A 72-year-old CKD 5 patient, non-diabetic, currently on peritoneal dialysis. He consulted you regarding kidney transplantation, as his sister (59 years old) with 111 mismatch is willing to donate a kidney for him. How do you council him regarding the following:
- Patient Survival
- Graft survival
- Primary failure rate
- Acute rejection rate
- DGF rate
- If living donation did not go ahead, will you offer him a marginal kidney (ECD – Expanded Criteria Donor) kidney?
- What are the strongest predictors of death in elderly recipients?
- What is the effect of HLA mismatch on graft survival?
- At the age of 72, would he benefit from kidney transplantation?
Patient Survival ;
Mortality rate was higher in older transplant recipients, reflecting the expected increased mortality in this group. It is recognized that mortality rate in older people with ESRD is lower when treated with transplantation than alternative forms of RRT
Graft survival
Immunosuppressant dose reduction in older renal transplant recipients has been associated with improved recipient and graft survival, reduction in cardiovascular risk, reduced drug side effects and cost savings
Primary failure rate
it is more common in elderly recipients as most kidneys are received from ECD. It is well established that ECD kidney have a higher rate of primary graft failure than SCD kidneys; But in this patient a live kidney transplant is being contemplated, so primary graft failure per se is less, but we have to take in consideration the HLA mismatch which will affect graft survival
Acute rejection rate
Studies showed a significant reduction in the rate of biopsy-proven acute rejection of renal grafts in older patients. Prevention of rejection is generally easier in older patients due to natural immune senescence , allowing reduced dosage of immunosuppressant medication.
DGF rate
Is higher in elderly recipients as most of the kidneys are often from deceased donor program with elderly donors and prolonged cold ischemia time affecting the normal graft function.
If living donation did not go ahead, will you offer him a marginal kidney (ECD – Expanded Criteria Donor) kidney?
Yes, I will offer ECD kidney for older recipient because it is better than to wait for a period looking for living donor .
What are the strongest predictors of death in elderly recipients?
The predictors of death in elderly recipients are diabetes, cardiovascular and cerebro vascular causes, obesity, arrhythmia and infections.
What is the effect of HLA mismatch on graft survival?
HLA mismatches are important predictor of overall graft survival. More the mismatches more chance of de novo DSA and ABMR. Frequent rejection episodes trigger more hospital admissions, infections which intern affect the overall patient and graft survival
At the age of 72, would he benefit from kidney transplantation?
Prevention of rejection is generally easier in older patients due to natural immune senescence , allowing reduced dosage of immunosuppressant medication. This in turn improve the risk for cardiovascular risk .According to this justification it causes improvement in both graft and patient survival .
Reference;
1-Panda A, Arjona A, Gapey E, et al: Human innate immunosenescence: causes and consequences for immunity in old age. Trends Immunol. 2009, 30 (7): 325-333. 10.1016/j.it.2009.05.004.
2- Frei U, Noeldeke J, Machold-Fabrizii V, et al: Prospective age-matching in elderly kidney transplant recipients – a 5-year analysis of the eurotransplant senior program. Am Journal Transplant. 2008, 8 (1): 50-57.
3- Huang E, Segev DL, Rabb H: Kidney transplantation in the elderly. Semin Nephrol. 2009, 29 (6): 621-635. 10.1016/j.semnephrol.2009.07.011.
Kidney transplantation is best option of renal replacement therapy, because of longer life expectancy , better quality of life , cost effectiveness . Studies demonstrate ,longer life expectancy in elderly patient ( above 60 years old ) with deceased donor kidney transplantation
compared to elder patient on dialysis .
The risk of graft failure is not significantly different between younger and older than the age 65 after adjustment for co morbidities .
Age by itself is not an obstacle to kidney transplantation. It has survival benefit even in individuals older than 75 year when selected carefully .
Death rates after deceased donor kidney transplant were lower than those for dialysis patients on the waiting list for all subgroups. The death rate varies according to post transplant period. Early (45days) post transplantation the risk of death is higher in transplanted patient than in waiting list dialysis patient. The long-term mortality risk (_18 months) was 56% lower for transplant
Recipients.
The relative mortality risk for diabetic elderly recipients was 47% lower when compared
with waiting list dialysis patient .
The relative mortality risk for hypertensive elderly recipients was 44% lower when compared
with waiting list dialysis patient.
Glomerulonephritis also has low mortality risk (although statistically not significant)when compared
with waiting list dialysis patient.
Elderly recipients of ECD kidneys also had a survival benefit compared with waiting list patients.
One- and 3-yr graft survival rates after deceased donor transplant were 80.9% and 66.9%, respectively. The corresponding graft survival rates after living donor transplant were 90.1% and 79.3%, respectively. Death-censored graft survival was 90.4% at 1 yr and 85.2% at 3 yr for deceased donor transplant recipients. For living donor transplant recipients, 1- and 3-yr death-censored graft survival rates were 95.8% and 93.1%, respectively.
The most predictive factor for 5-year mortality included
§ age >80,
§ body mass index <18,
§ the presence of congestive heart failure,
§ chronic obstructive pulmonary disease,
§ immobility,
§ Being institutionalized.
Factors associated with increased 5-year survival were
§ non-white race,
§ a primary cause of end-stage renal disease other than diabetes,
§ employment within 6 months of dialysis initiation, and
§ dialysis start via arteriovenous fistula.
Elderly patient has survival benefit by transplantation , especially diabetic and hypertensive patient when life expectancy is more than 1.8 y . although early post operative mortality is higher but long term mortalty is better than dialysis patient .
Both deceased (both ECD and non-ECD)and living donor has survival benefit. Patient with ECD kidneys had a 25% reduction in mortality risk compared with waiting list dialysis patient .
HLA mismatching was still a critical prognostic factor that affects graft and recipient survival. HLA-DR mismatching has a substantial impact on recipient’s graft survival. HLA-A mismatching has minor but insignificant impact on graft survival outcomes.
Elderly patient usually has less acute rejection than young pathent because of immunosenscence . but if elderly patient develop rejection he is more likely to reduce graft and patient survival .
In a large registry, 5-year death-censored graft survival after rejection was 59.9% in recipients aged 65 years or older as compared to 82.1% in recipients aged 18 to 35 years .
Geertje J. Dreyer and Johan W. Fijter D. Transplanting the Elderly: Mandatory Age- and Minimal Histocompatibility Matching. Front. Immunol., 12 March 2020
Pravisani R, Isola M, Baccarani U, Crestale S, Tulissi P, Vallone C, et al. Impact of kidney transplant morbidity on elderly recipients’ outcomes. Aging Clin Exp Res [Internet]. 2021;33(3):625–33.Available from:https://doi.org/10.1007/s40520-020-01558-4
. Faravardeh A.Eickhoff M. Jackson S.et al. Predictors of graft failure and death in elderly kidney transplant recipients. Transplantation. 2013; 96: 1089-1096
Renal transplantation in older patient has good outcome compared to patients remaining on dialysis.
Graft survival in older patient is good due to decreased immune response .
Increased donor age and HLA mismatching considered risk for delayed graft function
If living donation not feasible go ahead I will advice the patient for ECD
The most common causes of death in this case are CVD and infection.
Effect of HLA mismatch in this age group is less than young group because of immuno -scencesence
It was found that in in age more than 70 years transplantation has better outcome than dialysis.
Although graft survival of HLA-mismatched kidneys is reduced compared with HLA-matched kidneys, patient survival of highly sensitized recipients of HLA-mismatched kidneys is higher when compared with highly sensitized transplant candidates who remain on the waiting list and are undergoing dialysis.
graft survival is more better with 000 mismatch
acute rejection rate is more with increased level of mismatch
increased level of mismatch is associated with more denovo DSA and antibody mediated rejection
yes if living donation did not go ahead patient should accept marginal kidney due to patient survival in transplantation is better than dialysis
strongest predictors of death in elderly recipients : DM , HTN
REFERENCES
renal transplantation in older patient carry good prognosis compared with patient remain on dialysis
graft survival in this patient is good due to decreased immune response in old age
increased donar age and HLA mismatching consider risk for delayed graft function
if living donation did not go ahesd I will advice the patient for ECD
the most common cause of death in this patient are CVD and infection
the effect of HLA mismatch in this age group is less than young group because of immunoscencesence
in age more than 70 year the transplan better than dialysis
kidney transplantation among elderly patients was increasing by five fold in the recent years , as we have more elderly patients on dialysis based on registry data from UK more than 50% of ESKD above 65 years and 1/3 above 70years
many studies found that the kidney transplantation in older recipient associated with better graft survival for well matched donor and better quality of life and cost effective compares to dialysis , so the age of both the recipient and donor no more consider as contraindication for transplantation and the out come of transplantation in older people is encouraging even in recipients with comorbid disease like HTN , DM , the risk of DGF is more with older donor age(EDC ,DD allocation )and reach up to 40% also among old recipients the rate of death with functioning graft is more ,compared to young recipient due to CVD , infection ,primary failure rate is high in first year post transplantation due to cardiovascular events , infection , lower HLA mismatch will have better graft survival and less risk of BPAR in the first year post transplant due to low immune response in elderly
if the LD did not go ahead its preferred to go for ECD- from DD allocation also based on good evidence associated with better graft survival as compared to long-waiting list on dialysis
in older recipient kidney transplant the rate hospital re -admission is higher compared to young transplant
1–Transplantation: April 27, 2007 – Volume 83 – Issue 8 – p 1069-1074
doi: 10.1097/01.tp.0000259621.56861.31
2-Dempster et al. BMC Geriatrics 2013, 13:79 http://www.biomedcentral.com/1471-2318/13/79
Renal transplantation has better impact on old patient survival if compared to the same group of patients remained on dialysis.
Survival of the graft may be affected by the age of the donor and also the 3 mismatch.
The rate of acute rejection in this patient is decreased due to the immunoscencesence and the gradual decline in immune system function with the advance of age.
Delayed graft function rate may be high due to the age of the donor and the quality of the graft.
If living donation did not go ahead for this patient, a marginal kidney could be used as it will improve the patient survival of this age group in comparison to dialysis and remaining on the waiting list.
Due to the immunoscencesence in that group of age, ,HLA mismatching does not have the same effect on the graft survival if compared to its effect on the younger patients.
Renal transplantation in older patients improves the survival rate in comparison to dialysis, so the patient will get benefit from kidney transplantation in this age.
Ref:
Renal Transplantation in Elderly Patients Older Than 70 Year… : Transplantation (lww.com)
1. Mortality from the procedure itself is higher in the 100 days after tx then mortality is higher among esrd on dialysis .
2.3 .graft survival is at high risk due mismatch and old age donor
But still here has an advantage of old age recipient .
4. Due to decrease immunosense in old age require lower immunosuppression and less acute rejection rate .
5 . increased donor age and HLA mismatching are risk factors for delayed graft function in this patient.
6 sure, I will do .
7cvs and malignancy and pvd
8..
Lower survival rate .
9 yes it will improve quality of life
Patient Survival
When you do comparison with younger recipient 10y survival will be lower for sure
But in comparison to same age group on dialysis and waiting list…25%to 75% improvement in the arm who did kidney tranplantation (except in first 100days in which risk of death increase 3folds)
Graft survival and acute rejection rates
Graft survival is related to factors related to recipient like diabetis,hypertension and peripheral vascular disease,cPRA and history of previous rejection or events of rejection post transplant
And factors related to donor like living/deceased ,SCD/ECD but if all factors was comparable except age graft survival is better elderly patients because of immune system sencesence
Primary failure rate and delayed graft function rate are high in this group because most of them received ECD but again more studies need to be conducted with control of others confoundings which have negative impact.
If living donation did not go ahead, will you offer him a marginal kidney (ECD – Expanded Criteria Donor) kidney?
Yes but on individualized base and after risk stratification and discussion with the patient as DGF post operative associated with great risk of death at this age group.
What are the strongest predictors of death in elderly recipients
Infection, cardiovascular disease and DGF
What is the effect of HLA mismatch on graft survival
Still mismatch specially in DR associated with lower graft survival but alot of studies shower lesser effect in this age group because of immunoscencesence so yes i will accept donor with 222mismatch
At the age of 72, would he benefit from kidney transplantation
Yes in multiple aspects like morbidity,mortality and better quality of life in comparison to dialysis group
Finally our center experience in Transplantation of this age group
1st during preoperative assessment…. cardiovascular assessment is much more advanced than younger group and sometimes we needed to do diagnostic percutaneous angiography before proceeding for transplantation
Also evaluation of aortoiliac vessels needed for anastomosis usually evaluated with ct angiography and not by duplex which usually done in younger patients
Psychological assessment is mandatory to evaluate cognitive disorders
And also frailty assessment is done
As regard immunosuppressant medications… induction by non depleting basilixmab is preferred even with low immunological risk for rapid reduction in immunosuppressant medications and avoid its complications
References:
1) Camilleri B, Pararajasingam R, Buttigieg J, et al. Renal transplantation in the elderly: outcomes and recommendations. Transplant Rev 2020;34:100530.
2) McKay D, Jameson J. Kidnet transplantation and the ageing immune system. Nat Rev Nephrol 2012;8:700-708.
3) Meier-Krische HU, Srinivas TR, Kaplan B. Interaction between acute rejection and recipient age on long-term renal allograft survival. Transplant Proc 2001;33:3425-3426
Recipient’s age can’t limit the advantages of kidney transplantation. Even in elderly patients like this patient its benefits are obvious. Patient survival in elderly patients with kidney transplantation was better comparing those who remained on dialysis.
In comparison with younger recipients, elderly patients showed higher risk of death. With increasing age, patient survival decreased in elderly patients but deaths with functioning graft were increased. The most common reasons for death in this patients were cardiovascular diseases and infections.
Graft survival was lower in elderly patients with kidney transplantation. This can be explained with higher rate of deaths with functioning graft in these patients because in studies based on death- censored graft survival, similar results comparing younger patients were reported.
Primary failure rate is higher than younger patients but rate of acute rejection will be low because of elderly age of recipient and living related donor. DGF rate won’t be influenced by advanced age alone.
If living donor transplantation is not an option, extended criteria donor will be a good option compared to stay on dialysis.
The most important predictors of death in elderly patients are cardiovascular disorders, malignancies and infections.
Lower HLA- mismatch has significant improvement in graft survival. A meta-analysis conducted on 23 cohort studies showed more HLA-mismatch increases rate of graft failure. Graft failure increased by 12% with each more HLA-DR mismatch increment but this was insignificant for HLA-B mismatch. HLA-A mismatch had no influence on graft survival.
Benefits of kidney transplantation is not limited to young age and even in elderly patients like this patient survival rate will increase compared to dialysis.
References:
1. Remuzzi, G., Cravedi, P., Perna, A., Dimitrov, B. D., Turturro, M., Locatelli, G., Rigotti, P., Baldan, N., Beatini, M., Valente, U., Scalamogna, M., & Ruggenenti, P. (2006). Long-Term Outcome of Renal Transplantation from Older Donors. New England Journal of Medicine, 354(4).
2. Shi, X., Lv, J., Han, W., Zhong, X., Xie, X., Su, B., & Ding, J. (2018). What is the impact of human leukocyte antigen mismatching on graft survival and mortality in renal transplantation? A meta-analysis of 23 cohort studies involving 486,608 recipients. BMC Nephrology, 19(1).
☆ Patient survival
• is improved on comparison with those on dialysis (although there is higher risk of mortality in early post transplantation period especially in the first year)
• but is reduced on comparison to younger renal transplant recipient (as mortality rate is increased with increased age and death risk is higher in elderly)
————————–
☆ Graft survival
Is low in elderly than younger recipients (as elderly mostly received kidneys from old donors) so there is high rate of graft failure in elderly.
————————–
☆ The rate of acute rejection is significantly reduced in elderly recipients regardless the used immunosuppressive (may be due to immunosenescence).
But this rate is increased with increasing age of the donor Kidneys.
—————————–
☆ The DGF rate is affected by age of recipients (higher in elderly kidney recipients than younger recipients) , but is not affected by HLA-DR mismatching.
Also, increased rate of DGF is noticed more in frail patients than non-frail.
—————————-
☆ Living donor transplantation has a better outcomes than deceased donor transplantation. However, if LD is not accessible, transplantation of kidneys with extended criteria has a better outcomes than dialysis.
—————————
☆ The strongest predictors of death in elderly recipients: cardiovascular diseases, infections, delayed graft function, peripheral vascular disease, past history of graft failure and frailty of the patient.
—————————–
☆ One HLA-DR mismatching is linked to low rate of graft survival, so zero mismatching of HLA-DR leads to improvement of graft survival, decreased rate of graft rejection, and therefore decreased requirements of excessive immunosuppressive drugs.
—————————–
☆ Transplantation in elderly patients aims to enhance quality of their lives in terms of better vitality, physical activity, mental health and social connections on comparison with those on dialysis.
——————————-
☆ Reference
• Camilleri, B., Pararajasingam, R., Buttigieg, J., & Halawa, A. (2020). Renal transplantation in the elderly: Outcomes and recommendations. Transplantation reviews (Orlando, Fla.), 34(2), 100530. https://doi.org/10.1016/j.trre.2020.100530
• Sarah So, Eric H.K. Au, Wai H. Lim, Vincent W.S. Lee, Germaine Wong, Factors Influencing Long-Term Patient and Allograft Outcomes in Elderly Kidney Transplant Recipients, Kidney International Reports, Volume 6, Issue 3, 2021, Pages 727-736, ISSN 2468-0249, https://doi.org/10.1016/j.ekir.2020.11.035
• Dreyer GJ, de Fijter JW. Transplanting the Elderly: Mandatory Age- and Minimal Histocompatibility Matching. Front Immunol. 2020;11:359. Published 2020 Mar 12. doi:10.3389/fimmu.2020.00359
• Faravardeh A, Eickhoff M, Jackson S, et al. Predictors of graft failure and death in elderly kidney transplant recipients. Transplantation. 2013;96(12):1089-1096. doi:10.1097/TP.0b013e3182a688e5
Tricky consultation as usual when it comes to elderly Tx recipients, but always worth ensuring that eligible candidates for Tx had the opportunity, my counseling plan would focus on the following parameters and honest reflection and non-biased patient orientation:
Regarding patient survival
Ideally, patient survival should improve on Tx compared to dialysis. Moreover, the quality of life, socio-economic and psychological effects are much better on Tx. However, still bearing in mind that older recipients have a higher risk of dying during the first year of Tx (6.8% vs. 2.1%; p = 0.03) (1)
Regarding Graft survival
Graft survival is affected by multiple factors as mismatch (will discuss separately), age of the donor, Presence of DSA. Generally, elderly recipients had a poorer graft survival when compared to younger kidney transplant recipients. That`s due to the higher risk of TCMR due to older age, HLA-DR mismatch, and delayed graft function. Dempster et all 2019, showed in their study that Graft loss at 1 year was higher in kidneys from older donors (15.3% vs. 7.6%; p = 0.04) (1).
Regarding primary failure rate
Is common in older kidney recipients from older donors especially if expanded criteria donor (ECD).
Regarding acute rejection rate
Acute rejection rate in older population unsurprisingly low compared to younger recipients and that may be due to natural immunosenescence which also allow us to use a reduced dose of immunosuppression consequently reduce cardiovascular risk, drug side effects, and post-transplant infections (2,3)
DGF rate
Older donor to older recipient comes with a higher risk of delayed graft function especially in DCD, The incidence is much less especially with a living donation, but still a possibility.
If the living donation did not go ahead, I will offer him EDCD, but I will let him know first that it carries a higher risk of DGF, primary failure, and lower graft survival. However, my opinion would still support this patient for Tx rather than waiting on Dialysis.
The strongest predictors of death in elderly recipients
coronary artery disease, graft failure, peripheral vascular disease, and cause original kidney disease (4).
What is the effect of HLA mismatch on graft survival?
HLA mismatching act as an important prognostic factor affecting both graft and recipient survivals. HLA- DR will have an important impact on graft survival while HLA- A has an insignificant role. However, a New Zealand study group had demonstrated in their research that HLA mismatch is associated with a higher risk of graft failure and rejection
References
1- Dempster, N.J., Ceresa, C.D., Aitken, E. et al. Outcomes following renal transplantation in older people: a retrospective cohort study. BMC Geriatr 13, 79 (2013). https://doi.org/10.1186/1471-2318-13-79
2- Panda A, Arjona A, Gapey E, et al: Human innate immunosenescence: causes and consequences for immunity in old age. Trends Immunol. 2009, 30 (7): 325-333. 10.1016/j.it.2009.05.004.
3- Friedman AL: Cautious renal transplantation for the elderly is realistic. Nephron Clin Pract. 2011, 119 (Suppl 1): c14-c18.
4- Faravardeh, Arman, et al. “Predictors of graft failure and death in elderly kidney transplant recipients.” Transplantation 96.12 (2013): 1089-1096.
5- Al-Otaibi T, Gheith O, Mosaad A, Nampoory MR, Halim M, Said T, et al. Human leukocyte antigen-DR mismatched pediatric renal transplant: patient and graft outcome with different kidney donor sources. Exp Clin Transplant. 2015;13(Suppl 1):117–23.
6- Croke R, Lim W, Chang S, Campbell S, Chadban S, Russ G, et al. HLA-mismatches increase risk of graft failure in renal transplant recipients initiated on cyclosporine but not tacrolimus. Nephrology. 2010;15:38.
Dear All
I acknowledge your contribution. Well done
1-I will tell him the mortality rate in his group of age was 32% and the main cause of death was cardiac then infections then malignancy .
2-The graft survival will be low because the mortality rate was high ,so they dead with functioning graft and the 5 years graft survival was 20%.
3-They have low rate of acute rejection due to their change in the immune system that called immunosenescence ;the rejection rate in the first 6 month was 19% compared to a younger group and the same as primary failure and delay graft function.
4-Yes I will offer him expanded criteria donor because it is more suitable for his age although the living donor is better.
5- The important predictor of death in elderly is cardiovascular status .
6- Effect of HLA mismatch in graft survival was significant mainly if it is in DR ; it exposed the graft for possible rejection and decrease the graft survival rate.
6-Yes sure there’s benefits in transplanting the old patients at least to improve the quality of life .
The numbers of transplanted kidney in elderly patients has been increased , in the United Kingdom , the numbers of transplanted reached 22% with age between 60-69 and 8% with age above 70 .
In the United States (US), adults aged 65 years and above received kidney transplant represent 18.4% of the recipients compared to 3.4% in 1990.
Several studies showed increased survival with renal transplant when compared to staying on dialysis with reduction in mortality by 25–78%. even with ECD kidneys , mortality reduced X25%.
For patients older than 70 years, mortality decreased by 41% after renal transplant compared to those maintained on Dialysis .
In spite of improved mortality with transplantation but was associated with an initial increase in mortality compared to remaining In waiting list , in the first 2 weeks which was 2.8 times higher than those remaining on dialysis, then risk of death became equal in both groups at 106 days .
Patients survival in old and young renal recipients :
Old age recipient are in great risk of death compared to younger recipients as showmen by the following studies:
In Karim et al., study following the patients for 4.4 years, the mortality rate in old age group (70-79)was 32% and decreased to 22% for those aged 60–69 years, while 6% for those younger than 50 years.
They found the main causes of death were cardiac causes (21%) then infection (21%) and lastly malignancy (20%) .
In other study by Heldal et al., the 5 year Patient survival for Renal transplant recipients was 56% in recipients with age above 70 years compared to 72% in those recipients aged 60–69 years while reached 91% in those aged between 45 and 54 years .
In the study by Huang et al., 2 years patient survival in recipients age above 80 was73% and was 86% in age 70–79 years compared to recipients aged 60–69 years which was 89% , also compared to the Patient survival for whom on dialysis aged 80–84 years was 44%.
Older patients are 7 times more likely to die with a functioning graft compared with younger patients aged 18–29 years .
Graft survival :
elderly patients has graft survival less than younger recipients , as they are more likely to receive kidneys from older donors, so they are associated with an increased risk of graft failure .
Acute rejection:
Elderly patients with kidney transplants are associated with a reduced risk of Acute rejection , which was 19.7% compared to 28% in those aged 18_29 years old .
This explained by the effect of aging on immune system .
In spite that the effect of acute rejection on Patient and graft survival may be more severe in the elderly transplant patients .
Meier-Kriesche et al., study showed that graft loss associated with acute rejection after 5 years post-transplant in patients aged 65 years or more years is 3 times more than those aged 18–35 years .
Infection rates and associated complications:
The older patients are at a higher risk of developing infections, which increase risk of complications.
Both bacterial and viral infections have been reported to be particular problems in elderly RTRs particularly urinary infections, BK viraemia and polyoma virus associated nephropathy.
Quality of life
there is improvement in the quality of life in elderly patients with renal transplant compared to those still in waiting list on Dialysis.
Outcomes based on pre-transplant characteristics
Age is not a contraindication to renal transplantation but we still in need for careful selection of the potential elderly transplant candidate which is very important to avoid the increased risk of death with a functioning graft.
Yes, also I will offer him a marginal kidney (ECD) if living donation not going .
The strongest predictors of death in elderly recipients:
-Infection
-Cardiovascular Problems .
-Graft Failure.
Effect of HLA mismatch on graft survival:
HLA mismatching is significantly associated with increased risks of graft failure , death-censored graft failure and all-cause mortality .
reference
Camilleri ,B., Pararajasingam, R., et Al. (2020).Renal transplantation in the elderly: Outcomes and recommendations ,1-11.DOI: 10.1016/j.trre.2020.100530
Kidney transplant in old age group offers a better survival rate than keeping the patient on waiting list or on dialysis there is alot of benefits but also presence of risks of transplantation so both should be taken in consideration while taking transplant decision.
Keeping the patient long time on dialysis affect the result of transplantation so doing transplant earlier even when it’s from ECD is better and ideal for this patient.
Common risk factors post transplant in old age group are infection, death due to infection, cardiovascular disease and malignancies all these risks are higher in advanced age group in compared with younger but risk of acute rejection is lower in old age while chronic allograft rejection is higher in old age patients.
Type of immunosuppressant ,induction and withdrawal of immunosuppressant all should be taken in consideration.
Patient Survival:
Graft survival:
Primary failure rate:
Acute rejection rate:
DGF rate:
If living donation did not go ahead, will offer him a marginal kidney to decrease waiting time on dialysis
the strongest predictors of death in elderly recipients are cardiovascular complications and infections
the effect of HLA mismatch on graft survival
he will benefit from kidney transplantation
A- Patient survival after kidney transplantation depends on several factors
a- Age : elderly recipient are at higher risk for death than yonger recipient and death mainly from CVD , Infections and malignancies .
b- Comorbidity ; DM , Atherosclerosis , Pre-emptive transplantation , ethinicity ( better outcome in Hispanic than African americans.(1)
B- Acute rejection : sudden deterioration in graft function, either T cell mediated or AMR. The rate of acute rejection is lower with advancing age of both recipient and donor this may be due to immunosenescence (2).
C- Graft survival : depends on
· Recipient age ( as graft in elderly recipient suffer less acute rejection episodes , thus its survival is better than younger recipients and most elderly die with functioning graft )
Other comorbidities as DM, atherosclerosis.
· Advanced donor age, atherosclerosis.
· Delayed graft function
· Degree of HLA matching more important in deceased donor than in living ones
· HLA antibodies and presense of DSA
· Pre-emptive transplantation
· Prolonged cold ischaemic time (CIT)
· Rejection episodes: the more rejection episodes , the poorer graft outcome.
–Delayed graft function
Defined as the need for dialysis post-transplantation.
-Primary graft failure :
Defined as return to dialysis or preemptive retransplantation.
So for this patient , I would advice him to preceed with transplantation due to its favorable out come in elderly specially that he has a living related donot with resenable HLA matching and he isnot diabetic , thus I expect he will have a good survival chance with a functioning graft and less expected acute rejection episodes.
6- For this patient , I would offer him ECD as transplantation carries better quality of life than maintaining on dialysis.
7- Commonest causes for death in elderly recipients : Cardiovascular diseases , infections , malignancy.
8- Degree of HLA mismatch more important in living than deceeded donor and the higher degree of mismatch the more rejection rate.
1- Orsenigo, E., Socci, C., Carlucci, M., Zuber, V., Fiorina, P., Gavazzi, F., … & Staudacher, C. (2005, July). Multivariate analysis of factors affecting patient and graft survival after renal transplant. In Transplantation proceedings (Vol. 37, No. 6, pp. 2461-2463). Elsevier.
2-McKay D, Jameson J. Kidney transplantation and the ageing immune system. Nat Rev Nephrol 2012;8:700–8. https://doi.org/10.1038/nrneph.2012.242.
Dear all, an essential message from this scenario is; Age per se is no more a contraindication for transplant. Still, transplanting an old patient with a live or deceased donor graft is better than dialysis.
A 72-year-old CKD 5 patient, non-diabetic, currently on peritoneal dialysis. He consulted you regarding kidney transplantation, as his sister (59 years old) with 111 mismatch is willing to donate a kidney for him. Counciling regarding the following
HLA mismatching was still a critical prognostic factor that affects graft and recipient survival. HLA-DR mismatching has a substantial impact on recipient’s graft survival. HLA-A mismatching has minor but insignificant impact on graft survival outcomes.
transplantation in elderly people has medical and ethical challenges; however, dialysis in such age > 70years old carries a high risk of post-operative complications, graft rejection either acute or chronic as old age mostly has other comorbid conditions such cardiovascular, PVD which is strong predictor of death.
mismatch will need more immunosuppression which is not preferable in old age
kidney transplant still a better modality of RRT but in age > 70 has an increased risk of death during the first year after transplantation compared to the age matched dialysis patients remaining on the waiting list.
The mortality risk remained increased in the immediate post-operative period and became comparable with the risk of death on dialysis during the first year, before decreasing considerably to a beneficial long-term effect
So, elderly patients beyond 70 years of age on dialysis treatment, who fulfill the established medical criteria for waitlisting, will benefit from kidney transplantation compared to continuing dialysis. There is a marked long-term survival benefit which is highly significant after the introduction of newer immunosuppressive protocols.
It is well accepted that the best possible organ for an end-stage renal disease patient is from a fully HLA-compatible kidney. For an LR donor with 1 mismatch, there is a 43% higher risk of allograft failure, whereas with 6 mismatches is more than double the risk. A similar pattern is seen in LU allografts; with 1 mismatch, there is a 52% increased risk of failure and more than twice the risk with 6 mismatches. Connolly et al. showed that among 516 primary deceased donor kidney recipients, zero DR-mismatched transplants had significantly better survival than those with even a single DR mismatch at both 1 year (92.8 vs. 84.5%) and 5 years (88.3 vs.73.9%) (P < 0.0001). Moreover, in separate reports from the Collaborative Transplant Study, it was shown that HLA mismatches were associated with death with functioning graft and with post-transplant lymphoproliferative disease.
Though old age is not a contraindication for transplantation, however, Doxiadis et al, reported in a multivariate analysis that donor age is reported for primary grafting failure while Meier‐Kriesche et al. in his data analysis of USRDS registry that elderly recipients are more prone to develop chronic allograft nephropathy. Additionally, patients aged 60 years and older are reported to have longer hospitalizations at the early post-transplant period, greater mortality risk secondary to cardiovascular events and more infectious episodes in the first few months after transplantation and these are the strongest predictors of death in the elderly recipients. However, they tend to have fewer acute rejection episodes.
Even though patient survival decreases with advancing age, transplanted patients above the age of 60 have a survival advantage when compared to maintenance dialysis. The annual death rate for patients older than 60 years was reported at 10% on the waiting list, vs 7.4% if get a transplant. Generally, as in this patient, living donation is preferred if it is available, though the degree of HLA mismatching between him and his donor should be kept in mind. If not, still having a kidney from a deceased donor or a marginal donor is still associated with better survival than keeping this patient on dialysis.
References:
1. Zachary AA, Leffell MS. HLA Mismatching Strategies for Solid Organ Transplantation – A Balancing Act. Front Immunol. 2016 Dec 7;7:575. doi: 10.3389/fimmu.2016.00575. PMID: 28003816; PMCID: PMC5141243.
2. Connolly JK, Dyer PA, Martin S, Parrott NR, Pearson RC, Johnson RW. Importance of minimizing HLA-DR mismatch and cold preservation time in cadaveric renal transplantation. Transplantation. 1996 Mar 15; 61(5):709-14.
3. Doxiadis II. Compatibility and kidney transplantation: the way to go. Front Immunol. 2012 May 14;3:111. doi: 10.3389/fimmu.2012.00111. PMID: 22593759; PMCID: PMC3350869.
4. Alalawi F, Alnour H, Sharma A, Shaheen I, Kim JJ. Renal Transplant Recipient Workup; Obstacles and Challenges. J Renal Transplant Sci. 2019;2(1):60-72.
Kidney transplantation in the elderly is associated with lower patient and graft survival when compared with transplantation at younger age groups . But old age is not a contraindication for kidney transplantation provided that the patient had good functional status, and transplantation in elderly provides a survival advantage and quality of life improvement when compared to dialysis .
Another important factor when considering transplantation in the elderly is the time patient had on dialysis, early transplantation is associated with better graft and patient survival.
Delayed graft function and primary non-functioning is also increase in the elderly because of peripheral vascular disease and cardiovascular diseases also increased in the elderly. the donor quality also affects the DGF and primary non-functioning .
Acute rejection risk is lower in the elderly due to immunosenesence but when acute rejection occurs , it had more deleterious effect on patient and graft survival than it does on younger patients.
If his living donor is compatible , negative FCXM negative CDC , we can proceed with transplantation.
If the living donation didn’t go ahead , deceased donation is an option .
to decrease the waiting time , ECD kidneys provides good survival chance.
The most common cause of death in elderly kidney transplant recipients is cardiovascular and infection.
Dear All
Thank you for your wonderful contribution. Feel free to contribute more and press “complete” after you finish
Patient survival :
Numerous studies were shown less mortality in elderly recipient in comparison to dialysis patients.
There’s evidence of survival benefits for elderly who received kidney transplantation compared to be staying in dialysis .
Common causes of death with functional graft in elderly recipients were cardiac diseases and infections.
Graft survival:
It’s decreased in comparison to Young recipient , Decreased graft survival reflects increasing in risk of death with functional graft , There was improvement in graft survival with every decade increase in recipient age.
Primary failure rate :
Many studies were shown no significant difference in delay graft failure between young and old recipient.
Acute rejection rate and delay graft failure:
Studies were shown decrease risk of acute rejection in first 6 month after transplantation and this is due to change of immune system occurring with age and independent of baseline immunosuppresion .
* If living donation did not go ahead, will you offer him a marginal kidney (ECD – Expanded Criteria Donor) kidney?
– studies were shown decrease risk of death of elderly recipients received ECD kidney than staying waiting list. It is also shown that recipients with age above 65 y had life expectancy 5.6 y after receiving ECD kidney after 2 y on dialysis.
* What are the strongest predictors of death in elderly recipients?
– Cardiac diseases, infection and malignancies.
* What is the effect of HLA mismatch on graft survival?
May develop ABMR , decrease graft survival rate and affect patient survival.
* At the age of 72, would he benefit from kidney transplantation?
– Elderly Transplantation improves quality of life leading to better physical functioning , improving bodily pain ,general health ,vitality and social function compared to those on dialysis.
References
[1] Hole B, Gilg J, Casula A, Methven S, Castledine C. Chapter 1 UK renal replacement
therapy adult incidence in 2016: national and centre-specific analyses. Nephron
2018;139:13–46. https://doi.org/10.1159/000490959.
[2] Annual Report on Kidney Transplantation. NHSBT. http://www.odt.nhs.uk/pdf/
organ_specific_report_kidney_2014.pdf; 2018.
[3] Pippias M, Stel VS, Kramer A, Abad Diez JM, Aresté-Fosalba N, Ayav C, et al. Access
to kidney transplantation in European adults aged 75–84 years and related outcomes: an analysis of the European Renal Association–European Dialysis and
Transplant Association Registry. Transpl Int 2018;31:540–53. https://doi.org/10.
1111/tri.13125.
[4] Vanholder R, Stel VS, Jager KJ, Lameire N, Loud F, Oberbauer R, et al. How to increase kidney transplant activity throughout Europe—an advocacy review by the
European Kidney Health Alliance. Nephrol Dial Transplant 2019;34:1254–61.
https://doi.org/10.1093/ndt/gfy390.
[5] McAdams-Demarco MA, James N, Salter ML, Segev DL, Walston J. Trends in kidney
transplant outcomes in older adults. J Am Geriatr Soc 2014;62:2235–42.
Elderly recipients Kidney transplant
Patient Survival::- patient survival, QoL and cost effectiveness is higher in kidney transplantation compared to dialysis-
-longer waiting time might decrease the clinical and economical benefit of KT, so Living related KT may offer benefit
-mortality risk is higher in the waiting list patients than in age matched KT recipients regardless the type of donor.
-kidney with CPRA >85% and even diabetic deceased donor – higher survival in older recipient vs waiting list
Graft Survival
-Most patient dies with functioning graft (DWFG)
-rate of graft loss is generally comparable with younger recipients
-1 or 2 HLA-DR mismatches give a higher chance on TCMR and the development of DnDSA
-2 HLA DR mismatches had worse graft survival after 3 and 7 years vs 0/1 mismatches
Primary failure rate /DGF
-generally elderly kidneys are given to elderly recipient which increases the DGF rate and reduces the graft survival
-older KT recipient less like to have BPAR than younger ones
Acute rejection rate
-encounter less acute rejections due to immunosenescence
– if encounter rejection, high likehood end up in graft failure
ECD for elder recipient
Older KT recipient with an ECD found to have lower mortality than for patients remaining on dialysis,but tended to be higher compared with patients who received an SCD transplant
Strongest predictors of death in elderly recipient
-peripheral vascular disease, HLA antibodies, arrhythmias , LVEF less than 56% and fragility score risk factors for death
-DGF, donor age or IS therapy were not independently associated with patient survival our graft failure
Effect of HLA mismatch on graft survival
-1 or 2 HLA-DR mismatches give a higher chance on TCMR and the development of DnDSA
-2 HLA DR mismatches had worse graft survival after 3 and 7 years vs 0/1 mismatches
At the age of 72, would he benefit from kidney transplantation?
multiples studies now showed that transplanting older than 65 years old had been benefitted in term of patient survival, QoL and cost effectiveness compared with age matched patient in waiting lists.
· Age per se is no more contraindication to transplantation. As chronological age is less important than physiological age, and the comorbidities and their severity and duration.
· So, the careful selection and tough evaluation to the patients before operations is a critical issue. And patients with ESRD be screened aggressively for CVD and malignancy.
· Transplantation decreases the mortality as compared with waitlist patients. Although; mortality increase in the first year post-transplantation as compared with the young recipient.
· There is no tool better in predicting the DD outcome in elderly R.
· LD is still the best option; (it is equal or greater than SCD). Followed by SCD, but LD > 65 yrs or older is preferable to waiting for SCD. lastly ECD.
· There is no difference in outcome between older and younger LDs, older LD is better than ECD.
· The risk of the donation should be explained to the patients; both immediate perioperative risk and the potential for future diseases as hypertension and ESRD.
· LD > 60 yrs did not have a significant difference in major and minor complications and death after nephrectomy.
References
4. Camilleri B, Pararajasingam R, Buttigieg J, Halawa A. Renal transplantation in the elderly: Outcomes and recommendations. Transplant Rev. 2020;34(2).
5. Pravisani R, Isola M, Baccarani U, Crestale S, Tulissi P, Vallone C, et al. Impact of kidney transplant morbidity on elderly recipients’ outcomes. Aging Clin Exp Res [Internet]. 2021;33(3):625–33. Available from: https://doi.org/10.1007/s40520-020-01558-4
6. Knoll GA. Kidney transplantation in the older adult. Am J Kidney Dis [Internet]. 2013;61(5):790–7. Available from: http://dx.doi.org/10.1053/j.ajkd.2012.08.049
Elderly Kidney transplant recipeient
Patient Survival
-Kidney transplant is superior to dialysis in term of patient survival, QoL and cost effectiveness
-these survival benefit might differ between countries – dialysis survival appeasers to be better in europe compared to US which might show expected survival benefit with transplantation might be lower
-longer waiting time might decrease the clinical and economical benefit of KT, so Living related KT may offer benefit
-mortality risk is significantly in the waiting list patients than in age matched KT recipients regardless the type of donor.
-kidney with KDPI >85% and even diabetic deceased donor – higher survival in older recipient vs waiting list
Graft Survival
-Most patient dies with functioning graft (DWFG)
-rate of graft loss is generally comparable with younger recipients
-1 or 2 HLA-DR mismatches give a higher chance on TCMR and the development of DnDSA
-2 HLA DR mismatches had worse graft survival after 3 and 7 years vs 0/1 mismatches
Primary failure rate /DGF
-generally elderly kidneys are given to elderly recipient which increases the DGF rate and reduces the graft survival
-older KT recipient less like to have BPAR than younger ones
Acute rejection rate
-encounter less acute rejections due to immunosenescence
– if encounter rejection, high likehood end up in graft failure
ECD for elder recipient
Older KT recipient with an ECD found to have lower mortality than for patients remaining on dialysis,but tended to be higher compared with patients who received an SCD transplant
Strongest predictors of death in elderly recipient
-peripheral vascular disease, HLA antibodies, arrhythmias , LVEF less than 56% and fragility score risk factors for death
-DGF, donor age or IS therapy were not independently associated with patient survival our graft failure
Effect of HLA mismatch on graft survival
-1 or 2 HLA-DR mismatches give a higher chance on TCMR and the development of DnDSA
-2 HLA DR mismatches had worse graft survival after 3 and 7 years vs 0/1 mismatches
At the age of 72, would he benefit from kidney transplantation?
multiples studies now showed that transplanting older than 65 years old had been benefitted in term of patient survival, QoL and cost effectiveness compared with age matched patient in waiting lists.
references
Dempster et al. BMC Geriatrics 2013, 13:79 http://www.biomedcentral.com/1471-2318/13/79
Lemoine M., Beauport D.T., Lobbedez Th., Choukroun G. et al. Risk Factors for Early Graft Failure and Death After Kidney Transplantation in Recipients Older Than 70 Years. Kidney international reports(2019) 4, 656–666.
Geertje J. Dreyer and Johan W. Fijter D. Transplanting the Elderly: Mandatory Age- and Minimal Histocompatibility Matching. Front. Immunol., 12 March 2020
Patient Survival,
After a median follow-up of 4.4 years, the death rate for those aged 70–79 years was 32 percent, and 22 percent for those aged 60–69 years, according to Karim et al. This compares to 6% for those who are <50 years. Cardiovascular disease (21%) and infection (11%) were the leading causes of mortality(21%), as well as malignancy (20%) .
A lower rate of AR may be due to
changes in the immune system that occur with ageing referred to as
immunosenescence.
Graft survival
When compared to younger receipients, elderly individuals have a lower graft survival rate. Elderly patients are more likely to receive kidneys from older donors, which is linked to a higher risk of graft failure. The lower GS, is most likely the result of a reflection of the higher risk of death in older recipients with a functional graft,Since death-censored graft survival (DCGS) is comparable to, if not better than patients who are younger.
Acute rejection rate
Elderly recipients are associated with a reduced risk of AR.The AR rate was 28% in those aged 18–29 years compared to 19.7% in those aged 65 years and older.
Primary failure rate,DGF rate
since kidneys are given old to old the rate of DGF is high as compared to younger receipients.
If living donation did not go ahead, will you offer him a marginal kidney (ECD – Expanded Criteria Donor) kidney?
ECD listing is especially recommended for older patients who do not have an LD and will have to wait a long time for a standard criterion donor.
What are the strongest predictors of death in elderly recipients?
1) BMI
2)Hypertension
3)Diabetes
4)Coronary heart disease
5)Waiting time
6)Duration of dialysis
7)HLA antibodies
8)Arrhythmia
9)LVEF <56%
10)Antiaggrecants
Risk Factors for Early Graft Failure and Death After Kidney Transplantation in Recipients Older Than 70 Years-Mathilde Lemoine et al
What is the effect of HLA mismatch on graft survival?
In conclusion, HLA-DR matching has the potential to improve immunologic long-term outcomes and transplant survival in elderly patients. This would lower the likelihood of graft immunogenicity and rejection events (which are linked to protracted hospital stays), as well as the risk of over-immunosuppression and reduce the loss of key nephrons in already-fragile donor kidneys.The study compares the outcomes of HLA-DR-compatible with HLA-DR-incompatible kidney transplantation in patients aged 65 and older who had been listed for kidney transplantation.
Immunologic outcome in elderly kidney transplant recipients: is it time for HLA-DR matching? Fabian Halleck et al
At the age of 72, would he benefit from kidney transplantation?
Several studies conducted in ESRD patients over the last 20 years, including the elderly have suggested that Renal Transplant over dialysis is superior in terms of survival duration.However, RT receipients aged 70 and more, particularly those aged 80 and up, had a greater mortality risk than those aged 60 to 69.
Criteria for and Appropriateness of Renal Transplantation in Elderly Patients With
End-Stage Renal Disease: A Literature Review and Position Statement on Behalf
of the European Renal Association-European Dialysis and Transplant Association
Descartes Working Group and European Renal Best Practice-Liviu Segall, MD et al
Patient survival :
Numerous studies were shown less mortality in elderly recipient in comparison to dialysis patients.
There’s evidence of survival benefits for elderly who received kidney transplantation compared to be staying in dialysis .
Common causes of death with functional graft in elderly recipients were cardiac diseases and infections.
Graft survival:
It’s decreased in comparison to Young recipient , Decreased graft survival reflects increasing in risk of death with functional graft , There was improvement in graft survival with every decade in recipient age.
Primary failure rate :
Patient survival: Because of old age, patient’s survival around the procedure may be less than standing on peritoneal dialysis, but long-term survival will be excellent and better than continuing PD.
Graft survival: because of a lower rate of acute rejection in elderly patients due to lower lever of immunogenic response (immunosenescence), death censored graft survival will be good and acceptable, but because of older age, graft lost with a functioning kidney will be more than younger recipients.
The primary failure rate in elderly recipients is more than in younger recipients because of comorbidities like cardiovascular diseases in elderly recipients and a higher rate of perioperative complications and mortality.
In spite of the recipient’s advanced age, because of living donor transplantation, the probability of DGF will not be high if the procedure is well done.
As the next option for this patient, I will offer a marginal kidney to him, albeit I will give consultation to him about the advantages and disadvantages of ECD for him. The rational for this offering is that we can match the grafts with high percent KDPI with candidates with high percent EPTS and it is accompanied by acceptable long-term patient and graft survival.
HLA mismatch can lead to acute and chronic rejection and is associated with lower graft survival, so it is suggested to use appropriate immunosuppressive agents and concise monitoring of recipients regarding DSA levels.
Kidney transplantation is appropriate at any age and the age per se is not limitation for performing kidney transplantation. Although at the time around the procedure the rate of mortality may be higher than staying on dialysis, but long- term patient survival and quality of life will be better than being dialyzed.
Comorbidities, especially cardiovascular diseases, are the strongest predictors of death in elderly recipients. Frailty can influence mortality as well.
Thanks, Esmat for your excellent reply
Will you accept him for 222 mismatched kidneys?
The assessment of the transplant candidacy of elderly patients with advanced CKD is challenging Patients over the age of 70 years are the fastest-growing segment of the ESKD population worldwide. There is no formal upper age limit at which patients may no longer be accepted for transplantation.
As of mid-2016, over 22% of all patients on the waiting list for renal transplantation in the United States are 65 years of age or older; over 5% are 70 years or older.
Data from the United States shows that, as a group, patients 60 years or older, who are considered appropriate transplant candidates and receive a renal transplant, survive longer than dialysis patients and have a better survival rate than patients who remain on the transplant waiting list.
Older transplant recipients have an increased risk for death due to CVD in the few months after renal transplantation. Older patients may be at increased risk for infection and malignancy related to immunosuppression that explained by the metabolism of immunosuppressive drugs may be slowed by aging.
The assessment of older patients should also consider their cognitive abilities and their capacity to ambulate and care for themselves in the post-transplantation period.
Most older patients seek improved quality of life in their later years, which they may resent spending on dialysis. Older patients may have unrealistic expectations about their quality of life after transplantation—the transplant will not make them younger! So it is a challenging situation; that’s why meticulous assessment of these age group for transplantation has to take a place before choosing the appropriate donor.
. kidney transplantation is the treatment modality of choice for people with ESRD. It is safe and successful in the older patient and improves patient survival over remaining on dialysis 1. HLA mismatch was significantly associated with a high risk of graft failure, rejection 2, all cause of motality 3, and delayed graft function.
– If a living donation did not go ahead, Iwill offer the patient a marginal kidney.
The strongest predictor of death in elderly recipients:
– comorbidities(cardiac diseases)4
-infections
– malignancy.
-gradual deterioration of immune system (immunosenescence) 5
– Graft failure
– Age of the recipient is 72, he is an elderly patient but can benefit from kidney transplantation.
-HLA mismatching eas associated with an increased risk of overall graft failure,death-censored graft failure, and all-cause of mortality.HLA –DR mismatch associated with worse overall graft survival.6
References:
1.Ferrari P, Weimar W, Johnson RJ, Lim WH, Tinckam KJ. Kidney paired donation: principles, protocols, and programs. Nephrol Dial Transplant. 2015;30(8):1276–85.
2. Croke R, Lim W, Chang S, Campbell S, Chadban S, Russ G, et al. HLA-mismatches increase risk of graft failure in renal transplant recipients initiated on cyclosporine but not tacrolimus. Nephrology. 2010;15:38.
3. Abramowicz D, Cochat P, Claas FH, Heemann U, Pascual J, Dudley C, et al. European renal best practice guideline on kidney donor and recipient evaluation and perioperative care. Nephrol Dial Transplant. 2015;30(11):1790–7.
4. Faravardeh A.Eickhoff M. Jackson S.et al. Predictors of graft failure and death in elderly kidney transplant recipients. Transplantation. 2013; 96: 1089-1096
5. Musso C.G. Giordani M.C. Imperiali N. Aging kidney transplantation. Rev Invest Clin. 2016; 68: 68-74 6.What is the impact of human leukocyte antigen mismatching on graft survival and mortality in renal transplantation? A meta-analysis of 23 cohort studies involving 486,608 recipients
Xinmiao Shi,1 Jicheng Lv,2,3,4,5 Wenke Han,6,7 Xuhui Zhong,1 Xinfang Xie,2,3,4,5 Baige Su,1 and Jie Dingcorresponding author1
BMG nephrol: 2018; 19: 116.
Thanks, Reem
But will you accept him for 222 mismatched kidneys?
●●PATIENT SURVIVAL
4.8 % will in the first year then 7 .7% during year 2 up to 5 then 1% after each further year
●●Graft SURVIVAL
••If donor alive : the survival will be higher
than deceased
••In HLA – DR MISMATCH :
There will be 12% increase in the DECREASED survival rate .
•• In HLA- A MISMATCH :
There will be 6 % increase in the DECREASED survival rate
••In HLA- B MISMATCH :
There will NO EFFECT ON SURVIVAL RATE.
■■ The degree of HLA MISMATCH is a STRONG PREDICTOR of the 10 year graft survival rate .
●●PRIMARY FAILURE RATE
●●ACUTE REJECTION RATE:
The degree of HLA MISMATCH is a STRONG PREDICTOR of 1 year acute rejection Rate
●●DELAYED GRAFT FUNCTION RATE :
Post Tx long term complications include:
Will depend on:
_ DsA levels
Specially in HLA CLASS 2 mismatch ( DR,
DQ).
((THE DQ EFFECT RISE IN THE
SUBSEQUENT rtx operations rather 1st
one.??))
_ PTLD
21% increase in risk in 1 HLA – DR
mismatch
56% increase in risk in 2 HLA- DR
mismatch.
_ BONY FRACTURES
_ DM
_ HTN
●● MARGINAL KIDNEY SUSCEPTIBILY
The answer in one of the aspects of this question lies between is it better to take kidney drom DCD OR DCB
DCD: DONAR corculatory DEATH
DBD: DONAR BRAIN DEATH
Previous UK Transplant Registry analyses have shown that while DCD kidneys are more susceptible to cold ischemic injury and have a higher incidence of delayed graft function, short- and medium-term transplant outcomes are similar in recipients of kidneys from DcD and DBD donors.
○○https://www.researchgate.net/publication/293327849_Long-Term_Safety_of_Living_Kidney_Donation_in_an_Emerging_Economy
●●STRONGEST PREDICTORS OF DEATH IN ELDERY”
The degree of HLA MISMATCH is a STRONG PREDICTOR of Death
—>HLA mismatches may correlate with risk of death with a functioning graft (DWFG) because of requirement for higher immunosuppression doses and more antirejection therapy.
—>Multivariable analysis showed that mismatches for HLA class II were more strongly associated with both hospitalization and DWFG than mismatches for HLA class I.
—>HLA-A + B + DR mismatches were significantly associated with DWFG during year 1 ((p < 0.001)),
a correlation that diminished but persisted during years 2-5 ((p < 0.001)).
○○https://www.researchgate.net/publication/38054269_Delayed_Graft_Function_and_the_Risk_for_Death_with_a_Functioning_Graft
●●EFFECT OF HLA MISMATCH ON THE GRAFT SURVIVAL :
The degree of HLA MISMATCH is a STRONG PREDICTOR of the DGF.
●● AT AGE 72:
SURE THE PTN WILL STILL HAVE BENEFIT FROM RTX
Transplant is associated with improve quality of life ,compare to dialysis ,regardless of age.
Report of 45% of patient on RRT are 65 years old in Europe and 41% in usa (1, 2).
Improving chance of transplantation in these elderly patient, necessitate expansion of
donor criteria like donation from old (3) .
So old age is not absolute contraindication to the procedure.
Being seventies prone to more risk of transplant complication ,rejection ,failure ,though
its not more than young age.
Both delayed graft function and graft loss are common in elderly patient as do 1 year
mortality(4) .
Death censored graft survival at 5 years was 82% elderly and compare to 87% young
,not statistical different at 5 years.(5) , but death with functioning graft (DWFG) is main
cause of late graft loss (6,7,8) .
acute rejection is less common in elderly patient., due to immunosenescence(aging of
immune system) (7) ,which made them more prone to infection .the leading cause of
their late i.e post five years DWFG .
Other complication of transplant is is not more common than young for example
prevalence’s of diabetes mellitus, hypertension, acute rejection, cytomegalovirus,
polyomavirus, and urinary infection.
Patients with 2 HLA-DR mismatches had worse graft survival rates after 3 and 7 years
after transplantation compared to 0 or 1 HLA-DR mismatch (80%, 76% and 73% for 0, 1
and 2 HLA-DR mismatches 7 years after transplantation (8).
Reference:
1- Geertje J. Dreyer and Johan W. de Fijter et al,Transplanting the Elderly: Mandatory Age- and Minimal Histocompatibility Matching. Front. Immunol., 12 March 2020 .
3- Vinant Bhargava 1, Priti Meena 1, Krishna Agrawaal et al, Outcomes of Kidney Transplantation in the Elderly Recipients. Indian J Nephrol, Jul-Aug 2021;31(4):370-376.
4-Niall J Dempster 1, Carlo D L Ceresa et al ,Outcomes following renal transplantation in older people: a retrospective cohort study. BMC Geriatric. 2013 Jul 24;13:79.
5- Ubiracé Fernando Elihimas Júnior et al, Logistic Regression Model in a Machine Learning Application to Predict Elderly Kidney Transplant Recipients with Worse Renal Function One Year after Kidney Transplant: Elderly KTbot. J Aging Res. 2020 Aug 19;2020:7413616.
6- Geertje J. Dreyer et al, Transplanting the Elderly: Mandatory Age- and Minimal Histocompatibility Matching. Front. Immunol., 12 March 2020.
The physiologic age is more important. the degree of mismatch will lead us to choose appropriate induction as well as maintenance immunotherapy protocol. in the mentioned case speaking in general one could expect a standard survival rate ( good as transplantation, favorable more than dialysis). regarding graft survival as many colleagues commented older patients have less frequent acute rejection rates but on the other side older donors grafts are associated with a higher frequency of rejection (of course this is multifactorial and does not fit to all in the same way). If the living donation did not go away I would offer cadaveric transplantation. the higher the quality of graft the better the outcome I think. suitable immune suppression protocol needed (figure2)
72 years old patient who is fit should be transplanted. in the case of an available living donors, this could be done. here I well evaluate from point of contraindications to being operated. regarding deceased donors, this patient may be at the bottom of the list according to country policies.
graphic1: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618718/figure/F1/?report=objectonly
graphic 2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618718/figure/F2/?report=objectonly
Well done Mahmud
“The physiologic age is more important”. You are the first one who highlighted this important observation.
AGE IS NOT A CONTRAINDICATION FOR KIDNEY TRANSPLANTION.
actually in this scenario,we have to explain to him that pt survival is worse either being hd dependent or waiting for decseased kidney donor comapred to his living donor offer from his siste and to explain to him that the graft survival is a little bit low as he will take kidney from an old person ,and primary failure rates are high comapred to yonger recpients
rejection rate will be less compared to younger recipents , hence we can minmize his immunosuppresion as much as we can as he is ahplotype match.
he is also at risk of dgf comapred to younger recepient.
if this offer from his kidney will not go ahead , i will offer him edc kidney and i will asses his EPTS and accoring to his perecntage i will offer him sutiable decesd donor according to kdpi .
the oldeer the recpient ,the higher predictors of death , in first year after tranplantion cvs and infetion then malignacise will be short listed are the most commomn cause of death , after one year , infcetion then malignacies will get the upper hand.
the higher the mismatch the higher chance of rejection espicilay tcmr in fisrt year of transplantion.and then the bad graft survival due to high rejection rates.
again the age is not a contarindications of transplantion but many studies showed that beyon 75 of age tarsnpalntion will much carry much risks on pt survival comapred being on rrt.
Patient survival:
No doubt that this patient should be encouraged about the operation whatever his age was , As Renal transplantation improves survival , lower mortality and better quality of life than patients on dialysis .
The strongest predictors of death in elderly renal transplant recipients include cardiovascular diseases, peripheral vascular diseases, delayed graft functions and infections .
living donor graft is always better than deceased regarding the delayed graft function , graft survival and patient survival .
HLA importance nowadays is less regarding the living donor in many centers , on the contrary in the deceased graft , apart from this the fact that our patient is old , with less likely the incidence of AMR due to immunosenecense .
Immunosuppression according to our patient will entail induction , which will allow lower doses of maintenance triple therapy rapid decrease of the steroids dose incriminated in the CVS complications which are already higher in this age group
Assessment of frailty as mentioned by our colleagues is an important point .
REFERANCES:
DempsterNJ, Ceresa CD,Aitken E, Kingsmore D. Outcomes following renal transplantation in older people: a retrospective cohort study. Dempster et al. BMC Geriatrics 2013, 13:79.
Geertje J. Dreyer and Johan W. Fijter D. Transplanting the Elderly: Mandatory Age- and Minimal Histocompatibility Matching. Front. Immunol., 12 March 2020
Molnar MZ, Streja E, Kovesdy CP, et al. Age and the associations of living donor and expanded criteria donor kidneys with kidney transplant outcomes. Am J Kidney Dis 2012; 59:841.
If you have another couple, a donor who is 68 years old male and a 50 years old female recipient, and again 111 mm, what would be your approach?
living donation….first will assess the donor well as regard comorbidities
if safe and the recipient agrees will proceed
age per say is not contraindication for donation or transplantation
result of transplantation from living old age donor is similar to young age deceased donor
Maryvonne Hourmant, Lydie Lerat, Georges Karam. Donation from old living donors: how safe is it?.
Nephrol Dial Transplant. 2013 Aug;28(8):2010-4.
Think of the couple in the original question and the other one. What would be your possible approach?
will still go for transplantation for sure , but beware that the donor is older then 65 years , and accordingly graft survival is less , more liability for delayed graft function compared to younger donor age . But still better patient survival than dialysis . careful assessment of the donor should be done as well as meticulous post Tx follow up .regarding IS, induction , and our triple therapy with relative rapid decrease of steroids dosage.
reports showed that there is a significant increment in the number of donors who are more than 60 years old, these donors will expand donor pool and cover the increasing demand for organs, but these donors should be investigated thoroughly as most of them having hypertension, lower GFR and other comorbidities. studies showed that kidneys from > 60 years old donor have comparable 5 year graft survival to kidneys from < 60 years old donors and better graft and recipient survival compared to young deceased donors.1
recipient gender has an impact on graft survival, studies showed that > 45 year old female who received a kidney from male donor has poor graft outcome.2
references:
1.Serrano O.K., Yadav K.,Bangdiwala A.,Vock D.M, et al. Age alone is not a contraindication to kidney donation: Outcomes of donor nephrectomy in the elderly.Clinical Transplantation. 2018;32:e13287.
2. Lepeytre F., Dahhou M., Zhang X., Boucquemont J., et al. Association of Sex with Risk of Kidney Graft Failure Differs by Age. J Am Soc Nephrol 28: 3014–3023, 2017.
1- Transplantation offers better survival for patients compared with dialysis .
Worldwide over 40% of patients receiving renal replacement therapy (RRT) are aged 65 years or older.
Only 3% of patients aged 65 years or older accepted on the waiting list actually received a kidney transplant offer.
older patients must be evaluated carefully with the standard recipient pretransplantation work up especially history of malignancy.
Mortality early after transplantation is higher in elderly with a large French registry study reporting a 3-fold higher mortality risk in the first 3 postoperative months as compared to waitlisted counterparts (1).
recipients aged over 65 years had a 7-fold increased risk to die with a functioning graft. Besides age, ESRD caused by systemic vascular diseases such as hypertension or diabetes mellitus was an independent risk factor for premature death (2).
the most important cause of death more than 5 years after transplantation was due to infection.
It has become widely accepted that older transplant recipients may encounter less acute rejection episodes after transplantation as compared to younger recipients due to immunosenescence (3).
However, if they do experience acute rejection, this episode is more likely to compromise graft- and/or patient survival a higher donor age is significantly associated with higher rejection rates (4).
older recipient age was protective for the occurrence of acute rejection, this was clearly outweighed by the dominant negative effect of donor age and increased immunogenicity of the organ reflected by more rejection and more donor specific antibody (DSA) formation with increased HLA-DR mismatch (5).
1 or 2 HLA-DR mismatches give a higher chance on TCMR and the development of DSAs which both results in decreased allograft survival , patients with 2 HLA-DR mismatches had worse graft survival rates after 3 and 7 years after transplantation compared to 0 or 1 HLA-DR mismatch.Lemoine et al. (6) showed that anti HLA antibodies are an independent risk factor for patient death and graft loss within the 1st year in patients older than 70 years.
This increased immunogenicity in recipients of a more vulnerable kidney allograft could be due to more endothelial activation in the context of ischemia-reperfusion injury, bacterial and viral infections resulting in a more pro-inflammatory cytokine environment, increased expression of HLA molecules and/or recruitment of antigen-presenting cells .
With the acceptance of older donors, the proportion of extended criteria donors (ECD) also increased significantly. Since 2015 donors in the US have been assessed by the Kidney Donor Profile Index (KDPI) score, which is associated with the life expectancy of the graft.
Kidneys with a KDPI > 85%, or high risk kidneys, are expected to function for more than 5.5 years (7).
Recipients of a high-risk kidney had a significantly lower mortality risk ghan patients on waiting list and in our case i would recommend ECD for this patient.
graft survival is worse even with 1 HLA-DR mismatch. Therefore, prospective HLA-DR matching with zero mismatches would be a potentially the best strategy to improve rejection free survival without the need of excessive immunosuppression,Since most DSAs are directed against HLA class II antigens, HLA-DR matching is likely to reduce the need for more intense clinical immunosuppression and/or additional acute rejection treatments, ensuing reduction of excess infectious cause morbidity and mortality while delivering the prospect of prolonged life expectancy.
In this case 111mismatch would be agood option in old patient.
DGF is a strong predictor of death especially with increasing immunosuppression ,deterioration of renal function and volume overload.
Reference
1 Legeai C, Andrianasolo RM, Moranne O, Snanoudj R, Hourmant M, Bauwens M, et al. Benefits of kidney transplantation for a national cohort of patients aged 70 years and older starting renal replacement therapy. Am J Transplant. (2018)
2 Ojo AO, Hanson JA, Wolfe RA, Leichtman AB, Agodoa LY, Port FK. Long-term survival in renal transplant recipients with graft function. Kidney Int. (2000) .
3 Rana A, Murthy B, Pallister Z, Kueht M, Cotton R, Galvan NTN, et al. Profiling risk for acute rejection in kidney transplantation: recipient age is a robust risk factor. J Nephrol. (2017).
4 Oberhuber R, Ge X, Tullius SG. Donor age-specific injury and immune responses. Am J Transplant. (2012) .
5 Halleck F, Khadzhynov D, Liefeldt L, Schrezenmeier E, Lehner L, Duerr M, et al. Immunologic outcome in elderly kidney transplant recipients: is it time for HLA-DR matching? Nephrol Dial Transplant. (2016) .
6 Lemoine M, Titeca Beauport D, Lobbedez T, Choukroun G, Hurault de Ligny B, Hazzan M, et al. risk factors for early graft failure and death after kidney transplantation in recipients older than 70 years. Kidney Int Rep. (2019) .
7 Rao PS, Schaubel DE, Guidinger MK, Andreoni KA, Wolfe RA, Merion RM, et al. A comprehensive risk quantification score for deceased donor kidneys: the kidney donor risk index. Transplantation. (2009) .
Well done Mohammad
If the mismatch was 222, will you still offer him the kidney?
My opinion that such a degree of mismatch from a living donor make the manipulation of immunosupreesive drugs is imp.
Yes sir, i will prefer it over being in wait-list of deceased donation
Thanks, Mohammed
I agree with you. It would be better than dialysis.
KT in patients older than 70 years is a safe procedure if the recipients are carefully selected.
The clinicians should consider the cardiovascular risk of these patients before registration on the waiting list, especially in recipients with low LVEF or arrhythmia. Then, the risk of acute rejection must be considered because of its severe consequences
HLA antibodies were independent risk factors associated with graft failure or patient death during the first year of KT, which has already been reported. Among the posttransplantation characteristics, donor deceased from cardiovascular cause was also an independent risk factor.
the risk of death of the elderly KTR remains higher than in wait-listed patients during at least 3 months, leading to a time to equal survival of more than 1 year.
Patient survival at 1, 3, and 5 years was 90.1%, 82.5%, and 68.1%, respectively. Infection was the most common cause of death , followed by cardiovascular disease and cancer .
The most common reasons for death-censored graft loss were rejection episodes and vascular events, including artery or vein thrombosis
Mathilde Lemoine,1,∗ Dimitri Titeca Beauport,2 Thierry Lobbedez,3 Gabriel Choukroun,4 Bruno Hurault de Ligny,3 Marc Hazzan,5 Dominique Guerrot,1,6 and Dominique Bertrand1
Saran R., Li Y., Robinson B. US Renal Data System. 2015 Annual Data Report: Epidemiology of Kidney Disease in the United States. Am J Kidney Dis. 2016;67(3 Suppl 1) Svii, S1–S305.
First and foremost, age is just a number. Kidney transplant option should be offered as a rule to everyone o.n dialysis. Individual assessment should be done before rejecting someone’s chances of getting a transplant
Counselling regarding:
Patient survival, Graft survival, Primary failure rate, Acute rejection rate, DGF rate:
Although as compared to younger kidney transplant recipients, the 10 year patient survival and graft survival is lower (but the death censored graft survival is similar), there is 25-78% reduction in mortality among elderly transplant recipients as compared to remaining on dialysis. (1) Rates of acute rejection in elderly recipients are lower as compared to young kidney transplant recipients (due to immunosenescence). (2) But rates of acute rejection increase with age of donor and graft loss in association with acute rejection in elderly recipients is 3 times higher than a younger recipient. (3)
Primary failure rate as well as delayed graft function (DGF) rate will be decreased in old recipients (but if the donor is elderly, the risk of DGF and primary failure rate increases).
In this case, the donor is 59 year old sister, so risk of acute rejection, DGF and primary failure rate should be lower.
If living donation did not go ahead, will you offer him a marginal kidney (ECD – Expanded Criteria Donor) kidney?
Yes. A living donor is ideal, but if a living donor is not available, ECD kidney can be offered as the patient survival is better than remaining on waitlist.
What are the strongest predictors of death in elderly recipients?
These include recipient characteristics (like age, co-morbidities like cardiovascular disease, PVD, infections etc, frailty) and donor characteristics (like donor age, donor source – living/ standard criteria donor/ ECD)
What is the effect of HLA mismatch on graft survival?
Although the greater the HLA mismatch, poorer the graft survival, but at this age, it does not have that much relevance as compared to younger recipients
At the age of 72, would he benefit from kidney transplantation?
Yes. Improvement in quality of life is an important advantage with transplant. Although detailed counselling should be done, especially regarding increased mortality in first year post-transplantation as compared to remaining on dialysis should be explained.
References:
1) Camilleri B, Pararajasingam R, Buttigieg J, et al. Renal transplantation in the elderly: outcomes and recommendations. Transplant Rev 2020;34:100530.
2) McKay D, Jameson J. Kidnet transplantation and the ageing immune system. Nat Rev Nephrol 2012;8:700-708.
3) Meier-Krische HU, Srinivas TR, Kaplan B. Interaction between acute rejection and recipient age on long-term renal allograft survival. Transplant Proc 2001;33:3425-3426.
1- A 72-year-old CKD 5 patient, non-diabetic, currently on peritoneal dialysis. He consulted you regarding kidney transplantation, as his sister (59 years old) with 111 mismatch is willing to donate a kidney for him. How do you council him regarding the following:
Elderly patients with life expectancy more than a year are expected to have improved survival and quality of life after receiving a renal transplant compared to dialysis.
The first 100 days after renal transplantation increase the risk of mortality in elderly transplant recipient especially related to surgical causes, however after these early 3 months the life expectancy was found to be 10 years in renal transplant recipients aged between 60 to 74 years compared to 6 years for their peers on dialysis (2).
He could have ECD transplant because it was found that there was no difference in mortality between ECD and standard criteria donor transplant in recipient aged more than 70 years (3).
Graft survival in elderly recipients depends mainly on type of donor, age of donor, duration on dialysis, frailty and cognitive impairment.
· Five-year Graft survival in elderly renal transplant recipients was higher with living donors (70 %) than SCD (60%) than ECD (46%) (3).
Is more in elderly than young recipient especillay if they have cognitive impairement
There are many risk factors for DGF including donor related and recipient related, Old age is one of the donor main factors for DGF.
It is more with deceased donors than living
Ischaemic heart disease, PVD, Cardiovascular disease, infection
· Because of low immune response, elderly has lower rate of acute rejection episodes than young (4), so HLA mismatch is not a big issue like in young.
Yes, better QOL, more survival.
Prof Halwa comments:
Dear All
What do you think of offering this recipient a kidney from a 67-years-old deceased donor who is hypertensive (on 2 medications) and has a 26-year history of type 2 DM? His creatinine before retrieval was reported as 162 ug/ml (baseline 78 ug/ml with evidence of AKI).
This 72-year-old recipient is on the waiting list for 1.5 years
Thanks, Riham/Mina
This elderly patient should receive a good kidney. The elderly would not tolerate a protracted course of DGF, fluid overload, and of course a big operation. Well done
How frailty and cognitive impairment affect graft survival?
REFERANCES
1-https://www.usrds.org/qtr/default.aspx (Accessed on December 05, 2018).
2- Schold JD, Meier-Kriesche HU. Which renal transplant candidates should accept marginal kidneys in exchange for a shorter waiting time on dialysis? Clin J Am Soc Nephrol 2006; 1:532.
3-Molnar MZ, Streja E, Kovesdy CP, et al. Age and the associations of living donor and expanded criteria donor kidneys with kidney transplant outcomes. Am J Kidney Dis 2012; 59:841.
4- Meier-Kriesche HU, Ojo A, Hanson J, et al. Increased immunosuppressive vulnerability in elderly renal transplant recipients. Transplantation 2000; 69:885.
Thanks, Amit for quoting my paper
Patient survival is much better with transplantation than staying on regular dialysis.
Short and sweet Mahmoud, well done
The EDRD population is now increasing in age with half of them considered elderly ( 2/3 above 60 , 1/3 above 70)
So it is important to consider transplantation options for this age group
Although patient and graft survival of elderly population is lower compared to younger patients ,
yet transplantation of recipients greatly enhance their survival and decreases mortality 41 to 61% ,compared to staying on dialysis . 11
The chances for the old patients to be transplanted is much better by accepting expanded criteria donors , rather than waiting a standard criteria donor
The main issue post transplantation is the hight incidence of complications , mainly infectious complications which is the main cause of death in this age group ( cardiovascular causes are the main cause of death in younger patients ) 1
Incidence of acute rejection in this age group is lower compared to younger patients due to immunosenescence,
Yet if happens , it tend to affect the patient and graft survival adversly 2.3.4
But another point , in this age group , the wide acceptance of ECD ,increases rates of acute rejection
An important point in transplantation in this age group, where higher donor age and grafts are of less standard criteria ,
Is the degree of HLA mismatch and subsequently DSAs formation ,
Which significantly reduced patient and graft survival
So , it’s is advised to test for DSAs post transplant, for whom who were at increased immunological risk pre transplant 5.6.7
The degree of HLA compatibility between donor and recipients are tested nowadays with the degree of HLA mismatch, however DSAs can recognise polymorphic AA sequence ( called epitope ) rather than whole HLA antigen , making epitope matching more important than whole antigen matching 8
Another factor affecting DSA formation is the immunosuppressive drugs used as maintainence for this age group,
CNIs are the cornerstone in any IS protocol ,however owing to its nephrotoxicity and the fact that older recipients receiving older donor kidneys , makes this age group more susceptible for CNI nephrotoxicity .
Studying the possibility of CNI withdrawal in this age group is ongoing, results concluded incidence of acute rejections are high and survival is lower compared to CNI included protocols .10
More studies on the optimum maintenance IS protocol for this age group is still required
Studies found that ciclosporin use is associated with more DSA formation than tacrolimus
Also tacrolimus trough levels below 5 ng/dl after 1st year ,is associated with more DSA formation. 9
1) El-Zoghby ZM, Stegall MD, Lager DJ, Kremers WK, Amer H, Gloor JM, et al. Identifying specific causes of kidney allograft loss. Am J Transplant. (2009) 9:527–35. doi: 10.1111/j.1600-6143.2008.02519.x
2) Meier-Kriesche HU, Ojo A, Hanson J, Cibrik D, Lake K, Agodoa LY, et al. Increased immunosuppressive vulnerability in elderly renal transplant recipients. Transplantation. (2000) 69:885–9. doi: 10.1097/00007890-200003150-00037
3) Rana A, Murthy B, Pallister Z, Kueht M, Cotton R, Galvan NTN, et al. Profiling risk for acute rejection in kidney transplantation: recipient age is a robust risk factor. J Nephrol. (2017) 30:859–68. doi: 10.1007/s40620-016-0354-x
4). Heldal K, Hartmann A, Leivestad T, Svendsen MV, Foss A, Lien B, et al. Clinical outcomes in elderly kidney transplant recipients are related to acute rejection episodes rather than pretransplant comorbidity. Transplantation. (2009) 87:1045–51. doi: 10.1097/TP.0b013e31819cdddd
5) Tait BD, Susal C, Gebel HM, Nickerson PW, Zachary AA, Claas FH, et al. Consensus guidelines on the testing and clinical management issues associated with HLA and non-HLA antibodies in transplantation. Transplantation. (2013) 95:19–47. doi:
6) Tambur AR, Campbell P, Claas FH, Feng S, Gebel HM, Jackson AM, et al. Sensitization in transplantation: assessment of risk (STAR) 2017 working group meeting report. Am J Transplant. (2018) 18:1604–14. doi: 10.1111/ajt.14752
7) Susal C, Aykut G, Morath C, Fichtner A, Unterrainer C, Scherer S, et al. Relevance of donor-specific antibody monitoring after kidney transplantation: findings from the collaborative transplant study and the heidelberg transplant center. HLA. (2019) 94(Suppl. 2):11–5. doi: 10.1111/tan.13665
8) Duquesnoy RJ. A structurally based approach to determine HLA compatibility at the humoral immune level. Hum Immunol. (2006) 67:847–62. doi: 10.1016/j.humimm.2006.08.001
9). Susal C, Dohler B. Late intra-patient tacrolimus trough level variability as a major problem in kidney transplantation: a collaborative transplant study report. Am J Transplant. (2019) 19:2805–13. doi: 10.1111/ajt.15346
10) Abramowicz D, Del Carmen Rial M, Vitko S, del Castillo D, Manas D, Lao M, et al. Cyclosporine withdrawal from a mycophenolate mofetil-containing immunosuppressive regimen: results of a five-year, prospective, randomized study. J Am Soc Nephrol. (2005) 16:2234–40. doi: 10.1681/asn.2004100844
11) Knoll GA. Kidney transplantation in the older adult. Am J Kidney Dis. 2013 May;61(5):790-7. doi: 10.1053/j.ajkd.2012.08.049. Epub 2012 Dec 20. PMID: 23261121.
Thanks, Wessam
Can you elaborate more on this sentence “But another point, in this age group, the wide acceptance of ECD, increases rates of acute rejection”?
I mean despite the lower immune responses in elderly ( immunosenescence) and consequently decreased rates of acute rejection in this age group ,
Yet the wide acceptance of the expanded criteria donors with older age donors , this is associated with increased rates of acute rejections , delayed graft functions , and overall survival of the graft
Different studies show that patients survival in elderly patients >65 years is better than patients of same age group on dialysis, in spite of that in early post transplantation the mortality is increased. But when compare elderly with younger patients the survival is lower in elderly & commonly the elderly patients die with functioning graft( most common cause of graft failure in elderly).
Graft survival found to be lower in elderly recipients & this can be explained by graft is obtained from elderly donor which increase risk of graft loss.
Acute rejection rate is less in elderly recipients than younger recipients & this explained immunosensecence occurred due to changes In immune system that happened normally with aging& the older donor loss their regenerative ability to tissue injury the increased immunogenicity.
HLA mismatching increase the risk of acute rejection, DGF, & graft loss.There are multiple risk factors that increase rate of patients death including:
Because there is an evidence of survival benefits in all age group comparing with patients on dialysis in addition to improved quality of life, mental health. Also age is not barrier to transplantation our patient will benefit from transplantation.
References:
This is very stimulating Ban
Will you explain to your colleagues how these risk factors you mentioned and patient and graft survival?
I’ll encourage him
Patient survival improved
Graft survival not bad (mismatch 3)
Primarily failure rate I don’t know
acute rejection according to dsa level and the induction used
Delayed graft function rate high due to the age of donor
If it no go ahead I’ll encourage him for expanded criteria as more quality of life and more survival with less comorbidity
The strogest predictor if death in elderly patient l think during operation
HLA mismatch decrease graft survival as it need more immunosuppressant and low tolerance
Finally at his age he will get benefit from transportation as it improve survival and quality of life
Thanks, Wael for your excellent contribution.
Suppose it 6 mismatches, will you still encourage him?
A- Patient survival after kidney transplantation depends on several factors
a- Age : elderly recipient are at higher risk for death than yonger recipient and death mainly from CVD , Infections and malignancies .
b- Comorbidity ; DM , Atherosclerosis , Pre-emptive transplantation , ethinicity ( better outcome in Hispanic than African americans.(1)
B- Acute rejection : sudden deterioration in graft function, either T cell mediated or AMR. The rate of acute rejection is lower with advancing age of both recipient and donor this may be due to immunosenescence (2).
C- Graft survival : depends on
· Recipient age ( as graft in elderly recipient suffer less acute rejection episodes , thus its survival is better than younger recipients and most elderly die with functioning graft )
Other comorbidities as DM, atherosclerosis.
· Advanced donor age, atherosclerosis.
· Delayed graft function
· Degree of HLA matching more important in deceased donor than in living ones
· HLA antibodies and presense of DSA
· Pre-emptive transplantation
· Prolonged cold ischaemic time (CIT)
· Rejection episodes: the more rejection episodes , the poorer graft outcome.
Delayed graft function
Defined as the need for dialysis post-transplantation.
Primary graft failure :
Defined as return to dialysis or preemptive retransplantation.
So for this patient , I would advice him to preceed with transplantation due to its favorable out come in elderly specially that he has a living related donot with resenable HLA matching and he isnot diabetic , thus I expect he will have a good survival chance with a functioning graft and less expected acute rejection episodes.
For this patient , I would offer him ECD as transplantation carries better quality of life than maintaining on dialysis.
Commonest causes for death in elderly recipients : Cardiovascular diseases , infections , malignancy.
vDegree of HLA mismatch more important in living than deceeded donor and the higher degree of mismatch the more rejection rate.
1- Orsenigo, E., Socci, C., Carlucci, M., Zuber, V., Fiorina, P., Gavazzi, F., … & Staudacher, C. (2005, July). Multivariate analysis of factors affecting patient and graft survival after renal transplant. In Transplantation proceedings (Vol. 37, No. 6, pp. 2461-2463). Elsevier.
2-McKay D, Jameson J. Kidney transplantation and the ageing immune system. Nat Rev Nephrol 2012;8:700–8. https://doi.org/10.1038/nrneph.2012.242.
More than 50 % of ESRD patients are ≥ 65 years (1). in 2016, 21% of ESRD waitlisted patients were ≥ 65 years.
A- Regarding long term survival
B- Regarding immunosuppression plan, elderly differ from young in the following :
1- Because of immunosenecense, elderly has lower rate of acute rejection episodes than young (4), so HLA mismatch is not a big issue like in young
2- elderly are more prone to side effects of immunosuppressive drugs, most importantly is infection
3- CNI side effects are more in elderly this is because elderly usually take kidneys from older donors who have vulnerable kidney and also the activity of cytochrome b450 is usually reduced in elderly thus having higher level of CNI in blood
C- Regarding immunosupression protocol
– Induction is the same as for young, some recommend against the use of ATG.
– Maintenance immunosuppression is the same as for young and then modify according to side effects of immunosuppression which are more common in elderly such as leukopenia, thrombocytopenia, infection, malignancy thus it usually end by removing antimetabolite.
One study demonstrate higher incidence of infection with MMF when compared to azathioprine (5), Other found better patient and graft survival with MMF when compared to azathioprine (6)
D- Regarding graft survival
E- Most important predictors of death in elderly renal transplant recipients are
cardiovascular disease, infection, graft loss
REFERANCES
1-https://www.usrds.org/qtr/default.aspx (Accessed on December 05, 2018).
2- Schold JD, Meier-Kriesche HU. Which renal transplant candidates should accept marginal kidneys in exchange for a shorter waiting time on dialysis? Clin J Am Soc Nephrol 2006; 1:532.
3-Molnar MZ, Streja E, Kovesdy CP, et al. Age and the associations of living donor and expanded criteria donor kidneys with kidney transplant outcomes. Am J Kidney Dis 2012; 59:841.
4- Meier-Kriesche HU, Ojo A, Hanson J, et al. Increased immunosuppressive vulnerability in elderly renal transplant recipients. Transplantation 2000; 69:885.
5- Johnson DW, Nicol DL, Purdie DM, et al. Is mycophenolate mofetil less safe than azathioprine in elderly renal transplant recipients? Transplantation 2002; 73:1158.
6- Meier-Kriesche HU, Morris JA, Chu AH, et al. Mycophenolate mofetil vs azathioprine in a large population of elderly renal transplant patients. Nephrol Dial Transplant 2004; 19:2864.
7- The 2010 SRTR report on the state of transplantation http://www.ustransplant.org/annual_reports (Accessed on February 12, 2012).
8- Gill JS, Gill J, Rose C, et al. The older living kidney donor: Part of the solution to the organ shortage. Transplantation 2006; 82:1662.
Thanks, Sherif
I’m impressed with your answer.
Dear All
Dr Sherif and others (not everyone) addressed important issues regarding transplanting elderly patients which are frailty and cognitive impairment.
He said
“Assessment of frailty and cognitive impairment is very important since they are associated with poor graft survival”.
How frailty and cognitive impairment affect graft survival?
cognitive impairment may happened in the form of memory loss and decreased attention, also miscommunication because of language problem…etc , all these will hinder ISD taking on time or even their administration, also defect in judgment on any problem related to his medical condition like cardiac or chest c/o also urine output …all these will be against transplantation except if there is a caregiver who will facilitate the mission.
frailty may involves unintentional weight loss, weakness, and exhaustion , which may also be exaggerated by ISD including steroid.
Thanks Riham
Do you mean immunosuppression drugs by ISD?
Please explain the abbreviations in the future
sorry for inconvenience
immunosuppressive drugs ISD
Frailty is very common in ESRD patients on Dialysis and hence a proper evaluation is important. Frailty is associated with more than 2 times higher risk of death as well as delayed graft function, having a negative effect on the graft prognosis. (1,2)
Cognitive impairment is also 2 to 5 times more common in dialysis population as compared to general population. (3) There is a high chance of skipping of immunosuppressive doses due to forgetfulness leading to risk of graft rejection.
References:
1) MaAdams-Demarco MA, Law A, King E, et al. Frailty and mortality in kidney transplant recipients. Am J Transplant 2015;15:149-154.
2) Garinjik-Wang IM, Govindan P, Grinnan JW, et al. Frailty and delayed graft functionin kidney transplant recipients. Arch Surg 2012;147:190-193.
3) Tamura MK, Yaffe K. Dementia and cognitive impairment in ESRD: diagnostic and therapeutic strategies. Kidney Int 2011;79:14-22.
Riham/Amit
Excellent, short and sweet with references
Frailty (which is assessed using 5 items : weight loss, weakness, exhaustion, walking speed and physical activity) and cognitive impairment are strongly associated with poor graft survival and increased mortality this is because of the high likehood of forgetting immunosuppressive drugs, negilcance of follow up visits
Although there is no evidence to asses frailty score for transplant recipients before transplantation, its incidence between 5-9% in people above 65 y and increase to be more than 60% between dialysis patients , which reflects on risk of hospital readmission and increase risk of death independently on age .
Post transplant mortality increasing in frail recipients than non frail ones .
If Cognitive impairment cause memory impairment in level made patients non-compliant for medication (immunosuppressive medication) will increase risk of graft loss , so early recognition of cognitive function important to keep certain patients on regular appointments for memory prescription .
With the increase in life expectancy in the developed countries, and parallel increase in DMII, hypertension, vascular diseases including coronary artery diseases, the incidence of chronic kidney diseases and end stage renal diseases are becoming more and more problematic especially with the increase in economic and health care burden. The improvement in renal medical care and developments in renal replacement therapies does not improve the overall survival as expected.
Kidney transplantation remains the optimal treatment of end stage renal disease. The incidence of end stage renal disease among older population becoming more prevalent and despite old age, these patients are still considered candidates for kidney transplantation and age is not a contraindication. Kidney transplantation is associated with better quality of life, better survival rate, better cardiovascular outcomes when comparing to dialysis regardless of patient’s age, comorbidities, HLA mismatch and kidney donor profile index.
Older population are characterized with lower immune response because of natural immunosenescence. With this reduced immune response, older patients are less likely to develop acute rejection comparing to younger patients, which could be ideal to reduce the induction and maintenance immunosuppressive therapies. Reduction in immunosuppression is associated with better graft survival, less infection, less medication s side effects and drug-drug interactions especially in older ages with polymedicated patients for conditions other than kidney transplant
.
In our clinical scenario, this elderly patient with 72 years old will definitely benefit from kidney transplantation. patient survival is higher in kidney transplantation comparing to waitlisted dialysis patients. With natural immunosenescence, and reduced immunosuppressive therapies, graft failure will less likely be affected by immune mediated failure- acute rejection, but could be affected by delayed graft function possibly due to vascular anastomosis or if ECD.
Acute rejection rate is less common in this age group. If living donation didn’t go ahead, patient may benefit from ECD. Previous failed graft and DGF, peripheral vascular disease are the strongest predictors of death in this age group. HLA mismatch does not carry high risk for rejection compared to younger population. instead these patients may benefit from reduced immunosuppression doses.
The number of elderly patients with ESRD who require renal transplantation is increasing as the world become older. chronological age is no longer a contraindication.
Renal transplantation is the preferred RRT on all ages (so this elderly patient will benefit from renal transplantation) and provides a survival benefit over those who remain on dialysis together with improved quality of and less risk for deaths.
Patient and graft survival: In a retrospective analysis for 193 elderly patients> 60 years carried by Sanchez et (2020)al showed that patient survival was 89%, 70% and 55% at 1, 5 and 10 years respectively whereas the 1,5,10-year death-censored graft survival rate was 90%, 86%, and 75% respectively and the main mortality causes were infections and cardiovascular deaths.
In another Cohort study carried by Sara su et al.(2021) involving 1324 elderly decease donor transplant on the wait-list between June 2006 and December 2016, the 1,5 years patient survival was 95.1 and 79 % respectively whereas the 1, 5 year survivals with a functioning graft were 95.7% and 82.4% respectively
Primary non function, delayed graft function and acute rejection rate: In a retrospective cohort study carried by Niall J. et al(2013) older kidney recipients are more likely to receive kidneys from old donors. Accordingly, there primary failure rate in the first year following transplantation was 11.9% vs. 7.8% with DGF 40.7% vs. 16.9% .However elderly had lower biopsy proven acute rejection (BPAR) which was 6.8% vs. 22% attributed to natural immunosenescence , so, Prevention of rejection is generally easier in older patients allowing reduced dosage of immunosuppressant medication
Elderly related strongest comorbidities are ischemic heart disease, peripheral vascular disease, Frailty are important risk factors for premature deaths and post -operative complications after kidney transplantation.
In the absence of living donation ECD kidney (old-for-old implemented in the Euro-transplant Program and the US Kidney Allocation System) is a reasonable transplantation option which still offers a survival benefit over dialysis, and reduces waiting time for transplantation
Since most donor specific antibodies (DSAs) a1re directed against HLA class II antigens. HLA-DR matching improves graft survival and reduce rejection episodes and reduces the need for more intense immunosuppression thus reducing the risk of serious infections and cardiovascular risks. So, a tailor made strategy for immunosuppression is needed rather than the standard protocol
1 or 2 HLA-DR mismatches give a higher chance of development of donor specific antibodies and T-cell mediated rejection and decreased allograft survival
2 HLA-DR mismatches had worse graft survival compared to 0 or 1 HLA-DR mismatch
References:
· Patient and graft survival of elderly kidney transplant recipients: A ten years follow-up. Sanchez et al; Transplantation, September 2020
· Outcomes following renal transplantation in older people: a retrospective cohort study, Niall J et al, BMC Geriatric.2013; 13: 79
· Immunologic outcome in elderly kidney transplant recipients: is it time for HLA-DR matching? Fabian Halleck et al, Nephrol Dial Transplant, 2016. 31: 2143–2149
· Factors Influencing Long-Term Patient and Allograft Outcomes in Elderly Kidney Transplant Recipients. Sarah Su et al. Kidney international reports, March 2021, Pages 727-736