*2.8.2.3. Laparoscopic donor nephrectomy - alternative to increase the rate of living donation*

One great potential means for obtaining more kidneys is throw live donation. When compared with cadaveric renal transplantation, living donor transplantation has several advantages, in fact well known, which includes better graft survival, more rapid renal function after trans‐ plantation, shorter hospitalization and finally lower cost. However, several barriers exists for potential living donors. Significant time is involved when one donates a kidney. Many individuals do not have adequate financial and social support available that would allow them to make a personal sacrifice and a time commitment necessary for kidney donation. Moreover, the relatively prolonged convalescence can have significant financial impact on donor. Finally, fear of pain as well cosmetic concerns, associated with flank incision, can militate against kidney donation.

Laparoscopic living donor nephrectomy (LLDN) with all its alternatives (transperitoneal approach, retroperitoneal approach, hand assisted laparoscopic nephrectomy) was introduced in 1995 by Ratner and Kavoussi [62].

Laparoscopic nephrectomy is more technically demanding than other standard abdomi‐ nal laparoscopic procedures. The surgeon experience is crucial for minimizing potential morbidity. Significant operative differences are between open and laparoscopic donor nephrectomy. The later approach requires a different set of technical skills than that associated with traditional open surgery. The endoscopic video image is only two dimen‐ sional and much narrower when compared with direct vision afforded by open surgery. The types of instrumentation available for working throw the small incision afford only restricted degrees of freedom when compared to the human hand. Moreover, the tactile sensation, currently can not be transmitted through the instrument. The differences are giving a longer operative time with one or even two hours when compared with open donation. All these drawbacks are only partially eliminated by robotic surgery, even if now there is a three dimensional vision of operative field and the mobility of the working instruments is better than that of human hand.

**Laparoscopic Open P value**

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266+/-174 393+/-335 0.027

0.8+/-0.5 2.6+/-1.0 <0.001

4.0+/-2.3 6.4+/-3.1 0.003

*Allograft rejection.* The pneumoperitoneum and retropneumoperitoneum reduces renal blood flow and urine output. The potential for ischemia can make the donor kidney more allogenic by inducing MHC class II expression. This problem could be avoided giving donors intrao‐ peratively a 6-8 liters of crystalloid to promote brisk diuresis, and having an accurate dissection of the renal pedicle and harvesting the kidney only in full diuresis. Biopsy proved rejection in laparoscopically obtained kidney occurred in 30% of cases compared with 35.4% of cases of kidneys harvested by open procedure. At 12 months, creatinine clearance in recipient of kidney

Laparoscopic nephrectomy gives less postoperative pain, quicker convalescence, better cosmetic results when compared with traditional open operation. In experienced hands, this procedure is accomplished without increasing the risks to donor safety and allograft function. Complications are comparable to those reported in historic series using open surgery. Longer operative time and the need of disposable equipment result in greater hospital costs. However, quicker convalescence permit patients to resume activities sooner and produce market cost

During the past decade, several innovative protocols have been adopted to overcome trans‐ plantation across a positive cross-match or an ABO blood group barrier. Protein A immu‐ noadsorbtion, high dose intravenous immunoglobuline (IVIG), low dose iv Ig in combination with plasmapheresis, rituximab, splenectomy, all of them alone or in combination, can abrogate a positive cross-match and enhance the chance of a highly sensitized patients to receive a cross-match negative organ. Similar strategies can be used for ABO incompatible

donors and are particularly effective when the titter of blood group antigen is low.

from laparoscopic and open procedure were both 66 mL/min. (p = not significant).

**Operative time (min.)** 232+/-33 183+/-27 <0.001 **Hospital stay (days)** 3.0+/-0.9 5.7+/-1.7 <0.001

Oral narcotics 4 12 <0.001 Acetaminophen 3 17 <0.001

**Estimated blood loss (mL)**

**Analgesia (days of use)**

**Resumed oral intake (days)**

**Returned to work (weeks)**

**Table 4.** Open versus laparoscopic donor nephrectomy

savings both for patients and employer.

*2.8.2.4. HLA sensitized and ABO incompatible donor and recipient*

Even so, laparosccopic renal donation and robotic laparoscopic harvesting offers both introperatively and postoperatively great benefits to the donor.

Due to magnification provided by the optical system and the video camera, in experienced hands, the dissection of the renal pedicle is more accurate and if it is realized through retro‐ peritoneal approach it is much more direct and quicker than classical approach.

The decreased size of the incision for extracting kidney and placement of that incision in the lower abdomen, significantly reduce postoperative pain when compared with traditional opened surgery; it also reduce traumatism of the abdominal wall, which is followed by a quicker and better healing and mobilization postoperatively and quicker reintegration of the patient in society.

Usually, these patients resume their oral intake in the first postoperative day and normal alimentation in maximum two days after surgery.

All retrospective comparations between open and laparoscopic kidney donation show that analgesic requirements for LLDN and robotic LDN, were 30% lower than those for open procedures. Need for oral pain medication is also reduced.

Return to physical demanding work also occurs, on average, 17th days sooner for the laparo‐ scopic group compared with classic operation.

*Recipient and graft survival.* All retrospective review of the recipient who received a kidney through laparoscopic or robotic laparoscopic donation compared with those who received kidney via standard open nephrectomy shows no statistical differences if the groups are matched in regard with the number of HLA mismatches, donor relationship, diabetes, previous transplant, gender, or race.

*Allograft function.* The majority experience in the field attest that all grafts functioned intrao‐ peratively and no clinical significant injury occurred to the graft.


**Table 4.** Open versus laparoscopic donor nephrectomy

Laparoscopic nephrectomy is more technically demanding than other standard abdomi‐ nal laparoscopic procedures. The surgeon experience is crucial for minimizing potential morbidity. Significant operative differences are between open and laparoscopic donor nephrectomy. The later approach requires a different set of technical skills than that associated with traditional open surgery. The endoscopic video image is only two dimen‐ sional and much narrower when compared with direct vision afforded by open surgery. The types of instrumentation available for working throw the small incision afford only restricted degrees of freedom when compared to the human hand. Moreover, the tactile sensation, currently can not be transmitted through the instrument. The differences are giving a longer operative time with one or even two hours when compared with open donation. All these drawbacks are only partially eliminated by robotic surgery, even if now there is a three dimensional vision of operative field and the mobility of the working

Even so, laparosccopic renal donation and robotic laparoscopic harvesting offers both

Due to magnification provided by the optical system and the video camera, in experienced hands, the dissection of the renal pedicle is more accurate and if it is realized through retro‐

The decreased size of the incision for extracting kidney and placement of that incision in the lower abdomen, significantly reduce postoperative pain when compared with traditional opened surgery; it also reduce traumatism of the abdominal wall, which is followed by a quicker and better healing and mobilization postoperatively and quicker reintegration of the

Usually, these patients resume their oral intake in the first postoperative day and normal

All retrospective comparations between open and laparoscopic kidney donation show that analgesic requirements for LLDN and robotic LDN, were 30% lower than those for open

Return to physical demanding work also occurs, on average, 17th days sooner for the laparo‐

*Recipient and graft survival.* All retrospective review of the recipient who received a kidney through laparoscopic or robotic laparoscopic donation compared with those who received kidney via standard open nephrectomy shows no statistical differences if the groups are matched in regard with the number of HLA mismatches, donor relationship, diabetes,

*Allograft function.* The majority experience in the field attest that all grafts functioned intrao‐

peritoneal approach it is much more direct and quicker than classical approach.

instruments is better than that of human hand.

148 Current Issues and Future Direction in Kidney Transplantation

alimentation in maximum two days after surgery.

scopic group compared with classic operation.

previous transplant, gender, or race.

procedures. Need for oral pain medication is also reduced.

peratively and no clinical significant injury occurred to the graft.

patient in society.

introperatively and postoperatively great benefits to the donor.

*Allograft rejection.* The pneumoperitoneum and retropneumoperitoneum reduces renal blood flow and urine output. The potential for ischemia can make the donor kidney more allogenic by inducing MHC class II expression. This problem could be avoided giving donors intrao‐ peratively a 6-8 liters of crystalloid to promote brisk diuresis, and having an accurate dissection of the renal pedicle and harvesting the kidney only in full diuresis. Biopsy proved rejection in laparoscopically obtained kidney occurred in 30% of cases compared with 35.4% of cases of kidneys harvested by open procedure. At 12 months, creatinine clearance in recipient of kidney from laparoscopic and open procedure were both 66 mL/min. (p = not significant).

Laparoscopic nephrectomy gives less postoperative pain, quicker convalescence, better cosmetic results when compared with traditional open operation. In experienced hands, this procedure is accomplished without increasing the risks to donor safety and allograft function. Complications are comparable to those reported in historic series using open surgery. Longer operative time and the need of disposable equipment result in greater hospital costs. However, quicker convalescence permit patients to resume activities sooner and produce market cost savings both for patients and employer.

#### *2.8.2.4. HLA sensitized and ABO incompatible donor and recipient*

During the past decade, several innovative protocols have been adopted to overcome trans‐ plantation across a positive cross-match or an ABO blood group barrier. Protein A immu‐ noadsorbtion, high dose intravenous immunoglobuline (IVIG), low dose iv Ig in combination with plasmapheresis, rituximab, splenectomy, all of them alone or in combination, can abrogate a positive cross-match and enhance the chance of a highly sensitized patients to receive a cross-match negative organ. Similar strategies can be used for ABO incompatible donors and are particularly effective when the titter of blood group antigen is low.

*Plasmapheresis and intravenous immunoglobuline as a rescue therapy for a positive cross-match live donor kidney transplants.* The positive cross-match can present a virtually an insurmountable barrier to kidney transplantation. Anti HLA antibodies have been identified as the predomi‐ nant cause of early graft failure from hyperacute rejection and acute humoral rejection.

but the problem is that the blood group O donors are universal donors for all blood groups. They can give the kidney directly to their recipients than rather to a stranger. When the crossmatch is positive with own one's recipient, but this recipient has a negative cross-match with blood group A or B donor from another couple, the problem is solved by exchanging the kidneys between these pairs. Another reason for kidney exchange is when the O to A or B pair get a better HLA matching from 6 miss-matches to 0-3 miss-matches by swapping the kidney

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The pairs involved in a paired exchange program are interviewed to exclude any coercion of the donor, they are informed about the advantage and the risk of the living donation and the informed consent is obtained. Beside that, all donors undergo psychological evaluation.

The inclusion criteria pursued the goal of exchanging equivalent kidneys with equivalent size, anatomy, similar renal function and similar age. The donor are assessed preoperatively by high resolution iv pyelograms, quantitative renal scan and spiral CT scan or MRI. As a general rule, the donors accept to join this program as this is the only way to help their relatives or friends. The transplants involving two or three pairs can be performed simultaneously excepting the session with more than three pairs when the transplants are performed succes‐ sively. All the transplants are performed by the same surgical team in respect to the principle

The basic principle of kidney exchange is the equivalent exchange. To accomplished this, high resolution preoperative work-ups required and unpredicted situation which can hinder

By using kidney exchange, the recipient benefit from the better matching as well as the known advantages of living donation. Paired kidney exchange reduce the duration of dialysis before

In the countries where the living donation is the main source of organs, cross-over transplan‐ tation may become more popular as it increase the number of transplants. The kidney exchange

*Transplantation of ABO incompatible pairs.* Developed initially in countries with predominant living donation, transplantation of a ABO incompatible kidney is a demanding task but it was possible mainly due to development of more potent immunosuppressive drugs which reduces the risk of hyperacute rejection [67]. In japan, transplantation of a ABO incompatible kidney from a living donor is preferred to a deceased donor graft but the experience already acquired was extended in many other countries for recipients having only a ABO incompatible donor

The procedure involves a pretransplant treatment in order to remove the ABO antibody and to prevent furture production. Thus, Rrituximab is administred one month before transplan‐ tation followed by plasmapheresis 7 to 14 days before transplantation. With Rituximab there is no need for splenectomy and plasmapheresis is done in alternate days or even daily in order to reduce the ABO antibody titer under 8. The plasma removed is replaced with albumin solution and a combination of albumin and fresh frozen solution just immediately before

harvesting are avoided. This way, simultaneously harvesting is not mandatory.

program has to be promoted as it offers solutions where apparently there is none.

with a A or B to O pair.

willing to donate [68].

to equivalent quality of the surgical act.

transplantation and expand the pool of living donors.

Once the consequence of performing a transplant, in the face of a circulating donor specific alloantibody were fully appreciated and routine pre-transplant cross-matching emerged as a standard, hyperacute rejection became rare, but a large population of a highly sensitized patients who have a little hope of receiving transplant has been subsequently identified.

Some of the longest waiting times for a kidney transplant are observed in patients who are allo-sensitized because of a prior transplant, blood transfusions or pregnancy. Some of these recipients have live donor, meet standards criteria for living donor transplantation, but have a positive cross-match with their donor. A combination of plasmapheresis and IVIG under the cover of standard doses of calcineurin inhibitors or rituximab, together with mycophenolate mofetil and steroids, can effectively and durably remove donor specific anti-HLA antibody, preemptively desensitize the recipient who had positive cross-matches with a potential live donor, allowing the transplantation of this patients using a live donor without cases of hyperacute rejection [63].

This preemptive therapy is initiated several weeks before a planned live donor transplant. Our standard protocol was designed to include oral immunosuppressants before first plasmaphe‐ resis treatment followed by a maximum six plasmapheresis on alternate days. The recipients, also received seven days of IVIG (100 mg/kg/day).

Cross-over transplantation and paired kidney exchange as a method to fill the gap of positive cross-match and ABO incompatibility. The gap between the number of donors and number of patients waiting for a kidney transplant continues to widen. Fewer patients get transplants every year because of the organ shortage. This patients can receive a donor from a living donor such a family member, a friend, or even a foreign individual.

The pool of such kidneys has not been fully utilized because not all living donors are compat‐ ible with their recipient. Patients with available living donor continue dialysis and many of them die because of ABO incompatibility, cross-match positive, low HLA-matching. Since the report made by Rapaport, when was set the bases of kidney exchange between two donorrecipient pairs in order to obtain a better compatibility, things have changed [64-66]. A spouse donor would give her kidney to an unrelated recipient who matched her blood type. That recipient's mate would provide a kidney for the donor's ill spouse. This swap would imply more than two pairs in order to obtain best compatibility. A cross-over renal transplantation or a paired kidney exchange transplantation is defined by a living kidney donation or a living kidney cadaver pool donation and exchange between two or more such couples who are hindered by ABO incompatibility or positive cross-match to give the kidneys not to the own recipients but solve the problem by cross-exchange the kidney between the pairs to make more matches.

The most frequent reason for ABO incompatibility, preventing living donors from donating is a blood group A or B donor and a blood group O recipient. There are many vice-versa pairs but the problem is that the blood group O donors are universal donors for all blood groups. They can give the kidney directly to their recipients than rather to a stranger. When the crossmatch is positive with own one's recipient, but this recipient has a negative cross-match with blood group A or B donor from another couple, the problem is solved by exchanging the kidneys between these pairs. Another reason for kidney exchange is when the O to A or B pair get a better HLA matching from 6 miss-matches to 0-3 miss-matches by swapping the kidney with a A or B to O pair.

*Plasmapheresis and intravenous immunoglobuline as a rescue therapy for a positive cross-match live donor kidney transplants.* The positive cross-match can present a virtually an insurmountable barrier to kidney transplantation. Anti HLA antibodies have been identified as the predomi‐ nant cause of early graft failure from hyperacute rejection and acute humoral rejection.

Once the consequence of performing a transplant, in the face of a circulating donor specific alloantibody were fully appreciated and routine pre-transplant cross-matching emerged as a standard, hyperacute rejection became rare, but a large population of a highly sensitized patients who have a little hope of receiving transplant has been subsequently identified.

Some of the longest waiting times for a kidney transplant are observed in patients who are allo-sensitized because of a prior transplant, blood transfusions or pregnancy. Some of these recipients have live donor, meet standards criteria for living donor transplantation, but have a positive cross-match with their donor. A combination of plasmapheresis and IVIG under the cover of standard doses of calcineurin inhibitors or rituximab, together with mycophenolate mofetil and steroids, can effectively and durably remove donor specific anti-HLA antibody, preemptively desensitize the recipient who had positive cross-matches with a potential live donor, allowing the transplantation of this patients using a live donor without cases of

This preemptive therapy is initiated several weeks before a planned live donor transplant. Our standard protocol was designed to include oral immunosuppressants before first plasmaphe‐ resis treatment followed by a maximum six plasmapheresis on alternate days. The recipients,

Cross-over transplantation and paired kidney exchange as a method to fill the gap of positive cross-match and ABO incompatibility. The gap between the number of donors and number of patients waiting for a kidney transplant continues to widen. Fewer patients get transplants every year because of the organ shortage. This patients can receive a donor from a living donor

The pool of such kidneys has not been fully utilized because not all living donors are compat‐ ible with their recipient. Patients with available living donor continue dialysis and many of them die because of ABO incompatibility, cross-match positive, low HLA-matching. Since the report made by Rapaport, when was set the bases of kidney exchange between two donorrecipient pairs in order to obtain a better compatibility, things have changed [64-66]. A spouse donor would give her kidney to an unrelated recipient who matched her blood type. That recipient's mate would provide a kidney for the donor's ill spouse. This swap would imply more than two pairs in order to obtain best compatibility. A cross-over renal transplantation or a paired kidney exchange transplantation is defined by a living kidney donation or a living kidney cadaver pool donation and exchange between two or more such couples who are hindered by ABO incompatibility or positive cross-match to give the kidneys not to the own recipients but solve the problem by cross-exchange the kidney between the pairs to make more

The most frequent reason for ABO incompatibility, preventing living donors from donating is a blood group A or B donor and a blood group O recipient. There are many vice-versa pairs

hyperacute rejection [63].

matches.

also received seven days of IVIG (100 mg/kg/day).

150 Current Issues and Future Direction in Kidney Transplantation

such a family member, a friend, or even a foreign individual.

The pairs involved in a paired exchange program are interviewed to exclude any coercion of the donor, they are informed about the advantage and the risk of the living donation and the informed consent is obtained. Beside that, all donors undergo psychological evaluation.

The inclusion criteria pursued the goal of exchanging equivalent kidneys with equivalent size, anatomy, similar renal function and similar age. The donor are assessed preoperatively by high resolution iv pyelograms, quantitative renal scan and spiral CT scan or MRI. As a general rule, the donors accept to join this program as this is the only way to help their relatives or friends. The transplants involving two or three pairs can be performed simultaneously excepting the session with more than three pairs when the transplants are performed succes‐ sively. All the transplants are performed by the same surgical team in respect to the principle to equivalent quality of the surgical act.

The basic principle of kidney exchange is the equivalent exchange. To accomplished this, high resolution preoperative work-ups required and unpredicted situation which can hinder harvesting are avoided. This way, simultaneously harvesting is not mandatory.

By using kidney exchange, the recipient benefit from the better matching as well as the known advantages of living donation. Paired kidney exchange reduce the duration of dialysis before transplantation and expand the pool of living donors.

In the countries where the living donation is the main source of organs, cross-over transplan‐ tation may become more popular as it increase the number of transplants. The kidney exchange program has to be promoted as it offers solutions where apparently there is none.

*Transplantation of ABO incompatible pairs.* Developed initially in countries with predominant living donation, transplantation of a ABO incompatible kidney is a demanding task but it was possible mainly due to development of more potent immunosuppressive drugs which reduces the risk of hyperacute rejection [67]. In japan, transplantation of a ABO incompatible kidney from a living donor is preferred to a deceased donor graft but the experience already acquired was extended in many other countries for recipients having only a ABO incompatible donor willing to donate [68].

The procedure involves a pretransplant treatment in order to remove the ABO antibody and to prevent furture production. Thus, Rrituximab is administred one month before transplan‐ tation followed by plasmapheresis 7 to 14 days before transplantation. With Rituximab there is no need for splenectomy and plasmapheresis is done in alternate days or even daily in order to reduce the ABO antibody titer under 8. The plasma removed is replaced with albumin solution and a combination of albumin and fresh frozen solution just immediately before transplantation to correct the coagulation. A key point is the administration of IVIG immedi‐ ately after each plasmapheresis. The plasmapheresis is continued in the first two weeks after transplantation if ABO antibody titer was over 256 before Rituximab, if there is an increase of ABO antibody more than three times after transplantation, and if the serum creatinine increases more than 15% in two weeks after transplantation. The immunosuppression includes Tacrolimus, mycophenolate mofetil and steroids. In the first three weeks, the patient is at high risk of developing hyperacute humoral rejection, thus a graft biopsy is warranted whenever the serum creatinine increase over 15% in two weeks [69].

**•** Commercial donation will result in the rich having access to organs for transplantation while

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**•** Donors will be exploited by unscrupulous middleman and sometimes, even by the sur‐

**•** The pour don't know how to handle the money that comes to them and will make no permanent difference in their poverty. This perception may be based on experience with lottery winners and other recipients of a sudden winfall. Donors will have widely differing abilities to plan for the future and would be difficult to predict what they will do with the payment for their donation. The possibility off misuse of money does not justify the

**•** During its entire history, transplantation has relayed on the altruism of donors and their families. Commercial donation would change the fundamental character of organ donation and likely would lead to the disappearance of altruistic donor. If any transplants are payed for, all will have to be. Most of payed donors are giving an organ to a specific individual. Payed donors would not have a choice about recipient. Thus, altruistic donation should

**•** The initial enthusiastic support of organ transplantation has been replaced by suspicion. Although no evidence has proved the charges that are widely accepted urban myths regarding transplantation. This includes stories of people, particularly south-american children being kidnapped and killed for their organs, and people being drugged and kidnaped only to awaken in an alley with a flank incision and no kidney on that side. The myths can only be dispelled by the education, nothing else. Moreover, the possibility exists that skillful paper editors and television producers will exploit current practices for

Available data on the outcome of organ vending for the donors, indicates that the most of them have a pour outcome. On the other side, recipient of vended organ are subject to an increased risk for complications, particularly infections, likely as a result of a break-down of trust and honesty that is a byproduct of commercialization of organ donation. Evidence from several countries has shown that commercialization of organ donation comes at the expense of

The modest increase in cadaveric renal transplant in USA has been achieved in principally by extending use of older and younger donors [71]. Fortunately, the death from motor vehicle accidents has decreased over the passed 20 years mainly due to laws meant to increase the safety on the road: the seat belt laws, passive restraints, child safety seats, and stricter drunk driving laws. The greatest number of lives saved by improved highway safety has been specially at the 15 to 40 years old age group. On the other hand, another concern is related to the estimation that 10% of potential donors might be ineligible because of HIV infection [72].

geons. The medical care of both donor and recipient will suffer generally.

overriding the donors wish to give up a kidney.

program for the related and unpaid living unrelated donation.

the pour do not.

continue.

purposes of sensationalism.

**3. Cadaveric donation**

The use of specific immunoadsorbtion instead of plasmapheresis is not only less aggressive but also more effective since it allows more than two plasma exchange equivalent per one session [70].

Even if renal transplantation agains ABO blood group is expensive and, due to the increased immunosuppression, increases the infectious and malignancy risk, graft function at five years is slightly similar to transplantation of ABO compatible grafts [68].

### **2.9. Commercial renal transplantation**

World Health Organization condemned the sales of organs since 1989. Sales of organs and tissues has been made illegal in the majority civilized states of the world. The difference between altruistic donation of a kidney and selling off a kidney is viewed as similar to the difference between marriage and prostitution. The first is a sacrament, the second a sin.

Reimbursement for expenses related to the donation process, such as for traveling and lodging is not prohibited, although a formal mechanism to make such reimbursements is not available everywhere, a factor that could act as a decentive to donation for some potential donors.

Iran is currently the only country in which payed donation is officially sanctioned, almost all the donors are pour and uneducated and follow-up studies have shown that their lives are not improved.

Despite the legal constraints on organ sales, commercial kidney transplantation is a common phenomena in many parts of the world, and in some cases has been linked to criminal activity. The donors are typical pour or under great financial stress, the recipients are often wealthy or come from other wealthier countries, and middleman or brokers are often involved.

Arguments against payed donation shows:


Available data on the outcome of organ vending for the donors, indicates that the most of them have a pour outcome. On the other side, recipient of vended organ are subject to an increased risk for complications, particularly infections, likely as a result of a break-down of trust and honesty that is a byproduct of commercialization of organ donation. Evidence from several countries has shown that commercialization of organ donation comes at the expense of program for the related and unpaid living unrelated donation.
