Correction of postkidney transplant anemia reduces progression of allograft nephropathy

Abstract

Retrospective studies suggest that chronic allograft nephropathy might progress more rapidly in patients with post-transplant anemia, but whether correction of anemia improves renal outcomes is unknown. An open-label, multicenter, randomized controlled trial investigated the effect of epoetin-β to normalize hemoglobin values (13.0-15.0 g/dl, n=63) compared with partial correction of anemia (10.5-11.5 g/dl, n=62) on progression of nephropathy in transplant recipients with hemoglobin <11.5 g/dl and an estimated creatinine clearance (eCrCl) <50 ml/min per 1.73 m(2). After 2 years, the mean hemoglobin was 12.9 and 11.3 g/dl in the normalization and partial correction groups, respectively (P<0.001). From baseline to year 2, the eCrCl decreased by a mean 2.4 ml/min per 1.73 m(2) in the normalization group compared with 5.9 ml/min per 1.73 m(2) in the partial correction group (P=0.03). Furthermore, fewer patients in the normalization group progressed to ESRD (3 versus 13, P<0.01). Cumulative death-censored graft survival was 95% and 80% in the normalization and partial correction groups, respectively (P<0.01). Complete correction was associated with a significant improvement in quality of life at 6 and 12 months. The number of cardiovascular events was low and similar between groups. In conclusion, this prospective study suggests that targeting hemoglobin values ≥13 g/dl reduces progression of chronic allograft nephropathy in kidney transplant recipients.

Figure 1.

Trial profile. Among the 128 patients randomized in the study, 3 were excluded in group B because none had a single Hb determination; the remaining patients represent the ITT population. Very few patients were excluded during follow-up.

Figure 2.

Changes during the 24 months of follow-up in mean Hb levels. Red circles and line are for patients in group A, and black circles and line are for patients randomized to group B. The difference between the two groups was significant after the 3-month phase of correction.

Figure 3.

Changes during 24 months of follow-up in (A) eCrcl calculated with the Cockcroft–Gault formula and (B) eGFR calculated with the abbreviated MDRD formula. Red circles and line are for patients in group A, and black triangles and line are for patients randomized to group B. The difference between groups became significant after 12 months, showing that the rate of decline of renal function was lower in patients with complete anemia correction (group A) than in patients with partial anemia correction (group B).

Figure 4.

Death-censored Kaplan–Meir graft survival. Red line is for patients in group A, and black line is for patients in group B.

Figure 5.

Effect of anemia correction on quality of life. Variation in QoL assessment using the (A) Medical Outcomes Study 36-Item Short-Form Health Survey questionnaire and (B) Kidney Transplant Questionnaire-25 questionnaire between baseline and 6 months. During the follow-up, improvement in QoL assessed using the SF-36 was observed only in group A for most items, whereas with the KTQ questionnaire, improvement was significant only for fatigue. Values are expressed as adjusted means. Positive changes indicate improvement in the quality of life, whereas negative changes indicate worsening of the quality of life. PF, physical functioning; RP, role physical; BP, physical pain; GH, general health; VT, vitality; SF, social functioning; RE, role emotional; MH, mental health.