III. The third and fourth renal transplant; Technically challenging, but still a valid option
- Summarise the challenges encountered on retransplantation?
- Briefly address the various techniques for third and fourth transplants addressed in this article
Q1:
Patient considered for third and fourth TXS have a lot of medically, immunologically and surgically challenges. They are usually highly sensitized and have higher acute rejection. So they need more potent immunosuppression which increases risk of opportunistic infections or malignancy.
In addition, cardiovascular comorbidities are more prevented among these patients due to long time on dialysis complication of previous surgical intervention are sometimes challenging too.
Q2:
Surgical techniques using for third and fourth kidney TX are as following:
1. Trans –peritoneal kidney Re-TX:
Using a lower midline laparotomy incision these kidneys are transplanted the graft is intraperitoneal. Challenges are: late recovery, pain control and prolonged ileus sometimes requiring TPN.
2. Retro-peritoneal heterotopic kidney TX:
This technique results in more perioperative transfusion and more surgical time and higher thrombosis and obstruction were seen.
In one study lymphocele, urinary fistula, wound dehiscence and abscess formation were seen.
3. Retroperitoneal kidney re-TX using the vessels of the previous kidney TX: This technique needs previous TX nephrectomy and it vessels were used for vascular anastomosis and ureter implantation was done in to the bladder dome.
4. Orthotropic kidney TX(OKT).
When iliac vessels are unsuitable this technique is used. First native nephrectomy is performed and then TX renal vein anastomosed to its vein or splenic vein or IVC. Urinary tract was anastomosed using pyelopyelic, pyeloureteral or uretero-ureteral ones.
The main cause of graft loss in all of these techniques was immunological.
1- Summarise the challenges encountered on retransplantation?
2- Briefly address the various techniques for third and fourth transplants addressed in this article
The challenges encountered on retransplantation:
-Technical surgical problem(especially aspect) and wound related complications.
-Long history of immunosuppressive status with high risk of either infection or malignancy.
-High risk of rejection as the patient is highly sensitized.
Techniques for third and fourth transplants:
1- TRANS-PERITONEAL KIDNEY RETRANSPLANTATION.
2- RETRO-PERITONEAL HETEROTOPIC KIDNEY RETRANSPLANTATION. (Third and subsequent transplants performed extra peritoneally are more time-consuming and require more transfusions in the perioperative).
3- RETROPERITONEAL HETEROTOPIC KIDNEY RETRANSPLANTATION USING THE VESSELS OF THE PREVIOUSLY TRANSPLANTED KIDNEY.
4- ORTHOTOPIC KIDNEY TRANSPLANTATION.
(Used if the iliac vessels are not suitable for engrafting).
surgical problem(especially vascular aspect)
**Summarise the challenges encountered on retransplantation?
Despite many surgical complications associated with third and fourth transplantation which require long immunosuppression period which may result either infections or malignancy , the number of patients increasing for the third and fourth transplantation due to chronic allograft dysfunction which threatens patients to return to dialysis.
Several techniques :
1- TRANS-PERITONEAL KIDNEY RETRANSPLANTATION.
2-RETRO-PERITONEAL HETERTROPIC KIDNEY RETRANSPLANTATION.
3-RETROPERITONEAL HETERTROPIC KIDNEY RETRANSPLANTATION USING THE VESSELS OF THE PREVIOUS KIDNEY TRANSPLANTATION.
4-ORTHOTOPIC KIDNEY TRANSPLANTATION.
1. Summaries the challenges encountered on re-transplantation?
1- Highly sensitized patients
2- Technical difficulties due to numerous surgical interventions
3- Immunosuppression for long time causing wound related complications, risk of malignancy and infections complications
4- Multiple comorbidities, like DM causing protracted ileus and the need for nutritional support
5- Pain control
2- Briefly address the various techniques for third and fourth transplants addressed in this article
1- TRANS-PERITONEAL KIDNEY RETRANSPLANTATION
2- RETRO-PERITONEAL HETEROTOPIC KIDNEY RETRANSPLANTATION
3- RETROPERITONEAL HETEROTOPIC KIDNEY RETRANSPLANTATION USING THE VESSELS OF THE PREVIOUSLY TRANSPLANTED KIDNEY
4- ORTHOTOPIC KIDNEY TRANSPLANTATION
Same article from previous module probably technical error.
Renal transplantation is the treatment of choice for end stage renal disease. It is well established that first and second kidney transplantation are associated with better outcomes when comparing to waitlisted dialysis. From surgical point of view, operative techniques are universally applied with minimal technical variations depending on experience.
Third and fourth retransplantation may offer advantages over dialysis but this should be studied in more precise studies with a careful selection of the patients. However there is no globally agreed method for third and fourth transplants, from technical point of view, which are significantly more complex. This is explained by difficulties in the previous surgeries, adhesions, anastomosis, intra and post-operative complications.
Majority of patients are highly sensitized from previous transplantations and retransplantations requiring higher doses of induction and maintenance immunosuppression compared to first and second transplantation.
Delayed graft function and Graft failure is a strong predictor of morbidity and mortality mainly in the early postoperative period
From surgical point of view, Several techniques for third and fourth kidney transplantation were described:
-TRANS-PERITONEAL KIDNEY RETRANSPLANTATION
-RETRO-PERITONEAL HETEROTOPIC KIDNEY RETRANSPLANTATION
-RETROPERITONEAL HETEROTOPIC KIDNEY RETRANSPLANTATION USING THE VESSELS OF THE PREVIOUSLY TRANSPLANTED KIDNEY
-ORTHOTOPIC KIDNEY TRANSPLANTATION
Graft survival and survival rates were variable in the studies depending on the surgical approach, patients risk and post-operative complication. But third and fourth retransplantations are valid options for waitlisted dialysis patients but associated with surgical complexities and postoperative complications.
Of course first and second transplant are best offer for the patient on regular dialysis, and we knew that chronic allograft nephropathy is eventual outcome so the chance of third and fourth transplant is present and challenging because of multiple comorbidity, longtime of dialysis, previous transplantations makes technique difficulties and challenging, presence of wound related complications, also sensitization status and obligatory use of aggressive induction and maintenance protocols…all these factors and more make third and fourth transplant challenging.
Different techniques :
1. TRANS-PERITONEAL KIDNEY RETRANSPLANTATION
2. RETRO-PERITONEAL HETEROTOPIC KIDNEY RETRANSPLANTATION
3. RETROPERITONEAL HETEROTOPIC KIDNEY RETRANSPLANTATION USING THE VESSELS OF PREVIOUSLY TRANSPLANTED KIDNEY
4. ORTHOTOPIC KIDNEY TRANSPLANTATION
· Challenges encountered for retransplantation
Third and fourth transplantation is inferior to first and second although it is considered a survival chance.
The operation is technically more difficult along with the prolonged immunosuppression ,wound related complications which can be challenging
Most patients have higher risk of acute rejection neccesitating aggressive immunosuppression which increases the occurence of malignancy and infection.
· The various techniques for third and fourth transplants
-Transperitoneal kidney retransplantation through a lower midline laparotomy incision.
-Retro periotineal heterotopic kidney retransplanation performed extraperitoneally with increased possibility of arterial thrombosis and urinary obstruction .
-Retro periotineal heterotopic kidney retransplanation using the previously transplanted kidney vessels where the incision is done over over the failed transplant kidney, followed by dissection of the renal vessels then transplant nephrectomy , so far no surgical complications were established.
-Orthotopic kidney transplantation is used for special group of patients as those with severe atherosclerosis of the aorto- iliac arteries when the iliac vessels are unfit for vascular anastomosis. Studies revealed acceptable patient and graft survival with this technique
Retroperitoneal heterotopic transplantation was considered as the primary choice either with or without transplant nephrectomy
Challenges encountered in the 3rd and 4th transplant can be summarized in the following :
1- Surgical challenges
– Technical difficulties due to multible operations done before.
– Wound complications are more common due to prolonged immunosuppression
– Post operative surgical complications are more common.
2- Medical challenges
– Higher rate of rejection because these patients are highly sensitized.
– Increase rate of infection and malignancy due to prolonged and aggressive courses of immunosuppression used either for induction, maintenance or for desensitization.
– Multiple comorbidities usually these patients have.
Surgical approaches :
1- Trans-peritoneal approach using lower midline incision and the graft is placed in intraperitonial space either in midline or in the iliac fossa.
2- Reteroperitoneal heterotopic approach.
3-Reteroperitoneal hetertopic approach using the vessel of previous transplanted graft
4- Orthotopic kidney transplant where the graft is put at the same site (usually the left) of native kidney after native nephrectomy and splenectomy, splenic artery of the recipient is anastmosed to the renal artery of the graft, renal vein of the recipient is anastmosed to renal vein of the graft and ureter of recipient is anastmosed to ureter of the graft.
Summarise the challenges encountered on re transplantation?
1-Numerous surgical interventions making the operation more technically demanding.
2-A long history of immunosuppression with subsequent wound related complications and multiple co-morbidities which may affect the patient and graft survival.
3-Sensitisation history may also create a dilemma in immunological manipulation post-transplantation.
4-Aggressive immunosuppression increases the risk of malignancy and infection.
5- Parental preparations of the other adjunctive immunosuppressive drugs (Azathioprine and Mycophenolate Mofetil) may not be readily available.
6-Recovery following midline laparotomy for renal transplantation in a patient who is immunocompromised with multiple comor-
bidities and multiple surgeries is not straight- forward.
7- Protracted ileus particularly in diabetics is a problem which may require nutritional support.
8- Pain control is also a challenge following a midline laparotomy incision compared to a transverse or oblique incision .
9- The intra peritoneal graft is adherent to the bowel which increases the risk of postoperative complications
Briefly address the various techniques for third and fourth transplants addressed in this article
1-Trans peritoneal kidney transplantation.
2-Retro peritoneal heterotopic kidney re transplantation.
3-Retroperitoneal hertrotopic kidney re transplantation using the vessels of the previously transplanted kidney .
4-Orthotopic kidney transplantation.
Summarize the challenges encountered on re-transplantation
Address the various techniques for the third and fourth re-transplantation
in mid-line or in the iliac fossa : the healing of mid-line laparotomy is not straight forward ,protracted ileus is problem in diabetics which require nutrition support , the intra-peritoneal graft is adherent to the bowel increasing the risk of post-operative complications
graft loss was mainly immunologically , third re-transplantation failed due to arterial thrombosis .
2. Retro-peritoneal hetero-topic kidney transplantation
no difference in complication rate between second and third transplantation,significant delayed graft function and blood transfusion , may be complicated by acute rejection and small bowel perforation
3. Orthotopic kidney transplantation
when the iliac vessels are unsuitable for vascular anastomosis
1-More surgical intervention
-use IS for long time
-sensitization history
-higher risk of acute rejection require aggressive immunosuppression with more complications mainly malignancy and infection.
-shortage of kidney donors and long waiting list.
2-Various techniques
*-tans-peritoneal kidney re Tx:
-more time for wound relieve
-need IV IS till patient can take oral form and no available IV formula from MMF or azathioprine
-protracted ileus in DM patient
– nephrectomy of failing kidney cannot be done in same sitting
-graft adherent to bowel
*retro peritoneal heterotopic kidney
-low incidence of arterial thrombosis and urinary obstruction
– increase risk of DGF.
*retro peritoneal heterotopic kidney transplantation using vessels of previously transplanted kidney
*orthotopic kidney Tx
-preferred if iliac vessels are not suitable for engrafting.
The most challenging part in 3rd and 4th Tx is immunological not surgical .
●Patients comorbidities:
After long term immunosuppression patient is vulnerable to infections and cardiac failure DIC
●surgical challenges:
●sensitization after repeated Tx
Review article
Ann-transplantation , 2012
level of evidence level 5 expert opinion , review 23 studies (retrospective and case series ).
In this review paper the author address the surgical and medical challenges associated with 3rd and fourth transplantation
Summary
-Main causes of mortality in 3rd and 4th kidney retransplants are cardiac failure,
disseminated intravascular coagulopathy and sepsis .
-Malignancy and infection problems are increased by extensive immunosuppression.
-Several methods for transplanting the third and fourth kidneys were described:
*Trans-peritoneal approach
*Reteroperitoneal heterotopic approach.
*Reteroperitoneal hetertopic approach using the vessel of previous transplanted graft
*Orthotopic kidney transplant
-All of the techniques discussed above are linked to a greater probability of surgical complications and mortality, which is to be expected in this patient population. However, continuous monitoring for malignancy and infection in this high-risk group may help to improve patient survival.
1-more surgical intervention
-use immunosuppression for long time
-sensitization history also make dilemma in immunological manipulation post transplantation
-higher risk of acute rejection require aggressive immunosuppression thus more complication (malignancies& infection)
-lack of available donor kidneys and long waiting list.
2-various techniques
*tans-peritoneal kidney retransplantation
but in this technique
-more time for wound relieve
-need IV immunosuppression till patient can take oral form and no available IV formula from MMF or azathioprine
-protracted ileus in DM patient
-can’t do nephrectomy of failing kidney in same sitting
-graft adhered to bowel
*retro peritoneal heterotopic kidney
offer
-low incidence of arterial thrombosis & urinary obstruction
-But increase risk of DGF.
*retro peritoneal heterotopic kidney transplantation using vessels of previously transplanted kidney.
*orthotopic kidney transplantation
-recommended if iliac vessels are not suitable for engrafting.
Immunological challenges are due to highly sensitized nature of recipients. they
have de novo anti HLA antibodies predisposing them to rejection and overall poor
graft survival.
Despite above all they do have a survival advantage especially in younger
patients and those with low immunological risk where the first transplants work for
a period of 10 to 15 years and subsequent ones are needed to sustain life
The third and fourth renal transplant; Technically challenging, but still a valid option
Kidney transplantation offers a better quality of life and long survival as compared to dialysis. The first and second kidney transplantation have established surgical techniques between surgeons. Third and fourth transplants are valid, although, they are significantly more complex technically, and highly risky because the recipients are comorbid, highly sensitized from the previous graft, putting them in need of a more potent immunosuppression regime to prevent rejection, than the first and second transplantation. Strong immunosuppression will put the patient at high risk of infection, like wound infection postoperative as well, risk of malignancy increase.
Technics of the operation:
1- Trans-Peritoneal Kidney Re-transplantation:
Trans-peritoneal via a lower midline laparotomy incision. The graft is placed intraperitoneal in the midline or in the iliac fossa. The renal artery is anastomosed to the external, internal, or common iliac artery. Renal vein to IVC, external or common iliac vein. The ureter is implanted to the urinary bladder dome intraperitoneal. Recovery is not smooth in this approach. Protracted ileus and pain are major complications. Post-operative intravenous immunosuppression use in some centers increases the risk of infection.
2- Retro-Peritoneal Heterotopic Kidney Re-Transplantation:
These patients usually had extensive previous abdominal surgery. Preoperative CT angiography was performed to check the most suitable side for transplantation. The engrafting was carried out using standard technique (the renal artery and vein are anastomosed to the external/common iliac artery and vein respectively) dissection of the iliac vessels starts toward the groin. Intraperitonealization of the transplanted kidney is usually done to allow tension-free muscle closure. None of the surgical complications leads to graft loss.
Graft and patient’s survival, complication rate, and acute rejection rate, all are better following third kidney transplantation as compared to fourth transplantation.
3- Retroperitoneal Heterotropic Kidney Re-Transplantation Using the Vessels of the Previously Transplanted Kidney.
Before this operation, we need to exclude renal artery stenosis. Which can be done by Tc99M technetium scan and duplex scan. Incision made orthotopically over the failed transplant kidney which has to be removed before transplant the new one. The renal artery and vein of the previously transplanted kidney were used as the vascular conduit for the new kidney.
4- Orthotopic kidney transplantation
This is used for selected patients when the iliac vessels are deemed unsuitable for vascular anastomosis. The main indications are severe artherosclerotic aorto-iliac disease and bilaterally retained failed kidney transplant. The recipient’s urinary tract is always carefully dealt with to avoid injury to its vascularity. The transplanted renal artery is anastomosed to the splenic artery, and the renal vein is usually anastomosed to the native renal vein.
· The third and fourth transplants have low rates, despite their possibility.
· It is difficult, if impossible to establish a standard technique for them.
· Higher surgical complication rate and mortality.
· They have a survival benefit for the patient.
· Appropriate patient counseling is important to step before considering transplantation.
· Regular surveillance for malignancy and infection of these patients may improve patient survival.
1.Challenges ;
2.Techniques ;
The most challenging part in 3rd and 4th Tx is immunological not surgical .
●Patients comorbidities:
After long term immunosuppression patient is vulnerable to infections and cardiac failure DIC
●surgical challenges:
Wond dehecense and hernia .
●sensitization after repeated Tx . ☆☆ ☆ (( Techniques in transplant))☆☆☆
1. TRANS-PERITONEAL KIDNEY RETRANSPLANTATION..
(Incision):midline laparotomy incision.
(Anastomosis): renal artery to iliac artery
Renal vein to ivc.The ureter is implant-
ed intraperitoneally into the bladder dome using one of the standard techniques.
(Site ):mid line /iliac fossa . Transperitoneal
(Compications) :attached to viscera /difficultty to do a transplant nephrecto-
my of the failing kidney in the same sitting if re-quired for spacing.
2.RETRO-PERITONEAL HETEROTOPIC KIDNEY RETRANSPLANTATION:
It is perfered by author .
3. RETROPERITONEAL HETEROTOPIC KIDNEY RETRANSPLANTATION USING THE VESSELS OF THE PREVIOUSLY TRANSPLANTED KIDNEY .
4. Orthotopic transplantation .
Review article
Ann-transplantation , 2012
level of evidence level 5 expert opinion , review 23 studies (retrospective and case series ).
In this review paper the author address the surgical and medical challenges associated with 3rd and fourth transplantation
he summarized different surgical techniques and related challenges and risks including higher risk related to vascular anastomosis like vascular injury dissection’s, thrombosis also the risk of RAS , wound related infection dehiscence and pain management with midline trans-peritoneal surgical incision also post operative intravenous IS medications with challenges related to drug level monitoring and IV preparation for MMF , azathioprine. recipient of 3rd or fourth transplant usually from pediatric and young adults higher rate of sensitization and allocation to incompatible donor that mandate use of intense induction and maintenance IS medication with increasing risk of post transplant morbidity and mortality due to infection like BKV infection and increase risk of malignancy , higher rate of mortality due to heart failure , infections with Disseminated coagulopathy. The overall graft survival is lower compared to first and second transplant due to increase risk of chronic allograft rejection and chronic allograft nephropathy in third and fourth transplant but still have better graft survival as compared to dialysis.
1- Review article
2- Summary of each techniques
Procedure
Complications
a) wound dehiscence -requiring urgent surgery
b) arterial thrombosis
Graft survival
a) 1year-88%, 2 year-66% and 3 year-58%
b) Graft failure mainly due to chronic allograft nephropathy
Patient Survival
a) 100% at 5 years
b) 97% at 10years
Procedure
Complications
Mazzucchi et al
a) Transfusion in 52% retransplanted patients
b) arterial thrombosis
c) ureteral obstructions
d) increase in the DGF rate in retransplants -52%
e) no difference in acute rejection rate
Blanco et al
a) acute rejection rate -30%
b) overall surgical complication -26.6%
c) chronic allograft nephropathy
Graft survival
Mazzucchi et al
a) 1year graft survival – 57.1% for retransplants and 86% for first transplant patients
Blanco et al
a) 1 year-87%,
b) 5 year-76%
c) 10 years -57%
Patient Survival
a) 1 year-97%,
b) 5 year-86%
c) 10 years -76%
Procedure
Complications
a) No surgical complications
Procedure
Complications
a) overall rate was 15.9%
b) renal artery stenosis -3.1%
c) renal artery thrombosis -1.7%
d) renal vein thrombosis requiring graft nephrectomy -1.2%
e) urine leak -7.6%
f) urinary obstruction -0.9%
g) kidney stones -1.3%
Patient survival
a) 1 year- 92.23%
b) 10 years- 78.3%
c) 20 years- 62.5%
Graft survival
a) 1 year- 87.7%
b) 10 years- 59.3%
c) 20 years- 34.5%
-is an alternative to heterotopic transplantation if the iliac vessels are not suitable for engrafting
This A review article.
An expert opinion .
Second and forth transplant is associated with more challenges, surgery is more
demanding due to previous operation and patient are more sensitized due to multiple
transplant ,with delayed wound healing and more comorbidities’.
Death is more due to heart failure ,sepsis and DIC. Risk of acute rejection necessitate
more aggressive. Immunosuppression with inherited risk of malignancy(PTLD);and
infection.
Multiple surgical techniques. Are used:
1- Trans peritoneal kidney transplantation:
Traditionally, third and fourth renal grafts are transplanted trans peritoneally through a
lower midline laparotomy incision.
The graft is placed in the intraperitoneal space in the midline or in the iliac fossa.
The renal artery is anastomosed to the external, internal or common iliac artery.
The renal vein is anastomosed to IVC, external iliac or common iliac vein.
The ureter is implanted intraperitoneally into the bladder dome using one of the standard
techniques.
2- Ritropertonial heterotopic kidney Retransplantation :
Engrafting was completed using standard technique (the renal artery and vein are
anastomosed to the external/common iliac artery.
3- RETROPERITONEAL HETEROTOPIC KIDNEY RETRANSPLANTATION USING THE
VESSELS OF THE PREVIOUSLY TRANSPLANTED KIDNEY :
.Incision was done Careful dissection of the renal vessels and subsequent transplant
nephrectomy was performed avoiding extensive dissection of the iliac vessels.
The renal artery and vein of the previously transplanted kidney were used as the
vascular conduit for the new kidney.
The ureter was implanted into the bladder dome over a stent.
4. ORTHOTOPIC KIDNEY TRANSPLANTATION :
This technique is used for selected patients when the iliac vessels are deemed
unsuitable for vascular anastomosis.
main indications for OKT are severe atherosclerotic aorto-iliac disease and bilaterally
retained failed kidney transplant.
The patient is placed in a right lateral position. Nephrectomy is performed through a left
lumber incision though the bed of the 12th rib with rib resection.
The left kidney and splenic vessels are exposed retroperitoneally.
The entire length of the renal vein is preserved by dividing the vein very close to renal
parenchyma .
The renal artery is often diseased and cannot be used in most cases. The recipient’s
urinary tract is always carefully dissected.
In all cases, the splenic artery is exposed immediately beneath the parietal peritoneum,
behind the medial surface of the adrenal gland .
The transplanted renal vein usually is anastomosed to the native renal vein.
The transplanted renal artery was anastomosed to the splenic artery .
The urinary tract is reconstructed by performing pyelo-pyelic anastomosis or pyelo-
ureteral anastomosis and uretero-ureteral anastomosis over a double-J stent .
Author recommend the retroperitoneal heterotopic transplantation as the first option
with or without transplant nephrectomy when appropriate.
Appropriate patient counselling is important .
It is a review article, level of evidence 5
-Surgical procedures on previously performed iliac fossae can provide additional difficulties. Significant fibrosis and scarring may make it difficult to identify the appropriate tissue planes, requiring more sophisticated vascular surgery and increasing the risk of collateral injury and consequences. Anastomotic and overall operational durations may be prolonged, which has been linked to increased morbidity.
-Most published series indicate a significantly higher frequency of surgical, immunological, and infectious problems in 3rd and 4th kidney transplants.
-When compared to first or second kidney transplants, graft survival is lower.
-Third and fourth kidney transplants still offer a significant survival advantage over dialysis.
-Even when prolonged to three or more transplants, repeat transplantation increases patient survival and quality of life.
-It’s technically difficult to operate on the iliac fossa again. Several studies have revealed increased operational times, blood loss, vascular thrombosis, adjacent organ injury, and perioperative infections and ureteric problems
-bacterial infection increased in the third renal transplant recipients compared with the first renal transplant recipients
-Due to intensive immunosuppression, RTRs for the third or fourth kidney transplant may have an underlying undiscovered cancer or subclinical infections.
-Patients who are highly sensitive have a higher rate of acute rejection, necessitating the use of immunosuppressive drugs.
Summary
-Main causes of mortality in 3rd and 4th kidney retransplants are cardiac failure,
disseminated intravascular coagulopathy and sepsis .
-Malignancy and infection problems are increased by extensive immunosuppression.
-Several methods for transplanting the third and fourth kidneys were described:
*Trans-peritoneal approach
*Reteroperitoneal heterotopic approach.
*Reteroperitoneal hetertopic approach using the vessel of previous transplanted graft
*Orthotopic kidney transplant
-All of the techniques discussed above are linked to a greater probability of surgical complications and mortality, which is to be expected in this patient population. However, continuous monitoring for malignancy and infection in this high-risk group may help to improve patient survival.
References
–Barnes, J.C., Goodyear, S.J., Imray, C.E., Lam, F.T., Kashi, H.S., Tan, L.C., Higgins, R. and Imray, C.H., 2017. Kidney retransplantation from HLA‐incompatible living donors: A single‐center study of 3rd/4th transplants. Clinical transplantation, 31(11), p.e13104.Available at :https://onlinelibrary.wiley.com/doi/full/10.1111/ctr.13104
Although third and fourth transplantations are better treatments for RRT compared to dialysis, there are problems to them, such as complicated surgical techniques, increasing rate of highly sensitization patients that need more aggressive induction and more potent immunosuppression and associated comorbidities.
Different techniques used for third, fourth, and even fifth transplantations include:
1- Trans-peritoneal (using midline incision with iliac vessels anastomosis)
2- Retro-peritoneal in heterotopic form
3- Retro-peritoneal using previously transplanted kidney vessels and nephrectomy of previously transplanted kidney
4- Orthotropic kidney transplantation (OKT) is used in case the iliac vessels are not suitable for anastomose in vessels. In this case, the artery of the transplanted kidney is anastomosed to splenic artery or native renal artery and its vein is usually anastomosed to native renal vein and in special conditions, to splenic IVC. Urinary tract is transplanted by performing anastomose (pyelo-pyelic or pyelo-ureteral or uretero-ureteral). Despite the problems with the said surgical methods, the reason for graft loss is ABMR and CAN in most of the cases.
The third & forth retrnasplantation offers a survival advantage slightly inferior to the first & second transplantation, however, it is more complex & challenging , due to
1- technically is more difficult with less surgical options.
2- comorbid patients affecting the patient & graft survival.
3-highly sensitized patients with higher acute rejection rate , that requiring aggressive immunosuppression medications. The later increase the risk of malignancy & infection.
The main cause of graft loss in those patient is immune mediated rather than the surgical complications .
Techniques of The third & forth retransplant :
1-Transperitoneal kidney transplant :
( rarely inferior mesenteric artery used end to end , try to avoid using the anastomosis with the aorta as inflow due to high risk of renal artery stenosis.
2-Retroperitoneal heterotopic kidney transplant:
3- Retroperitoneal heterotopic kidney transplantation using the vessels of the previously transplanted kidney.
4-Orthotopic kidney transplant:
This is a Review article, level 5 evidence
Renal transplantation is still the best renal replacement therapy for ESRD who still demonstrate both survival benefit and better quality of life compared to dialysis.
Re-transplantation for the third and the fourth time and even the fifth still offer a survival advantage but is slightly inferior to the first 2 transplants
There are a lot of challenges facing this procedure which may be related to the procedure itself or to the recipient that could be added to the challenge of the limited donor pool.
Challenges related to the procedure:
Relevant scarring and fibrosis on the previously operated iliac fossae could present a surgical challenge
Both cold and warm ischemia time could be prolonged because of the complex vascular anastomosis and longer operative time
Limited surgical options, lack of a standard surgical techniques and narrow operative field which may necessitate doing nephrectomy of the previous transplants to provide more space for the new graft.
Wound dehiscence and poor wound healing with longer hospital stay
Challenges related to the Recipient:
Previous transplantation could hinder the recipient sensitized with high PRA (associated with hyper-acute rejection, DGF and poor graft survival rate)and this may need desensitization before the procedure in addition to intensifying both induction and maintenance immunosuppression increasing the risk of both infection and malignancy.
The need to do proper psychological assessment of the recipient and assessing his compliance to immunosuppressive medications which could the cause of previous graft loss and these could make him not a proper candidate for re-transplantation
Techniques for third & fourth transplantation:
Type of study is reveiw
Kidney transplantation is considered the best choice or option for ESRD which offers longer survival rate to the patients.
Third and fourth kidney transplantation carries alot of difficulties because the patient is highly sensitized and difficulties related to the operation but still the cause of graft loss in the subsequent transplants is related to the immune system and it’s not related to technical complications.
Techniques that are used :
1_ trans_peritoneal kidney retransplantation
2_ retro_peritoneal heterotopic kidney transplantation
3_retroperitoneal heterotopic kidney transplantation using vessels of the previously transplanted kidney
4_ orthotopic kidney transplantation
Dear All
I acknowledge your replies. It was a great week. I can see many of the colleagues are doing well and putting in an effort.
*Third and fourth transplant had many functional,immunological and surgical complications but the patients deserve to get transplant kidney rather than back to dialysis .
* There are four surgical techniques:
1- Transperitoneal kidney retransplantation
2-Retroperitonel Heterotopic Kidney
3-Retroperitonel heterotopic retransplantion using the vessels of previous transplant kidney
4-Orthotopic Kidney transplantation
Although repeated transplantation is favored because it affects the quality of life it has somehow worse outcomes mainly due to sensitization and risk of infection. transplants from related donors were better than those repeated from deceased donors. additionally, this is highly dependent on the source of the translated kidney (type of donor) and time elapsed till the second transplantation. In more repeated third and fourth transplants the challenge is mainly technical (surgical) in addition to the high probability of sensitization
As many colleagues commented some techniques explained in the paper are: Transperitoneal Kidney Retransplantation, retroperitoneal heterotopic, retroperitoneal heterotopic using vessels of the previously transplanted kidney, and orthotopic Kidney transplantation.
3rd and 4th transplantation are very challenging as the patients are highly sensitized , immuonosuppresed for very long periods with subsequent increased risks of infections and malignancy , on dialysis for longer periods , co morbidity which affect patient and graft survival ,
Besides the surgical challenge of implanting 3rd or 4th kidney
Techniques used :
1) intraperitoneal approach
Through a midline laparotomy incision , kidney is placed intra-peritoneal , artery is anastomosed to ext , internal i,common iliac arteries
,vein is anastomosed to IVC , common, int or external iliac
2) retroperitoneal
Hook steak incision in one of the iliac fossae, carful dissection of the iliac vessels and anastomosis is done over the iliac vessels
3) retroperitoneal using the old renal vessels
Incision is made over the previously failed kidney
Transplant nephrectomy is done ,and renal vessels are used as vascular conduit for the new graft
4) orthotopic kidney transplant
This technique is used with iliac vessels are not suitable any more for anastomosis
The patient is placed on his right lateral position , left nephrectomy is done , artery of the graft is usually anastomosed to splenic artery,
Vein of the graft is anastomosed to native renal vein
1-There are numerous obstacles facing this process mainly
-surgical complinations due to previous operations with subsequent adhrsions .
-immunological sensitizations as the main cause of graft loss is immunologic specially chronic graft loss.
– complications from long term immunesuppression drugs specially cardiovascular and poor wound healing .
Different surgical approaches
1- TRANS-PERITONEAL KIDNEY RETRANSPLANTATION : this the classic approach through a lower midline laparotomy incision to place the graft transperitoneum or in iliac fossa.
2- RETRO-PERITONEAL HETEROTOPIC KIDNEY RETRANSPLANTATION : vessels were anastomosed same as stander technique ( anastomosing the renal artery and vein with either external or common iliac artery and vein ).
3- RETROPERITONEAL HETEROTOPIC KIDNEY RETRANSPLANTATION USING THE VESSELS OF THE PREVIOUSLY TRANSPLANTED KIDNEY : after Tc99M technetium scan and duplex study of these vessels to exclude stenosis and confirm adequate perfusion .
4- ORTHOTOPIC KIDNEY TRANSPLANTATION : only if the iliac vessels of the recipient were not suitable .
Its a review article
Level of evidence 5
Challenges are there in every transplantation but of course every retransplantation is more difficult due to not only technical difficulties with anatomical distance and fibrosis ,but also sensitization of the patient with the previous grafts and the need for more intense immunosuppression with all its complications
Mainly hidden malignancy
First and second transplantation showd increase in patient and graft survival with better quality of life but third and fourth Tx Didn’t seem to show the same good results
Techniques for third and fourth transplantations described in this article:
1 Trans-Peritoneal Kidney Retransplantation using lowe midline incision putting the graft in right iliac fossa.
2 Retro-Peritoneal Heterotopic Kidney Re transplantation.
3 Retro-Peritoneal Heterotopic Kidney Re transplantation with implantation in the vessels Of the Previouse graft .
4 orthotopic kidney transplant.
Review Article
Level 5
Third and fourth transplants are surgically challenging because of anatomical variations distortion ,and adhesions due to previous transplant surgery, medically challenging too because of high risk of sensitizations and immunosupression too
Types:
Trans-Peritoneal Kidney Retransplantation.
Retro-Peritoneal Heterotopic Kidney Retransplantation through vessels of
Tx kidney before
Retro-Peritoneal heterotopic Kidney retransplantation.
Orthotopic Kidney Transplantation.
Summarise the challenges encountered on retransplantation?
it is surgically more technically demanding.
patients are highly sensitised with higher acute rejection rate
have more comorbidities which affects patient and graft survival
have limited surgical options due to previous operations,
previous immunosuppression leads to wound related complications
and long periods on dialysis leads to sensitisation.
Briefly address the various techniques for third and fourth transplants addressed in this article
1)Trans peritoneal kidney transplantation
immunosuppression needs to be given iv which is problematic
protracted ileus is common
pain control is a challenge
intra peritoneal graft is adherent to bowel
difficult to do transplant nephrectomy with the same incision
2)Retro peritoneal heterotopic kidney retransplantation
3) Retroperitoneal heterotopic kidney transplantation using the vessels of the previously transplanted kidney.
need to rule out renal artery stenosis of the failed kidney
4)Orthotopic kidney transplantation
preferred when iliac vessels are deemed unsuitable for vascular anastomosis.
This is a review article with level of evidence 5
As survival of patients on dialysis and kidney transplantation is improving, there is increased number of patients in need for 3rd and fourth transplantation. There are many challenges like surgical challenge ( these patients had multiple operations , and the surgical field is complicated) and immunological challenges( there patients generally is highly sensitized , and need more aggressive immunosuppression ) , also these patients have multiple comorbidities , had long time on dialysis . For all these reasons the 3rd and fourth kidney transplantation is more difficult than 1st and 2nd transplantation.
Types of surgical techniques :
There is no agree consensus on the best surgical approach , and which one to be used depends on the presence of vascular disease, the comorbidities , and the surgeon preference.
Challenges encountered on retransplantation :
However, despite these risks, patients have a significant survival benefit along with better quality of life as well as overall lower health care costs vs the patient remaining on dialysis following a failed transplant.
Good
This is a review article.
Level of evidence 5.
Review article, level of evidence V
Challenges in retransplantation:
Techniques for third & fourth transplantation
Dear All
I have noticed that many of the colleagues do not notice our questions. See Prof Ala question posted above.
Briefly address the various techniques for third and fourth transplants addressed in this article?
1- Trans-peritoneal Kidney Re-transplantation.
2- Retro-peritoneal Hetertropic Kidney Re-transplantation.
3- Retroperitoneal Hetertropic Kidney Re-transplantation Using The Vessels Of The Perviously Transplanted Kidney.
4- Orthotropic Kidney Transplantation.
Many numbers of patients assessed for kidney transplantation, but there are a lot of risk factors which put this transplantation in a challenge.
There’s study for sixty patients underwent third and fourth transplantation results in four mortalities.
Patients who assessed for third and fourth kidney transplantation are highly sensitised and this made them to be put under aggressive immunosuppressive treatment to avoid as much as possible to be rejected.
Several techniques for third and fourth transplantation described.
* Trans-peritoneal Kidney Re-transplantation >>
Graft done trans-peritoneal through midline laparotomy incision and followed by intravenous immunosuppression until patients fit for oral therapy.Many comorbiditis may be percipitated as protracted lieus , pain and especially if recipients may undergrow transplant nephrectomy of previous failed kidney sharing same site required for spacing.
* Retro-Peritoneal Heterotropic Kidney Re-transplantation>>>
One study was done for eight patients, four are received from deceased donors and other four received from living donors. All patients had previously extensive abdominal surgery. This study concluded that extra peritoneal third transplantation is time consuming and may require more transfusions in perioperative period.
Other study underwent for 30 patients received their third kidney transplantation from deceased donors concluded in validity of third transplantation despite higher complications which not threats graft. Other study analyse graft survival , complications rate and acute rejection rates results in showing that graft failure mainly due to ABMR despite aggressive induction therapy was given.
* Retroperitoneal Hetertropic Kidney Transplantation Using The Vessels Of previously Transplanted Kidney .
There were no surgical complications.
* Orthotopic Kidney Transplantation >>>
It is a challenge results in excellent graft survival in unsuitable pelvic vessels.
Discussion :
Published studies were for fewer numbers of patients.
Hagen et al. Reported inferior graft survival for third or fourth transplantation compared to first one.
Third and fourth transplantation despite higher surgical complications are option for some patients.
References >>>
1- Loupy A, Anglicheau D, Timsit MO et al: Impact of surgical procedures and complications
on outcomes of third and subsequent kidney
transplants. Transplantation, 2007; 83: 385–91
2-Horovitz D, Caumartin Y, Warren J et al: Outcome of third renal allograft retransplants versus primary transplants from paired donors.
Transplantation, 2009; 87(8): 1214–20
3-Nourbala H: Using the inferior mesenteric artery for a third renal transplant. Br J Urol, 1998;
82: 296
4-Nourbala MH, Ghaheri H, Kardavani B: our experience with third renal transplantation: results, surgical techniques and complications.
Int J Urol, 2007; 14: 1057–59
5- Folkert O, Belzer FO, Neal G et al: Technical
complication after renal transplantation. Morris Kidney Transplantation. Saunders, Philadelphia, PA, 1988
6-Teodor P: Grantcharov and Jacob Rosenberg:
Vertical Compared with Transverse Incisions
in Abdominal Surgery. Eur J Surg, 2001; 167:
260–67.
Summarise the challenges encountered on re-trainsplantation?
a- Technically challenging procedure and associated with more complications.
b- Highly sensitized patients from previous transplant, with higher chance of acute rejection.
c- Increased risk related to intensive immunosuppression.
d- Increased risk of malignancy.
Briefly address the various techniques for third and fourth transplants addressed in this article
1) Trans peritoneal approach with lower midline incision and graft placement in intraperitoneal space or iliac fossa.
2) Retroperitoneal heterotopic approach.
3) Retroperitoneal heterotopic approach using the vessels of previously transplanted kidney
4) Orthotopic kidney transplant.
Type of article? Review
Level of evidence? V
This article is a narrative review with a low level of evidence (level 5)
Some issues related to third and fourth kidney transplantation make them challenging, consisting of technical difficulties are associated with numerous surgical interventions, sensitization and higher rate of acute rejection and, as a consequence of them, the need for aggressive immunosuppression and, as a result, the increased risk of infections and malignancies.
Various techniques were applied for the third and fourth kidney transplantation, including: trans peritoneal kidney transplantation, retro peritoneal heterotopic kidney transplantation, retroperitoneal heterotopic kidney transplantation using the vessels of the previously transplanted kidney and orthotopic kidney transplantation.
There isn’t any standard technique for third and fourth kidney transplantation and it is accompanied by the complexity of the procedure. Retro peritoneal heterotopic kidney transplantation with or without transplant nephrectomy can be considered as the first option when it is appropriate.
Some studies have demonstrated patient and graft survival in the third and fourth kidney transplantation lower or similar to first and second kidney transplantation with more surgical complications. However, the main cause of graft loss is immune mediated including acute rejection or chronic allograft nephropathy.
Thank you all for the responses.
Who do you think the patient best fits the scenario of the 3rd and 4th transplant?
1- Patients which are not highly sensitized
2- Patients with little comorbidities, with no cognitive impairment and not frail
3- Patient who find living donor with HLA compatible kidney
4- Patients with no history of malignancy related to immunosuppressive drugs
5- Patients with no history of infections such as BK, CMV that lead to reduction of immunosuppression and graft failure
I think i would recommend third or fourth transplantations for
1 patient who is not highly sensitized
2 younger patients with no comorbidities
3 patients who are carefully investigated for hidden malignancy or infections especially CMV
Bk
Children or young adults are the best examples of needing a 3rd or 4th transplant. A graft for a child may be lost while he is still in active life, which means more than one transplant. Thus, there will be more immunological and surgical challenges and complications with the advancing age and more grafts.
Third and fourth retransplantation may offer advantages over dialysis but this should be studied in more precise studies with a careful selection of the patients. However there is no globally agreed method for third and fourth transplants, from technical point of view, which are significantly more complex.
pt also have higher rate of rejection because these patients are highly sensitized.Increase rate of infection and malignancy due to prolonged and aggressive courses of immunosuppression used either for induction, maintainiance or for desensitization.
the various techniques for third and fourth transplants addressed in this article:
1-Trans-Peritoneal Kidney Retransplantation.
2- Retro-Peritoneal Heterotopic Kidney Retransplantation.
3- Retro-Peritoneal Heterotopic Kidney Retransplantation Using The Vessels Of The
PreviouslyTransplanted Kidney.
4- Orthotopic Kidney Transplantation
1. Summarise the challenges encountered on retransplantation?
Challenges encountered in re-transplanted are both due to the surgical procedure as well as post-procedure graft function. But first and foremost challenge is getting the next kidney for transplant. Re-transplantation is technically demanding due to prior surgery and is associated with wound associated complications due to prior prolonged immunosuppression. Patients who undergo re-transplant usually have multiple co-morbidities which complicate clinical management and they are highly sensitized, with higher risks of acute rejection hence requiring increased immunosuppression, which in turn increases the risk of infections and malignancy.
2. Briefly address the various techniques for third and fourth transplants addressed in this article
Various techniques for 3rd and 4th transplant include:
1) Transperitoneal approach with lower midline incision and graft placement in intraperitoneal space or iliac fossa after mobilizing the bowel.
2) Retroperitoneal heterotopic approach
3) Retroperitoneal heterotopic approach with utilising vessels of previously transplanted kidneys (after graft nephrectomy), utilized in patient with previous SPK (simultaneous pancreas kidney transplant). Prior radiological evaluation of the previous graft vessels is important.
4) Orthotopic kidney transplant (after graft nephrectomy) in patients with severe atherosclerotic aorto-iliac disease and bilateral prior renal grafts.
1- challenges encountered on retransplantation :
a- the surgical procedure is more complex and include a higher complications rate as well as a higher mortality rate.
b- the recipient is already more sensitized from prevoius grafts and so he will need a careful selection of possible donors. also, the degree of immunosuppression will be more intensive.
c- graft survival is lower if compared to 1st or 2nd transplantation. graft loss is mainly due to immunological mechanisms rather than surgical complications.
d- exhaustion of the available donor pool with intensifying the problem of lacking donors.
2- the various techniques of 3rd & 4th re-transplantation :
a- transperitoneal : using the native vessels for vascular anastomosis.
b- retroperitoneal heterotropic : also using the native vessels.
c- retroperitoneal heterotropic using vessels of previous renal grafts.
d- orthotopic ; using unusual native vessels as splenic, mesenteric or IVC itself, for vascular anastomosis
· This is a review article
· Level 5 evidence
· Challenges encountered for retransplantation
Third and fourth transplantation is inferior to first and second although it is considered a survival chance.
The operation is technically more difficult along with the prolonged immunosuppression ,wound related complications which can be challenging
Most patients have higher risk of acute rejection neccesitating aggressive immunosuppression which increases the occurence of malignancy and infection.
· The various techniques for third and fourth transplants
-Transperitoneal kidney retransplantation through a lower midline laparotomy incision.
-Retro periotineal heterotopic kidney retransplanation performed extraperitoneally with increased possibility of arterial thrombosis and urinary obstruction .
-Retro periotineal heterotopic kidney retransplanation using the previously transplanted kidney vessels where the incision is done over over the failed transplant kidney, followed by dissection of the renal vessels then transplant nephrectomy , so far no surgical complications were established.
-Orthotopic kidney transplantation is used for special group of patients as those with severe atherosclerosis of the aorto- iliac arteries when the iliac vessels are unfit for vascular anastomosis. Studies revealed acceptable patient and graft survival with this technique
Retroperitoneal heterotopic transplantation was considered as the primary choice either with or without transplant nephrectomy
Review article
Level of evidence 5
Challenges encountered in the 3rd and 4th transplant can be summarized in the following :
1- Surgical challenges
– Technical difficulties due to multible operations done before.
– Wound complications are more common due to prolonged immunosuppression
– Post operative surgical complications are more common.
Medical challenges
– Higher rate of rejection because these patients are highly sensitized.
– Increase rate of infection and malignancy due to prolonged and aggressive courses of immunosuppression used either for induction, maintainiance or for desensitization.
– Multible comorbidites usually these patients have.
Surgical approaches :
1- Trans-peritoneal approach using lower midline incision and the graft is placed in intraperitonial space either in midline or in the iliac fossa.
2- Reteroperitoneal heterotopic approach.
3-Reteroperitoneal hetertopic approach using the vessel of previous transplanted graft
4- Orthotopic kidney transplant where the graft is put at the same site (usually the left) of native kidney after native nephrectomy and splenectomy, splenic artery of the recipient is anastmosed to the renal artery of the graft, renal vein of the recipient is anastmosed to renal vein of the graft and ureter of recipient is anastmosed to ureter of the graft.
1-A review article
2-level of evidence 5
The third and fourth transplants are much more difficult.
Due to past procedures, immunosuppression, and extended durations on dialysis, patients are often extremely sensitive, concomitant with restricted surgical alternatives.
There is a common misconception that third and fourth retransplantation would provide no benefit to this group of patients and will be deemed inefficient use of the limited supply of organs.
Recent research has shown that third and fourth transplantation improves survival but is somewhat inferior to first and second transplantation, although no recognized procedure exists.
Despite the surgical difficulty, immune-mediated graft loss is the leading cause of transplant loss in this patient group, not surgical problems.
the approach for 3rd and 4th transplant:
The challenges of third and fourth transplantation are :
(1)-numerous surgical interventions making the operation more technically demanding, a long history of immunosuppression with subsequent wound related complications and multiple co-morbidities which may affect the patient and graft survival.
(2)Sensitisation history may also create a dilemma in immunological ma- nipulation post-transplantation. They are always highly sensitised with higher acute rejection rate requiring aggressive immunosuppression com- pared to first and second transplantation
(3)On the other hand, aggressive immunosuppression increases the risk of malignancy and infection complications
Inspite of the surgical challenge, the main cause of graft loss in this cohort of patient is immune mediated rather than the surgical complications.
techniques for third and fourth kidney transplantation include:
1. TRANS-PERITONEAL KIDNEY RETRANSPLANTATION
2. RETRO-PERITONEAL HETEROTOPIC KIDNEY RETRANSPLANTATION
3. RETROPERITONEAL HETEROTOPIC KIDNEY RETRANSPLANTATION USING THE VESSEL
4. ORTHOTOPIC KIDNEY TRANSPLANTATION
All the techniques mentioned above are associated with higher surgical complication rate and mortality which is quite expected in this patient population, but there is a survival advantage in transplanting these patients.
Recipients of third and fourth transplantation have many risk factors which made this procedure challenging, these risk factors are numerous previous surgeries that make surgical techniques are difficult, long history of immune suppression with subsequent wound related complications such as infection and poor healing, multiple comorbidities that can affect patient and graft survival. sensitization history is also challenging in these patients. Aggressive immunosuppression increases the risk of malignancy.
Several techniques for third and fourth transplantation:
1. Trans-peritoneal kidney transplantation
2. Retro-peritoneal hetrotropic kidney transplantation
3. Retro-peritoneal hetrotropic kidney transplantation using the vessels of the previously trasplanted kidney
4. Orthotopic kidney transplantation
It is difficult to recommend a particular technique as the standard operation for the third and subsequent transplantation due to anatomical variation in those patients, retro peritoneal hetrotropic method with or without transplant nephrectomy considered as the first option . Appropriate patient counseling is essential before transplantation.
Third and fourth transplantation despite the higher rates of surgical complications still considered a valuable option for these patients
Thank you, Huda
You raised essential points:
The need for transplant nephrectomy before the 3rd or 4th may be due to early graft failure , Some vascular complications , pyonephrosis, malignancy and rupture graft . transplant nephrectomy may affect the immunological status of the recipient , as an organ adsorbent of the circulating immune cells that was removed , the recipient is more liable for higher sensitization according to some studies