scholarly journals Increased Immunogenicity and Cause of Graft Loss of Old Donor Kidneys

2001 ◽  
Vol 12 (7) ◽  
pp. 1538-1546
Author(s):  
JOHAN W. DE FIJTER ◽  
MARKO J. K. MALLAT ◽  
ILIAS I. N. DOXIADIS ◽  
JAN RINGERS ◽  
FRITS R. ROSENDAAL ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Graft Survival ◽  
Negative Impact ◽  
Graft Loss ◽  
Graft Function ◽  
Significant Risk ◽  
Donor Age ◽  
Independent Predictive Factor ◽  
Long Term Outcome ◽  
Old Donor

Abstract. Donor age was identified recently as a major factor that determines long-term outcome after transplantation, but the mechanism that is responsible for increased graft loss of old donor kidneys is unknown. The influence of donor age on graft survival was assessed retrospectively in 514 consecutive first cadaveric transplants that were treated with cyclosporine maintenance immunosuppression. Donor age ≥50 yr (relative risk [RR] = 1.7; 95% confidence interval [CI], 1.2 to 2.6), acute rejection (RR = 2.0; 95% CI, 1.3 to 3.0), and type of rejection (RR = 3.3; 95% CI, 2.0 to 5.3) had a significant impact on graft survival. However, when subsets of patients who entered subsequent intervals after transplantation were analyzed, donor age was not an independent predictive factor of graft loss. Donor age (RR = 1.53; 95% CI, 1.19 to 1.98), human leukocyte antigen-DR mismatch (RR = 2.28; 95% CI, 1.78 to 2.92), and recipient age (RR = 1.34; 95% CI, 1.05 to 1.72) were associated significantly with acute rejection episodes. Delayed graft function alone was not associated independently with the occurrence of early acute rejection (RR = 1.24; 95% CI, 0.96 to 1.61). The timing of the rejection episodes of old donor kidneys was not different, and the excess rejection prevalence was attributable entirely to interstitial (grade I) types of rejection. Interstitial rejection episodes in kidneys from old donors had a significant (P< 0.05) negative impact on graft survival. Beyond the first year, poor renal function and proteinuria were significant risk factors for graft loss, regardless of rejection. Our data fit best the hypothesis that increased graft loss of older donor kidneys results from an increased incidence of acute interstitial rejection episodes in the early posttransplantation months. It is proposed that kidneys from older donors are more immunogenic than kidneys from young donors and that acute rejection episodes result in functional deterioration. Contrary to interstitial rejection in kidneys from younger donors, kidneys from old donors seem to have an impaired ability to restore tissue.

scholarly journals Relationship between early proteinuria and long term outcome of kidney transplanted patients from different decades of donor age

2019 ◽  
Author(s):  
Davide Diena ◽  
Maria Messina ◽  
Consuelo De Biase ◽  
Fabrizio Fop ◽  
Edoardo Scardino ◽  
...  
Keyword(s):  
Graft Survival ◽  
Age Groups ◽  
Graft Function ◽  
Significant Risk ◽  
Low Grade ◽  
Donor Age ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Post Transplant ◽  
The Impact

Abstract Background Proteinuria after kidney transplantation portends a worse graft survival. However the magnitude of proteinuria related to patient and graft survival and its correlation with donor and recipient characteristics are poorly explored. Methods This study investigated the impact of post transplant proteinuria in the first year in 1127 kidney transplants analyzing the impact of different donor ages. Proteinuria cut off was set at 0.5 g/day. Results Transplants with proteinuria > 0.5 g/day correlated with poor graft and patient outcome in all donor age groups. In addition, 6-month-1-year proteinuria increase was significantly associated with graft outcome, especially with donors > 60 years old (p < 0.05; Odd Ratio 1.8). 1-year graft function (eGFR < or ≥44 ml/min) had similar impact to proteinuria (≥ 0.5 g/day) on graft failure (HR 2.77 vs HR 2.46). Low-grade proteinuria (0.2-0.5 g/day) demonstrated a trend for worse graft survival with increasing donor age. Also in kidney-paired analysis proteinuria ≥ 0.5 effect was more significant with donors >50 years old (OR 2.3). Conclusions Post-transplant proteinuria was increasingly harmful with older donor age. Proteinuria ≥ 0.5 g/day correlates with worse outcomes in all transplanted patients. Prognostic value of proteinuria and eGFR for graft and patient survival was comparable and these two variables remain significant risk factors even in a multivariate model that take into consideration the most important clinical variables (donor age, rejection, delayed graft function and cytomegalovirus viremia among others).

scholarly journals Relationship between early proteinuria and long term outcome of kidney transplanted patients from different decades of donor age

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Davide Diena ◽  
Maria Messina ◽  
Consuelo De Biase ◽  
Fabrizio Fop ◽  
Edoardo Scardino ◽  
...  
Keyword(s):  
Graft Survival ◽  
Graft Function ◽  
Significant Risk ◽  
Hazard Ratio ◽  
Low Grade ◽  
Donor Age ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Post Transplant ◽  
The Impact

Abstract Background Proteinuria after kidney transplantation portends a worse graft survival. However the magnitude of proteinuria related to patient and graft survival and its correlation with donor and recipient characteristics are poorly explored. Methods This study investigated the impact of post transplant proteinuria in the first year in 1127 kidney transplants analyzing the impact of different donor ages. Proteinuria cut off was set at 0.5 g/day. Results Transplants with proteinuria > 0.5 g/day correlated with poor graft and patient outcome in all donor age groups. In addition, 6-month-1-year proteinuria increase was significantly associated with graft outcome, especially with donors > 60 years old (p <  0.05; Odd Ratio 1.8). 1-year graft function (eGFR < or ≥ 44 ml/min) had similar impact to proteinuria (≥ 0.5 g/day) on graft failure (Hazard Ratio 2.77 vs Hazard Ratio 2.46). Low-grade proteinuria (0.2–0.5 g/day) demonstrated a trend for worse graft survival with increasing donor age. Also in kidney-paired analysis proteinuria ≥0.5 effect was more significant with donors > 50 years old (Odd Ratio 2.3). Conclusions Post-transplant proteinuria was increasingly harmful with older donor age. Proteinuria ≥0.5 g/day correlates with worse outcomes in all transplanted patients. Prognostic value of proteinuria and eGFR for graft and patient survival was comparable and these two variables remain significant risk factors even in a multivariate model that take into consideration the most important clinical variables (donor age, rejection, delayed graft function and cytomegalovirus viremia among others).

scholarly journals Relationship between early proteinuria and long term outcome of kidney transplanted patients from different decades of donor age

2019 ◽  
Author(s):  
Davide Diena ◽  
Maria Messina ◽  
Consuelo De Biase ◽  
Fabrizio Fop ◽  
Edoardo Scardino ◽  
...  
Keyword(s):  
Graft Survival ◽  
Age Groups ◽  
Graft Function ◽  
Significant Risk ◽  
Low Grade ◽  
Donor Age ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Post Transplant ◽  
The Impact

Abstract Background Proteinuria after kidney transplantation portends a worse graft survival. However the magnitude of proteinuria related to patient and graft survival and its correlation with donor and recipient characteristics are poorly explored. Methods This study investigated the impact of post transplant proteinuria in the first year in 1127 kidney transplants analyzing the impact of different donor ages. Proteinuria cut off was set at 0.5 g/day. Results Transplants with proteinuria > 0.5 g/day correlated with poor graft and patient outcome in all donor age groups. In addition, 6-month-1-year proteinuria increase was significantly associated with graft outcome, especially with donors > 60 years old (p < 0.05; Odd Ratio 1.8). 1-year graft function (eGFR < or ≥44 ml/min) had similar impact to proteinuria (≥ 0.5 g/day) on graft failure (HR 2.77 vs HR 2.46). Low-grade proteinuria (0.2-0.5 g/day) demonstrated a trend for worse graft survival with increasing donor age. Also in kidney-paired analysis proteinuria ≥ 0.5 effect was more significant with donors >50 years old (OR 2.3). Conclusions Post-transplant proteinuria was increasingly harmful with older donor age. Proteinuria ≥ 0.5 g/day correlates with worse outcomes in all transplanted patients. Prognostic value of proteinuria and eGFR for graft and patient survival was comparable and these two variables remain significant risk factors even in a multivariate model that take into consideration the most important clinical variables (donor age, rejection, delayed graft function and cytomegalovirus viremia among others).

scholarly journals Relationship between early proteinuria and long term outcome of kidney transplanted patients from different decades of donor age

2019 ◽  
Author(s):  
Davide Diena ◽  
Maria Messina ◽  
Consuelo De Biase ◽  
Fabrizio Fop ◽  
Edoardo Scardino ◽  
...  
Keyword(s):  
Graft Survival ◽  
Age Groups ◽  
Graft Function ◽  
Significant Risk ◽  
Low Grade ◽  
Donor Age ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Post Transplant ◽  
The Impact

Abstract Background Proteinuria after kidney transplantation portends a worse graft survival. However the magnitude of proteinuria related to patient and graft survival and its correlation with donor and recipient characteristics are poorly explored. Methods This study investigated the impact of post transplant proteinuria in the first year in 1127 kidney transplants analyzing the impact of different donor ages. Proteinuria cut off was set at 0.5 g/day. Results Transplants with proteinuria > 0.5 g/day correlated with poor graft and patient outcome in all donor age groups. In addition, 6-month-1-year proteinuria increase was significantly associated with graft outcome, especially with donors > 60 years old (p < 0.05; Odd Ratio 1.8). 1-year graft function (eGFR < or ≥44 ml/min) had similar impact to proteinuria (≥ 0.5 g/day) on graft failure (HR 2.77 vs HR 2.46). Low-grade proteinuria (0.2-0.5 g/day) demonstrated a trend for worse graft survival with increasing donor age. Also in kidney-paired analysis proteinuria ≥ 0.5 effect was more significant with donors >50 years old (OR 2.3). Conclusions Post-transplant proteinuria was increasingly harmful with older donor age. Proteinuria ≥ 0.5 g/day correlates with worse outcomes in all transplanted patients. Prognostic value of proteinuria and eGFR for graft and patient survival was comparable and these two variables remain significant risk factors even in a multivariate model that take into consideration the most important clinical variables (donor age, rejection, delayed graft function and cytomegalovirus viremia among others).

scholarly journals Successful rescue therapy with mycophenolate mofetil in kidney transplantation improves the long-term graft survival

Medicina ◽  
2007 ◽  
Vol 43 (12) ◽  
pp. 953 ◽  
Author(s):  
Jaanus Kahu ◽  
Aleksander Lõhmus ◽  
Madis Ilmoja ◽  
Ülle Kirsimägi ◽  
Gennadi Timberg ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Kidney Transplantation ◽  
Graft Survival ◽  
Cyclosporine A ◽  
Negative Impact ◽  
Rescue Therapy ◽  
Graft Loss ◽  
Graft Function ◽  
Significant Difference

Objective. The aim of this study was to compare the graft survival after kidney transplantation in patients treated with azathioprine (AZA) or mycophenolate mofetil (MMF) and analyze the significance of different risk factors for graft survival. Material and methods. A total of 137 patients, transplanted between January 1996 and June 2001, were retrospectively divided into two groups: patients who received AZA together with cyclosporine A and methylprednisolone (AZA group, n=72) and patients who received MMF either immediately or were switched from AZA to MMF during 3 months (MMF group, n=65). Results. According to Kaplan-Meier analysis, a 1-year graft survival was 79% in the AZA group and 85% in the MMF group; a 6-year graft survival was 51% and 67%, respectively (P=0.046). Multivariate Cox survival model demonstrated that MMF therapy reduced the risk of graft loss by 34% (P=0.028), while delayed graft function increased the risk of graft loss (risk ratio 2.26, P=0.009). A statistically significant difference in total cholesterol level (6.7 vs. 5.7 mmol/L, respectively; P=0.002), mean systolic blood pressure (145 vs. 134 mmHg, P=0.009), and cyclosporine A daily dose (238 vs. 203 mg, P=0.015) between the AZA and MMF groups at 1 year was revealed. Conclusion. MMF rescue therapy improves the long-term graft survival compared to AZA despite high early rejection rate and avoids the negative impact of acute rejections on graft survival.

scholarly journals Recipient pre-existing chronic hypotension is associated with delayed graft function and inferior graft survival in kidney transplantation from elderly donors

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249552
Author(s):  
Caterina Dolla ◽  
Alberto Mella ◽  
Giacinta Vigilante ◽  
Fabrizio Fop ◽  
Anna Allesina ◽  
...  
Keyword(s):  
Graft Survival ◽  
Population Stratification ◽  
Logistic Regression Model ◽  
Univariate Analysis ◽  
Graft Function ◽  
The Other ◽  
Delayed Graft Function ◽  
Donor Age ◽  
Old Donor ◽  
Transplant Procedure

Background Pre-existing chronic hypotension affects a percentage of kidney transplanted patients (KTs). Although a relationship with delayed graft function (DGF) has been hypothesized, available data are still scarce and inconclusive. Methods A monocentric retrospective observational study was performed on 1127 consecutive KTs from brain death donors over 11 years (2003–2013), classified according to their pre-transplant Mean Blood Pressure (MBP) as hypotensive (MBP < 80 mmHg) or normal-hypertensive (MBP ≥ 80 mmHg, with or without effective antihypertensive therapy). Results Univariate analysis showed that a pre-existing hypotension is associated to DGF occurrence (p<0.01; OR for KTs with MBP < 80 mmHg, 4.5; 95% confidence interval [CI], 2.7 to 7.5). Chronic hypotension remained a major predictive factor for DGF development in the logistic regression model adjusted for all DGF determinants. Adjunctive evaluations on paired grafts performed in two different recipients (one hypotensive and the other one normal-hypertensive) confirmed this assumption. Although graft survival was only associated with DGF but not with chronic hypotension in the overall population, stratification according to donor age revealed that death-censored graft survival was significantly lower in hypotensive patients who received a KT from >50 years old donor. Conclusions Our findings suggest that pre-existing recipient hypotension, and the subsequent hypotension-related DGF, could be considered a significant detrimental factor, especially when elderly donors are involved in the transplant procedure.

scholarly journals Risk Factors for 1-Year Graft Loss After Kidney Transplantation

2019 ◽  
Vol 14 (11) ◽  
pp. 1642-1650 ◽  
Author(s):  
Farid Foroutan ◽  
Erik Loewen Friesen ◽  
Kathryn Elizabeth Clark ◽  
Shahrzad Motaghi ◽  
Roman Zyla ◽  
...  
Keyword(s):  
Risk Factors ◽  
Kidney Transplant ◽  
Graft Survival ◽  
Graft Loss ◽  
Graft Function ◽  
Delayed Graft Function ◽  
Donor Age ◽  
Degree Of Certainty ◽  
Recipient Age ◽  
High Degree

Background and objectivesWith expansion of the pool of kidney grafts, through the use of higher-risk donors, and increased attention to donor management strategies, the 1-year graft survival rate is subject to change. It is, therefore, useful to elucidate 1-year graft survival rates by dissecting the characteristics of the low-risk and high-risk kidney transplant cases. The objective of our study was to evaluate factors purported to influence the risk of 1-year graft loss in kidney transplant recipients.Design, setting, participants, & measurementsWe searched bibliographic databases from 2000 to 2017 and included observational studies that measured the association between donor, recipient, the transplant operation, or early postoperative complications, and 1-year death-censored graft loss.ResultsWe identified 35 eligible primary studies, with 20 risk factors amenable to meta-analysis. Six factors were associated with graft loss, with moderate to high degree of certainty: donor age (hazard ratio [HR], 1.11 per 10-year increase; 95% confidence interval [95% CI], 1.04 to 1.18), extended criteria donors (HR, 1.35; 95% CI, 1.28 to 1.42), deceased donors (HR, 1.54; 95% CI, 1.32 to 1.82), number of HLA mismatches (HR, 1.08 per one mismatch increase; 95% CI, 1.07 to 1.09), recipient age (HR, 1.17 per 10-year increase; 95% CI, 1.09 to 1.25), and delayed graft function (HR, 1.89; 95% CI, 1.46 to 2.47) as risk factors for 1-year graft loss. Pooled analyses also excluded, with a high degree of certainty, any associations of cold ischemia time, recipient race, pretransplant body mass index, diabetes, and hypertension with 1-year graft loss.ConclusionsRecipient age, donor age, standard versus extended criteria donor, living versus deceased donor, HLA mismatch, and delayed graft function all predicted 1-year graft survival. The effect of each risk factor is small.

MO941CLINICAL OUTCOMES IN KIDNEY RE-TRANSPLANTATION

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Clara Pardinhas ◽  
Rita Leal ◽  
Francisco Caramelo ◽  
Teofilo Yan ◽  
Carolina Figueiredo ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Kidney Transplant ◽  
Graft Survival ◽  
Graft Failure ◽  
Graft Function ◽  
Delayed Graft Function ◽  
First Year ◽  
Kidney Transplant Recipients ◽  
Post Transplant

Abstract Background and Aims As kidney transplants are growing in absolute numbers, so are patients with failed allografts and thus potential candidates for re-transplantation. Re-transplantation is challenging due to immunological barriers, surgical difficulties and clinical complexities but it has been proven that successful second transplantation improves life expectancy over dialysis. It is important to evaluate re-transplantation outcomes since 20% of patients on the waiting list are waiting for a second graft. Our aim was to compare major clinical outcomes such as acute rejection, graft and patient survival, between patients receiving a first or a second kidney transplant. Method We performed a retrospective study, that included 1552 patients submitted to a first (N=1443, 93%) or a second kidney transplant (N=109, 7%), between January 2008 and December 2018. Patients with more than 2 grafts or multi-organ transplant were excluded. Demographic, clinical and histocompatibility characteristics of both groups were registered from our unit database and compared. Delayed graft function was defined has the need of dialysis in the first week post-transplant. All acute rejection episodes were biopsy proven, according to Banff 2017 criteria. Follow-up time was defined at 1st June 2020 for functioning grafts or at graft failure (including death with a functioning graft). Results Recipients of a second graft were significantly younger (43 ±12 vs 50 ± 13 years old, p&lt;0.001) and there were significantly fewer expanded-criteria donors in the second transplant group (31.5% vs 57.5%, p&lt;0.001). The waiting time for a second graft was longer (63±50 vs 48±29 months, p=0.011). HLA mismatch was similar for both groups but PRA was significantly higher for second KT patients (21.6±25% versus 3±9%; p&lt;0.001). All patients submitted to a second KT had thymoglobulin as induction therapy compared to 16% of the first KT group (p&lt;0.001). We found no difference in primary dysfunction or delayed graft function between groups. Acute rejection was significantly more frequent in second kidney transplant recipients (19% vs 5%, p&lt;0.001), being 10 acute cellular rejections, 7 were antibody mediated and 3 were borderline changes. For the majority of the patients (85%), acute rejection occurred in the first-year post-transplant. Death censored graft failure occurred in 236 (16.4%) patients with first kidney transplant and 25 (23%) patients with a second graft, p=0.08. Survival analysis showed similar graft survival for both groups (log-rank p=0.392). We found no difference in patients’ mortality at follow up for both groups. Conclusion Although second graft patients presented more episodes of biopsy proven acute rejection, especially at the first-year post-transplant, we found no differences in death censored graft survival or patients’ mortality for patients with a second kidney transplant. Second transplants should be offered to patients whenever feasible.

P1677KIDNEY ALLOGRAFT HISTOLOGY IN RECIPIENTS WITH TRANSPLANTATION VINTAGE LONGER THAN 10 YEARS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Tomoko Namba-Hamano ◽  
Takayuki Hamano ◽  
Masahiro Kyo ◽  
Yutaka Yamaguchi ◽  
Kawamura Masataka ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Graft Survival ◽  
Odds Ratio ◽  
Proportional Hazards ◽  
Graft Loss ◽  
Cox Proportional Hazards ◽  
Regression Analyses ◽  
Histological Findings ◽  
Donor Age

Abstract Background and Aims Few studies have evaluated long-term graft histology. The aims of this study were to reveal the histological characteristics peculiar to long-term graft and to identify clinical manifestations and histological findings predicting graft survival after biopsy. Method In this retrospective study, we enrolled all allograft biopsies conducted in two institutions between 2002 and 2018 in recipients who had underwent transplantation 10 years before (n=107). The revised Banff criteria were used to evaluate histological findings. For a baseline cress-sectional study, we employed logistic regression analyses, to explore clinical factors associated with each histological parameter. Restricted cubic spline functions were used for non-linear associations. In longitudinal study, log-rank test and Cox proportional hazards models were used to evaluate the death-censored graft loss. Results Median (IQR) of time after transplantation, recipient age at biopsy, and donor age were 13 (11, 19), 49 (42, 59), and 51 years (43, 58), respectively. Median (IQR) eGFR and proteinuria at biopsy was 29 (24,40) mL/min/1.73m2 and 0.46 (0.18,0.80) g/day, respectively. Seventeen patients (16%) had FSGS lesion, which was the most common glomerular abnormality in this cohort. Figure 1 shows the distribution of histological parameters. Donor age, in addition to proteinuria, was found to be associated with the presence of FSGS lesion [Odds ratio 2.37 (95%CI 1.16-4.88) per 10-year]. When constructing a non-linear model, estimated prevalence of FSGS lesion was increased in grafts from donors of &gt; 40 years old (Figure 2). Logistic regression analyses revealed that eGFR at biopsy and transplantation vintage were associated with the presence of ci [Odds ratio 0.48 (95%CI 0.32-0.71) per 10 mL/min/1.73m2, and 1.17 (1.05-1.30) per 10-year, respectively]. We also found that eGFR at biopsy and proteinuria were associated with the presence of ct [Odds ratio 0.40 (95%CI 0.26-0.63) per 10 mL/min/1.73m2, and 2.02 (1.07-3.84) per 1g/day, respectively]. Figure 3 shows Kaplan-Meier curves for death-censored graft survival after biopsy. During 3.5 years of observation, 33% of patients lost their graft functions. Log rank tests revealed that the risk of graft loss is increased in the groups with the presence of ct (p=0.001), and FSGS lesion (p=0.0001), and higher score of cg (p&lt;0.0001). In multivariate Cox proportional hazards model, the highest score of cg in addition to grater proteinuria and lower eGFR at biopsy showed higher risk of graft loss after biopsy [Hazard ratio 3.26 (95% CI 1.25-8.53) as compared to cg0, 1.64 (1.09-2.46) per g/day, and 0.39 (0.24-0.64) per 10 mL/min/1.73m2, respectively]. Conclusion The grafts from older donors, especially older than 40 years old, have FSGS lesion more frequently. Only cg score, not ct score or FSGS lesion, predicts graft survival after biopsy in patients with long transplantation vintage, independently from clinical information.

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