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86
becomes more common—up to 15%–60% peaking at around 3–6months post-
transplant—most commonly due to persistent secondary hyperparathyroidism
along with more active vitamin D (1,25-OH vitamin D) being activated by the
kidney allografts. Most patients remain asymptomatic, and no specic treatment
is needed other than ensuring stopping calcium supplementation and avoiding
overzealous vitamin D replacement (no more than 800 international units of cho-
lecalciferol) while ensuring that active vitamin D (calcitriol) be discontinued. If
hypercalcemia is more severe (>12mg/dL) and PTH is elevated (generally >5
times the upper limit of normal), a loop diuretic may be added; thiazide-type
diuretics should be avoided, and patients should be reminded to stay well-
hydrated. Hypercalcemia generally resolves once PTH and other hormonal
changes have normalized. Uncommonly up to 0.5%–5% of kidney transplant
recipients have persistent hypercalcemia after 1-year post-transplantation [108].
• Phosphorus: Hypophosphatemia is quite common (40%–90%) in post-transplant
recipients. Patients have persistent secondary hyperparathyroidism and elevated
FGF23, but in the presence of a kidney allograft with functioning nephrons, renal
phosphorus wasting ensues [108]. At mildly to moderately low phosphorus lev-
els (1.5–2.3 mg/dL), symptoms are uncommon but if hypophosphatemia is
severe (<1.5mg/dL or 0.5 mmol/L), muscle weakness and fatigue might be
noted. As with calcium abnormalities, low phosphorus levels usually nadir at
3–6months and normalize by 1year post-transplant. First-line treatment is to
liberalize dietary intake of phosphorus—which can be difcult for some chronic
kidney disease patients who might be accustomed to dietary phosphorus restric-
tion. Adequate intake of high biological value protein (up to 1–1.2 to 1.4g/kg/
day) and dairy products should be encouraged. Mildly low phosphate levels
(1.5–2.3mg/dL) are usually well tolerated. If dietary intervention is inadequate,
oral replacement may be used. Commonly used preparations include potassium
and sodium phosphate (K Phos Neutral
®
) which contains 250mg phosphorus
(8mmol), 12mg potassium (1.1mEq), and 298mg sodium (13mEq) per tablet.
Potassium phosphorus/sodium phosphorus power (Phos-NaK powder), which
contains 250 mg (8 mmol) phosphorus, 280 mg (7.1 mEq) potassium, and
160mg (7.1mEq) sodium per 1.5-g package.
• Persistent hyperparathyroidism: After a successful kidney transplantation, para-
thyroid hyperplasia or adenoma may regress but this involution takes time and is
rather slow. As many as 50% of kidney transplant recipients continue to have
persistently elevated parathyroid hormone by 1 year post-transplantation and
almost a quarter still do after 5 years [108]. Risk factors for persistent
hyperparathyroidism include longer time on dialysis prior to transplant, higher
level of pre-transplant parathyroid hormone, hypercalcemia and hyperphospha-
temia. In some cases, the parathyroid adenoma(s) may become autonomous (also
known as tertiary hyperparathyroidism), secreting PTH and causing hypercalce-
mia and hypophosphatemia, high bone turner as evident by elevated alkaline
phosphatase and low bone-mineral density and recurrent kidney stones.
Hypercalcemia by itself can elicit renal vasoconstriction causing allograft dys-
function and further exacerbate volume depletion by causing nephrogenic diabe-
B. Boonpheng and I. C. De Castro
87
tes insipidus. In these cases, surgical management with subtotal parathyroidectomy
or total parathyroidectomy with autotransplantation can be considered in consul-
tation with the transplant center. Stabilizing the metabolic abnormalities with
medical therapy such as cinacalcet (Sensipar
®
) in the meantime is reasonable–
starting at 30–60mg/day in most cases. Other supportive therapy may also be
necessary including a loop diuretic, a bisphosphonate and volume repletion.
• Vitamin D: Although there is no specic consensus or data showing benets
specic to kidney transplant recipients, it is generally recommended to keep
25-OH vitamin D level >30ng/mL.One randomized controlled trial showed
skeletal benets in terms of fracture prevention of high dose vitamin D supple-
mentation (100,000 IU cholecalciferol every 2 weeks for 2 months and then
monthly for 22months) compared to the low dose regimen (12,000IU cholecal-
ciferol every 2weeks for 2months and then monthly for 22months) but no extra-
skeletal benets (new onset diabetes, cardiovascular disease, or infection) in
kidney transplant recipients with 25-OH vitamin D <30ng/mL [109].
• Bone disease: Due to steroids, underlying bone abnormalities, hypophosphate-
mia and persistent hyperparathyroidism related to chronic kidney disease, kidney
transplant recipients experience rapid bone density loss within the rst 6months
after transplantation and a smaller rate of bone loss can persist up to 2years
[110]. Kidney transplant recipients have been shown to experience a higher rate
of fractures compared to the general population [111] and major fragility frac-
tures such as femoral neck fracture or vertebral compression fracture are associ-
ated with higher mortality in this population [112]. Other major risk factors
include female sex, older age, being underweight, physical inactivity, longer or
higher steroid exposure, concomitant persistent hyperparathyroidism, hypophos-
phatemia, vitamin D insufciency and diabetes. There is no consensus on timing
of screening or evaluation of bone loss or osteoporosis. General practice is to
check serum calcium, albumin, phosphorus, vitamin D, PTH and alkaline phos-
phatase (or other bone turnover markers) when kidney allograft function has
become stable—usually after 1–3months. Ideally, screening and treatment of
osteoporosis should be done when persistent hyperparathyroidism and other
bone-mineral abnormalities as well as vitamin D have all been corrected. Bone
density (BMD) measurement using the dual X-ray absorptiometry (DEXA) with
or without a plain lm of vertebral spine is recommended at baseline pre-
transplantation and within 3-months post-transplant. Prevention of osteoporosis
or bone loss is the same as in the general CKD population: weight-bearing physi-
cal activity, adequate calcium intake of 1000mg elemental calcium per day and
supplement if needed, maintaining vitamin D at 30–50ng/dL (if normocalce-
mic). Prednisone should be tapered to maintenance dose of 5mg/day as soon as
able by the transplant team. If a kidney transplant recipient has osteoporosis
(previous history of symptomatic or radiologic fragility fracture, osteoporosis by
BMD criteria, T-score ≤−2.5) or osteopenia with a high risk for osteoporotic
fracture, treatment with a bisphosphonate or denosumab or teriparatide may be
considered once CKD-MBD or persistent hyperparathyroidism has resolved—
generally after 6–12 months post-transplant. The decision and the choice of
4 Primary Care of the Adult Kidney Transplant and Kidney-Pancreas Transplant…
88
treatment can be complex and should be coordinated with a nephrologist or the
transplant team. Primary care providers should ensure serum calcium, albumin
and phosphorus are being monitored at least every 6months within the rst 1–2-
year post-transplant and vitamin D should be monitored annually. If treatment
for osteoporosis is initiated, BMD should be repeated every 1–2years depending
on the risk of fracture.
• Another feared bone complication in kidney transplant recipients is avascular
necrosis of the bones, with steroid use being one of the most important risk fac-
tors and steroid-sparing regimens have been shown to reduce its incidence down
from up to 20% to less than 5%. The femoral neck is the most commonly involved
site and is associated with morbidity in kidney transplant recipients [113]. There
are no well-established screening guidelines and high index of suspicion is
essential for early diagnosis and intervention.
4.1.8.10 Electrolyte Abnormalities
• Hyperkalemia is relatively common in patients with poor allograft function. It
can also occur in the setting of normal allograft function as a side effect of CNIs
which impair renal potassium excretion, but the degree of hyperkalemia is usu-
ally mild (5–5.5mEq/L) [38]. Trimethoprim-sulfamethoxazole (TMP-SMX) for
Pneumocystis jiroveci pneumonia (PJP) prophylaxis, ACEis/ARBs or mineralo-
corticoid receptor antagonists (MRAs) can also exacerbate or trigger hyperkale-
mia. If allograft function is normal, high potassium food intake alone does not
trigger hyperkalemia in most kidney transplant recipients. Evaluation in those
with normal or mildly impaired allograft function includes medication review,
ensure adequate blood specimen collection and handling to rule out pseudohy-
perkalemia due to a hemolyzed specimen, rule out supratherapeutic CNIs and
obstructive nephropathy. Treatment is aimed at promoting renal potassium excre-
tion which includes stopping offending medications if able, adding a diuretic—
commonly a thiazide-type diuretic such as chlorthalidone or indapamide or a
long-acting loop diuretic such as torsemide. Fludrocortisone can counteract the
effect of CNI by promoting potassium excretion but it also promotes sodium
reabsorption leading to hypertension so it is not a rst-line therapy, but it might
be considered temporarily in those with normotension. Another option is to use
potassium binders such as sodium zirconium cyclosilicate (Lokelma
®
) or pati-
romer (Valtassea
®
), to increase gastrointestinal excretion of potassium. However,
the timing of administration relative to other medications is crucial; it should be
taken 2–3h before or after other medications.
• Hypokalemia is quite uncommon. Early after transplant it may be observed in the
setting of good allograft function and high urine output when tubular function is
still recovering. Beyond the immediate post-transplant period, persistent hypo-
kalemia should raise suspicion for a concomitant condition, such as hypomagne-
semia. Transplant renal artery stenosis or unrecognized primary
hyperaldosteronism should also be considered, especially if hypokalemia is
B. Boonpheng and I. C. De Castro
89
associated with new onset or worsening hypertension. Low potassium intake is
rarely the cause of hypokalemia since the kidney allograft has excellent
potassium- preserving ability.
• Hyponatremia or hypernatremia are uncommon beyond the immediate post-
transplant period in kidney transplant recipients with stable kidney function.
Evaluation is the same as in the general population. Mild hyponatremia espe-
cially in the setting of polyuria or polydipsia early post-transplant should raise
suspicion for hyperglycemia-induced hyponatremia. In the setting of acute ill-
ness, hyponatremia may be one of the signs of secondary adrenal insufciency
in those maintained on long-term maintenance steroid, but overall the clinical
picture is usually obvious. In such case, appropriate stress dose steroids should
be given.
• Hypomagnesemia is relatively common in kidney transplant recipients due to
CNI-induced kidney magnesium wasting [38]. Hypomagnesemia can also con-
tribute to hypokalemia and hypocalcemia and has been associated with pancre-
atic islet cell dysfunction and post-transplant DM.All kidney transplant recipients
should be encouraged to increase dietary magnesium intake but most also need
magnesium supplementation in divided doses. Persistently severe hypomagnese-
mia <1.5mg/dL despite supplementation should raise suspicion for suprathera-
peutic CNI levels. Potassium-sparing diuretics such as spironolactone or
amiloride may be used to reduce renal magnesium wasting if high dose magne-
sium supplementation is poorly tolerated due to GI side effects such as diarrhea;
potassium levels need to be monitored because of the additional risk of
hyperkalemia.
4.1.8.11 Hematologic Abnormalities
• Anemia: In the immediate post-transplant period, anemia is quite common due
to advanced chronic kidney disease; iron, B12 or folate deciency; discontinua-
tion of erythropoiesis-stimulating agents (ESA); volume expansion; and bone
marrow suppression due to induction and maintenance immunosuppression,
especially the anti-metabolites (MMF or azathioprine) and mTORi. As the kid-
ney allograft function recovers, anemia generally improves and commonly nor-
malizes by 3-months post-transplant. However, mild anemia (Hb 10–11.5g/dL)
persists in some patients due to medications such as TMP-SMX, valganciclovir
or ACEi/ARB, well as a mild degree of chronic inammation. However, an acute
drop in hemoglobin or progressive anemia in the setting of normal or mildly
reduced allograft function (>45–50mL/min/1.73m
2
) should be evaluated as in
the general CKD population with basic evaluation including iron, folate, vitamin
B12 status, reticulocyte count, complete blood count and peripheral blood smear
review, haptoglobin, LDH, creatinine. Special considerations should be given to
the possibility of thrombotic microangiopathy (TMA), blood loss, and infections
such as parvovirus B19, EBV or CMV, all of which can suppress bone marrow
production. Dapsone, an alternative to TMP-SMX for PJP prophylaxis, can also
4 Primary Care of the Adult Kidney Transplant and Kidney-Pancreas Transplant…
90
trigger intravascular hemolysis in G6PD deciency kidney transplant recipients.
Acute graft dysfunction and rejection can also contribute to anemia. Treatment is
directed at the etiology.
• Leukopenia is also not uncommon in transplant recipients. In addition to causes
common to the general population, etiologies to consider in kidney transplant
recipients include immune suppression, especially induction with rATG or alem-
tuzumab, and the use of maintenance regimens containing an anti-metabolite
and/or mTORi; antibiotics such as TMP-SMX; the antiviral agents, valganciclo-
vir, ganciclovir, and acyclovir; as well as infections themselves—commonly
CMV, parvovirus B19 and other systemic infections. Treatment will depend on
the underlying etiology.
• Thrombocytopenia is also common due to medications such as the anti-
metabolites, prophylactic antibiotics or antivirals. Occasionally thrombocytope-
nia can be an early sign of systemic TMA especially if accompanied by hemolytic
anemia and acute kidney injury.
• Post-transplant Erythrocytosis (PTE) is dened as persistently elevated Hct to
>51% or >17g/dL after transplant. It typically develops early, within 8–12months
post-transplant in those with excellent allograft function. Incidence is <10%.
Pathophysiology remains unknown but it is believed the native kidneys along
with direct stimulation of red blood cell productions by angiotensin II and defec-
tive regulation of EPO play a role. Important risk factors include polycystic kid-
ney disease, glomerulonephritis, male sex, hypertension, high pre-transplant
hemoglobin, and presence of native kidneys [114]. In a quarter of patients, PTE
resolves spontaneously within 2years. However, any late onset PTE requires
further evaluation to rule out common EPO-producing malignancies such as
renal cell carcinoma (RCC) in the native kidneys and the kidney allograft, hepa-
tocellular carcinoma, and cerebellar hemangioblastoma. Sometimes transplant
renal artery stenosis (TRAS) can present with PTE—vascular studies with
duplex ultrasound or CT angiography to evaluate both the iliac arteries and the
renal artery should also be performed. Generally, treatment is only recommended
when Hct is above >51–54% or Hb >17–18g/dL to prevent symptoms such as
headache, hypertension and thromboembolic complications. First-line treatment
is ACEi or ARB, which is usually very effective. Aspirin 81mg daily may also
be considered if there is no other contraindication and the bleeding risk is low. In
more severe or refractory PTE, phlebotomy may be necessary.
4.1.8.12 COVID-19 andKidney Transplant Recipients
Kidney transplant recipients, similar to other solid organ transplant recipients, are at
higher risk of severe disease and mortality from SARS-CoV-2 infection, especially
in older patients and those with a recent transplant. In addition, due to immunosup-
pression, responses to immunization may not be optimal compared to the general
population [115]. Treatment depends on the severity and timing of symptom onset
with particular attention to managing immunosuppression, prompt antiviral therapy
B. Boonpheng and I. C. De Castro
91
and immunomodulatory therapy in addition to supportive care. For stable patients
managed in the outpatient setting, nirmatrelvir/ritonavir (Paxlovid
®
) needs particu-
lar attention due to severe drug interaction with CNIs—the ritonavir component can
boost the CNI levels. Therefore, if there are no other options and nirmatrelvir/rito-
navir is deemed necessary, CNI needs to be dose reduced or even held temporarily
with careful therapeutic drug monitoring, with close consultation or management
by the transplant team, which may involve the transplant nephrologist, pharmacist,
and infectious disease specialist (see Chap. 3). Consultation with the transplant
team nephrologist is strongly advised.
In moderate to severe disease, the transplant team may consider reducing immu-
nosuppression—most commonly the anti-metabolite and/or CNI—on a case-by-
case basis, weighing the risk of severe disease against the risk of rejection.
Hospital-based therapies are beyond the scope of this book (see Chap. 8).
Some kidney transplant recipients develop recurrent or de novo glomerular dis-
eases following SARS-CoV2 infection or vaccination [116].
Donor-derived SARS-CoV-2 infections in kidney transplant recipients have not
been documented so far and kidneys from donors with positive SARS-CoV-2 or
with COVID infection may be used–with data showing comparable short to inter-
mediate term outcomes to donors with negative SARS-CoV-2 [117].
4.1.8.13 Peri-Operative Management ofKidney Transplant Recipients
For non-transplant related surgery in kidney transplant recipients, general peri-
operative management is similar to that of the general chronic kidney disease popu-
lation. Important caveats are emphasized. First, for pre-operative assessment, it
should be kept in mind that kidney transplant recipients generally have a high bur-
den of cardiovascular risk factors as well as cardiovascular diseases—sometimes
subclinical. For non-emergency surgery, optimization of these risk factors should be
attempted with judicious use of further evaluation when it would change manage-
ment. Second, for those maintained on a chronic low-dose steroid, ACTH stimula-
tion test might be considered to assess adrenal reserve or “stress dose” hydrocortisone
could be considered—depending on the severity of the “surgical stress” while
avoiding overzealous steroid replacement to prevent steroid-related adverse effects.
Third, for those maintained on a regimen containing an mTORi (sirolimus or evero-
limus), the surgery team should be made aware of the potential impairment in
wound healing [118]. Although there is no consensus, if the surgery is elective and
tissue integrity after surgery is paramount—i.e., an anastomotic leak could be cata-
strophic, then consultation with the transplant centers for switching or changing
immunosuppressive regimen at least 4–6 weeks prior to the scheduled surgery
should be considered. Finally, clinicians should be aware of atypical presentations
of certain intra-abdominal surgical emergencies due to masked inammatory
response by the maintenance immunosuppressive drugs and altered anatomy such
as an acute appendicitis when the kidney allograft is placed within the right iliac
fossa pushing the location of the appendix upwards.
4 Primary Care of the Adult Kidney Transplant and Kidney-Pancreas Transplant…
92
For post-operative management, when the patient is placed on strict NPO status,
steroids can be converted to equivalent dose of IV methylprednisolone and tacroli-
mus can be given sublingually i.e. the capsules can be opened and the powered
content placed under the patient’s tongue (the sublingual dose should be initiated at
50% of the usual oral dose) [119] while the anti-metabolites may be held temporar-
ily. However, if the kidney transplant recipients need to be on strict NPO for pro-
longed period of time (>3–5days), then IV CNIs need to be considered—tacrolimus,
cyclosporine, and mycophenolate are available as IV formations, but their dosing
and adjustment is complex and best managed by the transplant centers with ade-
quate support from specialized pharmacists.
For a more general discussion of metabolic complications in solid organ trans-
plant recipients, see Chap. 11. For further details pertaining to infectious complica-
tions, see Chap. 8.
4.1.8.14 Outpatient Visits inPrimary Care
Clinical pearls for the outpatient evaluation of kidney transplant recipients in the
primary care clinic are given in Table4.4.
4.1.9 Pediatric Kidney Transplant Recipients Transitioning
toAdult Care
Late adolescence to young adulthood is a vulnerable period—with tremendous
changes physically, psychologically, and biologically, there exists a continuum of
when an adolescent individual reaches adulthood in different domains. Furthermore,
Table 4.4 Clinical pearls for the primary care provider—evaluating kidney transplant recipients at
outpatient clinic visits (see text for details, also see Chap. 2 for discussion of general history-taking)
Initial visit:
Review pre-transplant and initial post-transplant course
: Indication for transplant, pre-
transplant dialysis, dialysis access (if still present), type of donor, anatomic location of
transplant, type of induction immunosuppression
Creatinine nadir
Early complications (delayed graft function, surgical complications, infection, rejection)
Symptoms, exam, medications, laboratory studies similar to follow-up visits
Follow-up visits:
Symptoms: Urine output, hematuria, pain, symptoms of volume depletion or excess, side effects
of medications, symptoms of infection
Exam: Blood pressure, heart, lung, abdomen exam, volume status
Medications: Current regimen, adherence, side effects, goal trough levels
Laboratory and other studies: Adherence to surveillance schedule set forth by the transplant
team; surveillance for rejection (biopsy vs donor-specic antibodies); creatinine, proteinuria,
BK virus (if checked)
Home blood pressure: Review readings (if being followed)
Metabolic complications: Assess and treat
if sudden worsening of hypertension, consider renal artery duplex
B. Boonpheng and I. C. De Castro
93
those with childhood-onset kidney disease may exhibit delayed neurocognitive or
psychosocial development. However, in rigid health systems, insurance or other fac-
tors often impose a strict age cut-off between the pediatric side and the adult side—
causing problems for some pediatric kidney transplant recipients aging out of
pediatric care but who still need specialized attention that may not entirely t within
the realm of general adult internal medicine. This transition period can be a signi-
cant challenge. In younger kidney transplant recipients, the period between 17 and
24years of age has been shown to be associated with the highest rate of kidney
allograft loss—interestingly irrespective of their age at transplantation [120] and
this observation has been conrmed by multiple studies across different healthcare
systems [121].
Non-adherence to immunosuppressive medications is one of the most pressing
issues. Post-transition adherence tends to worsen [121, 122] with a prevalence of
almost a third of adolescent kidney transplant recipients and almost half of graft loss
in this age group can be attributed to non-adherence [123]. This group of patients
are best served in the transition clinic model associated with transplant centers in
which pediatric and adult multidisciplinary transplant teams closely collaborate
with a formal transfer process. On the adult side, primary care providers should be
familiar with adolescent psychosocial development, potential intellectual disability
and common congenital anomalies of the kidney and urinary system (CAKUT),
which sometimes need ongoing attention in collaboration with urology or other
specialists. It is also important to learn about local resources, train staff, and build a
multidisciplinary team to help guide these medically complex patients. If a kidney
transplant recipient relocates, they should be encouraged to notify the original trans-
plant center and transfer to a local transplant center and establish care with a local
primary care provider who can work in close collaboration with the transplant team
in order to ensure a smooth transition of care. In the event that the primary care
providers are the patients’ rst contact then it is essential to notify the original trans-
plant center to obtain proper transfer information and facilitate establishing with the
new local transplant center. Finally, insurance coverage and nancial arrangement
should be considered and planned for in advance—although Medicare does provide
coverage for lifelong immunosuppression, it does not provide coverage for other
related medications that kidney transplant recipients may need and these patients
may need to nd their own insurance coverage once they reach the age of 26 if they
were previously covered under their parent’s private or group insurance.
4.1.10 Pregnancy andSexual Health
In general, female kidney transplant recipients recover hormonal axis, gonadal
function, ovulation, and fertility quickly after a successful transplant—as early as a
few weeks after transplantation. The overall fertility rate is much better after kidney
transplantation compared to end-stage kidney disease without transplantation, but it
remains much lower than in the general female population [124]. In female kidney
transplant recipients who desire pregnancy, it is essential to counsel patients about
4 Primary Care of the Adult Kidney Transplant and Kidney-Pancreas Transplant…
94
planning. Counseling about contraception and conception are done even prior to
active kidney transplant listing or kidney transplantation. Timing of pregnancy is
generally advised after 1–2years if the overall transplant course has been stable
with no rejection episode or potentially fetotoxic infections such as CMV or EBV;
however, patients’ age, fertility potential, and overall plan should also be considered
and individualized [124]. Once the transplant nephrologists assess that the patient
can conceive with acceptable risks, immunosuppressive medications should be
adjusted in advance prior to conceiving. Generally, MMF or MPA and mTORi are
contraindicated due to unacceptable risk of teratogenicity and the immunosuppres-
sive regimen should be switched to azathioprine in addition to continuing a CNI and
steroid with close monitoring for at least 6weeks while those on mTORi based regi-
men should be switched to azathioprine for at least 8–12weeks [124]. Maintenance
belatacept during pregnancy appears to be safe but long-term large-scale data are
not available [125]. In the meantime, these patients should be monitored by mater-
nal fetal medicine specialists prior to conception. Pregnancy planning in kidney
transplant recipients is complex and ideally should be managed by a multidisci-
plinary team at transplant centers but primary care providers play an essential role
in reminding patients about contraception, folic acid supplementation and the criti-
cal importance of a planned pregnancy (See Chap. 13).
In male kidney transplant recipients, hormonal abnormalities and libido improves
and fertility returns relatively quickly as well—as soon as a few weeks post-
transplant paralleling the improvement in kidney allograft function. However, erec-
tile dysfunction might persist in some men due to side effects of comorbidities and
certain medications such as anti-hypertensives. Sexually active males should be
counseled about effective contraception. Men who plan to father a child should not
be maintained on an mTORi since it can interfere with spermatogenesis [126]—
therefore, patients should be at least informed about this risk and ideally should be
switched to non-mTORi based regimen at least 8–12weeks prior to conception.
4.2 Pancreas Transplant Recipients
4.2.1 Introduction
Although there have been remarkable advancements in the medical treatment of
diabetes mellitus in recent years, pancreas transplantation remains the only deni-
tive treatment that allows for restoration of euglycemia without the potential risk of
life-threatening hypoglycemia. As such, pancreas transplantation is the treatment of
choice for eligible patients with type 1 diabetes mellitus and select insulin- dependent
type 2 diabetes mellitus.
The rst successful pancreas transplantation was performed in 1966 at the
University of Minnesota by Drs. William Kelly and Richard Lillehei as part of a
multi-visceral procedure that included the transplantation of a pancreas, duodenum
B. Boonpheng and I. C. De Castro
95
and kidney from a deceased donor to a patient with type 1 diabetes and diabetic
nephropathy [127]. Blood glucose levels in the recipient were noted to decrease
almost immediately upon completion of the surgery and the patient went on to live
for 3months before dying of an apparent pulmonary embolism. In the following
years, as surgical techniques, patient selection, and immunosuppressive strategies
have improved, so too has the success of pancreas transplantation.
In the last three decades, there have been more than 35,000 pancreas transplanta-
tions performed in the USA based on OPTN data as of January 2024. Interestingly,
the number of annual pancreas transplantations in the USA peaked in 2014, with
1483 transplants performed, and then decreased steadily over the ensuing decade.
The post pandemic recovery did not occur in pancreas transplantation as in other
organs [128]. The number of pancreas transplants in the United States decreased to
918in 2022 from 963in 2021. The number of simultaneous pancreas-kidney trans-
plants decreased to 810in 2022 from 820in 2021, but the largest decrease was in
pancreas transplant alone: 62in 2022 compared with 92in 2021. Pancreas-after-
kidney transplants decreased to 46in 2022 from 51in 2021. Meanwhile, outcomes
after pancreas transplant continued to improve and in 2022 were probably the best
they have ever been. Technical failures, immunologic loss, and short- and long-term
graft and patient survival have all shown a positive trend. Multiple events and fac-
tors could explain this paradoxical decrease in pancreas transplant despite improv-
ing outcomes. The decline in pancreas transplantation may be related to newer
diabetes therapies, improvement in medical management of diabetes, decreased risk
tolerance by centers and patients, broader sharing with an increase in cold ischemic
time, and lack of widespread surgical expertise for pancreas procurement and
transplant.
Pancreas transplant recipients can be categorized into three primary groups:
• Simultaneous pancreas-kidney (SPK) transplant: This is the largest group, con-
sisting of patients with insulin-dependent diabetes mellitus and end-stage kidney
disease (ESKD) who receive a pancreas and kidney transplant from a single
deceased donor. SPK transplants account for more than 80% of all pancreas
transplants.
• Pancreas after kidney (PAK) transplant: This group includes patients with ESKD
who have already undergone a kidney transplant, typically from a living donor,
and later receive a pancreas transplant. Both SPK and PAK recipients require
lifelong immunosuppression to maintain the kidney allograft, so the added risk
of a pancreas transplant is mainly related to the increased surgical complexity.
• Pancreas transplant alone (PTA): This group consists of patients with relatively
preserved kidney function who receive only a pancreas transplant. Since these
patients would not otherwise need immunosuppressive therapy, serious consider-
ation must be given to the risks versus benets. While PTA can improve quality
of life and reduce end-organ complications from diabetes, it also subjects the
patient to the risks of surgery and lifelong immunosuppression, including higher
rates of infection and malignancy [129].
4 Primary Care of the Adult Kidney Transplant and Kidney-Pancreas Transplant…