Committee I

Committee XII

Renal Transplantation

Prof. Dr. Hazem Rashad (Chair), Professor of Urology, Alexandria University

Ass. Prof. Ahmed Fahmy, Assistant Professor of Urology, Alexandria University

Dr. Ahmed Eissa, Lecturer of Urology, Tanta University

Dr. Ahmed Elsherbiny, Lecturer of Urology, Tanta University

Contents
XII.1 List of Abbreviations
  • ACR - Acute cellular rejection
  • ADPCKD - Autosomal dominant polycystic kidney disease
  • AMR - Antibody-mediated rejection
  • ASB - Asymptomatic bacteriuria
  • BK - Polyoma (BK) virus
  • CDC - Chronic kidney disease
  • CDC - Complement-dependent cytotoxicity
  • CMV - Cytomegalovirus
  • CT - Computerized Tomography
  • DSA - donor-specific antibodies
  • EBV - Epstein-Barr Virus
  • ECG - Electrocardiogram
  • FSGS - Focal segmental glomerulosclerosis
  • GFR - Glomerular filtration rate
  • GN - Glomerulonephritis
  • HLA - Human leucocyte antigen
  • HSV - Herpes Simplex Virus
  • HTLV - Human T-cell lymphotropic virus
  • LLDN - Laparoscopic living-donor nephrectomy
  • MMR - Measles/Mumps/Rubella
  • MRA - Magnetic resonance angiography
  • PRA - Panel of reactive antibodies
  • RAT - Renal artery thrombosis
  • RCT - Randomized controlled trial
  • TB - Tuberculosis
  • UTI - Urinary tract infection
  • VCUG - Voiding cystourethrogram
  • VUR - Vesicoureteric reflux
  • VZV - Varicella-Zoster Virus

XII.2 Abstract

XII.2.1 Objective:
Our Objective is to provide evidence-based data to surgeons performing kidney transplantation essential to improve both the safety and the outcome of the procedure. Our goal is to transform available evidence in literature and clinical practice into recommendations for best practice use by all kidney transplant surgeons.

XII.2.2 Methods:
Our specialized panel reviewed available literature on kidney transplantation, including all published urological associations guidelines, review articles, meta-analysis and large prospective multicentric studies. Recommendations were stated in accordance with the Egyptian guidelines grading system (Strong and weak).

XII.2.3 Results:
In this guideline, we classified kidney transplantation into three main categories: pre-transplant assessment, transplant surgery (donor and recipient), and post-transplant management and complications. Despite the importance of the medical aspects in managing transplant patients, we opted to emphasize on the surgical aspects that concerns all transplant surgeons, the targeted group of this guidelines. Medical preparation, immunosuppression and medical complications will be discussed in brief, as they are beyond the scope of this guidelines.

XII.2.4 Conclusion:
Our guidelines provide important recommendations to all Egyptian transplant surgeons to ensure safe clinical practice and better outcome when performing kidney transplantation.

XII.3 Introduction:
Guidelines are summaries of the highest level of evidence in literature, according to published data from experts in the field. Following the guidelines does not necessarily guarantee the outcome but will assist urologists in providing patients with safe clinical practice that has been reproducibly reported to achieve best and safest results. The goal of our guidelines is to provide urologists and transplant surgeons, performing kidney transplantation, with an updated evidence-based review of literature on renal transplant, hence the guidelines will emphasize on the surgical aspects of kidney transplantation. Published data from meta-analysis, large prospective multi-centric studies, review articles and Egyptian literature, as well as guidelines form known associations were thoroughly reviewed (1-5). Recommendations in the guidelines are in accordance with the Egyptian Guidelines Grading System (Strong and weak).

XII.4 Patients’ selection
  • We recommend that all patients with chronic kidney disease (CKD) G4-5 (glomerular filtration rate [GFR] < 30ml/min/1.73 m2 ) are to be considered for kidney transplantation regardless of sex, gender, race or socioeconomic status, except in CKD patients with metastatic untreatable malignancies, severe irreversible restrictive or obstructive lung disease, un-supported patients with serious mental retardation, non-compliance, unstable psychiatric disorder, active substance abuse, severe decompensated liver or cardiac failure (unless liver and cardiac transplantation are considered; respectively).
  • We recommend pre-emptive kidney transplantation with kidneys from living donors as the treatment of choice in CKD patients.
  • We encourage using living related donors as the main source of kidney donation followed by un-related donors.
  • We recommend that the following conditions exclude any potential donor from kidney donation:
  • Age < 21 yrs
  • 50 yrs (living-unrelated) or >60 yrs (living-related)
  • Hypertension
  • Diabetes Mellitus or abnormal glucose tolerance test
  • History of thrombosis or embolism
  • Severe peripheral vascular disease
  • Chronic lung disease with impaired oxygenation
  • Recent malignancy with long time to possible recurrence
  • Urological abnormalities, bilateral recurrent renal stones, or severe vascular anomalies
  • Impaired renal function (GFR < 80 ml/min/1.73m²)
  • Proteinuria> 300 mg in 24 hrs
  • Active HIV, Hepatitis B or C infection

XII.5 Legal considerations in kidney transplantation
  • Kidney transplantation in Egypt must be only done in licensed transplant centers, after obtaining an official approval from the higher supreme committee for organ transplantation, Ministry of Health.
  • We recommend that an informed consent must be taken from both recipients and donors prior to kidney transplantation.
  • We recommend that donor’s decision to withdraw at any stage prior to surgery should be respected and supported in a manner that protects confidentiality.

XII.6 Pre-Transplant Assessment
XII.6.1 Patients’ Education and counselling
Table XII:1 Recommendations for Patients’ education and counseling

Recommendation

Strength Rating
1. Counselling and education represent an integral part of preoperative preparation of renal transplant recipients. Strong
Patient education may improve patients’ recovery after surgery, reduce the postoperative psychological stress, and allow early recovery of healthy lifestyle. (6,7) All potential transplant candidates and their primary care givers are encouraged to attend a “patient education” session before the formal evaluation process. Patients are educated on the benefits and risks of renal transplantation, the necessity for frequent outpatient visits in the early postoperative period, the potential adverse effects of immunosuppression, lifestyle adjustments (cessation of cigarette smoking, weight loss…etc), stress coping strategies, the effect of transplantation on existing medical conditions, and the importance of compliance with immunosuppressive therapy. (7,8)

XII.6.2 Transplant Workup
The purpose of the evaluation is to identify contraindications to kidney transplantation and correct medical and psychological conditions that may affect the transplant outcome.

Table XII:2 Recommendations for Donor assessment

Recommendations

Strength Rating
History taking
A comprehensive and detailed history taking is strongly recommended and it should cover the following aspects:

1- Age, smoking, alcohol, or drug dependence
2- Medical conditions (such as history of peripheral edema, gout, nephrolithiasis, diabetes mellitus, cardiovascular disease, and current or previous malignancy)
3- Transmissible infection (such as TB, HIV, and hepatitis)		 Strong
Clinical Examination
Full clinical examination of the donor is recommended, and it should include but not limited to:

1- Cardiovascular examination (blood pressure, ECG, chest X-ray)
2- Calculation of BMI
3- Examination for abnormal masses or swelling
4- Surgical scars
5- Mental health		 Strong
Laboratory & Radiological investigations
Laboratory investigations should include at least:

1- Urinalysis for detection of hematuria, proteinuria, and glucose and urine culture (at least two times are recommended).
2- General laboratory examination (complete blood count, liver function test, coagulation profile, lipid profile, thyroid function, blood electrolyte, fasting blood sugar…. etc)
3- Assessment of renal function (urea, creatinine, eGFR)
4- Evaluation of infection (HBV, HCV, HIV, CMV, EBV)
5. Blood group/HLA typing		 Strong
Renal imaging (e.g., computed tomographic angiography, renal scan,,,,, etc) should be performed in all donor candidates to assess renal anatomy and function before nephrectomy. Strong
T.B: Tuberculosis, HIV: Human immunodeficiency virus, CMV: cytomegalovirus, HLA: Human leucocytic antigens, ECG: electrocardiogram
Table XII:3 Recommendations for Recipient assessment

Recommendations

Strength Rating
History taking
A comprehensive and detailed history taking is strongly recommended for renal transplant recipients and it should cover the following aspects:

1- Age, smoking, alcohol, or drug dependence
2- Medical conditions (such as history of peripheral edema, gout, nephrolithiasis, diabetes mellitus, cardiovascular disease, and current or previous malignancy)
3- Transmissible infection (such as TB, HIV, and hepatitis)
4- Renal disease assessment (etiology, assessment of the native renal biopsy if possible, history of previous transplant, and previous graft loss)		 Strong
Clinical Examination
Full clinical examination of the recipient is recommended, and it should include but not limited to:

1- Cardiovascular examination (blood pressure, ECG, chest X-ray, echocardiogram)
2- Calculation of BMI
3- Examination for abnormal masses or swelling
4- Surgical scars
5- Psychological and mental assessment
6- Conditions that may require pre-transplant surgical treatment (inguinal hernia, and peripheral vascular disease)		 Strong
Examination for malignancy (as per local guidelines) Strong
Laboratory & Radiological investigations
1. Laboratory investigations should include at least:

1. Urinalysis and culture (at least two times are recommended).
2. General laboratory examination (complete blood count, liver function test, coagulation profile, lipid profile, thyroid function, blood electrolyte, fasting blood sugar, and renal function tests)
3. Evaluation of infection (HBV, HCV, HIV, CMV, EBV)
 Strong
2. Imaging studies should include abdominal US and abdominopelvic CT Strong
3. Native renal biopsy is indicated to identify the underlying cause of renal failure (if unknown) as it may help predicting the risk of recurrence Weak
Immunological tests
1. ABO grouping and HLA typing (class I and II) must be done to all recipients Strong
2. DSA assessment must be done to all recipients prior to transplantation Strong
3. Cross match must be done prior to all kidney transplantations Strong
DSA: donor-specific antibodies
XII.6.2.1 General Assessment
General assessment starts with a detailed history and physical examination. The history should focus on the etiology of the renal disease with a review of the native kidney biopsy if available. It may help to assess the risk of recurrence in the transplanted kidney. A detailed history of any prior transplant courses including the causes of graft loss, medication compliance, and previous transplant complications should be obtained in re-transplant candidates. For candidates with ESRD secondary to congenital and urological abnormalities, appropriate urological evaluation is required.

Issues of specific importance to the surgeon include the patient’s previous surgical history, vascular examination, overall risk for anesthetic complications, and the presence of any pathologic process that might require pretransplant surgical treatment (i.e., inguinal hernia, peripheral vascular disease, symptomatic polycystic kidney disease). Candidates’ BMI should be measured as obesity is associated with adverse outcome and poses technical challenges with surgery.

XII.6.2.2 Informed consent
Table XII:4 Recommendations of informed consent

Recommendations

Strength Rating
For renal transplantation surgery in Egypt, it is mandatory to obtain an informed written consent from both the donor and the recipient and to obtain an approval from the Egyptian Supreme Committee of Organ Transplantation Strong
Like other surgeries, an informed consent should be obtained from both the donor and the recipient. However, it should be noted that the informed consent for donation should ensure precise understanding of the related risks and benefits of donation and it should be obtained from the donor candidate; in the absence of any of the concerned personnel such as the intended recipient, family members and other persons who could influence the donation decision. (9)

Substitute decision makers should not be used on behalf of a donor candidate who lacks the capacity to provide informed consent (e.g., children or those who are mentally challenged), except under extraordinary circumstances and only after ethical and legal review. Donor’s decision to withdraw at any stage of transplantation prior to surgery must be respected and protected. (10)

XII.6.2.3 Laboratory Assessment
Laboratory investigations for both recipients and donors must include complete blood picture, urine analysis and culture, ABO group, renal and liver function tests, fasting glucose level, coagulation profile, 24 hrs urine protein, serum electrolytes, lipid profile and HLA typing. Serum PSA level must be assessed in all male recipients above the age of 45 yrs. Recent PAP smear (within 6 months) should be done in all adult female recipients and mammography in females >50 yrs. Screening for tuberculosis (TB) using PCR for TB in urine is encouraged in suspicious cases, including recipients from endemic areas. Occult blood in stool is to be tested in recipients >60 yrs., patients with lower GI symptoms, diverticular disease, or positive family history of lower GI malignancy. (Strong)

Virology workup of recipients and donors must include Hepatitis B, Hepatis C, Human immunodeficiency Virus (HIV), Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV). (Strong) Screening for Herpes Simplex Virus (HSV), Varicella-Zoster Virus (VZV), Polyoma (BK) virus and Human T-cell lymphotropic virus (HTLV) is encouraged (weak).

XII.6.2.4 Radiological Assessment
Radiological imaging of recipients includes echocardiography, chest X ray and an ultrasound for the abdomen and pelvis. Additional imaging modalities are required according to individual cases. Plain Computerized Tomography (CT) for the abdomen and pelvis is frequently required to accurately assess the abdomen, exclude any pathology, evaluate the vascular anatomy such as the presence of atherosclerosis with calcification, assess Autosomal dominant polycystic kidney disease (ADPCKD) patients and the potential need for native nephrectomy….etc. Imaging studies on the lower urinary tract are required in specific cases. Urodynamic evaluation is required in recipients with suspected bladder storage or emptying dysfunction.

Radiological assessment of potential donor includes echocardiography, chest x-ray, abdominal sonography, triphasic multi-slice CT abdomen and pelvis, CT angiography, and diuretic renal scan. Further imaging modalities can be required for selected cases. (Strong)

XII.6.2.5 Vascular Assessment
Vascular Assessment is suggested in all transplant recipients; nevertheless, it is recommended to be done in all candidates with symptoms of ischemic leg disease, femoral bruits, claudication, or absent pedal pulses. Selective iliac angiography, abdominal CT angiography, or Magnetic resonance angiography (MRA) are among the additional imaging studies that can be used in such cases.

XII.6.2.6 Cardiac Assessment
  • We recommend that all transplant donors and recipients undergo cardiac assessment prior to kidney transplantation. Cardiovascular disease is the leading cause of death in recipients after kidney transplantation. Cardiac assessment is essential to optimize the cardiac condition prior to surgery, as well as to exclude recipients with decompensated cardiac failure.
  • We recommend electrocardiogram (ECG) and echocardiography to be done to all transplant donors and recipients prior to surgery. Additional tests are to be done, accordingly, for specific or symptomatic cases.

XII.6.2.7 Vaccination
  • We recommend that all potential transplant recipients should be fully immunized before transplantation.
  • We recommend live vaccines to be administered at least 6 weeks before kidney transplantation.
  • We recommend that transplant recipients should receive the following vaccinations prior to transplant: Diphtheria, Pertussis, Hepatitis B, Haemophilus Influenza-B, Meningococcal (conjugate), Pneumococcal (conjugate and/or polysaccharide), Influenza and Measles/Mumps/Rubella (MMR).
  • We recommend post-transplant vaccination to be resumed one year after kidney transplantation, except for seasonal flu vaccine which can be given 4 weeks after transplantation.
  • We recommend no live vaccines to be given after kidney transplantation.
  • We recommend yearly influenza immunization to all transplant recipients post transplantation.

XII.6.2.8 Specific Assessment
  • We recommend performing cystoscopy to assess the lower urinary tract, upper and lower GI endoscopy to selected kidney transplant recipients. (strong)
  • We recommend urodynamic evaluation only in suspected cases of bladder filling or emptying dysfunction. (weak)

XII.6.2.9 Immunological considerations
  • We recommend a negative crossmatch preferably using flowcytometry before kidney transplantation.
  • We suggest performing crossmatch using complement-dependent cytotoxicity (CDC) as a less favorable alternative.
  • We recommend assessing anti-HLA and donor-specific antibodies (DSA) in all transplant recipients prior to transplantation. According to which immunological risk can be assessed. We recommend highly sensitized recipients to be desensitized prior to transplantation.
  • We recommend classifying transplant recipients according to history of previous transplantation, multiple pregnancies, repeated blood transfusion, high panel of reactive antibodies (PRA), HLA mismatching, and the presence of HLA antibodies to; low, intermediate or high immunological risk groups.
  • We recommend using induction immunosuppression in all high-risk recipients, preferably using a T-cell depleting antibodies (anti-thymocyte globulin) induction therapy. We recommend using any induction therapy in intermediate-risk group whether with monoclonal or polyclonal antibodies, while the use of induction in low-risk group is preferred.
  • We recommend the use of multi-drug regimen immunosuppressive therapy to all recipients post transplantation.
  • We recommend to routinely assess the blood levels of measurable immunosuppressive drugs in all recipients after transplantation.

XII.7 Transplant procedure
XII.7.1 Donor Nephrectomy:
XII.7.1.1 Choice of kidney
Table XII:5 Recommendtions for Choice of donor kidney

Recommendations

Strength Rating
Generally, the better functioning kidney should stay in the donor; but if all the factors (including the quality and function) are equivalent, it may be recommended to remove the left kidney as it has a longer vein. Strong
Generally, the best kidney should stay with the donor. Differential function of 50% ±2 is the cutoff for considering equality of the function of both kidneys. Factors influencing which kidney to harvest include split function, arterial, venous and ureteral anatomy, and any other renal abnormalities (i.e. cysts). Extrarenal findings such as previous operations and scars or perceived difficulty in positioning on one side may also play a role. While in case all factors, including function and quality, are equivalent, the kidney with the lowest risk for surgical complications in the recipient is selected. It is then generally preferable to remove the left kidney since it has a longer renal vein that makes the recipient operation easier. (11,12)

XII.7.1.2 Surgical approach
Table XII:6 Recommendations of Donor nephrectomy

Recommendations

Strength Rating
1. Restrict living-donor nephrectomy to specialized centers. Strong
2. Offer long-term follow-up to all living kidney donors. Weak
3. The surgeon should have adequate training and experience for the surgical approach used for the donor nephrectomy. Weak
4. Pure or hand-assisted laparoscopic nephrectomy is considered as the standard of care for living-donor nephrectomy. Strong
5. Perform open living-donor nephrectomy in centers which lack the required facilities for endoscopic techniques or in patients with extensive adhesions. Strong
6. Perform laparo-endoscopic single site surgery and robotic surgery-assisted living donor nephrectomy in specialized centers only with great experience in renal transplantation. Weak
Several systematic reviews and meta-analyses comparing between open and laparoscopic approaches, supported laparoscopic living-donor nephrectomy (LLDN) as the standard of care. LLDN offers similar rates of graft function and rejection, urological complications, and patient and graft survival. On the contrary, LLDN is associated with significantly lower postoperative pain, less analgesic requirements, and shorter hospital stay and time to return to work. (12-14)

“Mini-open” laparoscopy or hand-assisted laparoscopy by trained surgeons should be offered as optimal approach to donor nephrectomy. However, in some circumstances, such as donors with extensive previous surgery and/or adhesions, and at centers where laparoscopy is not routinely performed, open nephrectomy (flank or laparotomy) may be acceptable. (15) Generally, laparo-endoscopic single site surgery and robotic -assisted living donor nephrectomy should be performed in highly specialized centers only. Non-transfixing clips, (e.g., Weck Hem-o-lok) should not be used to ligate the renal artery in donor nephrectomy; instead, renal artery transfixation by suture ligature or anchor staple within the vessel wall should be used. (16)

In the absence of reasons to procure the right kidney (vascular, urological, or other abnormalities), the left kidney should be procured in laparoscopic donor nephrectomy because of the relative technical ease associated with a longer venous pedicle. We suggest laparoscopic procurement of the right rather than the left living donor kidney may be performed if the surgeon has adequate training and experience. Procurement of a living donor kidney with 3 or more arteries should only be undertaken by surgeons with adequate experience. (17)

XII.7.2 Surgery on the Renal Transplant Recipient:
XII.7.2.1 Immediate preoperative preparation
Table XII:7 Recommendations of Recipient's preparation

Recommendations

Strength Rating
Dialysis or conservative measures may be considered to manage fluid and electrolyte imbalance before the surgery taking into consideration the likelihood of immediate graft function Weak
Operating on patients taking anti-platelet and anti-coagulation agents
1. Anti-platelet therapy should not be stopped in patients on the transplant waiting list. Weak
2. A multidisciplinary team consisting of urologist, cardiologist, hematologist, and nephrologist should be considered in the counseling of kidney transplant candidates who take anti-platelet and/or anticoagulant. Weak
Prevention of venous thrombosis including deep vein thrombosis during and after renal transplant
1. Routine post-operative prophylactic anti-coagulants in the form of unfractionated or low molecular-weight heparin is not recommended for low-risk living donor transplant recipients. Weak
Peri-operative antibiotics in renal transplant
1. Single-dose perioperative prophylactic antibiotics represents a good alternative to multi-dose antibiotics in routine renal transplant recipients. Strong
Specific fluid regimes during renal transplantation
1. Renal graft function is improved by optimizing patient’s hydration throughout the entire process of transplantation (pre, peri, and postoperative). Strong
2. Use balanced crystalloid solutions for intraoperative intravenous fluid therapy Weak
3. Use target directed intra-operative hydration to decrease delayed graft function rates and optimize early graft function. Strong
Dopaminergic drugs in renal transplantation
1. Do not routinely use low-dose dopaminergic agents in the early postoperative period. Weak
The timing of renal transplantation surgery is a point of special interest. Kidney transplantation is an elective or semi-elective surgery performed on patients who have undergone careful preoperative assessment and preparation. There are numerous advantages to preemptive kidney transplantation (transplantation before dialysis) including a survival advantage. Yet, rates of preemptive kidney transplantation are still low. (18-20)

The decision to dialyze a patient before transplantation depends on the timing of the previous dialysis, clinical assessment of volume status, and serum electrolyte levels, particularly potassium. (17) Noteworthy, pre-transplant dialysis is associated with an increased incidence of delayed graft function because of the danger of intraoperative or postoperative hyperkalemia in oliguric patients. In this setting, dialysis should be considered for patients with serum potassium level of more than 5.5 mEq/L. In well-dialyzed patients, preoperative dialysis for fluid removal is usually unnecessary and if it is needed it should be done with care to maintain the patient at or somewhat above dry weight to facilitate postoperative diuresis. (21)

As regards the operative risk in patients using anti-coagulant and/or anti-platelet, there are some evidence that continuing anti-platelet therapy with aspirin, ticlopidine, or clopidogrel does not confer a significantly greater risk of peri- or postoperative complications.(22,23) Furthermore, a small randomized controlled trial (RCT) performed in Egypt demonstrated no significant difference in early postoperative graft loss or thromboembolic complications with or without prophylactic anticoagulation. (24)

Interestingly, a multicentric, prospective RCT showed no difference at one month in surgical site, bacterial, fungal, or viral infection between those receiving a single-dose broad-spectrum antibiotic at induction of anesthesia compared with those receiving antibiotic twice daily for 3–5 days. (25)

XII.7.2.2 Native kidney
Table XII:8 Recommendations for Native nephrectomy

Recommendations

Strength Rating
1. Pre-transplant routine native nephrectomy is not recommended unless there is recurrent upper urinary tract infection or high risk of malignancy. Strong
2. Native nephrectomy (uni- or bi-lateral) is recommended in patients with autosomal dominant polycystic kidney disease (ADPKD) in case of severe and/or recurrent symptomatic complications such as bleeding, stones, or infection. Strong
3. Ipsilateral native nephrectomy can be performed concomitant with transplantation in patients with asymptomatic ADPKD when there is not enough space for the transplant kidney. Strong
Pre-transplant recipient native nephrectomy is not the standard practice in kidney transplantation and usually both native kidneys are left in place. Several indications exist for native nephrectomy either unilateral or bilateral including symptomatic or complicated autosomal dominant polycystic kidney disease, suspicious renal or urothelial cancer, recurrent infection associated with nephrolithiasis, and/or heavy proteinuria and hypoalbuminemia. (26-28)

XII.7.2.3 Surgical approach:
Table XII:9 Recommendations for surgical technique

Recommendation

Strength Rating
1. Open approach to renal transplantation is the approach of choice Strong
2. Renal transplantation should be limited to highly specialized centers Strong
3. Right or left iliac fossae are the common sites for placement of the graft during first or second single kidney transplant Weak
4. It is recommended to carefully ligate perivascular lymphatics during vascular dissection of the iliac vessels to reduce the risk of postoperative lymphocele Weak
5. A drain can be placed to reduce the incidence of postoperative lymphoceles Weak
Generally, the patient is placed in the supine position and a “hockey-stick”-shaped incision is performed in the lower quadrant starting the midline (approximately one to two finger breadths above the pubic bone) and curving upwards as it extends laterally until it reaches the edge of the rectus muscle. Finally, the incision is extended superiorly along the lateral margin of the rectus muscle. The graft is commonly placed in a retroperitoneal location (either the right or left iliac fossa; however, right iliac fossa is preferred as the right iliac vein is more superficial. (29,30) On the other hand, some surgeons routinely place drains, while others do not. We strongly suggest putting drain, as placement of a drain may reduce the incidence of lymphoceles. (31)

XII.7.2.4 Vascular anastomosis:
Table XII:10 Recommendations for Vascular anastomosis

Recommendations

Strength Rating
1. The length of donor renal vein is an important determinant of the technique of vascular anastomosis. In case of short vein consider one of the available techniques to optimize the venous anastomosis such as transposition of the recipient’s iliac vein. Weak
2. The external iliac vein is most commonly used for outflow. The renal vein is anastomosed to the iliac vein in an end-to-side fashion. Weak
3. The external or common iliac arteries are most commonly used for arterial anastomosis with the donor’s renal artery in an end-to-side arterial fashion. Weak
4. End-to-end anastomosis between the internal iliac artery and graft artery can be used as an alternative to the external or common iliac arteries. Weak
5. An intimal rupture/flap of the donor and the recipient arteries must be repaired before the arterial anastomosis. Thus, thorough inspection of the intima of both the donor and recipient artery is a must. Strong
6. Careful preoperative surgical planning is recommended in case of ≥ third transplant to guarantee appropriate arterial inflow and venous outflow with sufficient space for graft implantation Strong
For adult recipients, the vascular anastomoses are usually performed to the iliac vessels. The venous anastomosis is performed first. Commonly, the external iliac vein is used for the outflow, where the optimal site of anastomosis depends on the position and lie of the allograft kidney. In certain conditions where the graft renal vein is short or the recipient iliac vein is deep, the branches of the recipient’s internal iliac vein can be ligated and divided to bring the vein in a more superficial position. Generally, an end-to-side tension free venous anastomosis is performed. Clamps can be placed proximally and distally on the vein, or a single auricular clamp may be used. A venotomy of appropriate size is made. There are several ways to perform the actual anastomosis, none of which have proven advantage over the others. (32,33)

For arterial inflow, the common, external, or internal iliac artery may be used with similar postoperative results. (34) Generally, the external iliac artery is preferred; however, if it is diseased or narrow in caliber there should be no hesitation in using the common iliac artery. Noteworthy the best option to choose the site of anastomosis is to place the kidney in the fossa then choose the site where the artery will lie more naturally without tension, redundancy, or angulation. (35) Overall, the arterial anastomosis is performed in a way similar to that of the vein.

Finally, the clamp on the iliac vein is flashed open, and if no bleeding, removed carefully. Massive bleeding should prompt immediate re-clamping and suture repair. Then the distal arterial clamp is removed. The renal artery is occluded with a pickup. The proximal arterial clamp is released. After approximately three heartbeats, the occlusion of the renal artery by the pickup is released. The distal arterial clamp is removed first, followed by the proximal arterial clamp. (32,34)

XII.7.2.5 Ureteral anastomosis:
Table XII:11 Recommendations for Ureteral anastomosis

Recommendations

Strength Rating
1. In patients with normal urological anatomy, it is recommended to use Lich-Gregoir-like extravesical ureteric implantation technique to reduce the risk of urinary tract complications Strong
2. In very short or poorly vascularized allograft ureter, consider pyelo/uretero-ureteral anastomosis Strong
3. Routine use of ureteric stenting in the transplanted ureter with early removal (within 30 days) is suggested to reduce major urinary complications Weak
4. Duplex allograft ureters are not an indication to abandon the procedure, and they can be implanted either separately or combined in the same principle as a single ureter Strong
The continuity of the urinary tract is established by anastomosing the allograft ureter to the bladder. Several techniques are available for the ureterovesical anastomosis; however, the most important factors to ensure the vascularity and perfusion of the ureter are the tension-free anastomosis and the lack of redundancy. The distal ureter is prepared by ligating the accompanying ureteral vessels, trimming excess length of ureter and spatulating its distal end. It is advisable to create a tunnel at the distal graft ureter to decrease urinary reflux. (35,36)

XII.8 Post-Transplant complications
XII.8.1 Medical Complications
XII.8.1.1 Infection
XII.8.1.1.1 7.1.1.1-Bacterial Infections

Table XII:12 Recommendations for Baterial infection

Recommendations

Strength Rating
1. Six-month antibiotic prophylaxis is recommended to guard against different microbial infections in transplant patients. Prophylaxis should be adjusted according to patients’ age, comorbidities, history of infection, and immunosuppressives used. Strong
2. Close monitoring is recommended for patients with asymptomatic bacteriuria following renal transplantation; however, no treatment is required. Strong
3. In patients with symptomatic urinary tract infections:

1- Removal or replacement of urinary tract device such as (urethral catheter or stent).
2- Urine culture and sensitivity.
3- Start empirical treatment with fluoroquinolones, amoxicillin-clavulanate or third generation cephalosporin.
4- If persistent, shift to antimicrobial shown by the urine culture and sensitivity.		 Strong
Bacterial infections are among the most common complications following renal transplantation surgery and they represent one of the leading causes of graft rejection in the first few months. This may be explained by the higher prevalence of urinary tract infection (UTI) in renal transplant recipients compared to general population.(37,38) Interestingly, a recent systematic review and meta-analysis reported that the prevalence of UTI following renal transplantation surgery in the Middle East countries is 37.9% of which, the most common causative organisms were Escherichia Coli, Klebsiella, Coagulase Negative Staphylococcus, and Enterococci (accounting for 57.5%, 15%, 15%, and 11.2%, respectively). (38)

The management of asymptomatic bacteriuria (ASB) in transplant patients is highly controversial, as the overuse of antibiotics may be associated with the development of resistant bacterial strains and increased cost of management, while, theoretically ASB may increase the risk of symptomatic UTI and worsen the graft function, however most recent evidence in the literature showed that the management of ASB does not have an impact on the development of symptomatic UTI or graft function. (37,39)

XII.8.1.1.2 Viral Infections

Poloyoma (BK) virus

Table XII:13 Recommendatons for Polyoma (BK) virus

Recommendation

Strength Rating
1. Screening for BK Polyoma virus using plasma quantitative polymerase chain reaction should be performed monthly in all renal transplant patients for nine-months, then every three months till the end of the 2nd year, then annually till the end of the fifth-year post-transplant. Strong
2. BK Virus nephropathy is diagnosed by needle biopsy of the allograft. Strong
3. When BK virus levels in the plasma reaches 10,000 /ml, reduce the level of immunosuppressive medications to guard against BK virus nephropathy. Strong
Latent BK polyoma virus may become reactivated in the transplanted kidneys due to the use of strong immunosuppressive medications to maintain the graft function that may lead to BK nephropathy. (40) The prevalence of BK virus nephropathy following renal transplantation is 10%; however, the virus can be isolated in the urine of 30-60% and the blood of 10-30% of transplant patients. (41) Currently, there are no specific treatment available for BK virus nephropathy, thus it is recommended to start treatment as plasma PCR levels reach 10,000 copies/ mL as it reflects a high risk for the development of nephropathy. The main management strategy for BK virus infection is the reduction of immunosuppressive agents in the form of reduction of Calcineurin inhibitors by 25-50% with the discontinuation of antimetabolites. (41,42)

Cytomegalovirus (CMV)

Table XII:14 Recommendations for Cytomegalovirus

Recommendation

Strength Rating
1. Risk for Cytomegalovirus (CMV) infection after renal transplantation is high in the following conditions:

1- CMV positive donor and negative recipient
2- CMV positive donor and recipient
3- CMV negative donor and positive recipient		 Strong
2. CMV prophylaxis with ganciclovir, or valganciclovir is recommended for at least three months after transplantation. Strong
3. Prophylactic doses of valganciclovir should be adjusted according to the creatinine clearance. Strong
4. CMV prophylaxis is recommended for at least 6 weeks, whenever a lymphocyte depleting agents are considered for the management of rejection episodes. Strong
5. Oral valganciclovir or intravenous ganciclovir are recommended for the management of transplant patients with mild or moderate CMV infection, while in case of severe CMV infections, intravenous ganciclovir is used. Strong
6. In case of persistent CMV infection despite of the antiviral treatment, consider reducing the immunosuppressive therapy. Strong
CMV is the most important virus in solid organ transplantation as it is associated with significant morbidity of the recipient. The risk of CMV infection is based on both the donor and recipient, thus CMV serology is recommended for all donors and recipients. (40)

Epstein-barr virus (EBV)

Table XII:15 Recommendations for Epstein Barr virus (EBV)

Recommendation

Strength Rating
1. Screening for Epstein-Barr virus (EBV) by nucleic acid testing should be performed monthly in high-risk renal transplant patients (positive donors) for 3-6 months, then every three months till the end of the 2nd year. Weak
2. EBV high risk transplant patients should be monitored for EBV infection following treatment of acute rejection. Weak
3. It is recommended to reduce immunosuppressive therapy for EBV positive transplant patients. Strong
Importantly, EBV disease may be associated with increased risk of some cancers including EBV-associated lymphomas. (42)

XII.8.1.1.3 Fungal Infections

Table XII:16 Recommendations for Fungal infection

Recommendations

Strength Rating
1. Pneumocystis Jirovecii prophylaxis using trimethoprim-sulfamethoxazole is recommended for 3-6 months after renal transplantation. Strong
2. Prophylactic doses of trimethoprim-sulfamethoxazole are recommended for at least 6 weeks during and following episodes of acute rejection to guard against Pneumocystis Jirovecii. Strong
3. Treatment of Pneumocystis Jirovecii Pneumonia should include intravenous trimethoprim-sulfamethoxazole, corticosteroids, and reduction of immunosuppressive drugs. Strong
4. Prophylactic doses of oral clotrimazole, or fluconazole are recommended for 1-3 months after renal transplantation to protect against esophageal candida. Strong
Generally, the incidence of invasive fungal infections in kidney transplant patients ranges from 5% to 9.2%. Most of the fungal infections occurs within six months of transplantation. (43,44)

XII.8.1.2 Rejection
Table XII:17 Recommendations for Rejection

Recommendation

Strength Rating
1. Renal biopsy should be done before treating an acute rejection episode except if deferring treatment is considered of high risk to the patient Strong
2. We recommend using a 16-gauge needle and to obtain at least 2 core renal tissue biopsies for more accurate diagnosis Strong
3. We suggest testing for human leucocyte antigen (HLA)-specific antibodies if suspecting rejection Weak
4. Acute cellular rejection (ACR) should be managed with high-dose intravenous steroids as a first line of treatment Strong
5. ACR refractory to steroids should be treated with lymphocyte-depleting antibodies as a second line of treatment Weak
6. Antibody-mediated rejection (AMR) can be treated with intravenous steroids, plasmapheresis, intravenous immunoglobulin, monoclonal anti-CD20 antibody, lymphocyte-depleting antibodies Weak
7. We suggest modifying/intensifying the maintenance immunosuppressive therapy after treating acute rejection episode Weak
Rejection after kidney transplantation should be suspected in all recipients with persistently delayed or deteriorating graft function, as well as proteinuria. (45) Renal biopsy is recommended prior to initiating treatment, except in the few conditions where the patient would be at risk if treatment is delayed. Rejection is histologically diagnosed according to Banff criteria. (46) With a negative pretransplant crossmatch, hyperacute rejection is rarely seen. Acute rejection can be cellular or antibody-mediated (vascular). Acute cellular rejection should be treated with bolus high-dose intravenous methylprednisolone followed by anti-thymocyte globulin in steroid-refractory cases. (47,48) In addition, antibody-mediated rejection (AMR) can be treated with therapeutic Plasma Exchange, Intravenous Immunoglobulin, anti-CD20 antibody. (49) There is some evidence in literature that suggests modifying and intensifying the maintenance immunosuppressive protocol after treatment of acute rejection reduces the risk of subsequent attacks. (50,51) Chronic rejection is suspected with slowly deteriorating graft function and should be confirmed by a renal biopsy. (52)

XII.8.1.3 Malignancy
Table XII:18 Recommendations for Post-transplant malignancy

Recommendations

Strength Rating
1. A personalized malignancy screening strategy should be tailored according to each patients’ history, comorbidities, and tobacco use. Strong
2. This personalized strategy should include screening for the following cancers based on the patients’ risks and the local guidelines:

1- Renal cell carcinoma.
2- Hepatocellular and colon cancers.
3- Bladder cancer.
4- Prostate cancer.
5- Lung cancer.
6-Breast and cervical cancers.
 Weak
3. For de novo cancers after renal transplantation, it is recommended to reduce the immunosuppressive medications. Weak
Generally, transplant recipients may be at higher risk for development of different malignancies. A recent observational study of 1,417 transplant patients showed that the incidence of de novo malignancy after transplantation is 10.9%. Renal cell carcinoma was the most commonly reported malignancy (27.4%), followed by gastrointestinal (16.8%), urological (13.4%), lung (10.1%), gynecological (8.4%), hematological (7.8%), cancers of unknown primary (3.9%). (53) The risk of other cancers such as Kaposi’s sarcoma, non-Hodgkin’s lymphoma, non-melanoma skin cancers, and melanoma may also be increased in transplant patients. (54)

Currently, there is no consensus for the management of localized allograft renal cell carcinoma; however, different treatment options may be recommended including graftectomy, nephron sparing surgery or focal ablation of the tumor. (55)

XII.8.1.4 Post-transplantation Diabetes Mellitus
Table XII:19 Recommendations for Post-transplant Diabetes Mellitus

Recommendation

Strength Rating
1. All non-diabetic transplant patients should be monitored by fasting plasma glucose, oral glucose tolerance test, and or hemoglobin A1c at:

1- Weekly for first month after transplantation.
2- Every three months for the first year.
3- Then annually.
 Strong
2. All transplant patients with new onset diabetes mellitus should be monitored with fasting plasma glucose, oral glucose tolerance test, and or hemoglobin A1cwith the initiation or increasing the dose of calcineurin inhibitors, mTORi, or corticosteroids. Weak
3. For new onset diabetes after renal transplantation consider reducing the dose of diabetogenic immunosuppressives. Furthermore, consider using daily aspirin for protection against cardiovascular complications. Weak
The pathogenesis of new-onset diabetes mellitus following renal transplantation is complex and multifactorial, however, it may be generally related to changes in insulin resistance and insulin secretion. (56)

1.1.1 De novo or recurrent glomerulonephritis
Table XII:20 Recommendations for Post-transplant Glomerulonephritis

Recommendation

Strength Rating
1. Kidney transplant patients who originally suffered different types of glomerulonephritis (as a primary disease) should be screened for proteinuria, microhematuria, or other urinary abnormalities to detect de novo or recurrent glomerulonephritis. Strong
2. If screening is suggestive for recurrent or de novo glomerulonephritis, percutaneous allograft biopsy is recommended to confirm the diagnosis. Strong
3. In case of confirmed diagnosis on biopsy consider the following:

1-Plasma exchange for patients showing focal segmental glomerulonephritis.
2-High doses corticosteroids and cyclophosphamide for patients presenting with recurrent antineutrophil cytoplasmic autoantibody-associated vasculitis or anti-glomerular basement membrane disease.
3-Angiotensin converting enzyme-inhibitors or angiotensin II receptor blockers are recommended for patients with proteinuria and recurrent glomerulonephritis
 Strong
Recurrence of glomerulonephritis (GN) is reported to be the third common cause of late graft loss after kidney transplantation (5-8% at 10 years); however, most renal diseases should not be considered as contraindications of renal transplantation. Recurrence of GN in transplanted kidney is usually late, except with primary focal segmental glomerulosclerosis (FSGS) which may lead to early graft loss.(57,58)

XII.8.2 Surgical Complications
XII.8.2.1 Urological complications
XII.8.2.1.1 Ureteral Stenosis and Obstruction

Table XII:21 Recommendations for Ureteral Obstruction

Recommendation

Strength Rating
1. Persistent hydronephrosis of the allograft on ultrasound in patients with renal function deterioration is suggestive for ureteric stricture or obstruction. Strong
2. Initial treatment strategy of post-transplantation ureteric stricture consists of:

1- Relief of obstruction by the placement of percutaneous nephrostomy.
2- Antegrade pyelography for the localization and characterization of the stricture.
 Strong
3. Contrast enhanced CT is recommended for evaluation of post-transplant ureteric obstruction as it can provide information about intrinsic and extrinsic causes of obstruction. Weak
4. Management of ureteral stricture differs according to the length of the stricture:

1- Stricture <3 cm can be treated endoscopically using balloon dilatation or laser incision.
2- Strictures ≥3cm in length or failed endoscopic treatment in patients with <3 cm strictures should be treated by surgical reconstruction.
 Strong
Ureteral stricture may occur in 2-10% of renal transplant patients with the distal ureter being the most commonly involved location. (59) Ureteral ischemia is responsible for 90% of post-transplant ureteric strictures. Generally, ureteric obstruction can be classified into early (<3 months), which results from ureteric stricture, technical errors during ureteric implantation, external compression, or kinking of the ureter. On the other hand, late obstruction may be due to ureteral ischemia, fibrosis, lymphocele, or vasculitis secondary to acute rejection. (60)

XII.8.2.1.2 Urinary Leak

Table XII:22 Recommendations for Unrinary Leak

Recommendation

Strength Rating
1. Urine leak is suspected by the reduction of urine output and high creatinine level in drain fluid. Strong
2. Management of urinary leakage consists of:

1- Double J stenting and indwelling urethral catheter or percutaneous nephrostomy.
2- If endoscopic management failed consider surgical treatment.
 Strong
Urinary leakage may occur as a result of ureteral necrosis or poor surgical technique. It can be classified according to the source of leakage into ureteral or vesical. Generally, the prevalence of post-transplantation urinary leakage ranges from 0 to 9%. (61) Ureteric stenting has been proposed to reduce the risk of urine leak, however, a recent systematic review and meta-analysis demonstrated that routine ureteric stenting do not significantly reduce the risk of urine leak but may increase the risk of UTIs. (62) Furthermore, another systematic review and meta-analysis showed that early removal of the ureteral stent (around three weeks) reduce the risk of UTIs without compromising the risk of urine leak compared to late removal (> 3 weeks). (63)

XII.8.2.1.3 Hematuria
Table XII:23 Recommendations for Hematuria

Recommendation

Strength Rating
1. Consider conservative treatment option in the form of bladder irrigation for post-transplantation hematuria. Strong
2. In case of persistent hematuria consider endoscopy and fulguration of bleeding sites. Strong
XII.8.2.1.4 Vesicoureteric Reflux

Table XII:24 Recommendarions for Veicoureteric reflux

Recommendation

Strength Rating
1. Voiding cystourethrogram (VCUG) is recommended to diagnose vesicoureteric reflux (VUR) in transplant recipients showing persistent hydroureteronephrosis in the absence of clinically significant stricture. Strong
2. Minimally invasive techniques such as injection of bulking agents are recommended as the primary treatment options for VUR. Weak
3. In case of failed endoscopic treatment or high grade VUR ureteric re-implantation or pyelo-ureterostomy with the native ureter may be indicated Weak
Vesicoureteric reflux (VUR) can be observed in up to 86% of transplant recipients and it commonly related to the surgical technique. The impact of VUR on graft function and pyelonephritis is still debatable; however, antibiotic prophylaxis, endoscopic treatment have been considered for management of low to moderate grade VUR. (60)

1.1.1.1 Lymphocele
Table XII:25 Recommendations for Lymphocele

Recommendation

Strength Rating
1. Large or symptomatic lymphocele should be treated by percutaneous drain placement. Strong
2. Sclerosing agents such as povidone iodine, ethanol or fibrin glue reduce the recurrence rate of lymphocele. Strong
3. Open or laparoscopic marsupialization is recommended if conservative treatment with drain placement failed. Strong
Lymphocele is a common complication following renal transplantation that affects approximately 1-26% of all recipients. (59) Lymphoceles may result from the damage of the perivascular lymphatics around the iliac vessels due to the extensive dissection. Furthermore, other risk factors may play a role in the development of lymphocele such as obesity, diabetes, immunosuppressive drugs, and delay in graft function. Lymphocele is a serious complication as it may affect the graft function and it may be associated with increased risk of deep venous thrombosis. (64)

XII.8.2.1.5 Urolithiasis

Table XII:26 Recommendations for Urolithiasis

Recommendation

Strength Rating
1. Complete history taking and metabolic evaluation of the patients are required to identify the underlying cause of urolithiasis. Strong
2. Non contrast enhanced CT is the main imaging study for evaluation of post-transplant urolithiasis. Strong
3. If the stone causes obstruction of the urinary tract, consider double J stenting or percutaneous nephrostomy to relieve obstruction. Strong
4. For stones <15 mm, consider shockwave lithotripsy, antegrade or retrograde ureteroscopy or nephroscopy as the main treatment options. Strong
5. For stones >20 mm, consider percutaneous nephrolithotomy as the main treatment options. Weak
Urolithiasis after renal transplantation is a relatively rare complication that may occur in up to 1.8% of patients. The average time to allograft stone disease diagnosis is 30.5 months. (65) Generally, urolithiasis may result from post-transplantation hyper-filtration, renal tubular acidosis, and disturbance of serum and urinary electrolytes level. (61)

XII.8.2.2 Wound complications
Table XII:27 Recommendations for Wound complications

Recommendation

Strength Rating
1. In case of wound infection and superficial collection, ultrasound guided drainage of the collection and systemic antibiotics (according to culture and sensitivity of the fluid) is recommended. Strong
2. Risk factors for wound dehiscence include old age, diabetes mellitus, obesity, anemia, hypoalbuminemia, and longer surgical time. Weak
3. Wound dehiscence can be treated according to the type:

1- Superficial wound dehiscence is managed by washout and debridement
2- Complete fascial wound dehiscence is managed by primary repair with (in the absence of infection) or without synesthetic mesh reinforcement
 Strong
4. Incisional hernia can be managed by open or laparoscopic repair Weak
Wound complications are relatively common following kidney transplantation surgery (10.5-15.5%). These complications include wound infection, superficial dehiscence, complete fascial dehiscence, wound collection, and incisional hernia. Several risk factors may contribute to the occurrence of wound complications such as smoking, malnutrition, diabetes mellitus, obesity, and poor surgical techniques. (66) These complications are challenging and may be associated with increased duration of hospitalization and cost.

XII.8.2.3 Vascular complications
XII.8.2.3.1 Hemorrhage and hematomas

Table XII:28 Recommendations for Hemorrhage and hematomas

Recommendation

Strength Rating
1. Small asymptomatic hematomas require follow up without any intervention. Weak
2. Large hematomas causing graft dysfunction or hemodynamic instability can be managed by CT or US guided drainage or exploration Weak
XII.8.2.3.2 Graft thrombosis (arterial or venous)

Table XII:29 Recommendations for Graft thrombosis

Recommendation

Strength Rating
1. Perform color doppler US in case of graft thrombosis (arterial or venous) suspicion Strong
2. Poor or impaired graft perfusion is a strong indication for surgical exploration Strong
3. If an arterial or venous thrombosis is confirmed during the surgical exploration perform surgical thrombectomy if the allograft is salvageable Weak
4. In case of non-viable allograft, nephrectomy of the allograft is indicated Strong
5. Prophylactic anticoagulant is not recommended as a preventative measure against transplant vein thrombosis Strong
Graft thrombosis (either arterial or venous) is a rare complication that may occur in up to 3.5-4% of kidney transplant patients. This complication usually occurs as a result of technical errors during kidney harvesting or the anastomosis. (61) Renal vein thrombosis is an early complication that might present with lower limb edema, swollen allograft, anuria, and ultimately allograft loss. (67) Similarly, renal artery thrombosis (RAT) usually presents with significant reduction in the urine output with elevated serum creatinine.(68) Overall, color doppler US is the imaging study of choice for evaluation of those patients as it shows poor renal perfusion in case of arterial thrombosis and absence of venous flow with abnormal arterial signal (plateau-like reversed diastolic flow) in case of venous thrombosis.(68) Once a graft thrombosis is diagnosed on color doppler US, surgical exploration is indicated and either allograft nephrectomy (in case of non-viable graft) or thrombectomy (in case of salvageable allograft) is recommended.(56) Prophylactic anticoagulant therapy after renal transplantation is not associated with reduced risk of graft thrombosis.(67)

XII.8.2.3.3 Transplant renal artery stenosis

Table XII:30 Recommendations for Transplant Renal artery senosis

Recommendation

Strength Rating
1. Perform color doppler US in case of suspicious transplant renal artery stenosis (refractory hypertension not responding to medical treatment and/or elevated serum creatinine in the absence of hydronephrosis or infection). Strong
2. In case color doppler US is not diagnostic, perform CT or MRI angiography. Strong
3. In mild transplant, renal artery stenosis (<50% of the arterial caliber) with the absence of symptoms and no deterioration of the allograft function, no intervention is required just consider color doppler US follow up Strong
4. Consider minimally invasive endovascular options (percutaneous transluminal angioplasty/stent) as the first line of treatment for transplant renal artery stenosis. Strong
5. Consider surgical intervention in the following conditions:

1- Failed minimally invasive endovascular options
2- Recent transplant
3- Complex stenosis (long, narrow, and/or multiple)
 Strong
Transplant renal artery stenosis is one of the well-recognized vascular complications following renal transplantation. Its incidence is highly variable ranging from 1-25%. It is associated with deterioration of the allograft function and development of cardiovascular complications including post-transplant hypertension. Generally, transplant artery stenosis are diagnosed between 3 and 24 months after the transplantation surgery. (69) Several risk factors play may play a role in the development of transplant renal artery stenosis including renal artery factors (caliber, atherosclerosis, or trauma), surgical technique (continuous versus interrupted sutures, absence of arterial patch, or injury of the iliac artery during the anastomosis), and immunological factors (CMV infection). (61,69) On color doppler US, a peak systolic velocity of >200 cm/s is alarming for significant transplant renal artery stenosis. (70)

XII.8.2.3.4 Arteriovenous fistula and pseudoaneurysm

Table XII:31 Recommendations for Arteriovenous fistula and pseudoaneurysm

Recommendation

Strength Rating
1. Perform color doppler US in case of suspicious pseudoaneurysm or arteriovenous fistula (hypertension, hematuria, and/or deterioration of the allograft function). Strong
2. Consider angiographic selective embolization as the first line of treatment for pseudoaneurysm and arteriovenous fistula Strong
3. Consider partial or complete allograft excision in case of failed other treatment options Strong
Arteriovenous (AV) fistulas and pseudoaneurysm are common vascular complications that occurs after percutaneous biopsy of the allograft in patients with suspected graft rejection. Fortunately, most of the AV fistulas and pseudoaneurysms are asymptomatic and resolve spontaneously; however, 30% of cases may become symptomatic and require intervention. (61,71)

XII.8.3 Other Complications
XII.8.3.1 Cardiovascular complications
Table XII:32 Recommendations for Cardiovascular complications

Recommendation

Strength Rating
1. Measure blood pressure at each follow up visit after renal transplantation. Strong
2. Perform a complete lipid profile for all transplant patients:

1- Within 2-3 months of the transplantation surgery
2- Within 3 months after the change of treatment or development of any condition that might cause dyslipidemia
3- Annually
 Weak
3. Counsel all kidney transplant patients to stop smoking Strong
4. Screen all transplant patients for obesity by assessing the patients’ weight, height, and body mass index at each follow up visit Weak
Renal transplant recipients are at higher risk for developing cardiovascular complications compared to general population. Furthermore, mild impairment of the renal function in this population is associated with higher risk of cardiovascular mortality. (72) Post-transplantation hypertension is the most common cardiovascular complications after renal transplantation. (69)

XII.8.3.2 Bone disease
Table XII:33 Recommendations for Bone disease

Recommendation

Strength Rating
1. Measure the serum calcium and phosphorous levels once weekly until stable, then the interval of measurement should be adjusted according to the chronic kidney disease progression and the baseline levels. Strong
2. Measure the serum level of vitamin D and parathormone within 3 months of the transplantation surgery, then the intervals of follow up should be adjusted based on the baseline levels and the chronic kidney disease progression. Weak
3. In patients with estimated GFR >30 ml/min/1.73 m2, the bone mineral density should be evaluated at 3 months’ post-transplantation, then the follow up should be determined based on the patient’s condition and baseline levels. Strong
Loss of organ function is associated with deterioration of the bone mass and increased risk of fracture. However, the transplantation surgery improves the patients’ quality of life, the bone health and the risk of fracture are not improved particularly during the first year following the transplantation. Furthermore, immunosuppressive agents may worsen the pre-transplant bone disease. (73)

XII.8.3.3 Fertility and sexual function
Table XII:34 Recommendations for Fertility and sexual function

Recommendation

Strength Rating
1. Assess patient’s sexual function after the transplantation surgery Weak
2. Female patients should wait at least one year before becoming pregnant Weak
3. Inform male patients about the potential fertility risks associated with the use of mTOR inhibitors Strong
Generally, patients with chronic kidney disease usually suffer from subfertility or infertility due to several causes including hypogonadism and/or erectile dysfunction. Fortunately, transplantation surgery is usually associated with improvement of sexual and reproductive health. (74,75)

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