2. A 46-year-old male kidney transplant recipient (112 mismatch) received 2 courses of steroid pulses for ACR. Currently, he is on tacrolimus-based triple immunosuppression. He started complaining of right groin pain during walking requiring regular analgesia. His recent s Cr is 176 µmol/L with 1.5 gm/day proteinuria (recent onset). His plain X-ray right hip is shown below:
- What is your diagnosis
- Any other investigation required?
- What is your management plan?
Thank you for your reply
To your knowledge, the plain X-ray was reported as NORMAL. Will this normal finding change your diagnosis?
What is the sensitivity and specificity of plain X-ray in diagnosing AVN?
You did not comment on the proteinuria; please comment and tell us how you would manage the proteinuria.
The Sensitivity 76-89%.
The Specificity 77-97%.
Diagnosing Pre-collapse ONFH by radiography is of low sensitivity.
Diagnosis and stratifying the strategy of management depend entirely on MRI and presence of symptom or not. As the MRI is sensitive 100% in diagnosing AVN.
Having negative radiograph and positive MRI finding would help in ascertaining it as class 1 as per ARCO updated classification, which is class 1 pre-collapse., This classification outlines the prognosis, risk of progression and management, as, in addition to the presence of symptoms, extent of involvement according to ARCO is crucial to consider.
He was found to have impaired allograft function and proteinuria of 1.5 gram /day.
He is on CNI, Tac. based immunosuppression.
Its related either to recurrent disease, chronic allograft rejection, infection associated nephropathy such as PBKN and CMVN and lastly, it could be related to the current usage of NSAIDs to control the pain.
I would approach the case with.US of the allograft with Doppler of the allograft artery.
Urine testing for hematuria, decoy bodies, casts, dysmorphic RBCs.
NSAIDS related AKI is usually demonstrating nephrotic syndrome with underlying combined tubulointerstitial nephritis and minimal change glomerular disease.
ACMR and ABMR are another probable underlying causes, therfore, its indicative to assess Tacrolilus teough level and DSA titer.
Tac toxicity might feature impaired allograft function as well.
PCR for CMV and PBKN has ti be conducted as well.
Ultimately allograft biopsy is indicative here to further verify the allograft dysfunction.
Management is directed towards the underlying etiology
Many thanks, Dr Jebur.
Ajay
Thank you Wael for your reply
The sensitivity of plain X-Ray is lower than that. Please review and come back to us.
Thank you for your reply
To your knowledge, the plain X-ray was reported as NORMAL. Will this normal finding change your diagnosis?
What is the sensitivity and specificity of plain X-ray in diagnosing AVN?
You did not comment on the proteinuria; please comment and tell us how you would manage the proteinuria
===================================================================
Reference
Excellent Dr Mahmoud
Well done.
Yes, a biopsy of the kidney. Also, plain X-ray has low sensitivity.
Thanks alot our Prof.Halawa
Using plain film, the sensitivity for detecting the early stages of the disease is as low as 41%. Plain radiographic evidence of AVN might appear when the disease is at an advanced stage.
Regarding proteinuria and allograft dysfunction, he will require a repeat allograft biopsy. He was on NSAIDS which can lead to proteinuria, additionally, he already has a previous episode of ACR, so he could have other or had a recurrence of the original disease (e.g., recurrent FSGS, etc–)
X-ray sensitivity is 40 % for the diagnosis of AVN.
Will this normal finding change your diagnosis?
I will proceed with MRI and refer the patient to an orthopedic.
how you would manage proteinuria?
-the proteinuria post-transplantation has multiple DD.
first proteinuria and high renal profile require renal biopsy. evaluate the original kidney disease. exclude TG. send tac level and DSA.
-NSAIDs can be the cause of proteinuria by causing
chronic tubulointerstitial kidney disease(with regular usage), and minimal change disease. To differentiate needs a renal biopsy.
Excellent
X-ray sensitivity is 40 % for the diagnosis of AVN.
Will this normal finding change your diagnosis?
I will proceed with MRI and refer the patient to an orthopedic.
how you would manage proteinuria?
-the proteinuria post-transplantation has multiple DD.
first proteinuria and high renal profile require renal biopsy. evaluate the original kidney disease. exclude TG. send tac level and DSA.
-NSAIDs can be the cause of proteinuria by causing
chronic tubulointerstitial kidney disease(with regular usage), and minimal change disease. To differentiate needs a renal biopsy.
Diagnosis:
Steroid induce avascular necrosis.
Investigations needed to confirm diagnosis:
Treatment :
Proteinuria management:
References:
Thankyou
To your knowledge, the plain X-ray was reported as NORMAL. Will this normal finding change your diagnosis?
NO, will not change my diagnosis, but mandate further imaging by MRI.
What is the sensitivity and specificity of plain X-ray in diagnosing AVN?
The sensitivity for detecting early stages of the disease is as low as 41% by plain X-ray
You did not comment on the proteinuria; please comment and tell us how you would manage the proteinuria.
The proteinuria he has is significant, it could be analgesic induced proteinuria, rejection, recurrence of primary disease…etc However kidney biopsy is a must here, in order to clarify the patient further management.
I’ll start him on RAS blocker.
Thankyou
Diagnosis:
It is a case of AVN also known osteonecrosis may be due to steroid use, aseptic necrosis
Common sites head of the femur but may affect shoulder , knee , hands and ankles
Investigations needed to confirm diagnosis:
X-ray but in early stages may be normal also sensitivity around 40% it shows crescent sign , osteopenia or fracture
MRI : is the investigation of choice and high sensitivity more than 90%
Treatment :
General measures :
Use low dose and short course steroid also oral steroid is preferred
Avoid alcohol use
Rest
Pharmacological
Bisphosphonate
Surgical
As core decompression with or without grafting
X-ray can be normal in the presence of AVN, its sensitivity is 40%, MRI is the most sensitive method for diagnosing AVN, in the presence of contraindications to MRI, SPECT-CT is able to provide a suitable alternative for diagnosis of AVN of the head of femur.
Regarding proteinuria:
many causes for it:
for sure a graft biopsy is needed to guide the management.
Thankyou
Normal plain X-ray dose not exclude AVN.
Dear Professor,
★ ★ Role of X-rays in the diagnosis of AVN of Hip:
★ ★ Approach to proteinuria in this patient:
Reference:
Stoica Z, Dumitrescu D, Popescu M, Gheonea I, Gabor M, Bogdan N. Imaging of avascular necrosis of femoral head: familiar methods and newer trends. Curr Health Sci J. 2009 Jan;35(1):23-8. Epub 2009 Mar 21. PMID: 24778812; PMCID: PMC3945237.
Thankyou
Plain X-ray is sensitive just %50-80, even CT may miss early osteonecrosis. MRI is more sensitive. (medscape…)
https://acsearch.acr.org/docs/69420/Narrative/ includes the revised version of the radiologic evaluation of osteonecrosis
Regarding proteinuria, generally, proteinuria of more than 1.5 gram draws attention to new pathology. This could be a recurrence of the primary disease. we need to add ACI/ARB to reduce quantitative proteinuria but for that reason along with AMR biopsy will help. CCBs are not enough on their own.
your knowledge, the plain X-ray was reported as NORMAL. Will this normal finding change your diagnosis?
No because sensitivity and specificity of X ray in early stage is low and x ray appear normal in early stage
What is the sensitivity and specificity of plain X-ray in diagnosing AVN?
Its around 40%
You did not comment on the proteinuria;
please comment and tell us how you would manage the proteinuria.
Presence of proteinuria in this case may related to analgesic nephropathy or recurrence of original renal disease or infection
This patient need evaluation regarding proteinuria ( urine analysis for RBC and WBC
DSA level and drug level
assess to role out infection
Renal biopsy is mandatory because it’s the confirmed for diagnosis
MRI bone is highly sensitive and specificity reach to 90% even in early stage; so it is the confirmed diagnosis
If the X-ray was normal I would not change my mind re the diagnosis. In the early part or phase of the disease, an x-ray may not be sensitive enough to be seen.
Plan X-ray sensitivity for detecting early stages of avascular necrosis is as low as 41%.
I a study conducted by the international journal of sciences and research compared plain X-ray with MRI, and the table below shows the accuracy of the two images. as one can see, in the early phase of the disease, the X-ray was unable to detect when compared to MRI.
file:///C:/Users/Nadine/AppData/Local/Temp/msohtmlclip1/01/clip_image001.png
Proteinuria in transplant patients has multiple diagnoses and must be evaluated carefully and studied. Renal biopsy should be the mainstay for diagnosis and other investigations if a cause is suspected.
References:
Stoica, Z., et al, Current health science Journal (2009). Imaging of Avascular necrosis of Femoral Head: Familiar methods and newer trends. 2009 Jan-Mar; 35(1): 23–28
emedicine.medscape.com/article/386808-overview
On the basis of x ray I will keep AVN as first provisional diagnosis for cortical breech and irregularity of the lower medial head of femur looking to current symptoms and history of steroid therapy
But I can also see some rounded opacities in x ray, traversing pelvic cavity. It seems to be along course of ureter so would also consider multiple ureteric calculi in native kidney ureter.
X-ray can’t diagnose low grades of AVN with sensitivity of 38 to 41%
To confirm the visible abnormality of femur head, I will go ahead with MRI of the joint.
‘With the background of two episodes of ACR and proteinuria with raised creatinine, graft biopsy is mandatory
Yes Dr Saini
Plain X ray may be normal in cases of AVN (like the current case) even several months after beginning of symptoms with sensitivity reaching 40% in detecting early lesions, So it is neither sensitive nor specific
MRI hip is the investigation of choice with sensitivity 100% in detecting even early AVN (1) which should be done bilaterally to exclude multifocal disease which is present on 2/3 of cases (2)
What is your management plan regarding proteinuira?
References
1. Mont MA, Ulrich SD, Seyler TM, et al. Bone scanning of limited value for diagnosis of symptomatic oligofocal and multifocal osteonecrosis. J Rheumatol 2008; 35:1629.
2. Weisinger JR, Carlini RG, Rojas E, Bellorin-Font E. Bone disease after renal transplantation. Clin J Am Soc Nephrol 2006; 1:1300.
Xray is not sensitive nor specific because it could be normal in early lesions
MRI is specific and it’s sensitivity reach more than 90%
For proteinuria a biopsy will be needed for further assessment as the original disease could be recurrent
At the same time non dihydropridine CCB as verapamil ,Isoptin can be used or ACEI or ARBS will cautious monitoring of kidney function and stopped if serum creatnine increased more than 20% of base line ,and statins as well will be usefull
Normal finding on x ray will not change my diagnosis of AVN
sensitivity (Sn) and Specificity (Sp) for X-ray and MRI respectively for various stages was
For STAGE I was 34.29, 29.12 and 98.45,95.12
For STAGE II was 75.12,68.23 and 99.17,98.27;
for STAGE III 98.56,93.12 and 99.69,98.36;
for STAGE IV 99.34,92.19and 100,99.19 .
for proteinuria the patient was taking analgesia may be NSAID he needs allograft biopsy
we may give also ACI /ARBS or CCB such as verapmil for proteinuria
if the x-ray is normal will not change my mind regarding the diagnosis of avascular necrosis of the vascular
the sensitivity of the x-ray
proteinuria need kidney biopsy
Normal plain x-ray does not exclude AVN especially in the early stages because of low sensitivity (about 40%). So, requesting MRI and bone scan and refer to an orthopedist would be a good option.
Proteinuria in this case might be related to the use of NSAIDs for AVN, but other differential diagnoses should be considered, too. Kidney biopsy is necessary for accurate diagnosis.
Q1- To your knowledge, the plain X-ray was reported as NORMAL. Will this normal finding change your diagnosis?
No because the plain x ray is not sensitive to diagnose early stages of AVN.I will request MRA with high sensitivity and specificity
Q2- What is the sensitivity and specificity of plain X-ray in diagnosing AVN?
Plain film radiography
the sensitivity of x ray in diagnosing early stages of AVN is as low as 41%. It does not detect stage 0 and 1 AVN. A time lapse of 1-5 years may needed for x ray finding to appear.
Q3- You did not comment on the proteinuria; please comment and tell us how you would manage the proteinuria.
Proteinuria post transplantation is a bad sign associated with reduced graft survival.
May be due to
1- Transplant glomerulopathy.
2- Denovo GN.
3- Recurrent GN.
4- GN associated with drug NSAID.
5- Sub nephrotic range proteinuria may also occur in interstitial nephritis.
Supportive measures:
1- Stop NSAID.
2- Fluid and salt restriction.
3- Protein restriction.
4- ACEI and ARBS for their anti-proteinuric effect.
Send for DSA ,TAC trough level. Review previous investigation or biopsy (FSGS- FOR SUSPECTED RECURRENCE)
This patient need graft biopsy which is essential for histopathological diagnosis.
What is your diagnosis
In our index case, the pain beside history of high dose steroid are the key for suspicion of avascular necrosis of the femur neck
Any other investigation required?
The most sensitive and specific imaging for AVN is MRI with sensitivity more than 90%. Early detection may require gadolinium.
What is your management plan
Rest
Electrical stimulation done intraoperatively or through electrode to skin to stimulate new bone formation
orthopedic interventions including core decompression, bone graft
X-ray has low sensitivity as 41% and would be evident in advanced stages. It shows bone deformities, such as flattening, subchondral radiolucent lines (crescent sign), and collapse of the femoral head.
as regard to the proteinura , it needs further investigation using biopsy for the graft to diagnose the definite cause
Among the main differential diagnoses would be the onset of septic arthritis (which could even be related to an opportunistic pathogen due to immunosuppression) and avascular necrosis of the femoral head.
Performing a magnetic resonance exam would be important to differentiate the two situations. X-ray has low sensitivity and specificity for both diagnoses.
Depending on the findings, it could progress with the need for a joint puncture or not. And then the definition by need for antibiotics.
With regard to proteinuria, which in the long term is harmful to the graft and increases the risk of developing cardiovascular disease, we have to assess its etiology through biopsy (it may be residual, rejection or another event) and assess the change in the immunosuppressive regimen.
Diagnosis ：AVN.
Other investigations :
MRI of right hip joint. However, risk of nephrogenic systemic fibrosis need to explain to patient.
renal graft biopsy.
FK level to exclude FK toxicity.
Check BK and CMV virus PCR.
Management :
1) Orthopedic referral KIV orthopedic intervention with bone biopsy for HPE.
2)Bisphosphonate.
3) Analgesic.
Clinical and based on history Avascular necrosis (osteonecrosis) of the hip, points toward diagnosis:
o Complain of right groin pain during walking
o High dose of steroid
o No mention of prophylaxis medication
§ Normal x-ray is expected in early stages
MRI
o MDT is mandatory , rest and analgesia
o Bisphosphonates act to slow bone resorption
o Statins are sometimes used to treat steroid-induced AVN
o Nonpharmacologic options with overall limited evidence include electrical stimulation, hyperbaric oxygen and extracorporeal shock wave therapy (ESWT).
Likely diagnosis is Avascular necrosis of femur head.It occurs in about 5-20% of renal transplant patients and other risk factors like long steroid use increase the risk further.
MRI without a contrast agent ,having sensitivity and specificity >99% remains the “gold standard while XRAYs can missed the diagnosis in the early stages of AVN due to low sensitivity.CT scan can be used in some cases.
Management plan: Supportive treatment of AVN includes bed rest ,use of NSAIDs for mild –moderate pain and for severe pain, sometimes opoids can be taken .Steroids to be stopped but only after ruling out rejection.Calcium and vit D supplements if needed.Physical therapy can also help in some cases and use of assisted walking devices like crutches ,canes .Specific treatment includes core decompression drilling and bone grafting and if all failed then total hip arthroplasty.
2.Proteinuria and Worsening Graft function.
For this ,we need thorough evaluation first –Allograft biopsy with C4d staining and also immunofluorescence needed to rule out rejection,followed by DSA and also possibility of NSaid interstitial nephritis to be ruled out . Infectious screening and Tac level are also must.Once the cause identified ,then treatment according to that.
REFERENCES:
1- Hedri H, Cherif M, Zouaghi K, et al. Avascular osteonecrosis after renal transplantation. Transplant Proc 2007; 39:1036.
2- Osmani F, Thakkar S, Vigdorchik J. The Utility of Conservative Treatment Modalities in the Management of Osteonecrosis. Bull Hosp Jt Dis (2013) 2017; 75:186
mostly avascular necrosis of head of femur due to steroids, and the normal x ray
hip MRI which detects early changes of AVN
discuss the case in the MDT with the orthopedics team, for possible coservative management followed by arthroplast
regarding proteinurea>> needs graft biopsy
AVN is difficult to diagnose by plain X-Ray film as it’s sensitivity are very low[ 41%] especially in early stages of the disease (stage 0&1).
The modality of choice for early detection of AVN is the MRI.
Treatment include both supportive measures and surgical .
The DDX of proteinuria in this case include :
So we must send for drug level , DSA , graft biopsy, infectious screen (CMV and BKV ) .
Right groin pain during walking in post transplant candidate on steroid regimen should raise the suspicious of avascular necrosis of femoral head(AVN). It has been reported in 5 to 20% of renal transplant patients in few reports.(1,2)
Plain X ray in initial case may remain normal for months after symptoms begin(as in this case). The earliest findings are mild density changes, followed by sclerosis and cysts as disease progresses. Sensitivity and specificity of plain radiograph varies between 76% to 97% (3).
MRI: has a sensitivity of upto 100% and can pick up initial phase when X ray is normal and advised here
Mangement:
References:
Diagnosis
Avascular necrosis of the femoral head.
It is a type of osteonecrosis due to disruption of blood supply to the proximal femur..
causes in this case :steroid therapy.
Other investigation required
MRI: is the most sensitive ( sensitivity more than 90%) diagnostic imaging procedure for early detection of AVN.
It can establish the diagnosis of AVN in symptomatic patient before radiologic changes become apparent. Even more it can detect early stages of AVN in high risk asymptomatic patients.
CT scan can be useful to exclude subchondral fractures, its sensitivity is about 55%
Skeletal scintigraphy,its sensitivity is about 55%.
Management
Management of the collapsing lesion is operative ( arthroplasty)
Management of the pre-collapse stage include conservative and operative
Operative
Core decompression give value in small to medium sized pre-collapse lesion.
Bone grafting for medium to large sized lesion.
Conservative
physical therapy,restricted weight bearing,alcohol cessation.
In plain Xray, the sensitivity for detecting early stages of disease is low as 41%, also it does not detect stage 0 and 1 AVN.
Proteinuria post-transplant may suggest acute allograft rejection, transplant glomerulopathy, de novo or recurrent disease or due to analgesic nephropathy
Kidney biopsy is needed to confirm the diagnosis.
Barney J, Piuzzi NS, Akhondi H. Femoral Head Avascular Necrosis. [Updated 2022 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.
Stoica Z,
Dumitrescu D, Popescu M, Gheonea I, Gabor M, Bogdan N. Imaging of avascular
necrosis of femoral head: familiar methods and newer trends. Curr Health Sci J.
2009 Jan;35(1):23-8.
Avascular osteonecrosis
Magnetic resonance imaging (MRI) is generally required preoperatively to demonstrate the level of anatomic detail required to plan surgery. The sensitivity and specificity of MRI for the diagnosis of osteonecrosis of the femoral head is >99 percent . In addition, MRI is better than plain radiography for assessing the extent of involvement and location of the lesion, which influences treatment choice and prognosis.
Several radiologic classification systems are available, but the updated Association Research Circulation Osseous (ARCO) staging system determine the best treatment approach. The extent of involvement and location of disease determine the choice of treatment. As an example, from the ARCO staging system for the hip, the extent of involvement is:
<15 percent of involved bone
15 to 30 percent of involved bone
>30 percent of involved bone
Supportive care for osteonecrosis consists of measures such as bed rest, offloading as tolerated (using assistive walking devices including crutches, canes, and walkers), and the use of analgesics and other potential therapies. Nonsteroidal antiinflammatory drugs (NSAIDs) may relieve pain. Opioid medications may be used for short periods of time when other pain medications are inadequate for moderate to severe pain while awaiting definitive surgery. Physical therapy may also help relieve some symptoms.
Although there are no medical treatments known to prevent progression, pharmacologic treatments have been tried. These include bisphosphonates, lipid-lowering agents, and anticoagulants and are discussed further below.
Surgical options for osteonecrosis generally include procedures that preserve the joint, and when the joint cannot be preserved, total joint replacement. The choice depends upon the extent of involvement and location of disease.
up to date
What is your diagnosis
My first DD with clinical scenario will be avascular necrosis of head of femur. However, X-ray looks normal because it is of low sensitivity around 40% in detecting AVN.
Any other investigation required?
MRI hip is the modality of choice, its sensitivity is above 90% and can detect early changes. Other modalities like bone scan and SPECT can be used if MRI is not available or contra-indicated.
What is your management plan?
Active issues: AVN of right neck of femur, Proteinuria> 1.5 g/day, high creatinine 176 umol/L. AVN of femur: management: use crutches to reduce weight bearing, pain control, avoid NSAIDS, reduction of steroid dose and bisphosphonates can be used.
Hip arthroplasty is the definitive treatment.
For proteinuria and high creatinine—à transplant biopsy should be done, DSA.
Q1- What is your diagnosis?
The diagnosis is avascular necrosis of femoral head.
Q2- Any other investigation required?
MRI and CT scan: These tests produce detailed images that can show early changes in bone that might indicate avascular necrosis.
Bone scan: is also helpful.
Q3- What is your management plan?
Treatment outcomes correlate directly with the stage of the disease.
No medical treatment has proven effective in preventing or arresting the disease process.
Conservative measures include :
1- Stop the offending drug.
2- limited weight bearing with crutches, and pain medications.
3- Immobilization may be helpful in some cases .
4- In advanced AVN, the disease course is unaffected by activity and will eventually require surgery.
5- Treatment with bisphosphonates may be helpful.
6- Iloprost, a vasoactive prostaglandin analog that is approved for inhalational treatment of pulmonary hypertension, has shown clinical and radiographic benefits in early-stage AVN when administered intravenously.
7- Statin therapy to prevent corticosteroid-induced AVN may be helpful.
8- Extracorporeal shockwave therapy (ESWT) has shown beneficial effects in early AVN of the femoral head.
Hyperbaric oxygen therapy (HBOT) has demonstrated beneficial effects in early AVN of the femoral head.
1- Avascular necrosis ( steriod induced )
2- Acute kidney injury with protienurea
For diagnosis of Avascular necrosis
1- X ray : could be normal in early stages of disease
2- MRI is the most sensitive and specific imaging modality for diagnosis
3- CT : for surgical planning, CT is primarily utilized to assess the degree and location of articular collapse and to identify early secondary degenerative joint disease
4- Vit D , Ca , PTH to rule out other medical causes
For AKI
1- Transplanted kidney U/S with Doppler to assess perfusion and RI index
2- Eosinophilic count in urine ( acute interstitial nephritis )
3- DSA
4- Kidney biopsy looking for rejection
5- Tac level
For AVN
Risk factors for AVN: some reported that high daily doses are a major contributing factor for development of AVN. Others authors describes the numbers of ‘pulse dose’ episodes are more critical for development of AVN.
Reduce dosage below 15 mg – 20 mg of total steroid per day, the risk of AVN of the femoral head is less than 3%.
Avoid pulses of steroid if possible
To do a graft biopsy to look for cause of proteinuria
AVN can be managed by:
The management of AVN will be discussed in MDT consist of transplant team and orthopedic surgeon
For AKI
We treat according the results of kidney biopsy and lab
X-ray has sensitivity of 40 % for the diagnosis of AVN.
Will this normal finding change your diagnosis?
MRI is needed with orthopedic consultation.
Post-transplantation has multiple causes:
proteinuria with high renal profile require renal biopsy. evaluate the original kidney disease& exclude TG. check tac level & DSA.
-NSAIDs can be underlying cause of proteinuria due to chronic tubulointerstitial kidney disease(with chronic use), and minimal change disease. Renal biopsy addresses the etiology.
Avascular necrosis of the femoral head due to steroid usage.
MRI is the best modality for the diagnosis of AVN with about 99-100% sensitivity especially in early stages. Bone scan is another modality for its diagnosis.
Medical treatment includes limiting weight bearing and using pain killers for small segment involvement. Other treatments are bisphosphonates, IV iloprost (a vasoactive prostaglandin analog), statins, extracorporeal shock wave therapy and hyperbaric oxygen therapy. Surgical treatment includes core decompression with or without bone graft in early stages and total hip replacement for advanced stages.
Reference: emedicine
Avascular necrosis of head femur is suspected, plain radiograph are not enough for early diagnosis.
MRI is used to diagnose early stage with high sensitivity.
Management should include referral to orthopedic surgeon, management may be conservative including bed rest, walkers and analgesia, joint preserving procedures or total hip arthroplasty.
Regarding proteinuria 1.5gm/day, the patient should perform allograft biopsy to determine the cause of proteinuria and determine further plan of management.
antiproteinuric measures as non dihydropyridines (verapamil) may be considered, ACE-I or ARBs can be used but with close monitoring of eGFR and hyperkalemia.
Bohndorf K, Roth A. Bildgebung und Klassifikation der aseptischen Hüftkopfnekrose [Imaging and classification of avascular femoral head necrosis]. Orthopade. 2018 Sep;47(9):729-734. German.Cherukuri A, Welberry-Smith MP, Tattersall JE, Ahmad N, Newstead CG, Lewington AJ, Baker RJ (2010) The clinical significance of early proteinuria after renal transplantation. Transplantation 89:200–207.
1-0 what is your diagnosis?
avascular necrosis of the hip joint induced by corticosteroid therapy.
the pathogenesis associated with osteonecrosis has not been established and several mechanisms have been proposed.
further investigation is an MRI hip
the sensitivity of the hip x-ray is 41%.
proteinuria needs a renal biopsy to see if any, or recurring disease, viral infection
control the blood pressure is mandatory
Could be AVN, would be needing MRI pelvis to confirm diagnosis.
yes, need graft biopsy to confirm the protienuria and cause of raising s.Cr.
Renal biopsy, DSA, MRI pelvis, pulse with methylprednisolone.
mechanisms of avascular necrosis with steroids:
Risk factors
Diagnosis:
What is your management plan?
It’s little bit complicated case with multiple points that should be considered
1. Regarding AKI and proteinuria
· Drugs induced by NSAID so should be stopped and other options should be considered after pain control referral.
· CMV and BK should be done
· CNI trough level
· DSA
· Complete clinical evaluation especially for volume status
· If there is no obvious cause, a kidney biopsy should be considered.
2. Regarding the probability of AVN
MRI should be done for a better evaluation of the current situation.
The problem is if we have ACR with AVN at the same time it will need a multidisciplinary team including orthopedics involvement and good patient counseling.
according to symptoms, the size and the stage of the lesion the management plan includes
REFERANCES
1. Shigemura T, Nakamura J, Kishida S, et al. Incidence of osteonecrosis associated with corticosteroid therapy among different underlying diseases: prospective MRI study. Rheumatology (Oxford) 2011; 50:2023.
2. Hedri H, Cherif M, Zouaghi K, et al. Avascular osteonecrosis after renal transplantation. Transplant Proc 2007; 39:1036.
3. Marston SB, Gillingham K, Bailey RF, Cheng EY. Osteonecrosis of the femoral head after solid organ transplantation: a prospective study. J Bone Joint Surg Am 2002; 84:2145.
4. Wang A, Ren M, Wang J. The pathogenesis of steroid-induced osteonecrosis of the femoral head: A systematic review of the literature. Gene 2018; 671:103.
5. Jones JP Jr. Fat embolism and osteonecrosis. Orthop Clin North Am 1985; 16:595.
6. Solomon L. Idiopathic necrosis of the femoral head: pathogenesis and treatment. Can J Surg 1981; 24:573.
7. Nishimura T, Matsumoto T, Nishino M, Tomita K. Histopathologic study of veins in steroid treated rabbits. Clin Orthop Relat Res 1997; :37.
8. Dilisio MF. Osteonecrosis following short-term, low-dose oral corticosteroids: a population-based study of 24 million patients. Orthopedics 2014; 37:e631.
9. Mont MA, Pivec R, Banerjee S, et al. High-Dose Corticosteroid Use and Risk of Hip Osteonecrosis: Meta-Analysis and Systematic Literature Review. J Arthroplasty 2015; 30:1506.
10. Abeles M, Urman JD, Rothfield NF. Aseptic necrosis of bone in systemic lupus erythematosus. Relationship to corticosteroid therapy. Arch Intern Med 1978; 138:750.
11. Mont MA, Ulrich SD, Seyler TM, et al. Bone scanning of limited value for diagnosis of symptomatic oligofocal and multifocal osteonecrosis. J Rheumatol 2008; 35:1629.
12. Weisinger JR, Carlini RG, Rojas E, Bellorin-Font E. Bone disease after renal transplantation. Clin J Am Soc Nephrol 2006; 1:1300.
13. Hungerford DS, Jones LC. Asymptomatic osteonecrosis: should it be treated? Clin Orthop Relat Res 2004; :124.
14. Osmani F, Thakkar S, Vigdorchik J. The Utility of Conservative Treatment Modalities in the Management of Osteonecrosis. Bull Hosp Jt Dis (2013) 2017; 75:186.
● WHAT IS YOUR DIAGNOSIS ?
Most probably avascular necrosis of neck femur , that is not evident in x ray as it has poor sensitivity.
● ANY OTHER INVESTIGATION?
Mri
Sensitive by 85% in differentiating AVN from NON -AVN disease
And up to 100% in differentiating it from normality
Specificity 98%
● MANAGEMENT PLAN :
It is mostly stage 0 or 1 ,being not apparent in x ray.
Both hibs showed be included as there is high incidence of being bilateral.
TTT includes:
•NSAIDs +/_
•Osteoporotic agents
•Statins
•Blood thinners
•Surgical decompression / bone graft/ bone reshaping
● WILL NORMAL X RAY CHANGE DIAGNOSIS
No
● SENSITIVITY & SPECIFICITY OF PLAIN XRAY :
Sensitivity around 40 %
Specificity :
● COMMENT ON PROTEINURIA AND MANAGEMENT PLAN
Nephritic range that has DD
it could be:
• Rejection ( ABMR or ACMR)
• Recurrence of original disease.
• Nsaids induced tubulo- interstitial disease
This mandates renal biopsy + DSA + urine analysis for casts +/- {decoy cells + Bk pcr + cmv pcr }.
References
https://pubmed.ncbi.nlm.nih.gov/3420260/
https://www.uptodate.com/contents/search
https://www.niams.nih.gov/health-topics/osteonecrosis
According to complain of right groin pain during walking requiring regular analgesi and history of receiving high doses if steroids,
2 pulse therapy added to regular daily steroids as part of triple immunosuppression protocol Avascular necrosis of the femoral head is suggested.
it is a type of osteonecrosis due to disruption of blood supply to the proximal femur.
It can occur due to a variety of causes, either traumatic or atraumatic in origin. These causes include fractures, dislocations, chronic steroid use, chronic alcohol use.
Despite evidence demonstrating the correlation between steroid use and osteonecrosis, the exact pathophysiology is not clear and probably multifactorial. The cause is most likely an aggregate of factors such as fat emboli, fat cell hypertrophy leading to increased intraosseous pressure, endothelial dysfunction, hyperlipidemia, and abnormality of the stem cell pool of the bone marrow; all of which contribute to ischemia and subsequent necrosis.
Diagnosis is made by pairing the clinical presentation with appropriate imaging. Imaging can include x-rays, radionuclide bone scanning, and magnetic resonance imaging (MRI)
Radiographs may show subchondral radiolucency, which is the pathognomonic “crescent sign,” indicating subchondral collapse.
MRI is the gold standard of diagnosis for osteonecrosis. Though both X-rays and radionuclide scans can aid in the diagnosis, neither is as sensitive as MRI; nor as reliable at showing radiographic evidence early in disease progression.
first Line is to stop the cause by trying to minimise steroid or use of stetoids free protocol,non-operative treatments or core decompression can show value in asymptomatic and symptomatic small to medium-sized pre-collapse lesions.
Medium to larger-sized lesions can have treatment with bone grafting (vascularized or non-vascularized), or osteotomies.
If femoral collapse has occurred or acetabular involvement is present, arthroplasty is indicated.
Patient Also have proteinuria of recent onset 1.5 gm / day with analgesic abuse renal biopsy is recommended with stop of analgesics .
Barney J, Piuzzi NS, Akhondi H. Femoral Head Avascular Necrosis. [Updated 2022 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing;
According to complain of right groin pain during walking requiring regular aanalgesi and hhistory of receiving high doses if steroids, 2 pulse therapy added to regular daily steroids as part of triple immunosuppression protocol Avascular necrosis of the femoral head is suggested.
it is a type of osteonecrosis due to disruption of blood supply to the proximal femur.
It can occur due to a variety of causes, either traumatic or atraumatic in origin. These causes include fractures, dislocations, chronic steroid use, chronic alcohol use.
Despite evidence demonstrating the correlation between steroid use and osteonecrosis, the exact pathophysiology is not clear and probably multifactorial. The cause is most likely an aggregate of factors such as fat emboli, fat cell hypertrophy leading to increased intraosseous pressure, endothelial dysfunction, hyperlipidemia, and abnormality of the stem cell pool of the bone marrow; all of which contribute to ischemia and subsequent necrosis.
Diagnosis is made by pairing the clinical presentation with appropriate imaging. Imaging can include x-rays, radionuclide bone scanning, and magnetic resonance imaging (MRI)
Radiographs may show subchondral radiolucency, which is the pathognomonic “crescent sign,” indicating subchondral collapse.
MRI is the gold standard of diagnosis for osteonecrosis. Though both X-rays and radionuclide scans can aid in the diagnosis, neither is as sensitive as MRI; nor as reliable at showing radiographic evidence early in disease progression.
first Line is to stop the cause by trying to minimise steroid or use of stetoids free protocol,non-operative treatments or core decompression can show value in asymptomatic and symptomatic small to medium-sized pre-collapse lesions. Medium to larger-sized lesions can have treatment with bone grafting (vascularized or non-vascularized), or osteotomies. If femoral collapse has occurred or acetabular involvement is present, arthroplasty is indicated.
Patient Also have proteinuria of recent onset 1.5 gm / day with analgesic abuse renal biopsy is recommended with stop of analgesics
AVN,Most likely the patient was used NSAID as anglesia whichis lead to AKI,Xray had low senstavity compared to the MRI which is indicated in this case.
also he need good hydration plus to replay the control of renal biobsy to exclude any sign of rejection as well as need to send PRA
The diagnosis of right hip pain which is more on walking requiring analgesia in the background clinical context of prolonged steroid exposure is Avascular necrosis or osteonecrosis of the right hip.
This patient is a renal transplant patient with 112 mismatch transplant and has suffered 2 episodes of acute cellular rejection and has received steroid pulses for the same…
The given X ray shows normal neck of the femur, but the head has some cortical irregularity with subchondral collapse of the femoral head indicating advanced AVN. The x ray is often normal in most of the cases and the sensitivity and specificity of X ray in the diagnosis of AVN is 45 – 50% only. The most useful investigation in diagnosis of AVN is MRI of the right hip. It will tell the diagnosis and also assess the prognosis of the disease. Other investigations like SPECT CT scan and CT scan of the hip also have varied sensitivity and specificity of 60 – 90%.
The treatment of AVN is a bed rest and reduced weight baring over the joint. Analgesics can be given and the ultimate treatment of choice would be Total hip replacement. Bone grafting and cement also will help in few mild cases…
There have been various studies in renal transplant patients comparing the total steroid doses either in pulses or in cumulative to the incidence of AVN. DE graff et al showed that total dose of 5000mg in cumulative have increased incidence of AVN in transplant patients.
Protenuria of 1.5gm/day with creatinine of 1.5mg% requires investigations…we need some more history regarding the basic disease of the patient as in which type of Glomerulonephritis..The sensitization history of the patient is important…The induction regimen used in this patient is also important as the patient developed 2 episodes of ACR requiring 2 steroid pulses…The most important history I would elicit is drug compliance…and I would also like to review the drug chart post operatively..I would also like to see if the Tacrolimus levels were optimum…The patient has history of use of Analgesia (maybe NSAIDS) which can be responsible for proteinuria and azotaemia..So eliciting history on the type of analgesia is important here… The patient has already proteinuria so bisphosphonates for use in AVN will be contraindicated….Graft biopsy is indicated for azotaemia and proteinuria ….If the graft biopsy is normal we can assume it is due to NSAIDS…Else we treat based on the biopsy findings
What is your diagnosis
Osteonecrosis or avascular necrosis
Secondary to renal transplant 5-20 % or steroids induced
For the AKI and proteinuria secondary to either rejection or NSAIDS TIN
Any other investigation required?
X ray alone is not enough and may remain normal for months
The sensitive study is MRI and we should do ARCO radiological scoring system to determind to severity and possible management
Radinuclotide bone scan may show false negative result up to 20%
For elevated cr and proteinuria we need to check tac level , r/o infection , obstruction , recurrence of disease or even rejection by sending DSA and doing biopsy
What is your management plan?
For AVN if we can use steroid free regimen , supportive measurement or bisphosphanate or surgical interventions if needed
For the AKI and proteinuria Depend on the cause
What is your diagnosis
Avascular necrosis of femoral head
Any other investigation required?
MRI is the best tool with sensitivity around 100% . The sensitivity of plain X ray is around 41%.
What is your management plan?
He will need rest, analgesia- pain team review.
Bisphosphonate , vitamin D and calicitonin can be used He will also need orthopaedic referral.
The options will be debridement and graft in early stages . later stages usually require of Hip replacement.
As regards proteinuria the management will depend upon the cause. Biopsy can be helpful in finding the cause. these can be chronic allograft rejection, recurrence of primary disease, infections and NSAID injury.
The patient will also require assessment of –
TAC levels
DSA
Infections screen-PCR for CMV and PBKN
Renal Doppler
What is your diagnosis
AVN; most likely due to steroids.
Any other investigation required?
· Plain X-ray is less sensitive in detecting AVN. It’s sensitivity is as low as 40%.
· MRI of the is more sensitive in diagnosing AVN of the hip.
What is your management plan?
1. AVN;
· analgesia and orthopedic referral.
· Attempts to use low dose steroids plus prophylactic bisphosphonate.
2. Proteinuria and rising SCr:
· Proteinuria may be explained by the followings; rejection(ACR or CAN), use of NSAIDs, chronic TIN or even recurrent primary disease(if any).
· Ultrasonography and Doppler study of the graft is required to review the graft size, vasculature and RI.
· Kidney biopsy is needed to establish the exact pathological process that lead to proteinuria and rising SCr.
· TAC level is required for fine adjustment and to rule out CNI adverse effects.
What is your diagnosis
AVN Avascular necrosis mainly due to steroids
AVN is the death of bone tissue due to a lack of blood supply. Also called osteonecrosis, it can lead to tiny breaks in the bone and cause the bone to collapse. The process usually takes months to years.
A broken bone or dislocated joint can stop the blood flow to a section of bone. Avascular necrosis is also associated with long-term use of high-dose steroid medications and too much alcohol.
Diagnosis
The use of magnetic resonance imaging (MRI) removes the delay in diagnosis. An MRI is considered the gold standard for diagnosing AVN of the hip because it can detect the disease more quickly than radiography.9 It has a sensitivity of more than 99%, can detect crescent signs earlier, and is capable of detecting bone marrow changes including edema and sclerosis sooner than plain radiographs.
According to Role of plain radiograph versus MRI in avascular necrosis of femoral head
Amit H Deshmukh1, Shalaka A Deshmukh2* study
sensitivity (Sn) and Specificity (Sp) for X-ray and MRI respectively for various stages was
For STAGE I was 34.29, 29.12 and 98.45,95.12
For STAGE II was 75.12,68.23 and 99.17,98.27;
for STAGE III 98.56,93.12 and 99.69,98.36;
for STAGE IV 99.34,92.19and 100,99.19 .
From this we can notice that for early stages plain X-ray is less sensitive and specific as compared to MRI.
Management plan
For AVN
Treatment
The goal is to prevent further bone loss.
Medications
In the early stages of avascular necrosis, certain medications may help ease symptoms:
Therapy
Your health care provider might recommend:
Surgical and other procedures
Because most people don’t develop symptoms until avascular necrosis is advanced, your health care provider might recommend surgery. The options include:
Regenerative medicine treatment. Bone marrow aspirate and concentration is a newer procedure that might help avascular necrosis of the hip in early stages. During surgery, the surgeon removes a sample of dead hipbone and inserts stem cells taken from bone marrow in its place. This might allow new bone to grow. More study is needed.
For proteinuria we need to know the cause before treatment so we must do renAl biopsy.
Reference
Myoclinic
Role of plain radiograph versus MRI in avascular necrosis of femoral head
Amit H Deshmukh1, Shalaka A Deshmukh2*
This index transplant recipient has 2 DR mismatches, 2 previous episodes of acute rejections managed by steroids and currently on triple immune suppression.
Currently he has 2 problems :
1. RT groin pain and he is receiving analgesia.
2. Worsening graft function with recent onset non-nephrotic range proteinuria
Given the history of steroids. The most likely diagnosis is avascular necrosis of the hip(osteonecrosis).
– Careful history and clinical examination is required to identify risk factors for AVN like excess alcohol intake, gout and dyslipidemia and to to exclude other causes of RT groin pain like:
Musculo-skeletal causes like degenerative of inflammatory arthritis
Soft tissue like ileo-psoas bursitis
Neurological conditions like lumbar radiculopathy
– steroids can cause more than 53% of AVN. This is correlated with both dose and duration of therapy.
In the above scenario, We do not need to forget that there is worsening of the graft functions with recent proteinuria. This could result from:
– The use of NSAIDS for pain control that can cause nephrotoxic ATN or acute interstitial nephritis with proteinuria or MCD. Bisphosphonates(pamidronate) may cause secondary FSGS.(careful drug history is important)
-ACR(steroid resistant) or mixed a rejection. So, we need to be exclude as ACR may trigger de novo DSA and chronic AMR(Tx biopsy is warranted)
– Assessment of TAC trough level
– Check for BK and CMV
– Careful history about the original kidney disease that may recur in the current transplant.
X ray can be normal in early cases of AVN, Accordingly, if the diagnosis is suspected clinically, MRI is required(highly sensitive and specific)
Regarding the transplanted graft, we need TAC trough level, infectious screening, transplant biopsy with C4d staining and DSA with Luminex SAB
– Complex case requiring multidiscipline approach
– For the RT groin pain:
– Medical management: Bed rest, analgesia may be beneficial in early stages(revise type and dose of analgesia), steroid free protocol is a dilemma in this case with previous ACR and progressive worsening of renal functions with proteinuria. However, we need to assess pros vs cons.
– Surgical treatment: referral to the orthopedic team for total hip replacement which is the definitive treatment in advanced stages
– For worsening graft function and proteinuria:
– Renal biopsy is a corner stone in this case to exclude steroid resistant ACR or chronic AMR especially if there is a need to withdraw steroids.
– DSA with Luminex SAB
– TAC trough level
– Check for BK and CMV
References
1. Alalawi F et al. The Impact of Avascular Necrosis (Avn) Risk on Decision-Making in Regard to Planning Immunosuppression in Renal Transplant Recipients. Ann Clin Nephrol. 2017.Vol.1 No.1
2. Hines JTet al, Osteonecrosis of the Femoral Head: an Updated Review of ARCO on Pathogenesis, Staging and Treatment. J Korean Med Sci. 2021 Jun 21;36(24)
Steroid induced avascular necrosis of femoral head.
MRI of hip joint.
He had recent onset proteinuria which needs biopsy.
– Avascular necrosis of the Hip .
– Regarding AVN of hip :
MRI is abetter tool for diagnosis , X ray can show no abnormality especially during early period .
– Regarding proteinuria :
Kidney biopsy will be helpful as many causes of proteinuria can exist here such as NSAIDs associated interstitial nephritis , acute rejection , chronic allograft injury , recurrence of primary disease or CNI toxicity .
– Tacrolimus level & DSA titre.
– Ca , po4 , PTH & alkaline phosphatase to asses for MBD .
– Orthopaedic referral for surgical options , debridement of necrotic tissue , fixation or hip replacement .
– Regarding proteinuria >>depend on the results
– Avascular necrosis (AVN)of the femur head due to the use of corticosteroids for treatment of acute rejection which is an independent risk factor for AVN development .
– MRI is the most sensitive and specific
CT scan is less sensitive
Technetium 99 bone scan
PET scan for early lesions
labs tests ;intactPTH level , bone alkaline phosphatase , serum Ca , PO4, eGFR, 25OH-vitamin D, C telopeptide level.
-steroids need to be withdrawn
This case is challenging needs MDT involving orthopaedic physician
For AVN
Bisphosphonates can be given although studies declared that alendronate has short-term efficacy in reducing pain, improving articular function.
Vitamin D and calcitonin
Extracorporeal shockwave therapy use with alendronate can be beneficial for early cases in improving the hip function
Hyperbaric oxygen therapy can be useful in early AVN of the femoral head
Statin therapy could have been used on preventive bases and it has antiproteinuric effect as well.
In early stages of AVN (precollapse), core decompression with or without bone graft is the most suitable treatment.
In late stages, characterized by collapse, femoral head deformity, and secondary osteoarthritis, total hip arthroplasty is the choice.
For ACR
It will be according to the biopsy
In fact aggressive T cell–depleting induction therapy using either anti-thymocyte globulin (ATG) or alemtuzumab can enable glucocorticoid withdrawal.
The maintenance immunosuppression protocol is tacrolimus with MMF
If Rejection is mixed PE with IVIG with or without rituximab
If NSAID were used as analgesic it has to be stopped
Reference
-Alalawi F, Alnour H, Kosi ME, Jin JK, Sharma A, Halawa A. (2017) The Impact of Avascular Necrosis (Avn) Risk on Decision-Making in Regard to Planning Immunosuppression in Renal Transplant Recipients. Ann Clin Nephrol. Vol.1 No.1: 1.
-Patel SB . et al . Avascular Necrosis Treatment & Management.Medscape Aug 19 .2022
Xray is not sensitive nor specific because it could be normal in early lesions
MRI is specific and it’s sensitivity reach more than 90%
For proteinuria a biopsy will be needed for further assessment as the original disease could be recurrent
At the same time non dihydropridine CCB as verapamil ,Isoptin can be used or ACEI or ARBS will cautious monitoring of kidney function and stopped if serum creatnine increased more than 20% of base line ,and statins as well will be usefull
What is your diagnosis?
Mostly of avascular necrosis of femoral bone ( Head )
Kidney transplant ( High risk group )
Typical pain (right groin pain during walking )
History of high dose steroids
His plain X-ray right hip : Normal
Graft dysfunction :
associated with proteinuria
may be steroid resistant ACR
or Mixed rejection ( cellular and Antibody mediated )
recurrence of primary GN
Investigations required?
X ray : Plain radiographic findings are unremarkable in early stages of AVN. However, the American College of Radiology (ACR) considers x-ray the appropriate initial imaging study in patients at risk for AVN
MRI is the most sensitive and specific imaging modality for diagnosis
CT : for surgical planning, CT is primarily utilized to assess the degree and location of articular collapse and to identify early secondary degenerative joint disease
No laboratory tests indicate or reveal the diagnosis of avascular necrosis (AVN) however Vitamin D , PTH , Ca levels are needed .
Bone Biopsy : not routinely done due to the availability of sensitive noninvasive tests such as MRI. .
For DGF :
DSA
Renal biopsy + C4d staining
FK trough level
Renal Duplex
Urine analysis
CMV PCR
Eosinophil in urine
CBC
Management plan?
For Femoral Bone :
Medical :
Plan for rapid withdrawal of steroids
limited weight bearing with crutches, and pain medications
Extracorporeal shockwave therapy (ESWT) has shown beneficial effects in early AVN of the femoral head
Hyperbaric oxygen therapy
Statin therapy to prevent corticosteroid-induced AVN may be helpful
Surgical :
In early stages (precollapse): core decompression with or without bone graft
In late stage : total hip arthroplasty
Graft Dysfunction :
According to etiology
resistant ACR : ATG
Mixed AR : Plasma Exchange + Rituximab
Recurrent GN according to primary disease
Interstitial nephritis due to NSAIDs use : Steroids
Ref :
Saito M, Ueshima K, Fujioka M, Ishida M, Goto T, Arai Y, et al. Corticosteroid administration within 2 weeks after renal transplantation affects the incidence of femoral head osteonecrosis. Acta Orthop. 2014;85: 266–270.
Naiker IP, Govender S, Naicker S, Dawood S, Haffejee AA, Seedat YK. Avascular necrosis of bone following renal transplantation. South Afr Med J Suid-Afr Tydskr Vir Geneeskd. 1993;83:
Schachtner T, Otto NM, Reinke P. Cyclosporine use and male gender are independent determinants of avascular necrosis after kidney transplantation: a cohort study. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc—Eur Ren Assoc. 2018;
Diagnosis:
Steroid induce avascular necrosis of hip
Investigations needed to confirm diagnosis:
MRI: with high sensitivity & specificity for early detection of AVN
Treatment :
Surgical: Hip replacement.
Renal impairment and proteinuria:
-Graft biopsy
Avascular necrosis of the femoral head is one of the most common skeletal complications among renal allograft recipients complaining of hip pain, incidence ranges between 3 and 41%.Bilateral hip involvement is more common and seen in up to 85% of affected patients.
Causes of musculoskeletal pain and bone pain:
In renal allograft recipients, ischaemia occurs very early e often within 12 weeks of the transplantation, but most patients are diagnosed within two years of transplantation
Any other investigation required?
X ray may appear normal in the initial stage, MRI is the best imaging modality for early detection of AVN. Early changes may be picked up in as early as two weeks of onset and critical changes by 12 weeks.
Ryu et al reported that MRI was only 66% sensitive in diagnosing AVN of the femoral head whereas single photon emission computed tomography (SPECT) was 100% sensitive
What is your management plan?
Risk factors for AVN: some reported that high daily doses are a major contributing factor for development of AVN. Others authors describes the numbers of ‘pulse dose’ episodes are more critical for development of AVN.
Reduce dosage below 15 mg – 20 mg of total steroid per day, the risk of AVN of the femoral head is less than 3%.
Avoid pulses of steroid if possible
To do a graft biopsy to look for cause of proteinuria
AVN can be managed by:
The management of AVN will be discussed in MDT consist of transplant team and orthopedic surgeon
References
Hiralal, Alok K. Udiya, Anuj Thakral, Manish K. Jha, Siddarth Mishra, Narayan Prasad, R.K. Sharma,
Avascular necrosis of hip (AVN) in post renal transplant recipient: Case report & review of literature,
Indian Journal of Transplantation,
Volume 8, Issue 1,
2014,
Patient has right groin pain during walking. Recent onset of proteinuria 1.5 gm/day.
The patient is on tacrolimus based triple IS.
Plain X ray taken is normal.
Diagnosis
Possible diagnosis is avascular necrosis of the femoral head. It is a common skeletal complication following kidney transplantation.
Patients taking tacrolimus and steroids small dose can have association with this condition. However, it is also noted that generally in comparison with cyclosporin treated patients, tacrolimus administration results in preserved bone mineral density and lower incidence of vertebral fractures as well as lowering risk of AVN.
In addition, there can be a discrepancy between plain X ray and MRI. Plain X ray can be normal in AVN while MRI
The radiological features of AVN generally become apparent within 12 months of the onset of symptoms.
Increased rejection episodes increase steroid dosage which in turn increases the risk of AVN in these patients.
Other investigations
Management plan
References
The index case is a kidney transplant recipient on tacrolimus, MMF and steroids with a history of acute cellular rejection treated by 2 courses of steroid pulses.
The patient has 2 issues:
a) Pain in right groin while walking, requiring analgesics: In view of history of steroid pulse, possibility of avascular necrosis (AVN) of femoral head should be considered (1). Pain X ray right hip shown is normal, which is possible in early stages of AVN (2). In this scenario, MRI should be done, which has a sensitivity and specificity of 99% (3). Short-term use of high dose steroids has been shown to be associated with AVN (4).
b) Proteinuria with graft dysfunction: This patient has recent onset proteinuria of 1.5 gram per day in addition of elevated serum creatinine. It could be due to recurrence of basic disease, steroid resistant rejection, or mixed rejection, or due to onset of transplant glomerulopathy, or NSAID use related (6).
For AVN: MRI of the hip joint will help in diagnosis.
For proteinuria and graft dysfunction: A kidney biopsy, DSA levels, Tacrolimus drug levels, Lipid profile, Serum albumin.
For AVN: Involvement of orthopedic surgeon. Analgesic as per requirement. Reduction in weight bearing is required (using cane/ crutches/ walker). Surgical intervention as per the stage of AVN and opinion of the orthopedic surgeon (4). Reduction/ withdrawal of steroids will be needed (5).
For proteinuria and graft dysfunction: Treatment as per the etiology – on the basis of kidney biopsy. Use of ACE inhibitors or ARBs, BP control, management of dyslipidemia, weight reduction, and cessation of smoking should be done (7).
References:
1) Stoica Z, Dumitrescu D, Popescu M, Gheonea I, Gabor M, Bogdan N. Imaging of avascular necrosis of femoral head: familiar methods and newer trends. Curr Health Sci J. 2009 Jan;35(1):23-8. Epub 2009 Mar 21. PMID: 24778812; PMCID: PMC3945237.
2) Zalavras CG, Lieberman JR. Osteonecrosis of the femoral head: evaluation and treatment. J Am Acad Orthop Surg. 2014 Jul;22(7):455-64. doi: 10.5435/JAAOS-22-07-455. PMID: 24966252.
3) Lieberman JR, Berry DJ, Mont MA, Aaron RK, Callaghan JJ, Rajadhyaksha AD, Urbaniak JR. Osteonecrosis of the hip: management in the 21st century. Instr Course Lect. 2003;52:337-55. PMID: 12690862.
4) Weinstein RS. Glucocorticoid-induced osteonecrosis. Endocrine. 2012 Apr;41(2):183-90. doi: 10.1007/s12020-011-9580-0. Epub 2011 Dec 15. PMID: 22169965; PMCID: PMC3712793.
5) Hedri H, Cherif M, Zouaghi K, Abderrahim E, Goucha R, Ben Hamida F, Ben Abdallah T, Elyounsi F, Ben Moussa F, Ben Maiz H, Kheder A. Avascular osteonecrosis after renal transplantation. Transplant Proc. 2007 May;39(4):1036-8. doi: 10.1016/j.transproceed.2007.02.031. PMID: 17524885.
6) Amer H, Cosio FG. Significance and management of proteinuria in kidney transplant recipients. J Am Soc Nephrol. 2009 Dec;20(12):2490-2. doi: 10.1681/ASN.2008091005. Epub 2009 Oct 9. PMID: 19820126.
7) Shamseddin MK, Knoll GA. Posttransplantation proteinuria: an approach to diagnosis and management. Clin J Am Soc Nephrol. 2011 Jul;6(7):1786-93. doi: 10.2215/CJN.01310211. PMID: 21734095.
_ the most propable diagnosis in such patient with steroid therapy and received 2 courses of methyl prednisolone with groin pain is avscular necrosis of neck of femur (although it can not be detected in xray as it has low sensitivity of about 40 %).
_ other investigations required:
_ MRI on hip joint is the best diagnostic modality.
_ presence of significant protinuria and graft dysfunction essentially requires graft biopsy , the differential diagnosis could be:
1. Drug induced tubulointerstitial nephritis .
2. Acute rejection as he has prior ACR.
3. Transplant glomerulopathy due to suboptimal treated episodes of rejection
4. Recurrence of original kidney disease as FSGS or MPGN.
_ Management plan:
_ minimize steroids use and depends on MMF to minimize steroid adverse effects on the bone.
_ start ACEi to control protinuria together with control of blood pressure and dyslipidemia
_ traetment if the cause according to allograft biopsy
Diagnosis:
Avasculr necrosis
Diagnosis:
by
1- MRI may reach up to 100% sensitivity
2- Plain x ray may be pending for few month
Management:
asymptomatic patients with a small-sized lesion (involving <15 percent of the femoral head), supportive care rather than any form of a joint-preserving surgery (Grade 2C). This approach is largely based on observational data that asymptomatic lesions that involve less than 15 percent of the femoral head may resolve without surgical intervention.
•For asymptomatic patients with a medium-sized lesion (involving between 15 and 30 percent of the femoral head), joint-preserving surgical procedure such as core decompression (or one of its variants) or bone grafting rather than supportive therapy (Grade 2C). The rationale for this approach is also based on indirect evidence from symptomatic patients with medium-sized lesions, which are more likely to progress to collapse.
•For asymptomatic patients with large-sized lesions (involving >30 percent of the femoral head), supportive therapy until symptoms develop. These patients are highly likely to progress to femoral head collapse, which will likely be treated with total hip arthroplasty.
For proteinuria post kidney transplant:
1-Could be due to infection,rejection or recurrence of original disease
We need to know what type of analgesics taken by the patient and to stop any NSAIDs.
He is for renal biopsy that either de novo glomerulonephritis or recurrent one
There is osteo-arthritic changes on the head of the femur and some eaten parts most likely a-vascular necrosis of the head of the femur as a side effect of steroid therapy.
Other investigations are MRI – bone density scan – serum calcium, phosphorus and parathyroid hormone level.
confirming the diagnosis is essential and this patient should be evaluated by the orthopedic team .
correction of calcium, phosphorus and vitamin D should be done.
surgical change of the head of the femur may be needed
A vascular necrosis of femoral head secondary to steroid therapy
Avascular osteonecrosis (AVN) is a disabling bone complication that can occur after kidney transplantation (KT).
Being overweight/obese, having pre-transplant diabetes or hyperparathyroidism at transplantation, developing acute rejection, and receiving higher cumulative corticosteroid doses were associated with AVN occurrence. Multivariate analysis revealed that BMI ≥ 26 kg/m2 and higher cumulative corticosteroid doses were predictive of AVN. In conclusion, overweight/obesity is a strong risk factor for AVN. Despite a low maintenance dose, the use of corticosteroids mostly for treatment of acute rejection remains an independent risk factor.
It is very important that avascular necrosis is diagnosed early in the disease process since the success of the treatment is related to the stage at which the treatment starts.
There are several possible diagnostic modalities:
Clinically
Patients are often seen because of pain in the groin, but symptoms can also radiate to the knee or buttocks.
On examination, there is usually a painful range of motion, especially on forced internal rotation
It is also important to track any risk factors before the start of the examination
Radiology
X-ray
When standard anteroposterior and frog-leg lateral radiographs show obvious avascular necrosis of the femoral head, it is not necessary to perform an MRI.
MRI
This is the best method for cases that are radiographically occult or not obvious on radiographs. It has been found to be 99%sensitive and 98% specific for this disease
Management
1-non operative measures
– reduce weight-bearing.
-The concept of this method is to reduce the forces on the hip joint. This (interventional) treatment has various modalities, such as a cane, crutch, walker, or two crutches.
2-Pharmacological treatment
Vasodilators, e.g. iloprost (PGI2), are used to reduce intraosseous pressure thus, increased blood flow.
Statins act to decrease the differentiation of stem cells into fat cells, by reducing intraosseous pressure for better perfusion.
Anticoagulants, e.g. enoxaparin are used to prevent the progression of osteonecrosis due to hypercoagulability and thromboembolic events.
Bisphosphonates, such as alendronate, prevent osteoclasts action thus reducing bone resorption.
Pain medication such as NSAIDs and Opioid care for pain modulation.
Despite intra-articular steroid injections been fast-acting pain relieving agents, they are normally short-termed and their use can cause significant deterioration of avascular necrosis.
3-Operatives measures
There are several possible ways to treat avascular necrosis of the hip: core decompression, Core decompression with electrical stimulation, Osteotomy, Non-vascularized bone-grafting, and Vascularized grafts. The joint preservation interventions are core decompression, osteotomy, bone grafts, and use of cellular therapies; while reconstructive interventions are arthroplasty.
Proteinuria
1-Proteinuria is common after kidney transplantation and typically urine protein levels are below 500 mg/d. However, even these low levels are associated with reduced graft survival.
Most allografts with proteinuria >1500 mg/d have new glomerular pathology. In contrast, lower levels of proteinuria are generally associated with nonglomerular, nonspecific histologic changes.
Glomerular disease, including :-
recurrent, de novo, and undefined glomerulonephritis, was found on 66% of renal allograft biopsies in transplant recipients with proteinuria >3 g/d
So we need to do biopsy
2-sirolimus has been associated with posttransplantation proteinuria.
Reference
1. Xie XH, Wang XL, Yang HL, Zhao DW, Qin L. Steroid-associated osteonecrosis: Epidemiology, pathophysiology, animal model, prevention, and potential treatments (an overview). J Orthop Translat. 2015 Apr;3(2):58-70.
2- Jaffré C, Rochefort GY. Alcohol-induced osteonecrosis–dose and duration effects. Int J Exp Pathol. 2012;93(1):78-9
3-↑ Jump up to: 6.0 6.1 6.2 6.3 6.4 6.5 Mont MA, Jones LC, Hungerford DS. Non-traumatic avascular necrosis of the femoral head: ten years later. J Bone Joint Surg Am. 2006;88:1117-1132
4-Lai KA, Shen WJ, Yang CY, Shao CJ, Hsu JT, Lin RM. The use of alendronate to prevent early collapse of the femoral head in patients with nontraumatic osteonecrosis. A randomized clinical study. J Bone Joint Surg Am. 2005;87(10):2155-9.
5- Agarwala S, Shah S, Joshi VR. The use of alendronate in the treatment of avascular necrosis of the femoral head: follow-up to eight years. J Bone Joint Surg Br. 2009;91(8):1013-8.
6-↑ Jump up to: 12.0 12.1 Immonen I, Friberg K,
Grönhagen-Riska C, von Willebrand E, Fyhrquist F. Angiotensin-converting enzyme in sarcoid and chalazion granulomas of the conjunctiva. Acta Ophthalmol (Copenh). 1986;64(5):519-21.
7- Significance and Management of Proteinuria in Kidney Transplant Recipients
Hatem Amer and Fernando G. Cosio
J Am Soc Nephrol 20: 2490–2492, 2009. doi: 10.1681/ASN.2008091005
What is your diagnosis
Avascular necrosis of the head of right femur secondary to steroid.
Any other investigation required?
MRI for bilateral hip joints :sensitivity of up to 100 % for the diagnosis of osteonecrosis . The changes can be seen early in the course of disease when radiographs or other studies are negative.
Renal biopsy:He had high creatinine and proteinuria.
What is your management plan?
–Supportive care for osteonecrosis consists of measures such as bed rest, offloading as tolerated , and the use of analgesics and other potential therapies .
-Nonsteroidal antiinflammatory drugs (NSAIDs) may relieve pain. Opioid medications may be used for short periods of time when other pain medications are inadequate for moderate to severe pain while awaiting definitive surgery.
– Physical therapy may help relieve some symptoms.
-Orthopedic consultion.
Reference:
Uptodate
There is irregularity of the lower medial end of the head of femur with loss of synovial space. It’s likely steroid induced avascular necrosis of femur head.
MRI is the test which can confirm the diagnosis of the same.
Reduction of steroid and moving to steroid free protocol is the mainstay to prevent further progression of Avon and promote healing. But patient already had 2 episodes of ACR and is still having proteinuria with raised creatinine.
So I will first go for graft biopsy to find the exact status of the graft and then plan the immunosuppression with minimisation of steroids.
‘Other management points for AVN include:
The working diagnosis in this patient is Avascular necrosis for the femur head. This pathology occurs when blood flow to the head or proximal part of the femur has been compromised. It is also known as osteonecrosis. As a result, it manifests as necrosis which causes debilitation to the patient like difficulties walking, and can easily fracture. It has many causes but prolonged use of steroids is one of the famous causes.
Other causes are:
1) joint or bone trauma
2) fatty deposits in blood vessels
3) medical conditions like sickle cell disease and Gautier’s disease.
To confirm the diagnosis there are certain studies that may require and they are:
1) X-rays; in the early stages of the disease, it may not show but as it progresses it can show bone changes.
2) MRI and CT scan: the studies show early changes to the bone and can identify avascular necrosis.
3) Bone scan: radioactive material can be injected into the vein where the lesion can be seen.
The management of the pathology is as follows:
1) Analgesics: NSAIDS is used as first-line but in transplant patients, it is not advisable.
2) Osteoporosis drugs
3) Medications to lower cholesterol levels
4) Medications that may increase blood flow to the vessels like ventavis
5) Blood thinner but needs to be monitored.
6) Physiotherapy referral
7) Orthopaedic referral to some: core depression, bone transplant, bone reshaping or osteotomy, joint replacement, and regenerative medicine treatment.
References:
http://www.mayoclinic.org/diseases-conditions/avascular-necrosis/diagnosis-treatment/drc-20369863
Thankyou ,proteinuria?.
*DX: Avascular necrosis of head femur.
*MRI is considered the most sensitive, specific diagnostic radiological examination for avascular necrosis of head femur. It can diagnose very early lesions specificity in up to 90 %.
*Management : Decrease or steroid free regimen steroids ,use bisphosphonates , avoid alcohol consumption, surgery: Bone graft , Osteotomy, hip replacement
*Regarding Proteinuria management: proteinuria 1.5gm with rising creatinine indicate possible rejection or possible recurrence of primary kidney disease, so renal biopsy should be done , management according to the result , anti-proteinuric measures: control blood pressure target blood pressure around 140/80 , anti-hypertensive medications : CCB as; non-dihydropyridin group or ACEIs or ARBs).
References:
Chan K. and Mok C.: Glucocorticoid-Induced Avascular Bone Necrosis: Diagnosis and Management. Open Orthop J., 2012;6: 449-457.
Thankyou
Avascular osteonecrosis (AVN) is a disabling bone complication that can occur after kidney transplantation (KT)
Plain film radiography
Magnetic resonance imaging (MRI)
His recent s Cr is 176 µmol/L with 1.5 gm/day proteinuria (recent onset).This may be due to
Graft rejection, recurrence of primary disease, or infection
Treatment will be according to the diagnosis PLUS biopsy, ACEi
References
3. Resnick D, Niwayama G. Osteonecrosis: diagnostic techniques, special situations and complications. In: Resnick D, editor. Diagnosis of Bone and Joint Disorders. 3. Philadelphia: WB Saunders Co; 1995. pp. 3495–3558. [Google Scholar]
6. Bassett L, et al. MRI in the Early Diagnosis of Ischemic Necrosis of the Femoral Head. Clin. Ortho. 1987;214:237–248. [PubMed] [Google Scholar]
7. Beltran J., et al. emoral Head AVN: MR Imaging with Clinical-Pathological and Radionucide Correlation. Radiology. 1988;166:215–220.[PubMed] [Google Scholar]
Well done
Thankyou. Proteinuria