What are the key considerations for a patient undergoing kidney transplantation, including donor and recipient criteria, surgical steps, and management of postoperative complications?

Kidney Transplantation: Comprehensive Educational Presentation

Donor Selection Criteria

Mandatory Initial Screening

All potential living donors must undergo ABO blood typing (performed twice), HLA typing for MHC Class I and II, and crossmatching against the intended recipient before proceeding with further evaluation. 1, 2

Medical Eligibility Requirements

• Age considerations: Biologically related donors are generally preferred, with donor selection based on degree of HLA matching and younger donor age when multiple candidates are available 1
• Cardiovascular risk stratification: Cardiac stress testing is indicated for men ≥45 years or women ≥55 years, history of smoking, family history of premature coronary artery disease, hypertension, or abnormal ECG findings (left ventricular hypertrophy, left bundle branch block, ST-T abnormalities) 1
• Renal function: Donors must demonstrate adequate GFR and absence of proteinuria or hematuria that would contraindicate donation 3
• Smoking status: Donors who smoke must commit to quitting at least 4 weeks prior to donation and lifelong abstinence to reduce perioperative complications and long-term health risks 1

Psychosocial and Ethical Requirements

A multidisciplinary transplant team must verify the donor candidate's voluntary willingness to donate without undue pressure, with at least one key team member not involved in recipient care participating in donor evaluation to minimize conflict of interest. 1

• Donors must receive education and counseling on individualized risks and benefits, methods to minimize risks, and need for postdonation follow-up 1
• Transplant programs must establish defensible policies describing acceptable psychosocial criteria, including constraints on acceptable donor-recipient relationships 1
• Privacy regarding all aspects of the evaluation and decision-making process must be protected 1

Absolute Contraindications

• Unwillingness or coercion to donate 1
• Medical conditions that place donor at unacceptable short-term or long-term risk above program-established thresholds 1
• Active malignancy or transmissible infections that pose risk to recipient 1

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Recipient Selection Criteria

General Eligibility

Kidney transplantation is the treatment of choice for patients with end-stage renal disease, with pre-emptive transplantation (before dialysis initiation) associated with superior patient and graft survival. 1, 3

Immunologic Compatibility

• ABO compatibility: Primary consideration for donor eligibility, with blood typing performed twice before transplantation 2
• HLA matching: Improves long-term outcomes and should be assessed for all donor-recipient pairs 2
• Crossmatching: Donor-specific crossmatching excludes organs from recipients with preexisting anti-donor immunity 2
• Donor-specific antibodies: Anti-HLA antibodies must be assessed in all intended recipients 1

Special Populations

• Older recipients (≥60 years): Can achieve comparable outcomes to younger recipients when matched with appropriate donors, particularly expanded criteria donors (ECD) matched for nephron mass and recipient size 4
• High immunologic risk: Should avoid ECD kidneys due to increased rejection risk 4
• Peripheral arterial disease: Independently predicts longer hospitalization time and requires careful consideration 5

ABO-Incompatible Transplantation

Donor candidates who are ABO or HLA incompatible with their intended recipient should be informed of kidney paired donation programs and incompatibility management strategies, though ABO-incompatible transplantation should only be performed at experienced centers with effective protocols. 1, 2

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Surgical Technique and Considerations

Preoperative Preparation

• Guideline-based evaluation: All donors require comprehensive preoperative assessment to minimize cardiac, pulmonary, bleeding, anesthesia-related, and other perioperative complications 1
• Smoking cessation: Must be achieved at least 4 weeks before surgery 1
• Donor nephrectomy approach: Laparoscopic donor nephrectomy has contributed to increased living donation rates 1

Surgical Steps (Standard Approach)

• Donor nephrectomy: Performed with careful preservation of renal vasculature and ureter
• Recipient preparation: Typically involves placement in iliac fossa with vascular anastomosis to external iliac vessels
• Vascular anastomosis: Renal artery to external iliac artery, renal vein to external iliac vein
• Ureteral implantation: Ureteroneocystostomy with or without stent placement

Special Surgical Considerations

For combined liver-kidney transplantation (CLKT), the "Indiana Approach" involves performing liver transplantation first while maintaining the kidney on hypothermic pulsatile perfusion, with delayed kidney implantation 2-3 days later to optimize physiologic environment and avoid bilirubin crystallization in renal tubules. 1

Induction Immunosuppression

• Rabbit antithymocyte globulin (r-ATG) or alemtuzumab induction commonly used 4
• Maintenance typically includes tacrolimus, mycophenolate mofetil, and steroids 4

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Postoperative Complications

Early Complications (First 30 Days)

Delayed Graft Function (DGF)

• Definition: Need for dialysis in the first week after transplantation 1
• Risk factors: ECD donors, donation after cardiac death (DCD), prolonged cold ischemia time 1
• Monitoring: Track percentage of patients requiring dialysis in first week, stratified by donor type 1

Surgical Complications

• Vascular thrombosis: Requires immediate surgical exploration
• Urine leak: May present with decreased urine output, rising creatinine, and fluid collection on imaging
• Bleeding: May require blood transfusion or reoperation 1
• Wound complications: Surgical site infections tracked as quality metric 1

Cardiovascular Events

• Myocardial infarction, cardiac arrest, stroke: Occur in early postoperative period and should be tracked as quality indicators 1
• Deep vein thrombosis/pulmonary embolism: Require prophylaxis and surveillance 1

Infectious Complications

• Bacterial infections: Pneumonia, urinary tract infections, bacteremia, surgical site infections 1
• Monitoring: Track 30-day complication rates overall and by specific infection type 1

Late Complications (31-365 Days and Beyond)

Viral Infections

CMV Disease

• Prophylaxis protocol: All kidney transplant recipients receiving T-cell-depleting antibody therapy for rejection must receive valganciclovir 900 mg daily (adjusted for renal function) for 6 weeks, regardless of baseline CMV serostatus 6
• Monitoring: Weekly CMV quantitative plasma NAT or pp65 antigenemia during high-risk periods 6
• Critical pitfall: Do not omit prophylaxis based on CMV serostatus alone—even CMV R+ patients benefit from prophylaxis after T-cell depletion 6

BK Virus Nephropathy (BKVN)

• Surveillance protocol: Screen monthly for first 3-6 months using quantitative plasma NAT, then every 3 months through first year 7
• Additional screening: After any treatment for acute rejection or with unexplained creatinine elevation 7
• Treatment threshold: Reduce immunosuppression immediately when plasma BK viral load persistently exceeds 10,000 copies/ml 7
• Reduction sequence: Reduce or temporarily discontinue antimetabolites (mycophenolate mofetil or azathioprine) first 7
• Critical pitfall: Do not delay immunosuppression reduction while awaiting biopsy confirmation when plasma viral load exceeds 10,000 copies/ml—early intervention prevents progression 7
• Adjunctive therapy: Consider low-dose cidofovir (1 mg/kg IV weekly without probenecid) only for biopsy-proven, progressive BKVN despite maximal immunosuppression reduction 7

Acute Rejection

• Monitoring: Screen for BK virus reactivation after rejection treatment, as both immunosuppression reduction and augmentation affect BK virus risk 6, 7
• CMV prophylaxis: Mandatory 6-week course after T-cell-depleting antibody therapy 6

Chronic Allograft Dysfunction

• Monitoring: Track graft function closely during all interventions 6
• Risk factors: Donor and recipient age, waiting time for transplantation 8

Readmissions

Unplanned readmission to any hospital within 30 days of discharge should be tracked as a quality metric, as it reflects both surgical complications and adequacy of discharge planning. 1

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Quality Metrics and Outcomes

Key Performance Indicators

• Pre-emptive transplantation rate: Percentage of CKD patients receiving living donor transplant before starting dialysis 1
• Wait list mortality: Percentage of patients who die before receiving transplant 1
• DGF rate: Percentage requiring dialysis in first week, stratified by donor type 1
• 30-day complication rate: Overall and by specific complication type (infection, cardiovascular, transfusion, unplanned operation) 1
• 30-day readmission rate: Unplanned readmissions to any hospital 1
• 31-365 day complication rate: Late infections (CMV, BK, pneumonia, UTI, bacteremia) and cardiovascular events 1

Donor and Recipient Age Considerations

The use of expanded criteria donors (ECD) has no significant impact on patient or graft survival when appropriately matched to recipients, with donor and recipient age and waiting time being the primary factors affecting outcomes. 8

• ECD kidneys should be matched to recipient size (BMI <25 kg/m²) and recipients >40 years with low immunologic risk 4
• Dual kidney transplantation may be considered for optimal nephron mass matching 4
• Patient survival rates are comparable between older (≥60 years) and younger recipients when appropriately selected 4

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Multiple Choice Questions for Residents

Question 1

A 52-year-old male with history of smoking presents as a potential living kidney donor for his brother. According to current guidelines, which of the following is the MOST appropriate next step in his cardiovascular evaluation?

A) Proceed directly to donation without cardiac testing
B) Obtain echocardiogram only
C) Perform cardiac stress testing
D) Obtain coronary CT angiography
E) Defer donation due to smoking history

Correct Answer: C 1

Explanation: Cardiac stress testing is indicated for men ≥45 years with history of smoking. While smoking cessation is required at least 4 weeks before donation, smoking history alone is not an absolute contraindication if the donor commits to lifelong abstinence.

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Question 2

A kidney transplant recipient develops acute rejection on postoperative day 10 and receives rabbit antithymocyte globulin (r-ATG). According to KDIGO guidelines, what is the MOST appropriate CMV prophylaxis strategy?

A) No prophylaxis needed if recipient is CMV IgG positive
B) Valganciclovir 900 mg daily for 3 weeks
C) Valganciclovir 900 mg daily for 6 weeks (adjusted for renal function)
D) Ganciclovir IV for 2 weeks followed by oral valganciclovir for 4 weeks
E) CMV monitoring only without prophylaxis

Correct Answer: C 6

Explanation: KDIGO guidelines recommend 6 weeks of CMV chemoprophylaxis with valganciclovir after T-cell-depleting antibody therapy, regardless of baseline CMV serostatus. This is a Grade 1C recommendation with strong evidence supporting this practice.

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Question 3

A 45-year-old kidney transplant recipient has routine surveillance showing plasma BK viral load of 15,000 copies/ml on two consecutive weekly measurements. Creatinine is stable at 1.4 mg/dL. Current immunosuppression includes tacrolimus, mycophenolate mofetil, and prednisone. What is the MOST appropriate management?

A) Continue current immunosuppression and repeat BK viral load in 1 week
B) Obtain kidney biopsy before making any changes
C) Reduce mycophenolate mofetil dose immediately
D) Start cidofovir therapy
E) Switch tacrolimus to cyclosporine

Correct Answer: C 7

Explanation: When plasma BK viral load persistently exceeds 10,000 copies/ml, immunosuppression should be reduced immediately. The typical reduction sequence starts with reducing or temporarily discontinuing antimetabolites (mycophenolate mofetil). Do not delay reduction while awaiting biopsy confirmation, as early intervention prevents progression to nephropathy.

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Question 4

A 62-year-old patient with ESRD is being evaluated for kidney transplantation. An expanded criteria donor (ECD) kidney becomes available. Which of the following recipient characteristics would make this patient the MOST appropriate candidate for this ECD kidney?

A) High panel reactive antibody (PRA) of 85%
B) BMI of 32 kg/m² with low immunologic risk
C) Age >40 years, BMI of 23 kg/m², low immunologic risk
D) Previous failed transplant with acute rejection
E) Active CMV viremia

Correct Answer: C 4

Explanation: ECD kidneys should be matched to recipients with appropriate size (BMI <25 kg/m²), age >40 years, and low immunologic risk. High immunologic risk patients should avoid ECD kidneys due to increased rejection risk. This matching strategy achieves outcomes comparable to standard criteria donors.

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Question 5

During evaluation of a potential living kidney donor, ABO blood typing is performed. According to current guidelines, what is the MINIMUM number of times blood typing must be performed before proceeding with donation?

A) Once, if performed by certified laboratory
B) Twice, to reduce risk of unintended blood type incompatible transplantation
C) Three times, at different time points
D) Once, with confirmatory crossmatch
E) Blood typing frequency is at transplant center discretion

Correct Answer: B 1, 2

Explanation: ABO blood typing should be performed twice before donation to reduce the risk of unintended blood type incompatible transplantation. This is a safety measure to prevent catastrophic hyperacute rejection from ABO incompatibility.