Clinical details of index patient:
Female patient 56 years with CKD for 9 years and now stage 5 due to diabetic
DM in the last 27 years currently on insulin with frequent episodes of hypoglycaemia
unawareness especially during the last 3 years.
Plain X-Ray pelvis shows left sided iliac artery calcification and phleboliths.
Prospective kidney donor (28-years old female, family member, no DSA and
hypertensive controlled on one agent).
Possible options for diabetic control:
Although she is insulin dependent diabetic and have frequent attacks of hypoglycaemic
unawareness, she is not eligible for a pancreas transplant alone due to low GFR (1).
So, her treatment option according to the OPTN/SRTR 2013 Annual Data Report should
Simultaneous kidney and pancreas transplantation (SPK).
Kidney transplant alone (living or deceased donors) +/- pancreas after kidney
• Provided that the patient:
Ø C-peptide < 2 ng/ml, or Ø C-peptide > 2 ng/ml plus BMI < 30 kg/m2. Islet Transplantation (1,2). Continuous subcutaneous insulin infusion (CSII) There is a lack of randomized trials that directly compare between pancreas versus islet transplantation. Only few observational studies have compared the two procedures. Insulin independence was 75% in pancreas transplanted patients versus 59% in islets transplanted patients as stated from single centre trial. On the other hand, the long-term adverse events as hospitalization length and frequency, infections, immunological complications and re- intervention for surgical complications were less in islets transplanted patients. These observations were supported by data registries of islet and pancreas transplantation (3-6). Patient selection and operative experience plays an important role in outcomes in pancreas transplantation. Based on Organ Procurement and Transplantation Network (OPTN)/International Pancreas Transplant Registry (IPTR) annual data report, 2015, one year patient survival in SPK was 96.9%, and 100% for PAK. At five-year, survival was 89.6% for SPK and 91.1% for PAK. Most common cause of death is due to cardiovascular disease (2). SPK associated with graft survival rate of 83% at one year and 51% at 10 years while it was 74% at one year and 24% at 10 years for PAK (7). Regarding islet transplantation, data from the Collaborative Islet Transplant Registry (CITR) showed that 70%, 55%, 35% of the type 1 diabetes recipients were insulin independent at one, two and three years consecutively. CSII could be an option for management of hypoglycaemia unawareness. Several studies evaluated the effect of CSII on hypoglycaemia awareness and on glucose profile. The results showed decline in severe hypoglycaemic episodes especially when short-acting insulin analogue was used and an improvement of quality of life (8-12). The complications post pancreas transplantation could be divided into surgical, medical, early and late complications. Surgical complications decreased dramatically over the last decade. Nonetheless, surgical complications considered as the second cause of allograft loss post immunologic cause (13). Low blood flow predisposes the graft to thrombosis. Preservation injury predisposes to pancreatitis. Higher risk of bleeding post reperfusion due to abundant lymphatic and ganglion tissue surrounding it. The duodenal graft which tolerate cold ischemia poorly and is a contaminated viscus may predispose to leaks and infections (14). Bladder drainage could lead to electrolyte imbalance, haematuria, recurrent urinary tract infections and reflux pancreatitis. Enteric drainage may lead to duodeno-enteric leaks (15). Other important complications include primary non-function, delayed graft function, rejection, infectious complications and malignancy (2,16). Work up of this prospective recipient: Pretransplant assessment for pancreas transplantation is still controversial and, no standardised guidelines yet (17). The contraindications of pancreas transplantation are resembling any transplantation as shown in table 1 (18, 19). The general principle of recipient assessment as for all solid organ transplantation based on pretransplant assessment to detect factors that increase major morbidity, graft loss or risk of death. So, evaluation process is similar in general to evaluation of kidney transplant (Table 2) (20). The nature of diabetes complications gives a direct regimen for risk assessment. This includes complications related to macrovascular disease (as peripheral vascular diseasePVD, stroke and coronary artery disease CAD) and microvascular disease (as retinopathy and autonomic neuropathy as gastropathy, cystopathy, and orthostatic hypotension) (17). Evaluation process includes comprehensive medical history, physical examination, and review of records for significant past surgical and problems. History of renal failure should be specifically investigated. Psychological evaluation is a prerequisite for serious psychosocial problems or noncompliance (19). The clinical evaluation should be emphasized on the presentation of diabetes (age of diagnosis, insulin dose requirements), prior cardiovascular disease, the complications of diabetes, and episodes of hypoglycaemic unawareness (17). Clinical assessment from the surgical perspective focus on factors that may lead to technical complications as a history of previous abdominal surgery, obesity (body mass index >30
kg/m2), and presence and severity of PVD (17).
As with kidney transplantation, laboratory evaluation includes standard laboratory studies,
viral serological panels and tissue typing, c-peptide and haemoglobin A1c. Assessment of c-
peptide level help to differentiate the type of diabetes. However, differentiation can be difficult
in many cases due to accumulation due to renal failure (19-21).
Assessment of bladder function with urodynamic studies and voiding cystourethrography may
be needed. Cancer screening should follow the standard guidelines in the potential candidates
Autonomic gastrointestinal disturbances (gastroparesis and constipation) should be assessed
through motility studies as it may affect tolerance to the oral immunosuppressive medications
Radiological assessment should aim to screen for gallstone disease, abnormal mass and native
kidney pathology (nephrolithiasis and/or renal malignancy) and can be done with ultrasound
or computed tomography (CT) scan (19).
The pelvic x-ray of the recipient shows left sided iliac artery calcification which need for
vascular assessment by non-contrast multislice CT scan which delineates vascular calcification
with pulse volume recordings (PVRs) or electron beam computed tomography (17, 54).
Vascular calcification strongly predicts cardiovascular events and all-cause mortality in
transplant recipients. The problem with pelvic arterial disease may be a cause for difficult graft
placement on the left side, technical graft failure and may enhance the risk of limb amputation
(54). Also, the pelvic x-ray shows phleboliths which is not unusual in this case and generally
considered harmless (55).
There is no consensus regarding the cardiovascular assessment in the diabetic patient with end
stage renal disease. For low-risk patients, the evaluation could involve electrocardiogram
(ECG), echocardiography, non-invasive functional assessment such as an exercise or
pharmacologic (dobutamine) stress test. Its sensitivity of 75% and specificity of 71%, for
stenosis > 70% in ESRD patients (17,19,20).
Coronary angiography should be used for high-risk patients (age > 45 years, diabetes > 25
years, +ve smoking history, long-standing hypertension, history of cerebrovascular disease, or
previous major amputation due to PVD) coronary angiography should be used. Also, if history
and examination suggest poor functional status from decreased cardiac reserve or if initial
noninvasive cardiac studies are abnormal (19,20).
The potential donor has the following criteria:
Young age female.
No data about race, lifestyle and obesity.
Hypertension on single agent (controlled).
No history about pregnancy.
We must recognize that each potential donor is unique, and no single evaluation protocol is
applicable to all living donors, so it is important to tailor medical evaluation to uncover
conditions that may significantly increase the risk of a donation to the potential donor.
This potential donor evaluation process includes an assessment of mental and physical health
and the immunologic compatibility. The general lines to the medical and psychosocial
evaluation of the prospective donor outlined in table 3 (22).
Hypertension counselling in this patient will include assessment and control of modifiable risk
factors as kidney donation associated with non-physiological reduction in the GFR which may
accelerate the progression of hypertension more than expected with normal aging and this
effect may be more in African American descent (23-27).
Hypertension is a risk and contributing factor for CKD in the general population (28). The
hypertensive nephrosclerosis leads to scarring of the kidney and may not be detected by routine
assessment of kidney function and albuminuria. Aging processes or this subclinical pathology
may impair compensation and decrease GFR post donation (29,30).
Race also affect hypertension consequences as in nondiabetic African Americans, response to
mild-to-moderate primary hypertension treatment may not cease progression of kidney disease
while in European Americans slow kidney disease progression could be achieved when
controlling hypertension (31-39).
So, she will be assessed for duration of hypertension, how well controlled has it been, and
whether there been a known target organ event. The assessment of degree of BP control is not
standardised in transplant centers, but it is reasonable to use 24-h ambulatory BP monitoring
as it has great value in target organ damage risk prediction and provide daytime and night BP
This donor should undergo a rigorous diagnostic evaluation of target organ damage as she is
hypertensive although she is controlled on one agent. Kidney function should be assessed using
serum creatinine for initial assessment of estimated glomerular filtration rate followed by
exogenous radionuclides filtration markers (iothalamate, 51Cr-EDTA iohexol or 99mTc-
DTPA). Assessment of urine albumin excretion should be made according to guidelines
recommendations using urine albumin-to-creatinine ratio in two occasions (44).
Evaluation of cardiovascular risk of this prospective donor should also include smoking
history, obesity (body mass index calculation), dyslipidaemia (fasting lipid panel) and diabetes
mellitus (fasting blood glucose, HbA1c, and oral glucose tolerance testing). Standard chest X
– rays, electrocardiograms with echocardiography for assessment of cardiovascular structure
and function (left ventricular hypertrophy) (45-48).
The prospective donor is in the child-bearing age with no history described for previous
pregnancy or future plan. At the same time donation effect on pregnancy is a major concern of
donors in child-bearing age. So, assessment of history of hypertensive disorders in previous
pregnancies is important. It is mandatory to confirm absence of pregnancy before donation
using quantitative human chorionic gonadotropin (?-hCG) pregnancy test. Future childbearing
plans should be discussed with the donor as there is a possibility of worsening hypertension or
being diagnosed with gestational hypertension or pre-eclampsia (44,49,50).
She must also be informed that hypertensive disorder with pregnancy associated with increased
risk of development of kidney disease especially with previous diagnosis of hypertension
So, based on the given data and risk assessment of this potential donor, she should be informed
about the increased risk of kidney and cardiovascular disease and to be excluded from the
Early postoperative care:
1. Infection and thrombosis prophylaxis:
This usually achieved by antibiotic prophylaxis start from surgery and usually extend for 2-5
days’ post transplantation. Antifungal prophylaxis may be used up to three months’ post-
surgery, antiviral prophylaxis is used as per schedule from three to six months. Pneumocystis
Jirovecii prophylaxis used up to one year (13).
Low-dose aspirin started before surgery as an anticoagulant then during first-week post-surgery
low- molecular- weight dextran usually started. Any history of thrombosis mandated sustained
anticoagulation therapy (16).
2. Prevention of acute rejection:
This can be prevented and treated by Immunosuppressive therapy. The key component of post-
transplant surveillance for immunosuppression is frequent and close monitoring of serum drugs
level as they have a narrow therapeutic window, multiple interactions and potential
3. Monitoring of graft function:
This followed by regular assessment of blood glucose, HbA1c, C–peptide levels and amylase.
If bladder drainage is used, the urinary levels of amylase are observed. As well, if pancreatic
drain is used drainage levels of amylase is observed (20).
4. Intensive care unit follow-up:
This can be done by strict monitoring of cardiac parameters, fluid and electrolyte balance, and
metabolic status. Frequent monitoring of haemodynamic, nasogastric drainage, urine output
and wound drainage is mandatory (19).
Follow-up for surgical complications:
1. Graft thrombosis:
By repeated assessment of serum electrolytes, glucose, vital signs and Doppler studies. Acute
onset of pain with swelling of the graft and sharp rise of serum glucose and amylase mandate
rapid intervention for the possibility of venous thrombosis. Rapid rising of serum glucose while
decreasing serum amylase raise possibility of arterial thrombosis (22).
It could be immediate during perioperative period and usually self-limiting. Late pancreatitis
mostly occurs in bladder drained pancreas due to reflux of urine and should be differentiated
from acute rejection. It could also result from abdominal distention, constipation and ileus.
Low-grade fever, tender graft, increased serum amylase with no affection of endocrine function
necessitate urgent Ultrasound examination which reveals oedematous pancreas (22).
3. Cystitis and urethritis
It is common in bladder- drained pancreas transplants and recipients with neurogenic bladder.
Repeated urinalysis and urine culture and sensitivity is a prerequisite. Post void residual urine
assessment and a voiding cystourethrogram usually done when suspected neurogenic bladder.
Cystoscopic evaluation may be necessary in selected cases (22).
4. Intrapancreatic abscess:
Usually occurs late due to chronic rejection or viral infection. Radiological assessment is
mandatory for proper diagnosis (20).
Follow-up for medical complications:
Monitoring of pancreas allograft function:
Repeated evaluation of urine and serum amylase levels is a non-invasive assessment of
allograft function and help in rejection diagnosis for bladder drainage pancreas
transplant but it is not feasible in enteric drainage pancreas (56).
Repeated assessment of glucose and HbA1c are routinely done. Insulin sensitivity could
also be assessed by oral glucose tolerance, quantitative insulin sensitivity check index
(QUICKI) and homeostasis model assessment of insulin sensitivity (HOMA-IS) (56,
A. Serum and Urinary Amylase:
Used as indirect diagnosis of rejection for bladder drainage pancreas transplant but it is not
feasible in enteric drainage pancreas (56).
Indirect diagnosis of pancreas rejection in SPK when originate from the same donor (56).
Although the advances in the diagnosis of rejection, biopsy still the gold standard test
especially when noninvasive testing fail to detect the aetiology of the allograft dysfunction
3. Glucose Level Monitoring:
Impaired glucose tolerance (IGT) or post-transplant hyperglycaemia is an indicator of reduced
graft function, increased risk of graft loss and may affect patient survival. So, post-transplant
hyperglycaemia is an alarming sign which needs full evaluation (Table 4) (56,59-61).
Screening, assessment and management plan of hypertension, hyperlipidemia, bone and
mineral disease, infections, hematopoiesis and malignancy follow the guidelines
Discussion and conclusions:
For our patient which is insulin dependent diabetes glycaemic control is optimized with
continuous subcutaneous insulin infusion via a pump. However, she may not achieve optimal
glycaemic control and frequent disabling and life-threatening hypoglycaemia, and
complications remain common. On the other hand, our patient has advanced kidney disease
which will also need renal replacement therapy. So, pancreas transplantation in combination
with a kidney is therefore considered an important treatment option either through
simultaneous pancreas–kidney transplantation or kidney transplantation followed by pancreas
There is increasing evidence to suggest that, SPK offers the best outcome in terms of survival,
graft survival and quality of life. Other benefits suggesting SPK over PAK in this case include;
one round of induction immunosuppression, same HLA source, can be achieved in patients
with type II DM and in patients of advanced age, restore euglycaemia in most cases, reduce
Cardiovascular mortality, and shorter waiting time (63-65).
Living donor option for kidney transplantation may be preferred to achieve earlier dialysis
independence; however, pancreas graft survival is better in SPK than PAK and risk of
developing complications later life in our prospective donor should be considered (62).
Absence of a major surgical procedure in Islet cell transplants is an advantage over whole-
organ transplantation. Also, if the procedure success it can provide excellent control of blood
glucose. However, the poor long-term outcomes and that our patient will need for renal
replacement therapy making this procedure is not a feasible option (62).