1. A 51-year-old male DM, HTN, IHD had received 3 cadaveric kidney transplants before. The first and second graft lasted 6 and 8 years respectively, both failed secondary to chronic CNI toxicity. The third kidney failed 2 years back due to chronic ABMR. He received basiliximab, alemtuzumab and ATG inductions for his previous 3 transplants. His cPRA 93%, he was offered a kidney from his sister with 000 mismatch no DSA. His cross match is shown below.
- Explain why the crossmatch is negative
- Will you consider desensitization for this patient?
- What is your induction plan, and why?
- Will you consider protocol biopsies for him, if yes why?
- Will you consider steroid free regimen for him, if yes or no, why?
- What is the main surgical concern in this patient?
(Curtsey Dr Mohamed Gafar, KSA)
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Explain why she has a negative crossmatch
she has a negative cross match which means she has no antibodies in her serum towards the HLA donor’s antigen. So, in this case, she has a negative cross-match to Tand B cells .
Will you consider desensitization for this patient
This patient has a very high cPRA 93% and a negative cross-match and zero mismatches. in such cases, we may go for a transplant without desensitization.
What is your induction plan? And why?
Despite of the 3 previous transplants, this patient will consider a low immunological risk for that we may go for basiliximab for induction.
Will we go for a protocol biopsy for him? And why?
Yes will I strongly recommend protocol biopsy in a such patient, as he has two failed grafts with CNI toxicity .so we may need to detect these changes early unless we may use CNI free regime like belatacept. Adding to that he has a history of rejection.
Will you consider a steroid-free regime? And why?
With this patient’s history with the previous three transplants, I will not go for steroid free as he is having a past history of rejection.
What is the main surgical concern in this patient?
He has three previous transplants and this will leads to a lot of adhesions with technical problems in the insertion of the new graft AND TRANSPLANTED OF THE NEW URETERS THIS MAY RAIS A LOT OF POST operative UROLOGICAL complications.
A lot of vascular problems regarding anastomosis of the fourth graft
The crossmatch seeks to assess whether there is formation of antibodies by the recipient when in contact with the HLA antigens of the donor’s cell membranes. As the donor is his sister, there was a reasonable chance of this compatibility.
Despite the high cPRA (population investigation), the individual assessment did not show HLA or ABO incompatibility (favorable for being first-degree relatives), or even high DSA values that could indicate desensitization.
As a low-risk patient, we could perform induction with corticosteroids or basiliximab only.
Yes, despite being a low-risk transplant, a biopsy protocol would be performed because the patient had a previous episode of rejection and in maintaining this we will avoid CNI due to previous events, adding risk for this transplant.
No. Due to the need to replace the CNIs, the use of steroids will be important in the maintenance scheme.
Given the number of previous transplants, the patient may present urological difficulties, for example: adhesions in sites already used, insertion of the ureter. It may also present vascular difficulties due to the size of the native vessels, the performance of anastomoses (end-to-end X end-to-side)
Explain why the crossmatch is negative
000 Mismatch
however high PRA , there is no donor specific antibodies
Will you consider desensitization for this patient?
No need for desensitization as
As cross matches are negative in addition to absence of DSA
What is your induction plan, and why?
However excellent mismatch , negative cross matches with absence of DSA
as it’s the fourth time for kidney transplantion with possibility of presence of non HLA antibodies also history of chronic ABMR so I will go for Induction with Basiliximab or ATG .
Will you consider protocol biopsies for him, if yes why?
Protocol biopsy may be considered as there is history of CNI toxicity and hx of Chronic ABMR .
Will you consider steroid free regimen for him, if yes or no, why?
Yes I will use
to decrease the target level of CNI due to previous history of recurrent CNI toxicity
What is the main surgical concern in this patient?
detection space for transplantion due to presence of previous 3 allograft
Adhesions and Intra-abdominal fibrosis
Assessment of the recipient blood vessels for anastomosis
1- the current case has negative cross match as no HLA mismatch , it is 000 plus absence of DSA.
2- He does not need desensitization as long as the cross match is negative despite being the 4th transplant and Capra is 93% means that he has only chance of 7% to get compatible donor.
3. Induction therapy better to have basiliximab as cross match is negative and has 000 mismatch, and the patient also has high risk for infections and malignancy after repreated and prolonged courses of immunosupressives in the previous transplants.
4. I will prefer to have protocol biopsy for early detection of rejection and CNI induced nephrotoxicity.
5.I think that steroid free protocol will be risky in this patient and is better to use TAC based triple immunosupressives
-also, use of mTORi can be used with CNI minimization protocols after the period of 1st month and after wound healing.
6- the main surgical concerns are having no room for the 4th graft in addition to difficult vascular anastomosis , in addition to the extensive fibrosis and adhesions after repeated Transplantation which will eventually leads to more complex surgical procedure and prolonged ischemia time.
T cell > 52 considered positive and B cell > 55 considered positive, the patient T and B cell are below that level hence it is reported negative.
No, as the patient DSA is 0 and X match negative.
Pulse steroid with Basiliximab
Yes in view of having CNI toxicity in 2 of his previous transplant , better to be detected early and hence managed properly before losing the graft.
Also to detect ABMR.
With his past history, I would not, I prefer to keep the steroid to avoid increasing his CNI doses.
The third and fourth transplantations showed 1- and 5-year graft survivals of 88% and 76.4% and 71.4% and 42.9%, respectively
Recipients of a third transplant pose a surgical challenge because the operation takes place in an already deceived body. Hence 3 main complications may be encountered
Presence of
1-fibrosis in view of previous 3 surgeries.
2- lacking of proper spacing for the new allograft.
3- good vessels for allograft innervation
Surgical complications were reported in up to 41% of patients, according to L. Izquierdo et al (2010). Specifically, vascular complications and the need for blood transfusions. Other factors include technical failures, increased comorbidity as a result of extended dialysis, and increased rejection rates as a result of patient sensitization.
For the new grafts, the surgeons used either the right or left fossa, as well as an orthotopic location. A perirenal hematoma was the most common complication; others were minor, such as a urinary fistula, lymphocele, ureteral stenosis, artery kinking that required surgery, and venous thrombosis with graft loss.
As stated previously, this technique may be useful in certain cases, such as obesity or re-transplantation with poor vascular status. It is a difficult procedure reserved only for patients who were unable to use iliac fossae.
References:
L. Izquierdo, L. Peri, M. Piqueras, I. Revuelta, R. Alvarez-Vijande, M. Musquera, F. Oppenheimer and A. Alcaraz. Third and Fourth Kidney Transplant: Still a Reasonable Option. ransplantation Proceedings, 2010-09-01, Volume 42, Issue 7, Pages 2498-2502
Potential recipient is 000 mismatch with no DSA and hence crossmatch is negative
As he has no DSA, desensitization is not necessary in this situation. cPRA predicts getting a suitable donor (7% chance in this case), instead of sensitization risk.
Even though there is a low immunological risk due to the 000 mismatch, with given history of three previous transplants, I would prefer ATG induction.
Because of three previous transplants and one graft rejected due to chronic ABMR, I will consider a protocol biopsy.
I’d like to start with maintenance triple drug immunosuppression (Tacrolimus, MMF, and prednisolone), and after a month (when wound healing and stable graft function achieved), I’d like to switch to mTOR inhibitors (a CNI-free regimen) due to a history of graft loss due to chronic CNI toxicity.
Because of previous 3 transplants, surgical challenges are high:
Another option is considering an orthotopic transplant in this patient
Explain why the crossmatch is negative
as there is no DSA and 000 mismatch
Will you consider desensitization for this patient?
no I will not consider desensitization as cross match is negative and no DSA
What is your induction plan, and why?
the patient is high risk as this is the forth transplant , also history of chronic ABMR
due to possibility of non HLA antibodies
induction with ATG
Will you consider protocol biopsies for him, if yes why?
it is better for early detection any type of rejection or drug toxicity
Will you consider steroid free regimen for him, if yes or no, why?
patient need triple immunosuppressive tac based
What is the main surgical concern in this patient.
first no space for the forth, also adhesions and fibrosis
must be assessed by CTA
A negative crossmatch means that the
recipient’s antibodies do not attack the donor’s which means the kidney is suitable for transplant.this occur in this case because ether the anitigens are not highly expressed in the donor lymphocytes. For the sensitized renal transplant candidate, finding a donor for whom the candidate has no or very low levels of preformed HLA antibodies is the preferred approach and is associated with better allograft outcomes. (1)
Will you consider desensitization for this patient?
No . This patient has PRA of 92%. Desensitization to HLAs involves treatment with immunomodulating therapies designed to reduce levels of anti-HLA antibodies in order to make kidney transplantation possible. (2) This patient has most likely non HLA antibodies. The risk outweigh the benefit.
What is your induction plan, and why?
This patient is considered high risk, because of the previous 2 kidney tanspalnt, with a history of AMR. So, ATG is preferred.
Will you consider protocol biopsies for him, if yes why?
Even in the setting of a negative crossmatch, presence of DSA is associated with decreased allograft survival(1). He needs protocol biopsies to detect AMR early on.
Will you consider steroid free regimen for him, if yes or no, why?
This patient has high risk of rejection due to the failed previous 2 transplant and history of AMR.so steroid free regimen carries a high risk of graft loss.The largest epidemiological study to date has reassured the transplant community that the selective use of steroid-free immunosuppression in kidney transplant patients provides no inferior outcome in patient and graft survival at intermediate term. Steroid-free regimens have the potential to improve cardiovascular risk profile. The challenges that remain are to identify the subset of kidney transplant patients who may not benefit from steroid-free immunosuppression and to demonstrate the survival advantage of steroid-free immunosuppresion in suitable kidney transplant candidate(3)
What is the main surgical concern in this patient?
In a third transplant, both graft and patient survival are significantly inferior to primer ones. Careful selection is required to minimize the patient risk and graft loss.(4)
A study on the 30 third transplantations was performed .Recipient mean age was 40 years (range, 21-57 years). Twenty-one patients (70%) had hepatitis C virus infection and 16 (53%) were hypersensitized (panel-reactive antibodies [PRA] >50%), with a mean time on dialysis since second graft loss of 65 months (range, 1-250 months). The imaging tests showed iliac calcifications in 14 patients (47%). The graft was preferably placed in the iliac fossa (27/30). Twenty-five patients (83%) had prior graft nephrectomy and transplantectomy was performed at the same surgery in 2 cases. Immunosuppressive protocol was quadruple therapy in 23 patients (77%). At a mean follow-up of 43 months, 24 grafts were functioning. Mean serum creatinine was 1.5 mg/dL and Modification of Diet in Renal Disease (MDRD) clearance was 64.5 mL/min. Six grafts were lost: 3 due to acute rejection, 2 due to chronic allograft nephropathy, and 1 due to venous thrombosis. Four patients died: 2 due to infectious complications, 1 due to hepatic encephalopathy, and 1 to an accident with a functioning graft. The acute rejection rate was 30% and 4 patients had an acute humoral rejection episode. The main surgical complication was lymphocele in 7 cases (23%). Estimated survival at 5 years was 76% for grafts and 86% for patients. Graft survival worsened among patients with PRA > 80% and among those who had lost the previous grafts in the first month posttransplantation (P < .05). In conclusion, the outcomes of the third kidney transplantations was promising. However, worse graft survival should be expected among hyperimmunized patients and among those who had lost previous grafts early in their course.(5)
1-Douglas S. Keith, Gayle M. Vranic, Approach to the Highly Sensitized Kidney Transplant Candidate, CJASN Apr 2016, 11 (4) 684-693; DOI: 10.2215/CJN.
2-Abu Jawdeh BG, Cuffy MC, Alloway RR, Shields AR, Woodle ES. Desensitization in kidney transplantation: review and future perspectives. Clin Transplant. 2014 Apr;28(4):494-507. doi: 10.1111/ctr.12335. Epub 2014 Mar 12. PMID: 24621089.
3-Luan FL, Steffick DE, Ojo AO. Steroid-free maintenance immunosuppression in kidney transplantation: is it time to consider it as a standard therapy? Kidney Int. 2009 Oct;76(8):825-30. doi: 10.1038/ki.2009.248. Epub 2009 Jul 22. PMID: 19625995; PMCID: PMC3831511
4-Telkes G, Piros L, Szabó J, Huszty G, Eitler K, Kóbori L. Outcomes of first versus third kidney transplantations: propensity score matching and paired subgroup analysis-a single-centre experience. Langenbecks Arch Surg. 2021 May;406(3):863-871. doi: 10.1007/s00423-020-02063-y. Epub 2021 Jan 17. PMID: 33454840; PMCID: PMC8106582
5-Blanco M, Medina J, Gonzalez E, Dominguez M, Rodriguez A, Pamplona M, Andres A, Leiva O, Morales JM. Third kidney transplantation: a permanent medical-surgical challenge. Transplant Proc. 2009 Jul-Aug;41(6):2366-9. doi: 10.1016/j.transproceed.2009.06.105. PMID: 19715921.
1.Crossmatch testing is to identify any preformed donor-specific anti-human leukocyte antigen (HLA) antibody (DSA) present in a patient’s serum that is directed against a particular donor.
000 mismatch and there is no DSA.
2.Crossmatch is negative and no DSA, no role for desensitization
3.Induction plan, the patient is highly sensitized and cPRA 93%,
Induction of highly Sensitized patients by T cell depleting therapies (Thymoglobulin or Almetuzemab) leads to a better graft survival and low rejection risk.
Brennan et al., found that rejection rates were halved in high‐risk patients received anti-thymocyte globulin versus Basiliximab at 1 year and at 5 year, also the severity of acute rejection events were extremely lower with anti-thymocyte globulin.
4.Yes,protocol biopsy is needed
T cell and antibody-mediated rejection can have a subclinical phase, protocol biopsies provide an early opportunity to intervene before the onset of clinical allograft dysfunction. Protocol biopsies are usually done after reperfusion to establish baseline, between 3 and 6 months to identify subclinical rejection, and at 6-12 months to assess chronicity and persistent inflammation that have prognostic implication. Treatment of both subclinical T cell and antibody-mediated rejection prevents progression of rejection and development of interstitial fibrosis/tubular atrophy or transplant glomerulopathy.
Protocol biopsies are more likely to benefit patients at higher risk for rejection, including those who are highly sensitized, transplanted across donor-specific antibody barriers, or on calcineurin inhibitor/corticosteroids sparing regimens.
5.NO, the patient highly sensitized and at high risk for rejection, steroid free protocols cannot be used.
The analysis data taken from OPTN/UNOS revealed that the using of steroid as maintenance therapy for patients with PRA more than 60% was associated with improved death censored graft survival and without negative effect on patient survival.
6.surgery is done in previously operated iliac fossae , scarring and fibrosis may make identification of correct tissue planes more difficult.
Flow cytometry crossmatch is a wet crossmatch in which a patient’s plasma (in which preformed antibodies are present) is mixed with the potential donor’s lymphocytes (on which HLA and non-HLA antigens are on its surface). FXCM negative crossmatch means recipient plasma doesn’t contain antibodies against this specific donor or antibody levels are very low to be detected.
As long as wet FCXM is negative, no role for desensitization
The immunological risk of this patient is considered low to moderate risk. Although there is no mismatch but they are not identical twins these means still there is still a difference in the antigens expressed on the cell surface. Regarding the patient’s previous history he was exposed to multiple different foreign antigens because of the previous 3 kidney transplants and also mostly he received them before a blood transfusion which make this patient highly sensitized and this was shown in the CPA result of 92%. I would prefer to go with basiliximab and methylprednisolone induction followed by maintenance triple immunosuppression TAC, MMF, and steroids.
Protocol biopsy considers a useful tool that provides early diagnosis of any underlying pathological process but is still an invasive maneuver associated with complications. At the center experience, we usually follow up with our patients with UE1, urine PCR, CBC, TAC trough level, and DSA. Biopsy only upon indications
If he indicated for steroid-free regimen based on any finding during patient preparation so, he will need depleting induction by ATG to afford good immunosuppression coverage for this highly sensitized patient. Otherwise, I would prefer to keep him on triple immunosuppression with steroids included.
This is the 4th kidney transplant which means the operation will be challenging regarding
A lot of adhesion, bleeding
Small roaming space for the new graft with the possibility of nephrectomy of one of the previous kidneys.
Vessels will be atherosclerotic and may afford poor perfusion of the graft
Bladder anastomosis will be difficult because of adhesions and multiple suturing of the bladder
References:
1-Abu Jawdeh BG, Cuffy MC, Alloway RR, Shields AR, Woodle ES. Desensitization in kidney transplantation: review and future perspectives. Clin Transplant. 2014;28(4):494-507. doi:10.1111/ctr.12335.
2-Ajlan, A., Aleid, H., Ali, T.Z. et al. Standard induction with basiliximab versus no induction in low immunological risk kidney transplant recipients: study protocol for a randomized controlled trial. Trials 22, 414 (2021). https://doi.org/10.1186/s13063-021-05253-1.
3-Wilkinson A. Protocol transplant biopsies: are they really needed?. Clin J Am Soc Nephrol. 2006;1(1):130-137. doi:10.2215/CJN.00350705.
4-Haller MC, Royuela A, Nagler EV, Pascual J, Webster AC. Steroid avoidance or withdrawal for kidney transplant recipients. Cochrane Database of Systematic Reviews 2016, Issue 8. Art. No.: CD005632. DOI: 10.1002/14651858.CD005632.pub3. Accessed 16 September 2022.
Previous 3 transplantations, the last one was lost with ABMR 000 mismatch donor.
The index case has a high PRA of 93%. PRA high is due to the presence of anti-HLA ab, these AB may be either donor-specific or donor non-specific. This recipient has 7% chance to get a donor for which he has no AB.
The cross-match is negative, it could be due to no DSA, and negative T and B cells IgG by MFI. Which means the recipient has no antibodies against his donor lymphocyte cells.
CXM negative can be due to low titer DSA or non-complement fixing Ab.
As the patient is at high risk due to 3 previous transplantations, and last one lost due to ABMR, it is ideally SAB assay should be done, to exclude clinically relevant low titer DSA.
Sensitization is not necessary in this case, as the cross-match is negative and no DSA.
Induction therapy in this moderate-risk patient according to his immunological status (negative CXM, DSA) is Basiliximab and methylprednisolone.
Protocol biopsy: I will do high risk had H/O ABMR
No role for steroid-free regime
Surgical challenges:
As he has 3 times transplantations, there is fibrosis and adherence. Changes in the anatomy.
The place of the new graft can be difficult, vascular anastomosis to iliac vessels and the ureter and UB anastomosis also difficult and needs an expert surgeon.
Explain why the crossmatch is negative
Mismatch 000, no DSA, DSA nil, negative FCX, Low MFI (52 T-cell, 55 B-cell).
It could be related to non-HLA Ab.
Epitope mismatch could be used as a more sensitive method for compatibility between don and recipients.
Will you consider desensitization for this patient?
The target of desensitization is to achieve a negative cross-match and in this case the cross-match is already negative, so no need for desensitization.
What is your induction plan, and why?
It is a low risk immunological offer (000 mismatch, no DSA, negative cross match) —à Basiliximab (IL2R antagonist) is an option. However, it is still considered high risk transplant because it is the 4th, I will opt for ATG.
Will you consider protocol biopsies for him, if yes why?
Protocol biopsy is considered because of history of CNI toxicity and chronic AMR.
Will you consider steroid free regimen for him, if yes or no, why?
I will use steroids because of history of CNI toxicity.
What is the main surgical concern in this patient?
This will be his 4th transplant, so it is highly challenging operation because of previous 3 transplants.
It is expected to face excessive scarring, adhesions. Vascular anastomosis will be difficult with expected calcified vessels. Uretero-vesical anastomosis will be another challenge. The recipient may need previous graft nephrectomies. Expected technical difficulties can lead to prolonged ischaemia time which will affect the graft and patient outcomes.
This highly sensitized donor with cPRA 93% which mean that he has antibodies against 93% of the donor pool database is quiet lucky to have a suitable donor (his sister) which is one of the remaining 7% He does not have DSA specifically to her, that’s why the cross match is negative. This does not mean he does not have antibodies, as he may still have non DSA or non HLA antibodies. Epitope matching as requested by Edwards and his colleagues for this highly sensitized patients and identifying acceptable and unacceptable antigens may be required using SAB C1q assay to identify its complement binding ability and its clinical relevance
The cross match is negative, no DSA is present. Therefore, no desensitization is required.
Induction therapy with Basiliximab would be my choice due to absence of DSA and 000 mismatch with the donor (low immunological risk).
In view for his previous history of graft losses and being highly sensitized, protocol biopsy should be considered with C4d staining for early detection of subclinical rejection. However, it is a center based. Some centers follow protocol biopsy, others go for checking serum creatinine and proteinuria and due biopsy as needed.
In view of the previous history of 3 graft losses and the last was due to chronic ABMR, I would not be using a steroid-free regimen.
Finding a suitable place to place the graft due to previous fibrosis, adhesions and distorted anatomy and graft nephrectomy may be required resulting in prolonged cold ischemia time.
challenges with vascular anastomosis and Ureteroneocystostomy.
Poor wound healing, Wound dehiscence and increased risks of infection with immunosuppression.
References:
1. Benkö T et al. Long-term outcome of third, fourth and fifth kidney transplantation: technical aspects and immunological challenges. Clin Kidney J. 2019 Feb 25;12(6):895-900.
· Q1: Because there is no donor specific antibody and the donor and the recipient are zero mismatch.
· Q2: No, this patient doesn’t need desensitization because of no DSA.
· Q3: Induction with basiliximab is reasonable since they are zero mismatch with no DSA.
· Q4: Protocol biopsy is suggested since the risk of subclinical rejection is still high duo to third TX.
· Q5: I wouldn’t recommend steroid-free regimen.
· Q6: The two main surgical concerns are:
1: transplant nephrectomy for spacing
2: Investigation of iliac vessels by CTA.
his had no mismatch so there’s no DSA that why the crosshatch is negative
No I will not did desensitization for just high PRA
ATG induction because this the fourth transplant so high risk
yes because he is on high risk of rejection
No his maintenance immunosuppressive therapy should contain steroid
The cross match is negative due to the absence of DSA, mismatch is zero .the calculated PRA expresses antibodies but not directed to his sister’s HLA, probably resulted from previous transplantations.
The need of desensitization in such patient despite having previous 3 failed transplants is not indicated, being of better matched the fore coming living kidney, no DSA, just good induction therapy and triple immunosuppressive regimen according to the centre’s protocol.
The induction plan should be optimum induction by basiliximab (no DSA,minimal side effects,zero mismatch) along with triple immunosuppressive regimen(tacrolimus based ,MMF and corticosteroids) keeping in mind that one of them was rejected due to antibody mediated rejection necessitating frequent close monitoring.
Protocol biopsies are favorable in such patients, to detect any tendency for rejection episodes, as it is his fourth transplant, precious kidney from related donor, monitor early drug toxicity exposure effects, viral infections later on if occult.
Considering steroid free regimen for this patient is not a wise choice, to extend the survival of this fourth related kidney graft, possibility of rejection is not uncommon (history of failed graft due to ABMR), also to synergize the effect of other immunosuppressive therapy with minimal toxicity offered.
The main surgical concern for this patient:
Previous adhesions , distorted anatomy occurred by the previous 3 operations, site of vascular anastomosis may be challenging requiring highly expert vascular team ,the space for the fore coming kidney may be difficult to obtain in the intraoperative setting urges the need of experienced urological team ,all these factors are additive factors to the risk of long extension of the operation with more ischemia time and increased bleeding tendency which may more units for blood transfusion , the potential hazards of injury or tear of surrounding tissues cannot be guaranteed.
Explain why the crossmatch is negative
The HLA missmatch is 0.0.0 and no DSA
Will you consider desensitization for this patient?
NO, although this pt is highly sensitized with cPRA 93% but still there is low risk of AMR with with this 0.0.0 mismatch.
What is your induction plan, and why? Basiliximab
Will you consider protocol biopsies for him, if yes why?
I will consider protocol biopsies to make sure that the pt do not has rejection that has not been picked up by the blood tests or to see if the grafted kidney is being affected by the medication since this pt has two previous rejection episodes due to CNI toxicity.
Will you consider steroid free regimen for him, if yes or no, why?
No, I will not consider steroid free regimen for this pt because this pt has historyof 3 previous transplant rejection.
What is the main surgical concern in this patient?
The fourth transplants are significantly more complex Patients are often highly sensitized, comorbid with limited surgical options due to the previous operations, immunosuppression and long periods on dialysis[1].
The surgical risks include: prolonged duration of surgery, prolonged second warm ischemia time (WIT-2), greater amount of blood loss, and an increased risk of iliac vessels injury, due to the postsurgical adhesions. Combined with more comorbidity and higher sensitization grade of the recipient this may lead to worse kidney transplantation outcomes [2].
It is important to note that surgical procedures on previously operated iliac fossae can present additional technical challenges. Relevant scarring and fibrosis may make identification of correct tissue planes more difficult, necessitating vascular surgery and risking complications. Cold ischaemia time (CIT) and warm ischaemic time (WIT) may be extended because of the complex and prolonged anastomotic procedures and have been associated with longer overall operative time, impacting morbidity [3].
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REFERENCES
[1] Ahmed Halawa. The third and fourth renal transplant; technically challenging, but still a valid option. Ann Transplant. 2012.
[2] Piotr Domagala, Tamar A.J. et al. Surgical Safety and Efficacy of Third Kidney Transplantation in the Ipsilateral Iliac Fossa
[3] Tamas Benkö, Patrizia Halfmann, et al. Long-term outcome of third, fourth and fifth kidney transplantation: technical aspects and immunological challenges
Clinical Kidney Journal, V 12, Iss, 2019, 895–900,
1) No DSA
2) Not to consider desensitization.
3) Induction : Basiliximab. No DSA. 000 mismatch.
4) Yes for protocol biopsy. For differential diagnosis of graft failure eg ABMR.
5) Suggested for steroid regimen. High rejection risk.
6) Previous transplant scar adhesion render technical difficulty for this transplant.
Q1-Explain why the crossmatch is negative?
The crossmatch is negative because the recipient has no DONOR SPECIFIC ANTIBODIES .
Q2- Will you consider desensitization for this patient?
No , as the patient has no DSA there is no need for desensitization .
Q3- What is your induction plan, and why?
Although this patient has tree previus rejected graft and the last one was due to ABMR ,
But there is no DSA and 000 mismatch this means that this patient can be considered as low risk group and can be treated by basiliximab induction . with close monitoring .
Q4- Will you consider protocol biopsies for him, if yes why?
Yes I do , because this is the fourth transplant and the last graft was lost because of immunological rejection means that patient has a risk of rejection protocol biopsy is helpful in diagnosing the early subclinical rejections .
Q5- Will you consider steroid free regimen for him, if yes or no, why?
No I will not, because this patient at high risk of rejection with steroid free regimen.
References:
1- Lan J H, Kadatz M, Chang DT, et al. Pretransplant Calculated Panel Reactive Antibody in the Absence of Donor-Specific Antibody and Kidney Allograft Survival. CJASN 16: 275–283, February, 2021.
2- Halawa A. The third and fourth transplant; Technically difficult, but still a valid option. Ann Transplant. 2012; 17(4):m125-1346- What is the main surgical concern in this patient?
*The crossmatching tests the presence of specific antibodies in serum of recipient against the donor.
The crossmatching is negative due to absence of Donor specific Antibodies. The patient expresses antibodies that are not directed against his sister evidenced by his high cPRA.
*There is no indication for performing desensitization as the cross match is –ve , no DSAs.
This is a highly sensitized patient, HO 3 previous transplants with cPRA 93% .
Induction therapy by rATG.
*I wouldn’t implement protocol biopsy , but close follow up of renal function , follow up post transplant DSA’s after 3 months then every 6 months .
*I wouldn’t implement steroid free regimen in this patient with HO 3 previous failed transplants.
* Previous multiple ureterocystostomy , space for the current graft , bleeding , atherosclerotic vessels will remain major surgical obstacles .
References:
1-MorathC,Döhler B, KälbleF, et al. Pre-transplant HLA Antibodies and Delayed Graft Function in the Current Era of Kidney Transplantation Front. Immunol., 26 August 2020.
2-Redfield RR, Scalea JR, Zens TJ, et al. The mode of sensitization and its influence on allograft outcomes in highly sensitized kidney transplant recipients. Nephrol Dial Transplant 2016; 31:1746.
3-Opelz G, Collaborative Transplant Study. Non-HLA transplantation immunity revealed by lymphocytotoxic antibodies. Lancet 2005; 365:1570.
Explain why the crossmatch is negative
the crossmatch is negative as there are no DSA.
Will you consider desensitization for this patient?
The donor is sister with 000 mismatch and no DSA, desensitization is not required
What is your induction plan, and why?
Since, the patient is now for 4th transplant and has sensitization due to previous three transplants, induction would be by Inj ATG
Will you consider protocol biopsies for him, if yes why?
Since the patient has high immunological risk due to previous transplants, we would monitor graft with renal function closely and SOS DSA
We would have very low threshold for graft biopsy.
Will you consider steroid free regimen for him, if yes or no, why?
Since the recipient has sensitization by three transplants and on the backdrop of chronic ABMR, steroid free regimen would not be a good idea.
What is the main surgical concern in this patient?
Halawa A. The third and fourth renal transplant; technically challenging, but still a valid option. Ann Transplant. 2012 Dec 31;17(4):125-32.
No antibodies *DSA
No, zero mismatch crossmatch is negative
Basiliximab , low risk
Yes, he has previous multiple loss of transplant due to causes that may be detected by biopsy before change in RFT (subclinical)
No, despite being no mismatch and negative cross match in this transplant, he still has hx of 3 previous rejection.
Space for new graft.
Vascular anastomosis
*The -ve cross-match means he has no specific antibody against his LRKD -ve FCM crossmatch.
*Although the patient has compatible HLA Donor with zero mismatch but, he is considered highly sensitized as he has CPRA 93% with history of 3 transplants. This recipient does not need any desensitization as he has -ve crossmatch, no DSA.
*The recipient has 0 mismatch between his LRKD , with no DSA, more-over history of previous massive induction regimen in previous transplants but patient highly sensitized so; Basiliximab will be sufficient with close post-operative follow-up.
*I will consider off-course protocol biopsy for such patient although its risks to catch any ABMR.
* I will not consider steroid free protocol in that recipient with history of 3 transplants due to the high risk of rejection. Steroid free regimens will make me increase the CNI dose and level although patient has history of rejection due to CNI toxicity in the previous 2 grafts.
*The surgical concern will be directed towards 1.finding a space for new graft ,The patient will need to do nephrectomy at same set of transplantation by expert team of vascular and urologist after pre-operative decision regarding the applicable side regarding anatomy and vasculature.2. Even-more , we should take into consideration: There maybe difficulty in vascular anastomosis which may lead to anastomotic leak. Urinary leakage as well. 3.There is high incidence of IO in the post operative period due to old massive post-operative adhesions which may be present.
This patient had 3 previous transplants, the first and second transplants were lost due to chronic CNI toxicity and the 3rd transplant due to Chronic ABMR. This patient is currently offered a live related renal transplant with full match or zero mismatch, with no DSA although he is highly sensitized. He has a cPRA of 93% and he will have a positive cross match to most of the 93% of the patient donor pool, but his sister is within the 7% of the donors against which he is compatible…
Explain why the crossmatch is negative?
From the provided results in form of HLA 000 mm and NO DSA, cross match is expected to be Negative but for confirmation SAB (single antigens bead) better to done.
Will you consider desensitization for this patient?
Desensitization is not required in this case while HLA mm 000, NO DSA and negative cross match.
What is your induction plan, and why?
HLA mm000, NO DSA and negative XM categorized the patient as Low immunological risk So Basiliximab is suitable for induction, but it is important to put in mind this is the fourth episode of K-TX and the patient is highly sensitized and c-PRA is 93%.
Will you consider protocol biopsies for him, if yes why?
Yes I will consider the biopsy protocol when the CNI are included in the maintenance medications with that history of rejection.
Will you consider steroid free regimen for him, if yes or no, why?
NO I will not consider steroid free regimen for this patient because he had history of three transplants previously and rejection episode. Also having high percent of c-PRA.
What is the main surgical concern in this patient?
An important surgical concerns include: determination of suitable opening in the presence of previous surgeries which were associated with adhesions and fibrosis putting in consideration the adequate space for new graft.
The negativity of crossmatch is due to being non-donor-specific. His sister is fully matched. son, the risk of hyperacute or acute rejection is very low. For this reason, we do not need desensitization, but we need induction. Induction can be with a less potent agent like Basiliximab or low-dose ATG. I prefer to keep ATG for the future.
Steroid avoidance is not logical in a sensitized patient with high cPRA. Rather than protocol biopsy, close monitoring and biopsy on need may be better.
two transplantations will complicate the surgery, we need a space for the third kidney, and we may have problems with anastomosis.
Negative cross match:
Neither mismatching nor detected DSA so it is fully matching.
Desensitization:
Not needed as cross matching is negative.
Induction plan:
As mentioned above , being low immunological risk , induction with basiliximab & methyl prednisolone will be suitable.
Protocol Biopsy: scheduled biopsies are needed considering previous rejection.
Steroid free regimen:
I would continue on steroids as he is at high immunological risk (three previous transplant and the last one with chronic ABMR)
Main surgical concern:
spacing ( need for nephrectomy), adhesions, vascular anastomosis difficulties.
The negative cross match indicate that he has no specific antibody against his sister. The negative flow citometry is also explained by the low MFI (Threshold is 2,500 MFI)
I would not consider this patient for desensitization though he is an high risk patient in view of his previous 3 transplant. However, the cross-match is negative with no DSA. The aim of desensitization is to increase transplant candidates’ access to transplantation by decreasing HLA antibody and the number of unacceptable antigens for listing to decrease known DSA.
He is at low immunological risk (HLA mismatch & negative cross-match mean) therefore I would organize Basiliximab induction with Pulse Methyleprednislone and maintenance Immunosuppression (TAC- MMF and steroid).
Will you consider protocol biopsies for him, if yes why?
I would organize a biopsy for early detection of subclinical rejection in view of his previous three transplant (high immunologic risk) chronic CNI toxicity and Chronic antibody-mediated rejection with negative DSA
I would continue on steroids as he is at high immunological risk (three previous transplant and the last one with chronic ABMR)
Anatomical reason:
-space for the new transplant
-Adhesions,
-wound healing
-Infections (patient has diabetes and he is on long term immunosuppression)
-Anastomosis both vascular and urological (vascular disease in view of diabetes, limited anatomical space to create anastomosis from previous transplant and long term immunosuppression).
There is no DSA. we need to see the full result of luminex testing to know if there is low titer anti-HLA antibodies that do not cause a positive CXM.
As long as CXM is negative and there is no DSA, there is no need for desensitization.
induction with basiliximab 20 mg at day 0 & 4 can be used in addition to MP pulse and maintenance IS with Tac, MMF, and prednisolone.
Yes, the patient is sensitized from the previous 3 transplants, the last one is lost due to ABMR, so careful evaluation with protocol biopsy is required.
No, studies recommend steroid free regimen for low risk patients, this patient had 3 failed grafts and the last one lost due to ABMR.
spacing ( need for nephrectomy), adhesions, vascular anastomosis difficulties.
Negative cross match
Neither mismatching nor detected DSA so it is fully matching.
_ Desensitization :no need as cross matching is negative
_ Induction Protocol:
Although patient has high c PRA percentage ,and history suggestive of high immunological risk, basiliximab will be enough based on current immunological assay; to be considered not high risk patient.
_ Protocol Biopsy: scheduled biopsies are needed considering previous rejections
including ABMR..
_Steroid free regimen:
Not used due to previous rejections and CNI intoxication, targeting lower CNI trough levels using triple regimen.
_Surgical concerns: include nephrectomy for space, adhesions, technical surgical issues and wound healing.
sorry by mistake
_ Negative cross matching:
Neither mismatching nor DSA was detected
_ Desensitization:
Not needed as cross matching is negative
_ Induction protocol:
Basiliximab will be enough, not considering high immunological risk due to negative XM and absence of DSA although high c PRS and history suggestive of high immunological risk; not present in the current situation.
_ Protocol Biopsy:
Scheduled biopsy will be needed due to several previous rejections including ABMR one.
_ Steroid free regimen:
Use of triple regimen including steroid is needed based on previous rejections and CNI toxicity.
_Surgical concerns :eg
Need for nephrectomy for space ,presence of adhesions, vascular calcifications ,healing issues and ureteroneocystostomy.
– Presence of high PRA means presence of anti HLA ab , which may be donor specific or non specific
– Here the crossmatch is negative as there is no DSA & negative T & B cell igG by MFI .
– It means that the potential recipient here has no perfomed AB against his potential donor lymphocytes .
– Generally this patient may considered as high immunological risk due to multiple previous transplantations, BUT here with this excellent matched donor , this transplant will be considered as low risk , so no need for sensitization .
– As mentioned above , being low immunological risk , induction with basiliximab & methyl prednisolone will be suitable.
– Yes , protocol biobsy here will be of great value for :
1- Diagnose subclinical rejection
2- Diagnose early CNI toxicity which can happen even with low target trough level
– NO , this patient should be on steroid for these reasons :
1- Hx of previous ABMR
2- With the hx of CNI toxicity , we will consider lower target of CNI , so will augment immunosuppression by adding steroid
– Many surgical concerns in this patient as mentioned by all my colleagues , starting from need for nephrectomy to find space , adhesions from previous surgeries , poor healing & increased risk of infection due to immunosuppressive medications & difficulties in vessel anastomosis esp. with also being DM & IHD & difficulties in ureteroneocystostomy due to previous multiple transplants .
This patient had 3 previous cadaveric transplant so he is highly sensitized which is obvious by presence if cPRA 93%
But he has no specific AB to his sister so he has negative crossmatch
Also being his sister they may experience some dgree of HLA MATCHING alleles .
the main goal of desensitization is obtaining negative crossmatch which already the case her so no need for desensitization
the patient us considered highly immunological risk as he had 3 previous transplants so i will give induction by ATG .
The Patient had 3 previous transplant he lost the last graft due to chronic ABMR–
protocol biopsy will help to detect early and subclinical ejections also follow up of DSA is recommended .
With History of CNI toxicity i will go with steroids dependent protocol and keep trough level if tacrolimus around 5-7 after 6 months with follow-up by DSA level and protocol biopsy
what is the main surgical concern in this patient?
-site of the incision according to previous grafts site
– graft rephrectomy may be needed.
-Adhesion will be major surgical concern.
-delayed wound healing and high risk of infection due to immunesuppression,Dm,weak muscles.
– vascular anastomosis might be difficult in diabetic patient with repeated grafts .
– assessment of cardiovascular condition and aortoilliac vessels of the patient as he is diabetic, hypertensive, with IHD,on long term stetoids with high possibility of atherosclerosis.
Explain why the crossmatch is negative?
· a positive flow cytometry crossmatch is unlikely below a threshold of 2,500 MFI
and very likely above a threshold of 5,000 MFI
· 000 mismatch and no DSA
· Possible due to absorption of HLA-DSA by the allograft (1)
Will you consider desensitization for this patient? No at the moment as
· No ABO-mismatch
· No DSA
· Negative crossmatch
What is your induction plan, and why?
· Basiliximab, methylprednisolone as 000 mismatch, no DSA and negative
cossmatch
· ATG not indicated as may increase risk of malignancy (PTLD) and the patient is not sensitised
Will you consider protocol biopsies for him, if yes why? Yes
· He has a high immunologic risk
· Has history of CNI toxicity
· Possible Histologic antibody-mediated rejection with negative DSA
Will you consider steroid free regimen for him, if yes or no, why?
· No, he has high risk for rejection.
· I may need lower dose of CNI due to history of toxicity
What is the main surgical concern in this patient?
· viable and functional native ureter may not be available
· cardiovascular disease and Aortoiliac disease should be excluded as previous
transplantation, CNI, and steroids increase the risk of atherosclerosis.
· Often only a small segment of iliac vessels is available and grafts were
anastomosed to the external iliac vessels in the majority of cases
· There may be no enough space for the new graft and may need nephrectomy
· Dissection of the bladder for ureteroneocystostomy may be difficult because of
scarring. (2)
(1) https://journals.lww.com/transplantjournal/Fulltext/2021/11000/Histologic_Antibody_mediated_Kidney_Allograft.17.aspx#:~:text=Histologic%20Antibody%2Dmediated%20Kidney%20Allograft%20Rejection%20in%20the%20Absence%20of%20Donor%2Dspecific%20HLA%20Antibodies
(2) Professor Ajay Kumar Sharma own surgical views on 3rd and 4th transplantation
Cross match is negative as zero mismatch and no DSA.
No need of desensitization.
My induction plan is baciliximab.
Yes I would like protocol biopsy. As previously CNI toxicity twice.
Of course steroid will be needed because previous history of CNI toxicity, so reduced CNI will be better with steroid backup.
It will be a surgical challenge because
Explain why the crossmatch is negative
Negative FCM XM in this patient, with high cPRA 93% is explained by the absence preformed DSA, both class I & class II HLA, and the absence of non HLA IgG Ab at time of testing.
However , cPRA was done 2021, 3 years after FCM XM, its possible the patient was exposed to new sensitizing events adding new Ab, FCM XM should be repeated.
High cPRA signifies the presence of anti-HLA non DSA Ab , non HLA Ab, or autoAb,
Will you consider desensitization for this patient?
No. patient is low risk. negative FCM XM. Tissue typing 000 mismatch, no DSA.
What is your induction plan, and why?
Basiliximab. This patient is standard risk immunologic profile. Tissue typing is 000 mismatch, no DSA. Yet he is highly sensitized due to his previous three transplants..
Rexposure to ATG, ALemtizumab could be harmful and predispose to life threatening infections and malignancy
Will you consider protocol biopsies for him, if yes why?
Ideally it would be beneficial to consider protocol biopsy in this patient. Provided that he had a history of 2 grafts loss secondary to CNIs toxicity and one graft loss due to chronic ABMR
Will you consider steroid free regimen for him, if yes or no, why?
NO. based on history of previous rejections and chronic ABMR. The patient was already exposed to 2 previous attacks of graft loss due to CNIs toxicity, so it is mandatory to direct our minds towards minimization of CNI, steroids then is a backbone of his IS mentainence protocol
What is the main surgical concern in this patient?
Over crowded space. Nephrectomy should be taken in consideration
This patient is DM, HTN, atherosclerosis, vascular calcifications is expected
Pelvic adhesions due to previous surgeries
Cross match is negative because this donor is 0 mismatch and he doesn’t have antibodies against this specific donor. I will consider him lucky that with PRA of 93% he has found a good donor.
No need for desensitization
I will give him basiliximab as this is 0 mismatch and this gentleman has been previously heavily immunosuppressed.
with this Cross match I might not do protocol biopsies though my threshold will be very low for biopsy
He is not a candidate for steroid free protocol with a PRA of 93% and previous graft loss due to ABMR
I think finding a suitable place for transplant would be big surgical challenge for this patient
Many thanks Dr Ben Mezher, Dr Amal Anan, Dr F Batista, And Dr Ameri Elaf,
Let us move to week 4.
Ajay
Thanks
Prof Ajay
Negative cross-match:
Although the patient had 3 transplant & high cPRA ( highly sensitized), but his cross match was negative mean that he had no specific antibodies against his donor ( his sister), but he may had antibodies against other persons.
Desensitization :
This patient considered as high risk patients due to history of previous 3 transplantations, but now he didn’t need desensitization due to negative cross-match & no DSA
Induction
Zero HLA mismatch & negative cross-match mean the patient can receive induction with basiliximab ( low risk ) & maintained on triple immunosuppression including steroids.
Protocol biopsy:
Due to failing of the 3 previous transplant ( last one due to ABMR), protocol biopsy is important for early detection of subclinical rejection or signs of drug toxicity.
Steroid use:
This patient should kept on steroid based immunosuppression regimen because he lost a graft due to acute rejection & steroid based regimen have better long term outcome.
Surgical concern:
Cross match is negative due to absence of donor specific antibodies .
However absences of donor specific antibodies not really means that there were no antibodies but the presented antibodies here not specific for the donor.
cPRA is 93% means that patient had 93% antibodies of related donor.
in fact, it is better to repeat cross match as it was done since 2019.
– No role for desensitization here.
The patient despite of 000 mismatch and no donor specific antibodies she considered highly immunological risk my opinion to give induction by ATG despite their risk of infection but to avoid risk of graft loss.
Patient with history of previous 3 transplant and last of them due to chronic ABMR
– patient needs close monitoring by
– renal panel
– 24 h urinary protein.
-DSA.
– protocol biopsy to detect early rejection due to history of chronic ABMR.
No, due to history of chronic ABMR.
– I will consider graft rephrectomy for spacing of new graft with hazard of post transplant
Bleeding and injuries to nearby organs as bowel.
– follow up of surgical incision as carrying risk of infection and delayed healing in presence of immunesuppression.
– poor transplant scarring and previous ureteoneycystomies may handle Surgeon to find space on bladder for new graft.
No mismatch or DSA levels, so she is fully match
No, Crossmatch is negative
This patient has high cPRA values, probably due to non-HLA antigens, which deserves to expand her investigation to other rejection markers.
We do not have Alemtuzumab or Basiliximab in Brazil, leaving the induction exclusively with rATG, which must be considered due to the high risk of rejection that it has been triggering in previous transplants added to the high cPRA
Yes, several previous rejections, including antibody-mediated. Biopsies scheduled or showing minimal change in renal filtration should be performed.
No, both due to the status of previous rejections and also due to the history of CNI intoxication, and a triple regimen should be used, prioritizing mTor inhibitors. MMF and Prednisone must be used together.
You should consider native nephrectomy as well as additional care with bands and adhesions from previous procedures to avoid vascular occlusion and other complications.
usually sensitization consider for antibodies removal or ABO incompatibility
this patient DSA negative so desensitization should not be offered .
induction therapy by i.v basiliximab because low immunological risk.
yes i will consider he has high cPRA and previous history of ABMR ,so it is wise to detect early or subclincal rejection in such type of patient.
#Explain why the crossmatch is negative
The negative FCXM may be due to:
The circulating antibodies in the patient’s serum are not against donor’s cells antigens, but against other HLA antigens from his previous sensitization ( previous 3 transplants), in addition to that, the HLA mismatch is 0-0-0, so it is not DSA,
Or it could be due to non HLA antibodies.
# Will you consider desensitization for this patient?
No, I will not consider desensitization for this patient, because the cPRA 93% means that this patient has limited chance to receive kidney from other donors, but in this donor( his sister) there is no DSA and negative crossmatch, as the main goal of desensitization is to reduce or eliminate DSA also it associated with many complication and costly, so there is no indication .
#What is your induction plan, and why?
With donor 0-0-0 mismatch, no DSA, negative FCXM,(low immunological risk) so the induction plan is Basiliximab.
# Will you consider protocol biopsies for him, if yes why?
No, I will not consider protocol biopsies, but he need follow up with renal function, DSA, Proteinuria and CNI drug level, advise the biopsy if necessary.
# Will you consider steroid free regimen for him, if yes or no, why?
No, I will not consider steroid free regimen, for the previous history of 3 rejections(CNI toxicity, chronic AMR),so to prevent rejection event
# What is the main surgical concern in this patient? Surgical procedures on previously operated iliac fossae can present additional technical challenges. Relevant scarring and fibrosis may make identification of correct tissue planes more difficult, necessitating vascular surgery and risking complications. Cold ischaemia time (CIT) and warm ischaemic time (WIT) may be extended because of the complex and prolonged anastomotic procedures and have been associated with longer overall operative time, impacting morbidity.
Also we may need
nephrectomy to make space for the other kidney
1.Barocci S, Valente U, Fontana I. et al. Long-term outcome on kidney retransplantation: a review of 100 cases from a single center. Transplant Proc 2009; 41: 1156–1158 [PubMed] [Google Scholar]
2.Blanco M, Medina J, Gonzalez E. et al. Third kidney transplantation: a permanent medical-surgical challenge. Transplant Proc 2009; 41: 2366–2369 [PubMed] [Google Scholar]
Negative T and B cell IgG by MFI and no DSA detected by cross match but consider complement-dependent cytotoxicity crossmatch (CDC), & flow cytometry. cPRA >93% means patient is highly sensitised
No, because no DSA and 000 matching
IV basiliximab to avoid acute rejection plus steroid
ATG has high risk of infection and malignancy
Yes // patient need close monitoring by renal biopsy protocol to avoid sub clinical rejection because patient had previous 3 failed kidney transplant 2 of them because Chronic allograft rejection last one ABMR from 2 years
No // because of previous rejection should be continuing on low dose steroid with tacrolimus and MMF.
Because of previous 3 transplant should be evaluated to role out intra abdominal adhesion and fibrosis and consider grafts nephrectomy to find good space for new graft.
Vascular evaluation by angiogram for iliac artery
anastomoses adhesion and fibrosis.
Explain why the crossmatch is negative
The crossmatch is negative because there are no specific antibodies in the serum of potential KTR to donor’s lymphocyte. cPRA of 93% reflects the likelihood of donor’s antibody to cross-react with Ag in the donor pool. In this case scenario, finding a suitable donor in the donor pool is about 7% which is extremely difficult. This patient is very lucky, finding his sister as a suitable and matching donor with negative crossmatch.
Will you consider desensitization for this patient?
Despite of having PH of multiple transplant and CAMR, I will not consider a desensitization protocol for this patient for the followings:
a) His potential donor is fully matching.
b) Negative crossmatch and no DSA against the donor tissue.
c) Considering benefit-risk ratio in this patient, desensitization will add more to infection risk with less benefit when viewing his HLA-match, crossmatch results and no DSA.
What is your induction plan, and why?
I will use Basiliximab as an induction agent, provided his full matching donor without DSA against donated kidney.
Will you consider protocol biopsies for him, if yes why?
Protocol biopsy will be considered in this case for the followings:
a) PH of kidney transplant(3 times) categorized him as high-risk transplant.
b) PH of CAMR needs surveillance biopsy to early detetct and treat subclinical rejection.
Will you consider steroid free regimen for him, if yes or no, why?
No; I will not
a) Despite of having 000 mismatch, negative XM and no DSA, I will not consider steroid-free regimen in this patient with past history of 3 transplants and CAMR in the last one.
b) This patient is immunologically unpredictable as he may develop new antibodies in the post-transplant period(de novo DSA) and the source of antibody production (sensitization) is there (his previous allografts).
c) Adding to above, a patient with history of multiple transplants needs prolonged immunosuppressive regimes or he might go to transplant nephrectomy in the setting of re-transplantation to lower the PRA level and minimize the immunological risk.
What is the main surgical concern in this patient?
a) Repeated surgery of the iliac fossa is associated with high rate of blood loss and long surgical procedure time which may increase the risk of thrombotic events and cause DGF.
b) Technical difficulties regarding anastomotic techniques; the graft vasculature to recipient blood vessels and the graft’s ureter to recipient’s bladder.
I like this expression Dr Assafi:
‘immunologically unpredictable’
cross match : the patient’s serum is incubated with lymphocytes from a
panel of representative donors in the presence of complement , this patient high cPRA indicates that this patient has antibodies against 93% from the donor pool but his sister is from the remaining 7 %
the importance of high cPRA is to put the patient on the top of waiting list from cadaver as its difficult to find a compatible donor and to mange him as high risk patient to develop ABMR
NO , the indication for desensitization is ABO incompatible or the presence of DSA which is both not found in our patient .
this patient has negative DSA , 0-0-0 mismatch so he needs basiliximab
But really in our transplant center this patient will be given ATG as he has history of previous transplantation three times , and high cPRA 93% , and history of ABMR
Yes , this high risk case for development of rejection due to high cPRA 93% , and history of ABMR and he needs also regular DSA follow up
surly NO , high risk of rejection and history of CNI toxicity so will accept the range on lower limit of normal range
Finding space for the new graft and previous iliac arteries surgeries.
This may be associated with longer cold ischemia time, longer operation duration,
thanks
Explain why the crossmatch is negative
means that the recipient does not have antibodies against the donor HLA(no HLA,no DSA)
Will you consider desensitization for this patient?
As negative cross matching no need for desensitization here
What is your induction plan, and why?
He needs induction therapy as cPRA 93% Induction by basiliximab and methylprednislone as protocol
Will you consider protocol biopsies for him, if yes why?
Yes we will as his history of chronic ABMR and chronic CNI toxicity
Will you consider steroid free regimen for him, if yes or no, why?
No , our patient with hx of previous 3 transplant and chronic ABMR Also being use steroid for long time ,he will have risk of rejection when considering such regimen
What is the main surgical concern in this patient?
He needs highly professional urologist and vascular surgeon
As with his previous transplantations highly increased risk of adhesions and fibrosis also nephrectomy for trans plated kidneys to find space for the new one
Ct angio for his pelvic and lower limbs veins is must
Explain why the crossmatch is negative
– The negative crossmatch could be explained by the absence of donor-specific antibodies despite the high CPRA
Will you consider desensitization for this patient?
– No, negative crossmatch and no DSA (000 mismatches).
– High cPRA with negative crossmatch was not associated with immune reactivity post-transplant as long as crossmatch is negative.
What is your induction plan, and why?
– Induction plan by basiliximab, methylprednisolone
– Maintenance with triple immunosuppressive drugs
– ATG induction has hazards for PLTD and infection rates, also with the negative crossmatch and absence of DSA there is no need for intense immunosuppression
Will you consider protocol biopsies for him, if yes why?
– Yes.
– This is the fourth transplant, more risk of developing DSA, especially with a previous history of rejection
Will you consider a steroid free regimen for him, if yes or no, why?
– No, it could be associated with risk for rejection with the high cPRA and previous ABMR.
What is the main surgical concern in this patient?
– Finding space for the new graft and previous iliac arteries surgeries.
– This may be associated with longer cold ischemia time, longer operation duration, and more blood loss. This may end with inferior graft outcome compared with first transplant better still than being on dialysis
References:
1- Lan J H, Kadatz M, Chang DT, et al. Pretransplant Calculated Panel Reactive Antibody in the Absence of Donor-Specific Antibody and Kidney Allograft Survival. CJASN 16: 275–283, February, 2021.
2- Domagala P, van den Berg T, Tran K, et al. Surgical Safety and Efficacy of Third Kidney Transplantation in the Ipsilateral Iliac Fossa. Ann Transplant. 2019; 24: 132–138.
3- The third and fourth renal transplant; Technically
4- challenging, but still a valid option
5- The third and fourth renal transplant; Technically
6- challenging, but still a valid option
7- The third and fourth renal transplant; Technically
8- challenging, but still a valid option
3- Halawa A. The third and fourth transplant; Technically difficult, but still a valid option. Ann Transplant. 2012; 17(4):m125-134.
Well done Radwa but I will keep repeating:
A high cPRA means he has antibodies against 93% of a pool of antigens that do not exist in his specific donor so:
A high cPRA means his chance to get a donor ( other than his sister is poor.
High immunological risk is determined by MFI of his antibodies which are very low here and not cPRA.
Ajay
thanks a lot professor Dawlat for the easy and informative explanation .
I have gained a lot by this explanation.
Hi Dr Radwa Ellisy,
My response is in relation to your comment as I quote in italics, “longer cold ischemia time, longer operation duration.”
Yes, it can be tricky and surgically challenging. Hence, it is alsys good to keep another surgical colleague in reserve as a standby.
Many years ago, it took 4 hours to reach blood vessels and it was 5 am when I requested my younger colleague Mr. Avneesh Kumar to come and transplant. Mutual help is crucial for optimum outcomes. I like to take up such challenges but such a patient need not be transplanted by someone who has spent such a long time in dissenting blood vessels.
With best wishes
,Ajay