Renal Transplantation Nalaka Gunawansa 30.05.2015

THE HISTORY OF TRANSPLANTATION AS DEPICTED IN ART The possibility to transplant limbs and organs predates the modern technology of organ transplantation. The legend of the “Miracle of the Black Leg” describes two surgeon brothers – 15th century The legend relates their miraculous removal of the diseased leg of a Caucasian Roman named Justinian and its replacement with the leg of a recently deceased black African. The Miracle of Cosmas & Damian (15th c.)

History of Kidney Transplantation 1902 - The first successful experimental kidney transplants IN ANIMALS – Austria 1909 - The first kidney transplant experiments were performed in humans in France using animal kidneys. 1933 - The first human-to-human kidney transplant REJECTION 1940’s - Sir Peter Medawar at the University of London experimented with the immunologic basis of organ rejection. Early 1950’s - Cortisone-like medications were used to suppress the human immune system

Kidney Transplantation Surgical Milestones Ulman, 1902 – kidney to neck vessels Carrel, 1912 – vascular techniques Kolff, 1940’s – dialysis machine Hume, 1947 – kidney to arm vessels Murray, 1956 – identical twin transplant into the iliac fossa

Alexis carrel Alexis Carrel 1912

Hume, 1950’s – kidney to femoral vessels

History of Kidney Transplantation 1954- First successful kidney transplant Total body irradiation for immunosuppression Steroids Now Multiple immunosuppressants Monoclonal antibodies Plasmapharesis

Nobel Prize in Physiology or Medicine 1990 Joseph E. Murray (1/2) Discoveries concerning organ transplantation in the treatment of human disease In 1954, the first successful human kidney transplant was performed between twins in Boston. Transplants were possible in unrelated people if drugs were taken to suppress the body's immune reaction Great events in history of transplantation 2006-7year Immunology

Murray, 1956 – current transplant position

Current status Live donor renal transplants Deceased donor – brain dead/ cardiac death HLA, anti HLA antibodies, T-B Cell cross match, PRAs, DSAs ABO incompatible transplants Xenotransplant / Tolerance

Kidney transplantation is the most effective therapy for ESRD Ojo, J Am Soc Neph, 2001;12:589

Medical Safety of Living Kidney Donation Living kidney donation - removal of one kidney does not impair survival or long-term kidney function. Extensively screened – HEALTHY Life long follow up

Anatomy of Renal Transplantation

Heterotropic transplant Orthotropic transplant – liver/ lung Heterotropic transplant – kidney Native kidney – only specific indications for removal Infection Space issues

The transplant renal a is anastomosed to the ipsilateral internal or external iliac a, the renal v to internal or external iliac v and the transplant ureter to the bladder.

Factors Determining Transplantation Outcomes Type of donor (cadaveric vs. living) Matching and sensitization Racial Differences Recipient Age Donor Age Ischaemia times Delayed graft function Acute rejection, chronic rejection Years on dialysis Underlying disease leading to ESRD

Waitlist and Transplant Activity for Kidneys, 1999-2008

One Year Unadjusted Graft Survival by Year, Living and Deceased Donor Kidney Transplants

complete follow up data 415 LDRT 18 Lost to follow up 397 (95%) complete follow up data 32 (8%) Graft Failures 365 (92%) Graft survival 8 SGF 24 PGF 5 re-transplanted 19 dead 5 re-transplanted or 3 on waiting list 337 (85%) overall patient survival at 5 yrs

Waiting List/ Deceased Donor Kidney Disparity Am J Transplantation, 2(10): cover, 2002

Paired Donor Exchange Pair #1 Pair #2 Recipient = A Recipient = B Donor = B Donor = A Blood-type incompatible Recip/Donor pairs exchange blood-type compatible kidneys

Organ Preservation Time Heart: 4-6 hours Lungs: 4-6 hours Liver: 12 hours Pancreas: 12-18 hours Kidneys: 72 hours

The Surgical Procedure Many pitfalls and Technical glitches

Renal transplant: Venous anastomosis

Renal transplant: Arterial anastomosis

Surgical Complications Graft thrombosis: Caused by thrombosis of donor renal A or V. Usually happens in first week. Diagnosed by ultrasound with doppler studies. Almost always requires explant of kidney. Urine leak: Major ureteric complications Urine leak/ hydronephrosis May or may not have abdominal pain. Diagnose with nuclear medicine scans (DTPA or MAG3). Surgical repair and/or relief of obstruction.

Renal A / vein thrombosis

Renal Artery Stenosis

Delayed Graft Function Need for dialysis in the first week after transplantation. Causes: ATN from prolonged cold ischemia. Acute rejection. Recurrent disease. Usually requires biopsy for diagnosis and management.

Late Ureteral stenosis (5%) Reflux (30-80%) and acute pyelonephritis (10%) Kidney stones (1%) Tx Renal artery stenosis (10%) AVF & pseudo-aneurysm after renal biopsy (10%) Lymphocele (1-20%)

2. Urinary Leak First transplant month. (2-5%) Presents with urine extravasation and ARF, fever, pain and distended abdomen. Diagnosis is via U/S which demonstrates a peritransplant fluid collection or via radioisotope scanning. Treatment is foley catheter insertion and surgery.

Urinary Leak

3. Obstructive Uropathy Occurs in early post transplant period (3-6%). The commonest causes are extrinsic compression of the ureter by a lymphocoele or due to a technical problem with the ureteric anastomosis to the bladder. Diagnosis is best achieved via U/S demonstrating hydronephrosis. Treatment is surgical.

Routine intraoperative ureteric stenting for kidney transplant recipients (Protocol) Wilson CH, Bhatti AB, Manas DM

Perigraft Fluid Collections Seroma & Hematoma Urinoma Lymphocele

4. Lymphocoele - Occurs within the first 3 post transplant months and is due to lymph leaking from severed lymphatics (5-15%). - Largely self limiting - Rarely cause pressure on the ureter - Percutaneous aspiration, open evacuation

Pseudoaneurysm / AV fistula

Live donor Healthy donors Selecting the kidney – DTPA, CTA Better kidney for the donor Preferentially left Reconstruction if needed (multiple arteries) Open / Robotic/ Total Laparoscopic/ hand assisted laparoscopy

Recipient Antibiotics Fluid management Pressure control and renal perfusion Reperfusion Post-op mobilization/ DVT prophylaxis

Renal transplant: Reperfusion Documented pressure drop >20% of starting SBP sustained for > 5 mins

Imaging Post-transplant Allograft doppler Can diagnose vascular complications, ureteric stenosis Preliminary diagnosis of rejection, pyelonephritis Aid in guided biopsy, stenting if required

Summary The science and art of transplantation in ever evolving Better understanding of immune modulation The demand highly exceeds the demand for organs Embark on deceased donors, cardiac death, extended criteria donors, ABO incompatible Surgically- quick and safe transplant Post transplant vigilance

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