 24-hour trough concentrations > 15 ng/mL associated with decreased hemoglobin • Possibly secondary to inhibition of sirolimus-sensitive cytokine pathways that are essential in hematopoiesis Kahan BD, et al. Transplantation. 1998;66:1040-1046.
Risk factors for AnemiaNon-Anemic vs Anemic Vanrenterghem, AJT 2003; 3:835
Etiology • Chronic Kidney Disease • Drugs • Immunosuppressive agents- CNI, MMF, AZA, Sirolimus • ACE In vs. ARB • Iron Deficiency • Malignancy • Infections • Active infections • Parvovirus B19
Iron Deficiency • Highly prevalent especially in early post-transplant period. • Not examined in routine practice Hypochromic RBC<2% Transferrin <231 Serum Iron <62 TSAT <16% Serum Ferritin <32.2 0 1 2 3 4 Odds Ratio Lorenz, JASN 2002
Iron Use in KT • IV Iron (Sodium Ferric gluconate) • Gillespie et all in pediatric and young adult RT • Hgb increased from 101±16 to 114±21(p=0.0092)
Etiology • Chronic Kidney Disease • Drugs • Immunosuppressive agents- CNI, MMF, AZA, Sirolimus • ACE In vs. ARB • Iron Deficiency • Malignancy • Infections • Active infections • Parvovirus B19
Erythropoietin Use and KT • Is it beneficial to use Epo immediately after RT? • Other benefits of EPO • TRESAM study shoed under-utilization of epo even in patients with severe anemia • 207/3969 (5.2%) were on epo • Mild anemia= 44/731 (6%) • Moderate anemia=55/465 (11%) • Severe anemia= 61/343 (17.8%) Vanrenterghem,AJT 2003; 3:836
EPO Early after KT • Anemia may occur due to blood loss, inflammatory status and defective EPO production • Increased risk of tissue hypoperfusion and cellular hypoxia • RCT 100 u/kg RhuEPO thrice a week as long as Hgb <12 • Use of EPO in the immediate post-transplant period reduces time to reach Hgb 12 but marginal, dose needed was high Van Biesen, Transplantation 2005;79:367-368
Can Epo retard progression? • University of Wisconsin • 2 groups: early EPO (18-294 days)(N=119) vs. late EPO (>294 days)(N=57) vs. control Becker, NDT 200217:1667
6.6% 2.2%
Impact of Anemia on Allograft Loss and Patient Mortality • Retrospective cohort 626 KT patients • Prevalence of anemia • 1 month = 72% • 3 months= 40 % • 12 months= 20.3% • PTA cohort • Inferior patient survival • Higher CV death Imoagene-Oyedeji, JASN. 2006 Oct 11
Impact of Anemia on Allograft Loss and Mortality • Risk factors for 12 month PTA • Anemia at 3 months • Donor age • 3-mo creatinine • Risk factors for Mortality • 12-mo PTA • 12 mo creatinine • Age at transplantation • Hep C (+) Imoagene-Oyedeji, JASN. 2006 Oct 11
Impact of Anemia on Allograft Loss and Mortality • Prospective study of 825 Renal transplant patients followed for 8.2 years • 251 patients died, 401 allografts lost • Anemia was associated with 25% greater risk of allograft loss • But not associated with mortality Winklemeyer, NDT, 2006 Oct 13
Post-Transplant Anemia • PTA is prevalent and may be significant • CKD is most common cause but others need to be ruled out • Check iron parameters • Consider use of erythropoietin in Kidney transplant patients • *Impact on graft survival and mortality
Pre- op Anemia 57.4 14 10.3 18.4
Creatinine and Anemia Pre-op 8.87 11.2 9.97 10.44
Anemia at 1 week 81 Percentage 22 20 13
Creatinine and Anemia1 week 2.01 1.35 1.01 1.12