Herein, the significance of post-transplant glomerulonephritis (PTGN) has been revisited to investigate whether PTGN induces allograft failure. The aim of this study was to identify the incidence of PTGN and its association with allograft failure, as well as to analyze the risk factors for PTGN.
Among the 996 Korean patients who underwent kidney transplantation in a multicenter cohort from 1995 to 2010, 764 patients were enrolled in this study.
The incidence rate of PTGN was 9.7% and 17.0% at 5 and 10 years of follow-up, respectively. PTGN was diagnosed in 17.8% of the recipients with results of biopsy tests or clinical diagnosis identifying glomerular diseases as the underlying cause, compared with 0.0%, 4.4%, 4.9%, 5.5%, and 5.7% of the recipients with renal vascular diseases, renal interstitial diseases/pyelonephritis/uropathy, diabetic renal disease, hereditary renal diseases, and diseases with unknown etiologies, respectively. Allograft survival was significantly decreased in patients with PTGN. PTGN was associated with a fourfold increase in graft failure with a hazard ratio of 7.11 for both acute rejection and PTGN. Results of the risk factor analysis for PTGN revealed that the underlying glomerular renal diseases and treatment methods using drugs such as tacrolimus and basiliximab significantly increased PTGN development, after adjusting for other risk factors.
We conclude that PTGN is strongly associated with poor kidney allograft survival. Therefore, optimal management of recurrent or
Chronic glomerulonephritis (GN) is one of the main etiologies of end-stage renal disease (ESRD), and is an indication for kidney transplantation in 30–50% of the recipients with renal diseases
Along with the major impact of interstitial fibrosis, tubular atrophy, and chronic rejection on allograft outcome, recurrence or
GN of all types may recur or develop soon after kidney transplantation and the prevalence of PTGN depends on the original underlying kidney disease. For example, the prevalence rate is 20–50% in membranoproliferative GN (MPGN) Type I, 80–100% in MPGN Type II, 20–50% in focal segmental glomerulosclerosis (FSGS), 13–50% in immunoglobulin A nephropathy (IgAN), and 10–30% in membranous nephropathy (MN)
Our recent work highlights the significant effect of IgAN recurrence on allograft outcome, the results of which revealed that chronic changes negatively affected allograft outcome more significantly than IgAN recurrence
Therefore, we aimed to investigate and identify the incidence, risk factors, and the effect of PTGN on graft survival in both patients with chronic GN and patients with ESRD of unknown etiology.
We enrolled 764 of the 996 patients who underwent kidney transplantation at Seoul National University Hospital, Seoul National University Bundang Hospital, and Seoul National University Boramae Medical Center between 1995 and 2010. We excluded patients who were under 18 years of age and those who were retransplanted or underwent multiorgan transplantation. This study was approved by the Seoul National University Hospital Institutional Review Board. All clinical investigations were conducted in accordance with the guidelines set by the 2008 Declaration of Helsinki.
Patient gender, age, comorbidities, donor type, human leukocyte antigen (HLA) status, original kidney disease, date of referral, date of transplantation, and regimens of immunosuppressant drugs were recorded. Original kidney diseases were classified into six groups as follows: glomerular diseases, renal vascular diseases, renal interstitial diseases/pyelonephritis (PN)/uropathy, diabetic renal disease, hereditary renal diseases, and diseases with unknown etiologies. These diseases were diagnosed based on the results of kidney biopsy tests or imaging studies such as computed tomography, magnetic resonance imaging, and kidney ultrasonography, or based on clinical judgments by physicians and researchers. Early referral was defined as the interval between the nephrologist's visit and the diagnosis of ESRD or the start date of renal replacement therapy greater than 1 year.
Hypertension was defined as a systolic blood pressure greater than or equal to 140 mmHg, diastolic pressure greater than or equal to 90 mmHg, or the concurrent use of antihypertensive medications. Diabetes mellitus was diagnosed in patients with random blood glucose concentration levels greater than or equal to 200 mg/dL, fasting plasma glucose levels greater than or equal to 126 mg/dL on at least two separate occasions, or in patients using antihyperglycemic drugs.
Clinical parameters such as serum creatinine, estimated glomerular filtration rate (eGFR), hematuria, and daily proteinuria that could have influenced the development of PTGN while performing biopsy of the kidney were collected. Serum creatinine levels were measured using an assay based on Jaffe's method and eGFR was calculated using Modification of Diet in Renal Disease formula (MDRD): GFR (mL/minute/1.73 m2)=186×(Scr)1.154×(age in years)−0.203×(0.742 if female).
Biopsies of the allograft were performed when eGFR fell below 60 mL/minute or clinically significant hematuria (gross hematuria or red blood cell count ≥5/high power field in urinalysis and microscopy) or proteinuria [random urine protein-to-creatinine ratio (PCR) >0.5] developed. All protocol biopsies were excluded from the study. Acute rejection or PTGN was diagnosed by accurate histological classification based on the results of kidney biopsy. However, biopsy-unproven cases but with clinical indications that are mentioned above were not classified as PTGN. The date of diagnosis of PTGN was recorded as the date of biopsy. Graft failure was defined as the requirement for permanent dialysis or allograft nephrectomy, retransplantation, and censoring the recipient's death.
A standardized immunosuppression protocol involving a combination of a calcineurin inhibitor and steroids was initiated within 24 hours of surgery. The choice of calcineurin inhibitor, either cyclosporine A (CsA) or tacrolimus, was determined by the transplantation team. The initial dose of CsA was 10 mg/kg per day by the oral route; target trough levels were 200–400 ng/mL during the first 4 weeks and 100–200 ng/mL thereafter. The initial dose of tacrolimus was 0.16 mg/kg per day by the oral route; target trough levels were 8–15 ng/mL during the first 3 months and 3–8 ng/mL thereafter. Methylprednisolone (1 g/day) was administered by intravenous infusion on the day of transplantation, tapered to prednisone at 30 mg/day on post-transplantation day four, and then administered at the maintenance dose without withdrawal. Inhibitors of purine synthesis [e.g., mycophenolate mofetil (MMF)] were used in the initial immunosuppressive treatment based on clinical judgments considering risk factors such as HLA mismatch.
We compared the categorical variables using the Chi-square test and continuous variables expressed as the mean±standard deviation were compared using the Student
Patient demographics are shown in
Regarding donor type, living related donors were the most common, followed by deceased and living unrelated donors. A total of 569 (74.5%) patients were referred early to nephrologists. A total of 274 patients (35.9%) received pre-emptive transplantation. Tacrolimus and CsA were administered to 50.9% and 48.3% of recipients, while 42.1% received basiliximab pretransplantation. MMF was the most commonly used antimetabolite antirejection drug (75.1%).
During follow-up, 70 (9.2%) patients were diagnosed with PTGN. At diagnosis, serum creatinine level was 1.88±2.24 mg/dL, eGFR was 49.67±20.97 mL/minute, and random urine PCR was 2.57±3.18 g (Supplementary Table 1).
The incidence of PTGN increased with time after transplantation, from 4.9% at 2 years to 9.7% at 5 years, and 17.0% at 10 years of follow-up. PTGN occurred steadily throughout the follow-up period, while most acute rejection episodes developed early (
Regarding underlying kidney diseases, PTGN was diagnosed in 17.8% of patients with glomerular diseases, compared with 0.0%, 4.4%, 4.9%, and 5.5% of the recipients in renal vascular diseases, renal interstitial diseases/PN/uropathy, diabetic renal disease, and hereditary renal diseases group, and in 5.7% of the patients with diseases of unknown etiologies (
Allograft survival was markedly decreased in patients with PTGN (
In addition, we identified graft survival by the incidence of PTGN, acute rejection, and chronic rejection including chronic allograft nephropathy (CAN). In any combinations of the development of acute rejection and CAN, as PTGN developed, the risk of graft failure increased to a considerable extent (
When analyzing the effects of several types of PTGN on allograft survival, there was no significant difference between IgAN, FSGS, MPGN, and immune-mediated GN, and this difference was also verified using Kaplan–Meier analysis (Supplementary Table 2, Supplementary
Of the underlying kidney diseases, glomerular disease was a significant risk factor for PTGN (HR: 3.63, 95% CI: 1.73–7.65,
By contrast, there was no difference in PTGN development according to age, gender, donor type, timing of referral, and pre-emptive transplantation. HLA mismatch was also not significantly associated with the development of PTGN.
The use of antimetabolites such as MMF and azathioprine did not influence the development of PTGN. The administration of basiliximab before transplantation and the use of tacrolimus actually increased the incidence of PTGN, and in multivariate analysis, these results were found to be statistically significant (HR: 1.89, 95% CI: 1.08–3.32,
The aim of this study was to analyze PTGN incidence, its relationship with allograft failure, and the risk factors for PTGN development. PTGN increased over the duration of follow-up, reaching a cumulative probability of 17.0% after 10 years. The development of PTGN significantly decreased allograft survival. Among underlying kidney diseases, the highest occurrence of PTGN was in the glomerular diseases group, with the most common type being IgAN. Also, we demonstrated that PTGN significantly contributed to allograft dysfunction, and eventual graft loss, irrespective of the type of PTGN, and that PTGN incidence markedly increased in patients with baseline glomerular diseases and with the use of tacrolimus and basiliximab. We investigated the clinical courses and prognosis of patients, including PTGN and allograft survival in the unknown etiology group. In many previous studies, these outcomes were analyzed only in patients with pathologically confirmed or presumed glomerular diseases.
The results of our study are consistent with those of an earlier study, which reported that the incidence of PTGN among patients who underwent kidney transplantation after 2001 was significantly higher than those who underwent transplantation before 2001, and that the risk for allograft failure was definitely increased in patients with PTGN
PTGN developed steadily and consistently, and allograft loss due to PTGN increased throughout the follow-up period, while the incidence of allograft loss due to acute rejection was the highest 1 year after transplantation, but rapidly decreased thereafter
Moreover, the fact that administration of tacrolimus increased PTGN is confirmed by the results of a previous study in which recipients treated with tacrolimus instead of CsA had more frequent proteinuria and an increased risk of graft failure
Among underlying glomerular diseases, FSGS recurred in 5 of the 16 patients (31.3%), while the MPGN and IgAN recurrence rate were 25.0% and 15.5%, respectively. These results were comparable with usual recurrence rates reported previously. By contrast, MN did not recur compared with the expected rate of 10–30%; it is assumed that this difference is due to demographic differences in the study population of our centers, and that the recurrence rate will increase with longer follow-up periods
In addition, our findings differ from those of Karakayali et al. in that the recurrence rates were similar among patients taking either tacrolimus or CsA
Our study has a different level of significance compared with others, in that we demonstrated a positive correlation between the use of tacrolimus and basiliximab and PTGN. Even if better immunosuppression regimens decrease post-transplant complications, including treatment-resistant rejection and overall long-term mortality, prolonged graft survival and rejection-free survival were thought to contribute to the higher incidence of PTGN
After adjusting for multiple factors such as increased numbers of kidney biopsies, advances in medicine, and more accurate interpretations of pathologic results, our results appear to be meaningful. It is noteworthy that a cohort of three centers in Asia became the subject of this study and the duration of follow-up was long enough to obtain an accurate interpretation of these results.
Also, even in cases of underlying diabetic renal diseases, PTGN occurred to a considerable extent accounting for 4.9%. It suggests that some patients with diabetes mellitus and renal failure may have underlying glomerular diseases, and therefore the patients without typical features and courses of diabetic renal diseases should have kidney biopsies taken to evaluate underlying glomerular diseases.
There were several limitations to our study. First, it was not possible to distinguish
It is expected that the number of kidney transplants will increase, and developing effective immunosuppression treatment methods will reduce early and late complications, and enhance comprehensive outcomes and survival rates after transplantation. In this light, the importance of PTGN will be emphasized. We demonstrated that PTGN has a prominent and considerable influence on allograft survival like acute rejection, even in transplant recipients with ESRD of unknown etiology. We suggest that understanding the risk factors and prognosis of PTGN should play a significant role in the monitoring and management of renal allograft patients in the future.
In conclusion, PTGN was strongly associated with poor kidney allograft survival. A critical focus of post-transplant care should be the management of recurrent or
None declared.
Presented at Kidney Week 2011 of the American Society of Nephrology, Philadelphia, PA, November 8–13, 2011. Presented at American Transplant Congress 2012 of the American Society of Transplantation, Boston, MA, June 2–6, 2012. This work was supported by a grant from the
Supplementary data associated with this article can be found in the online version at
Baseline characteristics classified by underlying kidney diseases
Total ( | Glomerular ( | Vascular ( | Interstitial/PN/Uropathy ( | Diabetic ( | Hereditary and various ( | Unknown ( | |
---|---|---|---|---|---|---|---|
Era | |||||||
1995–2000 | 173 (22.6) | 72 (24.7) | 33 (25.2) | 12 (26.7) | 4 (4.9) | 13 (17.8) | 39 (27.7) |
2001–2005 | 235 (30.8) | 89 (30.5) | 45 (34.4) | 15 (33.3) | 23 (28.0) | 19 (26.0) | 44 (31.2) |
2006–2010 | 356 (46.6) | 131 (44.8) | 53 (40.4) | 18 (40.0) | 55 (67.1) | 41 (56.2) | 58 (41.1) |
HLA mismatch | |||||||
Unknown | 22 (2.9) | 8 (2.7) | 0 (0) | 0 (0) | 4 (4.9) | 1 (1.4) | 9 (6.4) |
0 | 100 (13.1) | 44 (15.1) | 13 (9.9) | 10 (22.2) | 6 (7.3) | 7 (9.6) | 20 (14.2) |
1–3 | 410 (53.7) | 162 (55.5) | 77 (58.8) | 23 (51.1) | 40 (48.8) | 33 (45.2) | 75 (53.2) |
4–6 | 232 (30.3) | 78 (26.7) | 41 (31.3) | 12 (26.7) | 32 (39.0) | 32 (43.8) | 37 (26.2) |
Male (recipient) | 446 (58.4) | 167 (57.2) | 83 (63.4) | 24 (53.3) | 55 (67.1) | 45 (61.6) | 72 (51.1) |
Male (donor) | 406 (54.0) | 161 (56.1) | 77 (58.8) | 21 (46.7) | 42 (52.5) | 42 (57.5) | 63 (46.3) |
Donor type | |||||||
Living related | 451 (59.0) | 190 (65.1) | 75 (57.3) | 27 (60.0) | 43 (52.4) | 34 (46.6) | 82 (58.2) |
Living unrelated | 141 (18.5) | 42 (14.4) | 35 (26.7) | 4 (8.9) | 18 (22.0) | 18 (24.7) | 24 (17.0) |
Deceased | 172 (22.5) | 60 (20.5) | 21 (16.0) | 14 (31.1) | 21 (25.6) | 21 (28.7) | 35 (24.8) |
Referral | |||||||
Early (≥1 y) | 569 (74.5) | 249 (85.3) | 71 (54.2) | 41 (91.1) | 78 (95.2) | 70 (95.9) | 60 (42.6) |
Late (<1 y) | 178 (23.3) | 38 (13.0) | 54 (41.2) | 4 (8.9) | 2 (2.4) | 3 (4.1) | 77 (54.6) |
Unknown | 17 (2.2) | 5 (1.7) | 6 (4.6) | 0 (0) | 2 (2.4) | 0 (0) | 4 (2.8) |
Pre-emptive | 274 (35.9) | 113 (38.7) | 50 (38.2) | 10 (22.2) | 22 (26.8) | 29 (39.7) | 50 (35.5) |
Diabetes mellitus | 93 (12.2) | 3 (1.0) | 2 (1.5) | 1 (2.2) | 82 (100.0) | 3 (4.1) | 2 (1.4) |
Hypertension | 523 (68.5) | 192 (65.8) | 131 (100.0) | 20 (44.4) | 58 (70.7) | 33 (45.2) | 89 (63.1) |
Immunosuppressants | |||||||
Calcineurin inhibitors | |||||||
Cyclosporine A | 369 (48.3) | 137 (46.9) | 71 (54.2) | 20 (44.4) | 42 (51.2) | 27 (37.0) | 72 (51.1) |
Tacrolimus | 389 (50.9) | 155 (53.1) | 58 (44.3) | 24 (53.4) | 38 (46.4) | 46 (63.0) | 68 (48.2) |
Others | 6 (0.8) | 0 (0) | 2 (1.5) | 1 (2.2) | 2 (2.4) | 0 (0) | 1 (0.7) |
Purine synthesis inhibitors | |||||||
Not use | 82 (10.7) | 35 (12.0) | 17 (13.0) | 5 (11.1) | 2 (2.4) | 8 (11.0) | 15 (10.6) |
MMF | 574 (75.2) | 215 (73.6) | 90 (68.7) | 34 (75.6) | 77 (93.9) | 56 (76.7) | 102 (72.3) |
Azathioprine | 107 (14.0) | 41 (14.0) | 24 (18.3) | 6 (13.3) | 3 (3.7) | 9 (12.3) | 24 (17.1) |
Others | 1 (0.1) | 1 (0.4) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
Basiliximab | 322 (42.1) | 115 (39.4) | 50 (38.2) | 20 (44.4) | 46 (56.1) | 38 (52.1) | 53 (37.6) |
Age at transplant | 41.49±11.97 | 38.69±11.06 | 46.18±10.60 | 35.22±12.71 | 52.10±9.18 | 39.84±13.43 | 39.65±10.46 |
Donor age | 38.80±12.26 | 38.25±11.71 | 38.58±10.95 | 37.98±12.52 | 40.44±14.77 | 40.79±12.92 | 38.38±12.57 |
HLA, human leukocyte antigen; MMF, mycophenolate mofetil; PN, pyelonephritis.
Data expressed as mean±standard deviation (in years).
Association between underlying kidney diseases and the incidence of PTGN
Underlying kidney disease | Patients with PTGN | |||||||
---|---|---|---|---|---|---|---|---|
IgAN | FSGS | MPGN | MN | Immune-mediated GN | Lupus nephritis | Incidence of PTGN (%) | ||
Glomerular | 292 | 42 | 4 | 2 | 1 | 2 | 1 | 52 (17.8) |
Biopsy proven | ||||||||
IgAN | 129 | 19 | 1 | 0 | 0 | 0 | 0 | 20 (15.5) |
FSGS | 16 | 4 | 1 | 0 | 0 | 0 | 0 | 5 (31.3) |
MPGN | 8 | 0 | 0 | 1 | 0 | 1 | 0 | 2 (25.0) |
MN | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 (0.0) |
Lupus nephritis | 14 | 0 | 0 | 0 | 0 | 0 | 1 | 1 (7.1) |
Other GN | 24 | 0 | 1 | 1 | 0 | 0 | 0 | 2 (8.3) |
Clinically diagnosed | 97 | 19 | 1 | 0 | 1 | 1 | 0 | 22 (22.7) |
Vascular | 131 | 0 | 0 | 0 | 0 | 0 | 0 | 0 (0.0) |
Interstitial/PN/Uropathy | 45 | 2 | 0 | 0 | 0 | 0 | 0 | 2 (4.4) |
Diabetic | 82 | 3 | 1 | 0 | 0 | 0 | 0 | 4 (4.9) |
Hereditary/various | 73 | 1 | 1 | 1 | 1 | 0 | 0 | 4 (5.5) |
Unknown | 141 | 6 | 2 | 0 | 0 | 0 | 0 | 8 (5.7) |
Total | 764 | 54 | 8 | 3 | 2 | 2 | 1 | 70 (9.2) |
FSGS, focal segmental glomerulosclerosis; GN, glomerulonephritis; IgAN, immunoglobulin A nephropathy; MN, membranous nephropathy; MPGN, membranoproliferative GN; PN, pyelonephritis; PTGN, post-transplantation glomerulonephritis.
Incidence rate of developing PTGN in each group of underlying renal diseases.
Effects of acute rejection and PTGN on graft failure
Univariate analysis | Multivariate analysis | ||||
---|---|---|---|---|---|
HR (95% CI) | HR (95% CI) | ||||
Acute rejection–PTGN– | 564 | Reference | Reference | ||
Acute rejection–PTGN+ | 46 | 3.84 (1.68–8.77) | 0.001 | 4.02 (1.74–9.29) | 0.001 |
Acute rejection+PTGN– | 132 | 4.79 (2.65–8.65) | <0.001 | 5.40 (2.94–9.93) | <0.001 |
Acute rejection+PTGN+ | 22 | 6.22 (2.62–14.76) | <0.001 | 7.11 (2.96–17.07) | <0.001 |
HR, hazard ratio; PTGN, post-transplantation glomerulonephritis.
Adjusted for the following variables: underlying renal diseases, the era of transplantation, human leukocyte antigen mismatch, age and gender of recipient and donor, donor type, timing difference of referral, pre-emptive transplantation, and administered immunosuppressants.
Patients without occurrence of both acute rejection and PTGN.
Patients with occurrence of PTGN, but without acute rejection.
Patients with occurrence of acute rejection, but without PTGN.
Patients with occurrence of both acute rejection and PTGN.
Effects of acute and chronic rejection, and PTGN on graft failure
Univariate analysis | Multivariate analysis | ||||
---|---|---|---|---|---|
HR (95% CI) | HR (95% CI) | ||||
Acute rejection–CAN–PTGN– | 536 | Reference | Reference | ||
Acute rejection–CAN–PTGN+ | 34 | 3.90 (1.42–10.69) | 0.008 | 2.71 (0.87–8.47) | 0.087 |
Acute rejection–CAN+PTGN– | 22 | 3.92 (1.30–11.79) | 0.015 | 4.05 (1.16–14.20) | 0.029 |
Acute rejection–CAN+PTGN+ | 12 | 5.63 (1.63–19.39) | 0.006 | 5.13 (1.34–19.61) | 0.017 |
Acute rejection+CAN–PTGN– | 98 | 3.85 (1.82–8.16) | <0.001 | 4.66 (2.03–10.68) | <0.001 |
Acute rejection+CAN–PTGN+ | 14 | 9.68 (3.76–24.92) | <0.001 | 11.20 (3.81–32.90) | <0.001 |
Acute rejection+CAN+PTGN– | 38 | 8.93 (4.27–18.66) | <0.001 | 9.40 (4.09–21.60) | <0.001 |
Acute rejection+CAN+PTGN+ | 10 | 2.28 (0.30–17.21) | 0.426 | 3.62 (0.39–33.34) | 0.256 |
CAN, chronic allograft nephropathy; HR, hazard ratio; PTGN, post-transplantation glomerulonephritis.
–, No development; +, Development.
Adjusted for the following variables: underlying renal diseases, the era of transplantation, human leukocyte antigen mismatch, age and gender of recipient and donor, donor type, timing difference of referral, pre-emptive transplantation, and administered immunosuppressants.
Multiple risk factors for developing PTGN
Univariate analysis | Multivariate analysis | |||
---|---|---|---|---|
HR (95% CI) | HR (95% CI) | |||
Underlying kidney disease | ||||
Unknown | Reference | Reference | ||
Glomerular | 3.63 (1.73–7.65) | 0.001 | 4.01 (1.82–8.84) | 0.001 |
Vascular | 0.00 | 0.953 | 0.00 | 0.953 |
Interstitial/PN/Uropathy | 0.83 (0.18–3.91) | 0.815 | 0.84 (0.17–4.04) | 0.826 |
Diabetic | 1.63 (0.49–5.46) | 0.428 | 1.88 (0.54–6.53) | 0.320 |
Hereditary/various | 1.27 (0.38–4.23) | 0.695 | 1.23 (0.36–4.22) | 0.743 |
Era | ||||
1995–2000 | Reference | |||
2001–2005 | 1.76 (0.94–3.31) | 0.080 | ||
2006–2010 | 2.52 (1.16–5.46) | 0.019 | ||
HLA mismatch | ||||
0 | Reference | |||
1–3 | 0.86 (0.43–1.74) | 0.680 | ||
4–6 | 1.04 (0.49–2.23) | 0.917 | ||
Age at transplant (y) | ||||
1st percentile | Reference | |||
2nd percentile | 0.84 (0.46–1.53) | 0.566 | ||
3rd percentile | 0.60 (0.30–1.23) | 0.165 | ||
4th percentile | 0.82 (0.43–1.59) | 0.564 | ||
Donor age (y) | ||||
1st percentile | Reference | |||
2nd percentile | 0.58 (0.31–1.09) | 0.090 | ||
3rd percentile | 0.62 (0.32–1.21) | 0.160 | ||
4th percentile | 0.62 (0.32–1.20) | 0.156 | ||
Male gender (recipient) | 0.74 (0.46–1.19) | 0.211 | ||
Male gender (donor) | 1.09 (0.67–1.75) | 0.734 | ||
Donor type | ||||
Living related | Reference | |||
Living unrelated | 1.08 (0.57–2.05) | 0.823 | ||
Deceased | 1.25 (0.69–2.26) | 0.468 | ||
Referral | ||||
Late referral | Reference | |||
Early referral | 0.84 (0.50–1.41) | 0.510 | ||
Pre-emptive transplantation | 0.59 (0.35–1.02) | 0.058 | ||
Immunosuppressant | ||||
Purine synthesis inhibitors | ||||
Not used | Reference | |||
Azathioprine | 0.49 (0.22–1.09) | 0.079 | ||
Mycophenolate mofetil | 1.27 (0.65–2.47) | 0.489 | ||
Calcineurin inhibitor | ||||
Cyclosporine A | Reference | Reference | ||
Tacrolimus | 2.26 (1.37–3.72) | 0.001 | 2.10 (1.25–3.54) | 0.005 |
Basiliximab | 2.05 (1.20–3.52) | 0.009 | 1.89 (1.08–3.32) | 0.027 |
CI, confidence interval; DM, diabetes mellitus; GN, glomerulonephritis; HLA, human leukocyte antigen; HR, hazard ratio; HTN, hypertension; PTGN, post-transplant glomerulonephritis.
Adjusted for the following variables: underlying renal diseases, the era of transplantation, HLA mismatch, age and gender of recipient, pre-emptive transplantation, and administered immunosuppressants.