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HOST RESPONSES
• BASIC CONCEPTS OF IMMUNOLOGY
• RECOGNITION OF DANGER
• MAJOR HISTOCOMPATIBILITY COMPLEXES
RECOGNITION OF DANGER
• DANGER ASSOCIATED MOLECULAR PATTERNS (DAMP)
• SENSED THROUGH PATTERN RECOGNITION RECEPTORS (PRRS) ON APCS
• APCS MADE UP OF VARIETY OF INNATE CELLS (MACROPHAGES AND DENDRITIC CELLS)
• MIGRATE TO LYMPHOID TISSUE AND PRESENT ANTIGEN TO T-CELLS.
• RESULTING RESPONSE BALANCED BY CO-STIMULATORY AND INHIBITORY SIGNALS
MAJOR HISTOCOMPATIBILITY COMPLEXES
• MHC CLASS I AND II
• SHORT ARM OF CHROMOSOME 6
• SIX MAIN LOCI IN HUMAN MHC : HLA-A,HLA-B AND HLA – C (CLASS – I)
• HLA – DP,HLA-DQ AND HLA-DR (HLA CLASS II)
MHC CLASS I & II
T CELLS
• MAJOR CELL-MEDIATED IMMUNITY PLAYER
• DEFENCE AGAINST WIDE RANGE OF PATHOLOGIES – INFECTION AND MALIGNANCIES
• TCR –HIGH SPECIFICITY RECEPTOR
• RECOGNISE ANTIGEN BOUND TO MHCS DISPLAYED ON APCS
• CD8 – POSITIVE T CELLS OR CYTOTOXIC CELLS
• CD4 –POSITIVE T CELLS OR HELPER CELLS
EARLY INFLAMMATORY RESPONSE
• INFLAMMATION AS CENTRE OF REJECTION
• BEGINS PRIOR TO ORGAN TRANSPLANTATION
• STARTING FROM HAEMODYNAMIC AND
NEUROENDOCRINE RESPONSES ASSOCIATED WITH
BRAIN STEM DEATH
• IN THE PROCESS OF MULTIORGAN RETRIVAL
AND SUBSEQUENT COLD PRESERVATION
ISCHEMIA-REPERFUSION INJURY
RESPONSIBLE FOR A SPECTRUM OF EARLY ORGAN DYSFUNCTION AFTER
TRANSPLANTATION.
ISCHEMIC INJURY
REPERFUSION INJURY
STERILE INFLAMMATION
ADAPTIVE IMMUNE RESPONSE TO IRI
ALLOIMMUNE RESPONSE
HISTORY
• HISTORY DATES BACK OT EARLY 1900S
• FLORESCO – ANASTOMOSIS OF RENAL GRAFTS TO ILIAC FOSSA IN 1905
• JABOULAY – ATTEMPTED USING PIG KIDNEY TO CURE ACUTE NEPHRITIS.
HE ANASTAMOSED RENAL GRAFT TO BRACHIAL ARTERIES OF THE PATIENT
• ALEXIS CARREL – NOBEL LAUREATE DEVELOPED TECHNIQUE OF VASCULAR ANASTAMOSIS
• PETER MEDAWAR – DESCRIBED THE PREVENTION OF REJECTION IN MICE,AND HUMAN ORGAN
TRANSPLANTATION
• JOSEPH MURRAY DONE FIRST SUCCESSFUL RENAL TRANSPLANTATION BETWEEN IDENTICAL TWINS IN 1954
MILESTONE
 Vascular anastamosis technique by Alexis carrel
 Discovery of immunological basis for rejection by Medawar
 Joseph murray first successful transplantation
 Discovery of Cyclosporine and other immunosuppressive medications
 Description of MHC antigens, and perfective preservation solutions
INDICATIONS OF RENAL TRANSPLANTATION
• BETTER LONG TERM OUTCOME THAN DIALYSIS
• THEY LIVE 10 YRS LONGER THEN THOSE PATIENT ON DIALYSIS
• THERE HAS BEEN CHANGE IN THE TREND OF ETIOLOGY OF RENAL FAILURE
• EARLIER ITS GLOMERULAR DISEASE LEADS THE COUNT BUT DIABETES AND HYPERTENSION BUGGED THAT
TREND RECENTLY.
• COMMON CAUSES OF RENA FAILURE NEED REPLACEMENT THERAPY ARE DIABETES, HTN, INTERSTITIAL
DISEASES
CYSTIC DISEASES AND CHRONIC ALLOGRAFT NEPHROPATHY
PATIENT SELECTION
• ARDOUS PROCESS
• ORIGINAL CAUSE OF KIDNEY FAILURE HAS TO BE FOUND PATIENT CAN BE ASSURED OF GRAFT SURVIVAL
PERIOD.
• RECIPIENTS MUST BE CAREFULLY EVALUATED FOR SURGICAL RISK AND THEIR ABILITY TO TOLERATE LONG
TERM IMMUNOSUPPRESSION
• PATIENTS WITH A GFR OF 30ML/MIN/1.72M2, AND STAGE 3 OR 4 CHRONIC KIDNEY DISEASE SHOULD BE
REFERRED TO A NEPHROLOGIST
• GFR < 20ML/MIN/1.72M2 EVALUATED FOR TRANSPLANT
CONTRAINDICATIONS
• HIV ?
• ONCE IT WAS A CONTRAINDICATION
• PATIENT SELECTION WITH APPROPRIATE CELL COUNTS (CD 4+ > 400CELLS/MM3)
• UNDETECTABLE VIRAL LOAD
PRIMARY RENAL DISEASE AND
RECURRENCE RATES
SCREENING OF RECIPIENTS
• DETAILED HISTORY OF THE ORIGINAL CAUSE OF DISEASE
• LENGTH OF TIME ON DIALYSIS (INDEPENDENT RISK FACTOR FOR POOR OUTCOMES)
• EXPOSURE TO TB,CMV,EBV AND HEPATITIS.
• FAMILY HISTORY OF RENAL DISEASE
• ROUTINE AGE APPROPRIATE SCREENING SCHEDULES LIKE PAP SMEAR,MAMMOGRAMS,COLONOSCOPY,DENTAL
PROPHYLAXIS AND BONE DENSITY.
• HISTORY OF HYPERCOAGULABLE STATE
• ESRD RISK FACTOR FOR CARDIVASCULAR DISEASE.
EXAMINING THE PATIENT
• CHECK FOR CAROTID BRUIT,ATRIAL FIBRILLATION, FEMORAL,DORASLIS PEDIS AND POSTERIOR TIBIAL
ARTERY BRUIT
• IF PATIENT PREVIOUSLY UNDERGONE AMPUTATION WITH PROBABLE VASCULAR CAUSE CT ANGIOGRAM
MIGHT WARRANT TO RULE OUT ILIAC VESSEL OCCLUSION.
DONOR SELECTION
• CAN BE OF LIVING OR DECEASED DONORS
• LIVING DONORS CAN BE OF RELATED AND UNRELATED.
DECEASED DONORS
• EXTENDED CRITERIA DONOR (DONOR AGE >60YRS OR FROM DONORS AGED 50 TO 59 YEARS WITH AT
LEAST TWO OF THE FOLLOWING: CEREBROVASCULAR ACCIDENT AS CAUSE OF DEATH, TERMINAL
CREATININE CONCENTRATION ABOVE 15 MG/DL, OR HISTORY OF HYPERTENSION.)
• STANDARD CRITERIA DONOR
• DONOR AFTER CARDIAC DEATH
KIDNEY DONOR PROFILE INDEX
• THIS PROFILE BASED ON 10 CLINICAL FACTORS
LIVING DONOR
• ELIGIBILITY CRITERIA
• AGE 18 TO 70
• BMI < 35
• NO CANCER OR ACTIVE INFECTION
• ADEQUATE RENAL FUNCTION
• ABO COMPATIBILITY ALSO IN CONSIDERATION (BUT CAN BE DONE ACROSS THESE BARRIERS)
CONTRAINDICATION
DONOR NEPHRECTOMY
• OPEN OR LAPROSCOPIC
• OPEN THROUGH FLANK INCISION
• LAPROSCOPIC NEPHRECTOMY DONE AND SPECIMEN RETREIVED THROUGH PFANNENSTIEL INCISION
• LEFT KIDNEY IS PREFERRED OVER RIGHT BECAUSE OF ADEQUATE LENGTH OF LEFT RENAL VEIN
• WHAT WILL BE THE RISK OF DEVELOPING RENAL FAILURE IN RENAL DONORS…..
• ITS SAME AS IN GENERAL POPULATION
DECEASED DONOR
DECEASED DONOR
PRESERVATION AND STORAGE
• COLD ISCHEMIA TIME USUALLY 12 HOURS FOR KIDNEY
• VARIOUS PRESERVATIVE SOLUTIONS SUCH AS UVW,HTK ARE USED
• STORED AT TEMP AROUND 0-4 DEGREE
RECIPENT OPERATION
• PLACED IN RETROPERITONEAL POSITION.
• DONOR RENAL VEIN ANASTAMOSED TO COMMON ILIAC VEIN
• DONOR ARTERY TO COMMON OR EXTERNAL ILIAC ARTERY
• URETER TO BALDDER MUCOSA IN END TO SIDE FASHION
POST SURGICAL COMPLICATION
• OVERALL RATE OF TECHNICAL COMPLICATION -5 TO 10%
• MOST MANIFESTED AS SUDDEN DROP OF URINE OUTPUT.
• DAILY MONITORING OF SERUM CREATININE AND HEMOGLOBIN LEVELS CRUCIAL IN FIRST DAYS.
• HEMORRHAGE- LIMITED SINCE KIDNEY WAS PLACED IN RETROPERITONEAL SPACE.
• PATIENT COMPLAINTS OF ACUTE FLANK PAIN
• USG HELPFUL IN SUCH SITUATION
• VENOUS THROMBOSIS – DEVELOP WITHIN FIRST WEEK.
• PATIENT DEVELOP SUDDEN HEMATURIA OR DECREASE URINE OUTPUT
• TRANSPLANTED VEIN MIGHT KINKED OR COMPRESSED EXTERNALLY.
• ARTERIAL THROMBOSIS (< 1 %)
• ARTERIAL STENOSIS – LATE COMPLICATION- ASYMPTOMATIC RISES OF CREATININE CONCENTERATION
• UROLOGIC COMPLICATION – AVOID INJURY TO PERIURETERIC TISSUE IN THE “GOLDEN TRIANGLE”-
ANATOMIC AREA DEFINED BY RENAL ARTERY,LOWERPOLE OF KIDNEY AND THE URETER.
• URETERIC STRICTURE
• URINE LEAK
• LYMPHOCELE
• INFECTION – COMMON COMPLICATION AFTER TRANSPLANT
• 80% RECIPIENTS EXPERIENCE UTI
• CMV,EBV,POLYOMAVIRUS.
• PNEUMOCYSTIS JIROVECI COMMON OPPORTUNISTIC INFECTION- BACTRIM OR PENTAMIDINE IS USED AS
PROPHYLAXIS.
OUTCOMES
THANK YOU

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Renal transplantation

  • 1.
  • 2. HOST RESPONSES • BASIC CONCEPTS OF IMMUNOLOGY • RECOGNITION OF DANGER • MAJOR HISTOCOMPATIBILITY COMPLEXES
  • 3. RECOGNITION OF DANGER • DANGER ASSOCIATED MOLECULAR PATTERNS (DAMP) • SENSED THROUGH PATTERN RECOGNITION RECEPTORS (PRRS) ON APCS • APCS MADE UP OF VARIETY OF INNATE CELLS (MACROPHAGES AND DENDRITIC CELLS) • MIGRATE TO LYMPHOID TISSUE AND PRESENT ANTIGEN TO T-CELLS. • RESULTING RESPONSE BALANCED BY CO-STIMULATORY AND INHIBITORY SIGNALS
  • 4. MAJOR HISTOCOMPATIBILITY COMPLEXES • MHC CLASS I AND II • SHORT ARM OF CHROMOSOME 6 • SIX MAIN LOCI IN HUMAN MHC : HLA-A,HLA-B AND HLA – C (CLASS – I) • HLA – DP,HLA-DQ AND HLA-DR (HLA CLASS II)
  • 5. MHC CLASS I & II
  • 6. T CELLS • MAJOR CELL-MEDIATED IMMUNITY PLAYER • DEFENCE AGAINST WIDE RANGE OF PATHOLOGIES – INFECTION AND MALIGNANCIES • TCR –HIGH SPECIFICITY RECEPTOR • RECOGNISE ANTIGEN BOUND TO MHCS DISPLAYED ON APCS • CD8 – POSITIVE T CELLS OR CYTOTOXIC CELLS • CD4 –POSITIVE T CELLS OR HELPER CELLS
  • 7. EARLY INFLAMMATORY RESPONSE • INFLAMMATION AS CENTRE OF REJECTION • BEGINS PRIOR TO ORGAN TRANSPLANTATION • STARTING FROM HAEMODYNAMIC AND NEUROENDOCRINE RESPONSES ASSOCIATED WITH BRAIN STEM DEATH • IN THE PROCESS OF MULTIORGAN RETRIVAL AND SUBSEQUENT COLD PRESERVATION
  • 8. ISCHEMIA-REPERFUSION INJURY RESPONSIBLE FOR A SPECTRUM OF EARLY ORGAN DYSFUNCTION AFTER TRANSPLANTATION. ISCHEMIC INJURY REPERFUSION INJURY STERILE INFLAMMATION ADAPTIVE IMMUNE RESPONSE TO IRI
  • 10. HISTORY • HISTORY DATES BACK OT EARLY 1900S • FLORESCO – ANASTOMOSIS OF RENAL GRAFTS TO ILIAC FOSSA IN 1905 • JABOULAY – ATTEMPTED USING PIG KIDNEY TO CURE ACUTE NEPHRITIS. HE ANASTAMOSED RENAL GRAFT TO BRACHIAL ARTERIES OF THE PATIENT • ALEXIS CARREL – NOBEL LAUREATE DEVELOPED TECHNIQUE OF VASCULAR ANASTAMOSIS • PETER MEDAWAR – DESCRIBED THE PREVENTION OF REJECTION IN MICE,AND HUMAN ORGAN TRANSPLANTATION • JOSEPH MURRAY DONE FIRST SUCCESSFUL RENAL TRANSPLANTATION BETWEEN IDENTICAL TWINS IN 1954
  • 11. MILESTONE  Vascular anastamosis technique by Alexis carrel  Discovery of immunological basis for rejection by Medawar  Joseph murray first successful transplantation  Discovery of Cyclosporine and other immunosuppressive medications  Description of MHC antigens, and perfective preservation solutions
  • 12.
  • 13. INDICATIONS OF RENAL TRANSPLANTATION • BETTER LONG TERM OUTCOME THAN DIALYSIS • THEY LIVE 10 YRS LONGER THEN THOSE PATIENT ON DIALYSIS • THERE HAS BEEN CHANGE IN THE TREND OF ETIOLOGY OF RENAL FAILURE • EARLIER ITS GLOMERULAR DISEASE LEADS THE COUNT BUT DIABETES AND HYPERTENSION BUGGED THAT TREND RECENTLY. • COMMON CAUSES OF RENA FAILURE NEED REPLACEMENT THERAPY ARE DIABETES, HTN, INTERSTITIAL DISEASES CYSTIC DISEASES AND CHRONIC ALLOGRAFT NEPHROPATHY
  • 14. PATIENT SELECTION • ARDOUS PROCESS • ORIGINAL CAUSE OF KIDNEY FAILURE HAS TO BE FOUND PATIENT CAN BE ASSURED OF GRAFT SURVIVAL PERIOD. • RECIPIENTS MUST BE CAREFULLY EVALUATED FOR SURGICAL RISK AND THEIR ABILITY TO TOLERATE LONG TERM IMMUNOSUPPRESSION • PATIENTS WITH A GFR OF 30ML/MIN/1.72M2, AND STAGE 3 OR 4 CHRONIC KIDNEY DISEASE SHOULD BE REFERRED TO A NEPHROLOGIST • GFR < 20ML/MIN/1.72M2 EVALUATED FOR TRANSPLANT
  • 16. • HIV ? • ONCE IT WAS A CONTRAINDICATION • PATIENT SELECTION WITH APPROPRIATE CELL COUNTS (CD 4+ > 400CELLS/MM3) • UNDETECTABLE VIRAL LOAD
  • 17. PRIMARY RENAL DISEASE AND RECURRENCE RATES
  • 18. SCREENING OF RECIPIENTS • DETAILED HISTORY OF THE ORIGINAL CAUSE OF DISEASE • LENGTH OF TIME ON DIALYSIS (INDEPENDENT RISK FACTOR FOR POOR OUTCOMES) • EXPOSURE TO TB,CMV,EBV AND HEPATITIS. • FAMILY HISTORY OF RENAL DISEASE • ROUTINE AGE APPROPRIATE SCREENING SCHEDULES LIKE PAP SMEAR,MAMMOGRAMS,COLONOSCOPY,DENTAL PROPHYLAXIS AND BONE DENSITY. • HISTORY OF HYPERCOAGULABLE STATE • ESRD RISK FACTOR FOR CARDIVASCULAR DISEASE.
  • 19. EXAMINING THE PATIENT • CHECK FOR CAROTID BRUIT,ATRIAL FIBRILLATION, FEMORAL,DORASLIS PEDIS AND POSTERIOR TIBIAL ARTERY BRUIT • IF PATIENT PREVIOUSLY UNDERGONE AMPUTATION WITH PROBABLE VASCULAR CAUSE CT ANGIOGRAM MIGHT WARRANT TO RULE OUT ILIAC VESSEL OCCLUSION.
  • 20. DONOR SELECTION • CAN BE OF LIVING OR DECEASED DONORS • LIVING DONORS CAN BE OF RELATED AND UNRELATED.
  • 21.
  • 22.
  • 23. DECEASED DONORS • EXTENDED CRITERIA DONOR (DONOR AGE >60YRS OR FROM DONORS AGED 50 TO 59 YEARS WITH AT LEAST TWO OF THE FOLLOWING: CEREBROVASCULAR ACCIDENT AS CAUSE OF DEATH, TERMINAL CREATININE CONCENTRATION ABOVE 15 MG/DL, OR HISTORY OF HYPERTENSION.) • STANDARD CRITERIA DONOR • DONOR AFTER CARDIAC DEATH
  • 24.
  • 25. KIDNEY DONOR PROFILE INDEX • THIS PROFILE BASED ON 10 CLINICAL FACTORS
  • 26. LIVING DONOR • ELIGIBILITY CRITERIA • AGE 18 TO 70 • BMI < 35 • NO CANCER OR ACTIVE INFECTION • ADEQUATE RENAL FUNCTION • ABO COMPATIBILITY ALSO IN CONSIDERATION (BUT CAN BE DONE ACROSS THESE BARRIERS)
  • 28. DONOR NEPHRECTOMY • OPEN OR LAPROSCOPIC • OPEN THROUGH FLANK INCISION • LAPROSCOPIC NEPHRECTOMY DONE AND SPECIMEN RETREIVED THROUGH PFANNENSTIEL INCISION • LEFT KIDNEY IS PREFERRED OVER RIGHT BECAUSE OF ADEQUATE LENGTH OF LEFT RENAL VEIN • WHAT WILL BE THE RISK OF DEVELOPING RENAL FAILURE IN RENAL DONORS….. • ITS SAME AS IN GENERAL POPULATION
  • 31. PRESERVATION AND STORAGE • COLD ISCHEMIA TIME USUALLY 12 HOURS FOR KIDNEY • VARIOUS PRESERVATIVE SOLUTIONS SUCH AS UVW,HTK ARE USED • STORED AT TEMP AROUND 0-4 DEGREE
  • 32. RECIPENT OPERATION • PLACED IN RETROPERITONEAL POSITION. • DONOR RENAL VEIN ANASTAMOSED TO COMMON ILIAC VEIN • DONOR ARTERY TO COMMON OR EXTERNAL ILIAC ARTERY • URETER TO BALDDER MUCOSA IN END TO SIDE FASHION
  • 33. POST SURGICAL COMPLICATION • OVERALL RATE OF TECHNICAL COMPLICATION -5 TO 10% • MOST MANIFESTED AS SUDDEN DROP OF URINE OUTPUT. • DAILY MONITORING OF SERUM CREATININE AND HEMOGLOBIN LEVELS CRUCIAL IN FIRST DAYS. • HEMORRHAGE- LIMITED SINCE KIDNEY WAS PLACED IN RETROPERITONEAL SPACE. • PATIENT COMPLAINTS OF ACUTE FLANK PAIN • USG HELPFUL IN SUCH SITUATION
  • 34. • VENOUS THROMBOSIS – DEVELOP WITHIN FIRST WEEK. • PATIENT DEVELOP SUDDEN HEMATURIA OR DECREASE URINE OUTPUT • TRANSPLANTED VEIN MIGHT KINKED OR COMPRESSED EXTERNALLY. • ARTERIAL THROMBOSIS (< 1 %) • ARTERIAL STENOSIS – LATE COMPLICATION- ASYMPTOMATIC RISES OF CREATININE CONCENTERATION • UROLOGIC COMPLICATION – AVOID INJURY TO PERIURETERIC TISSUE IN THE “GOLDEN TRIANGLE”- ANATOMIC AREA DEFINED BY RENAL ARTERY,LOWERPOLE OF KIDNEY AND THE URETER.
  • 35. • URETERIC STRICTURE • URINE LEAK • LYMPHOCELE • INFECTION – COMMON COMPLICATION AFTER TRANSPLANT • 80% RECIPIENTS EXPERIENCE UTI • CMV,EBV,POLYOMAVIRUS. • PNEUMOCYSTIS JIROVECI COMMON OPPORTUNISTIC INFECTION- BACTRIM OR PENTAMIDINE IS USED AS PROPHYLAXIS.