Objectives: We investigated the effect of pretransplant hemoglobin level on the outcome of kidney transplant.
Patients and Methods: Patients were divided in 2 groups: group A < 10 g/dL (80 patients; PTHb < 10 g/dL), and group B > 10 g/dL (69 patients; PTHb ≥ 10 g/dL), and were matched regarding donor age, recipient sex, blood group, donor-recipient HLA, and Cytomegalovirus status.
Results: The frequency of acute rejection, together with the timing of rejection, the need for antithymocyte globulin Fresenius rescue therapy, infection rate, and posttransplant surgical complications were comparable between both groups. While the 1-year actuarial patient and graft survival rates, delayed graft function, and slow graft function rates were comparable between both groups, longer hospital stay was required for group B (> 10 g/dL) patients (P = .005). Mean serum creatinine levels upon discharge (P = .02), at 6 months (P = .05), and 1 year (P = .02) after discharge were higher in group B (> 10 g/dL) patients. While posttransplant hemoglobin levels were lower than pretransplant levels, they were higher in group B (> 10 g/dL) compared with group A (< 10 g/dL), (P = .019).
Conclusions: Pretransplant hemoglobin level does not affect the outcome of kidney transplant, except for creatinine levels at 1 year.
Key words : Renal transplant, Dialysis, Transfusion.
Anemia is a potentially reversible cardiovascular risk factor, and a frequent complication of chronic renal disease, and renal transplant recipients (1, 2). It is reportedly caused by several factors including iron deficiency, gastrointestinal blood loss, immunosuppressive medications, and less frequently, by disorders such as hemolytic uremic syndrome or aplastic anemia (3). The prevalence of anemia in transplant recipients is high, especially during the early posttransplant period (4, 5), with rates of up to 40% being reported in some studies, which may increase with advanced kidney disease. Accordingly, a positive correlation between hemoglobin concentration and graft function (creatinine clearance) has been suggested (4), and appears to be associated with the extent of impaired renal function (5, 6) and also, with the immunosuppressive treatment including the antimetabolites azathioprine, and mycophenolate mofetil (3, 4, 7).
While anemia represents an important posttransplant cardiovascular risk factor (3), its management after renal transplant has not been investigated well. Corrective measures should be undertaken when hemoglobin fails to normalize (less than 11 g/dL in premenopausal females, or less than 12 g/dL in males and postmenopausal females) by 3 months posttransplant (7). The aim of this study was to assess the usefulness of correcting anemia by reaching pretransplant hemoglobin blood (PTHB) levels of 10.0 or above (using erythropoietin or packed red blood cell transfusions) before the transplant, and to determine if this will result in better transplant outcomes.
Subjects and Methods
Patient demographics: Patients were divided into group A (n=80) with normal
(< 10 g/dL) and group B (n=69) with high hemoglobin (≥ 10 g/dL).
Recipients’ mean ages were 42.1 ± 3.3 years vs 36.1 ± 2.6 years (P = .006), donor sex (M:F) distribution was 52:17 vs 48:32;
(P = .029), and donor-recipient relation (P < .001) were significantly different
between group B
(> 10 g/dL) and group A (< 10 g/dL), respectively. HLA matching, donor age, number of sensitized patients, and Cytomegalovirus status were similar between group A (< 10 g/dL) and group
B (> 10 g/dL) (P=NS). Indications for kidney transplant in group A (< 10 g/dL) and group B (> 10 g/dL) included chronic glomerulonephritis (7 vs 13), polycystic kidney disease (4 vs 6), chronic pyelonephritis (9 vs 7), interstitial nephritis (2 vs 3), arterial hypertension (3 vs 4), and others. The duration of pretransplant dialysis was 8.9 ± 2.9 months and 16.0 ± 3.8 months with pre-emptive dialysis done for 13 and 9 patients in group A (< 10 g/dL) and group B (> 10 g/dL).
Higher pretransplant (11.48 ± 0.28 g/dL vs 7.95 ± 0.29 g/dL) (P = .005), posttransplant hemoglobin blood level (7.75 ± 0.45 g/dL vs 7.14 ± 0.34 g/dL) (P = .019), and hemoglobin blood level difference (3.8 ± 0.37 vs 1.2 ± 0.27) (P = .005) were seen in group B (> 10 g/dL) versus group A (< 10 g/dL) patients. Packed red blood cell transfusions were administered to 21 patients in group A (< 10 g/dL), and to 12 patients in group B (> 10 g/dL) after kidney transplant (P=NS) when the posttransplant hemoglobin to levels dropped to below 5.0, or when symptoms had occurred.
Immunosuppressive regimen: Induction therapy was instituted for 31 patients (38.8%) in group A (< 10 g/dL) and for 54 patients (78.3%) in group B (> 10 g/dL) (P < .001). This consisted of daclizumab (13/31 vs 15/54) administered as 2 dosages (3 and 2) or 1 dose (10 and 13), or as an intraoperative bolus of antithymocyte globulin Fresenius (ATG-F; 18/31 vs 39/54) given as bolus (15 and 24) or extended regimen (3 and 15) in group A (< 10 g/dL) and group B (> 10 g/dL). Maintenance immunosuppression comprised of triple therapy in which cyclosporine (cyclosporine (N) or FK506 (F) was combined with an antimetabolite (mycophenolate mofetil [C] or azathioprine [A]) and prednisolone [P]). These consisted of FCP (31 and 24), FAP (1 and 0), NCP (41 and 40), and NAP (7 and 5) given to group A (< 10 g/dL) and group B (> 10 g/dL) patients (P = NS).
Main transplant outcomes: The main outcomes are summarized in Table 1. Acute rejection (AR) occurred in 12 patients in group A (< 10 g/dL) (15.0%) and in 15 patients in group B (> 10 g/dL) (21.7%) (P=NS). In addition, the timing of rejection, and the need for ATG-F rescue therapy were comparable between both groups. Infection rate was similar between the 2 groups, with a total of 30 infectious episodes in 22 patients in group A (< 10 g/dL), as compared to 28 infectious episodes in 23 patients in group B (> 10 g/dL), and comprised bacterial (18 vs 22), viral (10 vs 4), and fungal (2 vs 2) infections in group A (< 10 g/dL) vs group B (> 10 g/dL) patients. The 1-year actuarial patient (96.3% vs 95.7%) and graft (96.3% vs 94.3%) survival rates, together with delayed graft function (DGF; 2.5% vs 5.8%) and slow graft function (SGF; 5.0% vs 8.7%) rates were comparable between both groups. Longer hospital stays were recorded for group B (> 10 g/dL) than group A (< 10 g/dL) patients (12.55 ± 1.39 vs 9.01 ± 0.69 days) (P = .005).
Biochemical profile: Mean serum creatinine levels upon discharge (1.61 ± 0.10 vs 1.37 ± 0.12 mg/dL) (P = .02), at 6 months (1.37 ± 0.10 vs 1.26 ± 0.06 mg/dL) (P = .05), and 1 year (1.29 ± 0.07 vs 1.18 ± 0.06 mg/dL) (P = .02), but not at 1 month (1.44 ± 0.10 vs 1.39 ± 0.08 mg/dL) (P = NS), or 3 months (1.38 ± 0.10 vs 1.36 ± 0.09 mg/dL) (P = NS), were significantly higher in group B (> 10 g/dL) vs group A (< 10 g/dL) patients (Table 2). While posttransplant hemoglobin levels were lower in group A (< 10 g/dL) (7.14 ± 0.34 vs 7.95 ± 0.29 g/dL) and in group B (> 10 g/dL) (7.75 ± 0.45 vs 11.48 ± 0.28 g/dL) compared with pretransplant levels, they were still significantly higher in group B (> 10 g/dL) compared to group A (< 10 g/dL) patients (P = .019) (Table 2). Posttransplant surgical complications comprising ureteral stenosis (2 vs 0), bleeding (1 vs 0), renal artery stenosis (1 vs 3), and septic shock (1 vs 0) were comparable between the 2 groups.
Pretransplant hemoglobin level has no effect on the outcome of kidney transplant, except for the creatinine blood level at 1 year. Previous studies investigating hematologic adverse events, including changes in hemoglobin levels, demonstrated dynamic changes in hemoglobin levels following kidney transplant. Significant, negative correlations were noted between decreases in hemoglobin levels before and after conversion from 1 immunosuppressive agent to another (3, 4, 7), and increased hemoglobin was associated with increasing dialysis duration (8). Others suggested that physiologic hemoglobin may be advantageous for hemodialysis patients, as evidenced by progressive improvement in echocardiographic parameters upon hemoglobin normalization, with a special reference to hypertension, which was not aggravated at higher target hemoglobin (9).
Our study confirms that graft and patient survival are independent of pretransplant hemoglobin levels. This is in agreement with some (10), but not other studies (11), which demonstrate that maintaining hemoglobin between 11 g/dL and 12 g/dL (and hematocrit between 33% and 36%) before kidney transplant does not have any significant impact on graft or patient survival after kidney transplant. In addition, delayed graft function and slow graft function were not different between groups A (< 10 g/dL) and B (> 10 g/dL), which is reminiscent of a previous study, which documents a similar rate of delayed graft function, graft loss, or vascular thrombosis for kidney transplant patients with different pretransplant hemoglobin levels (12).
The exact mechanism underlying the effect of PTHb levels on creatinine levels
remains to be determined, which was previously suggested to involve interaction
with (inhibition of) angiotensin
I-converting enzyme. While this remains to be seen, other studies argued against (eg, a possibility of angiotensin I-converting enzyme inhibitor therapy did not alter hemoglobin levels) among kidney transplant patients with normal hemoglobin levels (13). Continued follow-up is needed to evaluate its effect on the long term.
Volume : 7
Issue : 4
Pages : 214 - 217
1From the Department of Surgery, Sacre'-Coeur Hospital, Baabda-Hazmieh, Lebanon
2Department of Surgery, Lebanese Hospital, Beirut, Lebanon
3Department of Medical Biochemistry, College of Medicine & Medical Sciences, Arabian Gulf University, Manama, Bahrain.
Address reprint requests to: Wassim Y. Almawi, PhD, Department of Medical Biochemistry, College of Medicine & Medical Sciences, Arabian Gulf University, PO Box 22979, Manama, Bahrain
Table 1. Main outcomes.
Table 2. Biochemical profile.