4. A 39-year-old male with excellent kidney function offered a kidney to his father who 65 years old, 111 mismatch, no DSA. His Crohn’s disease is under control by mesalazine where he had only one flare-up 6 years ago. No other significant medical history. No evidence of haematuria or proteinuria.
- What is your management?
- Substantiate your answer
Dear All
Thank you for replying to this challenging scenario that we faced a few years back. Suppose that he is the only donor for a recipient who is running out of access and there is no deceased donor programme.
Under what circumstances you would accept him?
When the patient is achieving Deep remission with the biologic agents or immune suppressants , which is indicated by activity index below 150 and complete mucosl healing., stem cells might be providing a long lasting remission as well.
1)I would accept the patient if he is in deep remission.
2)There is no hyperoxluria socondary to extensive bowel involvement .He has no renal stone disease.as reported.
3) In remission for more than 6 months.(he is 6 years in remission)
4) No evidence of inflammation or infection.
5) Post transplantation would be more stringent in surveillance and treatment of any relapse..
Excellent and clear answer.
Considering following factors I will accept him as a donor:
Free from disease.
Absence of oxalate stone.
Free from complications like tubular damage.
Absence of any associated disease.
Thank you, will you do a metabolic screening also?
Sir,
We should accept him after informing him the risk of complications of his Chron’s disease which would be in the form of recurrence of disease, bowel complications, renal failure due to amyloidosis/ glomerulonephritis or stone formation.
He is high risk for formation of oxalate stones due to malabsorption of oxalate and urinary hypocitraturia/ hypomagnesuria and acidic urine.
He should follow the following advice:
Thank you, Excellent answer.
Thank you, will you do a metabolic screening also?
Yes. will do that prof at least the baseline
At this senario I may accept this donor after the following :
1- Education of the patient about the risk of pre renal impairment and possible ATN related to complications thus ensuring adequate hydration all the time is mandatory
2- Education of the patient about the risk of recurrence of renal stones so ensuring healthy diet is nandatory
3- No recent flares
4- No evidance of intestinal complications like stricture or obstruction
5- Not associated with extra intestinal manifestations
6- Excellent kidney function with no proteinuria
7- Avoiding smoking which is associated with higher relapse rate
8- No need for steroids to control the disease activity
9- Good access to biologic therapy if needed
10- Complience and ensuring regular follow up after donation is mandatory
11- No history of perianal disease or rectal involvement which is associated also with higher risk of relapse
12- No history of recurrent flares
Thank you, will you do a metabolic screening also?
Yes … to exclude marked hyperoxalosis (which may preclude donation) and hypocitruria that is to add in the prevention of recurrence of renal stones
fully counseled about all complication he may develop and the risk prediction of ESKD, and to sign high risk informed consent, and to follow a restricted life style
Thank you, but this is not enough.
In that case may be accepted with above circumstances
Risk factors for renal insufficiency:
In the absence of these risk factors, he can be considered for donation
Thank you, will you do a metabolic screening also?
yes, to exclude hyperoxaluria
-There has been no new relapse recently.
-Compliance and making sure it is consistent with the medication. As relapse increase with non-adherence to medication.
-properly advised on any and all complications he may acquire as well as the risk prediction of ESKD.
-He has no history of intestinal resection.
-He has NO stone at the time of transplantation.
Thank you, will you do a metabolic screening also?
If diagnosed with microscopic colitis, collagenous colitis, lymphocytic colitis only, accept if:
Thank you, but this is a very short answer, and it is also not clear.
Sir,
We should accept him after informing him the risk of complications of his Chron’s disease which would be in the form of recurrence of disease, bowel complications, renal failure due to amyloidosis/ glomerulonephritis or stone formation.
He is high risk for formation of oxalate stones due to malabsorption of oxalate and urinary hypocitraturia/ hypomagnesuria and acidic urine.So
)I would accept the patient if he is in deep remission.
2)There is no hyperoxluria socondary to extensive bowel involvement .He has no renal stone disease.as reported.
3) In remission for more than 6 months.(he is 6 years in remission)
4) No evidence of inflammation or infection.
5) Post transplantation would be more stringent in surveillance and treatment of any relapse.
Thank you, and detailed metabolic screening
Donation may be considered where factors that have previously put the patient at risk of stone formation e.g. diet or medication, have been successfully modified, urine pH has been corrected to normal , In such cases no active disaese ,no hematuria ,no proteinuria ,no hyperoxluria,in remission more than 6 month and careful counselling of the donor is mandatory before and post -surgery.
Thank you, and detailed metabolic screening
When Crohn’s disease is in remission including both biological remission and clinical remission having Crohn’s Disease Activity Index (CDAI < 150)
Endoscopic remission (mucosal healing), normalization of serologic or fecal markers of inflammation, and even radiographic remission, in addition to clinical remission with complete absence of symptoms, no disease progression, no complications or disability, and normal quality of life.
Detailed predonation evaluation will be done with metabolic profile testing .
Gastroenterologist has to be involved with MDT discussion along with counceling of the donor and the recipient explaining the risks for the donor and extraintestinal complications for Crohn’s disease.
Thank you.
Is there is no avialble option for the current recipient, the donor must be couseld about risk of CKD after donation.
_ To accept him at least, he must be in complete remission, hyperoxaluria must be excluded by 24 h urinary oxalate, exclude presence of any infections.
_ post transplant close follow up of the donor, adequate fluid intake up to 3 liters per day, follow up by urinary oxalate and renal US for eraly detection of any metabolic derangement or stones, treatment of any disease activity and try to avoid nephrotocic medications.
_ use of total enteral nutrition and steroids are preferred over aminosalislyic acid and CNI to induce remission to limit nephrotic medications.
_ follow up urine analysis regularly to early detect any form of nephritis.
Thank you, Mai. What about the rest of the metabolic screening?
Can be accepted but after taking consent from the donor and good counseling for the hazards of Crohn’s on his kidney
with proper management of the disease to prevent or decrease future flares up with a biological treatment
No history of recent activity
endoscopic surveillance may be needed to ensure that there is no active pathology now
No proteinuria
Metabolic profile to ensure prevention of formation of renal stones
The Diet regimen includes good hydration and a decreased load of oxalate and urate
Urine alkalinization increased water intake and administration of citrate can prevent the recurrent formation of uric acid stones
avoid smoking
With close follow-up after kidney donations with the same precautions’
Thank you, Mohamed
If there are no other likely donors then one has to ensure that the disease is in remission. proper studies must be conducted to ensure this and the gastroenterologist must see the patient classify his status.
metabolic studies must be conducted to ensure stability. urinary test looking for kidney stones and urinary active sediments. one all has been met proper explanation must be explained to the donor and to the family members and proper documentation with witnesses to ensure there is no future legal implications. once all has been done then the patient can proceed with a donation in my opinion.
Thank you, Marius
Patients with chron’s disease have the risk of renal stones due to hyperoxaluria and amyloidosis as a result of chronic inflammation. in the paper published in 2019 (1), 7 patients with chron’s disease were evaluated retrospectively. the study concluded that patients in remission remained in recession, and those with the mild or moderate disease were controlled by infliximab and adalimumab. In this challenging scenario, we may accept the donor if obligated, but after making sure the patient has no proteinuria and recurrent renal stones. our case is in deep remission, so we expect good survival post-donation though not guaranteed. because the oxaluria is secondary, the recipient is not expected to have a high risk of urolithiasis
1- Grupper, Ayelet, et al. “Kidney transplantation in patients with inflammatory bowel diseases (IBD): analysis of transplantation outcome and IBD activity.” Transplant International 32.7 (2019): 730-738.
Thank you. Do not forget metabolic screening.
If we must accept him as a donor, he needs to be counselled in detail regarding the risks involved with respect to both intestinal and renal complications.
He should be under remission.
The donor should undergo detailed metabolic screen (urine and plasma biochemistry) as required for renal stone assessment (1).
He should be advised to stop all nephrotoxic medications, quit smoking, increase liquid intake to more than 2.5 litters/day, increase dietary calcium and reduce dietary fat intake (2). He should be under continuous and close follow-up with a gastroenterologist. He should be provided with magnesium and citrate supplementation. Post-operatively, he should remain under close follow-up with the transplant team as well.
Reference:
1) British Transplantation Society. Renal Association Guidelines for Living Donor Kidney Transplantation, 4th ed.; British Transplantation Society: Macclesfield, UK, 2018; Available online: https//bts.org.uk/wp-content/uploads/2018/07/FINAL_LDKT-guidelines_June-2018.pdf (accessed on 5 October 2022).
2) Gaspar SR, Mendonça T, Oliveira P, Oliveira T, Dias J, Lopes T. Urolithiasis and crohn’s disease. Urol Ann. 2016 Jul-Sep;8(3):297-304. doi: 10.4103/0974-7796.184879. PMID: 27453651; PMCID: PMC4944622.
Thank you, Amit for the excellent answer
Can be considered for donation after MDT discussion and ILDA consultation and to be in long remission, he is not on intense immunosuppression medication, has good nutrition with albumin above 30, has no metabolic risk, and is free of infections, has BMI above 18. Metabolic screen and NNCT to assess for any kidney stones, no proteinuria or hematuria, and no active infection.
surgical preparation includes
*preoperative nutritional support.
* IBD patients undergoing surgery have a higher risk of venous thromboembolic disease than patients with colorectal cancer and should receive anticoagulation prophylaxis with heparin as per the current guidelines recommendation
* post-operative wound care and rehabilitation.
* good hydration and avoid nephrotoxic medication, long-term combined follow-up with nephrologist and gastroenterologist
● Donor is young and has chronic inflammatory bowel disease that controlled with Mesalazine but can activate and had flares at any time that it may Leads to pathological complications which affect his remaining kidney after donation
● So if he is the only donor for urgent recipiant I will accept him after
** Strict full metabolic screening to exclude hyperoxalateuria , hypocitraturia ,
** Counsulting him about the high risk complications for his disease on kidney ( glomerulosclerosis , kidney stones )
** Advise him if he insists donation to
▪︎Keep a strict follow-up on his intestinal disease, especially in the case of an attack, ▪︎ avoid taking drugs harmful to the kidneys
▪︎ stick to a high water intake and a diet poor in salt, and oxalate and rich in calcium.
▪︎ And Provide him with citrate , magnesium and urine alkalizer supplements
Thank you, Huda
We shall accept him for donation under special circumstances:
-Pt in long term remission.
-No urinary or renal abnormalities.
-No extra-intestinal complications.
-Free colonic mucosa of signs of activity.
-Explain the risk of nephrolithiasis and renal complication for him.
-Advice about life style and precautions post donation.
Thank you, sir,
I will accept this patient if he is remission for more than 1 year and lowest possible maintenance dose for the immunosuppression and all metabolic causes of stone recurrence are well taken care of. However, continuous surveillance and monitoring for flare will be on going with lifestyle modification
Under what circumstances you would accept him?
1) Exclude perianal disease, rectal involvement, tobacoo use , steroid dependet disease.
2) Labs to evaluate for disease activity specially hyperoxaluria ;
3) Deeply controlled disease forr more than 6 months.
4) If there is no other potential donor to him, and long time on waiting list
In this case , I will accept him as a donor to save this recipient life.
1- Confirm Crohn’s lap and pathological remission with ESR ,CRP , fecal calprotectine and intestinal biopsy.
2- Exclude any renal dysfunction,
Drug induced TIN or amyloidosis: serum amyloid level , urinary eosinophils and may consider renal biopsy .
3- assess the risk for nephrinohisis: previous stone episodes , urinary PH , metabolic screen for hypercalciurea, hypocitraturia , hyperoxaloria , hyperuricemia
4-correct any metabolic disturbance as dyslipidemia and hyperglycemia
5- Cardiovascular , VTE and perioperative risk assessment.
6 – IBD expert should be involved in this case and discuss potential therapeutic option for this donor in case of post donation Crohn’s flare developed
IBD ( crohns disease & ulcerative colitis) is a systemic auto-immune disease characterized by relapse & remission with variable extra-intestinal manifestation (6%-46%). Renal involvement is one of the extra-intestinal manifestation, it can cause renal stone (mainly oxalate stone if there is extensive intestinal involvement) tubular dysfunction & rarely parenchymal renal disease & CKD.
Patients with IBS should be excluded from live kidney donation.
If he the only available donor for a recipient with running out of access & no deceased program available he should be :
It is to accept to accept him as we have to apply first the rule of doing harm first. Admitting that we do not have enough data with regard to out come of previous donors and we are not expecting to have it. on the hand to refuse him without strong evidence is also unfair.
After explanation of the situation and if he is in full remission for long term, years, not having renal stone, nor albmuninuria or abnormal oxaluria and he consented for that we can accept him after discussiion in MDT including gastro enterologist and plan long term follow up after donation.
1- If he is in complete remission (defined as chronic disease activity index <150 , CRP <5 mg/l and fecal calprotectin <250 µg/g) lasted at least 6 month
2- no hyperoxaluria or hypocitrituria
3- no stones
preventive strategies for stone
good hydration
increase calcium intake
potassium citrate
Can be accepted if in deep remission, no hyperoxaluria, no infection or inflammation. Afetr transplant survellance is must
He could donate a kidney when at least be in remission for 6 months without any more inflammation on colonoscopy. His urine metabolic profile for oxalate, calcium, citrate and urate and urine PH are acceptable. He received enough fluid and urinary alkalinization to reduce the probability of renal stones.
if there is no other option i will accept this transplantation in special condition.
1) i will discus the risk of kidney involvement in IBD.
2) I will consult the GIT specialist to assess the disease activity.
3) as a donor this man should be assessed carefully , kidney function, 24 hour urine for stone profile , presence of stone .
4) patient should be in complete remission with minimum immunsupresant medication.
5) close followup after donation . .
It is better to avoid him if there is another donor
But if he is the only donor we can accept him if no recent flares ,no extra intestinal manifestations ,no stricture or fistula ,good kidney function ,no hypweroxaluria ,goo access to biological therapy
What is your management?
Potential donor with history of chronic disease is liable for many complications especially extraintestinal complications , if involved kidneys may cause renal stones , tubulointerstitial nephritis , amyloidosis kidney and others in addition to complications of treatment.
This Potential donor is at risk of renal problems as well as surgical management for his primary condition.
So my opinion is that he is discarded as a potential donor . Despite being a good match with normal KFTs.
the donor has a disease that can be associated with renal risk. it carries the risk of renal stone (oxalate stone/ urate stone) or drug-induced interstitial nephritis, or amyloidosis. or even intestinal ureteric fistula.
therefore, I will not accept this donor.
if he insists, after good counselling he needs a metabolic profile screen, and re-assess his disease by a gastroenterologist.
patient with IBD if in deep remission and no extraintestinal complication and good compliance with followup can donor b accepted.
Crohn’s disease extra-intestinal renal manifestations include:
Risk factors for progressive disease are
He needs metabolic evaluation, especially to rule out hyperoxaluria, hypocitraturia, hypomagnesemia and lower urinary pH.
Considering no metabolic abnormality, having clinical remission with mesalazine and crohn’s disease activity index of <150 with hardly any factors of progressive disease, he is accepted as a donor
Informed consent and education concerning:
Reference:
Inflammatory bowel disease includes UC and Crohn’s disease which are associated with patchy inflammation treated by medical immunosuppression medications or surgical resection if needed. its also associated with extraintestinal manifestation including renal involvement either by the disease itself which may be associated with glomerulonephritis or by complications related to the disease or to medications like tubulointerstitial nephritis, amyloidosis, and 2ry hyperostosis, and nephrolithiasis.
Kidney donors are considered normal people with a low risk of developing ESRD. this potential donor is a patient with a moderate risk of developing renal disease which is why I will decline him as a potential donor but if he is insisting on donations there is no absolute contraindication for donation if he has had no relapse in the last year and has a normal metabolic profile with no history of stones and he will be accepted after proper counseling.
References:
1-Kim YN, Jung Y. Korean J Gastroenterol. 2019;73(5):260-268. doi:10.4166/kjg.2019.73.5.260.
2-Ambruzs JM, Larsen ChP. Renal Manifestations of Inflammatory Bowel Disease. Rheum Dis Clin N Am 44 (2018) 699–714.
Renal involvement has been considered as an extraintestinal manifestation and has been described in Crohn’s disease. The most frequent renal involvements in patients with inflammatory bowel disease are nephrolithiasis, tubulointerstitial nephritis, glomerulonephritis and amyloidosis.
The prevalence of nephrolithiasis among patients with IBD is higher than in the general population, ranging from 12% to 28%, especially in patients with IBD who have undergone surgical bowel procedures, such as total colectomy with ileostomy, small bowel resection or intestinal bypass. Diarrhoea and malabsorption, often described in IBD patients, are risk factors for renal stone formation.
Renal stones in patients with IBD are usually composed of uric acid and calcium oxalate. The formation of uric acid stones, linked with urine uric acid supersaturation, is promoted by low urine pH (resulting from alkali lost in the stool) and low urine volume.
Detailed medical and dietary history, serum chemistries and urinalysis, Additional metabolic tests consist of one or two 24-hour urine collections obtained on a random diet and analyzed at minimum for total volume, pH, calcium, oxalate, uric acid, citrate, sodium, potassium and creatinine.
This potential donor is:
Ø Young 35 years
Ø Stable Crohn’s disease is under control by mesalazine only one flare-up 6 years ago
Ø Good immunological match
He can be accepted as donor after gastroenterologist MDT approach and assessment.
Reference:
BTS/RA Living Donor Kidney Transplantation Guidelines 2018
Domenico Corica, Claudio Romano, Renal Involvement in Inflammatory Bowel Diseases, Journal of Crohn’s and Colitis, Volume 10, Issue 2, February 2016, Pages 226–235, https://doi.org/10.1093/ecco-jcc/jjv138
What is your management?
Substantiate your answer
Although this a good offer from this young donor with acceptable crossmatch , and no DSA . on the other hand the presence of a history of IBD in this patient make the process of transplantation is not straight forward. In spite of being in remission state but still there is a risk of future relapse . there is a close relation of IBD and renal involvement . this may affect the graft survival . there fore I will decline this donor .
The expected graft damage may be associated with .
1. Nephrolithiasis.
It occur in 12% to 28% of patients with IBD and it is higher than in the general population.
Diarrhoea and malabsorption , are risk factors for renal stone formation.
The previous surgery and the extent of disease contributes to nephrolithiasis the risk is higher in CD compared with UC, because of ileocolic involvement. Renal stones composed of uric acid and calcium oxalate.
2. Glomerulonephritis.
Glomerulonephritis is a form of renal involvement in patients with IBD (both CD and UC). Different histological presentation : Ig A nephropathy , IgM nephropathy , membranous, mesangiocapillary,
FSGS , Anti GBM ab . GN may be directly related to intestinal disease activity, and improvement of renal function after remission of bowel inflammation has been demonstrated. One study report the highlighted that the prevalence of IgA nephropathy was significantly higher in patients with IBD than in patients without IBD.
3. Tubulointerstitial nephritis:
Tubulointerstitial nephritis (TIN) is reported in IBD. As most patients uses drugs like , 5-aminosalicylate (5-ASA), cyclosporin A and tumour necrosis factor a (TNFa) inhibitor.
Then e, it is difficult to establish whether renal dysfunction can be considered an EIM or due to medical treatment. some papers have highlighted the link between tubule interstitial
damage and IBD activity.
4. Renal amyloidosis
Secondary amyloidosis (AA) is a rare but significant complication of IBD with bad prognosis .
disease. The incidence of AA ranges from 0.3% to 10.9% in CD patients and from 0% to 0.7% in UC patients. The time lapse between onset of IBD and diagnosis of AA is about 10–15 years after IBD diagnosis.
5. Drug-induced nephrotoxicity
The drug used in IBD like Aminosalicylates, azathioprine, cyclosporin and TNFa inhibitors may has renal side effect.
5.1. 5-Aminosalicylates and sulphasalazine:
renal impairment occur in 1 in 100 patients treated with 5-ASA, but the clinically significant damage occurs in only 1 in 500 patients. The result is conflict – some studies reported an incidence of interstitial nephritis of >1% but others suggested that 5-ASA treatment has no effect on renal function.
5.2. TNFa inhibitors.
TNFa inhibitors are used in the treatment of , IBD with good results in terms of tolerability, low-grade side effects and control of intestinal and extraintestinal manifestations.
Infliximab and Adalimumab are the most commonly used drug. TNFa inhibitors ( including ETANERCEPPT) can be involved in in glomerulonephritis or lupus nephritis
5.3. Azathioprine:
This reported in two case report azathioprine used in treatment of Wegener’s granulomatosis and rheumatoid arthritis respectively. In these reported cases renal involvement manifested as interstitial nephritis.
5.4. Cyclosporin A:
Treatment with CsA is characterized by nephrotoxicity. which manifests clinically as acute or chronic renal damage which depends on duration and dosage of treatment.
5.5. Tacrolimus:
Ogata et al reported an increase in serum creatinine levels up to 30% above baseline in 14.8% of their IBD patients treated with tacrolimus for 10 weeks .
A similar observation was made by Sandborn et al., who high lighted an increase in serum creatinine level of up to 30% in 38% of their patients treated with tacrolimus.
Reference :
1- Domenico Corica, Claudio Romano, Kidney transplantation in patients with inflammatory bowel diseases (IBD): analysis of transplantation outcome and IBD activity, Journal of Crohn’s and Colitis, 2016, 226–235 doi:10.1093/ecco-jcc/jjv138.
2- Pouria S, Barratt J. Secondary IgA nephropathy. Semin Nephrol 2008;28:27–37.
3- Wang J, Anders RA, Wu Q, et al. Dysregulated LIGHT expression on T cells mediates intestinal inflammation and contributes to IgA nephropathy. J Clin Invest 2004;113:826–35.
What is your management?
Substantiate your answer
Although this a good offer from this young donor with acceptable crossmatch , and no DSA . on the other hand the presence of a history of IBD in this patient make the process of transplantation is not straight forward. In spite of being in remission state but still there is a risk of future relapse . there is a close relation of IBD and renal involvement . this may affect the kidney survival . there fore I will decline this donor .
The expected kidney damage may be associated with .
1. Nephrolithiasis.
It occur in 12% to 28% of patients with IBD and it is higher than in the general population.
Diarrhoea and malabsorption , are risk factors for renal stone formation.
The previous surgery and the extent of disease contributes to nephrolithiasis the risk is higher in CD compared with UC, because of ileocolic involvement. Renal stones composed of uric acid and calcium oxalate.
2. Glomerulonephritis.
Glomerulonephritis is a form of renal involvement in patients with IBD (both CD and UC). Different histological presentation : Ig A nephropathy , IgM nephropathy , membranous, mesangiocapillary,
FSGS , Anti GBM ab . GN may be directly related to intestinal disease activity, and improvement of renal function after remission of bowel inflammation has been demonstrated. One study report the highlighted that the prevalence of IgA nephropathy was significantly higher in patients with IBD than in patients without IBD.
3. Tubulointerstitial nephritis:
Tubulointerstitial nephritis (TIN) is reported in IBD. As most patients uses drugs like , 5-aminosalicylate (5-ASA), cyclosporin A and tumour necrosis factor a (TNFa) inhibitor.
Then e, it is difficult to establish whether renal dysfunction can be considered an EIM or due to medical treatment. some papers have highlighted the link between tubule interstitial
damage and IBD activity.
4. Renal amyloidosis
Secondary amyloidosis (AA) is a rare but significant complication of IBD with bad prognosis .
disease. The incidence of AA ranges from 0.3% to 10.9% in CD patients and from 0% to 0.7% in UC patients. The time lapse between onset of IBD and diagnosis of AA is about 10–15 years after IBD diagnosis.
5. Drug-induced nephrotoxicity
The drug used in IBD like Aminosalicylates, azathioprine, cyclosporin and TNFa inhibitors may has renal side effect.
5.1. 5-Aminosalicylates and sulphasalazine:
renal impairment occur in 1 in 100 patients treated with 5-ASA, but the clinically significant damage occurs in only 1 in 500 patients. The result is conflict – some studies reported an incidence of interstitial nephritis of >1% but others suggested that 5-ASA treatment has no effect on renal function.
5.2. TNFa inhibitors.
TNFa inhibitors are used in the treatment of , IBD with good results in terms of tolerability, low-grade side effects and control of intestinal and extraintestinal manifestations.
Infliximab and Adalimumab are the most commonly used drug. TNFa inhibitors ( including ETANERCEPPT) can be involved in in glomerulonephritis or lupus nephritis
5.3. Azathioprine:
This reported in two case report azathioprine used in treatment of Wegener’s granulomatosis and rheumatoid arthritis respectively. In these reported cases renal involvement manifested as interstitial nephritis.
5.4. Cyclosporin A:
Treatment with CsA is characterized by nephrotoxicity. which manifests clinically as acute or chronic renal damage which depends on duration and dosage of treatment.
5.5. Tacrolimus:
Ogata et al reported an increase in serum creatinine levels up to 30% above baseline in 14.8% of their IBD patients treated with tacrolimus for 10 weeks .
A similar observation was made by Sandborn et al., who high lighted an increase in serum creatinine level of up to 30% in 38% of their patients treated with tacrolimus.
Reference :
1- Domenico Corica, Claudio Romano, Kidney transplantation in patients with inflammatory bowel diseases (IBD): analysis of transplantation outcome and IBD activity, Journal of Crohn’s and Colitis, 2016, 226–235 doi:10.1093/ecco-jcc/jjv138.
2- Pouria S, Barratt J. Secondary IgA nephropathy. Semin Nephrol 2008;28:27–37.
3- Wang J, Anders RA, Wu Q, et al. Dysregulated LIGHT expression on T cells mediates intestinal inflammation and contributes to IgA nephropathy. J Clin Invest 2004;113:826–35
There are renal complications in crohn’s disease included:
1.
Nephrolithiasis due to
secondary hyperoxaluria. Hyperoxaluria is caused by malabsorption, increased
oxalate in color and fewer oxalobacter formigenes in colon. In addition, if
they have diarrhea, they would be hypovolemic that worsens the condition with
crystal supersaturating.
2.
Amyloidosis: if the patient
has an uncontrolled inflammation for a long time.
3.
Tubulointerstitial nephritis
due to administered drugs for crohn’s disease (mesalazine).
Glomerulonephritis: There are increasing reports of IgA nephropathy,
membranous nephropathy and anti-GBM GN among patients with IBD. Therefore, he
is not an ideal donor because of the probability of his renal insufficiency in
the future regarding his IBO. If he persists on donating, a complete urine and
serum metabolic profile for calcium oxalate, citrate, urate is necessary. In
addition, he should receive high fluid intake, low sodium and enough calcium
diet after donation and receive magnesium and citrate supplementation to reduce
oxalate crystallization.
A potential donor, aged 39 y, known Crohn’s disease controlled with Mesalzine, last flare 6 years ago. Crohn’s disease can manifest with extra-intestinal manifestations like renal stones, Tubulo-interstitial-nephritis, Glomerulonephritis and amyloidosis.
Crohn’s disease associated renal stone disease is related to reduced level of urinary citrate and magnesium and increased level of urinary calcium. Other risk factors include altered intestinal permeability and recurrent use of antibiotics that reduces Oxalobacter formigenes concentration.
Pre-donation counselling is very important to explain potential risks of his primary GIT disease.
I would decline this donor offer and advise this patient to look for another donor either living or deceased.
However, I would accept this potential donor if he is the only available donor with long waiting time for this patient and multiple access problems and this donor is the only resort provided the donor has the following:
1- No renal stones.
2- Deep remission of Crohn’s disease for at least 6 months.
3- No Hyperoxaluria.
4- No current infection.
5- No current inflammation.
This donor is preferred o be excluded from donation as crohn’s disease is associated with extra-intestinal manifestations as renal involvement in the form of nephrolithiasis, glomerulonephritis including IgA nephropathy, membranous, mesangiocapillary GN and FSGS, also tubulointerstitial nephritis either as an extra-intestinal manifestation or drug induced as a result of treatment with 5-aminosalicylate, cyclosporine A or tumor necrosis factor inhibitor.
Renal amyloidosis is a rare complication but is significant and may progress to renal failure.
If the potential donor should be accepted for donation, he should be counselled about the risks of renal and intestinal complications
He should be in remission
Several measures will be done to decrease nephrolithiasis as decreasing dietary fat intake, increasing dietary calcium, increasing water intake and to receive supplementation with citrate and magnesium
Metabolic screening
The donor should be informed that he will have close and continuous follow up after donation.
Corica D, Romano C. Renal involvement in inflammatory bowel diseases. Journal of Crohn’s and Colitis. 2016 Feb 1;10(2):226-35.
What is your management?
Substrate your answer
· BTS/RA guidelines stated that donors who are likely to develop renal stones must undergo a detailed metabolic screening
· This donor is at high risk of developing surgical complications and extra-renal manifestations of chrons .Therefore, this donor should be excluded.
References:
Reindl W, Thomann AK, Galata C, Kienle P. Reducing Perioperative Risks of Surgery in Crohn’s Disease. Visc Med. 2019 Dec;35(6):348-354.
This candidate male donor 39 year old, young age, with history of Crohn’s disease in remission, with no evidence of renal affection, no hematuria or proteinuria with excellent renal functions, can be accepted for donation after clearance from the following:
History taking regarding lifestyle habits, diet, fluid intake, history of smoking, frequent surveillance visits to the gastroenterologist, weight gain and appetite. The family history of both renal disease and Crohn’s disease is mandatory. History of the recipient’s original renal disease is highly important too.
The essential investigation in this case is the full metabolic workup profile; serum calcium, oxalate citrate, 24 urinary calcium, oxalate, serum PTH, vitamin D, magnesium.
Gastroenterology consultation is the cornerstone step in this approach for assessment of fitness of donation mentioning he is in deep remission more than 6 years, on single monotherapy mesalazine, no extra-intestinal manifestations.
This donor should be counselled as his young age is more liable to allow the burden of chronic illness to develop as amyloidosis ,renal stones due to hyperoxaluria .Ample fluid intake is not luxurious in his condition ,cessation of smoking ,high calcium diet is the best prophylactic step to minimize oxalate burden , keeping the urinary PH above 6 is necessary to decrease the tendency for calcium oxalate crystal deposition ,along with citrate supplementation .
In the future close follow up is required with frequent assessment, metabolic workup, renal functions, imaging if needed. Avoiding dehydration predisposing factors as occupations, strenuous exercises, diarrhea and vomiting, humid weather.
Patient is in good remission. no GI symptoms, no signs of chronic inflammation, no stone.
I can accept donation. additionally, I will discuss thoroughly the all long term consequences.
Yes if the following criteria meet
1) MDT with gastroenterologist to ensure crohn’s disease is in complete remission. No extra intestinal manifestation of Crohn’s disease
2) Exclude calcium oxalate renal stone.
3) Exclude diabetes mellitus.
4) Blood investigation to exclude anaemia, hypoalbuminaemia, normal liver function test, nomal ESR/ CRP, Stool Occult blood negative for occult blood.
ill not accept this donor as
in a patient with Crohn’s disease, it is assciated with recurrent acute kidney failure and aimed to remark importance of receiving sufficient parenteral fluid and electrolyte support in those with short bowel syndrome.
Crohn’s disease have unfavorable effects on kidney functions due to malabsorption and dehydration such as acute kidney failure, calcium oxalate-uric acide stones and electrolyte abnormalities.
if no other donor, a proper councelling should be done
1. Hueppelshaeuser R, von Unruh GE, Habbiq S, Beck BB, Buderus S, Hesse A, et al. Eneteric hyperoxaluria, recurrent urolithiasis, and systemic oxalasis in patients with Crohn’s disease. Pediatr Nephrol. 2012;27:1103–9. [PubMed] [Google Scholar] [Ref list]
2. Jacobi J, Schnellhardt S, Opgenoorth M, Amman KU, Küttner A, Schmid A, et al. Severe metabolic alkalosis and recurrent acute on chronic kidney injury in a patient with Crohn’s disease. BMC Nephrol. 2010;11:6. [PMC free article] [PubMed] [Google Scholar] [Ref list]
3. DiBaise JK, Young RJ, Vanderhoof JA. Intestinal rehabilitation and the short bowel syndrome: Part 1. Am J Gastroenterol. 2004;99:1386–95. [PubMed] [Google Scholar] [Ref list]
Clinical course of inflammatory bowel disease presenting with flares and remissions.
Intestinal and extra-gastrointestinal manifestations may include:Renal failure Amyloidosis AA IgA nephropathy ,These complications can even lead to kidney failure
There is an association between oxalate nephropathy and inflammatory bowel disease because the prevalence of calcium oxalate urolithiasis in Crohn’s patients is 5 times higher than in the general population.
Furthermore, Crohn’s disease appears to be a predisposing factor for hemolytic-uremic syndrome because of recurrent gastrointestinal infections
This may put the donor at risk of developing chronic kidney disease .
Although he is in remission for 6 years but still he is at risk of flares.
So i wont accepte him as a donor and both donor and recipient must be counselled about possible risk factors.
Crohn’s disease is a chronic inflammatory disease and despite he is on remission for long time he may develop relapsing course and require long term treatment Crohn’s disease is a risk factor renal disease due to
So potential donor with crohn’s disease is not the better candidate
If he is the only donor
thanks
Kidney involvement may occur as an extraintestinal manifestations of IBS. The most important are:
1. Nephrolithiasis:
-occurs in 12-28% of IBD patients especially in patients with history of bowel
surgery. Also ileocolonic disease has a significant risk factor for nephrolithiasis.
-Renal stones in patients with IBD are usually composed of uric acid and calcium
oxalate.
-The formation of uric acid stones, due to urine uric acid supersaturation, which
exacerbated by
low urine pH (alkali lost in the stool) and low urine volume
-Hyperoxaluria is frequently found in patients with IBD due to increased intestinal
absorption of
oxalate, due to ileal disease and, consequently, increased urinary oxalate excretion,
causing calcium oxalate stones
-Recurrent nephrolithiasis may be related to the development of chronic kidney disease
and end-stage kidney disease
2. Glomerulonephritis:
-IgA nephropathy, IgM nephropathy, membranous, mesangiocapillary, focal segmental
and anti-GBM glomerulonephritis, were described
– GN could be related to intestinal disease activity, and improvement of renal function
after remission of bowel inflammation was found
– The prevalence of IgA nephropathy was significantly higher in patients with IBD than in
patients without IBD
3. Tubulointerstitial nephritis:
– Most cases related to drugs, such as: 5-ASA, cyclosporin A and TNFα inhibitor
-Could be due to IBD activity
4. Renal amyloidosis:
-Secondary amyloidosis (AA) is a rare but significant complication of IBD, and influence
prognosis more than the underlying disease
-Kidney affected in AA amyloidosis in 90% of cases. Manifested with proteinuria, nephrotic
syndrome and maybe renal failure.
-Sometimes renal failure can be present in the absence of significant proteinuria
5. Renal insufficiency
Lewis et al.132 evaluated the incidence of renal failure (GFR of <60ml/min/1.73m2) in a population of 251 patients with IBD (66.1% with CD). The results of this study showed a prevalence of RI of 15.9%
Donors with IBD considered to have high risk of acute and chronic kidney disease, and I will exclude them from donation
Renal Involvement in Inflammatory Bowel Diseases Domenico Corica, Claudio Romano
Nazzal L, Puri S, Golfarb DS. Enteric hyperoxaluria: an important cause of end-stage kidney disease. Nephrol Dial Transplant 2015 Feb doi: 10.1093/ ndt/gfv005.
Lewis B, Mukewar S, Lopez R, Brzezinski A, Hall P, Shen B. Frequency and risk factors of renal insufficiency in inflammatory bowel disease inpatients. Inflamm Bowel Dis 2013;19:1846–51.
The available donor to the recipient is his son who is 39 year old with normal renal function and normal urine sediment…He has Crohn’s disease and is on treatment with mesalazine for the same….The donor has been in remission for the last 6 years with no flare up…
Extra intestinal manifestation of Crohn’s disease or ulcerative colitis are seen in 5 to 30% of the cases…The renal manifestations of the Crohns’s disease are secondary amyloidosis, acute interstitial nephritis, Ig A nephropathy and MPGN pattern of glomerulonephritis…It is important to screen any patient for proteinuria and microscopic hematuria atleast once a year in IBD..
Secondary increased oxalate reabsorption is known to occur with IBD or any intestinal disease…So, this donor should have a full metabolic panel evaluated including urinary oxalate, urinary calcium, urinary potassium, urine spot creatinine urine pH before proceeding for donation…This is to ascertain the future risk of nephrolithiasis in the left over kidney of the donor as his crohn’s disease could have multiple flare ups….
I would proceed with organ donation after metabolic panel workup keeping in mind secondary oxalosis ….I would keep the donor under active clinical follow up and metabolic surveillance
I could not accept him as a donor as kidney involvement could occur as an extraintestinal manifestation of inflammatory bowel disease and could be affected by its medication.
Renal involvement could be
A. Nephrolithiasis:
1- hyperoxaluria due to bile salts malabsorption, increased colonic permeability to oxalate and oxalobacter formigenes decolonization
2- low urine PH and hypovolemia lead to urine uric acid supersaturation
B. Tubulointerstitial nephritis
Drug-induced: with 5 aminosalicylic acid, cyclosporin, tacrolimus, and TNF alpha
Nondrug induced occurs with disease activity
C. Amyloidosis: rare
D. Glomerulonephritis
IgA, IgM, membranous and anti GBM
Related to disease activity and improve with remission
references:
1- Corica D and Romano C. Renal Involvement in Inflammatory Bowel Diseases. Journal of Crohn’s and Colitis, 2016, 226–235doi:10.1093/ecco-jcc/jjv13
Crohn’s disease and ulcerative colitis usually have a chronic, relapsing course and require long-term treatment. These diseases will often have systemic effects, e.g. Fatigue or anemia, and there can be an association with other disorders, e.g. arthritis, which affects the donor’s general health.
If no other donor makes sure no history of renal stones and negative metabolic screening
A discussion with a gastroenterologist and also should be counseled regarding the risks to both intestinal and renal complications.
1- consult the gastroenterologist and patient counselling about his kidney donation and possibility of formed stone ..
first of all will investigate this patient any secondary hyperoxaluria
if he has no other option rather than this donor ,will accept if
no active on going inflammation (flare).
on evidence of seconary hyperoxalurea
regular follow up after donation
Patients with chron’s disease have the risk of renal stones due to hyperoxaluria and amyloidosis with increased mortality following transplantation .Grupper et al,2019 found that patients with chron’s patients IBD is associated with higher mortality following transplantation and hospitalization doe to infection and late hospitalization but stable course of inflammatory bowel disease.
We can accept that offer with precaution of confirmation of absence of proteinuria and recurrent renal stones .Based on remission, reasonable survival post-donation can be expected, and because oxaluria is secondary, high risk of stones is not expected
Grupper, Ayelet, et al. :Kidney transplantation in patients with inflammatory bowel diseases (IBD): analysis of transplantation outcome and IBD activity.” Transplant International 32.7 (2019): 730-738.
Reply to Professor Ahmed Halawa
We should accept him as a potential donor if the patient is on remission (at least 6 months), no renal stone and no other extraintestinal manifestation associated with crohn’s disease. We should inform him about the risks of potential donor with Crohn’s disease (surgical, increase risk of infection). As he is at increasing risk of developing renal stones he should have a metabolic screen .
Extraintestinal manifestations of IBD are varied and concentrated mainly on the joints, skin and eyes. Urinary tract or renal involvement is rare, and includes nephrolithiasis, tubulointerstitial nephritis and amyloidosis. Nephrolithiasis, caused by calcium oxalate or urate, has been reported in approximately 4–23% of patients with Crohn’s Disease and can be considered the most frequent renal manifestation in IBD. Drug-induced nephrotoxicity seems more frequent and has been described in adult populations. Aminosalicylates, azathioprine, cyclosporin and TNFα inhibitors may be involved in renal impairment. However, it is not always possible to clarify the mechanism of these drugs in kidney damage. In many cases it remains unclear whether renal impairment is an EIM or a drug adverse effect (1).
This patient is on remission for the last 6 years only on Mesalazine. However, he is young, at increased risk of thrombosis, three to four folds higher than subjects without IBD (2), infections and potential risk of relapse. Indeed CD has a relapsing course (CD has a relapsing course with almost 70 % requiring hospitalization) (3) and high surgical rate (50% of the patients need surgery in the first 10 years after the diagnosis) (4).
In view of the above explanation I would discourage him as a potential donor considering his young age, the potential risks associated with the disease (as above mentioned) and the surgical risks.
References:
1) Domenico Corica, Claudio Romano Journal of Crohn’s and Colitis, Volume 10, Issue 2, February 2016, Pages 226–235, https://doi.org/10.1093/ecco-jcc/jjv138
2) Clin Transl Gastroenterol. 2018 Apr; 9(4): 142.Published online 2018 Apr 3. Risk of thrombosis and mortality in inflammatory bowel disease. Adriana R. Andrade, MD, Luísa L. Barros, MD, Matheus F. C. Azevedo, MD, Alexandre S. Carlos, MD, Aderson O. M. C. Damião, MD, Aytan M. Sipahi, MD, and André Z. A. Leite
3) Aniwan, S., Loftus, E.V. The Natural History of Inflammatory Bowel Disease. Curr Treat Options Gastro 19, 2021;597–607.
4) Freeman HJ. Natural history and long-term clinical course of Crohn’s disease. World J Gastroenterol. 2014 Jan 7;20(1):31-6. doi: 10.3748/wjg.v20.i1.31. PMID: 24415855; PMCID: PMC3886024.
This potential kidney donor, has inflammatory bowel disease ( Crohn’s disease) which is controlled by mesalazine and no flare for 6years. Despite he is under control I will find it difficult to accept him. This is because of significant extra intestinal manifestation could be associated. In the kidney these include renal stones, glomerulonphrists, amyloidosis and interstitial nephrits.
There is no much data, I could find, with regard to Crohn’s disease itself and kidney donation and that is expected as the disease is not very common like diabetes,hypertension or hematuria. But there is data in relation to renal stone which is associated with Crohn’s disease. Also, we can apply the rule of doing no harm first in such case. Not to underestimate the glomerulonephritis and interstitial nephritis beside renal stone that could happen if the disease become active with affect the remaining kidney.
So he is not suitable as kidney donor.
*One study conducted that:
A total of 150 IBD patients (ulcerative colitis in 45%, Crohn’s disease in 55%) were included. Sixty-two patients were receiving 5-ASAs (95% coated mesalazine, mean dose 1.9±0.8g/day). Both serum creatinine levels and ClCr were similar in patients with and without 5-ASA treatment, and remained stable throughout the 4-year follow-up in patients taking 5-ASAs. In the multivariate analysis, 5-ASA treatment (or its dose) was not correlated with serum creatinine levels or ClCr. No interstitial nephritis was reported during follow-up.
Conclusion:
5-ASA-related renal disease was not found in the series, suggesting that the occurrence of renal impairment in IBD patients receiving these drugs is exceptional. The results do not support the recommendation of serum creatinine monitoring in patients receiving 5-ASA treatment.
*Also in the study by Elseviers et al, all IBD patients seen at the outpatient clinic of 27 European centres of gastroenterology during 1 year were registered and screened for renal impairment controlling for a possible association with 5- ASA therapy. Renal screening (calculated ClCr) was performed at baseline, after 6 and 12 months. Decreased ClCr was observed in 34 patients, among which 13 presented chronic renal impairment. Comparing patients with and without renal impairment, no difference could be observed in 5-ASA consumption.
REFERENCES
(1).L. Sutherland, D. Roth, P. Beck, G. May, K. Makiyama.
Oral 5-aminosalicylic acid for maintenance of remission in ulcerative colitis.
Cochrane Database Syst Rev, (2002),
(2).J.P. Gisbert, F. Gomollon, J. Mate, J.M. Pajares.
Role of 5-aminosalicylic acid (5-ASA) in treatment of inflammatory bowel disease: a systematic review. Dig Dis Sci, 47 (2002), pp. 471-488
The available donor is
Young age
III Mismatches
No DSA
History of crohn ‘s disease controlled on mesalazine with history of one flare up 6 years ago
No proteinuria or haematuria.
No other medical history
This donor if accepted may suffer long term complications from due to extra-intestinal manifestation like interstitial nephritis nephrolithasis due to electrolytes disturbances due to precipitating hypomagnesamia and hypercalcuria which need metabolic screening with dietary abnormalities.
On other hand there are risk for increasing risk for venous thromboembolism and delay healing of wound due to complicated infection
I will not accept that donor
Must not donate.
If diagnosed with microscopic colitis, collagenous colitis, lymphocytic colitis only, accept if:
In this cas ( running out of access and there is no deceased donor)
We would accept him under some strict conditions
Such donor with. in active Crohn’s disease for 6 years with total remission we can accept him for donation as he is in deep remission but we need to have full assessment as they are oxalate forming stone . Generally ,and because of donor pool limitation we may accept such donor after full discussion about the case.
AS we know Crohn’s disease can be associated with stone formation ,kidney tubular AKI and GN AS WELL ,so the recipient and donor should be aware of all risk around such transplant .
the recipient will be advised to take plenty of fluid ,and should have regular follow up post transplant .
We have A young potential living donor with hx of Crohn’s disease is under control by mesalazine last flare 6 years ago and excellent kidney function offered a kidney to his father who 65 years old.
This donor will have both medical and surgical problems after donation
He may developed many extraintestinal complications and the kidney one of them as he may develop renal failure due to amyloidosis and renal oxalate calculi especially if undergone bowel resections
Also glomerulonephritis as extraintestinal manifestation of Crohn’s disease.
Treatment with oral 5-aminosalicylic acid has been linked to interstitial nephritis.
Crohn’s disease and ulcerative colitis usually have a chronic, relapsing course and require long-term treatment. These diseases will often have systemic effects, e.g. Fatigue or anaemia, and there can be association with other disorders, e.g. arthritis, which effects the donor’s general health.
Lesions in the gastrointestinal tract of individuals with Crohn’s disease and ulcerative colitis caused by the disease can increase the risk of bacteria entering the blood stream. Bacteria in donated material can multiply to dangerous levels during storage.
So we need MDT including nephrologist, gastroenterologist ,urologist to make decision accepting this donor especially he has a history of remission 6 years ago
But my opinion is to decline such donor with systemic immune disease especially there is lack of guidelines and study upon accepting such living donors
Substitute your answer
>>>> The kidney can be an extraintestinal target of Crohn’s disease, which has been associated with renal failure due to amyloidosis and renal oxalate calculi in patients who have undergone bowel resections. Treatment with oral 5-aminosalicylic acid has been linked to interstitial nephritis. Renal failure caused by glomerulonephritis is a rarely reported extraintestinal manifestation of Crohn’s disease. In the cases reported in the literature, the inflammatory bowel disease is usually active.16 A possible link between inflammatory bowel disease and glomerulone-phritis is speculative, but for Crohn’s disease, it could be explained by increased permeability resulting in systemic absorption of antigens. These antigens could provoke a rise in serum levels of immunoglobulin (Ig)G and IgA with the development of immune complexes.
>>>> Secondary hyperoxaluria is most commonly of intestinal origin and may also lead to recurrence in the allograft. Patients have usually suffered from inflammatory bowel disease or morbid obesity. If the underlying defect is reversible (e.g., intestinal bypass for obesity), consideration should be given to surgical 200 reversal before transplantation. In urinating patients, the 24-hour excretion of oxalate should be checked to help assess the risk for recurrent oxalosis.
Reference
JPAC
Joint United Kingdom (UK) Blood Transfusion and Tissue Transplantation Services Professional Advisory Committee
Crohn’s Disease and Solid Organ Transplantation
Karel Geboes, MD, PhD
The prevalence of extraintestinal manifestations in inflammatory bowel diseases varies from 6% to 46%.
The aetiology of extraintestinal manifestations remains unclear. There are theories based on an immunological response influenced by genetic factors.
Extra-intestinal manifestations can involve almost every organ system. They may originate from the same pathophysiological mechanism of intestinal disease, or as secondary complications of inflammatory bowel diseases, or autoimmune diseases susceptibility.
The most frequently involved organs are the joints, skin, eyes, liver and biliary tract.
Renal involvement has been considered as an extraintestinal manifestation and has been described in both Crohn’s disease and ulcerative colitis. The most frequent renal involvements in patients with inflammatory bowel disease are nephrolithiasis, tubulointerstitial nephritis, glomerulonephritis and amyloidosis. IBD is a chronic idiopathic inflammatory disease with relapse and remission in nature.
Risk factors for progressive disease include :
smoking
age <40 years
perianal or rectal involvement
and
need for steroid to control the disease
Drugs used in the treatment of IBD also may lead to interstitial nephritis.
Gastrointestinal involvement may lead to frequent diarrhea with episodes of AKI Due to hypovolemia and infection
This prospective donor will not allowed to donate .
He is young and even if the disease now in remission for 6 years , there is enough time for unexpected events that will harm the remaining kidney. In edition to the various drugs used accordingly with its adverse effects.
If he insisted to donate and there is no other option so we must make sure from the following:
No evidence of stones.
normal metabolic profile
No extra GI manifestation
No proteinuria or Hematuria
Reference:
Renal Involvement in Inflammatory Bowel Diseases
Domenico Corica et al. J Crohns Colitis. 2016 Feb.
Inflammatory bowl disease lead to malabsorption of the oxalate so this potential donor had higher risk of calcium oxalate stone so as his disease controlled for the last 6 years I will accept him if I had no other donor than him and there’s no history of renal stone and negative metabolic screening
If the gastroenterologist clears the donor, I would accept him for kidney donation.
Thank you, See my question above
A 39-year-old male with excellent kidney function offered a kidney to his father who 65 years old, 111 mismatches, no DSA. His Crohn’s disease is under control by mesalazine where he had only one flare-up 6 years ago. No other significant medical history. No evidence of hematuria or proteinuria.
What is your management?
This is again a complex donor condition the donor is nonhealthy he had chronic inflammatory bowel disease although he is in remission now for 6 years and the disease is under control with mesalazine only, he is a young donor that his disease might progress at some point in the future and put him at medical , surgical complications, and medication side effect on a single kidney post donation like interstitial nephritis, AKI, secondary oxalosis, also he had a certain concern about the surgical risk at the time of donation as Crohn’s disease patient are at high risk of venous thromboembolism, poor surgical wound healing due to infection, fistula, and anastomosis leak.
I will decline his donation and will be referred to an independent living donor advocate to explain and discuss with him and his recipient all the above medical and surgical risks.
Substantiate your answer
there are specific medical and surgical concerns to be addressed in this case
1. The kidney can be an extra-intestinal target of Crohn’s disease and has been associated with renal failure due to amyloidosis and renal secondary oxalosis in patients who have suffered bowel resections and those with short bowel syndrome.
2. Treatment with oral 5-aminosalicylic acid has been linked to interstitial nephritis.
3. A probable link between inflammatory bowel disease and glomerulonephritis is theoretical, but for Crohn’s disease, it could be explained by increased permeability resulting in systemic absorption of antigens. These antigens could aggravate a rise in serum levels of immunoglobulin (Ig)G and IgA with the development of immune complexes mediating glomerulonephritis like Ig A nephropathy, also ANCA associated vasculitis .
4. perioperative complications and the risk of infection, anastomosis leak and postoperative wound infection, and nonhealing with increased risk of sepsis, and malnutrition (2).
5. Crohns Patients are at high risk of venous thromboembolism (2).
References
1. Geboes K. Crohn’s disease and solid organ transplantation. Gastroenterol Hepatol (N Y). 2008 Dec;4(12):877-8.
2.Reindl W, Thomann AK, Galata C, Kienle P. Reducing Perioperative Risks of Surgery in Crohn’s Disease. Visc Med. 2019 Dec;35(6):348-354.
Thank you, Saja, for the excellent answer and summary. See my question above
The index prospective donor has no significant medical history except Crohn’s disease which is under control with one flare-up 6 years ago.
Crohn’s disease is a chronic inflammatory bowel disease which has a relapsing course (1). About two-thirds require hospitalization and 50% of the patients require a surgery within 10 years of diagnosis (2). The relevance of Crohn’s disease in the prospective donor with respect to kidney transplantation is due to the increased risk of extraintestinal involvement like nephrolithiasis, tubulointerstitial nephritis, glomerulonephritis, amyloidosis etc in Crohn’s disease (3,4) The risk factors for renal stone formation in Crohn’s disease include metabolic abnormalities like hypocitraturia, hypomagnesuria and hypercalciuria, dietary (high dietary carbohydrate/fat and protein, and low dietary calcium and magnesium) and environmental (smoking, stress, air pollution) risk factors, altered intestinal permeability and recurrent antibiotic use reducing Oxalobacter formigenes concentration (1,3).
Risk factors for disease related complications include young age at diagnosis, extensive anatomical involvement, and concurrent primary sclerosis cholangitis (1).
According to the BTS/RA guidelines, any prospective donor with propensity to develop renal stones must undergo a detailed metabolic screening (5).
Any stressful incident, including surgery is a risk factor for relapse.
In view of risk of nephrolithiasis, tubulointerstitial nephritis, glomerulonephritis, amyloidosis etc in Crohn’s disease, this donor should be excluded. The patient should look for another living donor or get enrolled in deceased donor program.
References:
1) Aniwan, S., Loftus, E.V. The Natural History of Inflammatory Bowel Disease. Curr Treat Options Gastro 19, 2021;597–607.
2) Freeman HJ. Natural history and long-term clinical course of Crohn’s disease. World J Gastroenterol. 2014 Jan 7;20(1):31-6. doi: 10.3748/wjg.v20.i1.31. PMID: 24415855; PMCID: PMC3886024.
3) Gaspar SR, Mendonça T, Oliveira P, Oliveira T, Dias J, Lopes T. Urolithiasis and crohn’s disease. Urol Ann. 2016 Jul-Sep;8(3):297-304. doi: 10.4103/0974-7796.184879. PMID: 27453651; PMCID: PMC4944622.
4) Corica D, Romano C. Renal Involvement in Inflammatory Bowel Diseases. J Crohns Colitis. 2016 Feb;10(2):226-35. doi: 10.1093/ecco-jcc/jjv138. Epub 2015 Jul 29. PMID: 26223844.
5) British Transplantation Society. Renal Association Guidelines for Living Donor Kidney Transplantation, 4th ed.; British Transplantation Society: Macclesfield, UK, 2018; Available online: https//bts.org.uk/wp-content/uploads/2018/07/FINAL_LDKT-guidelines_June-2018.pdf (accessed on 5 October 2022).
Thank you, See my question above
Crohn’s disease is known to have extra-intestinal manifestation and atherosclerosis as well as predisposition to stone formation ( uric acid and oxalate stones). Later in life patients with established diagnosis of Crohn’s disease are prone to have amyloidosis. So, the kidney may be affected by the atherosclerosis, nephrolithiasis and amyloidosis.
I will accept this donor provided that:
a) There is no active disease( the potential donor is under control for 6years.
b) No extra-intestinal manifestations.
c) No stone formation nor a predisposing factor to stone formation. The potential donor should be sticked to high fluid intake and dietary advice in regards to Crohn’s disease( diet to be supplemented with calcium, magnesium or citrate).
Thank you, but he passed one stone five years ago.
Crohn’s disease has a relapsing remitting course requiring long term immunosupression and biological agents exposing patients to multiple issues like
Stone formation
infection
Renal Amyloidosis
Malignancy
so keeping all this in mind he should not be considered as a safe donor.
If he is the only donor we can consider him only
if he is in long term complete clinical remission
and cleared by Gastro for donation
He would require very close follow up post transplant
Thank you. Will you do metabolic screening as well?
This 39 year potential donor with Inflammatory bowel disease for his father should be counseled about the risks of renal involvement associated with disease which is around 4-23% and include nephrolithiasis, glomerulopathies (IgA nephropathy), Tubulointerstitial disease and amyloidosis. Also the drugs which have been used to treat the disease can affect the kidneys like 5-aminosalicylate , CNIs(Cyclosporine, Tacrolimus ) and that IBD is a relapsing disease which can occur in the donor later that will affect the quality of life .Keeping in view all this, I will not accept him as a donor.
REFERENCES:
Ambruzs JM, Larsen ChP. Renal Manifestations of Inflammatory Bowel Disease. Rheum Dis Clin N Am 44 (2018) 699–714
Thank you, See my question above
What is your management?
This potential donor offered kidney to his father with low immunological risk but has Crohns disease. There is no flare up in last 6 years . He is stable with Mesalazine. There are risks with kidney donation. these include:
Disease progression due to stress of donor Nephrectomy.
Urinary Stones- Like oxalate stones which can lead to renal obstruction and damage. Ultimately there can be high risk of ESRD.
Episode of disease relapse can lead to hypovolemia and renal damage.
There can be higher risk of Renal amylodosis, Glomerulonephritis , drug induced nephrotoxicity and Tubulointerstitial nephritis.
I will not accept him as renal donor.
Best would be to look for other suitable donor or deceased donor. If there is no other option then he can be considered for donation if-
There is normal metabolic profile
No evidence of stones
No extra GI manifestation
Normal metabolic profile
No proteinuria or Hematuria
Geboes K. Crohn’s disease and solid organ transplantation. Gastroenterol Hepatol (N Y). 2008 Dec;4(12):877-8.
Thank you, See my question above
However good match with No DSA But the donor is not a candidate due to the high risk of renal involvement in patients associated with Crohn’s disease and we must search for alternative living or deceased donors.
Renal affections include :
1- Nephrolithiasis
The prevalence of nephrolithiasis among patients with IBD is higher than in the general population, ranging from 12% to 28% , kidney stones in patients with Crohns disease are usually of uric acid and calcium oxalate
2-Glomerulonephritis :
IgA Nephropathy ( The correlation between IgA nephropathy and IBD could be explained by a genetic connection between IgA nephropathy and IBD)
IgM Nephropathy
Membranous
Mesangiocapillary
FSGS
3- Tubulointerstitial nephritis
4- Renal amyloidosis
5- Drug-induced nephrotoxicity
Aminosalicylates, cyclosporin, and TNFα inhibitors may cause renal impairment.
Ref :
Renal Involvement in Inflammatory Bowel Diseases
Domenico Corica, Claudio Romano
Journal of Crohn’s and Colitis, Volume 10, Issue 2, February 2016, Pages 226–235, https://doi.org/10.1093/ecco-jcc/jjv138
Thank you, See my question above
_ This young donor with Crohn’s disease is at high risk of kidney injury , so he must be precluded from donation even if he is in remission now for years and search for another donor even deceased one.
– the Crohn’s disease can predispose him post donation to:
_ Renal oxalate stones (which can lead to obstructive uropathy and CKD in this solitary kidney after donation) as secondary hyperoxaluria from lacking oxalobacter and its affection and alteration in Crohn’s disease).
_ Infectious episodes and disease activity with diarrhea that can cause volume depletion and hypo-perfusion of the kidney (exaggerated if single kidney).
_ in addition, the surgical stress of living donor nephrectomy can precipitate an attack of crohn disease.
_ Medications used for treatment, as mesalazine or 2nd line treatment if needed as CNI, infliximab can have nephrotocic effect.
_ interstitial nephritis, glomerulonephritis and renal amyloidosis also can occur in Crohn’s.
Thank you, See my question above
The kidney can be an extraintestinal target of Crohn’s disease:
CD has been associated with renal failure due to amyloidosis and renal oxalate calculi in patients who have undergone bowel resections.
Treatment with oral 5-aminosalicylic acid has been linked to interstitial nephritis.
Renal failure caused by glomerulonephritis is a rarely reported extraintestinal manifestation of Crohn’s disease.
Secondary amyloidosis (AA) has been reported ranges from 0.3% to 10.9% in CD.
Having such a high risk for the potential donor itself, I would not accept him as donor
If there is no alternative suitable donor and no Deceased donor available,
I would make sure:
Gastroenterologist and Transplant team need to asses the risk for the donor and MDT meeting should have shared decision to proceed transplantation.
Thank you, See my question above
What is your management?
The prevalence of extraintestinal manifestations (EIMs) in inflammatory bowel diseases (IBDs) varies from 6%–46%. Renal involvement has been considered as an EIM and has been described both in Crohn’s disease (CD) and in ulcerative colitis (UC). The most frequent renal diseases in patients with IBD are: nephrolithiasis, tubulointerstitial nephritis, glomerulonephritis and amyloidosis . Kidney pathologies in IBD may be associated with side effects of drugs.
Nephrolithiasis, caused by calcium oxalate or urate, has been reported in approximately 4–23% of patients with CD and can be considered the most frequent renal manifestation in IBD. Drug-induced nephrotoxicity seems more frequent and has been described in adult populations. Based on the existing literature, and considering that no precise guidelines are available, it is useful to periodically monitor renal function in IBD patients through observation of azotaemia and creatinine levels and, above all, monitoring GFR and creatinine clearance (CCr). Monitoring of blood and urine electrolytes, urinalysis and 24-hour urinary protein can be useful but not specific. The GFR seems to be the most reliable marker of renal function; it should be monitored before and after starting therapy with 5-ASA, CsA and TNFα inhibitors. However, so far there is no evidence that such monitoring of renal function and clinical management improves patient outcomes.
-It will not accept this donor.
Referrence:
-Domenico Corica, Claudio Romano .Renal Involvement in Inflammatory Bowel Diseases. Journal of Crohn’s and Colitis, Volume 10, Issue 2, February 2016, Pages 226–235,
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In case of complete remission can accept as donor but should counselling regarding risk of oxalate stone in case of flare up of his disease and malnutrition and risk of dehydration and complications of crohnis disease
Crohn’s disease have a chronic, relapsing course and needs long-term therapy . It has systemic effect as fatigue , anaemia, and arthritis, which affects the donor’s health status.
Gastrointestinal tract lesions in Crohn’s disease cases caused by the disease itself can increase the risk of bacteria enterance to the blood stream and bacteria in donated grafts can multiply to dangerous levels during storage.
The kidney can be an extraintestinal target of Crohn’s disease, associated with renal failure due to amyloidosis and renal oxalate calculi in patients who have undergone bowel resections.
Treatment with oral 5-aminosalicylic acid has been linked to interstitial nephritis.
Renal failure caused by glomerulonephritis is a rarely reported extraintestinal manifestation of Crohn’s disease.
So Crohns disease is an absolute contraindication for donation.
In this case in spite of having remission for 6 years it is advisable to seek another donor and reject the current donor.
Refernce
-Joint United Kingdom (UK) Blood Transfusion and Tissue Transplantation Services Professional Advisory Committee.Inflammatory bowel disease.DSG-WB Edition 203, Release 63.
-OHSU Kidney/Pancreas Transplant Protocol Handbook, Chapter 2.13, Pre-Transplant Evaluations LaPointeRudow, D., et al. A Clinician’s Guide to Donation and Transplantation. Lenexa, KS: Applied MeasurementProfessionals, Inc.; 2006. Chapters 16,17;
-Geboes K. Crohn’s disease and solid organ transplantation. Gastroenterol Hepatol (N Y). 2008 Dec;4(12):877-8.
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Crohn’s disease and ulcerative colitis usually have a chronic, relapsing course and require longterm treatment. These diseases will often have systemic effects, e.g. Fatigue or anaemia, and
there can be association with other disorders, e.g. arthritis, which effects the donor’s general
health.
Lesions in the gastrointestinal tract of individuals with Crohn’s disease and ulcerative colitis
caused by the disease can increase the risk of bacteria entering the blood stream. Bacteria in
donated material can multiply to dangerous levels during storage.
I will no accept him as a donor
WB&C-DSG 203 (01 June 2007) Release 63 (26 April 2022) page 127
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Summary:
A patient with a history of IBS is Chron’s disease and is taking mesalamine. Over the past 6 years, he hasn’t had any flares.
IBS is accompanied by various complications like:
1) Renal pathologies due to the extraintestinal manifestation of the disease. There are possibilities for forming:
a) nephrolithiasis
b) TIN,
c) FSGS,
d) membranous GN,
e) mesangiocapillary GN,
f) IgA and
g) amyloidosis.
h) Medications
The composition of the kidney stone is calcium oxalate and uric acid.
2) Intestinal pathology due to enteric hyperoxaluria increase the intestine to absorb oxalate. This in term has an effect on the kidneys but increases the excretion of oxalate and as such increase the risk of kidney stones.
The pathophysiology of TIN may be associated with medication like 5-aminosalicylate, cyclosporine, and the use of TNF alpha inhibitors.
Amyloidosis occurs due to chronic inflammation and gives secondary amyloidosis. It can deposit in the kidneys causing glomerulopathies which are accompanied by proteinuria and possible kidney failure.
The pathology of IBS is associated with malignancies to the gastrointestinal tract, blood cancer like leukemia, and also lymphoproliferative disorders.
IBS has risk factors that can worsen it:
1) Heavy smokers
2) Younger adults
3) Perforation, etc
The disease must be monitored closely and investigations must be conducted to ensure there is no flaring like:
1) CBC
2) Electrolytes
3) Urine test
4) ESR OR CRP
5) Ultrasounds to look for stones
6) Metabolic studies
7) Referral to gastroenterologist
8) Referral to nephrologist to ensure kidney functions are adequate
Once all is well I should believe the patient may be a candidate for a donor but with all the complications I will place very far on the donor list. It is too risky in terms of surgical procedures and the recurrence of flaring and to develop of kidney disease.
References:
BTS/RA Guidelines of Living Donor Kidney Transplantation
Thia KT, Sandborn WJ, Harmsen WS, et al. Risk factors associated with progression to intestinal complications of Crohn’s disease in a population-based cohort. Gastroenterology 2010; 139:1147.
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