I thought the new kidney will 
work!! 
Nephrology Grand round 
Aug 2014 
1
Disclosure 
• No financial holdings effect the content of the 
presentation. 
2
Basic overview of the topic 
 Sample case to identify risk factors 
 Definition & incidence 
 Importance 
 Risk factors at various stages of Transplant 
process 
 Thought process and basic work up 
3
Case Presentation 
• 53 yo male with h/o ESRD secondary to 
hypertension, DM, HTN and BPH is post op 
day 5, DBD/ECD renal transplant, KDPI 56%, 
cPRA 25%. 
• WIT 7hrs, CIT 24 hrs 
• Patient has been on HD before transplant for 4 
yrs through a left AVF. He makes little urine at 
baseline 
• Tacrolimus was started on day 2 at 4mg bid 
4
• Patient is on tapering dose of steroids and Cellcept. 
• Prophylactic medications : Bactrim, Valgancyclovir 
& Nystatin 
• Additional medication includes Pantoprazole and 
Ondansetron. 
• During OR he was hypotensive briefly down to 80s 
• His only complaint is mild RLQ abd pain and nausea 
with dec PO intake 
5
Exam 
• VSS stable except SBP 155/75 
• AAO in NA 
• S1+S2 no murmur 
• Mild bibasilar crackles with no inc effort of 
breathing 
• Abd with RLQ scar, TTP at graft site, + BS, no foley 
• Speech intact, moving all 4 limbs with intact 
strength. ?asterexis 
6
Significant Labs 
• WBC-normal, Hb 8.1 (7.5-9.5) 
• Na 132, K 5.9, HCO3 17, BUN 98, Cr 7.6 
• Cr has been slowly worsening since transplant 
from 4.3 on arrival 
• UA is 2+ blood, 1+ protein (1+ before Txp as 
well) 1+LE, 19 WBCs and 10 RBCs, Few 
granular casts on microscopy. 
7
Doc! Why my new Kidney is not 
working? 
Brief Differential 
8
Patient given a session of HD on 
Day 5 
He will be called to have 
D_____ G____ F_____ 
9
Soup Kitchen 
• DGF: Delayed Graft Function 
• DBD: Donation after Brain Death 
• DCD: Donation after Cardiac Death 
• ECD: Extended Criteria Donor 
• SCD: Standard Criteria Donor 
• KDPI: Kidney donor profile index 
• cPRA: calculated Panel Reactive antibody 
10
Definitions 
11
Who Gets more DGF? 
12
Does it matter? 
13
Does it matter? 
• Graft survival for DBD kidneys that fulfilled 
the criteria for DGF, according to 9 of the 10 
definitions, was associated with greater than 
three times the risk of graft loss, whereas 
none of the definitions of DGF were 
associated with failure of DCD kidneys 
14
15
Does it matter? 
• Associated with increased rate of rejection. 
• Incidence has increased consistently in last 25 
yrs. Likely because of using more DCD and 
ECD. 
16
Risk Factors 
17
The Pre-Procurement Period 
• Hypotension/Hypoxia/Anaerobic metabolism 
• DBD: 
– Loss of vascular tone 
– Inflammatory state 
– Complement activation 
– Adhesion molecule upregulation 
18
• DBD factors: 
– Use of Dopamine , agonist for HO-1(heme 
oxygenase) , antagonizes free radicles 
– Use of hormone replacement like steroids, 
vasopressin, thyroxin. 
– Length of ICU stay before withdrawal of care 
– Anticoagulation 
19
DCD Factors 
• Duration from withdrawal of care to cardiac 
death (warm ischemia time) 
– ATN, perivascular edema perpetuates ischemia at 
corticomedullary junction 
– <45 min , better outcomes 
• Length of stay in ICU 
20
ECD Factors 
The expanded criteria donor (ECD) is any donor 
over the age of 60, or a donor over the age of 50 
with two of the following: a history of high 
blood pressure, a creatinine greater than or 
equal to 1.5, or death resulting from a stroke 
• Commonly ECD organ are avoided if >20% 
glomeruli are sclerosed. 
21
Composite Donor Risk 
• The Kidney Donor Risk Index (KDRI) is an estimate of the relative risk of 
post-transplant kidney graft failure, that combines ten dimensions of 
information about a donor, including clinical parameters and 
demographics, to express the quality of the donor kidneys relative to 
other donors 
• The Kidney Donor Profile Index (KDPI) is a numerical measure That is 
derived by first calculating the Kidney Donor Risk Index (KDRI) for a 
deceased donor 
• http://optn.transplant.hrsa.gov/resources/allocationcalculators.asp?i 
ndex=81 
• Mapping: KDRI to KDPI : 
• http://optn.transplant.hrsa.gov/ContentDocuments/KDRI_to_KDPI_M 
apping_Table.pdf 
22
Composite Recipient Risk 
• Dialysis prior to transplantation (duration) 
• Diabetes 
• Obesity 
• Age >55 
• Male sex 
• Prolong wait period 
• High cPRA 
• Small for size kidney 
23
24
Procurement: Organ preservation Techniques 
• Cold storage 
• Preservation Fluids: Designed to reduce 
osmotic injury and delay acidosis with H+ 
buffers 
– UW (Uni of Wisconsin solution): Adenosine (reduces 
re-perfusion injury) and allopurinol. 
– HTK (Histidine-tryptophan-Ketoglutarate): Low K 
Organs >24 hr CIT have less DGF risk when reperfused 
with UW solution. 
25
Pulsatile machine perfusion 
26 
Machine perfusion: perfusion flow <0.4ml/min/gm, resistance >80mmHg and resistive index 
>0.5mmHg{ml/min/100gm of tissue} , protocols including directives for organ discard
Perioperative Period 
• Hypotension 
• Intraoperative fluid balance and ESRD pts with LVH 
• Anesthesia effect/Vasodilation 
• Reperfusion: 
– Due to preceding ischemic injury, pathologic vasoconstriction 
occurs with the activation of G protein coupled receptors. 
– Innate immune response (Neutrophils and Macrophages) 
signals from injured cell 
– Adaptive immune response, inc MHC expression in IR injured 
tissue through Ifγ, Cytokines and Chemokines, T-cell 
mediated. 
27
Postoperative period 
Day 1-7 
• Surgical Complications: 
– Vascular complications: Thrombosis ( pediatric 
kidneys and pt with APLAS), hematoma 
– Anatomic complications: urinary leak causing a 
urinoma, tight fascia around the kidney 
– Urologic complication: Urinoma, Ureteric Kinking 
and stenosis, Evulsion 
– Infection/Abscess 
28
• Drugs: 
– CNI (Tacrolimus) 
– Bactrim 
– PPIs 
• Urinary retention: After Foley is usually 
removed on day 4. 
29
Rejection 
• Acute Cell Mediated Rejection (ACR) 
• Antibody mediated Rejection (AMR) 
30
Basic thought process 
• Pre-Renal (Hypovolemic/Low renal blood 
flow), Thrombosis) 
• Renal (ATN, AIN, TMA, venous thrombosis & 
congestion) 
• Post renal (compression by fluid collection, 
urologic problems) 
• Rejection (ACR, AMR) 
31
Basic Workup to consider for DGF 
• Donor information (KDPI, pre-procurement history, 
available with UNOS) 
• Operative report for hypotension 
• Immunological risk: cPRA, cross match report 
• Tacrolimus levels 
• Allograft US with Doppler (?other imaging) 
• Urine micro (not so informative as old kidneys still 
make some urine) same problem with urine e-lytes 
• Review other drugs 
• Post void residuals & voiding trials 
32
• Biopsy provides the final differentiation (ATN, 
AIN, Rejection, TMA) but sometime its difficult 
to distinguish between AIN and Rejection 
33
Thank you! 
DGF Risk Calculator 
http://www.transplantcalculator.com/Transplant-Calculators/Delayed- 
Graft-Function.aspx 
Feedback appreciated… 
34

Delayed graft function: Kidney Transplant

  • 1.
    I thought thenew kidney will work!! Nephrology Grand round Aug 2014 1
  • 2.
    Disclosure • Nofinancial holdings effect the content of the presentation. 2
  • 3.
    Basic overview ofthe topic  Sample case to identify risk factors  Definition & incidence  Importance  Risk factors at various stages of Transplant process  Thought process and basic work up 3
  • 4.
    Case Presentation •53 yo male with h/o ESRD secondary to hypertension, DM, HTN and BPH is post op day 5, DBD/ECD renal transplant, KDPI 56%, cPRA 25%. • WIT 7hrs, CIT 24 hrs • Patient has been on HD before transplant for 4 yrs through a left AVF. He makes little urine at baseline • Tacrolimus was started on day 2 at 4mg bid 4
  • 5.
    • Patient ison tapering dose of steroids and Cellcept. • Prophylactic medications : Bactrim, Valgancyclovir & Nystatin • Additional medication includes Pantoprazole and Ondansetron. • During OR he was hypotensive briefly down to 80s • His only complaint is mild RLQ abd pain and nausea with dec PO intake 5
  • 6.
    Exam • VSSstable except SBP 155/75 • AAO in NA • S1+S2 no murmur • Mild bibasilar crackles with no inc effort of breathing • Abd with RLQ scar, TTP at graft site, + BS, no foley • Speech intact, moving all 4 limbs with intact strength. ?asterexis 6
  • 7.
    Significant Labs •WBC-normal, Hb 8.1 (7.5-9.5) • Na 132, K 5.9, HCO3 17, BUN 98, Cr 7.6 • Cr has been slowly worsening since transplant from 4.3 on arrival • UA is 2+ blood, 1+ protein (1+ before Txp as well) 1+LE, 19 WBCs and 10 RBCs, Few granular casts on microscopy. 7
  • 8.
    Doc! Why mynew Kidney is not working? Brief Differential 8
  • 9.
    Patient given asession of HD on Day 5 He will be called to have D_____ G____ F_____ 9
  • 10.
    Soup Kitchen •DGF: Delayed Graft Function • DBD: Donation after Brain Death • DCD: Donation after Cardiac Death • ECD: Extended Criteria Donor • SCD: Standard Criteria Donor • KDPI: Kidney donor profile index • cPRA: calculated Panel Reactive antibody 10
  • 11.
  • 12.
  • 13.
  • 14.
    Does it matter? • Graft survival for DBD kidneys that fulfilled the criteria for DGF, according to 9 of the 10 definitions, was associated with greater than three times the risk of graft loss, whereas none of the definitions of DGF were associated with failure of DCD kidneys 14
  • 15.
  • 16.
    Does it matter? • Associated with increased rate of rejection. • Incidence has increased consistently in last 25 yrs. Likely because of using more DCD and ECD. 16
  • 17.
  • 18.
    The Pre-Procurement Period • Hypotension/Hypoxia/Anaerobic metabolism • DBD: – Loss of vascular tone – Inflammatory state – Complement activation – Adhesion molecule upregulation 18
  • 19.
    • DBD factors: – Use of Dopamine , agonist for HO-1(heme oxygenase) , antagonizes free radicles – Use of hormone replacement like steroids, vasopressin, thyroxin. – Length of ICU stay before withdrawal of care – Anticoagulation 19
  • 20.
    DCD Factors •Duration from withdrawal of care to cardiac death (warm ischemia time) – ATN, perivascular edema perpetuates ischemia at corticomedullary junction – <45 min , better outcomes • Length of stay in ICU 20
  • 21.
    ECD Factors Theexpanded criteria donor (ECD) is any donor over the age of 60, or a donor over the age of 50 with two of the following: a history of high blood pressure, a creatinine greater than or equal to 1.5, or death resulting from a stroke • Commonly ECD organ are avoided if >20% glomeruli are sclerosed. 21
  • 22.
    Composite Donor Risk • The Kidney Donor Risk Index (KDRI) is an estimate of the relative risk of post-transplant kidney graft failure, that combines ten dimensions of information about a donor, including clinical parameters and demographics, to express the quality of the donor kidneys relative to other donors • The Kidney Donor Profile Index (KDPI) is a numerical measure That is derived by first calculating the Kidney Donor Risk Index (KDRI) for a deceased donor • http://optn.transplant.hrsa.gov/resources/allocationcalculators.asp?i ndex=81 • Mapping: KDRI to KDPI : • http://optn.transplant.hrsa.gov/ContentDocuments/KDRI_to_KDPI_M apping_Table.pdf 22
  • 23.
    Composite Recipient Risk • Dialysis prior to transplantation (duration) • Diabetes • Obesity • Age >55 • Male sex • Prolong wait period • High cPRA • Small for size kidney 23
  • 24.
  • 25.
    Procurement: Organ preservationTechniques • Cold storage • Preservation Fluids: Designed to reduce osmotic injury and delay acidosis with H+ buffers – UW (Uni of Wisconsin solution): Adenosine (reduces re-perfusion injury) and allopurinol. – HTK (Histidine-tryptophan-Ketoglutarate): Low K Organs >24 hr CIT have less DGF risk when reperfused with UW solution. 25
  • 26.
    Pulsatile machine perfusion 26 Machine perfusion: perfusion flow <0.4ml/min/gm, resistance >80mmHg and resistive index >0.5mmHg{ml/min/100gm of tissue} , protocols including directives for organ discard
  • 27.
    Perioperative Period •Hypotension • Intraoperative fluid balance and ESRD pts with LVH • Anesthesia effect/Vasodilation • Reperfusion: – Due to preceding ischemic injury, pathologic vasoconstriction occurs with the activation of G protein coupled receptors. – Innate immune response (Neutrophils and Macrophages) signals from injured cell – Adaptive immune response, inc MHC expression in IR injured tissue through Ifγ, Cytokines and Chemokines, T-cell mediated. 27
  • 28.
    Postoperative period Day1-7 • Surgical Complications: – Vascular complications: Thrombosis ( pediatric kidneys and pt with APLAS), hematoma – Anatomic complications: urinary leak causing a urinoma, tight fascia around the kidney – Urologic complication: Urinoma, Ureteric Kinking and stenosis, Evulsion – Infection/Abscess 28
  • 29.
    • Drugs: –CNI (Tacrolimus) – Bactrim – PPIs • Urinary retention: After Foley is usually removed on day 4. 29
  • 30.
    Rejection • AcuteCell Mediated Rejection (ACR) • Antibody mediated Rejection (AMR) 30
  • 31.
    Basic thought process • Pre-Renal (Hypovolemic/Low renal blood flow), Thrombosis) • Renal (ATN, AIN, TMA, venous thrombosis & congestion) • Post renal (compression by fluid collection, urologic problems) • Rejection (ACR, AMR) 31
  • 32.
    Basic Workup toconsider for DGF • Donor information (KDPI, pre-procurement history, available with UNOS) • Operative report for hypotension • Immunological risk: cPRA, cross match report • Tacrolimus levels • Allograft US with Doppler (?other imaging) • Urine micro (not so informative as old kidneys still make some urine) same problem with urine e-lytes • Review other drugs • Post void residuals & voiding trials 32
  • 33.
    • Biopsy providesthe final differentiation (ATN, AIN, Rejection, TMA) but sometime its difficult to distinguish between AIN and Rejection 33
  • 34.
    Thank you! DGFRisk Calculator http://www.transplantcalculator.com/Transplant-Calculators/Delayed- Graft-Function.aspx Feedback appreciated… 34