**2.2 Management of pre-existing medication**

Patients with advanced kidney disease are often on multiple medications, many of which can be safely discontinued at the time of transplantation, including most antihypertensive medication, phosphate binders, cinacalcet, and erythropoiesisstimulating agents. However, some medications should usually be continued as follows:


targets [11]. European Best Practices Guidelines for anaemia management recommend that ESA not be ceased in patients undergoing surgery, but no specific recommendations are made regarding transplantation [12].

Potential transplant recipients who are anti-coagulated with warfarin require urgent reversal of anticoagulation prior to surgery. There are often local protocols for warfarin reversal, but a typical approach would be 1–2 mg oral vitamin K administered as soon as the patient presents to hospital, followed by infusion of either fresh frozen plasma or a prothrombin complex concentrate, such as prothrombinex-VF, depending on the INR [13]. Whether intravenous heparin is required post-operatively will depend on the strength of the indication for anticoagulation, the degree of post-operative haemorrhage, and a decision regarding this should be made in consultation with the transplant surgeons. Where the risk of thrombosis is not excessively high, it is preferable to defer recommencing warfarin until at least 4 weeks post-transplant due to the frequent requirement for a transplant biopsy during this period.

Although non-vitamin K oral anticoagulants (NOACs) are currently not used routinely in end-stage kidney disease (ESKD) patients, indications for their use have been expanding into patients with more severe renal dysfunction. Nonetheless, NOACs should be avoided in ESKD patients on the active transplant list.

#### **2.3 Pre-operative management of diabetes and hyperglycaemia**

In Australia, over 23% of patients who are listed for a deceased donor transplant have diabetes [ANZDATA 2016]. The presence of autonomic neuropathy should be noted, as this may help predict haemodynamic instability and risk for graft hypoperfusion post-operatively. Similarly, gastroparesis may have important implications for immunosuppressive drug absorption if severe and retinopathy may complicate post-operative medication management if visual acuity is substantially reduced.

After admission for kidney transplantation, patients with type 2 diabetes should omit hypoglycaemic medication during the period of preoperative fasting, with regular capillary glucose monitoring performed every 1–2 h. Hypoglycaemia is managed with intravenous dextrose. If significant hyperglycaemia develops, an intravenous insulin infusion is the safest method to control glucose levels until the recipient is able to eat post-operatively. Patients with type 1 diabetes should commence an intravenous insulin infusion after admission to hospital to prevent the development of ketoacidosis.

#### **2.4 Immunosuppression**

After the decision has been made to proceed with a transplant, an immunosuppression regimen is selected. This regimen is usually initiated before the recipient goes to theatre so that immune function is attenuated prior to donor antigen exposure after reperfusion of the allograft. The choice of immunosuppressive regimen is individualised depending on the circumstances of the recipient and, in particular, the perception of immunological risk (**Table 2**).

Most patients undergoing kidney transplantation will receive induction immunosuppression, typically consisting of intravenous methylprednisolone combined with either a monoclonal antibody targeting CD25 (the high affinity α-chain of the IL-2 receptor) [14], such as basiliximab, or a lymphocyte-depleting antibody (such as thymoglobulin [15] or alemtuzumab [16–18]). Induction therapy is combined with ongoing maintenance immunosuppressive therapy, typically consisting of

**15**

*Perioperative Care for Kidney Transplant Recipients DOI: http://dx.doi.org/10.5772/intechopen.84388*

Very low risk Identical twin donor

Low risk HLA-identical sibling donor, no DSA Average risk HLA-mismatched donor, no DSA

immunosuppression are not discussed here.

*Immunological risk assessment for kidney transplantation.*

**2.5 Prophylactic medications**

*DSA, donor-specific antibody.*

**Table 2.**

(**Table 3**).

three immunosuppressive agents [19]. The most commonly prescribed combination in Australia and the USA currently is tacrolimus, mycophenolate and prednisolone [20, 21]. ABO-incompatible transplants as well transplants where there is a pretransplant DSA requiring plasma-exchange prior to transplantation are outside the scope of this chapter. Similarly, special circumstances including steroid-free

ABO-incompatible donor following desensitisation

High risk HLA-mismatched donor, detectable DSA, negative cross-match or

Very high risk HLA-mismatched donor, detectable DSA, positive cross-match

The administration of immunosuppression needs to be balanced against the increased risk of infection. With ESKD patients being routinely subjected to hospital environments, additional consideration should be given for prophylaxis in patients colonised with multi-resistant organisms. Patients with prior known serious or recurrent infections should be evaluated carefully and assessed for recurrence and presence of occult infection prior to proceeding with transplantation. In addition, gastro-protection, infection and VTE prophylaxis is charted

Despite some controversy for the use of surgical antibiotic prophylaxis, routine prescribing is common, generally following local practices and guidelines [22]. No consensus currently exists for optimal antibacterial prophylaxis, but the general approach is to minimise dose and duration of administration to prevent emergence of antibiotic resistance [23]. A Cochrane systematic review is currently being undertaken to evaluate the evidence for antibiotic prophylaxis in preventing postsurgical site infections in solid organ transplant recipients [24]. Where there are risk factors that may predispose the recipient to bacterial transmission from the donor, such as treated bacteraemia or urine infection, the duration of antibiotic

Prior to introduction of prophylaxis, PJP was an important cause of severe pneumonia, associated with an estimated 29–50% mortality [25]. Since the widespread use of co-trimoxazole prophylaxis, the incidence of PJP has declined to an estimated incidence of 0.8 case per 1000 person at 1-year post-transplant [26]. Co-trimoxazole prophylaxis is routinely prescribed in most transplant centres for 6–12 months post-transplant and many centres now advocate for continued prophylaxis following PJP outbreaks [27]. If co-trimoxazole is contraindicated, alternative

Prophylaxis against urinary tract infections (UTIs) is usually provided by the co-trimoxazole therapy administered for PJP prophylaxis. On the basis of limited evidence, perioperative UTI prophylaxis is recommended and in the case of co-

Systemic anti-fungal prophylaxis is not routinely administered to kidney transplant recipients [28]. However, oral nystatin or amphotericin is frequently

prophylaxis is adapted to cover the appropriate organisms.

agents are inhaled pentamidine isethionate or oral dapsone.

trimoxazole intolerance, another agent could be chosen [11].

*Perioperative Care for Kidney Transplant Recipients DOI: http://dx.doi.org/10.5772/intechopen.84388*


#### **Table 2.**

*Perioperative Care for Organ Transplant Recipient*

plant biopsy during this period.

development of ketoacidosis.

the perception of immunological risk (**Table 2**).

**2.4 Immunosuppression**

targets [11]. European Best Practices Guidelines for anaemia management recommend that ESA not be ceased in patients undergoing surgery, but no specific recommendations are made regarding transplantation [12].

Potential transplant recipients who are anti-coagulated with warfarin require urgent reversal of anticoagulation prior to surgery. There are often local protocols for warfarin reversal, but a typical approach would be 1–2 mg oral vitamin K administered as soon as the patient presents to hospital, followed by infusion of either fresh frozen plasma or a prothrombin complex concentrate, such as prothrombinex-VF, depending on the INR [13]. Whether intravenous heparin is required post-operatively will depend on the strength of the indication for anticoagulation, the degree of post-operative haemorrhage, and a decision regarding this should be made in consultation with the transplant surgeons. Where the risk of thrombosis is not excessively high, it is preferable to defer recommencing warfarin until at least 4 weeks post-transplant due to the frequent requirement for a trans-

Although non-vitamin K oral anticoagulants (NOACs) are currently not used routinely in end-stage kidney disease (ESKD) patients, indications for their use have been expanding into patients with more severe renal dysfunction. Nonetheless,

In Australia, over 23% of patients who are listed for a deceased donor transplant have diabetes [ANZDATA 2016]. The presence of autonomic neuropathy should be noted, as this may help predict haemodynamic instability and risk for graft hypoperfusion post-operatively. Similarly, gastroparesis may have important implications for immunosuppressive drug absorption if severe and retinopathy may complicate post-operative medication management if visual acuity is substantially

After admission for kidney transplantation, patients with type 2 diabetes should omit hypoglycaemic medication during the period of preoperative fasting, with regular capillary glucose monitoring performed every 1–2 h. Hypoglycaemia is managed with intravenous dextrose. If significant hyperglycaemia develops, an intravenous insulin infusion is the safest method to control glucose levels until the recipient is able to eat post-operatively. Patients with type 1 diabetes should commence an intravenous insulin infusion after admission to hospital to prevent the

After the decision has been made to proceed with a transplant, an immunosuppression regimen is selected. This regimen is usually initiated before the recipient goes to theatre so that immune function is attenuated prior to donor antigen exposure after reperfusion of the allograft. The choice of immunosuppressive regimen is individualised depending on the circumstances of the recipient and, in particular,

Most patients undergoing kidney transplantation will receive induction immunosuppression, typically consisting of intravenous methylprednisolone combined with either a monoclonal antibody targeting CD25 (the high affinity α-chain of the IL-2 receptor) [14], such as basiliximab, or a lymphocyte-depleting antibody (such as thymoglobulin [15] or alemtuzumab [16–18]). Induction therapy is combined with ongoing maintenance immunosuppressive therapy, typically consisting of

NOACs should be avoided in ESKD patients on the active transplant list.

**2.3 Pre-operative management of diabetes and hyperglycaemia**

**14**

reduced.

*Immunological risk assessment for kidney transplantation.*

three immunosuppressive agents [19]. The most commonly prescribed combination in Australia and the USA currently is tacrolimus, mycophenolate and prednisolone [20, 21]. ABO-incompatible transplants as well transplants where there is a pretransplant DSA requiring plasma-exchange prior to transplantation are outside the scope of this chapter. Similarly, special circumstances including steroid-free immunosuppression are not discussed here.

#### **2.5 Prophylactic medications**

The administration of immunosuppression needs to be balanced against the increased risk of infection. With ESKD patients being routinely subjected to hospital environments, additional consideration should be given for prophylaxis in patients colonised with multi-resistant organisms. Patients with prior known serious or recurrent infections should be evaluated carefully and assessed for recurrence and presence of occult infection prior to proceeding with transplantation. In addition, gastro-protection, infection and VTE prophylaxis is charted (**Table 3**).

Despite some controversy for the use of surgical antibiotic prophylaxis, routine prescribing is common, generally following local practices and guidelines [22]. No consensus currently exists for optimal antibacterial prophylaxis, but the general approach is to minimise dose and duration of administration to prevent emergence of antibiotic resistance [23]. A Cochrane systematic review is currently being undertaken to evaluate the evidence for antibiotic prophylaxis in preventing postsurgical site infections in solid organ transplant recipients [24]. Where there are risk factors that may predispose the recipient to bacterial transmission from the donor, such as treated bacteraemia or urine infection, the duration of antibiotic prophylaxis is adapted to cover the appropriate organisms.

Prior to introduction of prophylaxis, PJP was an important cause of severe pneumonia, associated with an estimated 29–50% mortality [25]. Since the widespread use of co-trimoxazole prophylaxis, the incidence of PJP has declined to an estimated incidence of 0.8 case per 1000 person at 1-year post-transplant [26]. Co-trimoxazole prophylaxis is routinely prescribed in most transplant centres for 6–12 months post-transplant and many centres now advocate for continued prophylaxis following PJP outbreaks [27]. If co-trimoxazole is contraindicated, alternative agents are inhaled pentamidine isethionate or oral dapsone.

Prophylaxis against urinary tract infections (UTIs) is usually provided by the co-trimoxazole therapy administered for PJP prophylaxis. On the basis of limited evidence, perioperative UTI prophylaxis is recommended and in the case of cotrimoxazole intolerance, another agent could be chosen [11].

Systemic anti-fungal prophylaxis is not routinely administered to kidney transplant recipients [28]. However, oral nystatin or amphotericin is frequently


#### **Table 3.**

*Perioperative prophylaxis.*

prescribed in the early post-operative period to reduce the risk of oropharyngeal candida infection [11]. The optimal duration of therapy is unknown, largely due to low event rates, but a typical approach would be therapy for the first month posttransplant [29].

Previous cytomegalovirus (CMV) infection is common, with a seroprevalence of up to 75% in transplant recipients [30]. The risk of developing CMV viraemia post-transplant depends on the serostatus of both donor and recipient as well as the induction immunosuppression agent (**Table 4**). The highest risk CMV infection is seen in seronegative recipients of a transplant from a seropositive donor, and is increased in patients treated with T cell depleting agents [31].

Several antiviral agents have been shown to reduce the risk of CMV infection (with the added benefit of also providing prophylaxis against herpes simplex and herpes zoster reactivation) in transplant recipients, including intravenous ganciclovir and oral acyclovir and valganciclovir, irrespective of donor status and induction immunosuppressive regimen [32]. Unfortunately, viral prophylaxis has shown little benefit in reducing the incidence of EBV-related PTLD [33]. Sustained prophylaxis benefit is observed with longer duration therapy (>3 months) with the main adverse effects being leukopenia with longer therapy duration [32]. Due to the observed benefit in reducing the incidence of CMV disease and cost effectiveness, 6 months antiviral prophylaxis is generally prescribed in high-risk CMV D+R− pairs [34]. An accepted alternative approach to universal prophylaxis is to monitor for CMV viraemia regularly post-transplant and initiate pre-emptive therapy should significant viraemia develop [32, 35].

Due to the gastro-erosive effects of prednisolone, ranitidine 150 mg twice daily for gastro-protection is usually recommended, noting the potential risk of interstitial nephritis and chronic kidney disease with proton-pump inhibitors (PPIs) [36, 37]. If ranitidine is contraindicated or ineffective, use of low dose PPIs as second line is recommended.

Deep venous thrombosis (DVT) has not been extensively evaluated in the literature. Kidney transplantation is categorised as a moderate risk group of patients for development of thromboprophylaxis conferring an estimated risk of DVT of 6% [38]. Limited studies have suggested the incidence to be lower with mechanical thromboprophylaxis alone [39]. Despite the lack of evidence, thromboprophylaxis

**17**

**Table 5.**

*Post-operative documentation.*

*Perioperative Care for Kidney Transplant Recipients DOI: http://dx.doi.org/10.5772/intechopen.84388*

*D, donor serostatus; R, recipient serostatus.*

*Prophylaxis for cytomegalovirus.*

**Table 4.**

CMV D−R− Usually no prophylaxis CMV D+R+ or D−R+ Valganciclovir for 3 months CMV D+R− Valganciclovir for 6 months

flow in the transplant vessels.

is generally initiated immediately post-operatively in the absence of contraindications or concerns of active haemorrhage. A combination of unfractionated heparin prophylaxis and mechanical calf compression is used, following local guidelines.

Although surgical and anaesthetic approaches and considerations are outside the scope of this chapter, intra-operative events have significant impacts on patient and graft outcomes. Review and documentation of intra-operative and immediate postoperative factors can help predict and guide subsequent clinical course (**Table 5**). Any surgical complications or anatomical challenges (notably presence of multiple renal arteries, difficult bench surgery and renal capsule tear) should be communicated by the transplant surgeons as these can help predict perioperative complications. If available, intraoperative Doppler assessments should be documented to confirm adequate post-perfusion flow parameters in the transplanted kidney. Where there is perioperative concern regarding allograft perfusion, or early unexpected oligoanuria, an early duplex ultrasound may be requested to confirm

Significant blood loss, requirement of inotropic support and intra-operative haemodynamic instability indicate suboptimal organ perfusion and are risk factors for delayed graft function (Section 5.4). Central venous line is placed at the time of surgery, and central venous pressure (CVP) is still used intra-operatively and in the immediate post-operative period. It is important to acknowledge controversies in absolute CVP targets, with studies advocating improved outcomes with high CVP (10–15 mmHg) targets at reperfusion [40, 41] and others observing increased kidney dysfunction with CVP >11 mmHg [42]. In general, intra-operative CVP trends can inform fluid management, but should not form the basis of a fluid management

Despite preoperative optimization, hyperkalaemia is common post-operatively due to tissue trauma and resorption of intra-abdominal blood. The presence of

Haemodynamics Blood pressure profile, CVP, need for inotropic support, blood loss volume Fluid balance Volume of intravenous fluid administration during procedure, urine output

Biochemistry Intraoperative insulin dextrose. Post-operative renal chemistry panel including urea,

strategy due to inconsistent correlation with intravascular volumes [43].

Donor graft Graft anatomy, backbench surgery, renal capsule tear Graft perfusion Appearance on cross-clamp release. Intraoperative Dopplers

creatinine and potassium *Assessment of listed factors helps guide and predict perioperative management*

**3. Intra-operative and immediate post-operative considerations**

*Perioperative Care for Kidney Transplant Recipients DOI: http://dx.doi.org/10.5772/intechopen.84388*


#### **Table 4.**

*Perioperative Care for Organ Transplant Recipient*

UTI prophylaxis 6 months co-trimoxazole

Oropharyngeal candidiasis

prophylaxis

Systemic fungal prophylaxis

*Perioperative prophylaxis.*

prescribed in the early post-operative period to reduce the risk of oropharyngeal candida infection [11]. The optimal duration of therapy is unknown, largely due to low event rates, but a typical approach would be therapy for the first month post-

VTE prophylaxis Unfractionated heparin and mechanical calf compressors unless contraindicated until patient mobile

Gastro-protection Ranitidine (or PPI) therapy while on high dose steroids

donor infection PJP prophylaxis 6–12 months co-trimoxazole. Consider lifelong therapy

uncertain

see **Table 4**

Bacterial prophylaxis Perioperative antibiotic therapy prescribed based on local guidelines and

CMV prophylaxis Oral valganciclovir. Duration depending on donor and recipient serostatus—

adapted for recipient multi-resistant organism colonization or potential

Oral nystatin or amphotericin for duration of admission. Optimal duration

Not generally prescribed due to low incidence of invasive fungal infection

Previous cytomegalovirus (CMV) infection is common, with a seroprevalence of up to 75% in transplant recipients [30]. The risk of developing CMV viraemia post-transplant depends on the serostatus of both donor and recipient as well as the induction immunosuppression agent (**Table 4**). The highest risk CMV infection is seen in seronegative recipients of a transplant from a seropositive donor, and is

Several antiviral agents have been shown to reduce the risk of CMV infection (with the added benefit of also providing prophylaxis against herpes simplex and herpes zoster reactivation) in transplant recipients, including intravenous ganciclovir and oral acyclovir and valganciclovir, irrespective of donor status and induction immunosuppressive regimen [32]. Unfortunately, viral prophylaxis has shown little benefit in reducing the incidence of EBV-related PTLD [33]. Sustained prophylaxis benefit is observed with longer duration therapy (>3 months) with the main adverse effects being leukopenia with longer therapy duration [32]. Due to the observed benefit in reducing the incidence of CMV disease and cost effectiveness, 6 months antiviral prophylaxis is generally prescribed in high-risk CMV D+R− pairs [34]. An accepted alternative approach to universal prophylaxis is to monitor for CMV viraemia regularly post-transplant and initiate pre-emptive

Due to the gastro-erosive effects of prednisolone, ranitidine 150 mg twice daily for gastro-protection is usually recommended, noting the potential risk of interstitial nephritis and chronic kidney disease with proton-pump inhibitors (PPIs) [36, 37]. If ranitidine is contraindicated or ineffective, use of low dose PPIs as second line is

Deep venous thrombosis (DVT) has not been extensively evaluated in the literature. Kidney transplantation is categorised as a moderate risk group of patients for development of thromboprophylaxis conferring an estimated risk of DVT of 6% [38]. Limited studies have suggested the incidence to be lower with mechanical thromboprophylaxis alone [39]. Despite the lack of evidence, thromboprophylaxis

increased in patients treated with T cell depleting agents [31].

therapy should significant viraemia develop [32, 35].

**16**

recommended.

transplant [29].

**Table 3.**

*Prophylaxis for cytomegalovirus.*

is generally initiated immediately post-operatively in the absence of contraindications or concerns of active haemorrhage. A combination of unfractionated heparin prophylaxis and mechanical calf compression is used, following local guidelines.
