Kidney graft survival has been mainly evaluated using an up to 10-year threshold. Instead, in this study our aim was to evaluate predictive variables that impact long-term kidney graft survival (≥10 years). We enrolled 892 patients in our analysis: 638 patients with functioning graft at 10 years PT and 254 patients with graft failure at 10 years PT (considering patient death with a functioning graft <10 years PT as graft failure). Between groups comparisons were done using Mann-Whitney and chi-square test. To determine independent predictive variables for long-term graft survival a multivariate-adjusted logistic regression was performed. Significant predictors of long term graft survival were lower 12-month PT creatinine (
For patients with end-stage renal disease (ESRD), a successful transplant (compared with dialysis) provides significantly higher survival rates and better quality of life [
We conducted a retrospective study and analyzed data from a total of 996 kidney transplants (KT) performed between July of 1983 and June of 2000, at Hospital de Santo António, Porto, Portugal. After discharge, recipients were followed at our outpatient clinic until graft loss or death. Recipient and donor information was collected from our computed database.
We included, in our analysis, all recipients with a graft survival beyond 3 months, and patients surviving beyond the first-year PT. Simultaneous multiple grafts recipients were excluded. Graft loss was defined as return to chronic dialysis, graft removal, a retransplant, or death.
We enrolled 892 patients in our analysis: 638 patients with functioning graft at 10 years of followup (Group I) and 254 patients with graft failure within 10 years PT (considering patient death with a functioning graft <10 years PT as graft failure) (Group II).
Delayed graft function was defined as the need for one or more dialysis treatments in the first posttransplant week.
All statistical analysis was performed using SPSS software for Windows (version 18.0; Chicago, USA). Results are presented as median and interquartiles range for continuous variables and as frequency and percentages (
The majority of the enrolled patients were men (59.4%), with median age 37.0 years [IQR 27.6–47.1] at the time of transplant. Median time on dialysis was 2.6 years [IQR 1.4–5.0], 96.3% were on hemodialysis. Most donors were also men (70.9%). Median posttransplant follow-up time was 176.2 months [IQR 138.2–222.4]. The median survival time of renal grafts was 149.9 months [IQR 109.6–190.8]. Enrolled population characteristics are presented in Table
Recipient, donor, and kidney transplant characteristics of the enrolled population (
Characteristics | Patients |
---|---|
Recipient | |
Age (years), median [IQR] | 37.0 [27.6–47.1] |
Male gender, |
530 (59.4%) |
Time on dialysis (years), median [IQR] | 2.6 [1.4–5.0] |
Body mass index (kg/m2), median [IQR] | 22.4 [20.3–24.2] |
Dialysis technique | |
Hemodialysis, |
864 (96.3%) |
Peritoneal dialysis, |
16 (1.8%) |
Prior kidney transplant, |
73 (8.1%) |
Positive CMV IgG, |
613 (68.3%) |
Prior blood transfusion (≥3 units), |
350 (39.1%) |
Hepatitis B/C+, |
230 (25.6%) |
Donor | |
Age (years), median [IQR] | 25.0 [18.0–39.0] |
Male gender, |
636 (70.9%) |
Serum creatinine (mg/dL), median [IQR] | 1.0 [0.8–1.2] |
Cadaveric donor, |
888 (99.0%) |
Transplant | |
0 mismatches HLA-B, |
181 (20.2%) |
1 mismatches HLA-B, |
249 (27.8%) |
2 mismatches HLA-B, |
428 (47.7%) |
PRA ≥ 30%, |
34 (3.8%) |
ATG induction protocol, |
411 (45.8%) |
Delayed graft function, |
294 (32.8%) |
Acute rejection, |
283 (31.5%) |
Serum creatinine at 12 months (mg/dL), median [IQR] | 1.40 [1.20–1.70] |
IQR: interquartile range; IgG CMV: immunoglobulin cytomegalovirus; HLA: human leucocyte antigen; PRA: panel reactive antibody; ATG: antithymoglobulin.
The group with graft function after ten years (Group I-G I) had more frequently positive status for cytomegalovirus IgG (73.9% versus 62.1%,
Comparison of recipient, donor, and renal transplant characteristics between the two groups (graft function after 10 years versus graft loss within 10 years).
Characteristics | G I (graft function after 10 years) | G II (graft loss within 10 years) |
|
---|---|---|---|
Recipient | |||
Age (years), median [IQR] | 36.1 [28.1–47.1] | 35.8 [26.9–47.2] |
|
Male gender, |
146 (57.5%) | 384 (60.2%) |
|
Time on dialysis (years), median [IQR] | 2.7 [1.3–4.7] | 2.5 [1.4–5.6] |
|
Body mass index (kg/m2), median [IQR] | 22.4 [20.3–24.2] | 22.2 [19.9–24.2] |
|
Prior kidney transplant, |
56 (8.8%) | 17 (6.7%) |
|
Positive CMV IgG, |
462 (73.9%) | 151 (62.1%) |
|
Prior blood transfusion (≥3 units), |
235 (36.8%) | 115 (45.3%) |
|
Donor | |||
Age (years), median [IQR] | 24.0 [18.0–36.0] | 29.0 [20.0–46.0] |
|
Male gender, |
454 (77.2%) | 182 (74.6%) |
|
Serum creatinine (mg/dL), median [IQR] | 1.0 [0.8–1.2] | 1.0 [0.8–1.2] |
|
Transplant | |||
0 mismatches HLA-B, |
139 (22.7%) | 42 (17.0%) |
|
1 mismatches HLA-B, |
189 (30.9%) | 60 (24.3%) | |
2 mismatches HLA-B, |
283 (46.3%) | 145 (58.7%) | |
PRA ≥ 30%, |
18 (3.5%) | 16 (7.6%) |
|
ATG induction protocol, |
313 (45.5%) | 98 (39.0%) |
|
Delayed graft function, |
187 (29.3%) | 107 (42.1%) |
|
Acute rejection, |
163 (25.3%) | 120 (47.2%) |
|
Serum creatinine at 12 months (mg/dL), median [IQR] | 1.30 [1.10–1.60] | 1.60 [1.33–2.10] |
|
IQR: interquartile range; IgG CMV: immunoglobulin cytomegalovirus; HLA: human leucocyte antigen; PRA: panel reactive antibody; ATG: antithymoglobulin.
Group I being more frequently received to the induction therapy with ATG (45.5% versus 39.0%,
The multivariate analysis (Table
Long-term graft survival predictors; multivariate-adjusted logistic regression.
Characteristics | OR | CI |
|
---|---|---|---|
Recipient | |||
Gender (male versus female) | 1.84 | 1.21–2.80 |
|
Time on dialysis (months) | 0.93 | 0.87–0.90 |
|
Positive CMV IgG (versus negative) | 1.59 | 1.02–2.49 |
|
Donor | |||
Age (years) | 0.98 | 0.97–0.99 |
|
Transplant | |||
0-1 HLA-B mismatch (versus 2) | 1.80 | 0.28–0.84 |
|
Absence of acute rejection (versus presence) | 0.64 | 0.41–0.99 |
|
Serum creatinine 12 months after (mg/dL) | 0.26 | 0.16–0.41 |
|
Variables included in the multivariable model: age and sex of the recipient, mean time on dialysis, recipient status for cytomegalovirus IgG, prior blood transfusions (<3 versus ≥3), age of the donor, number of HLA-B mismatches (0, 1 versus 2), PRA (<30 versus ≥30%), induction with antithymoglobulin, delayed graft function, acute rejection, and serum creatinine at 12 months after KT.
This study focused only on patients with more than 10 years of followup, referring to kidney transplant performed between the year of 1983 and 2000. Major differences of this cohort of patients from kidney transplantation nowadays consist of different and less effective immunosuppression, initially based on azathioprine and prednisolone, then based on cyclosporine and evolving towards introduction of mycophenolate mofetil and tacrolimus. Infectious prophylaxis was also less effective, translating to higher incidence of CMV disease. Due to improvements related with these issues significant progress has been made in graft and patient survival rates after kidney transplant, since the 1980s [
When this population was submitted to kidney transplantation expanded criteria donors were not included, and the vast majority were deceased donors (99%), but many other factors are common to most survival analyses in renal transplantation, such as donor age or gender and creatinine level at 12 months. In this study, univariate analysis and multivariate logistic model were used for analyzing factors influencing renal graft survival. Data analysis indicated that an optimal first year graft function (including absence of acute rejection episodes and creatinine level at 12 months) was of paramount importance for long-term graft survival.
Several studies implicated acute rejection as a major risk factor for chronic allograft failure [
The correlation between the elevated serum creatinine levels at 12 months and graft survival has been documented in several studies [
Other independent known determinants for graft survival include recipient age at transplantation, donor age, length of pretransplant dialysis, delayed graft function, and panel reactive antibody > 30% [
In renal transplantation, donor age is known to have an important influence on the outcome of the graft reflecting functional renal mass [
There is a long-standing debate about whether delayed graft function reduces the survival rate of a renal graft [
Traditionally, high panel reactive antibody (PRA) has been associated with increased immunologic risk and lower kidney graft survival [
As for HLA compatibility, it has been considered the most important independent factor for the 10-year survival rate of patients and the half-life of a patient’s first renal transplant. Cecka showed 10-year survival of dead renal transplant to be of 74% when HLA was matched between the donor and recipient and stated a reduction for 58% if it was mismatched [
The impact of CMV serology in kidney transplantation showed donor CMV-seropositive kidneys to be associated with significantly reduced graft survival for CMV-seronegative recipients but not CMV-seropositive recipients [
This study presents the limitations of any retrospective study moreover this complex cohort of patients, concerning different phases of immunosuppressive regimens and the lack of accurate information of the induction and maintenance immunosuppressive strategies used; restricts more broad inferences. Nonetheless, this is a study on a large number of patients, with a long-term followup (beyond ten years posttransplant) and we could find interesting results.
In summary, modifiable risks factors as an early KT, younger donor age, number of HLA B mismatches and an optimal first-year graft function (including absence of acute rejection episodes and creatinine level at 12 months) are of paramount importance for long-term graft survival. Measures that address these issues (careful donor selection, preemptive KT, and effective immunosuppressive protocols) are still warranted.
All authors declare no conflict of interests.