Dr. Mohammad Hussin kassem
Nephrology specialist .
Saudi German hospital - Dubai
2. Why early post kidney
means the first 3 months post kidney transplant
It start since the preparation for transplant .
The most exciting and anxious time for pts .
The time when the acute event happiend like :
The rejection ,
The high dose of medication and its side
The infections .
Some pateint needs readmission .
3. Prior to admission for
was discovered upon
transplant unite .
1- Physical examination:
Very important because may be the patient has any clinical
condition needs for intervention and delay the transplantation ,
4. Pre- transplant evaluation :
Repeat the blood grouping and cross matching
The crossmathe = in vitro transplant .
Repeat the viral marker in case the patient on dialysis
Routine tests (Lft , rft , cbc , urine test ….)
Medicine reconciliation ( blood thinner …)
Make sure No active infection .
Some elective cases need preparation by TPE , rituximab .
5. in the transplant unite :
Admission in transplant unites before few days
Physical examination , repeat lab test , CXR , ECG ,
arrange radiated blood and cryociptate .
Dialysis treatment prior to the operation with
Avoidance for excessive fluid removal .
Start with immunosuppressant as per protocol
Two days prior to the operation .
prepare the area ( shieving- desinfection )
Continue Blood pressure medicine except ARBS/ACEI .
6. Special Anesthesia protocol .
CVP line insertion ,
infusion immunosuppressant .
Monitor the hemodynamic status
feel up the CVP 10 to 15 mmhg .
Rare need for arterial line .
The cold and warm time .
Record the medication and the
The blood loss and the fluid and
blood products replacement ,
Record and replace The urine
In the OT
7. Donor nephrectomy protective
ensure adequate circulatory volume and
optimal renal blood flow.
The aim should be to keep intra-abdominal
pressure low(<12 mm Hg) .
ensure a positive fluid balance,
maintain an adequate urinary output with
mannitol and furosemide as needed.
8. Upon receive the patient from the OT :
Patient could be in general transplant care unite if stable .
The patient should be evaluated immediately . A-B-C .
Monitor urine out put and start replacement .
Pain management .
Endorsement from anesthesia team regarding the intraoperative
Frequent physical examination include check the
peripheral pulse in the feet .
a systolic blood pressure of <180 mm Hg is acceptable
systolic blood pressure should be kept over 100 mm Hg
and mean arterial pressure over 70 mm Hg
9. Hemodynamic evaluation and
fluid management .
Prior to transplant :
Keep the patient 1 kg over the dry weight .
In OT :
maintain the systolic blood pressure close to the patient’s
normal blood pressure
central venous pressure of 10 to 15 mm Hg in patients with
good left ventricular function .
Radiated Blood is given to maintain a hemoglobin
concentration of approximately 10 g/dL if there is CVD .
In transplant ward :
Monitor the vitals , monitor the urine out put and make the
10. The roles of replacement :
Depends on many factors and clinical examination as well as the
start of urination after the anastomosis .
Urine out put should be replaced hourly with half slain 100% up to
200 ml if the urine volume is grater than more than 200/hour give
200 ml+1/2 of each ml above 200 ml )
Some expert will give 100 % for the urine out put in first day .
All fluid should be replaced by IV until the patient is not NPO .
Electrolytes and fluid replacement individually based on clinical
and volume starts and the blood result .
Some patent may excretes up to 40 liter .
11. Post operative nursing order :
Expert nurse is a corner stone for success transplant .
1- Vital signs checked every hour for 12 hours, then every 2
hours for 8 hours, then every 4 hours for stable patients .
2- Intake and output every hour for 24 hours, then every 4 hours
3- Intravenous fluid per physician
4- Daily weight
5- Turn, cough, deep breath every hour, encourage incentive
spirometry every hour while awake
6- Out of bed on postoperative day 1,
ambulate daily thereafter
7- Head of bed at 30 degrees
8- Dressing changes daily as needed
12. 9- Check dialysis access for function every 4 hours
10- No blood pressure, venipuncture in extremity with
fistula or shunt .
11- Foley catheter to bedside drainage, irrigate gently
with 30 mL normal saline as needed for clots 12- Catheter
care every 8 hours .
13- Notify physicians if urine output drops to less than 60
mL/h for 2 consecutive hours or greater than 300 mL/h for
4 hours or greater than 500 mL/h for 2 consecutive hours
14- Notify physicians if systolic blood pressure > 180 mm
Hg or < 110 mm Hg .
15- NPO until changed by surgical team .
16- Chest radiograph immediately postoperatively
Postoperative Laboratory Orders Complete
13. Postoperative laboratory orders
CBC , electrolytes, creatinin, glucose, and
blood urea nitrogen every 6 hours for 24
hours, then every morning.
Calcineurin inhibitor level every morning
Chemistry panel including liver function
tests, urine culture, and sensitivity twice
15. Allograft function:
Immediate Graft Function
There is relation between the creatinine drop and the graft
function in the first year .
Slow Recovery of Graft Function:
nonoliguric and experience a slow decline in serum creatinine level
which does not normalize within the first postoperative week
Delayed Graft Function :
describe marginally functioning grafts that recover function after
several days to weeks , the patient may need dialysis in the first
! it is deferent than :
primary nonfunctioning , where the kidney allografts never function
and graft nephrectomy is usually indicated
17. Intra renal DGF:
Interstitial nephritis .
Recurrence of original disease .
18. ATN(Acute tubular necrosis) :
(ATN) is the most common cause of DGF .
ATN is uncommon in living donor kidney transplants
It is a consequence of ischemia and reperfusion injury (IRI)
Clinically, patients may develop oliguria after having an initial good
Renal blood flow is generally well preserved, leading to dissociation
between flow and excretory function.
Doppler (RI) > 80%
Studies suggest that endothelial injury upregulates and exposes donor
histocompatibility antigens, adhesion molecules, and costimulatory
molecules, heightening the risk for acute rejection that occurs at a
rate of approximately 50% greater than in kidneys that function
19. Prevention :
Avoidance of intraoperative and perioperative volume contraction, or
use of CNI-sparing protocols to avoid their vasoconstrictive effect.
avoid aggressive lowering of blood pressure .
For high risk patient a protocol consisting of induction therapy with anti-
thymocyte globulin daily for 4 doses and delayed introduction of CNI
until day 3 may be employed ( also may decrease the IRI) .
Avoid mTOR in the acute phase .
?Low-dose dopamine infusions of 1 to 5 μg/kg/min
?(CCB) to the donor or recipient, at the time of vasculature
?Could DGF (independent of other factors) affect long-term graft
DGF has financial and programmatic significance.
20. TREATMENT :
maintaining adequate immunosuppression and of repeating
biopsies every 7 to 10 days to assess for covert acute
Fluid balance and Control the electrolytes disturbance .
In case need for hemodialysis , Avoid the hypotension
Sodium polystyrene sulfonate (Kayexalate) should not be
administered in the early post-transplant period because it
may induce colonic dilatation and predispose to perforation.
21. ACUTE REJECTION:
There are three main
patterns diagnosed on
the basis of time of
or cellular immunity),
and clinical and
22. Accelerated Acute Rejection:
donor-specific antibodies present in the serum of the
recipient at the time of transplantation (ABO
it is very rare nowadays because flow cytometry
ATN , thrombosis ,
Renogram , renal Doppler , kidney biopsy and repeat the cross match .
Desensitization protocol :
plasma exchange /IVIG/ Rituximab .
23. Acute Cell-Mediated Rejection
occur between the first week and the first few months
after transplantation .
asymptomatic rise in serum creatinine or failure of the
serum creatinine to decrease below an elevated level
less frequently : fever, malaise, graft tenderness, and
oliguria are seen
mediated primarily by T lymphocytes ,monocytes and
Presence of neutrophile may indicate the acute bacterial
infection while the presnece of eosinophile
drug-induced interstitial nephritis
25. • No acute rejection. Absence of tubulitis or intimal arteritis, with or without interstitial inflammation.
• Borderline (suspicious) changes. Mononuclear cell infiltrate involving 10% or more of the nonscarred
cortical interstitium, but not meeting the threshold for diagnosis of type 1 acute rejection due to:
• Insufficient tubulitis (<5 lymphocytes in most severely involved tubular cross-section)
Insufficient inflammation (<25% of nonscarred cortex inflamed)
• Type 1 Acute Rejection : Interstitial inflammation in ≥25% of nonscarred cortical tissue with:
• 1A. Moderate tubulitis (5–10 lymphocytes in most severely involved tubular cross-section or
group of 10 tubular epithelial cells, excluding atrophic tubules)
• 1B. Severe tubulitis (>10 lymphocytes in most severely involved tubular cross-section or group
of 10 tubular epithelial cells, excluding atrophic tubules)
• Type 2 Acute Rejection :
• Intimal arteritis, with or without interstitial inflammation and/or tubulitis, with:
• 2A. Less than 25% luminal occlusion in the most severely involved artery (mild to moderate
• 2B. ≥25% luminal occlusion in the most severely involved artery (severe intimal arteritis)
• Type 3 Acute Rejection:
• Transmural arterial inflammation and/or arterial fibrinoid change and necrosis of medial smooth muscle
cells with accompanying lymphocytic inflammation
• (Adapted from Solez K, Colvin RB, Racusen LC, et al. Banff 07 classification of renal allograft pathology:
updates and future directions. Am J Transplant 2008;8:753–760.)
Banff 2007 Diagnostic Criteria for Acute Cell-
26. Acute Antibody-Mediated
It usually occurs early after transplantation,
usually it develops in the setting of preexisting
sensitization and the presence of donor specific
The hallmark micro vascular inflammation and injury
involving the glomerular and peritubular capillaries .as
glomerulitis and peritubular capillaritis
Less frequently seen morphologic lesions TMA & acute
tubular injury . See the classification .
It is mandatory to do PRA for all patient including the low
risk patient .
27. * C4d staining in peritubular capillaries. Indirect immunofluorescence using a mouse monoclonal antibody against C4d
followed by fluorescein-conjugated anti-mouse IgG shows strong linear staining in the walls of peritubular capillaries.
Tubular basement membranes are recognized by weak, nonspecific staining (×400).
C4 staining * Peritubular capillaritis
28. Banff 2013 Classification of Antibody-Mediated Rejection (ABMR)
in Renal Allografts
Acute/Active ABMR :
All Three Features Must be Present for Diagnosis:
1. Histologic evidence of acute tissue injury, including one or more of the following: Microvascular inflammation (glomerulitis and/or
peritubular capillaritis) Intimal or transmural arteritis Acute thrombotic microangiopathy, in the absence of any other cause Acute tubular
injury, in the absence of any other apparent cause
2. Evidence of current/recent antibody interaction with vascular endothelium, including at least one of the following: Linear C4d staining in
per tubular capillaries (in at least 10% of capillaries by immunofluorescence on frozen sections, or in any capillaries by
immunohistochemistry on paraffin sections) At least moderate microvascular inflammation (mild glomerulitis AND peritubular capillaritis, at
least moderate glomerulitis OR peritubular capillaritis; at least mild glomerulitis must be present when there is acute cell-mediated
rejection) Molecular markers, such as increased expression of endothelial-associated transcripts
3. Serologic evidence of Donor-Specific Antibodies (HLA or other antigens)
Chronic, Active ABMR;
All Three Features Must be Present for Diagnosis
1. Morphologic evidence of chronic tissue injury, including one or more of the following: Transplant glomerulopathy by light microscopy
and/or EM, if no evidence of chronic thrombotic microangiopathy Severe peritubular capillary basement membrane multilayering (requires
EM) Arterial intimal fibrosis of new onset, excluding other causes
2. Evidence of current/recent antibody interaction with vascular endothelium, including at least one of the following: Linear C4d staining
in peritubular capillaries (as with acute/active ABMR, above) At least moderate microvascular inflammation (as with acute/active ABMR,
above) Molecular markers, such as increased expression of endothelial-associated transcripts
3. Serologic evidence of Donor-Specific Antibodies (HLA or other antigens)
C4d Staining without Evidence of Rejection;
All Three Features Must be Present for Diagnosis :
1. Linear C4d staining in peritubular capillaries (as with acute/active ABMR, above)
2. No glomerulitis, peritubular capillaritis, transplant glomerulopathy, thrombotic microangiopathy, peritubular capillary basement
membrane multilayering, or acute tubular injury (in the absence of another apparent cause for this)
3. No acute cell-mediated rejection (Banff 2007 type 1A or greater) or borderline changes
(Adapted from Haas M, Sis B, Racusen LC, et al. Banff 2013 meeting report: inclusion of C4d-negative antibody-mediated rejection and
antibody-associated arterial lesions. Am J Transplant 2014;14:272–283.)
29. ACUTE AMR
DONOR Ab in serum
Neutrophile in Glomerular and
peri tubular capillaries
ACR vs. AMR ....
30. Treatment of acute rejection
High-dose steroids :
prevent the release of IL-1 by macrophages, block
IL-2-mediated synthesis by T helper cells, and
inhibit tumor necrosis factor-α (TNFα)
methylprednisolone (MP) 0.5 g for 3–5 days)
About 75% of primary acute rejection episodes are
reversible after treatment with MP .
seizures, anaphylaxis, and even sudden death ,
others complain of flushing, tremor, or nausea.
Hyperglycemia is frequent after MP infusion, and
some , patients may develop diabetes.
31. ATG :
Indicated in ACR not responding to MP and vascular
mode of action :
It lyses circulating T cells and perhaps favor the production of
T suppressor cells.
obtained by the immunization of rabbits with human
Rabbit ATG proved to be superior to horse ATG in reversing
acute rejection and in preventing recurrent rejection (Gaber et
ATG is expensive, may require hospitalization (ATG should
be administered in a central vein, needs premedication with
MP, and should be infused in at least 4–6 h)
32. OKT3 :
The monoclonal antibody OKT3 blocks the
antigen receptor complex CD3 and prevents
It is administered intravenously, usually at a
dose of 5 mg/day for 7–14 days .
IVIG : 0.5 g/KG daily for seven days usually in
(high dose protocol 2g/kg every 2-3 weeks )
Plasma exchange : ( replacement is the 4 %
rituximab (2doses 375mg/m2) .
Bortezomib : 1.3mg/m2/dose X 4 (3days
interval) borteasome inhibitors )
35. CNI toxicity :
cause renal and systemic vasoconstriction
may induce ischemia, with consequent tubular atrophy and
slowly progressive graft dysfunction, hypertension, and mild
to moderate proteinuria.
Avoid the drug-drug interaction .
Monitor the level , CCB . Free CNI in low risk PATEINT ?
36. Pathology :
Isometric vacuolization of
proximal tubular epithelium,
and vascular injury with loss of
smooth muscles, myocyte
cytoplasmic vacuolization, and
dropout from necrosis or
apoptosis, injured myocytes
are replaced by focal nodular
hyalinosis , Chronic CNI
toxicity shows a striped
pattern interstitial fibrosis with
proportional tubular atrophy
Can cause (TMA)
39. Creatinin still elevated
in 1-2 days
in 3-5 days
TPE / IVIG
40. Vascular Causes of DGF
Renal Artery Stenosis
may occur as early as the first week, but it is
usually a later complication
accelerated or refractory hypertension and
peripheral edema in the absence of proteinuria
elevated ratio (greater than 3) of PSV in the renal
artery compared to that in the external iliac artery is
more reliable than the various proposed threshold
values of PSV ranging from 100 to 300 cm/sec.
CTA or MRA can also be used to confirm RAS
41. Case .
20 years old female patient .
On follow up she has hypertension
and increase in the creatinin level 1.5
Us doppler and Msct showed sever
Angioplasty with stent was implanted ,
The creatinine improved to i mg/dl .
44. Case :
30 years old
In the 3th days there is sever pain over the graft .
Us and ct scan showed hematoma over the graft
Start creatinine to raised
Repeat the us showed no flow in the vein
46. Graft Thrombosis
occurs within the first 2 to 3
Mostly due to technical surgical
Signs and symptoms :
Hematuria / pain/
The diagnosis is usually made by
Doppler ultrasound or isotope flow
47. Risk factors for vascular
arteriosclerotic involvement of the donor or
intimal injury of graft vessels;
kidney with multiple arteries;
history of recurrent thrombosis;
younger recipients or donor age;
antiphospholipid antibody (anticardiolipin antibody
or lupus anticoagulant).
perioperative or postoperative prophylactic
anticoagulation should be considered
Treatment : remove the graft .
48. Postoperative Bleeding
the per nephric drain may fill with blood,
Conservative treatment ,
Surgical intervention if there is pressure on
the ureter or surrounding vasculature
49. Recurrent and De Novo Renal
The incidence of recurrent
and de novo glomerular
diseases among a large
cohort in the Renal
Allograft Disease Registry
(RADR) was approximately
3% over a mean follow-up
period of 5.4 years.
third most common cause of
graft failure beyond the first
year after transplantation
continuation of corticosteroids
was strongly associated with
protection from graft loss
within the first month
50. What we can do ?
Avoid serolimus .
Within 2 weeks of relapse PE, CNI based protocol , ACEI ,
rituximab in case of recurrence .
Retuximab prior to transplant ( mayo clinic protocol )
IgA nephroapthy :
induction therapy with rabbit antithymocyte globulin Keep the
steroid , , ACEI , tight control for blood pressure .
HUS /TMA :
In atypical HUS Genetic studey :
Plasma exchange effective in case of mutation factor H. I . Or
antibodies to factor H , less effective im MCP .
Eclusimab ./ combined liver and kidney transplanation .
Membranous ? Retixumab in some case .
Anti- GBM : wait for 6 months on dialysis and disapear the Anti-
52. Do novo TMA
DUE TO : antibody-mediated rejection .
immunosuppressive drug-induced (CNI and mTOR inhibitors);
TMA associated with ADAMTS-13 deficiency or the presence of
and the presence of lupus anticoagulant or anticardiolipin;
CMV infection, and less frequently systemic viral infection with
parvovirus B 19 or influenza A virus.
hepatitis C infection and anticardiolipin antibody positivity.
Treatment should be directed against the underlying cause.
Belatacept is a therapeutic option in patients with
immunosuppressant-associated TMA along with plasma exchange .
Some studies on IVIG .
54. Case :
50 years old male patient ,
ESRD for unknown cause /good urine output before
Underwent Living donation KTR .creatinine upon
discharge is 1.3 mg/dl
3 months later came with serum creatinine of 8 mg/dl .
Us hydronephrosis .
Nephrostomy done with kidney function improvment ,
creatinine became 1.1 mg/dl
Reexporation for ureter reimplantation , d/c creatinine
1.1 mg/dl . a
55. Urine leakage :
Due to the ureter ischemia or the short ureter during the first week of
Symptoms : abdomen distension , abdominal pain , high volume from
the drain , high creatinine in the drainage fluid .
Conservative tx :
Stent / nephrostomy ...
In case of persistant leakage the reexploration is indicated . .
56. Surgical Incision, Drains, and
! Sirolimus may delay wound healing
and increase the incidence of
lymphocele formation .
Foley removal on day 3 or 4
perinephric drainin the following if
drain is less than 100 mL/day and
After graft Doppler .
2 weeks remove the Surgical staples .
4- 5 weeks double-J stent removal .
57. MEDICAL MANAGEMENT IN THE FIRST :
lack of conclusive evidence that one class of antihypertensive
agent is superior to another in the transplant setting and
treatment should be individualized .
β blockers are generally used in the perioperative period
because they have been shown to reduce cardiovascular events
in high-risk candidates
ACEIs and ARBs should be avoided in early post transplat ,
later we may use if no RAS .
First choise : dihydropyridine ( amlodipine- nifedipine ,
Nondihydropyridine calcium channel blockers such as diltiazem
may permit CNI dose reduction ( carfull monitroing for CNI level
KDOQI guidline : target BP is less than 130/80 .
13% of ktr within first 2 weeks
41% of cases due to C-DIFF .
34 % due to SI of medication .
Metronidazol , oral vancomycin in sever case , anti motalty if c- diff is negative .
In the immediate post transplant the
hyperglycemia should be controlled with
an intravenous infusion of insulin ange
150-180 mg/dl .
then after transitioned from intravenous
insulin to a subcutaneous regime
In case the risk of NODAT, and type 2 DM
, consideration to use cyclosporine
steroid exposure should be minimized,
d/c prednisone within the first few days in
low immunologic risk pts .
serious complication of transplantation that is associated
with : dyslipidemia,
chronic allograft dysfunction,
Risk factors :
obesity, weight gain, hepatitis C, steroids, tacrolimus, and
restoration of insulin metabolism by the kidney allograft.
65. LAB abnormalities :
Anemia : common (bleeding , iron def
, meds , infection , …..)
Correct iron def , preferable radiated
PRBC ) , use ESA later one .
Leukopenia and thrombocytopenia :
antilymphocyte antibodies ,
Other meds , infection (CMV) .., TMA .
Urine test : hematuria .., …
66. THE DAY OF DISCHARGE
It is imperative that all patients (together with family members or caregivers)
attend the patient education session .
Explain ALL the medication .
Encourage fluid intake 3 liter and above if nedded .
Follw up plan for suture anf jj stent removal .
Monitor the blood pressure / weight daily / urine out put
Healthy life style :
encourage Exercises .
Advise for stop smoking .
Dietician consultation with avoid gain weight
67. Personal hygiene ,
hand washing , avoid the crowded places .
Well done cooking and carful about food hygiene .
Seek advise any symptoms like : fever , low urine output and
Back to work after 3 month on average
no objection for Pregnancy after one year of well functioning
kidney with avoidance for antiprolifrative ( MMF- sirolimus-
68. TIMING DRUG NOTE
On empty stomach CNI LIFE LONG
Dose should be adjusted by
Every 12 hours should be
Beore brekfast ppi For 2 months
After brekfast Prednesolon LIFE ONG
AFTER THE MEALS for 3
NYSTATINE FOR 3 MONTHS
Twicw a day Ciprofloxacin For one week
2 TABLETS CMV PREVENTION (
FOR 100 DAYS
2 hours after the food MMF Twice a day Life long
Bedtime Septrin 80/420 For 9 months
With food Mutlivitamines-
magnesium calcium and
vitamin D .
Once daily As directed .
69. Lab test :
• Urea , creatinin , sugar , cbc , CNI level ,
electrolytes panel with every visit .
• May required additional test if required
like iron profile ,,,,
• At the end of 3 months should done lipid
And Urine test and urine albumine as well
Renal doppler in 1,3,6 months after
70. Follow up plan :
Twice weekly for first 4 weeks .
Weekly for the next month .
Every two weeks after 2 months .