1. A study of the risk factors for post transplant erythrocytosis at
Sina and Baghiat -Allah Hospital
ABSTRACT
Background: Post-transplant erythrocytosis (PTE) is characterized by persistent
hematocrit level above 51%. This complication is reported to develop in 10-20% of the kidney
recipients, mostly 2 years after kidney transplantation. PTE is self limited in 25% of the patients;
however it may persist in patients with an increased susceptibility for thrombosis. The purpose of this
study was to assess the prevalence of the risk factors of PTE in our center.
Methods: 235 of the patients who had undergone renal transplant from 1999 through 2004 in at least 3
months prior to this study were enrolled. 45 of the patients with polycythemia were randomly selected.
Two patients with no sign of polycythemia were selected for each of these cases, age and sex matched.
The considered variables included demographic data, accompanied disease, history of blood
transfusion and the laboratory data.
Results: There was no significant difference between the age, history of hypertension, diabetes,
pretransplant hematocrit level, pretransplant history of transfusion, graft's function and source of
kidney. A significantly higher proportion of PTE patients were male, also the case group had a
significantly higher frequency for personal history of polycystic kidney disease, glomerulonephritis.
Conclusion: PTE is an important complication of kidney transplantation that can be fatal. There are
multiple risk factors that should be addressed to prevent this complication.
Keywords: Erythrocytosis, PTE, renal transplantation, thrombosis
Introduction
Nowadays we encounter more cases of post transplant complications, due to recent improvements in
renal transplant techniques and as a result, the increased chance of living in this group of patients. Post
transplant erythrocytosis is one of the complications occurring in 10 to 20% of the recipients most often
in the first 2 years following transplantation. It is defined as a permanently high level of hematocrit
usually more than 51%. Spontaneous recovery is reported in 1/4 of the patients within 2 years from the
onset of this problem, while in others, the problem remained for several years until the occurrence of
rejection. Being Masculine, having native kidneys, diabetes mellitus, and dysfunction or arterial
stenosis in the transplanted kidney are the known risk factors for such a disease (1, 2, 3). Although
smoking is not believed to be an essential factor, it is considered to be an important one. Some studies
have not revealed any relation between drug consumption specially corticosteroids, and this disease (3);
whereas many others have noted a higher prevalence of erythrocytosis in those taking cyclosporine
compared with Azathiopurine (Immuran) and prednisolone (4, 5). Thromboembolic accidents are
reported in 10-30% of these patients, which may lead to death in 1-2% of them (1, 6).

2. Considering the relatively high incidence of post transplant erythrocytosis (PTE) and its life threatening
complications, in-time diagnosis and treatment of the disease would play an important role in
preventing the aforementioned complications. Hence, the purpose of this study was to assess the
prevalence of the risk factors of PTE in our center.
Material and Methods
235 of our renal transplant clinics' patients whom had undergone renal transplant from 1999 through
2004 were enrolled in our study. The transplant was performed for all the subjects at least 3 months
prior to this study. Those with a positive history of polycythemia (hct > 51) prior to transplant, apparent
pulmonary disease, and polycythemia vera (thrombocytosis plus leukocytosis and splenomegaly) were
excluded. The patients' records and also their charts of each visit to transplant clinics were reviewed in
order to complete the pre designed questionnaire.
45 of the patients with polycythemia were randomly selected and classified as the Case Group. On the
other hand, for each of these cases, age and sex matched 2 patients were selected from those without
any sign of polycythemia and classified as Control Group. In other words, 45 cases and 90 controls
entered this study.
The variables considered in the study include age, gender, smoking habit, accompanied disease such as
hypertension and diabetes mellitus, phlebitis, pulmonary emboli, cerebrovascular accidents, underlying
renal disease, renal artery stenosis, obstruction of urinary tract, hydronephrosis, positive history of
nephrectomy, splenectomy and parathyroidectomy, history of blood transfusion before transplant (0,
1-3, 4-6 and more than 6 times). The laboratory data consists of hemoglobin and hematocrit rates prior
to transplant, liver enzymes, existence of the native kidneys, origin of the transplanted kidney and its
performance ( creatinine> 1.5 was considered as a low performance) as well as the treatment protocols.
Results were analyzed with SPSS version 11.5 using chi-square, student t-test and Mann- Whitney
tests. In addition, in order to assess the effect of risk factors on development of erythrocytosis, Binary
Logistic Regression analysis was carried out.
Results
The mean age of the case and control groups were 41.5 ± 12.1 and 38.4 ±14.1, respectively which did
not have a statistically significant difference (p value = 0.182). Moreover, there was not any significant
difference between the mean age of male and female patients enrolled in this study (40.5 ± 13.5 vs.
37.5 ± 13.5, p value = 0.2). Forty two out of 86 male subjects (48.8%) developed PTE, while this figure

3. among the females was a mere 3 (6.1%). Thus, males were at more risk for PTE compared with
females (p value<0.001, RR= 7.97 CI 95%: 2.6 – 24.4).
PTE was reported in 10 of the 17 smokers (58.8%) and 35 of the 118 non-smokers (29.7%). There was
a statistically significant relation between smoking and erythrocytosis (p value = 0.017, RR= 1.98 CI
95%: 1.29-3.22). It should be noted that only one of the members of the smoker group was female,
demonstrating a meaningful difference between smoking habits in different genders (p value = 0.005,
RR=6.9 CI 95%: 1.02-46.88). Mantel- Haenszel test revealed gender to have an altering effect on the
relation between smoking habit and the incidence of erythrocytosis (OR= 13.24, CI 95%: 3.77-46.5). In
other words, smoking indirectly influenced the development of PTE and being a masculine was the real
risk factor.
The number of patients developing PTE in each group is outlined in Table 1. There was no statistically
significant relation between any of these risk factors and PTE. Mann Whitney test did not showed any
relation between PTE and the number of previous transfusions (p value = 0.85).
Table 2 shows the subjects' laboratory data. Mild elevation in liver enzymes occurred in 6 (4.4%)
patients, 2 of which developed PTE.
When underlying renal diseases were addressed, it was noted that 16(72.7%) of 22 subjects with
glomerulonephritis and 6(75%) of 8 patients with PCKD, contracted PTE (p value=0.001, RR=2.72, CI
95%: 1.36-5.43 for GN and p value= 0.01, RR=2.44, CI 95%: 1.51-3.93). Table 3 shows the prevalence
of PTE in different underlying renal diseases reported in this study. As a matter of fact because all the
patients studied in this study had their native kidney, the influence of this factor in PTE could not be
assessed.
Doppler ultrasonography with the aim of observing renal artery stenosis was performed in 101 cases.
None of the 27 patients with PTE who had undergone this test had renal artery stenosis; however
6(8.1%) subjects of non- PTE group were reported to have stenosis. Statistical analysis showed no
significant difference between the two groups (p value= 0.189).
Three patients (2.2%) who had strictures in their urinary tract were all classified in the non PTE group.
Nephrectomy or splenectomy had been performed in 7(5.2%) of the cases, while neither
parathyroidectomy nor bilateral nephrectomy was reported in our subjects. Three of these cases
(42.9%) had contracted PTE (p value = 0.686). Hydronephrosis was seen in only 3 (2.2%) of patients,
all from the non PTE group.
A survey on therapeutic regimens showed PMC (Prednisolone, Mycophenolate Mofetil, Cyclosporine),
PIC (Prednisolone, Immuran, Cyclosporine) and PC(Prednisolone, Cyclosporine) the most frequent
regimens used in 33(32.4), 11(47.8) and 1(10%) of the patients in the case group. Prednisolone-
Immuran or Cyclosporine- Mycophenolate Mofetil was not used in any of the cases. Statistical analysis
did not reveal any relation between therapeutic regimen and PTE (p value = 0.097).
In a sub analysis carried out on the complications, CVA was reported in 2 patients: a case of PTE and a
non PTE case; in addition thrombophlebitis was also reported in a case in PTE group. No statistically
significant difference was seen in the two groups (p value = 0.319).

4. The Binary Logistic Regression test showed men to have PTE, 13.8 times more than women. Moreover
patients with PCKD and glomerulonephritis had 9.6 and 7.9 times higher risks to develop PTE. And
also PIC users compared with those using other regimen are 3.5 times more at risk.
Discussion
According to the results of this study being a man was the most important risk factor for PTE which is
the same as other studies; for instance, an American research in the mid 90's had shown 50% of PTE
patients to be men (1, 2, 3).
Although smoking was associated with higher risk of PTE in the primary analysis, final revisions
proved the contrary. As a matter of fact fewer women were smokers comparing to men and as
mentioned before, being a man was the real risk factor influencing PTE in this group. However several
other studies have mentioned smoking as a main risk factor (1, 2, 3).
PCKD patients were shown to have a higher risk of PTE in our study; as in this group of patients
anemia occurs less and on the other hand hemoglobin loss and renal failure are not proportional. In
addition, structural changes in the kidney of this group of patients may result in renin- angiotensin-
aldestrone activation which leads to development of PTE. Similar explanation for glomerulonephritis is
not available (7, 8).
PTE was more frequently reported in those administering PIC regimen. Considering different agents in
each group, Immuran is suggested to be the culprit; whilst as this drug is a known as the cause of
anemia and studies such as Perazella's has shown the effect of cyclosporine on developing PTE, this
theory is not totally accepted (1). On the contrary, Koziak and also the study carried out in Oregan
University have shown no difference in the level of hematocrit of patients using different cytotoxic
agents (2, 3).
In the present study, PTE did not result in a higher incidence of thromboembolic accidents; however,
other studies have mentioned 10-30% of PTE patients to be at risk of these complications (4, 5). The
lower incidence of thromboembolic complications in the very study may be the result of rapid
diagnosis and treatment in our patients.
Conclusion
Despite all the limitations, the study indicated several factors influencing PTE, more consideration of
which may reduce the complications. However, larger studies are needed in order to identify and
investigate all the risk factors.

5. Références
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Panjwani DD, Sabawi NM, White AG, Kumar Msa, Aref MS, Abouna GM. Post renal transplant
erythrocytosis: Existence of two distinct types. Clin Transplant 1990; 4: 23-25.
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6. Glicklich D, Burris L, Urban A, Tellis V, Greenstein S, Schechner R et al. Angiotensin converting
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Tables
Table 1- Number of patients developing PTE in each group of patients with known risk factors
HTN Diabetes History of Cadaver Dysfunction in the transplanted
transfusion donor kidney
Dysfunction in the transplanted
kidney
+(%) 22(36.7) 5(32.6) 21(33.9) 1(11.1) 12(36.4)
-(%) 23(30.7) 40(54.5) 24(32.9) 44(34.9) 33(32.4)
P value 0.642 0.424 0.90 0.143 0.671

7. Table 2- Reported lab data in case and control group
Case Control P value
Mean Hb prior 9.56 ± 2.3 9.78 ±2.3 0.61
to transplant
Mean Hct prior 28.42 ± 6.9 29.91 ± 7.0 0.24
to transplant

8. Table 3- The prevalence of PTE in different underlying renal diseases reported in this study
Underlying PTE

9. Renal Dis. PTE
+(%) -(%)
Diabetic 2(28.6) 5(71.4)
nephropathy
HTN 6(22.2) 21(77.8)
GN 16(72.7) 6(27.3)
PCKD 6(75) 2(25)
Obstructive 2(28.6) 5(71.4)
uropathy
congenital 0 5(100)
Idiopathic 13(22) 46(78)
Total 45 90