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Dialysis: Vascular Access, Complications & Recent Advances

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UNIT A

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1. Vascular Access for Hemodialysis

A. Arteriovenous Fistula (AVF) — Preferred access

• Surgically created direct anastomosis between an artery and vein (most commonly radiocephalic at the wrist, or brachiocephalic)
• Requires maturation time (~6–12 weeks) before use
• Lowest infection risk, longest survival, and least thrombosis
• Requires patent, adequate-caliber veins (assessed by duplex ultrasound pre-operatively)
• "Fistula First Breakthrough Initiative" (FFBI) has significantly increased AVF use and reduced central venous catheter (CVC) use in the USA

B. Arteriovenous Graft (AVG)

• Prosthetic conduit (usually PTFE) connecting artery to vein
• Can be used within 2–4 weeks of placement
• Higher rates of thrombosis and infection than AVF
• Preferred when native vessels are inadequate for fistula creation

C. Central Venous Catheter (CVC) — Last resort / bridge access

• Non-tunneled (temporary): Short-term use; inserted into internal jugular, subclavian, or femoral vein
• Tunneled (cuffed): e.g., Permcath / Hickman — Dacron cuff induces fibrosis to anchor and reduce infection; preferred for longer-term use when AVF/AVG unavailable
• Right internal jugular is preferred site (lower risk of stenosis vs. subclavian)
• Subclavian access is discouraged due to high risk of central venous stenosis impairing future AVF/AVG creation

Vascular Access Complications

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2. Peritoneal Access Devices

Types of Peritoneal Dialysis (PD) Catheters

Insertion Techniques

• Small 2–3 cm skin incision; anterior rectus sheath not incised
• Trocar + cannula inserted at 45° through rectus muscle toward pelvis
• Peritoneoscope confirms intraperitoneal position
• Air (600–1000 mL) insufflated to separate peritoneal surfaces
• Bowel loops, adhesions, bladder identified under direct vision
• Spiral sheath advanced to pelvis, dilated to 6 mm; catheter passed over stylet
• Deep cuff implanted in rectus muscle with implanter tool; superficial cuff in subcutaneous tissue
• Can be used immediately for intermittent dialysis (risk of pericatheter leak if used continuously)

• Midline or paramedian incision under general/spinal anesthesia
• Direct visualization; cuffs placed under direct view
• Longer wound healing; pericatheter leak less common early
• Higher infection and outflow failure rates than peritoneoscopic technique

• Veress needle or trocar used for access; guidewire-based placement
• Catheter position confirmed by fluoroscopy
• Fewer complications than open surgery in skilled hands

• Useful in patients with prior abdominal surgery/adhesions
• Direct visualization; omentectomy/omentopexy can be performed simultaneously

Complications of PD Catheter Insertion

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UNIT B

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3. Complications of Hemodialysis

A. Acute (Intradialytic) Complications

1. Intradialytic Hypotension (IDH) — Most common, 15–30% of sessions

• Definition (KDOQI): drop in SBP ≥20 mmHg or MAP ≥10 mmHg with clinical symptoms
• Causes: excessive/rapid ultrafiltration, impaired cardiac reserve, vasodilation from heat transfer, reduced plasma osmolality, dysautonomia, arrhythmia
• Management: Reduce UF rate, Trendelenburg position, 100–250 mL normal saline bolus; reassess dry weight
• Prevention: limit UF rate (<10–13 mL/kg/hr), individualized dialysate sodium, cooling dialysate, avoid intradialytic food, review antihypertensives, bioimpedance monitoring

• Reassess dry weight
• Reduce interdialytic sodium/fluid intake
• Adjust dialysate calcium and sodium
• Avoid food during dialysis
• Adjust antihypertensive timing
• Increase treatment duration/frequency

2. Muscle Cramps

• Often accompany rapid fluid removal and hypotension
• Management: reduce UF rate, quinine, carnitine, vitamin E

3. Nausea & Vomiting

• Related to hypotension, disequilibrium, or vagal response

4. Headache

5. Dialysis Disequilibrium Syndrome

• Rapid solute removal → cerebral edema (urea osmole effect)
• More common at dialysis initiation in severely uremic patients
• Prevented by slow, gentle first sessions

6. Air Embolism

• Due to faulty tubing connections; potentially fatal; requires immediate left lateral decubitus/Trendelenburg position

7. Dialyzer Reactions

• Type A: Anaphylactic; within 5–20 minutes; IgE-mediated; caused by membrane material or ethylene oxide sterilant; can be fatal
• Type B: Complement-mediated; chest/back pain; less severe; occurs later in session. Reduced with modern biocompatible synthetic membranes (polysulfone, polyacrylonitrile)

8. Arrhythmias

• Triggered by electrolyte shifts (K⁺, Ca²⁺, Mg²⁺), rapid fluid shifts, myocardial ischemia
• Atrial fibrillation prevalent in >20% of HD patients

9. Bleeding

• Anticoagulation (heparin) for circuit patency; regional citrate anticoagulation preferred in high bleeding-risk patients

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B. Long-Term (Chronic) Complications of Hemodialysis

1. Cardiovascular Disease — Leading cause of death

• Left ventricular hypertrophy (LVH): from hypertension, volume overload, anemia
• Coronary artery disease: accelerated atherosclerosis
• Myocardial stunning: repetitive HD-induced ischemia (shown by troponin release, regional wall motion abnormalities on echo)
• Pericardial disease: Uremic pericarditis (early dialysis or under-dialysis) vs. non-uremic (well-dialyzed); risk of tamponade; intensify dialysis ± anti-inflammatories ± pericardiocentesis
• Atrial fibrillation: Anticoagulation risk-benefit must be individualized

2. Infections

• Second leading cause of death
• Vascular access infections (especially CVC-related bacteremia) — biofilm on catheter surface
• Hepatitis B/C: Reduced by vaccination, isolation, universal precautions, serologic surveillance
• Uremia-induced immunodeficiency: impaired innate + adaptive immunity; reduced vaccine responses

3. Anemia

• Erythropoietin deficiency (primary driver), iron deficiency, chronic inflammation, blood loss
• Managed with erythropoiesis-stimulating agents (ESAs) + IV iron

4. Mineral Metabolism Disorders

• Secondary hyperparathyroidism → renal osteodystrophy, vascular calcification
• Calciphylaxis (calcific uremic arteriolopathy): rare, painful, life-threatening skin/subcutaneous calcification

5. Hypertension

• Volume-dependent; goal: achieve dry weight; control interdialytic Na⁺/fluid intake

6. Malnutrition (Protein-Energy Wasting)

• Due to hypercatabolism, inadequate intake, dialysate losses

7. Dialysis-Related Amyloidosis

• β₂-microglobulin accumulation → carpal tunnel syndrome, destructive arthropathy (usually after >10 years on HD)

8. Depression and Psychological Morbidity

• Serious, underrecognized; HD patients 3× more likely to commit suicide in Taiwanese registry data

9. Cancer Screening

• Routine screening may not be cost-effective in average HD patients; individualize based on life expectancy and transplant candidacy

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4. Peritoneal Dialysis Complications

A. Mechanical Complications

B. Metabolic Complications

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C. Peritonitis & Exit-Site Infection

Peritonitis (CAPD-Associated)

• Cloudy dialysate (cardinal sign)
• WBC in effluent >100/µL with >50% PMNs (ISPD criteria)
• In automated PD (APD) with short dwell time: % PMNs more important than absolute WBC count
• Send dialysate for: cell count + differential, Gram stain, culture in blood culture bottles (improves yield; centrifuge large volume first)

• Staphylococcus species: ~45% (coagulase-negative S. epidermidis, and S. aureus — especially in nasal carriers)
• Gram-negative bacilli
• Candida species (fungal peritonitis → catheter removal mandatory)
• Multiple organisms → suspect secondary peritonitis (bowel perforation)

• Empirical: intraperitoneal (IP) antibiotics covering both gram-positive (vancomycin or first-generation cephalosporin) and gram-negative organisms (aminoglycoside or third-generation cephalosporin)
• Route: IP delivery is preferred (directly into dialysate bag)
• Tailor to culture/sensitivity after 48–72 h
• Duration: typically 2 weeks (gram-positive); 3 weeks (gram-negative, S. aureus)
• Catheter removal indications: refractory peritonitis >5 days, fungal peritonitis, tunnel infection with refractory peritonitis, fecal peritonitis

Exit-Site Infection (ESI) & Tunnel Infection

• ESI: purulent discharge ± erythema/crusting at catheter exit site
• Tunnel infection: infection along subcutaneous catheter tunnel; painful induration/erythema over tunnel; diagnosed clinically ± ultrasound
• Causative organisms: S. aureus (most common), Pseudomonas aeruginosa (difficult to eradicate)
• S. aureus nasal carriage is a major risk factor
• Management: oral/IP antibiotics; refractory ESI or tunnel infection → catheter removal
• Prevention: topical mupirocin or gentamicin at exit site (reduces S. aureus and Pseudomonas ESI)

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UNIT C

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5. Dialysis Modalities: Nocturnal, Online & Daily Dialysis

A. Nocturnal Dialysis

• 6–8 hours, 3× weekly, while patient sleeps
• Advantages: longer duration → better solute removal (especially middle molecules, phosphate), less cardiovascular stress
• Observational data show: regression of left ventricular mass, improved bone mineral indices, better quality of life

• 3–4 nights/week × 6–8 hours
• Better BP control, reduced phosphate binders requirement
• Concerns: more rapid decline in residual kidney function, more vascular access interventions, patient recruitment difficulty
• One RCT (FHN Nocturnal Trial) confirmed improvements in LV mass and BP but failed to show survival benefit (Brenner & Rector)

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B. Short Daily Hemodialysis

• 5–6 sessions/week × 2–4 hours each
• NIH-sponsored FHN (Frequent Hemodialysis Network) Daily Trial — largest RCT:
  • ✅ Reduced LV mass
  • ✅ Improved self-reported physical health
  • ✅ Reduced predialysis serum phosphate
  • ✅ Reduced predialysis systolic BP
  • ❌ No improvement in survival or hospitalization rates
  • ❌ No improvement in serum albumin
  • ❌ No reduction in ESA dose
• Shorter interdialytic interval → less fluid accumulation, better hemodynamic tolerability

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C. Online Hemodiafiltration (HDF) / Online Dialysis

• Principle: combines diffusion (small solute removal) + convection (middle/large molecule removal), e.g., β₂-microglobulin, FGF-23, cytokines
• Requires ultra-pure water system and specific machine capability
• High-volume online HDF (≥23 L substitution volume per session) associated with:
  • Reduced all-cause and cardiovascular mortality in observational studies
  • Reduced dialysis-related amyloidosis
  • Better phosphate control and reduction in pruritus
• CONVINCE Trial (2023): Large multicenter RCT — online HDF reduced all-cause mortality by ~23% vs. high-flux HD (PMID: 40123557 — Systematic Review: "Alpha to Omega of Dialysis Access" 2025)
• Used increasingly in Europe; gaining ground worldwide as evidence base strengthens

Wearable and Portable Artificial Kidney (Research Frontier)

• Miniaturized dialysis devices aiming for continuous, ambulatory dialysis
• Prototype wearable artificial kidneys (WAK) under clinical trials; ESKD patients could theoretically dialyze continuously while ambulatory
• Challenges: anticoagulation, sorbent regeneration, miniaturized pumps, and regulatory approval

High-Cutoff (HCO) Dialyzers

• Designed to remove large middle molecules (e.g., free light chains in myeloma kidney, cytokines in sepsis-AKI)
• Under investigation in clinical trials

Incremental Dialysis

• Starting with once or twice weekly HD (rather than thrice-weekly) in patients with significant residual kidney function (RKF)
• Preserves RKF longer, reduces cost, better quality of life
• Growing evidence base for safety in carefully selected patients (eGFR >4–5 mL/min/1.73 m²)

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Summary Table

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BDTT-023-d/e/f: Telemedicine in Dialysis, Kidney Transplant Immunology, Donors & Special Transplant Programs

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UNIT D — Telemedicine in Dialysis Practice

Definition & Background

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Applications in Dialysis Practice

1. Remote Patient Monitoring (RPM) in Home HD & PD

2. Telehealth Consultation

• Video consultations replace in-center visits for stable patients
• Reduces patient travel burden (especially important for rural/remote patients)
• Allows prescribing adjustments, medication reviews, and education sessions remotely
• Particularly useful for pre-dialysis education, modality selection counseling, and diet/fluid counseling

3. Virtual Training for Home Dialysis Patients

• Step-by-step video guidance for PD exchanges and HD cannulation
• Reduces training time and supports caregiver confidence
• Platforms include telehealth apps with interactive protocols

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Evidence Base

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Benefits of Telemedicine in Dialysis

1. Fewer clinic visits → reduced patient burden, lower infection exposure
2. Early detection of fluid overload, hypertension, vascular access problems
3. Improved adherence through remote coaching and reminders
4. Support for home dialysis expansion — enables more patients to dialyze at home safely
5. Reduced hospitalizations via proactive problem-solving
6. Healthcare equity — access to specialist nephrology in underserved areas

Challenges & Limitations

• Digital divide: elderly/low-literacy patients struggle with technology
• Regulatory barriers: reimbursement policies vary by country
• Data security and patient privacy concerns
• Limited RCT evidence on mortality/hospitalization hard outcomes
• Provider workflow changes required
• Internet connectivity issues in rural/remote areas

Future Directions

• AI-driven prescription optimization: algorithms adjusting UF rates, session length based on real-time biometrics
• Wearable sensors: continuous BP and fluid monitoring between sessions
• Virtual reality for patient education
• Integration with electronic health records (EHR) for seamless care coordination

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UNIT E — Introduction to Kidney Transplantation Immunology, Procedure & Immunosuppressive Medications

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1. Immunology of Kidney Transplantation

The Alloimmune Response

Key Immunologic Concepts

• HLA Class I (A, B, C) — expressed on all nucleated cells; recognized by CD8⁺ cytotoxic T-cells
• HLA Class II (DR, DQ, DP) — expressed on antigen-presenting cells (APCs), activated endothelium; recognized by CD4⁺ helper T-cells
• HLA mismatch between donor and recipient drives alloreactivity

1. Signal 1: Antigen recognition — TCR binds HLA-peptide complex
2. Signal 2: Co-stimulation — CD28 on T-cell binds B7 (CD80/86) on APC → activates NF-κB and AP-1 → IL-2 production
3. Signal 3: Cytokine proliferation signal — IL-2 binds IL-2R → mTOR activation → T-cell proliferation

• CD4⁺ T-helper cells provide signals to B-cells → plasma cells → donor-specific antibodies (DSA)
• DSA bind donor HLA on graft endothelium → complement activation → C4d deposition → endothelial injury → antibody-mediated rejection (AMR)

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2. Types of Rejection

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3. Transplant Procedure (Brief)

• ABO blood group compatibility
• HLA typing (recipient and donor)
• Crossmatch: Donor lymphocytes + recipient serum — positive crossmatch = preformed DSA = contraindication (unless desensitized)
• Panel Reactive Antibody (PRA) / calculated PRA: measures degree of sensitization

• Heterotopic transplant: donor kidney placed in iliac fossa (extraperitoneal)
• Donor renal artery → recipient external iliac artery (end-to-side)
• Donor renal vein → recipient external iliac vein
• Ureter → bladder (ureteroneocystostomy, often with ureteral stent)
• Native kidneys left in situ (unless causing hypertension, infection, pain, or polycystic kidneys)

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4. Immunosuppressive Medications

Phase 1: Induction Therapy (at time of transplant)

90% of US recipients receive induction (SRTR 2018): 72% T-cell depleting, 20% IL-2 receptor antibody.

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Phase 2: Maintenance Immunosuppression

A. Calcineurin Inhibitors (CNI) — Backbone

B. Antiproliferative Agents

C. mTOR Inhibitors

D. Corticosteroids

• Mechanism: Suppress cytokines (IL-1, IL-2, TNF-α), inhibit NF-κB via IκB induction, inhibit phospholipase A2 via lipocortin → block prostaglandins/leukotrienes
• Induction: Methylprednisolone 250–500 mg IV
• Maintenance: Prednisone 5 mg/day (or steroid-free protocols)
• Acute rejection treatment: Methylprednisolone 3–5 mg/kg (250–500 mg) IV × 3–5 days
• Side effects: Diabetes, hypertension, hyperlipidemia, osteoporosis, avascular necrosis, cataracts, peptic ulcer disease, Cushing syndrome, infection

E. Belatacept (Costimulation Blocker)

• Fusion protein (CTLA4-Ig); blocks CD28–B7 co-stimulation (Signal 2)
• IV monthly infusion; avoids CNI nephrotoxicity
• Slight higher acute rejection risk; associated with post-transplant lymphoproliferative disorder (PTLD) in EBV-seronegative recipients
• Used in CNI-intolerant patients

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Phase 3: Treatment of Acute Rejection

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UNIT F — Donor Types, Paired Exchange, ABO-Incompatible & Sensitized Recipients

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1. Live Donor Transplantation

• Better graft survival (longer half-life)
• Shorter cold ischemia time
• Elective scheduling; better pre-transplant optimization
• Superior short- and long-term outcomes

• Comprehensive medical (rule out diabetes, hypertension, cardiovascular disease, CKD, malignancy), surgical, and psychosocial evaluation
• CT angiogram or MR angiogram of kidneys: defines vascular anatomy, excludes anomalies, determines which kidney to remove
• Left kidney preferred (longer renal vein → easier anastomosis)
• Donor mortality: ~0.03%

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2. Deceased Donor (Cadaver) Transplantation

A. Brain-Dead Donors (DBD — Donation after Brain Death)

• Cardiac function maintained on ventilator
• Organs well-perfused until procurement
• Standard deceased donor

B. Donors after Cardiac/Circulatory Death (DCD)

• Cardiopulmonary support withdrawn in controlled setting after catastrophic brain injury (not meeting brain-death criteria)
• Organ procurement after cardiac arrest → higher warm ischemia time
• Higher risk of delayed graft function (DGF), but comparable long-term outcomes to DBD
• DCD donors represent ~10% of deceased donors in the USA (rapidly increasing)

• Kidney Donor Profile Index (KDPI): Score 1–100; lower score = better predicted kidney longevity
• Estimated Post-Transplant Survival (EPTS) score for recipients: lowest EPTS (longest predicted survival) get the best KDPI kidneys
• Extended Criteria Donors (ECD): Age ≥60, or age 50–59 with ≥2 of: history of hypertension, terminal creatinine >1.5 mg/dL, or CVA as cause of death → higher DGF risk but expand donor pool

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3. Paired Kidney Exchange (PKE) Transplantation

Concept

• Pair A: Donor A (blood group A) → incompatible with Recipient A (blood group B)
• Pair B: Donor B (blood group B) → incompatible with Recipient B (blood group A)
• Exchange: Donor A gives kidney to Recipient B; Donor B gives kidney to Recipient A

Programs

• National Kidney Registry (NKR) — USA
• UK Living Kidney Sharing Schemes
• Extended to chains and non-directed altruistic donors (stranger/Good Samaritan donors initiate chains)

Outcomes

• Paired exchange accounted for 14% of living donor transplants in the USA in 2018 (up from 5% in 2009)
• No difference in graft or patient survival at 3, 5, and 7 years vs. direct living donor transplants (NKR data) — despite higher risk-factor burden (Comprehensive Clinical Nephrology, 7th Ed.)

Logistics

• Surgeries must be simultaneous (to prevent donor withdrawal after recipient receives kidney)
• Complex matching algorithms (maximize compatible pairs)

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4. ABO-Incompatible (ABOi) Transplantation

Background

Desensitization Protocol

1. Rituximab (anti-CD20) given 2–4 weeks pretransplant → depletes B-cells → reduces antibody production
2. Plasmapheresis (PE) — removes circulating anti-A/B isohemagglutinins (2–4 sessions until titers acceptable, typically IgG titer ≤1:8 to 1:16)
3. IVIG — after each PE session (100–200 mg/kg) or high-dose (1–2 g/kg) → modulates B-cell function
4. Some protocols add immunoadsorption columns (A/B antigen-specific) — more efficient antibody removal than PE
5. Maintenance immunosuppression as per standard protocol

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5. Transplantation in Sensitized Recipients

Who is Sensitized?

• Prior kidney transplant
• Blood transfusions
• Pregnancy

• PRA 0–20%: Low sensitization
• PRA 20–80%: Moderate
• PRA >80%: Highly sensitized (extremely difficult to find compatible donor)
• Virtual crossmatch (cPRA): Uses HLA antibody specificity to computationally predict crossmatch results

Options for Sensitized Recipients

Desensitization Protocol for HLA-Incompatible Transplantation

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Summary Table for Exam

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BDTT-023-d/e/f — Easy Exam Notes

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UNIT D — Telemedicine in Dialysis Practice

What is Telemedicine?

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How is it Used in Dialysis?

1. Remote Patient Monitoring (RPM)

2. Video Consultations

• Replace routine in-center visits for stable patients
• Used for: medication reviews, diet counseling, blood pressure review, pre-dialysis education
• Especially valuable for patients in rural or remote areas

3. Virtual Training

• Patients learn PD exchanges and HD cannulation via video guides
• Reduces time needed for in-person training

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Benefits

Challenges

• Digital divide — elderly patients struggle with technology
• Privacy concerns — patient data security
• Connectivity — poor internet in rural areas
• No RCT evidence yet on survival benefit
• Reimbursement — regulatory/payment policies vary by country

Future

• AI algorithms adjusting dialysis prescriptions automatically
• Wearable sensors for continuous BP and fluid monitoring
• Integration with Electronic Health Records (EHR)

📖 COVID-19 was a major accelerant for telemedicine adoption in dialysis globally. Patient acceptance is very high. — Lew et al., CJASN 2024

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UNIT E — Kidney Transplantation: Immunology, Procedure & Immunosuppression

Why Does the Body Reject a Transplanted Kidney?

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Key Immunology Concepts

HLA (Human Leukocyte Antigens)

• Proteins on cell surfaces that act as "identity badges"
• HLA Class I (A, B, C): on all nucleated cells → recognized by CD8⁺ T-cells
• HLA Class II (DR, DQ, DP): on immune cells & activated endothelium → recognized by CD4⁺ T-cells
• The more HLA mismatches between donor and recipient → higher rejection risk

Two Pathways of Rejection

T-Cell Activation — The 3-Signal Model

Signal 1: T-cell receptor sees donor HLA antigen
Signal 2: Co-stimulation (CD28 on T-cell binds B7 on APC) → NF-κB → IL-2 production
Signal 3: IL-2 binds IL-2 receptor → mTOR → T-cell proliferation

Key exam point: Each signal corresponds to a drug target!

• Signal 1 blocked by: CNIs (tacrolimus, cyclosporine) → block IL-2 production
• Signal 2 blocked by: Belatacept (CTLA4-Ig) → blocks CD28–B7 co-stimulation
• Signal 3 blocked by: mTOR inhibitors (sirolimus, everolimus)

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Types of Rejection (Simple Table)

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The Transplant Procedure (Simplified)

1. ABO blood group match
2. HLA typing of donor and recipient
3. Crossmatch test: Mix donor cells + recipient blood serum. If antibodies present → POSITIVE crossmatch = danger of hyperacute rejection → usually contraindication to transplant

• Donor kidney placed in the right or left iliac fossa (lower abdomen) — NOT where the original kidneys are (those stay unless problematic)
• Artery → external iliac artery
• Vein → external iliac vein
• Ureter → bladder (ureteroneocystostomy)
• Takes ~3–4 hours

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Immunosuppressive Medications

Phase 1: INDUCTION (at the time of transplant)

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Phase 2: MAINTENANCE (long-term)

A. Calcineurin Inhibitors (CNIs) — BACKBONE of maintenance

🧠 Memory: "Tacrolimus takes your Tremor and Type 2 diabetes" | "Cyclosporine = Curly hair + Calloused gums"

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B. Antiproliferative Agents — Stop lymphocyte division

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C. mTOR Inhibitors

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D. Corticosteroids

• Prednisone 5 mg/day (maintenance)
• Side effects: Diabetes, osteoporosis, Cushing syndrome, peptic ulcer, hypertension, cataracts, avascular necrosis of hip

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E. Belatacept (newer agent)

• Blocks Signal 2 (CD28–B7 co-stimulation)
• IV monthly infusion
• Avoids CNI nephrotoxicity
• Risk: PTLD in EBV-seronegative recipients (contraindicated)

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Phase 3: TREATMENT OF REJECTION

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Side Effects — Quick Memory Table

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UNIT F — Donor Types, Paired Exchange, ABOi & Sensitized Recipients

1. Live Donor Transplantation

• Better graft survival
• Shorter waiting time
• Planned surgery → better preparation
• Less ischemia time

• Must be healthy: no diabetes, hypertension, CKD, malignancy, cardiovascular disease
• CT or MR angiogram → look at kidney anatomy, decide which kidney to take
• Left kidney preferred (longer renal vein = easier surgery)
• Psychosocial evaluation to confirm voluntary, informed decision
• Donor mortality: very low (~0.03%)

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2. Deceased (Cadaveric) Donor Transplantation

A. Brain-Dead Donor (DBD)

• Patient declared brain-dead (irreversible loss of all brain function)
• Heart still beating on life support
• Best organ quality (good perfusion until retrieval)
• Most common type of deceased donor

B. Donation after Cardiac Death (DCD)

• Patient has devastating brain injury but doesn't meet brain-death criteria
• Family/team decides to withdraw life support
• Organs harvested after the heart stops
• More warm ischemia time → higher risk of delayed graft function (DGF)
• Long-term outcomes similar to DBD
• ~10% of deceased donors in USA

• KDPI (Kidney Donor Profile Index): 1–100; lower = better kidney
• EPTS (Estimated Post-Transplant Survival): Best kidneys go to recipients with best predicted survival

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3. Paired Kidney Exchange (PKE) Transplantation

The Problem

The Solution: Swap donors!

Imagine:
🔴 Patient A (blood group B) + Donor A (blood group A) → INCOMPATIBLE
🔵 Patient B (blood group A) + Donor B (blood group B) → INCOMPATIBLE

Solution: Donor A → Patient B    |    Donor B → Patient A ✅
Both patients get a compatible kidney!

Key Points

• Surgeries are simultaneous (so no one backs out after their recipient gets a kidney)
• Extended to chains — a non-directed (altruistic/stranger) donor starts a chain of transplants
• National Kidney Registry (USA): Computerized matching system
• PKE = 14% of living donor transplants in USA (2018), up from 5% in 2009
• Outcomes: Same graft and patient survival at 3, 5, 7 years vs. direct living donation

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4. ABO-Incompatible (ABOi) Transplantation

The Problem

The Solution: Remove those antibodies first!

If PKE can find a compatible pair, that's preferred over ABOi. But when no exchange is possible, ABOi with desensitization is a valid option.

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5. Transplantation in Sensitized Recipients

Who is Sensitized?

• Previous kidney transplant (most common)
• Blood transfusions
• Pregnancy

How is Sensitization Measured?

Options for Sensitized Patients

Desensitization Protocol

Plasmapheresis × 2–5 sessions (removes DSA from blood)
        +
IVIG (2 g/kg total) — neutralizes antibodies, modulates B-cells
        +
Rituximab 375 mg/m² — depletes B-cells → reduces DSA production
        +/- 
Bortezomib (1.3 mg/m² × 4 doses) — kills plasma cells → long-term DSA reduction
        +/-
Eculizumab — anti-C5 complement blocker → protects graft endothelium peri-transplant

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Summary — All 4 Special Transplant Scenarios

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One-Page Exam Cheat Sheet

IMMUNOSUPPRESSION REGIMEN (Standard):
   Induction:     rATG (high risk) or Basiliximab (low risk) + Methylprednisolone
   Maintenance:   TACROLIMUS + MMF ± PREDNISONE
   Rejection Rx:  TCMR → Steroids ± rATG
                  AMR  → Plasmapheresis + IVIG ± Rituximab

KEY DRUG SIDE EFFECTS:
   Tacrolimus     → New-onset Diabetes (NODAT)
   Cyclosporine   → Gum hyperplasia + Hirsutism
   MMF            → Diarrhea + Leukopenia
   Azathioprine   → NEVER with Allopurinol!
   Steroids       → Diabetes + Osteoporosis
   Sirolimus      → Poor wound healing

REJECTION TYPES:
   Hyperacute     → Pre-formed antibodies → minutes → Prevent with crossmatch
   Acute TCMR     → Days–weeks → Tubulitis → Steroids
   Acute AMR      → Days–weeks → C4d+ → PE + IVIG + Rituximab
   Chronic AMR    → Months–years → Transplant glomerulopathy → Leading cause of late graft loss

PAIRED EXCHANGE:
   PKE = 14% of US living donor transplants
   Simultaneous surgeries → Same outcomes as direct donation

DESENSITIZATION:
   ABOi  → Rituximab + Plasmapheresis + IVIG → Titer ≤1:8
   HLA+  → Plasmapheresis + IVIG ± Rituximab ± Bortezomib ± Eculizumab

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