1. The document discusses the management and follow-up of renal transplant patients, including important considerations at the initial visit post-transplant and routine follow-up visits. 2. It outlines the various risks transplant patients face, such as cardiovascular disease, diabetes, infection, malignancy, and drug-drug interactions. 3. Maintaining optimal immunosuppression while minimizing side effects is an art that requires monitoring multiple risk factors to support long-term graft and patient survival.

1. Ayman Refaie,MD
Chief, Transplantation & dialysis Unit
Urology & Nephrology Center
Mansoura University

2. 2

3. Keep the gift

4. The Transplant Anatomy
iliac (Adults)

5. The Transplant Anatomy
Lumbar (Pediatric)

6.  Early (post transplant, Transplant Center): Not the
scope of the talk
 Late (follow up):
 Emergency: Symptomatic (related to the graft)
Oliguria / anuria, LUTS, tender graft, etc….
 Out patient: Asymptomatic (routine follow up)
Elevated serum creatinine

7. Late (follow up):
Emergency: Symptomatic (related to the graft)
Oliguria / anuria, LUTS, tender graft, etc….
Out patient: Asymptomatic (routine follow up)
Elevated serum creatinine

8. Management of a renal transplant: The art

9. Successful renal transplant
Not Only Normal S. Creatinine
•Quality of life
•Other comorbidities
•Graft survival
•Graft loss

10. Follow up of a renal transplant:
The First Visit
What you should know?
EVERYTHING
(Medical report)

11. Follow up of a renal transplant:
The First Visit
File
Medical records
(Data Base)

12. Follow up of a renal transplant:
The First Visit
 Full medical history
(DM, HTN, Hepatitis, gout, specific infections, etc..)
 Full surgical history
(General, Native kidneys, urologic operations, etc …)
 Pretransplant data:
 Recipient: original kidney disease, preemptive or Dialysis (Type &
duration) , Senesitization (Bl. Tx., Pregnancy, previous transplant)
 Donor: Type, relation, age, BW, Matching, etc…

13. Follow up of a renal transplant:
The First Visit
The transplant procedure
Place of transplantation
Postoperative course and
complications
Surgical: Bleeding, leakage,
wound problems, obstruction, etc..
Medical: ATN, rejection, serious
infections, etc…

14. Follow up of a renal transplant:
The First Visit
The immunosuppressive
regimen
Induction therapy
Maintenance therapy (1ry &
2ry)
Compliance
Antirejection
Graft biopsy:
If yes, result

16. Follow up of a renal transplant:
The First Visit
Evaluation
Full clinical examination
Full chemistry (Cr. Cl), urinalysis,
CBC.
Drug levels (CsA, Tacrolimus,
Sirolimus, Everolimus)
Graft US & Doppler
Special: ECG, Fundus, DEXA, etc….

17. Follow up of a renal transplant:
Important items to be covered
Graft function
Hypertension (Agents and doses)
DM (Pre or PTDM, Regimen)
Cardiovascular disease
Hepatitis (HCV)
Hyperlipidemia
Bone disease

18. Follow up of a renal transplant:
Routine visits
Mini Lab Work
Creatinine
Urinalysis
CBC (Hgb, WBC, platelets)
Drug levels
(Additional tests are ordered on an individual basis)

19. Frequency of follow up

20. Graft Loss
The nightmare
for both
the patient and his physician

21. Death
56%
Chronic
rejection
21%
Noncompliance
13%
Other
6%
Recurrence
4% Cause of death2
USRDS 1st
kidney transplants 1995–2003
(excluding 30% unknown)
Cause of graft loss*1
*beyond the first year after transplantation
Cardiovascular disease
43.5%
Infection
26.3%
Malignancy
10.7%
Other
19.4%
What is the most common cause of graft
loss in kidney transplant recipients
beyond the first year after
transplantation?
Graft Loss

22. Death with a functioning graft
is the most common cause of graft loss in kidney transplant
recipients beyond the first year after transplantation
1. Peeters J, et al. Kidney Int. 1995;48(Suppl 52):S97−S101.
2. Kasiske B L. et al. Coronary Artery Disease. Presented at the American Society of Nephrology Renal Week 2006 San Diego
November, 14-19, 2006.
Death
56%
Chronic
rejection
21%
Noncompliance
13%
Other
6%
Recurrence
4% Cause of death2
USRDS 1st
kidney transplants 1995–2003
(excluding 30% unknown)
Cause of graft loss*1
*beyond the first year after transplantation
Cardiovascular disease
43.5%
Infection
26.3%
Malignancy
10.7%
Other
19.4%

23. Cardiovascular risk and kidney
transplantation
• Cardiovascular disease is much more common
among renal transplant recipients compared to the
general population
• The greater incidence of CVD is not entirely
explained by traditional risk factors, (blood pressure,
cholesterol, glucose). Thus, other factors may be
involved (immunosuppression, rejection, infection?)
Kasiske BL et al. J Am Soc Nephrol 2000;11:1735-1743

24. Meier-Kriesche, Kaplan et al. Transplantation 2003.
0 12 24 36 48 60 72 84 96 108 120
90
92
94
96
98
100
2.6-4.0
2.2-2.5
1.9-2.1
1.7-1.8
1.5-1.6
1.3-1.4
<1.3
Scr mg/dl
@1 /RR
Months post-transplant
%Cardiovasculardeathfreesurvival
1.0
1.03
1.19
1.37
1.49
1.67
2.26
Cardiovascular Death Events in 48,832 KTX by
SCr at One Year Post-Transplant

25. • Hypertension
• Diabetes
• Dyslipidemia
• Renal Disease
Cardiovascular Risk Profile of the Renal Transplant
Recipient

26. Pathogenesis of Hypertension
in Renal Transplant Recipients
Kew CE II et al. J Renal Nutrition. 2000;10:3–6.
• Pre-existing essential hypertension
• General-population risk factors
(obesity, smoking, alcohol, excessive salt intake)
• Renal dysfunction/rejection
• Renal-transplant artery stenosis
• Effects of native kidneys
• Immunosuppressive drugs

27. YES
• These high risk patients will derive
benefit for the heart, brain and
transplant kidney
Does treatment of high blood pressure in
renal transplant recipients reduce graft loss
and patient death?

28. Association of Hypertension at 1 Year
With Decreased Graft Survival
SBP = systolic blood pressure
Opelz G et al. Kidney Int. 1998;53:217–222.
%graftssurviving
50
60
70
80
90
100
0
0 1 2 3 4 5 6 7
Years post-transplantation
SBP No. pts
< 120 2,805
120–129 4,488
130–139 5,961
140–149 6,670
150–159 4,443
160–169 2,925
170–179 1,217
³ 180 1,242

29. Diabetes in Kidney Transplant Patients
• Associated with reduced patient survival
• Associated with reduced graft survival
• Histologic appearance of diabetic
kidney disease within 5 years

30. 450 / 2019 (22%)

31. 1. UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:854-865. 2. Holman RR, et al. N Engl J Med. 2008;359:1577-1589.
3. The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993;329;977-986.
4. Nathan DM, et al. N Engl J Med. 2005;353:2643-2653. 5. Gerstein HC, et al. N Engl J Med. 2008;358:2545-2559.
6. Patel A, et al. N Engl J Med. 2008;358:2560-2572. 7. Duckworth W, et al. N Engl J Med. 2009;360:129-139.
8. Ismail-Beigi F, et al. Lancet. 2010;376:419-430.
Study Microvascular CVD Mortality
UKPDS1,2
DCCT/EDIC3,4
ACCORD5,8
ADVANCE6
VADT7
Impact of Intensive Glycemic Therapy
Summary of Major Clinical Trials
Long-term follow-upInitial trial

32. The increased risk of malignancy in kidney
transplant patients
Kasiske BL, et al. Am J Transplant. 2004;4:905–913.
Colon, lung, prostate, gastric,
esophagus, pancreas, ovary and
breast
Testes and urinary, bladder
Cutaneous melanoma, leukemia,
liver and gynecological tumors
Kidney
Kaposi sarcoma, PTLD, skin cancer
Moderate
Risk
High risk
Cancer rates
vs. general
population
2
3
5
15
>20

33. Based on 2419 renal transplant recipients from the Munich Großhadern transplantation center
2520151050
60
50
40
30
20
10
0
Cumulativetumorincidence(%)
10.6 %
8.4 %
19.7 %
17.9 %
38.8 %
31.2 %
49.3 %
39.7 %
28.8 %
26.9 %
2.2 %
5.2 %
14.9 %
21.7 %
9.5 %
All tumors
Solid tumors (without skin cancer)
Age-adjusted normal population
Time after transplantation (years)
Cumulative tumor incidence after renal transplantation
Wimmer CD, et al. Kidney Int. 2007;71:1271–1278.

34. Factors Influencing The Longivity Of Renal
Allograft
 Donor age
 HLA matching
 Delayed graft function
 Ischemia time
 Number of acute rejection episodes
 Native kidney disease
 Ethnicity

35. Five factors had an independent negative impact on graft survival:
Donor’s age
Genetic considerations
Type of primary immunosuppression
Number of acute rejection episodes
Total steroid dose during the first 3 months

37. Riella et al. Transplantation Reviews 31 (2017) 1–9
Causes of chronic allograft injury

38. Drug – Drug Interaction
A Major Concern!

39. Clinically relevant drug interactions
with immunosuppressive medications
Interacting Agent Effect of Interacting Agent Recommendations/Monitoring
Calcineurin Inhibitors
Antifungals
Anidulafungin No significant effect
Amphotericin B Increased risk of nephrotoxicity Appropriate hydration; monitor renal
function closely
Caspofungin Increased hepatic enzymes with
cyclosporine
Monitor transaminases closely; Consider
alternatives if elevation in hepatic enzymes
occurs
Fluconazole Inhibits metabolism Monitor CNI levels closely
Ketoconazole Inhibits metabolism Monitor levels closely; Decrease CNI dose by
50-75%
Micafungin No significant effect
Posaconazole Inhibits metabolism Monitor CNI levels closely; Decrease
cyclosporine by 25% and tacrolimus by 66%
Voriconazole Inhibits metabolism Monitor levels closely; Decrease CNI dose by
50-75%

42. Clinically relevant drug interactions
with immunosuppressive medications
Antibiotics
Azithromycin Little effect
Clarithromycin Inhibits metabolism Empiric dose reduction; monitor CNI levels
closely
Erythromycin Inhibits metabolism Empiric dose reduction; monitor CNI levels
closely
Rifampin Induces metabolism Increase in dose; monitor CNI levels closely
Antiretrovirals
Protease inhibitors Inhibits metabolism Dose reduction; monitor CNI levels closely
Anticonvulsants
Barbiturates Induces metabolism Increase in dose; monitor CNI levels closely
Benzodiazepines No effect
Carbamazepine and
Oxcarbazepine
May induce metabolism Monitor CNI levels; may require increase in dose
Levertiracetam No effect
Modafanil Induces metabolism Dose reduction; monitor CNI levels
Phenytoin Induces metabolism Dose reduction; monitor CNI levels closely
Valproic acid No direct effect Monitor levels

44. Clinically relevant drug interactions
with immunosuppressive medications
Antihypertensives
ACEIs/ARBs May increase risk of hyperkalemia Monitor Potassium
Beta-blockers Carvedilol may inhibit Monitor CNI levels
Diltiazem,
verapamil, and
nifedipine
Inhibit metabolism Decrease CNI dose by 25%; monitor CNI
levels closely
Dihydropyridine
calcium channel
blockers
No effect
Colchicine and NSAIDS
Colchicine Inhibition of colchicine
metabolism; competitive inhibition
of cyclosporine metabolism
Dose adjustment of colchicine per package
labeling required
NSAIDS Increased risk of nephrotoxicity Avoid if possible; use for short period of time if
necessary with close monitoring
Lipid Lowering Agents
HMG Co-A
reductase
inhibitors
Increased statin exposure with
cyclosporine No effect with
tacrolimus
Significant dose reductions of statin; monitor
CPK

45. Clinically relevant drug interactions
with immunosuppressive medications
Lipid Lowering Agents
HMG Co-A reductase
inhibitors
Increased statin exposure with
cyclosporine No effect with tacrolimus
Significant dose reductions of statin;
monitor CPK
Psychiatric Drugs
Citalopram No reports Monitor CNI levels
Desvenlafaxine No reports Caution due to CYP 3A4 metabolism of
desvenlafaxine
Duloxetine No reports Monitor CNI levels
Fluvoxamine Inhibits metabolism Monitor CNI levels closely; dose
reductions may be necessary
Fluoxetine, paroxetine, and
citalopram
Little effect Monitor CNI levels
Haloperidol QT prolongation Monitor QTc interval
Lithium Increased risk of nephrotoxicity Monitor renal function closely
Nefazodone Inhibits metabolism Avoid if possible
Quetiapine and olanzapine QT prolongation Monitor QTc interval
Sertraline May inhibit metabolism Conflicting reports-monitor levels
closely
Venlafaxine Little effect Monitor CNI levels

46. Clinically relevant drug interactions
with immunosuppressive medications
Antimetabolites
MMF and MPA
Calcineurin inhibitors
Cyclosporine Reduction in MPA AUC Dose adjustment may be necessary
Antivirals
Acyclovir Possible Increase in AUC Monitor for adverse events
Ganciclovir Decreased clearance of ganciclovir Monitor for adverse events
Gastrointestinal Drugs
Antacids Decrease in AUC and Cmax Avoid concomitant administration
if possible
Proton Pump Inhibitors MMF-decrease in Cmax and Tmax
MPA—no effect
Caution with MMF
Phosphate Binders
Calcium-free phosphate
binders
Decrease in AUC and Cmax Administer 2 hours after MMF

47. Clinically relevant drug interactions
with immunosuppressive medications
Miscellaneous Drugs
Cholestyramine Decrease in AUC Concomitant use not recommended
Oral
contraceptives
Decrease in levonorgestrel AUC Caution with levonorgestrel
Anti-infectives
Ciprofloxacin and
amoxicillin/
clavulanic acid
Decrease in trough levels Caution
Norfloxacin and
metronidazole
Decrease in AUC Concomitant use not recommended with
combination
Trimethoprin/
Sulfamethoxazole
Small reduction in AUC Does not appear clinically significant
Rifampin Increase in exposure Monitor for adverse events
Xanthine Oxidase
Inhibitors
Allopurinol Increase in 6-mercaptopurine Avoid concomitant use

48. Clinically relevant drug interactions
with immunosuppressive medications
Mammalian Target of Rapamycin Inhibitors
Calcineurin Inhibitors
Cyclosporine Increase in sirolimus AUC Monitor levels; if given concomitantly,
give sirolimus 4 hours after cyclosporine
Antifungals
Ketoconazole Increase in Cmax, Tmax, and
AUC
Monitor levels; significant dose reduction
required
Voriconazole Increase in Cmax and AUC Monitor levels; significant dose reduction
required
Calcium Channel Blockers
Non-dihydropyridine
calcium channel blockers
Increase in Cmax and AUC Monitor levels; dose reduction may be
required
Antibiotics
Erythromycin Increase in Cmax and AUC Monitor levels; consider azithromycin as
an alternative
Rifampin Decrease in Cmax and AUC Monitor levels; significant dose increase
required
Antiretrovirals
HIV protease inhibitors Increase in AUC Monitor levels: dose reduction may be
required

49. A transplant with graft dysfunction
• Early (post transplant): Not the scope of the talk
• Late (follow up):
 Emergency: Symptomatic (related to the graft)
Oliguria / anuria, LUTS, tender graft, etc….
 Out patient: Asymptomatic (routine follow up)
Elevated serum creatinine

50. Late (follow up):
Emergency: Symptomatic (related to the graft)
Oliguria / anuria, LUTS, tender graft, etc….
Out patient: Asymptomatic (routine follow up)
Elevated serum creatinine

51. Differential diagnosis of allograft dysfunction
1. Pre-renal azotemia
•Volume depletion (diuretics, poor intake, vomiting, diarrhea)
•Vascular constriction (CNI toxicity, NSAID)
2. Intrinsic renal diseases
•ATN
•Acute rejection
•Pyelonephritis
3. Post-renal obstruction
•Perigraft fluid collection (urine leak, hematoma, lymphocele)
•Stones
•Enlarged prostate (BPH, prostate cancer)

52. Allograft dysfunction: diagnostic approach
1. History: Pre renal cause
2. Clinical: BP and Graft
3. Lab
•Urinalysis
•Check drug levels (CNI, CsA & Tarcolimus)
4. Radiology
•Graft US: gray scale and Doppler
If all are normal

53. Allograft dysfunction: diagnostic approach
1. History: Pre renal cause
2. Clinical: BP and Graft
3. Lab
•Urinalysis
•Check drug levels (CNI, CsA & Tarcolimus)
4. Radiology
•Graft US: gray scale and Doppler
If all are normal repeat S. Creatinine

54. Allograft dysfunction: diagnostic approach
1. History: Pre renal cause
2. Clinical: BP and Graft
3. Lab
•Urinalysis
•Check drug levels (CNI, CsA & Tarcolimus)
4. Radiology
•Graft US: gray scale and Doppler
If all are normal repeat S. Creatinine
5. Graft biopsy
•Three cores (LM, IF and EM)

55. Take home message
• Many kidney transplant patients are seen in general
medical practice
• Follow up of transplant patient is an art (cumulative
Experience)
• Always work with a transplant center and a nephrologist
who is well trained in immunosuppression management
• When in doubt, ask for help!

56. My
advise
for
further
reading

57. Thank you and ready for questions