ANEMIA IDENTIFIED ONE MONTH AFTER RENAL TRANSPLANTATION IS PREDICTIVE OF ANEMIA IDENTIFIED AFTER TWELVE MONTHS

The aim of this study was to evaluate whether anemia identified earlier than  months postengraftment in modern era could be predictive of anemia at  months. Cross-sectional and cohort studies based on retrospective analysis of existing clinical records were performed. Data on recipient’s age at transplantation, follow-up serum creatinine (SCR) and hemoglobin (Hb) on day  (D), at month  (M) and at month  (M) postengraftment were collected. Outcome was anemia identifi ed at  months (M) postengraftment. Th ere were  patients on D,  at M and  at M. Multiple linear regression model that included recipient’s age at transplantation, Hb and creatinine on D and tested the risk for anemia at M retained only the age in the model, with the coeffi cient of , (P=,). Th e same model at M retained Hb and age, with the coeffi cients of , (P=,) and , (P=,), respectively and at M it retained Hb and age, with the coeffi cients of , (P=,) and , (P=,), respectively. Anemia identifi ed at M after renal transplantation is predictive of anemia at M.


Introduction
Anemia is common after renal transplantation and is frequently under-treated (,).Prevalence of anemia is the highest by the time of transplantation because the target hemoglobin (Hb) levels in the end-stage renal disease between - g/ cm  are already within the anemic range, as defi ned by the criteria of World Health Organisation.By three months post-transplant, hemoglobin levels rise and then subsequently fall in those with progressive allograft dysfunction.At one year post-transplant about  of patients are anemic ().Thus, it takes  months after renal transplantation to evaluate renal anemia because non-renal reasons, such as perioperative blood loss, frequent phlobotomies and fluid shifts interfere with its proper evaluation up until  months postengraftment ().We conducted this study to evaluate whether anemia identified earlier than  months postengraftment in modern era could be predictive of anemia at  months.

Methods
We conducted cross-sectional and cohort studies based on retrospective analysis of existing clinical records at the University-based Internal medicine hospital in the town of Tuzla, Bosnia and Herzegovina.Inclusion criteria Data were collected from the records of patients transplanted and followed up at Tuzla transplant clinic from  - and from the records of patients transplanted elsewhere from  -, but followed up at Tuzla transplant clinic thereafter.Patients with incomplete or unavailable charts were excluded from the study.The study was approved by a local ethics committee.Anemia identified at  months (M) postengraftment was the outcome variable.Predictors Recipient's age at transplantation, follow-up serum creatinine (SCR) and hemoglobin (Hb) on day  (D), at month  (M) and at month  (M) postengraftment.Measurements Measurements were done on D, at M, M, and M.Anemia was expressed as decreased qualitative variable of hemoglobin (Hb) identified at M.As recommended by the American Society of Transplantation, it was considered present if the Hgb concentration was ≤  g/ cm  in men or ≤  g/ cm  in women.Recipient's age at transplantation, Hb and SCR were represented by quantitative variables in years, g/dm  and μmol/dm  , respectively.

Statistical analysis
The degree of association between Hb and serum creatinine on each measurement was assessed by a correlation analysis using Pearson coefficient after a log-transformation to correct for a lack of normality, where appropriate.Linear regression analyses were done to test the crude associations between Hb on each measurement before M, and Hb at M.Multiple linear regression prognostic model was applied on each measurement before M to identify the independent risk factors for anemia at M, using forward selection technique with a selection criterion of P<,.
Regression coefficient of the association between Hb on D and Hb at M was , (P=,) between Hb at M and Hb at M it was , (P=,).When the patients who were transplanted in recent years, since  until now were selected, regression coefficient was , (P=,).Regression coefficient of the association between Hb at M and Hb at M was , (P=,).Multiple linear regression model that included recipient's age at transplantation, Hb and creatinine on D and tested the risk for anemia at M retained only the age in the model, with the coeffi cient of . (P=,).The same multiple regression model at M retained Hb and age in the model, with the coefficients of , (P=,) and , (P=,), respectively and at M it retained Hb and age, with the coefficients of , (P=,) and , (P=,), respectively.Summary of Hb coefficients in its association with Hb at M in multiple linear regression model is shown in the Figure .

Discussion
In the early post-transplant period anemia assessment that can be attributed to renal reasons is not reliable because the perioperative blood loss, frequent phlobotomies and fl uid shifts interfere with its proper evaluation ().Th erefore, the studies that evaluate the impact of anemia on various outcomes usually start with anemia assessment performed only  months after transplantation ().Prominent risk factors for anemia in kidney transplant recipents (KTR) is impaired kidney function ().Because the kidney function is the main predictor of anemia (,,,,), we first tested the correlation between serum creatinine and Hb on each measurement before M (D, M and M) to identify the earliest time when creatinine and anemia could be related to each other and we found the significant correlation coefficient the earliest at M (Figure ).Th e crude association between Hb values before M and anemia identifi ed at M was signifi cant only after  months, with regression coeffi cient of , (P=,).However, when the patients who were transplanted in recent years, since  until now were taken into account, the signifi cant association was established already at M. Another important risk factor for anemia in kidney transplant recipents is recipient's age ().Therefore, other than kidney function, we adjusted the analysis also for recipient's age in multivariate linear regression model in order to control the confounding variables.Th us, the fi rst follow-up measurement that identifi ed in multivariate linear regression model the signifi cant association between Hb values before M and Hb at M was performed at M, in contrast to the experience accumulated so far indicating the M as the earliest time for establishing such an association (Figure ).We believe that shift of the earliest time from M to M may be the refl ection of an improved postoperative management in recent years, which decreased signifi cant perioperative blood loss, the frequency of phlobotomies and established proper fl uid balance earlier than at M.

Conclusion
Th ere is no correlation between anemia and renal function seven days after renal transplantation.Correlation between anemia and renal function exists one month and  months after renal transplantation Anemia identifi ed one month after renal transplantation can be predictive of anemia at twelve months.
Other than anemia at one month, the independent risk factor for anemia at twelve months is the recipient's age.