Renal Transplantation

Renal Transplantation Daniel Shoskes MD, FRCS(C) Professor of Surgery/Urology Glickman Urological and Kidney Institute Cleveland Clinic

Topics to Cover • Basic Transplant Immunology • Immunosuppressive Drugs • Evaluation of Recipient and Donor • Surgical Techniques and Complications • Early and Late Patient Management Issues

Renal Transplantation • Usually preferred form of renal replacement therapy • Cost effective if transplant lasts more than 2 years • Exchange disease of renal failure with "disorder" of being a transplant recipient • infections, cancer, diabetes, HTN, cardiac

Practical Immunosuppresion Facts • cyclosporine and tacrolimus • IV dosing -> 1/4 to 1/3 oral dose • drug interactions (cytochrome P450) • Raise: diltiazem, verapamil, ketoconazole, fluconazole, erythromycins, allopurinol, Reglan, ciprofloxacin, grapefruit juice • Decrease: Dilantin, phenobarbitol, rifampin, St. John's wort • Sirolimus (rapamycin) • Most difficult side effects are increased lipids, wound complications and reduced white count

Recipient Evaluation • Active infection • Malignancy • Recurrence of primary disease • Early mortality • Technical complications • Noncompliance • Lack of social or financial resources

Malignancy • Renal • No waiting period if incidental lesion • 2 years if symptomatic • Best to remove complex cystic mass • Bladder, Prostate, Testis • 2 years • beware need for BCG • evolving data suggests prostate cancer not a barrier (treated or untreated)

Recurrence of Primary Disease • High risk, High consequence • focal segmental glomerular sclerosis (FSGS), oxalosis (liver), hemolytic uremic syndrome (HUS) • High risk, low consequence • diabetes, IgA Nephropathy • Low to zero risk • polycystic kidney disease, primary reflux

Technical Issues • Peripheral Vascular Disease • safe kidney location, risk of steal • Lower urinary tract • clean intermittent self catheterization safe and effective • transplant to augment or diversion similar long term outcome • "dry TURP" prone to strictures and contractures • bladders will expand unless fibrosis

Native Nephrectomy • Suspicion of malignancy • Massive size • Grade 4-5 reflux • Massive proteinuria • Intractable hypertension • Recurrent stones • Recurrent UTI

Kidney Donors • >50% now living donor source in USA • cadaveric criteria expanded to include double kidneys at extremes of age and non-heart beating donors • brain death -> organ dysfunction • well matched cadaveric fares worse than poorly matched LRD

Risks to the Living Donor • Mortality 0.03% • Morbidity • Major 0.2% • Minor 8% • No increased risk of renal failure or hypertension compared to siblings • Extensive medical investigations give net survival benefit

Pros possibly smaller incision shorter hospital stay less pain medication faster return to work increased donor acceptance so far, graft survival is equivalent Cons increased operative time shorter blood vessels right kidney may pose challenge, violate “leave donor with better kidney” rule increased ischemic injury to kidney, DGF more common Laparoscopic Kidney Donation

Ischemia-Reperfusion and DGF • Ischemia and reperfusion at surgery produce injury that can promote inflammation and rejection • Delayed graft function strong predictor of graft survival independent of rejection • Pulsatile perfusion can improve early function, especially with long cold ischemia times • Perioperative maneuvers • hydrate with colloid • mannitol • furosemide • intra-arterial verapamil • low dose dopamine

Intra-operative Decisions • Preserve lower pole arteries (ureter) • Right renal vein -> caval extension • Can use cadaveric iliac vessels • Conjoin arterial branches or end-side • Small lower pole vessel end-end to inferior epigastric artery • Can use ipsilateral native ureter end-end without native nephrectomy

Common Questions • Preserve lower pole artery, tie off small upper pole • 2 ureters conjoined or separate • 1 donor kidney has minor anomaly -> always transplant THAT kidney • may tie off any small venous branch • close ureteral gap • Boari, Psoas Hitch, U-U, U-P, P-C, ileal

Surgical Risks • Vascular leak or thrombosis (1-2%) • re-operation, high risk to lose kidney • Urine leak or obstruction (4-5%) • may need re-operation, low risk to lose kidney • many endoscopic approaches, surgery for early leaks, necrotic ureter or endo failure • Lymphocele (5-10%) • percutaneous drainage, sclerosis, peritoneal window • Wound infection / hernia

Early Graft Dysfunction • Check Foley, fluid bolus, Lasix, drug levels, ultrasound, renal scan, biopsy • Ddx: ATN, acute rejection, drug toxicity, vascular compromise • (ACE inhibitor, renal artery stenosis) • Acute Rejection • Steroids • Antibody (thymoglobulin or OKT3)

BK Virus • Polyoma virus, latent in immunocompetent • Nephropathy in about 8% of recipients • Dx: Cytology, viuria, viremia, biopsy • Rx: minimize immunosuppression • GU Manifestations • nephropathy, graft loss • sterile pyuria (also in pregnancy) • ureteral stenosis • hemorrhagic cystitis

A transplant patient has a baseline serum Cr of 1.8 mg/dl and takes tacrolimus, MMF and steroids. Because of persistent hypertension, he is started on an ACE inhibitor. One week later the Cr is 3.1 mg/dl. The most likely explanation is: • Acute rejection • Renal artery stenosis • Hypotension and acute tubular necrosis • Acute renal vein thrombosis • Tacrolimus toxicity since the ACE inhibitor raised the blood levels

A transplant center is offered a cadaveric kidney from a 53 year old donor who died from head trauma. Terminal creatinine was 1.6 mg/dl. Patient had a history of hypertension well controlled with 1 drug for 2 years. It is a left kidney with 2 arteries and 2 ureters. Biopsy shows 30% glomerulosclerosis. The most likely reason to turn down this kidney is: • high terminal creatinine • donor age • 2 ureters • 30% glomerusclerosis • 2 renal arteries

Internet File Location • ftp://ftp.dshoskes.com

Renal Transplantation