renal transplantation

Renal Transplantation Dr.Varun Wats History • The first documented kidney transplant in the United States was performed June 17, 1950, on Ruth Tucker, a 44-year-old woman with polycystic kidney disease, at Little Company of Mary Hospital in Evergreen Park, Illinois, a Chicago suburb. Indications • • • • • • • Pts of end stage renal dsGlomerulonephritis Diabetic nephropathy Hypertensive nephrosclerosis Renal vascular disease Polycystic disease pyelonephritis • • • • Obstuctive uropathy SLE Analgesic nephropathy Metabolic diseases( Oxalosis, amyloid ) NOTE • CAREFUL PATIENT SELECTION IS ESSENTIAL FOR THE SUCCESSFUL OUTCOME OF THE PROCEDURE • THEREFORE FOLLOWING POINT TO BE KEPT IN MIND ALWAYS • NO UPPER AGE LIMIT FOR TRANSPLANTATION BUT PTS OLDERTHAN 65 YRS ARE LESS SUITABLE CANDIDATES • CAREFUL ASSESSMENT OF COMORBID CONDITIONS IS VERY IMPORTANT ESP CARDIO VASCULAR SYSTEM • ENSURE THAT URINARY TRACT IS FUNCTIONAL AND THERE IS NO NEED FOR CORRECTIVE UROLOGICAL SURGERY • PREEXISTING MALIGNANCY IS ABSOLUTE CONTRAINDICATION • PRESENCE OF INFECTION IS ABSOLUTE CONTRAINDICATION Sources of kidneys • LIVING DONORS – Most living donors are genetically related individuals. • Before donation it is essential to perform renal imaging ( selective renal angiography , CT guided angiography ) to delineate arterial supply of kidney NOTE • If left kidney has a single renal artery it is usually chosen as it has longer renal vein which simplifies transplantation DONOR NEPHRECTOMY • OPEN NEPHRECTOMY – Loin incision and retroperitoneal approach or midline abdominal incision and transperitoneal approach • LAPAROSCOPIC DONOR NEPHRECTOMY- This reduces pain and accelerates recovery for the donor with minimal effect on the outcome of the kidney. Deceased Donors • Fall in two groups • BRAIN DEAD DONORS • NON HEART BEATING (ASYSTOLIC) DONORS BRAIN DEAD DONORS • Here severe brain injury causes irreversible loss of capacity for consciousness combined with irreversible loss of capacity for breathing but the heart continues beating. Clinical testing after brain stem death • ABSENCE OF CRANIAL NERVE REFLEXES • Pupillary refles • Corneal reflex • Pharyngeal , tracheal reflex • Oculovstibular reflex • ABSENCE OF MOTOR RESPONSE- to a painful stimuli applied on head , face • ABSENCE OF SPONTANEOS RESPIRATION- preventilate with 100 % O2for 5 min , disconnect from ventilator for 10 min to confirm absence of respiratory effort. NOTE DON’T USE KIDNEYS FROM HIV PTS INFECTIONS LIKE HEPATITIS B ACTIVE SYSTEMIC SEPSIS LIKE MAJOR ABDOMINAL INFECTION • PRESENCE OF MALIGNANCY WITHIN THE PAST 5 YS • • • • NON HEART BEATING (ASYSTOLIC ) DONORS Classified according to Maastricht classification Category 1 – dead on arrival at hospital Category 2 – unsuccessful resuscitation in hosp Category 3 – awaiting cardiac arrest after withdrawal of support • Category 4- cardiac arrest while brain dead • • • • • In non heart beating donors the kidneys usually suffer from ischemic damage. • THEREFORE DELAYED GRAFT FUNCTION IS MORE COMMON IN THESE KIDNEYS AS COMPARED WITH HEART BEATING CADAVERIC DONORS Organ Procurement • In the donors midline abdominal incision given. • After dissection of organs to be procured they are perfused in situ with chilled organ preservation solution via aortic and portal cannula- this causes rapid cooling of organs , reduces their metabolic activity and preserves their viability • After removal the kidneys are further flushed with chilled preservation solution ( UW solution , Euro Collins solution ) and placed in plastic bags and immersed in ice and then transported. COMPATIBILITY • For the best possible outcome two types of tests are done • TISSUE TYPING ( HLA TYPING)- they are a group of highly pleomorphic cell surface molecules • Physiological function is as antigen recognition units • Two types- HLA class 1 ( A , B , C ) • HLA class 2 – ( DR , DP , DQ ) • Encoded by Major Histocompatibility complex ( MHC ) , cluster of genes on short arm chromosome 6. • In renal transplant pts attempts are made to match the donor and recipient MHC antigens for as many of relevant HLA antigens as possible. • In terms of transplantation HLA A > HLA B > HLA DR NOTE • Anti HLA antibodies develop after sensitization esp after blood transfusion in women who have been previously primed paternal HLA antigens during pegnancy. • These anti HLA antibodies cause hyper acute rejection. • THEREFORE THE DETECTION OF THESE IN PROSPECTIVE RECIPIENTS IS ABSOLUELY ESSENTIAL • ABO BLOOD GROUP COMPATIBILITYImp to remember that antibodies are not formed against the blood group antigen expressed by the person Permissible Transplants are DONOR GROUP O RECIPIENT GROUP O, A , B , AB A B A , AB B , AB AB AB Technique • Curved incision made in lower abdomen • Divide muscles of abdominal wall • Peritoneum swept upwards to expose iliac vessels • Transplant kidney is placed in iliac fossa in retroperitoneal position , leaving native kidneys I situ • Donor renal vein anastomosed end to side to side to ext iliac vein • Donor renal artery on carrel patch of donor aorta anastomosed end to side to ext iliac artery • Then ureter is then anastomosed to bladder• LICH GREGOIR technique-direct implantation of ureter into dome of bladder with mucosa to mucosa anastomosis • LEADBETTER POLITANO techniquesubmucosal anti reflux tunnel made • IMPORTANT TO ENSURE THAT KIDNEY IS LYING IN SATISFACTORY POSITION WITHOUT KINKING OR TORSION OF VESSELS COMPLICATIONS • VASCULAR COMPLICATIONS• Renal artery and vein thrombosis – – – – – – Incidence low Presents during first week Sudden pain and swelling at the site of transplant Renal artery – 1 % cases Renal vein – 5% cases Confirmed – doppler ultrasonography – Urgent surgical exploration , transplant nephrectomy required mostly – Low dose heparin prophylaxis decreases incidence • Renal artery stenosis -presents yrs after transplantation – Increasing hypertension, decreasing renal fx – Incidence 10 % – Diagnosis - angiography – Treated- angioplasty • Urological complications– Incidence – 10 % • Urinary leaks– – – – because of technical errors of ureteric anastomosis Ureteric ischaemia Present with leakage of urine from wound Treated- reimplantation of ureter into bladder • Obstruction of ureter– Early or late – Causes- technical error, ext pressure from haematoma, ischemic stricture – Painless deterioration in transplant function – Ureteric dilatation on USG – Initial treatment- percutaneous antegrade nephrostomy, insertion of stent – Best treatment- surgical reimplantation of ureter into bladder • Lymphocele– Peritransplant lymphocele usually asymptomatic – Occasionally become large- causing ureteric obs – Initial treatment- USG guided percutaneous drainage – Large or recurrent lymphocele – instillation of povidone iodine into cavity by percutaneous drain Graft rejection • Types– Hyperacute rejection – Acute rejection – Chronic rejection Hyperacute rejection • Occurs immediately within minutes and hours • Due to ABO or pre formed anti HLA antibodies • Cause extensive intravascular thrombosis • Kidneys particularly vulnerable • Avoided – ensuring ABO blood compatibility , Cross match test on recepient serum against HLA antigens of kidney donor. Acute rejection • • • • During first 6 months Mediated by T cells Characterised by mono nuclear cell infiltration Usually reversed by additional immunosuppressive therapy Chronic rejection • After first 6 months • Major cause of graft failure • Risk factors – – – – – – Previous episode of acute rejection Poor HLA match Long , cold ischaemic time CMV infection Raised blood lipids – Inadequate immuno suppression • Histologically- glomerular sclerosis, tubular atrophy Immunosuppressive therapy • Therapy given to reduce graft rejection • Various types are available Calcineurin blockers • Cyclosporin , Tacrolimus • Binds within T cell and blocks IL 2 gene transcription , which is a T cell growth factor • Most important side effect - nephrotoxicity Anti proliferative agents • Azathioprine , Mycophenolate mofatil (MMF) • Prevent lymphocyte proliferation • Side effect- bone marrow suppression Steroids • Potent anti inflammatory agents • Generally with drawn after 1 yr of stable graft function Triple therapy • In kidney transplant combination of calcineurin blocker , along with anti proliferative agents with steroids is given Antibody therapies • Anti bodies which bind to specifc cells or their components • Like – anti lymphocyte antibody, anti body directed against T cell , AB against IL 2 • Used in pts who are thought to be at a particular risk of graft rejection Complications of immunosuppression • Infections – bacterial , viral , fungal , protozoal • Malignancy- skin cancer , post transplant lymphoproliferative disorder Investigation of graft dysfunction • Early graft dysfx• Causes– Primary non function (irreversible ischaemic damage) – Hyperacute or acute rejection – Drug toxity (calcineurin ) – Infection ( CMV) – Mechanical obstruction ( ureter ) • • • • ManagementIrrigate urinary catheter in case it is occluded Correct hypovolaemia Doppler USG exam to rule out vascular thrombosis , urinary obs • Renal radionucleotide scan – inf renal perfusion and excretion • Withhold calcineurin blockers • Perform USG guided needle biopsy • Transplant nephrectomy may be required • Late graft dysfx• Causes – – – – – Chronic rejection Arterial stenosis Recurrence of original ds Mechanical obs • Management same as of early dysfx Outcome after transplant Pt survival 1 yr 5 yr Cadaveric renal transplant Living related transplant 90 % 80 % > 90 % > 80 % Note • The half life of grafts obtained from living donors is substantially longer than cadaveric grafts THANK YOU