Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5258_Библиотеки_им_академика_М_И_Перельмана.pdf
66
improved long-term allograft function and reduced development of de novo anti-
donor antibodies (DSA), it also carries a higher short- term acute rejection risk [39].
One major downside of this agent is the higher risk of acute rejection within the rst
year compared to the CNI-based regimen, although most of these episodes are mild
and responsive to treatment [39, 41]. As such, the most common strategy is to start
with a calcineurin inhibitor-based regimen and switch to an alternate agent if neph-
rotoxicity develops. Some experts advocate the use of quadruple regimen of belata-
cept, MMF, steroids with temporary tacrolimus bridging in the rst 9–12months to
overcome the risk of early acute rejection while maximizing preservation of long-
term allograft function [42].
• Mammalian target of rapamycin inhibitors (mTORi)
mTOR inhibitors, such as sirolimus and everolimus, inhibit immune cell signal-
ing and lymphocyte activation. Although some centers use these agents as rst-
line components in their maintenance immunosuppression regimens, the use of
mTOR inhibitors as initial agents is generally discouraged, as it has been associ-
ated with increased rates of delayed graft function and poor wound healing [34].
Though they have distinct side effects—such as hypercholesterolemia and pro-
teinuria—they are sometimes switched to in recipients at high risk for recurrent
malignancies, due to their anti-tumor effects [43, 44]. However, studies suggest
mTORi regimens do not consistently outperform CNI-based regimens in long-
term allograft function and may be linked to increased mortality [45].
Table 4.2 summarizes common immunosuppression regimens in kidney trans-
plant recipients. Protocols vary by transplant center and patient factors. For a gen-
eral overview of anti-rejection medications, see Chap. 3.
Table 4.2 Examples of immunosuppression regimens in kidney transplant recipients
Induction immunosuppression Maintenance immunosuppression
Standard or high rejection risk
• Rabbit antithymocyte globulin
(rATG)+intravenous corticosteroids
or
• Alemtuzumab (Campath)+intravenous
corticosteroids
Low rejection risk or unable to receive rATG
• Basiliximab (Simulect
®
)+intravenous
corticosteroids
Standard
• Calcineurin inhibitor (tacrolimus or
cyclosporine)
• Anti-metabolite (mycophenolate or
azathioprine)
• Corticosteroid (prednisone)
Others
Steroid-free
a
• Calcineurin inhibitor (tacrolimus or
cyclosporine)
• Anti-metabolite (mycophenolate or
azathioprine)
Calcineurin-free
a
• Mammalian target of rapamycin inhibitors
(MTORi) (sirolimus or everolimus)
• Anti-metabolite (mycophenolate or
azathioprine
or
• Belatacept + mycophenolate + prednisone
a
May have increased risk of rejection compared to other regimens
B. Boonpheng and I. C. De Castro
67
4.1.5 Assessment ofKidney Function inKidney
Transplant Recipients
Generally, the assessment of kidney function in transplant recipients is the same as
that in the non-transplant chronic kidney disease population. Serum creatinine is
routinely followed and the creatinine-based eGFR is calculated. The creatinine-
based CKD-EPI equation is most commonly used and has been shown to be reason-
ably precise [5]. The 2021 race-free CKD-EPI equation is the most recent adjustment,
which has been shown to perform similarly in kidney transplant recipients to the
2009 CKD-EPI equations that include race [46]. In addition, the 2024 Kidney
Disease Improving Global Outcomes (KDIGO) guidelines recommend using the
eGFR CKD-EPI equation based on both serum creatinine and cystatin C as the most
precise estimate in the general CKD population [5]. However, in kidney transplant
recipients (and other organ transplant recipients), equations that include cystatin C
have not been validated and might be less precise compared to creatinine-based
equations. Therefore, caution is warranted since serum cystatin C can be affected by
multiple non-GFR determinants such as glucocorticoids, inammation and cardio-
vascular disease, which are all common in transplant recipients [47].
A new eGFR equation especially developed and validated for use in kidney
transplant recipients has been shown to outperform the traditional CKD-EPI
2021 equations and potentially improve the accuracy of kidney function assess-
ment in kidney transplant recipients [48]. However, the validated population
consisted mainly of multi-ethnic patients in North America and Europe with
relatively small number of people of African ancestry. The performance of this
new equation in the broader population remains to be validated before wide
adoption in routine practice.
Urine studies including urine analysis and assessment of urine protein excretion
remain an important part of kidney function assessment. For proteinuria or albumin-
uria quantication, spot urine protein to creatinine ratio or urine albumin to creati-
nine ratio is more commonly checked rather than 24-h or timed urine collection due
to convenience of sample collection. However, the limitations of spot urine protein
quantication need to be kept in mind—as in the general CKD population, interpre-
tation of spot urine testing may be limited due to diurnal variation, activity or exer-
cise, acute illness, or a baseline urine creatinine excretion in the extremes of lean
body mass. Increased proteinuria and/or active urinary sediment can be an early
sign of rejection (both acute and chronic), recurrent or de novo glomerular disease,
or chronic allograft nephropathy.
4.1.6 Graft Function Surveillance
The typical approach to monitoring the function of the kidney allograft depends on
the amount of time since transplant and the stability of allograft function.
4 Primary Care of the Adult Kidney Transplant and Kidney-Pancreas Transplant…
68
4.1.6.1 Frequency ofMonitoring
While primary care providers are not likely to be involved in the patient’s care in the
immediate post-transplant period, it is helpful to review the transplant records. In
the rst week following transplantation, kidney transplant recipients are monitored
in the hospital, with daily measurement of the serum creatinine and quantication
of the urine output, taking into consideration any residual pre-transplant urine pro-
duction. Immediate graft function is dened as not requiring dialysis post- transplant,
while delayed graft function (DGF) is dened as the need for dialysis within 1week
following transplant, excluding those patients who require a single dialysis proce-
dure for acute hyperkalemia. Risk factors for DGF include increasing donor age and
KDPI, male sex, increasing cold ischemia time, and receipt of a deceased donor
transplant as compared to an allograft from a living donor [12, 49, 50].
• First week to months post-transplant: After hospital discharge, in the rst weeks
to months post-transplant, the serum creatinine is monitored once or twice per
week, and is expected to decrease in the setting of a properly functioning allograft
until it reaches steady state, at which time the post-transplant baseline creatinine
is established—generally by 3 months or sooner. For most patients, baseline
post-transplant creatinine levels are typically above 1.1mg/dL indicating an esti-
mated GFR of less than 60 mL/min/1.73 m
2
. The nadir will depend on such
variables as the overall quality of the donor organ, donor-recipient size mismatch
(a kidney from a smaller donor will yield a higher baseline creatinine when
implanted in a larger recipient), and ischemic injury—particularly with deceased
donor kidneys and calcineurin inhibitors, which cause renal vasoconstriction.
During this time the recipient’s urine is monitored for the presence of blood,
which is expected initially but should resolve in the weeks following removal of
the double-J ureteral stent, and proteinuria. The early onset of proteinuria, par-
ticularly when it is progressive in patients with a history of an underlying glo-
merular disease such as FSGS, can indicate recurrence of primary disease or de
novo glomerular disease and should prompt further workup.
• Six months post-transplant and beyond: As time from transplant increases
beyond 6months, the need for regular surveillance of allograft function persists
but the frequency of laboratory testing will decrease. It is in this period that the
care of kidney transplant recipients is transitioned to the general nephrologist
and the primary care physician since the risks of complications such as rejection
are thought to have decreased beyond this time. Although protocols vary by cen-
ter and specic patient variables, a typical kidney transplant recipient will require
monthly testing of serum creatinine, electrolytes, complete blood counts,
urinalysis, urine protein quantication, and immunosuppressive drug levels for
at least the rst year and then every 3 months thereafter. The immunosuppressive
drug level goal should be set by the transplant nephrologist based on the patient’s
overall immunologic risk and infection risk. Primary care providers should be
comfortable interpreting the results of these tests and should partner with trans-
plant specialists when an abnormality triggers the need for further evaluation.
B. Boonpheng and I. C. De Castro
69
Table 4.3
Suggested frequency of monitoring for stable kidney transplant recipients
a
Time after transplant
Lab and immunosuppression
monitoring frequency Clinic visit frequency
0–4weeks 1–2 per week 1–2 per week
4–12weeks Every 1week Every 1–2weeks
3–6months Every 2–4weeks Every 1–2months
6–12months Every 2–4weeks Every 2–4months
>1year Every 1–3months Every 3–6months
a
Protocols vary by transplant center
4.1.6.2 Clinical Evaluation
In addition to routine laboratory testing, patients should be seen and examined regu-
larly, as many risk factors for allograft dysfunction and other post-transplant compli-
cations have manifestations on physical examination. As is the case with laboratory
monitoring, if a patient is doing well, the frequency of follow-up visits may decrease
as time from surgery increases, with most long-term follow-up patients requiring
visits approximately once every 3 months (Table4.3). Close attention should be paid
to assessment of volume status, including blood pressure, weight, and peripheral
edema as both volume excess and depletion may cause allograft dysfunction. Patients
should be monitored for physical signs of medication toxicity, such as the develop-
ment of tremor with calcineurin inhibitors, as there is often an association between
the development of neurotoxicity and the incidence of nephrotoxicity [51]. Blood
pressure should be monitored at every visit and patients should also be encouraged
to measure blood pressure at home. Daily home blood pressure monitoring is stan-
dard practice in most programs for at least the rst 3months after transplant [52].
Patients may additionally be encouraged to continue monitoring home blood pres-
sure indenitely at a frequency determined by the patient and the transplant center.
4.1.6.3 Immune Surveillance andAllograft Injury Biomarkers
Some transplant programs incorporate routine post-transplant immune surveillance
in addition to general monitoring of allograft function since serum creatinine and
proteinuria are limited by a lack of sensitivity and specicity. Serum creatinine and
proteinuria are recognized to be late indicators of allograft injury. By the time serum
creatinine and proteinuria abnormalities can be detected, the allograft injury has
already been ongoing and advanced allograft damage has been sustained.
Historically, it was common to perform protocol-driven kidney biopsies. While
some programs continue this practice, it is becoming less common as less invasive
methods of surveillance are developed, shifting the risk/benet ratio.
• Donor-specic antibodies (DSA): The serial measurement of donor-specic
antibodies has become increasingly popular as support for protocol biopsies has
waned [53]. This is a semi-quantitative test that monitors the recipient’s serum
4 Primary Care of the Adult Kidney Transplant and Kidney-Pancreas Transplant…
70
for presence and level of antibodies against donor HLA.Flow cytometry using
microparticles (“beads”) coated with recombinant or soluble HLA antigens rep-
resentative of the donor HLA are used. Measurement of donor-specic antibod-
ies for patients with apparently normal allograft function may allow for earlier
detection of otherwise silent immunological phenomena, and, when positive,
may provide pre-clinical evidence of an allograft that is at risk for developing
overt antibody-mediated rejection. By denition, this type of protocol-driven
testing is performed for all patients, even those with normal allograft function,
and is fundamentally different from testing that is done “for cause,” as in the set-
ting of worsening allograft function, at which time further specialized testing is
strongly indicated regardless of surveillance protocol. Although primary care
providers are not typically the ones ordering these more specialized tests, gener-
alists should become familiar with the specic transplant center surveillance
protocols.
• Donor-derived cell-free DNA (dd-cfDNA): Dd-cfDNA tests for the presence of
extracellular DNA formed by nucleosomes cleaved by different nucleases that
are released in the bloodstream of a transplant recipient. Once released, dd-
cfDNA is rapidly cleared allowing almost real-time assessment of the allograft.
dd-cfDNA represents only a small fraction of total plasma cfDNA with approxi-
mately 90% of cfDNA originating from apoptotic circulating recipient leuko-
cytes. dd-cfDNA can be quantied by quantitative PCR or next-generation
sequencing and is a promising candidate biomarker for enabling comprehensive
monitoring of kidney allograft injury. Multiple techniques for measuring dd-
cfDNA have been reported, including many that do not require a donor sample.
Its baseline value is reached usually within the rst 2-weeks post-transplant.
High proportion of dd-cfDNA arises from nonspecic injury or inammation
observed during rejection or other inammatory events in the allograft—e.g.,
infection, ischemic injury, or de novo or recurrent glomerular disease [53].
Multiple studies have shown that dd-cfDNA detection has very high negative
predictive value (>90%) of ruling out allograft injury or rejection but it remains
a non-specic marker of allograft damage from any cause. It has not been shown
to be sensitive enough for non-severe rejection and has a relatively low positive
predictive value. Additionally, dd-cfDNA may detect inadequate immunosup-
pression resulting in subclinical immunologic allograft damage (once infection
has been ruled out), thus assuming a role in adjusting appropriate trough levels
of immunosuppressive regimens [53, 54]. These tests are commercially available
as AlloSure™, Prospera™, and TRAC™.
• Promising urinary biomarkers include urinary CXCL9 and/or CXCL10, which
are also non-specic markers of allograft injury [54]. Commercially available
test platforms are expected in the future.
• Genomics: Using non-invasive blood-based gene expression prole (GEP) as a
marker of subclinical rejection in patients with apparently normal allograft func-
tion, indicated by serum creatinine, is another promising technology. An exam-
ple of a commercially available platform is TruGraf Kidney™ [53, 54].
B. Boonpheng and I. C. De Castro
71
4.1.6.4 Biopsies
Common indications for renal allograft biopsy are increasing creatinine (typically
>20% increase from baseline) and increasing proteinuria. The risk of performing
kidney allograft biopsies has diminished over recent years, with the routine use of
smaller gauge biopsy needles and ultrasound guidance for the biopsy procedure.
The allograft kidney is located closer to the body surface than the native kidney,
making localization of the organ for biopsy more straightforward than for a native
kidney [55]. Protocol biopsies, as opposed to “for cause” biopsies, are used by sev-
eral centers for research purposes, in highly sensitized patients, in patients in steroid
avoidance, and CNI withdrawal maintenance regimens. The purpose of protocol
biopsies is to identify subclinical rejection for which treatment or immunosuppres-
sion adjustment may result to improved allograft survival. Subclinical rejection is
when there are histologic signs of rejection without overt clinical signs of allograft
dysfunction such as increased creatinine or proteinuria. With newer and almost uni-
form use of induction regimens, the incidence of subclinical rejection has declined.
Paucity of data has meant that clear proof that protocol biopsies improve long-term
graft function and survival is lacking and that the benets of treating subclinical
rejection detected by protocol biopsy in particular are not clear-cut [53]. Moreover,
the optimal timing of protocol biopsies and reliable methods to quantify the histo-
logic changes observed in biopsy specimens have yet to be determined. The cost,
risk and patient inconvenience of surveillance biopsies must be weighed against
potential gains from early interventions guided by the ndings.
4.1.7 Allograft Dysfunction
The differential diagnosis for kidney allograft dysfunction, which is typically evi-
denced by an increase in the serum creatinine or increase in proteinuria, is quite
broad and is inuenced by the time since transplant. Just as with native kidneys,
kidney allograft dysfunction can be characterized as acute or chronic, and can range
from mild to severe. It is important to remember that kidney transplant recipients
remain at risk for all of the common medical conditions to which native kidneys are
susceptible, including ischemic acute tubular necrosis and prerenal azotemia from
intravascular volume depletion, as well as more specic causes of kidney allograft
dysfunction such as surgical complications and rejection. Indeed, as patient and
allograft survival continue to improve, transplant recipients are at increasing risk of
developing chronic allograft dysfunction due to common causes such as diabetic
kidney disease and hypertension-related kidney disease.
An elevated serum creatinine found on routine surveillance blood tests will likely
be managed by the ordering nephrologist. However, there may be other times when
an elevated creatinine is obtained on testing at other times, such as in primary care,
urgent care, or emergency department visits. When a kidney transplant recipient is
found to have a creatinine that is elevated over baseline, if the time course is
4 Primary Care of the Adult Kidney Transplant and Kidney-Pancreas Transplant…
72
uncertain, then evaluation for typical causes of acute kidney injury is indicated,
including assessment for prerenal, intrinsic renal, and post-renal causes based on
history, examination, and laboratory studies, as well as evaluating for infection.
Additionally, one should strongly consider early consultation with the transplant
nephrologist to determine whether evaluation for rejection is needed.
4.1.7.1 Surgical Complications
Most surgical complications are diagnosed early in the post-transplant course and
thus may not come to the attention of primary care providers. It is important to have
some knowledge of specic complications that a patient has experienced, as there
may be implications for the likelihood of developing downstream complications
later on.
• Lymphoceles: At the time of transplantation, the recipient undergoes exten-
sive dissection of the lymphatic network surrounding the iliac vessels. This
can lead to the leakage of lymph and the formation of lymphoceles in approxi-
mately 5–15% of patients [56]. Lymphoceles often resolve without interven-
tion, although sometimes will persist and may require drainage if there is
compression of local structures including the ureter or the renal vein.
Uncommonly, patients may develop chronic lymphedema after kidney trans-
plant, thought to be related to impaired lymphangiogenesis. Several case
reports have suggested that this complication may be more common in patients
treated with mTOR inhibitors [57].
• Urine leak: Early urine leak is not uncommon, occurring in approximately 1–3%
of kidney transplants [58]. Urine leak is usually diagnosed when serum creati-
nine fails to improve and there is high post-operative output from the surgical
drains adjacent to the kidney. Diagnosis can be made by measuring the creatinine
level in the drain uid; if the drain uid contains urine then the creatinine level
will be considerably higher than the creatinine level measured in the serum.
Urine leaks are commonly addressed with either ureteral stenting or surgical
revision. Patients who require more complicated revision may be at risk for
future complications such as stenosis at the site of the ureteral anastomosis.
• Vascular: Vascular complications such as anastomotic stricture are one of the few
anatomical complications that can develop many years after transplantation. As
with native kidney renal artery stenosis, stenosis in the transplant renal artery can
be associated with worsening hypertension and uid retention with an exagger-
ated sensitivity to medications that interfere with the renin-angiotensin-
aldosterone system, such as ACE inhibitors and angiotensin receptor blockers
[59]. A bruit is sometimes present; however the absence of a bruit does not rule
out stenosis, and the presence of worsening hypertension in a kidney transplant
recipient should prompt further investigation including duplex ultrasonography
of the transplanted kidney vasculature and consultation with the nephrologist
involved with the patient’s care.
B. Boonpheng and I. C. De Castro
73
4.1.7.2 Acute Rejection
As with many issues related to kidney transplantation, the type of rejection to which
a kidney allograft is most susceptible depends on the time since transplantation.
• Hyperacute rejection is caused by preformed donor-specic antibodies, as in the
case of an ABO incompatible donor. It presents immediately within the rst
hours after transplantation. This complication is relatively rare in the modern era
of transplantation, as preformed antibodies will be routinely detected by the per-
formed complement-dependent cytotoxicity (CDC) crossmatch, and a positive
crossmatch is considered a contraindication to transplantation.
• Acute rejection tends to present in the rst weeks to months after transplantation,
but it can also occur years after transplant especially when patients are not adher-
ent with their immunosuppression regimen or new medication interactions have
resulted in signicant subtherapeutic levels of immunosuppression. Acute rejec-
tion may be cellular—caused by the activation and proliferation of T-cells,
antibody- mediated—caused by the development of antibodies against donor
HLA antigens, or both. Acute rejection may present with decreased urine output,
allograft tenderness, and fever. However, in the era of modern immunosuppres-
sion most episodes of acute rejection are asymptomatic and are identied only
after an increase in the serum creatinine is observed. Creatinine elevation is gen-
erally thought to be a late marker for injury, at which time there is likely already
considerable histological injury—hence the move toward earlier detection strate-
gies such as DSA and/or dd-cfDNA monitoring protocols discussed above.
When there is suspicion for acute rejection—for example, an acute rise in the
creatinine is found in a patient who reports missing doses of immunosuppression
and/ or has low levels of immunosuppression—the transplant team should be con-
tacted urgently to discuss arranging a kidney biopsy. Standardized histological de-
nitions for acute cellular and antibody-mediated rejection have been established by
the Banff consortium [60, 61]. In general, acute cellular rejection is associated with
the presence of inammation in the renal tubules (tubulitis), interstitial compart-
ment and in the renal arteries (arteritis). Antibody-mediated rejection is suggested
by the involvement of small blood vessels (capillaritis) due to interaction between
antibodies and the endothelial cells resulting in glomerulitis and inammation of
peritubular capillaries; deposition of C4d, a split product in the complement cas-
cade, in the peritubular capillaries can sometimes be seen as well as the detection of
DSAs or other non-HLA antibodies.
Treatment of acute rejection depends on the specic type of rejection (cellular
vs. antibody-mediated) and the histological severity. Treatment for cellular rejection
often mirrors induction immunosuppression, with mild cases receiving pulse doses
of corticosteroids and more severe cases necessitating the use of lymphocyte-
depleting antibody preparations such as rATG [62, 63]. Treatment for antibody-
mediated rejection also depends on severity, as determined both by histology and by
antibody titers, and tends to target both the existing antibodies and the B-cells
responsible for antibody production. Protocols vary between centers but will
4 Primary Care of the Adult Kidney Transplant and Kidney-Pancreas Transplant…
74
typically employ a combination of intravenous immunoglobulin (IVIG), anti-CD20
antibodies such as rituximab, and plasmapheresis [64].
Rejection episodes have important clinical and prognostic signicance. The
development of one episode of acute rejection increases the risk for subsequent
rejection episodes. Furthermore, the cumulative effect of additional immunosup-
pressive agents used to treat rejection can signicantly increase the risk of develop-
ing short-term infectious complications, as well as long term complications such as
malignancy (see Chap. 8).
4.1.7.3 Chronic Allograft Nephropathy
The most common cause of kidney allograft failure after the rst year is a poorly
dened and incompletely understood entity that has historically been termed
chronic allograft nephropathy, transplant glomerulopathy or chronic rejection,
and more recently has been referred to as chronic allograft injury [65]. As there
are no consensus clinical or histopathological criteria for this diagnosis, the exact
incidence and pathophysiology remain uncertain. In general, a diagnosis of
chronic allograft injury is made when there is allograft dysfunction after the rst
3months post- transplant and no evidence of acute rejection or acute drug-related
injury. The histological criteria for diagnosis are complex, and under frequent
revision; however, the hallmark of chronic allograft nephropathy is the develop-
ment of interstitial brosis and tubular atrophy (IFTA) which may be graded as
mild, moderate, or severe [66].
The mechanisms underlying the development of chronic allograft nephropathy
are not fully understood; however, one unifying factor seems to be the presence of
chronic inammation in the allograft leading to progressive IFTA as described
above. Some of this inammation is likely to be immune-mediated, as it has been
observed that less well-matched allografts are more likely to develop chronic
allograft nephropathy [67]. Moreover, removal of immunosuppression, as in cases
of medication nonadherence, has been associated with the accelerated development
of chronic allograft nephropathy, underscoring the importance of life-long immuno-
suppression [67, 68].
4.1.8 Other Complications andPearls
4.1.8.1 BK Nephropathy
BK virus, a ubiquitous human polyomavirus, is a unique cause of complications in
kidney transplant recipients. Although most humans have been exposed to poly-
omaviruses, these viruses tend only to cause disease in immunocompromised
B. Boonpheng and I. C. De Castro
75
individuals. In adult kidney transplant recipients, almost all cases are due to reacti-
vation of the latent virus in the setting of immunosuppression. BK virus nephropa-
thy (BKVN) is a form of tubulointerstitial nephritis which occurs in the kidney
allograft of approximately 5% of kidney transplant recipients [69].
• Risk factors and pathophysiology: Primary BK virus exposure typically occurs
at a young age via respiratory secretions. The virus persists in the renal epithe-
lium and thus post-transplant complications associated with BK virus are thought
most likely to be derived from the donor. Although retrospective studies have
attempted to nd an association with specic immunosuppressive regimens, the
most signicant risk factor for the development of BKVN appears to be a high
degree of immunosuppression, regardless of the particular type or number of
agents used [69].
• Clinical presentation and diagnosis: BKVN typically presents as a slow, progres-
sive increase in the serum creatinine. High blood viral load can provide a strong
clue (generally if plasma viral load remains persistently ≥10,000 copies/mL for
more than 3weeks) but denitive diagnosis is made on kidney biopsy which will
demonstrate the presence of characteristic histopathologic changes and a posi-
tive immunohistochemical stain for the SV40 antigen. A positive SV40 stain is
highly specic for polyoma virus nephropathy but is less sensitive, owing to the
patchy nature of BKVN and the potential for absent virus on a small sample of
kidney tissue [69]. The diagnosis is supported by the presence of BK virus DNA
in the urine and in the blood, as detected by quantitative PCR.
• Screening: The presence of BK viruria and viremia should signicantly predate
the development of clinically evident BKVN.For this reason, it is common prac-
tice at most transplant centers to screen routinely for BK virus in the urine or
blood every 3–6months during the rst 2years after transplant. When BK viruria
is detected in the setting of normal allograft function it may prompt further test-
ing for BK viremia, and/or pre-emptive reduction in immunosuppression.
• Treatment: When BKVN nephropathy is diagnosed, the mainstay of treat-
ment is reduction in immunosuppression. Adjunctive use of intravenous
immunoglobulin, which generally contains antibodies against major geno-
types of BK virus, is sometimes considered in those who do not respond to
reduction to immunosuppression, are at high-risk for rejection, or have
known hypogammaglobinemia. Antiviral therapies such as leunomide or
cidofovir are sometimes used for persistent cases, although data is lacking
and largely anecdotal [69].
• There are infrequent case reports of immunocompromised individuals develop-
ing BKVN in the native kidney—this evaluation may be challenging and is best
left to the managing nephrologist [70].
• Ureteral stenosis is a relatively rare complication associated with BK virus. It
can present with hematuria and hydronephrosis with or without increase in serum
creatinine.
4 Primary Care of the Adult Kidney Transplant and Kidney-Pancreas Transplant…