2. Summary
Case presentations
History of diabetes
Clinical course (SPK)
Points of interest
Kidney pancreas transplantation
Basics
Risks/benefits with kidney pancreas transplantation
(SPK)
Try to get UCPCR in somewhere….
3. Case 1
Mrs PP
Type 1 Diabetes- diagnosed 1974
Proliferative retinopathy, treated and stable
Peripheral Neuropathy-problems soft tissue
infection Rt foot
Diabetic Nephropathy- CKD STAGE 4 when
referred to nephrology
Identical twin
4. Initial Management
Management of complications of Diabetic
nephropathy
Anaemia;-EPO and iv iron
CKD MBD;1-alpha calcidol, phosphate binder
Blood pressure control
Transplant discussions/work up
Keen to consider transplant
Identical twin
Discussions re kidney pancreas potential also
5. Why Transplant?
Kidney Rationale
Significant mortality advantage to having a renal
transplant
Without, survival <10 years (cardiovascular
mortality)
But why decide on pancreas now?
6. Projected years of life
(at time of placement on waiting list
Years 1991–97)
35 Non-diabetic dialysis
30 Non-diabetic Tx
Diabetic dialysis
25
Diabetic Tx
20
15
10
5
0
20–39 40–59 60–74
Age (yrs)
Wolfe et al. (1999)
7. Transplant work up
Living donor transplant considered potential
option
Twin referred for assessment
Question raised “What are my chances of
developing diabetes?”
Found to be strongly positive GAD and ISLET
antibodies
Further discussion –withdrawn as potential donor
8. Mrs PP Transplant Workup
Cardiac Immunological
Vascular HLA matching
Malignancy Panel reactive antibodies
Infection
Thrombophilia
Cross match at time of
Bladder surgery
Virus (Hep B/C/HIV, CMV)
Compliance
9. Kidney pancreas Trx Work up
Seen in Oxford
Now on Haemodialysis
Problems with hypo unawareness
Accepted for list
10. Kidney - pancreas transplantation
Combined Kidney Pancreas Rationale
Improve patient and graft survival
Better glycaemic control
Immunosuppressed anyway
Prevent or reverse diabetic complications
Improve quality of life
dialysis and insulin independent (60% 5 year)
11. SPK transplantation improves patient survival
when compared with cadaveric kidney
transplantation
Txp type 10 yr patient survival [%] Projected life yrs
SPK 67 23.4
KTA LRD 65 20.9
KTA Cad 46 12.9
From Ojo et al, AST May 2000
UNOS/USRDS: 17,137 diabetic txps 1988 - 1997
17. Effect of SPK transplantation on retinopathy
No
change, sometimes
worse
no proper trials or
studies
Is diabetic eye disease
too far advanced by
the time patient
receives a SPK txp ?
18. Effect of SPK transplantation on diabetic
neuropathy
10 year study of diabetics with and without functioning
pancreatic allografts
Minneapolis
Ann Neurology 1997 1] Clinical evaluation and autonomic tests
improved slightly
2] Motor and sensory conduction indices
significantly better
3] Improvement may take some time [2 years]
4] Significant deterioration in diabetic controls
20. Microvasc disease summary
Evidence to support improvement post
transplant
Neuropathy>nephropathy>retinopathy
Benefit outlives insulin independance
21. Effect of SPK transplantation on other
Macrovasc complications
May make
macroangiopathy worse
Recent European data
suggest that it may take at
least 5 years to get better
Improvement in outcomes
due to reduced cardiac
events
22. Why not ‘cure diabetes’earlier?
High perioperative mortality when other treatments
are available
Issues with rejection and sensitisation
Make future kidney transplant harder
Hard to detect rejection
Issues with long term immunosuppression
Infection
Cancer
Drug toxicity
Sometimes indicated
Severe Hypoglycaemia
PTA more common in USA
Islets
23. Balance of rejection v Drug toxicity
Creatinine is very sensitive marker of kidney
(+pancreas) rejection
High immunosuppressant levels esp Tacrolimus
can also cause acute and chronic kidney injury
Faced with an increased creatinine it is normally
either
Tacrolimus level
Acute rejection
One needs high dose immunosuppression, the
other needs reduction problem!
24. ADA guidelines (T1DM)
Established ESRD in patients who qualify for or already
have a kidney transplant (SPK or PAK)
Frequent acute and severe metabolic complications
(hypoglycaemia, hyperglycaemia, DKA) requiring
medical attention (PTA)
Consistent failure of insulin-based management to
prevent acute complications (PTA)
Clinical and emotional problems with exogenous
insulin therapy that are so severe as to be
incapacitating (PTA)
25. Kidney - pancreas transplantation far more common in the US
History
> 30 years
Kelly et
al, 1967, Minneapolis
Mainly in US
7 designated centres in
UK
Pancreas transplantation 1966 - 1998
26. Kidney - pancreas transplantation: patient
selection*
Renal failure
Dialysis dependent or GFR < 20ml/min
Low C peptide
Low cardiac risk
Minor peripheral or cerebrovascular disease
Compliant
Usually less than 50 years age
Now less than 60 years age
* Sollinger et al, Ann Surgery, 1998
27. Transplant
Called to Oxford 22/08/2010
Simultaneous pancreas kidney transplant
Return to theatre 23/08/2010 for drop in HB
Two nights in intensive care
Immunosuppression
Campath (alemtuzumab ) and steroid induction
Tacrolimus and mycophenolate maintainance
31. Post transplant course
Now 1 yr post SPK
Cr 127
Off insulin last glucose 5.7
Feels “fantastic”
32.
33. Mrs SC
54
Known MODY
(maturity onset diabetes of the young)
Previously enjoyed working as an HCA in hospital
34. Mrs SC
Son referred from Chesterfield Hospital 1997
Young onset diabetes
Diagnosed on OGTT age 13
“Long honeymoon”, (HbA1c 4.5-5.5 until age 15)
Then HbA1c rose and commenced insulin and
gained very good control
35. Mrs SC
DM diagnosed age 15, always on small amounts
of insulin, esp during pregnancies
Age 27 stopped insulin due to weight gain
Trial of OHA (gliclazide) unsuccessful
Back on insulin 2 years later, low doses
Retinopathy in early 30s - laser treatment
36. Family history
Late 60s
OHA
DM
Insulin DM 30s DM teens
MI 40s OHAs Insulin
DM age 15
insulin
retinopathy
nephropathy
SPK
Heterozygous
R272H mutation in
HNF1a gene
Arginine to Histine
DM 13
Insulin
37. Mrs SC
Post diagnosis of HNF1a MODY
Remained on low doses of insulin
No further trial of gliclazide
Moved to Cardiff
40. Mrs SC nephrology referral
ACEI started (bp and proteinuria)
EPO and IV iron started (anaemia)
Regular follow up
41. Mrs SC
Over next 2 years…
Cr drifted up
eGFR 22 by 2007
(CKD 3 30-60, CKD 4 15-30, ESRD <15)
Discussion about Renal Replacement Therapy
Dialysis – pt anxious ++
Transplant
Activated on transplant list end of 2007
42. Mrs SC
Transplant options
Kidney vs Kidney and Pancreas
Put on Simultaneous Pancreas Kidney (SPK) list
Pre emptive (before dialysis starts)
Specific advantages of early operation in diabetic
subjects
Wait longer = more complications=higher surgical risk
43. Mrs SC Transplant workup
No OGTT
No endocrine review
Various parts of patients notes record
T1DM, T2DM, IDDM, IDDM with low insulin dose.
Does this make sense?
44. Mrs SC
Simultaneous Pancreas and Kidney transplant
March 2008
Short waiting time
Younger donors/shorter list (benefit)
1 month peri operative stay
45. Mrs SC Peri-operative stay
Infection/abcess next to graft
Multiple Abx
Percutaneous drain
Necrosis then debridement of abdo wound
Acute rejection (in pancreas and kidney)
Anti Thymocyte Globulin (ATG)
47. Mrs SC
Cellular rejection
Methylprednisolone 1g for
3 days
Course of treatment dose
ATG
Increase baseline
immunosuppression
48. Mrs SC discharge
Tacrolimus and Mycofenolate
immunosuppression
No steroids
Antibiotics
Drain in situ
49. Mrs SC 2 months later
Jun 2008
Exploration of wound again
MI requiring angiogram
Increased creatinine ( renal biopsy no rejection)
Neutropenic
Side effect of Mycofenolate stopped
and tacrolimus monotherapy
50. Mrs SC
Relative stability until Jun 2009
Further increase in Cr to 230
Biopsy acute rejection and chronic scarring
Immunosuppression changed to Tac/rapamycin
and steroids
Poor outlook for graft survival, counselled about
early graft loss
51. Mrs SC
Currently:
Has never worked since transplant, now feels too
unwell and has retired
Intermittent depression
Normal OGTT, tested 3x post transplant
52. Mrs SC
Has been told her kidney and pancreas will fail
within 2 years
Will prob not get another transplant as has been
sensitised (anti HLA antibodies)
3 years post transplant prob back on insulin and
will need to start dialysis
53. How does SC feel
at the moment?
“Before surgery I was on insulin, but went
to work and enjoyed my job, I did not
have to take many pills”
“Now I take lots of pills, I cannot work and I
wish I never had the operation”
“I wish I had been told more before the
operation”
54. SC – First HNF1a patient with SPK
Diagnosis not known prior to operation?
Unclear how much of a trial of gliclazide she had
But diabetic complications anyway
Pre procedure data to suggest if she was T1DM
that best outcome is with SPK
Higher risk of Iatrogenic illness (early)
Normoglycaemia at moment
But soon back on dialysis and back on insulin
55. With hindsight?........
Borderline age
Borderline cardiac status (but does this matter..)
Other options? (LDK/DDK/Kidney+Islet/Islet alone)
How do we discuss transplant before surgery?
Bristol/Oxford
56. SPK transplantation improves patient survival
when compared with cadaveric kidney
transplantation
Txp type 10 yr patient survival [%] Projected life yrs
SPK 67 23.4
KTA LRD 65 20.9
KTA Cad 46 12.9
57. Kidney - pancreas transplantation
David Taube (WLRaTC)
£56,000 per txp
“In the wrong hands:-Mad, bad and frankly
dangerous”
When it goes well ……
When it goes badly ………………
“Careful patient selection, good donors and a
first class team are pre requisites for success”
59. SPK transplantation: summary and
conclusions
Optimal treatment for the young, selected
diabetic nephropath
Can make people worse
Outcome data show benefit over and above
kidney transplantion alone
Reversal of diabetic complications partial and
may take time