Kidney allograft biopsy is beneficial in diagnosis in case of DGF to Rule out acute rejection ,recurrence of original disease ,BKV nephropathy ,PTLD in some cases .and it also very important in determination of therapy in some cases like acute rejection :if antibody mediated rejection we will go with IVIG ,plasmapheresis and rituximab and if Cell mediated we will go with steroids ,Thymoglobulin in some cases .
So we should have solid indications for kidney biopsy as it has complications like hematoma ,bleeding and some cases it may lead to graft loss.
This article was published in American Journal of transplantation ,it recommended some indications for kidney allograft biopsy like:
1- unexplained rise in serum creatinine after kidney transplantation
2- serum creatinine did not reach to baseline after treatment of acute rejection
3- every 7-10 days during DGF
4- If expected kidney function was not achieved during the 1st 1-2 months after transplantation.
5- In case of proteinuria after kidney transplantation either new onset or unexplained proteinuria >3 g/24 hours.
they talked also about AKI definition and serum creatinine and that we cannot depend on it solely for diagnosis of acute rejection .
In case of DGF we should also rule out causes like dehydration ,CNI toxicity,urinary obstruction
They talked about role of protocol biopsy and its rule in diagnosing sublinical rejection and that sub clinical rejection leads to poor graft survival,some studies showed that sub clinical rejection is more in patients taking Azathioprine and cyclosporine and less in patients taking tacrolimus and MMF.
But still there is no evidence that protocol biopsy Is mandatory in diagnosing sub clinical rejection.
CNI toxicity and CAI also can be diagnosed by biopsy
In our center same indications for acute conditions but we do not perform protocol biopsy
Shereen Yousef
3 years ago
Kidney allograft biopsies may be performed for clinical indications, or protocol.
indicated biopsy is done when there is changes in the patient’s condition either clinical or laboratory.
protocol biopsy is done on a predefined intervals after transplantation, regardless of kidney function.
It is recommended to do allograft biopsy in the following conditions:
1 persistent, unexplained increase in serum creatinine.
2 serum creatinine has not returned to baseline after treatment of acute rejection.
3 every 7–10 days during delayed graft function.
4 if expected kidney function is not achieved within the first 1–2 months after transplantation.
5 new onset of proteinuria,
unexplained proteinuria ≥3.0 g/g creatinine or ≥3.0 g per 24 hours.
*Biopsies for an increase in serum creatinine;
Correction of any reversible cause of rising s cr must be done before biopsy these causes includes dehydration, urinary obstruction or acute CNI toxicity (by demonstrating high blood levels).
Persistant 25–50% increase in s cr over baseline (after excluding correctable factors) indicates biopsy to detect the nature of kidney injury including rejection, infections like BKV nephropathy, recurrent or de novo kidney disease or PTLD.
*Biopsies for DGF:
DGF ;is graft function low enough to require dialysis in the first week after kidney transplantation, or lack of improvement in pretransplant kidney function.
acute rejection during DGF is higher than in patients without DGF and s creat can’t be used to monitor graft function as the patient is on dialysis.
few data to determine when and how often biopsies during DGF should be obtained. But some studies performed biopsy every 7-10 days and acute rejection can be present for the first time on the second, third or even fourth biopsy.
*New-onset proteinuria :
Biopsy is also indicated for New-onset proteinuria which may indicate treatable causes of graft dysfunction, including acute rejection and thrombotic microangiopathy.
In patients who already have proteinuria, an increase exceeding a threshold usually defined as ‘nephrotic range’ proteinuria, for example ≥3.0 g/g creatinine or ≥3.0 g/24 h, may indicate treatable causes of graft dysfunction.
*Protocol biopsies:
protocol biopsies can detect subclinical acute rejection, CAI and CNI nephrotoxicity. Detection and treatment of subclinical acute rejection may be beneficial in preventing CAI and improves long-term graft survival.
the combination of tacrolimus and MMF is associated with lower incidence of subclinical rejection than cyclosporine regimen and the , use of protocol biopsies for diagnosis of subclinical rejection may not be appropriate in tacrolimus- and MMF-treated patients.
Protocol biopsies may be expensive but with excellent safty .
In my practice we dont do protocol biopsy
And its always done upon clinical or lab abnormalities
Last edited 3 years ago by Shereen Yousef
Ibrahim Omar
3 years ago
1- In your own words, summarise this article :
multiple causes can contribute to the decline in kidney graft functions after transplntation as graft rejection, delayed graft function, CNI toxicity, viral infections, lymphoproliferatrive disorders, …. etc. sometimes, a specfic intervention is needed to manage a certain cause.
kidney allograft biopsy is the most sensitive tool for diagnosis of most cuases. it is usually indicated if there is a specfic indication. however, kidney allograft biopsy was sugested to be done at certain intervals for earlier diagnosis of some disorders that need specific treatments. this was called protocol biopsy. the effects of protocol biopsy on graft function outcome was evaluated in many studies. most of these studies reported better graft outcome, especially the reported major complications of kidney biopsy are now extremly rare. however, the timing and frequency of protocol biopsy are still to be defined.
specfic indications of kidney allograft biopsy include the following :
1- persistant unexplained high S. creatinine.
2- acute rejection that is resistant to standard treatment as other pathologies may appear on top of acute rejection.
3- delayed graft function as the incidence of acute rejection is higher in those patients.
4- new onset or nephrotic range proteinuria.
2- Please reflect on your practice if possible.
I will adhere to the local policies then discuss with senior colleagues the possible application of protocol biopsy.
Wessam Moustafa
3 years ago
Kidney allograft biopsy is either indicated or protocol biopsy
Where indicated biopsy refers to changes in the patient clinical condition of laboratories.
Protocol biopsy is used for screening .
Biopsy should be taken with any unexplained persistent rise of serum creatinine to detect of differentiate between types of immunological injury and treat accordingly .
Biopsies also are indicated when there is failure to regain the function after treatment as this may indicated an added pathology .
In cases of delayed graft function, serum creatinine can’t point to when we should take a biopsy , so in such situations periodic biopsies should be obtained because incidence of acute rejection are higher with DGF.
Protocol biopsies may be beneficial in detection of subclinical rejection which doesn’t present with decline in GFR , treatment of such rejections is beneficial of the long term in reducing incidence of acute rejections and long term graft survival .
Other conditions that can be detected on protocol biopsies
include CNI toxicity, recurrent disease, transplant glomerulopathy, CAI and BKV nephropathy.
Biopsies are safe with major complications occur at an incidence of 1%
Protocol biopsies are expensive and this should be considered.
Heba Wagdy
3 years ago
Kidney allograft biopsy is either protocol biopsy (done at predefined time regardless kidney functions) or indicated biopsy (performed only with clinical or lab indication).
It detect histological changes requiring treatment Unexplained increase in serum creatinine
is mostly due to intragraft parenchymal injury, other reversible causes should be ruled out as dehydration, urinary obstruction or acute CNI toxicity before biopsy. Adequate biopsy can define causes of allograft dysfunction as rejection, BK virus nephropathy, recurrent or de novo kidney disease and allograft infiltration as PTLD. biopsy can determine type and severity of AR biopsy for lack of improvement of graft function
It is indicated to determine if there is new pathological process requiring additional treatment Biopsy for DGF: DGF is failure of improvement of kidney functions with need for dialysis in the first week post transplant
As the patient is already treated with dialysis due to DGF, so periodic biopsies are performed to diagnose AR, studies showed that AR may present on the second, third or fourth biopsy except if signs of resolving DGF appeared Protocol biopsy:
detect subclinical AR, CAI and CNI nephrotoxicity before decline in kidney functions
Studies suggested that detection and treatment of subclinical AR detected by protocol biopsies is beneficial to avoid CAI, decrease graft survival and improve the outcome.
The need for protocol biopsy is determined by the maintenance immunosuppression as Tac and MMF are associated with less incidence of AR so not appropriate to perform protocol biopsies for diagnosis of subclinical rejection.
protocol biopsies are expensive and detection of subclinical rejection is more expensive so RCTs are needed to determine the benefits and harms of protocol biopsies
Allograft biopsies are safe, the risk of reported major complications is 1% includes substantial bleeding, macroscopic hematuria, peritonitis or graft loss.
Biopsy may be hazardous in presence of bleeding disorder, infection or presence of large fluid collection
It is recommended to perform allograft biopsy with persistent unexplained increase in serum creatinine.
It is suggested to perform allograft biopsy:
after treatment of AR without improvement of serum creatinine to baseline.
every 7-10 days during DGF
within first 1-2 months after transplant if expected kidney functions not achieved
with new onset proteinuria and unexplained proteinuria >3g/24hours
saja Mohammed
3 years ago
this chapeter from american journal of transplantation in 2009 , address the recommendiation of indicated graft biopsy and protocal biopsies post kideny transplantation and we can see the evel of evidnce is low from 2C-2D , based on centre experience or expert opinion however the indication of garft biopsy its either part of protocal biopsy in which the garft biopsy performed in timely fixed intervales regardless of the garft function it will help to detect SCR , its safe but associated with high cost and patient preference one of the important factor to be consider , also its benefit duatful since the introduction of tacrolimus and MMF in maintenance protocals
while indicated graft biopsy is still widely used and indicated whenever thereis persistant reduction of graft function , DGF ,after excluding dehydration , CNI effect , urinary obsruction , another important indication worsening protienuria like urine p/c more than 3 gm/gm or 24h urine more than 3 gm
denov renal disease or recurrence of glomerulonephritis , BKV nephropthy
also indicated garft biopsy after 7-10 days from failed acute rejection treatment
in general both indicated garft biopsies and protocal biopsies considered safe procedurs can be done as OP , with less complication like bleeding in 1% and risk of garft loss < 0.03% , but protocal biopsies more cost and should consider patient preference and complaince as one of improtant factors
in our centre we only do graft biopsies once indicated
Radwa Ellisy
3 years ago
Indication of graft biopsy
1- As a part of protocol biopsy
To detect Subclinical rejection, CNI toxicity, or chronic allograft nephropathy
2- Indication biopsy:
a. Deterioration in kidney function
After exclusion of laboratory and individual variabilities
With persistent (25-50% elevation from baseline) after exclusion Dehydration, CNI induced toxicity, or urinary tract obstruction
The biopsy here is the gold standard to define the etiology, severity, appropriate treatment and od added prognostic value
b. Proteinuria (> 3 gram/ 24 hour)
c. Delayed graft function
To exclude associated or complicating acute rejection
No consensus about time or interval but every 7-10 days according to RCTs
d. Failed to achieve expected renal function after 1-2 months of transplantation
e. Failure of improvement of renal function after treatment of acute rejection to exclude another associated pathology and to determine the appropriate treatment (weak level of evidence) In our practice
We only do indication biopsy except for the last indication
Tahani Hadi
3 years ago
1-Graft biopsy has been done in different transplant centres either due to specific reasons ( indicated biopsy ) or to detect early different complications and to start early management( protocol biopsy).
2-This article explain the indications, benefits and risks for doing protocol graft biopsy in certain intervals .
3-Main patients who are needed to do graft biopsy:
– patient with elevated serum creatinine level for unknown reasons after excluding dehydration, infection ,CNI toxicity and obstruction.
– patient with delay graft function requiring dialysis with fluctuating S.creatinine level, graft biopsy must be done every 7 -10 days interval to detect any acute rejection as those patients are at risk to develop AR .
– new onset proteinuria or change in preexisting proteinuria level to detect recurrent or de novo kidney disease.
4- the biopsy risks and complications should be discussed with the patient before doing the biopsy like bleeding, hematuria,obstruction or even graft loss in addition to the cost .
5- some indications for graft biopsy or early detection of certain conditions like BKV nephropathy, de novo kidney disease and even CNI toxicity can not change the result or the outcome of these conditions.
6- subclinical rejection is affected and can be decreased by the type of immunosuppression regimen so it’s not mandatory to do graft biopsy for those patients on Tacrolimus and MMF .
Dalia Eltahir
3 years ago
Indications for kidney allograft biopsy 1- “a persistent, unexplained increase in serum creatinine. :” Serum creatinine persistently rise (above 30%) ,and causes like dehydration and obstruction should be excluded .Another diagnoses like rejection, infections can be reached . 2- “ serum creatinine has not returned to baseline after treatment of acute rejection. ”: if the patient received ant rejection and does not respond another diagnosis like ATN, CNI toxicity or infection. 3- “ expected kidney function is not achieved within the first 1–2 months after transplantation. 4- “If there is: new onset of proteinuria or unexplained proteinuria ≥3.0 g/g creatinine or ≥3.0 g per 24 hours. 5- Protocol biopsies : DGF can be associated with superimposed acute rejection. Protocol biopsies are indicated if DGF does not resolve and are advised to be every 7-10 days.
Subclinical rejection can occur without change in renal function . subclinical acute rejection in 14-day protocol biopsies was associated with poorer 10-year graft
survival. Treating subclinical rejection detected on protocol biopsies will result in reduction of acute rejection episode, histopathological changes and serum creatinine at 2 year.
Major complications of protocol biopsy are substantial bleeding, macroscopic hematuria with ureteric obstruction, peritonitis or graft loss.
The risk of major complications from renal graft biopsy is only 1% and of graft loss is 0.03% . In our country we do allograft biopsy on specific indications, which include acute kidney injury which not explained by clear causes, suspicion of antibody mediated rejection, suspicion of recurrence of primary disease and new onset proteinuria. We didn’t do protocol biopsy .
Esmat MD
3 years ago
Kidney allograft biopsy is performed in two settings, either indicated biopsy (when a change in kidney function occurs) or protocol biopsy (obtains at a predefined interval regardless of kidney function). Both biopsies are done with the aim of improving kidney function.
Rational
After exclusion of the causes such as obstruction, dehydration, and high CNI levels, intragraft parenchymal process, such as acute rejection, CAN, drug toxicity, recurrent or de novo kidney disease should be considered.
The optimal diagnosis and treatment of kidney dysfunction requires a kidney biopsy.
DGF is defined as a need for dialysis in the first week after kidney transplant. In DGF, change in serum Cr is not useful for ruling out acute rejection. So, protocol biopsy may be needed (biopsies have been obtained every 7-10 days), although biopsy may no longer be needed when there are signs that DGF is resolving.
New onset proteinuria and in patients who already have proteinuria, an increase beyond the threshold of 3 gr/day indicates treatable causes of graft dysfunction, including acute rejection and TMA.
A persistent increase in the plasma Cr level outside the normal range (25-50% over baseline in different studies) after ruling out of reversible causes is an indication of kidney biopsy to detect treatable causes of kidney injury, including rejection, infections like BK virus, recurrent or de novo kidney disease and infiltration with PTLD and appropriate treatment of these different etiologies of kidney injury.
In addition, biopsy is indicated in the case of acute rejection that does not respond to first line treatment with steroids.
The patient should be assessed for contraindications of kidney biopsy such as bleeding diathesis, large fluid collection, and infection.
Protocol biopsies
It is proposed thatprotocol biopsies can detect subclinical acute rejection, CAI and CNI nephrotoxicity. Detection and treatment of subclinical acute rejection may be beneficial in preventing CAI and reduced long-term graft survival. Treatment of subclinical rejection may improve outcomes.
The baseline immunosuppression therapy is an important determinant of subclinical rejection. Since the combination of tacrolimus and MMF is associated with lower incidence of subclinical rejection than cyclosporine-based therapy. Therefore, use of protocol biopsies for diagnosis of subclinical rejection may not be appropriate in tacrolimus- and MMF-treated patients.
The safety profile of protocol kidney biopsy is acceptable, with 1% and 0.03% risk of major complications and incidence of graft loss, respectively. Protocol biopsies, however, may be expensive.
Ben Lomatayo
3 years ago
Background; Kidney allograft biopsies are either indicated biopsy where there is graft dysfunction or protocol biopsy regardless of graft dysfunction. DGF is a form of AKI which requires dialysis in the first week after transplantation.
Rationale ; a) Unexplained rising serum creatinine, b) diagnosis & treatment of of allograft dysfunction, c) DGF, d) proteinuria
Biopsies for an increase in serum creatinine ; an unexplained increase in serum creatinine( > 30%) is mostly due to reduced renal function and represent good marker for subsequent graft failure(144,145).Reversible cause of increase creatine( e.g. dehydration, ureteric obstruction etc) should be excluded before allograft biopsy. The biopsy may reveal diagnosis such as acute rejection, BKV nephropathy, recurrence or de novo kidney disease, PTLD. Allograft biopsy may be useful to give information about type & severity of rejection(109).
Biopsy for lack of improvement in graft function; failure of renal function to improve after treatment of rejection, may indicate hidden diagnosis which requires different treatment( eg BKV nephropathy, CNIs toxicity, ATI). All these condition can not be diagnose without allograft biopsy.
Biopsies for DGF; acute rejection is more likely to be seen in patients with DGF than those without DGF(166-168). In fact biopsy is required every 7 to 10 days in patients DFG(167) until improvement in renal function or reduction in proteinuria is observed.
Protocol biopsies ; rejection and CNI toxicity can be seen in absence of reduce renal function and therefore protocol biopsies can of value here. Subclinical rejection can be associated with reduced graft function(176-179).Now days because of use of tacrolimus and MPA , the incidence of subclinical rejection is significantly reduced compared to the era of cyclosporine and azathioprine( 104,113,176,180,181).. other conditions that can diagnosed by protocol biopsies are CNI toxicity, CAI, BKV nephropathy, recurrent disease, & TG
Safety ; generally allograft biopsies are safe procedures(180, 184) and risks are bleeding, macroscopic haematuria with ureteric obstruction, peritonitis, graft loss. This occur in approximately 1% of the procedures(185-187%) and can done as an outpatient procedure. complications are seen in the first 4 hours following the biopsy.
Cost ; This is expensive procedure and can the cost can be up to US$ 3000/ biopsy according to Mayo clinic reports. The diagnoses of acute clinical rejection can cost up to US$ 114000(104)
In my practice we do biopsies routinely in cases of ; a) DGF, b) Allograft kidney dysfunction. We do not do the protocol biopsies
Hinda Hassan
3 years ago
Indications for kidney allograft biopsy 1- “a persistent, unexplained increase in serum creatinine. (1C):” when serum creatinine persistently rise (above 30%) ,and causes like dehydration, obstruction and toxicity of CNI are ruled out.They will help in reaching diagnoses like rejection, infections , kidney disease or PTLD. 2- “ serum creatinine has not returned to baseline after treatment of acute rejection. (2D)”: if rejection does not respond to treatment as the cause could be another pathology like ATN, CNI toxicity or infection. 3- “ expected kidney function is not achieved within the first 1–2 months after transplantation. (2D)” 4- “If there is: new onset of proteinuria (2C) or unexplained proteinuria ≥3.0 g/g creatinine or ≥3.0 g per 24 hours. (2C)” 5- Protocol biopsies : DGF can be associated with superimposed acute rejection. Protocol biopsies are indicated if DGF does not resolve and are adviced to be every 7-10 days.
Subclinical rejection can occur without change in renal function and its prevalence range
from 13% to 25% at 1–2 weeks, 11–43% at 1–2 months, 3–31% at 2–3 months and 4–50% at 1 year .
subclinical acute rejection in 14-day protocol biopsies was associated with poorer 10-year graft
survival. Treating subclinical rejection detected on protocol biopsies will result in reduction of acute rejection episode, histopathological changes and serum creatinine at 2 year.
Major complications of protocol biopsy are substantial bleeding, macroscopic hematuria with ureteric obstruction, peritonitis or graft loss.
The risk of major complications from renal graft biopsy is only 1% and of graft loss is 0.03% .
The cost is 3000$ per biopsy .114 000$ are the cost for detecting only one case of acute subclinical rejection . So the cost and patient preference are needed to be considered while weighing the benefit-risk of performing protocol biopsies .
in our practice in Sudan we perform graft biopsies for all mentioned indications except for protocol biopsies.
Professor Ahmed Halawa
Admin
3 years ago
THANK YOU All FOR YOUR CONTRIBUTIONS
Reem Younis
3 years ago
-Kidney biopsy either indicated kidney biopsy or protocol kidney biopsy. An ‘indicated biopsy’ is prompted by a change in the patient’s clinical condition and/or laboratory parameters. A ‘protocol biopsy’ is one obtained
at predefined intervals after transplantation, regardless of kidney function.
Indications of diagnostic biopsy:
1. An unexplained rise in serum creatinine 25–50% increase over baseline.
2. Failure for improvement in graft function and not a response to antirejection treatment.
3. Delay graft function.
4. if expected kidney function is not achieved within the first 1–2 months after transplantation.
5. If there is new-onset proteinuria that may indicate treatable causes of graft dysfunction, including acute rejection and thrombotic microangiopathy and in patients who already have proteinuria, an increase exceeding a threshold ‘nephrotic range’ proteinuria( ≥3.0 g/g creatinine or ≥3.0 g/24 h )that may indicate treatable causes of graft dysfunction.
-Protocol biopsy help in detecting and treating subclinical acute rejection and CNI toxicity but RCTs are needed to determine when the benefits of
protocol biopsies outweigh the harm
Ahmed Omran
3 years ago
Renal allograft biopsy is needed in main 2 situations ;protocol biopsy and when there is indication.
Protocol biopsy
planned biopsy in high risk patients aiming detection of subclinical acute rejection ,chronic allograft rejection and CNI toxicity.
Biopsy clinically indicated
1-Unexplained persistent rise in serum creatinine of more than 30% above baseline searching for underlying cause like acute rejection, recurrent disease, infection….
2-Treatment of acute rejection not associated with return of graft function to baseline.
3-to detect acute rejection in DGF
4-Unsatisfactory graft function in 1-2 months following Tx.
5-Worsening or new onset proteinuria more than 3 gm daily
With use of ultrasonography, procedure complications became very low ,but protocol biopsy needs patient education and compliance
Protocol biopsy is implemented usually to detect subclinical AR, chronic allograft injury and CNI toxicity. In era of Tac and MMF using immunosuppressive regimens, the role of protocol biopsies is decreasing ;essentially in high risk patients.
Mahmud Islam
3 years ago
Transplanted kidney biopsy although safe most of the time may be challenging. can be performed either on purpose for an indication such as an unexplained abrupt deterioration in renal function, new-onset proteinuria, or delayed graft function. during the course of DGF acute insults may be added on top and acute rejections as already probable with increased incidence during the course acute rejections may be missed during that table. for this reason, repetitive biopsies are indicated and may be very useful unless clinical scenarios suggest improvement otherwise. some studies showed tubular atrophy and fibrosis without effect on creatinine clearance as well as close/similar incidence of dysfunction that could not overweight the cost of repetitive biopsies and probable risks.
Mujtaba Zuhair
3 years ago
Kidney allograft biopsy can be protocol biopsy (done at regular interval post transplantation irrespective of kidney function) and indication biopsy (done when there is clinical indication ).
Indications :
unexplained increase in serum creatinine.
every 7-10 days in cases of delayed graft function .
the serum creatinine didn’t return to baseline after treatment of acutr rejection.
New onset proteinuria.
increase in pre-existing proteinuria to more than 3 gram/24 hours.
Protocol biopsy is bone at regular intervals to detect subclinical rejection. in the era of cyclosporine and azathioprine , the protocol biopsy was useful to detect subclinical rejection and treatment of subclinical rejection was associated with better graft survival and lower incidence of clinical rejection.
But in the era of tacrolimus and MMF , the incidence of subclinical rejection is much lower , because these drugs are more potent immunosuppressive drugs and the role of protocol biopsy is less important.
Complications :
sever macroscopic hematuria , urinary obstruction , peritonitis , graft loss . the incidence of these sever complication is low (<1%).
Mohamad Habli
3 years ago
Kidney allograft biopsies are performed either on scheduled basis as in protocol biopsies, or upon specific indications.
A protocol biopsy is performed timely irrespective of kidney function, whereas allograft biopsy is done whenever indication exist.
Kidney allograft biopsy is recommended when there is a persistent, unexplained increase in serum Cr. It is suggested that biopsy should be performed in the following circumstances: creatinine has not returned to baseline after treatment of acute rejection, every 7–10, if expected kidney function is not achieved within the first 1–2 months after transplantation, new onset of proteinuria , unexplained proteinuria ≥3.0 g/g creatinine during delayed function.
If Cr is increasing persistently, and is not explained by dehydration, urinary obstruction, or high CNI levels, kidney biopsy is indicated. The biopsy is also indicated to rule out infection (BKV nephropathy) in the settings of acute kidney injury and possible recurrence of primary disease or de novo renal disease or PTLD.
In my practice, allograft biopsy is done only upon specific indications, which include acute kidney injury which not explained by clear causes, suspicion of antibody mediated rejection, suspicion of recurrence of primary disease and new onset proteinuria.
Mohammed Sobair
3 years ago
1. In your own words, summaries this article
Kidney allograft biopsies: Either:
Indicated biopsy:
Is one that is prompted by a change in the patient’s clinical condition and/or laboratory
parameters?
Protocol biopsy:
One obtained at predefined intervals after transplantation, regardless of kidney function.
Indication:
Increase in serum creatinine persistent, unexplained.
Serum creatinine has not returned to baseline after treatment of acute rejection.
Delayed function, every 7–10 days.
Kidney function as expected is not achieved within the first 1–2 months after
transplantation.
New onset of proteinuria .
Unexplained proteinuria ≥3.0 g/g creatinine or ≥3.0 g per 24 hours.
Protocol biopsies:
Many disturbance of KT function can occur in absence of a measurable decline in
kidney function. e.g.:
Acute rejection, CAI and CNI toxicity.
protocol biopsies can detect clinically inapparent (subclinical) acute rejection, CAI and
CNI nephrotoxicity.
Treatment of subclinical rejection may improve outcomes.
Other conditions that can be detected by protocol biopsies include recurrent disease,
transplant glomerulopathy and BKV nephropathy.
Major complications from protocol biopsy approximately 1%:
Bleeding.
Macroscopic hematuria with ureteric obstruction,
Peritonitis .
graft loss.(0.03%)
1. Please reflect on your practice if possible.
In our practice we do indicated biopsy only no protocol biopsy is done.
Weam Elnazer
3 years ago
summary:
The subject of kidney allograft biopsy is addressed in the article, regardless of whether it was an indicated biopsy or a protocol biopsy.
Indicated biopsy if there was a creatinine rise where the cut-off threshold was not precisely defined but the increase was anticipated to be 30 per cent more than the baseline. After ruling out reversible reasons such as dehydration, CNI toxicity (high blood levels), illness, or nephrotoxic medicines, a kidney biopsy is routinely performed. Having a higher risk of acute rejection in DGF patients, which necessitates the use of dialysis in the first week after transplantation, justifies certain institutions doing protocol biopsy numerous times in the DGF for the diagnosis of CNI toxicity, BKV nephropathy, or acute rejection.
While the appropriate biopsy is performed in the DGF if there are no reversible causes of AKI present, the DGF does not do the procedure.
A protocol biopsy is performed in high-risk, sensitized persons who have a history of chronic kidney disease or who have had more than one transplant, in order to identify subclinical rejection, according to my practice.
There is no debate that increasing creatinine-and-or proteinuria or increasing.
reflect on practice:
the indication of renal biopsy, I already apply in my practice. But the protocol biopsy we are not applying because to confess the patient about the biopsy with normal renal function and the possibility of post renal biopsy complication is very difficult.
Amit Sharma
3 years ago
1. In your own words, summarise this article
Renal allograft biopsies are performed in 2 specific instances, namely indicated biopsies and protocol biopsies. An indicated biopsy is one which is done due to altered laboratory parameters or a due to change in clinical condition of the patient. Protocol biopsy is done at a pre-determined time after transplant, with no correlation with laboratory or clinical parameters.
In current era of real-time ultrasound guided kidney biopsies, the rate of complications is very low (<1%) which include major bleeding and hematuria with ureteric obstruction. Rarely (0.03%), a graft can be lost.
A) The conditions warranting an indicated biopsy include:
1) Persistent rise in serum creatinine by >30% above baseline, not explained by apparent causes like dehydration, obstruction, high CNI levels: The biopsy is needed to rule our renal parnchymal cause like acute rejection, infection (BKV nephropathy), recurrent or de novo renal disease or PTLD.
2) Absence of improvement of graft function to previous levels after treatment of acute rejection: This may be due to some other pathology superimposing on the acute rejection (like ATN, BKV nephropathy etc), which needs to be identified and treated.
3) Delayed Graft Function (DGF): A biopsy should be performed once in 7-10 days in patients with DGF to rule out supreimposed acute rejection.
4) If graft function is sub-optimal: Biopsy should be done to find out the cause of a less than satisfactory graft function even 1-2 months after transplant.
5) Proteinuria: Worsening of a pre-existing proteinuria to more than 3 gram per day or a new-onset proteinuria may be a marker of rejection, thrombotic microangiopathy, or recurrent/ de novo glomerular disease for which a biopsy is required.
B) A protocol biopsy is performed usually to detect subclinical acute rejection, CNI toxicity and chronic allograft injury. In era of Tacrolimus and MMF based immunosuppressive regimens, the role of protocol biopsies is very limited, mainly in high risk patients.
2. Please reflect on your practice if possible.
In our unit, only indicated biopsies are performed by the transplant team under ultrasound guidance.
Assafi Mohammed
3 years ago
Kidney Allograft Biopsy Graft biopsy is performed for the following possibilities:
Specific Clinical Indications: based on clinical or laboratory changes.
Surveillance Program(Protocol Biopsy): taken at predefined time post-transplantation for definite evaluation.
Specific Clinical Indications for Kidney Allograft Biopsy:
Persistently, unexplained rising serum creatinine: increment in SCr by more than 30% is considered a predictor of poor graft survival and subsequent failure.Reversible causes of AKI should be ruled out (dehydration, urinary obstruction and drug toxicity).
Acute Rejection: when there’s lack of improvement in graft function after first line therapy. To rule out new pathological process(eg; coexistent ATN, drug toxicity or BKV nephropathy).
In DGF: obtained as periodic biopsies to diagnose acute rejection.
New onset Proteinuria: may be a clue of subclinical Rejection or recurrence of primary disease.
Nephrotic rangeProteinuria: ≥ 3 g/day or ≥ 3g/g creatinine.
Surveillance Program(Protocol Biopsy): Rationale:
Can detect subclinical acute rejection.
Can establish the diagnosis of chronic Allograft Insult(CAI).
Can confirm diagnosis of CNI nephrotoxicity.
May help diagnosing recurrent disease, transplant glomerulopathy and BKV nephropathy.
Benefit-Risk Ratio should be considered when attempting protocol biopsy
Rationale for performing protocol biopsy.
Complication: substantial bleeding, macroscopic hematuria with ureteric obstruction, peritonitis or graft loss.
Financial cost.
We don’t perform protocol biopsy, only kidney allograft biopsy when there’s an indication as listed above.
Sherif Yusuf
3 years ago
In your own words, summarise this article
Graft biopsy is indicated in one of 2 situations :
A- Indication biopsy
Indication biopsy is done due to unexplained (after exclusion of CNI toxicity, dehydration, obstruction) graft dysfunction, and this includes:
DGF in this situation graft biopsy is done to identify the cause of DGF and also for detection of superimposed acute rejection, a 7-day protocol biopsy was found to be of great significance since the occurrence of subclinical rejection in this group is more common, and co-treatment of SCR may improve outcome. So renal biopsy is done weekly till improvement of renal function
AKI here graft biopsy can be done due to either AKI or lack of improvement of graft function with the treatment of a specific cause
Proteinuria which is either new-onset proteinuria > 0.5-1 gm or an increase in the proteinuria from baseline (from native kidney or graft)
B- Protocol biopsy
Protocol biopsy is doing renal biopsy for renal transplant patients in the first year of transplantation without the evidence of renal allograft dysfunction
Subclinical rejection (histologic evidence of acute rejection without clinically detected graft dysfunction) occur commonly in the first year and is associated with poor graft survival.
Early treatment of subclinical rejection can improve renal allograft survival
Renal allograft biopsy is a relatively safe procedure with the incidence of major complication 1%.
Please reflect on your practice if possible.
We are not doing protocol biopsies and only perform allograft biopsy in the setting of allograft dysfunction
Abdulrahman Ishag
3 years ago
Summary of the article ;
Kidney allograft biopsies are performed for specific clinical indications (‘indicated biopsy’), or as part of a surveillance program ( protocol) .
Indicated allograft biopsy is recommended in the following conditions ;
– Persistent increased serum creatinine, that is not explained by potential causes . When serum creatinine has not returned to base line after treatment of acute rejection .- -In delayed graft function to rule out acute rejection . -if expected kidney function is not achieved with in the first 1-2 months after transplantation. -New onset protienuria Unexplained proteinuria more than 3gm –
Biopsies for an increase in serum creatinine Kidney allograft biopsy is indicated ,when there is a decline in GFR without apparent reversible cause . It can detect potential causes of acute kidney injury (rejection ,infection ,recurrence and de novo kidney disease or infiltration with PTLD).also it can determine both type and severity of immunologic damage .Additional biopsies may be required when an abrupt change in the rate of progression is observed.
Biopsies for a lack of improvement in graft function Failure of response to the first line therapy in cases of acute rejection ,may be due to a new pathological process, such as coexistent acute tubular necrosis, drug toxicity or BKV nephropathy, that would require a different treatment approach. Therefore, a biopsy is indicated to determine the correct treatment. Biopsies for DGF
Observational studies have shown that the incidence of acute rejection during DGF is higher than in patients without DGF . Kidney function cannot be used as an indication for biopsy to diagnose superimposed acute rejection while the patients are already being treated with dialysis due to DGF, or when the serum creatinine does not fall from pre transplant values. It is therefore prudent to obtain periodic biopsies of the kidney during DGF to diagnose acute rejection.
Protocol biopsies; protocol biopsies can detect clinically unapparent (subclinical) acute rejection, CNI nephrotoxicity , recurrent disease, transplant glomerulopathy , CAI and BKV nephropathy. It is unclear whether the detection of these conditions by protocol biopsy improves outcomes. Protocol biopsies can be done safely as an outpatient procedure. The reported risk of major complications from protocol biopsy, including substantial bleeding, macroscopic hematuria with ureteric obstruction, peritonitis or graft loss, is approximately 1% . The reported incidence of graft loss from protocol biopsy is0.03%.
My own practice ; Usually we use to do an indicative allograft kidney biopsy .we do not perform protocol allograft kidney biopsy.
Riham Marzouk
3 years ago
Kidney allograft biopsy can be diagnostic /indicated biopsy or protocol biopsy
Protocol biopsy is done at predefined period regardless renal function to search for subclinical rejection to add benefit toward graft survival and improve outcome.
Diagnostic or indicated biopsy indications:
1- Increase in serum creatinine by 25% or more than baseline and persistent after exclusions of all pre-renal causes.
2- Sudden new onset proteinuria or unexplained proteinuria more than 3 gm/24 hrs which may indicate treatable cause of proteinuria
3- If no improvement of renal function after treatment of acute rejection; if no response of acute cellular rejection to pulse steroid , to add another treatment line like ATG or to discover another graft pathology to help in management.
4- During the course of DGF (need of dialysis in the first week post-transplant) every 10 days to search for rejection
5- If there is no achievement of good renal function after 1-2 months post-transplant
in my practice:
we did diagnostic biopsy , we never do protocol biopsy
Doaa Elwasly
3 years ago
-An ‘indicated biopsy’ is done when there is a variation in the clinical picture of a case or change of the blood tests.
A ‘protocol biopsy’ is done on particular after transplantation, regardless of kidney function. Biopsies to investigate abnormal serum creatinine
A study mentioned that a persistent 30% rise in serum creatinine was a good indicator of graft failure.
If there were no justification to decreasing of GFR, then an allograft biopsy is needed to detect any possible treatable causes of kidney injury, as rejection, infections like BKV nephropathy, recurrent or de novo kidney disease or PTLD Biopsies to explain worsening of graft function
This can occur due to a new pathology, as acute tubular necrosis, drug toxicity or BKV nephropathy, that need another therapy. Biopsies for DGF
periodic biopsies to discoveracute rejection
It is not settled when and how often biopsies during DGF should be taken . Infact some studies did i biopsies every 7–10 days, to dialysisng patients for DGF, which revealed that acute rejection can be dtected for the first time on the second, third or even fourth biopsy
On the other hand biopsy may not be needed when DGF is resolving Protocol biopsies
Multiple studies demonstrated that protocol biopsies can identify subclinical acute rejection, CAI and CNI nephrotoxicity, recurrent disease, transplant glomerulopathy, and BKV nephropathy but its effect on the outcome is not clear to be much beneificial.
While using protocol biopsies to diagnosis subclinical rejection may not be suitable in tacrolimus- and MMF-treated patients.
Multiple complications from protocol biopsy can occur , including bleeding, macroscopic hematuria with ureteric obstruction, peritonitis or graft loss, which doesn’t happen in more than nearly 1% of the cases.
Meanwhile the benefit of protocol biopsies in CsA/azathioprine-treated patients without induction therapy can be more than its harm but this is based on low evidence .
-The decision of doing the protocol biopsy is usually individualised according to each case on its own weighing the benefits and the risks
Ban Mezher
3 years ago
Graft biopsy is the gold standard method for diagnosis of infrarenal pathology causing renal dysfunction. It can be done when there is reduced GFR or proteinuria. It can be done when there is renal dysfunction (indicated biopsy) or done at determined intervals for screening of rejection (protocol biopsy). Persistent declined GFR >30% is a good indicator of progression of graft failure.
Before performing graft biopsy, several reversible causes of graft dysfunction should be ruled out ( dehydration, urinary obstruction & CNI toxicity). If theses causes are not resolved by treated or not present, the biopsy should be done to diagnose the exact cause of dysfunction e.g acute rejection, infection, PTLD, or recurrent of original disease.
It shown that the incidence of acute rejection is more among patients with DGF than patients with out DGF. So if graft function not improved with dialysis, graft biopsy may show features of acute rejection.
Protocol biopsy can detect subclinical acute rejection so early treatment improve the long term survival of graft. Also It can detect early the CNI toxicity, PTLD, recurrent of disease, transplant glomerulopathy & BKV nephropathy but there is no evidence support that early detection can improve the graft outcome.
Before performing graft biopsy, bleeding tendency should be assessed. But it considered as safe procedure & complications ( bleeding, macroscopical hematuria with ureteric obstruction, & graft loss) are around 1%, & graft loss in protocol biopsy is 0.03%.
Protocol biopsy is expensive, it cost around 3000$/ biopsy.
In my practice, we do indicated biopsy only. Most of our patients refuse protocol biopsy after discussion about the risk, benefit & cost.
Huda Al-Taee
3 years ago
In your own words, summarise this article
This article is part of 2009 KDIGO guidelines on kidney transplant recipient management, chapter of kidney allograft biopsy.
The article started with the recommendation of doing graft biopsy and their level of evidence.
In general, there are 2 types of graft biopsy: indication biopsy and protocol biopsy.
protocol biopsy is done for surveillance purposes while indication biopsy is done when there is clinical indication.
Clinical indication for allograft biopsy:
persistent, unexplained increase in serum creatinine.
lack of improvement in graft function
delayed graft function
new onset proteinuria
Persistent, unexplained increase in serum creatinine
Although serum creatinine has many limitation for estimating GFR, the rise in serum creatinine level is indicative of drop in GFR. So increment in serum creatinine level that is not explained by dehydration, urinary obstruction, high CNI level is due to intra-renal cause and to know the exact cause ( rejection, recurrent disease or others) to implement proper management, a graft biopsy should be done. studies defined the significant value for increment in creatinine level as 25-50% from baseline level, others consider 30% increase from baseline as a cutoff value.
Lack of improvement in graft function
when no improvement in graft function happend following treatment of rejection, a graft biopsy should be done to exclude the presence of other pathologies that could happen concomitantly with rejection such as ATN, drug toxicity, or BK nephropathy and require different treatment.
Delayed graft function
according to the observational studies, there is a higher incidence of rejection in patients with DGF than patients without DGF. so periodic biopsies of kidney with DGF is required to diagnose rejection as in this case one can not depend on serum creatinine level because the patient is on dialysis treatment.
New onset proteinuria
new onset proteinuria or unexplained proteinuria > 3 gm/day is an indication of graft biopsy as this proteinuria may be due to recurrent or de novo glomerular disease and these diseases are a potentially treatable cause of allograft dysfunction.
Protocol biopsies
The importance of protocol biopsy is the detection of subclinical rejection which is associated with reduced graft survival. according to a RCT, the diagnosis and treatment of subclinical rejection improve outcomes.
other conditions can be detected by protocol biopsy as: CNI toxicity, recurrent disease, transplant glomerulopathy, BK nephropathy.
The process is generally safe with low risk of complications(1%) such as bleeding, macroscopic hematuria with ureteric obstruction, peritonitis, graft loss(0.03%).
Protocol biopsies may be expensive, therefore the decision to do such biopsies should be shared with the patient.
Please reflect on your practice if possible
In my practice, most of the graft biopsies are done when there is clinical indication, we rarely do protocol biopsies and we make a shared decision with the patient if we want to do a protocol biopsy explaining the indications, risks, benefits, and the cost of the procedure.
Mohamed Essmat
3 years ago
The article addresses the kidney allograft biopsy topic , whether it was an indicated biopsy or protocol biopsy .
*Indicated biopsy whether if there was a creatinine increase in which the cut off point is not well set off but estimated 30% increase more than the baseline usually necessitates a renal biopsy after exclusion of reversible causes as dehydration , CNI toxicity ( high blood levels ) , infection or nephrotoxic drugs.
*DGF ,which entails the need of dialysis in the 1st week after transplantation , has more rates of acute rejection which justifies some centers that perform protocol biopsy several times in the DGF for detection of CNI toxicity , BKV nephropathy , or acute rejection .
while indicated biopsy is done in the DGF if there were no reversible causes of AKI are present .
According to my practice : Protocol biopsy is done for high risk , sensitized individuals , with history of 1ry glomerular disease , history of more then 1 transplant ; for detection of subclinical rejection .
regarding indicated biopsies ; there’s no argument that rising creatinine-and or proteinuria or increasing proteinuria with no apparent dehydration , high levels of CNI’s , -ve CMV , normal duplex and no obstruction by US , usually necessitates renal biopsy for detection of rejection , recurrence of the original kidney disease or others .
It’s worth saying that medical history , current IS , previous induction and/or desensitization , date of Tx , meticulous fluid balance especially early in the post Tx period affect the decision and the timing of the biopsy .
In your own words, summarise this article Indicated biopsy – prompted by a change in the patient’s clinical condition and/or laboratory parameters. Protocol biopsy– obtained at predefined intervals after transplantation, regardless of kidney function. Causes of Increased serum- First rule out
Dehydration
urinary obstruction
high CNI levels
other apparent causes then likely causes are-
acute rejection
CAI
drug toxicity
recurrent or de novo kidney disease
BKV nephropathy
A persistent 30% rise in serum creatinine was an excellent predictor of subsequent graft failure. Additional biopsies may be required when an abrupt change in the rate of progression is observed. Contraindication for a biopsy
bleeding diathesis
presence of large fluid collections or infection.
acute kidney injury absolute increase in serum creatinine of ≥0.3 mg/dL
a percentage increase in serum creatinine of ≥50% (1.5-fold from baseline)
a reduction in urine output (documented oliguria of less than 0.5 mL/kg/h for more than 6 h).
*do require at least two creatinine values within 48 h.
Biopsies to be obtained every 7–10 days, while patients are receiving dialysis for DGF. Protocol biopsies-
Use of protocol biopsies, therefore, for diagnosis of subclinical rejection may not be appropriate in tacrolimus- and MMF-treated patients.
Other conditions that can be detected on protocol biopsy are –
CNI toxicity
recurrent disease
transplant glomerulopathy
CAI
BKV nephropathy.
The risk of major complications from protocol biopsy is approximately 1% which includes-
substantial bleeding
macroscopic hematuria with ureteric obstruction
peritonitis
graft loss
The benefit of performing protocol biopsies is seen only in patients on CsA/azathioprine without induction therapy and in those may outweigh the harm.
Please reflect on your practice if possible
Protocol biopsies were not done in our centre. We used to do indication biopsies.
Kidney allograft biopsy is beneficial in diagnosis in case of DGF to Rule out acute rejection ,recurrence of original disease ,BKV nephropathy ,PTLD in some cases .and it also very important in determination of therapy in some cases like acute rejection :if antibody mediated rejection we will go with IVIG ,plasmapheresis and rituximab and if Cell mediated we will go with steroids ,Thymoglobulin in some cases .
So we should have solid indications for kidney biopsy as it has complications like hematoma ,bleeding and some cases it may lead to graft loss.
This article was published in American Journal of transplantation ,it recommended some indications for kidney allograft biopsy like:
1- unexplained rise in serum creatinine after kidney transplantation
2- serum creatinine did not reach to baseline after treatment of acute rejection
3- every 7-10 days during DGF
4- If expected kidney function was not achieved during the 1st 1-2 months after transplantation.
5- In case of proteinuria after kidney transplantation either new onset or unexplained proteinuria >3 g/24 hours.
they talked also about AKI definition and serum creatinine and that we cannot depend on it solely for diagnosis of acute rejection .
In case of DGF we should also rule out causes like dehydration ,CNI toxicity,urinary obstruction
They talked about role of protocol biopsy and its rule in diagnosing sublinical rejection and that sub clinical rejection leads to poor graft survival,some studies showed that sub clinical rejection is more in patients taking Azathioprine and cyclosporine and less in patients taking tacrolimus and MMF.
But still there is no evidence that protocol biopsy Is mandatory in diagnosing sub clinical rejection.
CNI toxicity and CAI also can be diagnosed by biopsy
In our center same indications for acute conditions but we do not perform protocol biopsy
Kidney allograft biopsies may be performed for clinical indications, or protocol.
indicated biopsy is done when there is changes in the patient’s condition either clinical or laboratory.
protocol biopsy is done on a predefined intervals after transplantation, regardless of kidney function.
It is recommended to do allograft biopsy in the following conditions:
1 persistent, unexplained increase in serum creatinine.
2 serum creatinine has not returned to baseline after treatment of acute rejection.
3 every 7–10 days during delayed graft function.
4 if expected kidney function is not achieved within the first 1–2 months after transplantation.
5 new onset of proteinuria,
unexplained proteinuria ≥3.0 g/g creatinine or ≥3.0 g per 24 hours.
*Biopsies for an increase in serum creatinine;
Correction of any reversible cause of rising s cr must be done before biopsy these causes includes dehydration, urinary obstruction or acute CNI toxicity (by demonstrating high blood levels).
Persistant 25–50% increase in s cr over baseline (after excluding correctable factors) indicates biopsy to detect the nature of kidney injury including rejection, infections like BKV nephropathy, recurrent or de novo kidney disease or PTLD.
*Biopsies for DGF:
DGF ;is graft function low enough to require dialysis in the first week after kidney transplantation, or lack of improvement in pretransplant kidney function.
acute rejection during DGF is higher than in patients without DGF and s creat can’t be used to monitor graft function as the patient is on dialysis.
few data to determine when and how often biopsies during DGF should be obtained. But some studies performed biopsy every 7-10 days and acute rejection can be present for the first time on the second, third or even fourth biopsy.
*New-onset proteinuria :
Biopsy is also indicated for New-onset proteinuria which may indicate treatable causes of graft dysfunction, including acute rejection and thrombotic microangiopathy.
In patients who already have proteinuria, an increase exceeding a threshold usually defined as ‘nephrotic range’ proteinuria, for example ≥3.0 g/g creatinine or ≥3.0 g/24 h, may indicate treatable causes of graft dysfunction.
*Protocol biopsies:
protocol biopsies can detect subclinical acute rejection, CAI and CNI nephrotoxicity. Detection and treatment of subclinical acute rejection may be beneficial in preventing CAI and improves long-term graft survival.
the combination of tacrolimus and MMF is associated with lower incidence of subclinical rejection than cyclosporine regimen and the , use of protocol biopsies for diagnosis of subclinical rejection may not be appropriate in tacrolimus- and MMF-treated patients.
Protocol biopsies may be expensive but with excellent safty .
In my practice we dont do protocol biopsy
And its always done upon clinical or lab abnormalities
1- In your own words, summarise this article :
1- persistant unexplained high S. creatinine.
2- acute rejection that is resistant to standard treatment as other pathologies may appear on top of acute rejection.
3- delayed graft function as the incidence of acute rejection is higher in those patients.
4- new onset or nephrotic range proteinuria.
2- Please reflect on your practice if possible.
I will adhere to the local policies then discuss with senior colleagues the possible application of protocol biopsy.
Kidney allograft biopsy is either indicated or protocol biopsy
Where indicated biopsy refers to changes in the patient clinical condition of laboratories.
Protocol biopsy is used for screening .
Biopsy should be taken with any unexplained persistent rise of serum creatinine to detect of differentiate between types of immunological injury and treat accordingly .
Biopsies also are indicated when there is failure to regain the function after treatment as this may indicated an added pathology .
In cases of delayed graft function, serum creatinine can’t point to when we should take a biopsy , so in such situations periodic biopsies should be obtained because incidence of acute rejection are higher with DGF.
Protocol biopsies may be beneficial in detection of subclinical rejection which doesn’t present with decline in GFR , treatment of such rejections is beneficial of the long term in reducing incidence of acute rejections and long term graft survival .
Other conditions that can be detected on protocol biopsies
include CNI toxicity, recurrent disease, transplant glomerulopathy, CAI and BKV nephropathy.
Biopsies are safe with major complications occur at an incidence of 1%
Protocol biopsies are expensive and this should be considered.
Kidney allograft biopsy is either protocol biopsy (done at predefined time regardless kidney functions) or indicated biopsy (performed only with clinical or lab indication).
It detect histological changes requiring treatment
Unexplained increase in serum creatinine
is mostly due to intragraft parenchymal injury, other reversible causes should be ruled out as dehydration, urinary obstruction or acute CNI toxicity before biopsy.
Adequate biopsy can define causes of allograft dysfunction as rejection, BK virus nephropathy, recurrent or de novo kidney disease and allograft infiltration as PTLD.
biopsy can determine type and severity of AR
biopsy for lack of improvement of graft function
It is indicated to determine if there is new pathological process requiring additional treatment
Biopsy for DGF:
DGF is failure of improvement of kidney functions with need for dialysis in the first week post transplant
As the patient is already treated with dialysis due to DGF, so periodic biopsies are performed to diagnose AR, studies showed that AR may present on the second, third or fourth biopsy except if signs of resolving DGF appeared
Protocol biopsy:
detect subclinical AR, CAI and CNI nephrotoxicity before decline in kidney functions
Studies suggested that detection and treatment of subclinical AR detected by protocol biopsies is beneficial to avoid CAI, decrease graft survival and improve the outcome.
The need for protocol biopsy is determined by the maintenance immunosuppression as Tac and MMF are associated with less incidence of AR so not appropriate to perform protocol biopsies for diagnosis of subclinical rejection.
protocol biopsies are expensive and detection of subclinical rejection is more expensive so RCTs are needed to determine the benefits and harms of protocol biopsies
Allograft biopsies are safe, the risk of reported major complications is 1% includes substantial bleeding, macroscopic hematuria, peritonitis or graft loss.
Biopsy may be hazardous in presence of bleeding disorder, infection or presence of large fluid collection
It is recommended to perform allograft biopsy with persistent unexplained increase in serum creatinine.
It is suggested to perform allograft biopsy:
after treatment of AR without improvement of serum creatinine to baseline.
every 7-10 days during DGF
within first 1-2 months after transplant if expected kidney functions not achieved
with new onset proteinuria and unexplained proteinuria >3g/24hours
this chapeter from american journal of transplantation in 2009 , address the recommendiation of indicated graft biopsy and protocal biopsies post kideny transplantation and we can see the evel of evidnce is low from 2C-2D , based on centre experience or expert opinion however the indication of garft biopsy its either part of protocal biopsy in which the garft biopsy performed in timely fixed intervales regardless of the garft function it will help to detect SCR , its safe but associated with high cost and patient preference one of the important factor to be consider , also its benefit duatful since the introduction of tacrolimus and MMF in maintenance protocals
while indicated graft biopsy is still widely used and indicated whenever thereis persistant reduction of graft function , DGF ,after excluding dehydration , CNI effect , urinary obsruction , another important indication worsening protienuria like urine p/c more than 3 gm/gm or 24h urine more than 3 gm
denov renal disease or recurrence of glomerulonephritis , BKV nephropthy
also indicated garft biopsy after 7-10 days from failed acute rejection treatment
in general both indicated garft biopsies and protocal biopsies considered safe procedurs can be done as OP , with less complication like bleeding in 1% and risk of garft loss < 0.03% , but protocal biopsies more cost and should consider patient preference and complaince as one of improtant factors
in our centre we only do graft biopsies once indicated
Indication of graft biopsy
1- As a part of protocol biopsy
To detect Subclinical rejection, CNI toxicity, or chronic allograft nephropathy
2- Indication biopsy:
a. Deterioration in kidney function
After exclusion of laboratory and individual variabilities
With persistent (25-50% elevation from baseline) after exclusion Dehydration, CNI induced toxicity, or urinary tract obstruction
The biopsy here is the gold standard to define the etiology, severity, appropriate treatment and od added prognostic value
b. Proteinuria (> 3 gram/ 24 hour)
c. Delayed graft function
To exclude associated or complicating acute rejection
No consensus about time or interval but every 7-10 days according to RCTs
d. Failed to achieve expected renal function after 1-2 months of transplantation
e. Failure of improvement of renal function after treatment of acute rejection to exclude another associated pathology and to determine the appropriate treatment (weak level of evidence)
In our practice
We only do indication biopsy except for the last indication
1-Graft biopsy has been done in different transplant centres either due to specific reasons ( indicated biopsy ) or to detect early different complications and to start early management( protocol biopsy).
2-This article explain the indications, benefits and risks for doing protocol graft biopsy in certain intervals .
3-Main patients who are needed to do graft biopsy:
– patient with elevated serum creatinine level for unknown reasons after excluding dehydration, infection ,CNI toxicity and obstruction.
– patient with delay graft function requiring dialysis with fluctuating S.creatinine level, graft biopsy must be done every 7 -10 days interval to detect any acute rejection as those patients are at risk to develop AR .
– new onset proteinuria or change in preexisting proteinuria level to detect recurrent or de novo kidney disease.
4- the biopsy risks and complications should be discussed with the patient before doing the biopsy like bleeding, hematuria,obstruction or even graft loss in addition to the cost .
5- some indications for graft biopsy or early detection of certain conditions like BKV nephropathy, de novo kidney disease and even CNI toxicity can not change the result or the outcome of these conditions.
6- subclinical rejection is affected and can be decreased by the type of immunosuppression regimen so it’s not mandatory to do graft biopsy for those patients on Tacrolimus and MMF .
Indications for kidney allograft biopsy
1- “a persistent, unexplained increase in serum creatinine. :” Serum creatinine persistently rise (above 30%) ,and causes like dehydration and obstruction should be excluded .Another diagnoses like rejection, infections can be reached .
2- “ serum creatinine has not returned to baseline after treatment of acute rejection. ”: if the patient received ant rejection and does not respond another diagnosis like ATN, CNI toxicity or infection.
3- “ expected kidney function is not achieved within the first 1–2 months after transplantation.
4- “If there is: new onset of proteinuria or unexplained proteinuria ≥3.0 g/g creatinine or ≥3.0 g per 24 hours.
5- Protocol biopsies : DGF can be associated with superimposed acute rejection. Protocol biopsies are indicated if DGF does not resolve and are advised to be every 7-10 days.
Subclinical rejection can occur without change in renal function . subclinical acute rejection in 14-day protocol biopsies was associated with poorer 10-year graft
survival. Treating subclinical rejection detected on protocol biopsies will result in reduction of acute rejection episode, histopathological changes and serum creatinine at 2 year.
Major complications of protocol biopsy are substantial bleeding, macroscopic hematuria with ureteric obstruction, peritonitis or graft loss.
The risk of major complications from renal graft biopsy is only 1% and of graft loss is 0.03% .
In our country we do allograft biopsy on specific indications, which include acute kidney injury which not explained by clear causes, suspicion of antibody mediated rejection, suspicion of recurrence of primary disease and new onset proteinuria. We didn’t do protocol biopsy .
Kidney allograft biopsy is performed in two settings, either indicated biopsy (when a change in kidney function occurs) or protocol biopsy (obtains at a predefined interval regardless of kidney function). Both biopsies are done with the aim of improving kidney function.
Rational
After exclusion of the causes such as obstruction, dehydration, and high CNI levels, intragraft parenchymal process, such as acute rejection, CAN, drug toxicity, recurrent or de novo kidney disease should be considered.
The optimal diagnosis and treatment of kidney dysfunction requires a kidney biopsy.
DGF is defined as a need for dialysis in the first week after kidney transplant. In DGF, change in serum Cr is not useful for ruling out acute rejection. So, protocol biopsy may be needed (biopsies have been obtained every 7-10 days), although biopsy may no longer be needed when there are signs that DGF is resolving.
New onset proteinuria and in patients who already have proteinuria, an increase beyond the threshold of 3 gr/day indicates treatable causes of graft dysfunction, including acute rejection and TMA.
A persistent increase in the plasma Cr level outside the normal range (25-50% over baseline in different studies) after ruling out of reversible causes is an indication of kidney biopsy to detect treatable causes of kidney injury, including rejection, infections like BK virus, recurrent or de novo kidney disease and infiltration with PTLD and appropriate treatment of these different etiologies of kidney injury.
In addition, biopsy is indicated in the case of acute rejection that does not respond to first line treatment with steroids.
The patient should be assessed for contraindications of kidney biopsy such as bleeding diathesis, large fluid collection, and infection.
Protocol biopsies
It is proposed that protocol biopsies can detect subclinical acute rejection, CAI and CNI nephrotoxicity. Detection and treatment of subclinical acute rejection may be beneficial in preventing CAI and reduced long-term graft survival. Treatment of subclinical rejection may improve outcomes.
The baseline immunosuppression therapy is an important determinant of subclinical rejection. Since the combination of tacrolimus and MMF is associated with lower incidence of subclinical rejection than cyclosporine-based therapy. Therefore, use of protocol biopsies for diagnosis of subclinical rejection may not be appropriate in tacrolimus- and MMF-treated patients.
The safety profile of protocol kidney biopsy is acceptable, with 1% and 0.03% risk of major complications and incidence of graft loss, respectively. Protocol biopsies, however, may be expensive.
Indications for kidney allograft biopsy
1- “a persistent, unexplained increase in serum creatinine. (1C):” when serum creatinine persistently rise (above 30%) ,and causes like dehydration, obstruction and toxicity of CNI are ruled out.They will help in reaching diagnoses like rejection, infections , kidney disease or PTLD.
2- “ serum creatinine has not returned to baseline after treatment of acute rejection. (2D)”: if rejection does not respond to treatment as the cause could be another pathology like ATN, CNI toxicity or infection.
3- “ expected kidney function is not achieved within the first 1–2 months after transplantation. (2D)”
4- “If there is: new onset of proteinuria (2C) or unexplained proteinuria ≥3.0 g/g creatinine or ≥3.0 g per 24 hours. (2C)”
5- Protocol biopsies : DGF can be associated with superimposed acute rejection. Protocol biopsies are indicated if DGF does not resolve and are adviced to be every 7-10 days.
Subclinical rejection can occur without change in renal function and its prevalence range
from 13% to 25% at 1–2 weeks, 11–43% at 1–2 months, 3–31% at 2–3 months and 4–50% at 1 year .
subclinical acute rejection in 14-day protocol biopsies was associated with poorer 10-year graft
survival. Treating subclinical rejection detected on protocol biopsies will result in reduction of acute rejection episode, histopathological changes and serum creatinine at 2 year.
Major complications of protocol biopsy are substantial bleeding, macroscopic hematuria with ureteric obstruction, peritonitis or graft loss.
The risk of major complications from renal graft biopsy is only 1% and of graft loss is 0.03% .
The cost is 3000$ per biopsy .114 000$ are the cost for detecting only one case of acute subclinical rejection . So the cost and patient preference are needed to be considered while weighing the benefit-risk of performing protocol biopsies .
in our practice in Sudan we perform graft biopsies for all mentioned indications except for protocol biopsies.
THANK YOU All FOR YOUR CONTRIBUTIONS
-Kidney biopsy either indicated kidney biopsy or protocol kidney biopsy. An ‘indicated biopsy’ is prompted by a change in the patient’s clinical condition and/or laboratory parameters. A ‘protocol biopsy’ is one obtained
at predefined intervals after transplantation, regardless of kidney function.
Indications of diagnostic biopsy:
1. An unexplained rise in serum creatinine 25–50% increase over baseline.
2. Failure for improvement in graft function and not a response to antirejection treatment.
3. Delay graft function.
4. if expected kidney function is not achieved within the first 1–2 months after transplantation.
5. If there is new-onset proteinuria that may indicate treatable causes of graft dysfunction, including acute rejection and thrombotic microangiopathy and in patients who already have proteinuria, an increase exceeding a threshold ‘nephrotic range’ proteinuria( ≥3.0 g/g creatinine or ≥3.0 g/24 h )that may indicate treatable causes of graft dysfunction.
-Protocol biopsy help in detecting and treating subclinical acute rejection and CNI toxicity but RCTs are needed to determine when the benefits of
protocol biopsies outweigh the harm
Renal allograft biopsy is needed in main 2 situations ;protocol biopsy and when there is indication.
Protocol biopsy
planned biopsy in high risk patients aiming detection of subclinical acute rejection ,chronic allograft rejection and CNI toxicity.
Biopsy clinically indicated
1-Unexplained persistent rise in serum creatinine of more than 30% above baseline searching for underlying cause like acute rejection, recurrent disease, infection….
2-Treatment of acute rejection not associated with return of graft function to baseline.
3-to detect acute rejection in DGF
4-Unsatisfactory graft function in 1-2 months following Tx.
5-Worsening or new onset proteinuria more than 3 gm daily
With use of ultrasonography, procedure complications became very low ,but protocol biopsy needs patient education and compliance
Protocol biopsy is implemented usually to detect subclinical AR, chronic allograft injury and CNI toxicity. In era of Tac and MMF using immunosuppressive regimens, the role of protocol biopsies is decreasing ;essentially in high risk patients.
Transplanted kidney biopsy although safe most of the time may be challenging. can be performed either on purpose for an indication such as an unexplained abrupt deterioration in renal function, new-onset proteinuria, or delayed graft function. during the course of DGF acute insults may be added on top and acute rejections as already probable with increased incidence during the course acute rejections may be missed during that table. for this reason, repetitive biopsies are indicated and may be very useful unless clinical scenarios suggest improvement otherwise. some studies showed tubular atrophy and fibrosis without effect on creatinine clearance as well as close/similar incidence of dysfunction that could not overweight the cost of repetitive biopsies and probable risks.
Kidney allograft biopsy can be protocol biopsy (done at regular interval post transplantation irrespective of kidney function) and indication biopsy (done when there is clinical indication ).
Indications :
Protocol biopsy is bone at regular intervals to detect subclinical rejection. in the era of cyclosporine and azathioprine , the protocol biopsy was useful to detect subclinical rejection and treatment of subclinical rejection was associated with better graft survival and lower incidence of clinical rejection.
But in the era of tacrolimus and MMF , the incidence of subclinical rejection is much lower , because these drugs are more potent immunosuppressive drugs and the role of protocol biopsy is less important.
Complications :
sever macroscopic hematuria , urinary obstruction , peritonitis , graft loss . the incidence of these sever complication is low (<1%).
Kidney allograft biopsies are performed either on scheduled basis as in protocol biopsies, or upon specific indications.
A protocol biopsy is performed timely irrespective of kidney function, whereas allograft biopsy is done whenever indication exist.
Kidney allograft biopsy is recommended when there is a persistent, unexplained increase in serum Cr. It is suggested that biopsy should be performed in the following circumstances: creatinine has not returned to baseline after treatment of acute rejection, every 7–10, if expected kidney function is not achieved within the first 1–2 months after transplantation, new onset of proteinuria , unexplained proteinuria ≥3.0 g/g creatinine during delayed function.
If Cr is increasing persistently, and is not explained by dehydration, urinary obstruction, or high CNI levels, kidney biopsy is indicated. The biopsy is also indicated to rule out infection (BKV nephropathy) in the settings of acute kidney injury and possible recurrence of primary disease or de novo renal disease or PTLD.
In my practice, allograft biopsy is done only upon specific indications, which include acute kidney injury which not explained by clear causes, suspicion of antibody mediated rejection, suspicion of recurrence of primary disease and new onset proteinuria.
1. In your own words, summaries this article
Kidney allograft biopsies:
Either:
Indicated biopsy:
Is one that is prompted by a change in the patient’s clinical condition and/or laboratory
parameters?
Protocol biopsy:
One obtained at predefined intervals after transplantation, regardless of kidney function.
Indication:
Increase in serum creatinine persistent, unexplained.
Serum creatinine has not returned to baseline after treatment of acute rejection.
Delayed function, every 7–10 days.
Kidney function as expected is not achieved within the first 1–2 months after
transplantation.
New onset of proteinuria .
Unexplained proteinuria ≥3.0 g/g creatinine or ≥3.0 g per 24 hours.
Protocol biopsies:
Many disturbance of KT function can occur in absence of a measurable decline in
kidney function. e.g.:
Acute rejection, CAI and CNI toxicity.
protocol biopsies can detect clinically inapparent (subclinical) acute rejection, CAI and
CNI nephrotoxicity.
Treatment of subclinical rejection may improve outcomes.
Other conditions that can be detected by protocol biopsies include recurrent disease,
transplant glomerulopathy and BKV nephropathy.
Major complications from protocol biopsy approximately 1%:
Bleeding.
Macroscopic hematuria with ureteric obstruction,
Peritonitis .
graft loss.(0.03%)
1. Please reflect on your practice if possible.
In our practice we do indicated biopsy only no protocol biopsy is done.
summary:
The subject of kidney allograft biopsy is addressed in the article, regardless of whether it was an indicated biopsy or a protocol biopsy.
Indicated biopsy if there was a creatinine rise where the cut-off threshold was not precisely defined but the increase was anticipated to be 30 per cent more than the baseline. After ruling out reversible reasons such as dehydration, CNI toxicity (high blood levels), illness, or nephrotoxic medicines, a kidney biopsy is routinely performed. Having a higher risk of acute rejection in DGF patients, which necessitates the use of dialysis in the first week after transplantation, justifies certain institutions doing protocol biopsy numerous times in the DGF for the diagnosis of CNI toxicity, BKV nephropathy, or acute rejection.
While the appropriate biopsy is performed in the DGF if there are no reversible causes of AKI present, the DGF does not do the procedure.
A protocol biopsy is performed in high-risk, sensitized persons who have a history of chronic kidney disease or who have had more than one transplant, in order to identify subclinical rejection, according to my practice.
There is no debate that increasing creatinine-and-or proteinuria or increasing.
reflect on practice:
the indication of renal biopsy, I already apply in my practice. But the protocol biopsy we are not applying because to confess the patient about the biopsy with normal renal function and the possibility of post renal biopsy complication is very difficult.
1. In your own words, summarise this article
Renal allograft biopsies are performed in 2 specific instances, namely indicated biopsies and protocol biopsies. An indicated biopsy is one which is done due to altered laboratory parameters or a due to change in clinical condition of the patient. Protocol biopsy is done at a pre-determined time after transplant, with no correlation with laboratory or clinical parameters.
In current era of real-time ultrasound guided kidney biopsies, the rate of complications is very low (<1%) which include major bleeding and hematuria with ureteric obstruction. Rarely (0.03%), a graft can be lost.
A) The conditions warranting an indicated biopsy include:
1) Persistent rise in serum creatinine by >30% above baseline, not explained by apparent causes like dehydration, obstruction, high CNI levels: The biopsy is needed to rule our renal parnchymal cause like acute rejection, infection (BKV nephropathy), recurrent or de novo renal disease or PTLD.
2) Absence of improvement of graft function to previous levels after treatment of acute rejection: This may be due to some other pathology superimposing on the acute rejection (like ATN, BKV nephropathy etc), which needs to be identified and treated.
3) Delayed Graft Function (DGF): A biopsy should be performed once in 7-10 days in patients with DGF to rule out supreimposed acute rejection.
4) If graft function is sub-optimal: Biopsy should be done to find out the cause of a less than satisfactory graft function even 1-2 months after transplant.
5) Proteinuria: Worsening of a pre-existing proteinuria to more than 3 gram per day or a new-onset proteinuria may be a marker of rejection, thrombotic microangiopathy, or recurrent/ de novo glomerular disease for which a biopsy is required.
B) A protocol biopsy is performed usually to detect subclinical acute rejection, CNI toxicity and chronic allograft injury. In era of Tacrolimus and MMF based immunosuppressive regimens, the role of protocol biopsies is very limited, mainly in high risk patients.
2. Please reflect on your practice if possible.
In our unit, only indicated biopsies are performed by the transplant team under ultrasound guidance.
Kidney Allograft Biopsy
Graft biopsy is performed for the following possibilities:
Specific Clinical Indications for Kidney Allograft Biopsy:
Surveillance Program(Protocol Biopsy):
Rationale:
Benefit-Risk Ratio should be considered when attempting protocol biopsy
We don’t perform protocol biopsy, only kidney allograft biopsy when there’s an indication as listed above.
In your own words, summarise this article
Graft biopsy is indicated in one of 2 situations :
A- Indication biopsy
Indication biopsy is done due to unexplained (after exclusion of CNI toxicity, dehydration, obstruction) graft dysfunction, and this includes:
B- Protocol biopsy
Please reflect on your practice if possible.
Summary of the article ;
Kidney allograft biopsies are performed for specific clinical indications (‘indicated biopsy’), or as part of a surveillance program ( protocol) .
Indicated allograft biopsy is recommended in the following conditions ;
– Persistent increased serum creatinine, that is not explained by potential causes .
When serum creatinine has not returned to base line after treatment of acute rejection .-
-In delayed graft function to rule out acute rejection .
-if expected kidney function is not achieved with in the first 1-2 months after transplantation.
-New onset protienuria
Unexplained proteinuria more than 3gm –
Biopsies for an increase in serum creatinine
Kidney allograft biopsy is indicated ,when there is a decline in GFR without apparent reversible cause . It can detect potential causes of acute kidney injury (rejection ,infection ,recurrence and de novo kidney disease or infiltration with PTLD).also it can determine both type and severity of immunologic damage .Additional biopsies may be required when an abrupt change in the rate of progression is observed.
Biopsies for a lack of improvement in graft function
Failure of response to the first line therapy in cases of acute rejection ,may be due to a new pathological process, such as coexistent acute tubular necrosis, drug toxicity or BKV nephropathy, that would require a different treatment approach. Therefore, a biopsy is indicated to determine the correct treatment.
Biopsies for DGF
Observational studies have shown that the incidence of acute rejection during DGF is higher than in patients without DGF . Kidney function cannot be used as an indication for biopsy to diagnose superimposed acute rejection while the patients are already being treated with dialysis due to DGF, or when the serum creatinine does not fall from pre transplant values. It is therefore prudent to obtain periodic biopsies of the kidney during DGF to diagnose acute rejection.
Protocol biopsies;
protocol biopsies can detect clinically unapparent (subclinical) acute rejection, CNI nephrotoxicity , recurrent disease, transplant glomerulopathy , CAI and BKV nephropathy. It is unclear whether the detection of these conditions by protocol biopsy improves outcomes.
Protocol biopsies can be done safely as an outpatient procedure. The reported risk of major complications from protocol biopsy, including substantial bleeding, macroscopic hematuria with ureteric obstruction, peritonitis or graft loss, is approximately 1% . The reported incidence of graft loss from protocol biopsy is0.03%.
My own practice ;
Usually we use to do an indicative allograft kidney biopsy .we do not perform protocol allograft kidney biopsy.
Kidney allograft biopsy can be diagnostic /indicated biopsy or protocol biopsy
Protocol biopsy is done at predefined period regardless renal function to search for subclinical rejection to add benefit toward graft survival and improve outcome.
Diagnostic or indicated biopsy indications:
1- Increase in serum creatinine by 25% or more than baseline and persistent after exclusions of all pre-renal causes.
2- Sudden new onset proteinuria or unexplained proteinuria more than 3 gm/24 hrs which may indicate treatable cause of proteinuria
3- If no improvement of renal function after treatment of acute rejection; if no response of acute cellular rejection to pulse steroid , to add another treatment line like ATG or to discover another graft pathology to help in management.
4- During the course of DGF (need of dialysis in the first week post-transplant) every 10 days to search for rejection
5- If there is no achievement of good renal function after 1-2 months post-transplant
in my practice:
we did diagnostic biopsy , we never do protocol biopsy
-An ‘indicated biopsy’ is done when there is a variation in the clinical picture of a case or change of the blood tests.
A ‘protocol biopsy’ is done on particular after transplantation, regardless of kidney function.
Biopsies to investigate abnormal serum creatinine
A study mentioned that a persistent 30% rise in serum creatinine was a good indicator of graft failure.
If there were no justification to decreasing of GFR, then an allograft biopsy is needed to detect any possible treatable causes of kidney injury, as rejection, infections like BKV nephropathy, recurrent or de novo kidney disease or PTLD
Biopsies to explain worsening of graft function
This can occur due to a new pathology, as acute tubular necrosis, drug toxicity or BKV nephropathy, that need another therapy.
Biopsies for DGF
periodic biopsies to discoveracute rejection
It is not settled when and how often biopsies during DGF should be taken . Infact some studies did i biopsies every 7–10 days, to dialysisng patients for DGF, which revealed that acute rejection can be dtected for the first time on the second, third or even fourth biopsy
On the other hand biopsy may not be needed when DGF is resolving
Protocol biopsies
Multiple studies demonstrated that protocol biopsies can identify subclinical acute rejection, CAI and CNI nephrotoxicity, recurrent disease, transplant glomerulopathy, and BKV nephropathy but its effect on the outcome is not clear to be much beneificial.
While using protocol biopsies to diagnosis subclinical rejection may not be suitable in tacrolimus- and MMF-treated patients.
Multiple complications from protocol biopsy can occur , including bleeding, macroscopic hematuria with ureteric obstruction, peritonitis or graft loss, which doesn’t happen in more than nearly 1% of the cases.
Meanwhile the benefit of protocol biopsies in CsA/azathioprine-treated patients without induction therapy can be more than its harm but this is based on low evidence .
-The decision of doing the protocol biopsy is usually individualised according to each case on its own weighing the benefits and the risks
Graft biopsy is the gold standard method for diagnosis of infrarenal pathology causing renal dysfunction. It can be done when there is reduced GFR or proteinuria. It can be done when there is renal dysfunction (indicated biopsy) or done at determined intervals for screening of rejection (protocol biopsy). Persistent declined GFR >30% is a good indicator of progression of graft failure.
Before performing graft biopsy, several reversible causes of graft dysfunction should be ruled out ( dehydration, urinary obstruction & CNI toxicity). If theses causes are not resolved by treated or not present, the biopsy should be done to diagnose the exact cause of dysfunction e.g acute rejection, infection, PTLD, or recurrent of original disease.
It shown that the incidence of acute rejection is more among patients with DGF than patients with out DGF. So if graft function not improved with dialysis, graft biopsy may show features of acute rejection.
Protocol biopsy can detect subclinical acute rejection so early treatment improve the long term survival of graft. Also It can detect early the CNI toxicity, PTLD, recurrent of disease, transplant glomerulopathy & BKV nephropathy but there is no evidence support that early detection can improve the graft outcome.
Before performing graft biopsy, bleeding tendency should be assessed. But it considered as safe procedure & complications ( bleeding, macroscopical hematuria with ureteric obstruction, & graft loss) are around 1%, & graft loss in protocol biopsy is 0.03%.
Protocol biopsy is expensive, it cost around 3000$/ biopsy.
In my practice, we do indicated biopsy only. Most of our patients refuse protocol biopsy after discussion about the risk, benefit & cost.
In your own words, summarise this article
This article is part of 2009 KDIGO guidelines on kidney transplant recipient management, chapter of kidney allograft biopsy.
The article started with the recommendation of doing graft biopsy and their level of evidence.
In general, there are 2 types of graft biopsy: indication biopsy and protocol biopsy.
protocol biopsy is done for surveillance purposes while indication biopsy is done when there is clinical indication.
Clinical indication for allograft biopsy:
Persistent, unexplained increase in serum creatinine
Although serum creatinine has many limitation for estimating GFR, the rise in serum creatinine level is indicative of drop in GFR. So increment in serum creatinine level that is not explained by dehydration, urinary obstruction, high CNI level is due to intra-renal cause and to know the exact cause ( rejection, recurrent disease or others) to implement proper management, a graft biopsy should be done. studies defined the significant value for increment in creatinine level as 25-50% from baseline level, others consider 30% increase from baseline as a cutoff value.
Lack of improvement in graft function
when no improvement in graft function happend following treatment of rejection, a graft biopsy should be done to exclude the presence of other pathologies that could happen concomitantly with rejection such as ATN, drug toxicity, or BK nephropathy and require different treatment.
Delayed graft function
according to the observational studies, there is a higher incidence of rejection in patients with DGF than patients without DGF. so periodic biopsies of kidney with DGF is required to diagnose rejection as in this case one can not depend on serum creatinine level because the patient is on dialysis treatment.
New onset proteinuria
new onset proteinuria or unexplained proteinuria > 3 gm/day is an indication of graft biopsy as this proteinuria may be due to recurrent or de novo glomerular disease and these diseases are a potentially treatable cause of allograft dysfunction.
Protocol biopsies
The importance of protocol biopsy is the detection of subclinical rejection which is associated with reduced graft survival. according to a RCT, the diagnosis and treatment of subclinical rejection improve outcomes.
other conditions can be detected by protocol biopsy as: CNI toxicity, recurrent disease, transplant glomerulopathy, BK nephropathy.
The process is generally safe with low risk of complications(1%) such as bleeding, macroscopic hematuria with ureteric obstruction, peritonitis, graft loss(0.03%).
Protocol biopsies may be expensive, therefore the decision to do such biopsies should be shared with the patient.
Please reflect on your practice if possible
In my practice, most of the graft biopsies are done when there is clinical indication, we rarely do protocol biopsies and we make a shared decision with the patient if we want to do a protocol biopsy explaining the indications, risks, benefits, and the cost of the procedure.
The article addresses the kidney allograft biopsy topic , whether it was an indicated biopsy or protocol biopsy .
*Indicated biopsy whether if there was a creatinine increase in which the cut off point is not well set off but estimated 30% increase more than the baseline usually necessitates a renal biopsy after exclusion of reversible causes as dehydration , CNI toxicity ( high blood levels ) , infection or nephrotoxic drugs.
*DGF ,which entails the need of dialysis in the 1st week after transplantation , has more rates of acute rejection which justifies some centers that perform protocol biopsy several times in the DGF for detection of CNI toxicity , BKV nephropathy , or acute rejection .
while indicated biopsy is done in the DGF if there were no reversible causes of AKI are present .
According to my practice : Protocol biopsy is done for high risk , sensitized individuals , with history of 1ry glomerular disease , history of more then 1 transplant ; for detection of subclinical rejection .
regarding indicated biopsies ; there’s no argument that rising creatinine-and or proteinuria or increasing proteinuria with no apparent dehydration , high levels of CNI’s , -ve CMV , normal duplex and no obstruction by US , usually necessitates renal biopsy for detection of rejection , recurrence of the original kidney disease or others .
It’s worth saying that medical history , current IS , previous induction and/or desensitization , date of Tx , meticulous fluid balance especially early in the post Tx period affect the decision and the timing of the biopsy .
In your own words, summarise this article
Indicated biopsy – prompted by a change in the patient’s clinical condition and/or laboratory parameters.
Protocol biopsy– obtained at predefined intervals after transplantation, regardless of kidney function.
Causes of Increased serum-
First rule out
Dehydration
urinary obstruction
high CNI levels
other apparent causes
then likely causes are-
acute rejection
CAI
drug toxicity
recurrent or de novo kidney disease
BKV nephropathy
A persistent 30% rise in serum creatinine was an excellent predictor of subsequent graft failure. Additional biopsies may be required when an abrupt change in the rate of progression is observed.
Contraindication for a biopsy
bleeding diathesis
presence of large fluid collections or infection.
acute kidney injury
absolute increase in serum creatinine of ≥0.3 mg/dL
a percentage increase in serum creatinine of ≥50% (1.5-fold from baseline)
a reduction in urine output (documented oliguria of less than 0.5 mL/kg/h for more than 6 h).
*do require at least two creatinine values within 48 h.
Biopsies to be obtained every 7–10 days, while patients are receiving dialysis for DGF.
Protocol biopsies-
Use of protocol biopsies, therefore, for diagnosis of subclinical rejection may not be appropriate in tacrolimus- and MMF-treated patients.
Other conditions that can be detected on protocol biopsy are –
CNI toxicity
recurrent disease
transplant glomerulopathy
CAI
BKV nephropathy.
The risk of major complications from protocol biopsy is approximately 1% which includes-
substantial bleeding
macroscopic hematuria with ureteric obstruction
peritonitis
graft loss
The benefit of performing protocol biopsies is seen only in patients on CsA/azathioprine without induction therapy and in those may outweigh the harm.
Please reflect on your practice if possible
Protocol biopsies were not done in our centre. We used to do indication biopsies.
Nice to see you back Prakash