3. You were offered kidneys from a 35-year-old DCD donor (donor after cardiac death) who suffered from hypoxic brain damage (committed suicide by hanging). He had cardiac arrest for 45 mins before being revived. No history of hypertension or DM, S Cr 190 µmol/L before retrieval. 002 mismatch and no donor specific antibodies (DSA). He is still passing urine (40 mls/h during the last hour and 1.8 L over the last 24 hours).
- How would you define DGF?
- What is the effect of DGF on the graft survival?
- What is the effect HLA DR mismatch on the outcome of transplantation?
DGF (Delayed graft function):is defined as AKI in 1st week of transplant that necessitates dialysis.
DGF affects graft increase the incidence of acute rejection and affects long term survival of graft function .
HLA DR is a major part of HLA matching and if there is no matches in it ,it leads to acute and chronic rejection and affection of long term survival of graft
Delayed graft function was defined as acute kidney injury occuring in the first week post transplantation and necessitate dialysis .
Delayed graft function was associated with poor overall graft outcomes.
The incidence of Delayed graft was higher with deceased donor than living donor due to more prolonged cold ischemia times, and mostly donor factors as DM and previous cardiac or other chronic diseases.
DGF was associated with increase incidence of acute cellular rejections, poor graft survival .
Effect HLA DR mismatch on graft survival
HLA-DR mismatches was associated with long term poor graft survival, acute and chronic ABMR .
How would you define DGF?
The need for hemodialysis during the first week after transplantation due to AKI.
What is the effect of DGF on the graft survival?
DGF increase the occurrence of Acute rejection which will ultimately affect the overall graft survival.
What is the effect HLA DR mismatch on the outcome of transplantation?
HLA mismatch especially DR increase the incidence of chronic rejection and decrease graft survival .
DGF : acute kidney injury occurs 1 week post transplantation and necessitate dialysis .
increase incidence of acute rejection and reduced graft survival rate .
increase incidence of chronic rejection .
affect graft survival especially from deceased donor.
How would you define DGF?
What is the effect of DGF on the graft survival?
What is the effect HLA DR mismatch on the outcome of transplantation?
DGF is defined as AKI in the 1st week post transplantation that necessitate dialysis .
DGF is associated with poor short-and long-term outcomes and associated with higher rates of rejection .
Zens TJ, Danobeitia JS, Leverson G, Chlebeck PJ, Zitur LJ, Redfield RR, et al: The impact of kidney donor profile index on delayed graft function and transplant outcomes: A single-center analysis. Clin Transplant 2018; 32: e13190.
DR mismatch is associated greater incidence of sensitization , more incidence of rejection and overall poor graft outcomes.
Meier-Kriesche HU, Scornik JC, Susskind B, Rehman S, Schold JD SOTransplantation. 2009;88(1):23.
HLA-DR mismatches are associated with overall poor graft survival. This is due to HLA DR being so polymorphic and many reactions of antigen and antibody interaction with ABMR can happen1. This is followed by HLA B and HLA A mismatches for propensity for overall graft survival. Increasing Compared with 0 mismatches in HLA-DR antigen, 1 mismatches and 2 mismatches were all associated with higher risk of overall graft failure, indicating that HLA-DR mismatches were significantly associated with a 12% higher risk of overall graft failure. 2
Three variables vs Zero HLA-DR mismatched grafts showed improved survival over those with 1 HLA-DR mismatch both at 1 year and at 5 years only if cold ischemia time was less than 26 hours.
Referecnes:
DGF defined as borderline functioning graft that can be recovered after days-weeks with hemodialysis. It occurs in around 10-12% of renal transplantation, & it more common in deceased donor than living donor.
The renal graft can functioning after 60 minutes of warm ischemia but DGF rate increased after 20 minutes.
DGF had both short & long term complications with reducing graft survival. DGF can cause ACR/ AMR & CAN, but there is no complete agreement about the effect of DGF on graft out come. 10 years survival found to be similar among recipients without DGF or ACR & DGF+/ACR-, but DGF with ACR was associated with poor graft function even at 1 year post transplantation.
Any increment of HLA mismatch was associated with increased risk of graft loss, death censored graft loss & all cause mortality. Several studies show that HLA-DR mismatch associated wit significant higher risk of graft loss reaching to 12 % of renal transplantation.
References:
transplantation, which necessitates dialysis intervention.
survivals.
DR mismatch is associate with high immunologic risk and portends inferior outcomes.
References:
1-Mannon R.B. Delayed Graft Function: The AKI of Kidney Transplantation. Nephron
2018;140:94–98.
2-Kalathi K Suresh et al .Induction Type and Outcomes in HLA-DR Mismatch Kidney
Transplantation. Transplant Proc. Jul-Aug 2019;51(6):1796-1800.
DGF could be defined as need for dialysis in first week following transplantation due to failure of renal graft to function immediately.
DGF is associated with increased incidence of acute rejection and affection of graft survival
HLA DR mismatch has deleterious effect on transplant outcome leading to DSA formation leading to rejection and graft loss.
REFERENCES:
Danovitch ,GM, Handbook of kidney transplantation,2018
DGF associated higher rejection rate, worse graft function, chronic allograft failure and impaired graft and patient survival ;but not if completely recovered early.Donor recipient (HLA)-DR mismatch has high immunologic risk and results in worse outcomes.
Avoiding HLADRB1 mismatching could reduce rejection incidence , but can prolong waiting time.
Effect of HLA mismatching could be not detected until 10 years after transplantation.
Multiple studies suggested that HLA-DRB1 mismatching is particularly harmful,, perhaps because HLA-DRB1 is a marker of closely linked HLA antigen loci, which were not considered (HLA-DRB3, DRB4, and DRB5 and HLA-DQ).
Avoidance of HLA-DRB1 mismatching alone would increase transplantation in non white individuals by 6.3% while decreasing the numbers in white patients by only 4.0%, with a resultant 2% decrease in graft survival.
Reference
-Mallon et al Defining Delayed Graft Function after Renal Transplantation
Simplest Is Best.
Transplantation Journal: November 27, 2013 – Volume 96 – Issue 10 – p 885-889
-Vu L T etal. HLA-DR Matching in Organ Allocation Balance Between Waiting Time and Rejection in Pediatric Kidney Transplantation .Arch Surg. 2011;146(7):824-829) Shi X, Lv J, Han W, et al. 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.
How would you define DGF?
Multiple definitions are available
According to dialysis
DGF means patient required dialysis in first week post transplant (day 1 can be excluded as some times patient came postoperative with pulmonary edema or hyperkalemia requiring dialysis)
According s.creatinine
Failure of decrease s.creatinine more than 25% in day 1 post operative.
What is the effect of DGF on the graft survival?
DGF is mostly caused by ischemic insult to kidney tissue which associated with increase risk of rejection causing low graft survival but if it was mild and associated with full recovery without rejection it will have impact on graft survival.
What is the effect HLA DR mismatch on the outcome of transplantation?
HLA DR mismatch associated with increase risk of donovo DSA , increase sensitization, decrease probability of 2transplant,2DR Mismatch associated with decrease 7year graft survival to 73% in relation to 80% in 0mismatch and associated with early acute rejection
REFERENCES
1. Wu W, Famure O, Li Y, Kim SJ. Delayed graft function and the risk of acute rejection in the modern era of kidney transplantation. Kidney Int. 2015;88(4):851–8.
2. Gill J, Dong J, Rose C, Gill JS. The risk of allograft failure and the survival benefit of kidney transplantation are complicated by delayed graft function. Kidney Int. 2016;89(6):1331–6.
3. Lim WH, McDonald SP, Russ GR, JR, Ma MK, Pleass H, Jaques B, Wong G. Association between delayed graft function and graft loss in donation after cardiac death kidney transplants-a paired kidney registry. Transplantation. 2017;101(6):1139–43.
4. Opelz G, Döhler B. Effect of human leukocyte antigen compatibility on kidney graft survival: comparative analysis of two decades. Transplantation 2007; 84:137.
5. Wiebe C, Gibson IW, Blydt-Hansen TD, et al. Evolution and clinical pathologic correlations of de novo donor-specific HLA antibody post kidney transplant. Am J Transplant 2012; 12:1157.
6. Coupel S, Giral-Classe M, Karam G, et al. Ten-year survival of second kidney transplants: impact of immunologic factors and renal function at 12 months. Kidney Int 2003; 64:674.
How would you define DGF?
There are many definitions for DGF but the most used one is need for dialysis in the first week of kidney transplant
What is the effect of DGF on the graft survival?
It is a risk factor for acute rejection and affect the graft survival
What is the effect HLA DR mismatch on the outcome of transplantation?
It considered high immunlogic risk due to polymorphism of DR so the possibility of ABMR is always there
References
Lim WH, McDonald SP, Russ GR, JR, Ma MK, Pleass H, Jaques B, Wong G. Association between delayed graft function and graft loss in donation after cardiac death kidney transplants-a paired kidney registry. Transplantation. 2017;101(6):1139–43
DGF is defined as delay in improving kidney function and the need for dialysis in the first week after kidney transplantation. Other definitions for DGF are low or absent urine output immediately after kidney transplantation, or failure of serum Cr to decline by more than 25% within 24 hours of transplant surgery.
The presence of DGF has a major adverse impact upon both short- and long-term allograft survival. DGF is associated with higher risk of acute rejection, increased formation of DSA, upregulation of HLA antigens, and triggering of the cytokine-adhesion molecules cascade, worse graft and patient outcomes and lower long-term graft and patient survival.
HLA-DR mismatches have a major impact on kidney allograft outcomes. HLA-DR mismatches have a much greater effect than HLA-B or -A. HLA-DR mismatches correlate with poor long-term survival. Prior sensitization against HLA-DR has also been associated with an increased risk for major adverse cardiac and cerebrovascular events as well as all-cause mortality in kidney transplant recipients.
How would you define DGF?
There are over 10 definitions of DGF recorded in the literature .In 69% of studies reviewed between 1984 and 2007 DGF was defined as the use of dialysis within seven days of the transplant. The criterion has shortfalls as dialysis may be used in the first week after transplant without confirmation of kidney damage .1
What is the effect of DGF on the graft survival?
What is the effect HLA DR mismatch on the outcome of transplantation?
LA-DR mismatches were significant associated with worse overall graft survival. Each incremental increase of HLA-DR mismatches was significant associated with 12% higher risk of overall graft failure. Compared with 0 mismatches in HLA-DR antigen, 1 mismatches and 2 mismatches were all associated with higher risk of overall graft failure, indicating that HLA-DR mismatches were significantly associated with a 12% higher risk of overall graft failure. 4
Three variables (HLA-DR mismatch, delayed graft function, and prolonged cold ischemia time) had a significant detrimental effect on both short- and long-term graft survival. Zero HLA-DR mismatched grafts showed significantly enhanced survival over those with 1 HLA-DR mismatch both at 1 year and at 5 years only if cold ischemia time was less than 26 hours (P=0.0009). Occurrence of delayed graft function significantly lowered graft survival at both 1 year and 5 years and the incidence was significantly associated with prolonged cold ischemia time5
1-Siedlecki A, Irish W, Brennan DC. Delayed graft function in the kidney transplant. Am J
Transplant. 2011;11(11):2279-2296. doi:10.1111/j.1600-6143.2011.03754.x.
2-Shoskes DA, Cecka JM. Effect of delayed graft function on short- and long-term kidney graft survival. Clin Transpl. 1997:297-303. PMID: 9919413.
3-Wu, W. K., Famure, O., Li, Y., & Kim, S. J. (2015). Delayed graft function and the risk of acute rejection in the modern era of kidney transplantation. Kidney International, 88(4), 851–858. doi:10.1038/ki.2015.190
4- Shi X, Lv J, Han W, Zhong X, Xie X, Su B, Ding J. 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 Nephrol. 2018 May 18;19(1):116. doi: 10.1186/s12882-018-0908-3. PMID: 29776389; PMCID: PMC5960106.
5-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. doi: 10.1097/00007890-199603150-00007. PMID: 8607172.
How would you define DGF?
is the need for dialysis in the first week of kidney transplant
What is the effect of DGF on the graft survival?
It is a risk factor for acute rejection and affect the graft survival
What is the effect HLA DR mismatch on the outcome of transplantation?
It considered high immunlogic risk due to polymorphism of DR so the possibility of ABMR is always there
●DGF :
Delayed graft function is failure of tx kideny to work after transplantation and the patient need dialysis for short time.
● it is correlated with acute rejection
But if normal kideny function after than there is no difference in survival .
●What is the effect HLA DR mismatch on the outcome of transplantation?
Increase risk of rejection and graft failure . Reference
Hand book of kidney transplantations 6th edition
How would you define DGF?
Delayed graft function (DGF) is defined as failure of the renal transplant to function immediately, with the need for dialysis in the first post-transplantation week.
What is the effect of DGF on the graft survival?
DGF is associated with higher rates of acute rejection but impaired long-term graft survival even when rejection is absent and discharge creatinine was normal.
What is the effect HLA DR mismatch on the outcome of transplantation?
HLA-DR mismatches are associated with increased risk of acute rejection and graft failure.
Reference;
Danovitch GM. Handbook of Kidney Transplantation. Sixth Edition, Wolters Kluwer, eISBN 9781496388841, 2017.
Dear Dr Ishag
Please expand more on your statement with references to the published evidence “DGF is associated with higher rates of acute rejection but impaired long-term graft survival even when rejection is absent and discharge creatinine was normal”.
DGF is defined in different ways, it is the acute transplant kidney dysfunction with the need for hemodialysis in the first week post transplant, it describes grafts that recovers function after several days to weeks, the patient is usually oliguric or anuric, also it can be defined as absent spontaneous reduction of serum creatinine post transplant
Slow graft function describes milder forms of graft dysfunction without the need for dialysis
It is associated with worse outcome and higher rejection rate, It leads to worse graft function, chronic allograft failure and impaired graft and patient survival except if recovered early and completely.
HLA-DR mismatches are associated with increased risk of acute rejection and graft failure.
Mannon RB. Delayed graft function: the AKI of kidney transplantation. Nephron. 2018;140(2):94-8.
Shi X, Liu R, Xie X, Lv J, Han W, Zhong X, Ding J. Effect of human leukocyte antigen mismatching on the outcomes of pediatric kidney transplantation: a systematic review and meta-analysis. Nephrology Dialysis Transplantation. 2017 Nov 1;32(11):1939-48.
Thanks Heba
Please expand more on your statement with references to the published evidence “DGF is associated with worse outcome and higher rejection rate, It leads to worse graft function, chronic allograft failure and impaired graft and patient survival except if recovered early and completely.”
How would you define DGF?
DGF is the need for dialysis within the first week after transplantation
What is the effect of DGF on the graft survival?
DGF shown to be associated with longer hospital stays, increased AR , lower baseline graft functions and decreased graft survival
What is the effect HLA DR mismatch on the outcome of transplantation?
In kidney transplantation, donor recipient HLA-DR mismatch signals high immunologic risk and possessed inferior outcomes. The incremental mismatches in HLA DR associated with increased risk of AR and lower graft survival
Mallon DH, Summers DM, Bradley JA, et al. Defining delayed graft function after renal transplantation: simplest is best. Transplantation 2013;96:885-889
Mannon RB. Delayed graft function: The AKI of kidney transplantation. Nephron 2018;140:94-98.
Regarding DGF
What abou if it was mild, associated with full recovery and not complicated by rejection?
Dear All
DGF especially recovering quickly (mild and recovered fully) does not have an impact on graft survival unless complicated by rejection. I agree, there is no accepted consensus regarding the definition of DGF. Agree, DR mismatch has the worst outcome compared to other HLA antigen mismatches
It is the acute kidney injury that occurs during the first week of kidney transplantation, requiring dialysis intervention.
It has several definitions including
-Dialysis based
Involving requiring dialysis in the first week postoperative(po) or excluding the first 24 h or needing 2 or more dialysis sessions in the first postoperative week or needing dialysis in the first 10 days postoperatively.
-Creatinine based
The creatinine is not decreasing 10% on 3 successive days in the first post operative week or creatinine being> 2.5 mg/dl at day 7 po or at day 10po or failure of declining of creatinine ratio to less than 30% in day 1 and 2 po
-Combination
Needing dialysis in first week or creat. not decreasing in first 24h
Or Needing dialysis in first week or creatinine being> 2.5 mg/dl at day 7 po
Mallon et al suggested the use of dialysis in the first postoperative week as the best definition because it is applicable and it is as predictive of long-term graft outcomes as more complex definitions of DGF but it poses an immediate clinical benefit as it reflects the duration of the initial hospital stay after transplantation.
DGF is accompanied with high rates of acute cellular rejection and shorter graft survivalsof donation after brain death (DBD) kidney transplants apart from which definition is applied either the creat or dialysis based definition
Another study byMallon et al, demonstrated that DGF does not appear to affect outcomes of donation after circulatory death (DCD) kidney transplants
Meanwhile it is a useful endpoint for clinical trials of both donation after brain death( DBD) and (DCD )kidneys because it is associated with increased healthcare cost and hospital stay and it may mask rejection episodes
Donor recipient (HLA)-DR mismatch implies high immunologic risk and leads to unfavourable outcomes.
Only HLA-DR matching is considered in the United Network for Organ Sharing (UNOS) organ allocation system.
Avoiding HLADRB1 mismatching can lower the rejection incidence , but can prolong the waiting time, which is also deleterious.
The effect of HLA antigen mismatching is usually undetectable until 10 years after transplantation.
There could be a “dose effect” when more HLA antigens were mismatched.
The importance of HLA antigen matching in the current era of immunosuppression therapy era is a controverse, but multiple studies suggested that HLA-DRB1 mismatching is particularly hazardous, perhaps because HLA-DRB1 is a marker of closely linked HLA antigen loci, which were not considered (HLA-DRB3, DRB4, and DRB5 and HLA-DQ).
Roberts et al declared that avoiding HLA-DRB1 mismatching alone would increase transplantation in non white individuals by 6.3% while decreasing the numbers in white patients by only 4.0%, with a resultant 2% decrease in graft survival.
Reference
-Mallon et al Defining Delayed Graft Function after Renal Transplantation
Simplest Is Best.
Transplantation Journal: November 27, 2013 – Volume 96 – Issue 10 – p 885-889
-Vu L T etal. HLA-DR Matching in Organ Allocation Balance Between Waiting Time and Rejection in Pediatric Kidney Transplantation .Arch Surg. 2011;146(7):824-829
Thanks, Dr Doaa
DGF especially recovering quickly (mild and recovered fully) does not have an impact on graft survival unless complicated by rejection. I agree, there no acceptable consensus regarding the definition of DGF. Agree, DR mismatch has the worst outcome compared to other HLA antigen mismatches
*DGF means need of heamodialysis during first week after kidney transplantation
*DGF (common in deceased donors & long ischemia time ) lead to poorer graft survival and more risk of rejection -high basal creatinine after transplant due to element of graft fibrosis , long hospital stay so high risk of post operative complication specially infection
*HLA DR consider the most important one in crossmatch and mismatch in it mean high risk of acute rejection and poor graft survival
Delayed graft function (DGF) is defined as requirement of dialysis in first week post-transplant, as per UNOS. (1) But there are many definitions of DGF based on different criteria. (2)
These include:
1) Dialysis based:
a) Need of dialysis in first week post-transplant
b) Need of dialysis in first week post-transplant excluding first 24 hours
c) Need of 2 or more dialysis in first week post-transplant
2) Creatinine based:
a) Serum creatinine more than 2.5 mg/dl after 7 days post-transplant
b) Serum creatinine more than 2.5 mg/dl after 10 days post-transplant
c) Failure of decrease in serum creatinine by 10% on 3 consecutive days in first week post-transplant
d) Fall in ratio of creatinine on post-operative day 1 and 2 by at least 30%
3) Combination of need of dialysis and creatinine:
a) Dialysis in first week post-transplant or failure of fall in creatinine
b) Dialysis in first week post-transplant or serum creatinine more than 2.5 mg/dl after 7 days post-transplant.
DGF has been shown to be associated with increased hospital stays, increased rejection episodes, worse baseline graft functions and decreased graft life. (3)
A kidney transplant with HLA-DR mismatch signifies a high risk transplant. It has been shown to be associated with poorer outcomes with In a meta-analysis, as compared to 0 DR mismatch, 1 DR mismatch had 12% increased risk of graft failure while 2 DR mismatch had 15% increased risk of graft failure.
References:
1) Lim MA, Bloom RD. Medical Therapies to Reduce Delayed Graft Function and Improve Long-Term Graft Survival. Are We Making Progress? Clin J Am Soc Nephrol 2020;15:13-15.
2) Mallon DH, Summers DM, Bradley JA, et al. Defining delayed graft function after renal transplantation: simplest is best. Transplantation 2013;96:885-889
3) Mannon RB. Delayed graft function: The AKI of kidney transplantation. Nephron 2018;140:94-98.
4) Shi X, Lv J, Han W, et al. 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.
4) Shi X, Lv J, Han W, et al. 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 Nephrol 2018;19:116
Thanks Amit
See my answer above.
What is the effect of DGF on the graft survival?
DGF has been associated with increased hospital stay, increased rejection, and shorter graft survival .
What is the effect HLA DR mismatch on the outcome of transplantation?
HLA-mismatches at the HLA-DR locus associated with the highest risk of acute rejection compared to mismatches at the HLA-A and HLA-B loci .
In the UNOS study, the association between HLA-mismatches and reduced graft survival appeared to be related to mismatches at the HLA-DR locus within the first year post-transplant, whereas mismatches at the HLA-AB loci were more important beyond the first year post-transplant.
CJASN January 2020, 15 (1) 13-15; DOI: https://doi.org/10.2215/CJN.13961119
Mannon RB: Delayed graft function: The AKI of kidney transplantation. Nephron 140: 94–98, 2018pmid:30007955 PubMedGoogle Scholar
01 November 2020 https://doi.org/10.1111/tri.13781The Evolution of HLA-Matching in Kidney Transplantation
By Hung Do Nguyen, Rebecca Lucy Williams, Germaine Wong and Wai Hon Lim
Submitted: April 13th 2012Reviewed: October 29th 2012Published: February 13th 2013
DOI: 10.5772/54747
Dear all
Why do we ask here about DGF in this particular scenario?
What is the difference between DGF and slow graft function?
Dear Professor:
In the current scenario the deceased donor has cardiac arrest for 45 minutes and suffered from hypoxic brain damage. In the same time for sure he developed non oliguric ATN secondary to prolonged cardiac arrest with renal hypoperfusion and his kidney if transplanted will most probably will end with delayed graft function. And if we calculate the UOP in the previous day it was around 75 ml/hour which dropped to 40 ml/hour in the last hour.
I have a recent experience with similar scenario currently we have a sensitized patient transplanted from deceased donor with negative FCXM and the deceased donor kidney proved by tissue diagnosis (during surgery) suffered of ATN. Recipient now in delayed graft function (on hemodialysis) and most probably secondary to oliguric ATN.
DGF: defined by requirement of dialysis during the first week post transplantation.
SGF: it is An intermediate phenotype between immediate graft function(IGF) and DGF slower initial postoperative decline in serum creatinine compared to IGF but without the need for dialysis. Failure of improvement of serum Cr by a given postoperative day (e.g., Cr ≥3 mg/ld. on POD5 or Cr ≥2.5 on POD7 or an inadequate percentage reduction in Cr over a given period (e.g., a creatinine reduction ratio (CRR) of <30% between POD1 and POD2.
Reference:
Zeraati AA, Naghibi M, Kianoush S, Ashraf H. Impact of slow and delayed graft function on kidney graft survival between various subgroups among renal transplant patients. Transplant Proc. 2009;41:2777–80.
The kidney is of bad quality due to History of brain injury, high Cr 190, prolonged cardiac arrest although it was making good urine. Slow graft function is condition when the Cr does not come down post-operatively as expected and there is indication for dialysis. DGF is reduction renal function that requires dialysis in the first week after transplantation.
There are many definitions of DGF , the most practical one is defined DGF as the need for HD in the first week after transplantation .
Donation after circulatory death is associated with greater risk of DGF than donation after brain death donation because the longer warm ischemia time.
DGF is associated with longer hospital stay , and increased risk of acute rejection.
In living donor transplantation , DGF is associated with double the risk of graft loss. In DBD transplantation , DGF is associated with 40% of increased risk of graft loss.
Interestingly, DGF (of less than 14 days ) in DCD had similar outcomes to patients without DGF DCD transplantation. But DGF of longer duration (more than 14 days) is associated with high risk of graft loss(1).
HLA DR mismatch is associated with poor graft outcome , and increased risk of acute rejection. the impact of DR antigen mismatch is greater than the impact of HLA A or HLA B mismatches(2).
References:
(1)Benedict L. Phillips | Maria Ibrahim | George H. B. Greenhall |
Lisa Mumford | Anthony Dorling | Chris J. Callaghan
Effect of delayed graft function on longer-term outcomes after kidney transplantation from donation after circulatory death donors in the United Kingdom: A national cohort study Am J Transplant. 2021;21:3346–3355.
(2) Xinmiao Shi, Jicheng Lv, Wenke Han, Xuhui Zhong, Xinfang Xie, Baige Su and Jie Ding
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
Shi et al. BMC Nephrology (2018) 19:116
https://doi.org/10.1186/s12882-018-0908-3
1- DGF
-defined as the need for dialysis during first week post transplantation, reflecting ATN of the graft
2- Impact of DGF
impaired short and long term graft function, increase incidence of rejection episodes and eventually graft failure and loss
1- Impact of HLA Dr mismatch on graft survival
The higher degree of HLA mismatch is associated with more frequent acute rejection episodes , poor short and long term graft survival , higher degree of sensitization in subsequent transplantations.
Delayed graft function is usually defined as the need for dialysis during the first week after renal transplantation. It has a negative prognostic factor on transplanted kidney. has a risk of increase in rejection.
ALL mismatches have high odds ratio in terms of risk of rejection (https://www.sciencedirect.com/science/article/pii/S0085253815304038)
HLA-DR mismatch is also important and related to the risk of acute rejection
Regarding this case, there is an additional risk of rejection due to donor being deceased with both brain injury and cardiac arrest history
Q- How would you define DGF?
DGF is defined as a failure of the renal allograft to function immediately post-transplant, that needs at least one dialysis session within the first week. DGF rate increase with the increase in the warm or cold ischemic time.
Q- What is the effect of DGF on graft survival?
DGF is associated with impairment of graft survival as it causes graft injury through antigen-dependent and antigen-independent mechanisms (1)
Q- What is the effect of HLA DR mismatch on the outcome of transplantation?
HLA-DR compatibility between donor and recipient has an effect on graft survival, better DR match is associated with a better outcome.
HLA-DR mismatching has a substantial impact on the recipient’s graft survival (2)
1. Shoskes DA, Cecka JM. Effect of delayed graft function on short- and long-term kidney graft survival. Clin Transpl [Internet]. 1997;297–303. Available from: http://europepmc.org/abstract/MED/9919413
2. Shi X, Lv J, Han W, Zhong X, Xie X, Su B, et al. 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 Nephrol [Internet]. 2018;19(1):116. Available from: https://doi.org/10.1186/s12882-018-0908-3
Define DGF?
The most often used criteria are the need for dialysis (even for a single session) within the first week after kidney transplantation.
DGF is related to worse kidney transplant performance as well as poor and shorter graft survival after kidney transplantation.
-The longer the period of delayed graft function, the greater the likelihood of a gradual deterioration in 10-year death-censored graft survival.
A mismatch in the HLA-DR gene is connected with the poorest result (evident in the first 6 m).
HLA DR mismatch is related to a greater acute rejection rate, a shorter transplant survival time, and a higher risk of infection.
Shi X, Lv J, Han W, et al. What is the impact of human leukocyte antigen mismatching on graft survival and mortality in renal transplantation.
Opelz G, Döhler B. Effect of human leukocyte antigen compatibility on kidney graft survival: a comparative analysis of two decades.
How would you define DGF?
DGF is defined as the development of AKI in the first week of kidney transplantation, requiring dialysis intervention.
What is the effect of DGF on the graft survival?
he development of DGF is associated with worse baseline kidney transplant function and shorter graft survival periods, which are anywhere from 3 to 5 year shorter graft half-life as demonstrated in a recent single-center analysis. DGF is significantly associated with rejection-with or without borderline changes-within the first year.
DGF after live donor kidney transplantation,is uncommon but associated with significantly worse outcomes.
Recipients of DCD kidneys with DGF experienced a higher incidence of overall and death-censored graft loss compared with those without DGF. Strategies aim to reduce the risk of DGF could potentially improve graft survival in DCD kidney transplants.
What is the effect HLA DR mismatch on the outcome of transplantation?
HLA-DRB1 mismatch is a risk factor for rejection which is a strong predictor of graft failure. DGF by it self is multifactorial and is strongly linked to the IRI. DGF trigger TCMR , interfere with early introduction of CNI. the higher the mismatch at DR locus ,the higher the risk of acute rejection and graft loss.
References.
Q1:
DGF is defined as AKI during fist week after kidney transplantation which requires dialysis.
Q2:
DGF has undesirable effects on graft survival and can increase risk of rejection. Especially in this case of DCD with high creatinine and high KDPI.
Q3:
HLA-DR mismatch is associated with higher rate of about 12-15% for allograft loss. Higher rates of death-censored graft loss or all-cause graft loss were seen with HLA class 2 mismatched.
How would you define DGF?
-Delayed graft function (DGF) refers to the acute kidney injury that occurs in the first week of kidney transplantation, which necessitates dialysis intervention.
What is the effect of DGF on the graft survival?
– DGF is associated with worse kidney transplant function and poor and shorter graft survival . Immunosuppressive therapy, particularly the maintenance use of CNIs is frequently minimized or not utilized (due to nephrotoxicity ) that can lead to rejection due to under-immunosuppression.
What is the effect HLA DR mismatch on the outcome of transplantation?
-HLA-DR per mismatch was significantly associated with higher risk of overall graft failure. 1 and 2 DR mismatches were significantly associated with a 12 and 15% higher risk of overall graft failure, respectively.
References :
1.Siedlecki A, Irish W, Brennan DC: Delayed graft function in the kidney transplant. Am J Transplant 2011; 11: 2279–2296.
2.Zens TJ, Danobeitia JS, Leverson G, Chlebeck PJ, Zitur LJ, Redfield RR, et al: The impact of kidney donor profile index on delayed graft function and transplant outcomes: A single-center analysis. Clin Transplant 2018; 32: e13190.
3.Xinmiao Shi, Jicheng Lv, Wenke Han, Xuhui Zhong, Xinfang Xie, Baige Su & Jie Ding. 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 volume 19, Article number: 116 (2018).
How would you define DGF?
DGF can be defined by multiple ways but the most accepted definition is the need for dialysis in the first week post transplant. This definition has many limitations as it comprises many pathophysiological conditions ranging from a transient events such as hyperkalemia or hypervolemia to a more severe vascular and immunological complications.1,2
Other definitions ranging from straightforward dialysis based definition to more complex definitions based on graft function, these are:3
What is the effect of DGF on the graft survival?
DGF has been associated with poor clinical outcomes including acute rejection, death with functioning graft, graft failure, and chronic graft dysfunction. All these events will lead to decrease graft survival.
the incidence of DGF ranges from 20-50% in deceased donor, and 4-10% in live donor transplantation.4
DGF has a duration-dependent effect on graft survival and this effect varies according to the kidney donor profile index( KDPI). A study found that the longer duration of delayed graft function is associated with progressive worsening of 10 years death censored graft survival. and in kidneys with KDPI> 85%, all patients have poor graft survival regardless of the duration of DGF.1
What is the effect HLA DR mismatch on the outcome of transplantation?
HLA-DR mismatching represents a high immunological risk and is associated with inferior outcome.5 In a meta-analysis, 1 & 2 DR mismatches were associated with 12 & 15% higher risk of graft failure.6
References:
Excellent
DGF is defined as need for at least one dialysis in the 1st week posttransplant
DGF mostly due to ischemic reperfusion injury and development of ATN, and it prolongs hospital stay and shortens graft survival and it predisposes to rejection.
Mary Ann Lim and Roy D. Bloom. Medical Therapies to Reduce Delayed Graft Function and Improve Long-Term Graft Survival. CJASN January 2020, 15 (1) 13-15.
with any incremental increase in HLA -DR mismatch will increase graft failure with 12% , so there is negative substantial impact on graft survival with HLA-DR mismatch.
Xinmiao Shi, Jicheng Lv, Wenke Han, Xuhui Zhong, Xinfang Xie, Baige Su & Jie Ding. 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. 2018. volume 19, Article number: 116.
References:
1-up date medicine , kideny transplantion in adults , evaluationand diagnosis ofacute kidney allgraft dysfunction.2021
2–The Neglectable Impact of Delayed Graft Function on Long-term Graft Survival in Kidneys Donated After Circulatory Death Associates With Superior Organ Resilience
Michèle J de Kok 1 2, Dagmara McGuinness 3, Paul G Shiels 3, Dorottya K de Vries 1 2, Joanne B Tutein Nolthenius 1 2, Leonie G Wijermars 1 2, Ton J Rabelink 1, Lars Verschuren 4, Karen S Stevenson 5, David B Kingsmore 5, Martin McBride 6, Rutger J Ploeg 1 7, Esther Bastiaannet 2, Alexander F Schaapherder 1 2, Jan H Lindeman 1 2,Ann Surg. 2019 Nov;270(5):877-883.
3-The impact of kidney donor profile index on delayed graft function and transplant outcomes: A single-center analysisTiffany J Zens 1, Juan S Danobeitia 1, Glen Leverson 2, Peter J Chlebeck 1, Laura J Zitur 1, Robert R Redfield 1, Anthony M D’Alessandro 1, Scott Odorico 1, Dixon B Kaufman 1, Luis A Fernandez 1,Clin Transplant. 2018 Mar; 32(3): e13190.
doi: 10.1111/ctr.13190.
4-Nagaraja P, Roberts GW, Stephens M, et al. Influence of delayed graft function and acute rejection on outcomes after kidney transplantation from donors after cardiac death. Transplantation 2012;94:1218–1223. [PubMed: 23154212].
5- up to date medicine , kidneytransplantion in adults:HLA matching and outcome. accessed 2021.
Your definition of DGF is the most correct one.
DGF Definition:
Acute Kidney Injury that occur in the first week post kidney transplantation and require dialysis intervention.
What is the effect of DGF on the graft survival?
Impact of DGF on the graft survival:
What is the effect HLA DR mismatch on the outcome of transplantation?
Effect of HLA DR mismatch on the outcome of transplantation:
Referrences
1.Siedlecki A, Irish W, Brennan DC: Delayed graft function in the kidney transplant. Am J Transplant 2011; 11: 2279–2296.
2.Shi X, Lv J, Han W, et al. 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 Nephrol. 2018;19(1):116. Published 2018 May 18. doi:10.1186/s12882-018-0908-3
How would you define DGF?
What is the effect of DGF on the graft survival?
What is the effect HLA DR mismatch on the outcome of transplantation?
REFERENCES
1. Wu W, Famure O, Li Y, Kim SJ. Delayed graft function and the risk of acute rejection in the modern era of kidney transplantation. Kidney Int. 2015;88(4):851–8.
2. Gill J, Dong J, Rose C, Gill JS. The risk of allograft failure and the survival benefit of kidney transplantation are complicated by delayed graft function. Kidney Int. 2016;89(6):1331–6.
3. Lim WH, McDonald SP, Russ GR, JR, Ma MK, Pleass H, Jaques B, Wong G. Association between delayed graft function and graft loss in donation after cardiac death kidney transplants-a paired kidney registry. Transplantation. 2017;101(6):1139–43.
4. Opelz G, Döhler B. Effect of human leukocyte antigen compatibility on kidney graft survival: comparative analysis of two decades. Transplantation 2007; 84:137.
5. Wiebe C, Gibson IW, Blydt-Hansen TD, et al. Evolution and clinical pathologic correlations of de novo donor-specific HLA antibody post kidney transplant. Am J Transplant 2012; 12:1157.
6. Coupel S, Giral-Classe M, Karam G, et al. Ten-year survival of second kidney transplants: impact of immunologic factors and renal function at 12 months. Kidney Int 2003; 64:674.
7. Hussain SK, Makgoeng SB, Everly MJ, et al. HLA and Risk of Diffuse Large B cell Lymphoma After Solid Organ Transplantation. Transplantation 2016; 100:2453.
8. Caillard S, Lamy FX, Quelen C, et al. Epidemiology of posttransplant lymphoproliferative disorders in adult kidney and kidney pancreas recipients: report of the French registry and analysis of subgroups of lymphomas. Am J Transplant 2012; 12:682.
9. Nikkel LE, Hollenbeak CS, Fox EJ, et al. Risk of fractures after renal transplantation in the United States. Transplantation 2009; 87:1846.
Well done
How would you define DGF?
DGF is defined as the need for dialysis in the first week post transplantation.
What is the effect of DGF on the graft survival?
DGF was associated with higher rates of acute rejection, but impaired long-term graft survival even when rejection was absent and discharge creatinine was normal.
Effect of delayed graft function on short- and long-term kidney graft survival
D A Shoskes et al
What is the effect HLA DR mismatch on the outcome of transplantation?
HLA-DR per mismatch was significantly associated with a 12% higher risk of overall graft failure. Compared with 0 DR-mismatches, 1 and 2 mismatches were significantly associated with 12 and 15% higher risk of overall graft failure, respectively.
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 et al