4. Urine dipstick showed 2+ of blood on investigation of a potential female donor who is 31-year-old. Urine microscopy showed granular casts. No evidence of DM or hypertension. She has excellent kidney function with no evidence of proteinuria
- What is the significance of this urine picture (haematuria and casts)?
- How do you proceed?
- Would your management differ if there were no granular casts on urine microscopy?
- Substantiate your answer
Thank You all
Although the guideline suggests the safety of kidney donation in individuals with TBMD, I strongly feel uncomfortable. Do you know why?
Because TBMD may be the beginning of progressive renal damage , the early spectrum of Alport syndrome , so it’s not completely regard as a benign condition.
Yes Asmaa.
The TBMN phenotype is associated with heterozygous carriers of COL4A3, COL4A4 mutations. Molecular genetic testing is the gold standard for diagnosing these diseases. Although genotype-phenotype correlations exist, the phenotype is influenced by modifying factors, which remain mainly undefined. make some difficulty in identifying them from Alport’s syndrome.
Reference:
Plevová P, Gut J, Janda J. Familial hematuria: A review. Medicina (Kaunas). 2017;53(1):1-10. doi: 10.1016/j.medici.2017.01.002. Epub 2017 Jan 31. PMID: 28236514.
The risk of ESRD is not completely zero, some people with TBMD developed ESRD
Yes that is right Dr Ben.
Thanks Prof
My approach is similar to Dr Ben and Dr Asmaa, if this turns out to be TBMD. I would suggest other options such as other donors among family and friends and cadaveric transplant.
I would keep this prospective donor in reserves just in case she may have to be considered as a donor for 2nd or 3rd transplant in a decade or so. That would reveal the natural history of TBMD in this index case to be tested by time.
One more opinion:
those with TBMD are older than 40 years and IgA and Alports can be excluded then such a donor might be considered with full explanation to the prospective donor and family.
Yes, prof
I agree with you, prof Ahmed
better to avoid the donor with TBMD
*The majority of patients with isolated hematuria, TBMN, and negative family history for kidney failure maintain normal kidney function and normal urine protein excretion on follow-up. However, follow-up is essential in order to identify those individuals who, for whatever reason, exhibit a progressive disease course.
*the presence of a heterozygous COL4A3/COL4A4 variant in a patient with hematuria and thin GBM should be considered a risk factor for chronic kidney disease, whether a clinician decides to diagnosis the patient with Alport syndrome or TBMN. Slowly progressive kidney function impairment can occur and is often manifested on kidney biopsy by focal segmental glomerulosclerosis.
*However, some data suggest that FSGS is frequently caused by COL4A3/COL4A4 variants.
it could be an early spectrum of Alport syndrome,
Thin basement membrane nephropathy (TBMN) is an autosomal dominant disorder often associated with mutations in either the COL4A3 or COL4A4 genes (encoding the &3 and &4 chains of type 4 collagen).
Individuals in whom both alleles of either gene are abnormal may have autosomal recessive Alport syndrome, and TBMN can be regarded as the carrier state for this condition.
TBMN is present in 10-50% of patients biopsied for PANVH and although often considered a benign diagnosis may carry some risk of progression.
Both proteinuria (10-20% of patients) and renal impairment (5%) have been described and often associated with additional pathological abnormalities including FSGS or IgA nephropathy (both of which would preclude donation).
A recent study of Greek-Cypriot families with familial haematuria identified COL4A3 or COL4A4 mutations in 16/57 families (28.1%), and in this population 10/87 (11.5%) heterozygous patients developed ESRD
Reference
Guidelines for Living Donor Kidney Transplantation Fourth Edition March 2018
BTS/RA Living Donor Kidney Transplantation Guidelines 2018 United Kingdom Guidelines
There can still be some risk of CKD and ultimately ESRD. It would be better to look for other suitable options and keep these in reserve.
Because heterozygous COL4A3/COL4A4 variant in a patient with hematuria and thin GBM should be considered a risk factor for chronic kidney
Some patients may develop proteinuria greater than 500mg/24 hours leading to hypertension and then renal impairment. It is hard to know which patients so that’s why it’s a challenging to know who to transplant
TBMD there is still exitance risk of ESRD so although is rare .
There can still be some risk of CKD and ultimately ESRD. It would be better to look for other suitable options and keep these in reserve.
Kidney donation with TBMD is controversial as still there is risk for slow progression to ESRD despite the benign nature of the disease. Potential donors with age more than 40 years in absence of proteinuria and hypertension could be considered for donation.
I agree with you, prof Ahmed
better to avoid the donor with TBMD
*The majority of patients with isolated hematuria, TBMN, and negative family history for kidney failure maintain normal kidney function and normal urine protein excretion on follow-up. However, follow-up is essential in order to identify those individuals who, for whatever reason, exhibit a progressive disease course.
TBMD associated with mutations in either the COL4A3 or COL4A4 genes,
Individuals in whom both alleles of either gene are abnormal may have autosomal recessive Alport syndrome, and TBMN can be regarded as the carrier state for this condition, which is associated with a 5-20% risk of progressive renal impairment
In this young patient, we need to confirm the diagnosis. If we are sure about the thin basement membrane, a donation may be acceptable but accompanying or probable future risks make us hesitate. as Alport syndrome may mimic TBM, we need to perform the genetic tests of Alport to make sure. Alport syndrome although hav different probable scenarios is not suitable for donation. Being young is co-factor of reluctance to accept
Donation from patients with TBMD remains controversial, given the lack of long term studies that address the outcomes of kidney donation in these patients.
The clinical course of TBMD is generally benign. However, the duration of most longitudinal studies has been too short to reflect prognosis. One study reported that 7% of patients with biopsy-proven TBMD had renal dysfunction with a serum creatinine level greater than 1.2mg/dl. Risk factors for progression are proteinuria, hypertension and abnormal renal function.
Although the long term prognosis of the majority of patients with thin basement membrane nephropathy is excellent, some patients develop proteinuria and progressive renal failure, especially those with documented heterozygous mutations in COL4A3 or COL4A4 genes.
although it is known that the thin basement membrane disease is a benign and it is not contra indicated for donation, But this a benign behaveure is not always . there some case with progression to CKD.
Because of probability that it would be an early presentation of Alport syndrome
Dear All
1. What will you do if the investigations of PNVH came back negative including cystoscopy, imaging and kidney biopsy?
2. The guidelines suggested that potential donors with TBM can proceed to donation. What is the long-term outcome of these donors as far the renal function is considered?
2.They generally maintain good renal function at least on mid-term.
References;
Midterm Outcome of Kidney Transplantation From Donors With Thin Basement Membrane NephropathyChanjoong Choi 1 , Sanghyun Ahn 1 , Seung-Kee Min 1 , Jongwon Ha 1 , Curie Ahn 2 , Yonsu Kim 2 , Hajeong Lee 2 , Sang-Il Min 1
Thank You
1-I accept her for donation ;
most of the isolated hematuria were found to be benign .
H. Almana Ital and his group; studied 27 donors (3.6%) were found to have isolated microscopic hematuria & underwent kidney biopsy. all of these donors had positive dipstick hematuria in urine & minimum of 3 red blood cells/hpf on urine microscopy. Eight (29.6%) biopsies showed histopathological abnormalities of which, thin basement membrane disease (n=6, 22.2%) was the commonest lesion followed by IgA nephropathy (n=2, 7.4 %).
2- Kidney transplantation from donors with TBM was found to be associated with favorable graft function .
Reference ;
1-Hassan E, Aleid H, Zulfiquar T, Ibrahim I, Almana H. Potential Kidney Donors with Asymptomatic Micorsocpic Hematuria: Histopathological Findings & Outcomes. Am J Transplant. 2016;16 (suppl 3)
2-Midterm Outcome of Kidney Transplantation From Donors With Thin Basement Membrane NephropathyChanjoong Choi 1 , Sanghyun Ahn 1 , Seung-Kee Min 1 , Jongwon Ha 1 , Curie Ahn 2 , Yonsu Kim 2 , Hajeong Lee 2 , Sang-Il Min 1
Thank You
Any patient presenting by unexplained hematuria the following should be suspected
So … If the investigations are negative including renal biopsy with EM assessment I will proceed to transplantation after 24 hours assessment of uric acid and Ca
TBMD
REFERANCES
1- Uptodate
Well done.
Thank You, Sherif; very impressive. I am concerned about TBMD as Alport’s syndrome and IgA nephropathy. All the 3 share the same genetic background.
TBM patients follow a benign disease course, which is one of the reasons that makes it difficult to distinguish from early stages of progressive renal diseases.However, in addition to hematuria, the TBMN patients have minimal proteinuria, normal renal function and uniformly thinned glomerular basement membranes as determined by electron microscopy.
5 year follow up could reveal stable kidney function without significant complications.
References
I appreciate your views on TBM, Nandita. However, will you go ahead or wait for natural history to reveal itself?
will proceed with no problem
long term outcome of the potential donors with TBM as regard renal function is going good without complications and it is safe to offer a kidney from TBM donor
Chanjoong Choi , Sanghyun Ahn , Seung-Kee Min , Jongwon Ha , Curie Ahn , Yonsu Kim 2, Hajeong Lee , Sang-Il Min. Midterm Outcome of Kidney Transplantation From Donors With Thin Basement Membrane Nephropathy. Transplantation. 2018 Apr;102(4):e180-e184.
C. Choi, A. Han, S.-Y. Kim, S. Cho, M.-J. Cho, C. Lee, S. Ahn, S.-K. Min, J. Ha, M. Park, S. Kim, I. Jung, S.-I. Min. Kidney Transplantation from Thin Basement Membrane Nephropathy Donor. 2016 American Transplant Congress.
Thank You
1- If all mentioned investigations came back negative, I would accept the donor.
2- However taking a renal graft from a donor with TBM appears to be safe for both the donor and the recipient but I think they should be followed up for longer duration post transplantation.
Thank You
Thin basement membrane nephropathy (TBMN) is the most common cause of persistent glomerular hematuria. Most individuals with TBMN show a benign course, although it can be difficult to distinguish it from the early stages of progressive renal diseases. However, only limited studies address the prognosis of donors with TBMN and their recipients.
Methods. From 2007 to 2016, 11 recipients received kidney grafts from donors with TBMN, and their clinical data were analyzed retrospectively. Follow-up protocol kidney biopsies were given to the recipients 10 days and 1 year after transplantation. The donors also received a follow-up evaluation of their renal function and were interviewed via telephone survey.
Conclusions. Kidney transplant donors with TBMN and their recipients maintained their renal function through midterm follow-up without significant complications. Therefore, kidney transplantation from donors with TBMN could be a safe option.
—Choi, Chanjoong, et al. “Midterm outcome of kidney transplantation from donors with thin basement membrane nephropathy.” Transplantation 102.4 (2018): e180-e184.
Thank You, Weam; very impressive. I am concerned about TBMD as Alport’s syndrome and IgA nephropathy. All the 3 share the same genetic background.
If the urological and nephrological evaluation is normal, I will accept the donor.
Guidelines suggested that patients with TBM can donate and their long-term outcome is good.
Thank You.
I will take her as a donor
The long-term prognosis is good in most patients with isolated hematuria and thin glomerular basement membranes (GBM)
Thin membrane nephropathy: a clinico-pathological study.
Aarons I, Smith PS, Davies RA, Woodroffe AJ, Clarkson AR Clin Nephrol. 1989;32(4):151.
Thin-basement-membrane nephropathy in adults with persistent hematuria.
Tiebosch AT, Frederik PM, van Breda Vriesman PJ, Mooy JM, van Rie H, van de Wiel TW, Wolters J, Zeppenfeldt EN Engl J Med. 1989;320(1):14.
Thank You.
Reference:
Choi C, Ahn S, Min SK, Ha J, Ahn C, Kim Y, Lee H, Min SI. Midterm Outcome of Kidney Transplantation From Donors With Thin Basement Membrane Nephropathy. Transplantation. 2018 Apr;102(4):e180-e184. doi: 10.1097/TP.0000000000002089. PMID: 29334529.
Thank You.
Thank You.
1. What will you do if the investigations of PNVH came back negative including cystoscopy, imaging and kidney biopsy?
I will accept this potential kidney donor and proceed for donor nephrectomy and transplant process. Although the possibility of IgAN is still there.
2. The guidelines suggested that potential donors with TBM can proceed to donation. What is the long-term outcome of these donors as far the renal function is considered?
Many individuals with TBMN but otherwise normal investigations have undoubtedly donated kidneys, either knowingly or unknowingly , and although adverse outcomes have not been reported these donors must be made aware of uncertainty over long-term safety1.
BTS/RA Living Donor Kidney Transplantation Guidelines 2018 119
Excellent Safi, this is why I’m always concerned about taking a kidney from those of TBMD
If no cause is found, and the biopsy is negative then it’s most likely that the donor has a possibility of thin basement membrane disease. If the donor still wishes to donate, we can proceed with the donation.
In an analysis done by Choi C et al, where all donors who were followed for 41.0 ± 39.1 months had maintained their renal function upon clinical follow-up without significant complications and concluded that kidney transplantation from donors with TBMN could be a safe option.
1. BTS Living donor guidelines (2011)
2. KDIGO Living donor guidelines
3. Choi C, Ahn S, Min SK, Ha J, Ahn C, Kim Y, Lee H, Min SI. Midterm Outcome of Kidney Transplantation From Donors With Thin Basement Membrane Nephropathy. Transplantation. 2018 Apr;102(4):e180-e184.
Thank You
If all came negative and donor wishes to donate , I will accept this donor
*the prognosis is good in most patients with isolated hematuria and thin glomerular basement membranes .
*most people with isolated hematuria, TBMN, and negative family history for kidney failure maintain normal kidney function and normal urine protein excretion on follow-up.
References:
BTS guidelines
uptodate
thankyou
1-If PNVH investigations are negative and the patient is still willing to donate, i will offer her kidney biopsy to find out the cause, ,mostly IgA nephropathy, TBM or Alport’s syndrome.
2-Midterm follow up study of 11 donors were followed for 41.0 ± 39.1 months and additionally contacted via telephone survey (in total, 56.8 ± 32.0 months). All the donors maintained their renal function upon clinical follow-up without significant complications and denied any discomfort at the time of the telephone interview.
Conclusions: Kidney transplant donors with TBMN and their recipients maintained their renal function through midterm follow-up without significant complications. Therefore, kidney transplantation from donors with TBMN could be a safe option.
References:
1-Transplantation 2018 Apr;102(4):e180-e184.
Midterm Outcome of Kidney Transplantation From Donors With Thin Basement Membrane Nephropathy Chanjoong Choi etal.
Weii done.
What about the question!!!
With her as a kidney donor, given that there is no increased risk of worse renal out come, the problem in our case is the presence of granular casts which make me hesitate in choosing her as a donor, however if no other option to the patient i’ll proceed with her as a donor.
and the long term outcome could be face in TBM donors and recipient as well [1,2].
[1] Choi C, Ahn S, Min SK, Ha J, Ahn C, Kim Y, Lee H, Min SI. Midterm Outcome of Kidney Transplantation From Donors With Thin Basement Membrane Nephropathy. Transplantation. 2018 Apr;102(4):e180-e184. doi: 10.1097/TP.0000000000002089. PMID: 29334529.
[2] Ierino FL, Kanellis J. Thin basement membrane nephropathy and renal transplantation. Semin Nephrol. 2005 May;25(3):184-7. doi: 10.1016/j.semnephrol.2005.01.012. PMID: 15880331.
1- exclude carrier state X-linked Alport syndrome by doing genetic testing as it has high recurrence post transplantation.
2-All studies of long-term outcome from TBMD donors are good in regard to normal graft function .
I will proceed if biopsy and other hematuria invetigation are negative.
Kidney transplant donors and recepients maintain renal function at mid term follow up. A longer follow up will be more helpful as there can be small risk of ESRD
What will you do if the investigations of PNVH came back negative including cystoscopy, imaging and kidney biopsy?
I will proceed with transplant.
2. The guidelines suggested that potential donors with TBM can proceed to donation. What is the long-term outcome of these donors as far the renal function is considered?
TBMN is a cause of persistent glomerular bleeding and affect about 1% of the population. It will give haematuria. Minimal proteinuria and the kidney function will be normal. However, there are certain situation like it adults it can cause proteinuria greater than 500 mg/day and may have renal impairment.
It is generally benign and has a good prognosis. Proper follow-up must be carried since there can be a possibility that the patient can develop hypertension, worsening proteinuria and probably leading to renal impairment
1- If all mentioned investigations came back negative, I would accept the donor.
2- However taking a renal graft from a donor with TBM appears to be safe for both the donor and the recipient but I think they should be followed up for longer duration post transplantation.
according to up to date
TBMD
A recent study of Greek-Cypriot families with familial haematuria identified COL4A3 or COL4A4 mutations in 16/57 families (28.1%), and in this population 10/87 (11.5%) heterozygous patients developed ESRD
BTS/RA Living Donor Kidney Transplantation Guidelines 2018
Based on repeat investigation, isolated microscopic hematuria is not itself a contraindication to kidney donation
Asymptomatic hematuria is a relatively common finding and only approximately 2% of those with hematuria were subsequently found to have serious disease
It may be benign conditions, such as exercise, menstruation
How do you proceed
A family history of kidney illness, uti, stones, or tumours should also be ruled out
A thorough urologic assessment may be necessary for donor candidates who have isolated microscopic hematuria that persists over time. To rule out bladder pathology, a cystoscopy may be required
PA US
CT UT
urine CS
Cystoscopy may be needed
A kidney biopsy may be necessary to exclude glomerular pathology
If associated with proteinuria or undiagnosed repeated hematuria ( such as Alport syndrome, thin basement membrane disease, and immunoglobulin A (IgA) nephropathy in the absence of any particular abnormalities).
Would your management differ if there were no granular casts on urine microscopy?
No I will go on the same way of the diagnotics approaches.
These findings of haematuria and casts without the presence of comorbidities such as DM and hypertension or proteinuria suggest that it is not a glomerular disease.
I perform an imaging exam (USG or tomography) to evaluate nephrolithiasis.
No, it proceeds in the same way, because hematuria in a young patient that is not related to menstruation has a significant chance of being treated for lithiasis.
I will go for this work up:
Repeat urine dip stick 2-3 times to confirm hematuria
Urine exam for dysmorphic RBCS
US and CT KUB
Urine culture
Pt with TBMN better to be avoided as a a donor as it may be early form of Al port syndrome
Hematuria can be because of glomerular and extra-glomerular causes. Microscopic examination of urine should be done as false positive may occur with dipstick like menustration,drugs etc. It is considered significant if more than two samples positive for dipstick and labeled as persistent non-visible hematuria.Granular cast are always because of renal issue so in the above 31 year female donor with urine dipstick showing +2 blood, urine microscopy showed granular cast indicates glomerular cause and in a young patient-thin basement membrane disease, IgA nephropathy,and Alport syndrome,urinary tract infections should be ruled out .
How do you proceed?
After taking detailed history and then examination, Complete blood picture followed by coagulation profile ,urine RE and culture for ruling out infection ,USG abdomen for kidney sizes and CMD followed by CT scan KUB ,24hrs urinary stone analysis followed by renal biopsy if all above tests inconclusive.
Cystoscopy may sometimes be needed in few cases for chronic infections or ruling out malignancy.
Donor with any glomerular disease should not donate except thin basement membrane disease.
Would your management differ if there were no granular casts on urine microscopy?
Yes, management will be little different as the differential which need to be ruled out if hematuria is present but no granular cast include glomerular disease (IgA nephropathy,TBMD)urinary tract infections, nephrolithiasis and bladder carcinoma.All above workup needed along with cystoscopy for excluding chronic infections or bladder malignancy. Kidney biopsy will also be needed . Donor with any glomerular disease should not donate except thin basement membrane disease
REFERENCE:
1- Andrews PA, Burnapp L. British Transplantation Society / Renal Association UK Guidelines for Living Donor Kidney Transplantation 2018: Summary of Updated Guidance. Transplantation. 2018 Jul;102(7):e307.
What is the significance of this urine picture (haematuria and casts)?
31 year old donor with microscopic hematuria 2+ and graunlar casts suggesting glomerular pathology
How do you proceed?
1st Repeat urine dipstick (needs 2 positive tests out of 3 samples)
Renal imaging with urine culture and sensitivity to exclude UTI, stone, or even malignancy.
The presence of hematuria 2+ together with granular casts indicates the importance of performing kidney biopsy
Would your management differ if there were no granular casts on urine microscopy?
No, hematuria 2 + ore more will require renal biopsy
Substantiate your answer
If biopsy showed glomerular injury or pathology other than thin basement membrane disease so donation is discarded.
yes this could be thin basement membrane disease , and it could be a variant of alport and may progress to CKD and ESRD.
If confirmed on two occasions, she has persistent asymptomatic non-visible hematuria (PANVH). The presence of granular cast is not of much significance unless there is proteinuria or RBC cast.
Evaluation includes(1):
My management will not differ if she doesn’t have cast
Reference:
Casts and hematuria may be related to glomerular disease which may cause expose the potential donor to the risk of end-stage renal disease.
A female patient presented with microscopic hematuria should be repeated first because it may be related to her period(contamination). Persistent microscopic hematuria can be glomerular or non-glomerular in origin to differentiate urine should be examined under light, IF and electron microscopy. Nonglomerular hematuria will be non-dysmorphic (biconcave) in shape so, ultrasound, urine culture, and cystoscopy will be needed for diagnosis of the underlying cause. Isolated glomerular dysmorphic microscopic hematuria is related to the main 3 diseases which include IgA nephropathy, Alport disease, and thin membrane disease that’s why such a patient will need to do immunology screening and kidney biopsy pretransplant if she insists on donation. Thin membrane disease is the only benign condition which less commonly associated with ESRD and can be accepted for donation although some thin membrane disease patient develops kidney disease.
No. Even in absence of granular casts, if the urine dipstick is 2+ hematuria should be evaluated and a diagnosis of the underlying cause is needed.
References:
1) Cavanaugh C, Perazella MA. Urine Sediment Examination in the Diagnosis and Management of Kidney Disease: Core Curriculum 2019. Am J Kidney Dis. 2019 Feb;73(2):258-272. doi: 10.1053/j.ajkd.2018.07.012. Epub 2018 Sep 21. PMID: 30249419.
2) 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 20 September 2022).
Potential female donor,31 years , urine dipstick showed +2 blood, urine microscopy showed granular cast.
We must repeat dipstick at least two separate occasions.Two or more positive tests,is considered persistent non-visible haematuria (PNVH), that may be due to urological cause or glomerular cause.
Question 1
The presence of haematuria with granular cast may predict kidney pathology.
Question 2
Workup in this case
Candidates with PNVH undergo testing for possible causes.
Appropriate testing includes
1.urine analysis and urine culture to assess for infection.
2.renal imaging to exclude stones and malignancy
3.cystoscopy in patient age more than 40 years to exclude bladder pathology
4.24-hour urine stone panel to assess for nephrolithiasis
5.If no cause is found and the donor need to donate,a kidney biopsy is recommended if haematuria is +1 or greater in dipstick to exclude glomerular pathology.
IgA nephropathy,MPGN and thin membrane disease are common glomerular pathology related to PNVH.
Glomerular pathology is a contraindication for kidney donation with the exception of thin membrane disease.
Question 3 the same approach
· Q1: In this donor, urine analysis should be repeated for at least two other times. If they are positive (including trace), the donor will be considered as PNVH. The presence of granular cast indicates clusters of urinary sediment elements (RBC, WBC, fat percentage, etc.) and indicates its origin from kidneys. Therefore, if replaced in repeated tests, it would be important.
· Q2: Kidney biopsy will be recommended in this case if hematuria persists on the repeated tests.
· Q3: I would repeat the urine test for 2 more times. If the donor has PNVH, urine culture and renal imaging are necessary to exclude infection, stone and malignancy. In donors older than 40, cystoscopy is performed.
If the donor still wants to donate a kidney, in spite of 1+ or more positive dipstick for hematuria, kidney biopsy is indicated again.
· Q4: Kidney biopsy may indicate thin basement membrane nephropathy (TBMD), Alport syndrome or IgA nephropathy.
The last two, exclude donation, but TBMD could donate if they insist.
In the case of family history for hematuria or Alport syndrome, genetic studies would be helpful and is recommended in addition to kidney biopsy.
What is the significance of this urine picture (haematuria and casts)?
31 y old female donor with urine microscopy showing hematuria 2+ and granular casts.
Make sure she is not menstruating. Repeat urine dip is essential. USS to exclude local urological causes and polycystic kidneys. Hematuria with granular casts raises the possibility of renal causes that can be confirmed with fragmented RBCs in urine.
How do you proceed?
History and examination: UTIs, stones, hearing loss, sore throats, connective tissue disorders, anti-coagulation and anti-platelets and family history of stones, CKD, Alport’s, ADPCKD, IgA nephropathy.
USS-KUB, urine culture, urine PCR, Cystoscopy especially with h/o smoking and occupational exposure or history of chemotherapy. Urine for dysmorphic RBCs, casts, and crystals.
Kidney biopsy; DD: thin basement membrane disease, Alport’s, IgA nephropathy.
Would your management differ if there were no granular casts on urine microscopy?
No, I will proceed as above
Substantiate your answer:
DD of hematuria includes thin basement disease, Alport’s syndrome and IgA nephropathy.
TBMD is AD, is diagnosed by kidney biopsy and EM examination that show thin basement membrane.
Alport disease or IgA nephropathy show progressive glomerular disease.
Donors with isolated TBMD can be accepted for donation with good recipient and donor outcomes.
Q1- What is the significance of this urine picture (haematuria and casts)?
Generally the hematuria cause is classified in to two group
first the glomerular origin hematuria .
second non glomerular origin hematuria.
The former one indicate glomerular disease which may preclude donation but the second group may has bleeding from urinary tract. The presence of granular cast suggests the cause most probably to be non -glomerular in origin.
Q2- How do you proceed?
According to BRITISH TRANSPLANTATIONSOCIETY This patient should be managed as follows :
1- the donors must have (dipstick) urinalysis performed on at least two occasions.
2- Two or more positive tests, including trace positive, is considered as persistent non-visible haematuria (PNVH).
3- If PNVH is present, we need to exclude
O infection,
O nephrolithiasis and
O urothelial carcinoma.
4- If no cause is found, cystoscopy is indicated in patients >40 years to exclude bladder pathology( not in this young patient)
5- If cystoscopy is normal then a kidney biopsy is recommended if haematuria is 1+ or greater on dipstick testing.
6- Glomerular pathology prevent donation (IgA nephropathy, alport syndrome), exception of thin basement membrane disease.
7- With a family history of haematuria or X-linked Alport syndrome, a renal biopsy and referral to a clinical geneticist are recommended.
Q3- Would your management differ if there were no granular casts on urine microscopy?
Yes , in such a case the urological ( non- glomerular ) cause of hematuria should be excluded . urology consultation is needed especially in those above 40 years old for cystoscopy .
Reffrences :
1- Andrews PA, Burnapp L. British Transplantation Society / Renal Association UK Guidelines for Living Donor Kidney Transplantation 2018: Summary of Updated Guidance. Transplantation. 2018 Jul;102(7):e307
Confirm the presence of hematuria by repeating the urine dip. However, being a female, we need to exclude menses and other causes of false hematuria like drugs, hemoglobinuria or myoglobinuria.
If true hematuria is confirmed, this is called persistent non visible hematuria(PNVH) and further work-up is required. Granular cast is an acellular cast and it is a sign of many kidney diseases( deeply pigmented granular cast – muddy brown is present in ATN)
How do you proceed?
If PNVH is confirmed we need to identify the cause through :
Work-up will include:
UACR and PCR to confirm the absence of proteinuria
Urine microscopy to check for red cell casts, dismorphic RBCS by phase contrast microscopy that indicates a glomerular pathology
urine culture to exclude infections
work-up for stone disease
urine cytology to detect malignant cells and cystoscopy if > 40 years to exclude urothelial malignancy especially in smokers
Renal imaging with ultrasound or CT-KUB to assess for kidney structure (ADPKD, stone, tumor, obstruction).
If no cause identified and the hematuria persists and she is still willing to donate, she should be offered kidney biopsy to find out the cause. The differential includes thin membrane disease, Ig A nephropathy and Alport’s syndrome. With thin membrane disease she can go for donation, but not the other two causes
No. in the absence of granular casts and if urine dipstick is positive for hematuria, the donor will require a kidney biopsy.
BTS guidelines stated that PNVH should be carefully evaluated to identify the source of hematuria(glomerular vs non-glomerular).
This donor should have a proper evaluation of the risk factors from a nephrologist outside the transplant team.
Glomerular hematuria is precluded from donation with the exception of TBMD.
Renal biopsy is a useful diagnostic tool to exclude other causes when the donor is still willing to donate. The use of IF (help to exclude IgA)and EM(to exclude hereditary nephritis) can be helpful resolve this dilemma.
References:
The significance of this urine picture:
Urine sample is examined at least two separate times before jumping into conclusions. Urine sample is also advised to be investigated with optimum donor fluid status e.g. not hydrated, not feverish.
Regarding the presence of 2+ blood, this number is below the significant value, however after full assessment at least twice causes of both glomerular and non-glomerular hematuria should be thoroughly investigated.
Phase contrast microscopy to discriminate the presence of dysmorphic RBCs is a must.
Causes of non-glomerular hematuria could vary between stones, myoglobinuria by rhabdomyolysis, cystitis (tumors), all these need further urological assessment up to cystoscopy or even biopsy if suggested malignancy exists. Metabolic work up is required as well.
While glomerular causes are usually indicative of intrinsic renal disease, commonly IgA nephropathy ,Alport syndrome ,thin basement membrane disease ,papillary necrosis … all these are contraindications for renal donation apart from thin basement membrane disease which is mostly associated with a benign course . Careful family history is necessary in such cases.
The presence of granular casts apart from dehydration status is suggestive also of renal disease which must be ruled out by successive repetition of the urinary samples and further evaluation is then needed.
Unless haematuria and granular casts are absent, further donation is excluded.
If no granular casts, and other investigations were normal, proceeding to donation can be resumed with meticulous follow up of the donor should be established even after donation.
According to the British transplantation society guidelines.
Guidelines for Living Donor Kidney Transplantation Fourth Edition March 2018
BTS/RA Living Donor Kidney Transplantation Guidelines 2018 United Kingdom Guidelines
The example is a female donor who is 31 years old with no evidence of hypertension or diabetes mellitus…She has normal renal function and no proteinuria…There are granular casts in the urine and there is no mention of the RBC in the urine… There are 2+ blood in the urine…
Urine dipstick blood 2+ positive means that it can be false positive also due to hemoglobinuria due to intravascular hemolysis or it can be due to rhabdomyolysis with myoglobin contributing to it…urine dipstick 2+blood positive also means some false positive due to oxidative reactions of the reagent in the drip stick…urine 2+ blood in dipstick cannot be taken as evidence of hematuria unless there is associated microscopic hematuria which is seen by microscopy…..We need to examine the urine for microscopy … Microscopic hematuria on the urine means it can be glomerular or non glomerular in origin…Phase contrast microscopy is useful is identification of the hematuria if it is glomerular or non glomerular in origin…A non glomerular origin of hematuria involves a cystoscopy to identify to rule out of bladder pathology as per BTS guidelines before donation…..If there is glomerular hematuria we have to perform a kidney biopsy before decision of kidney donation…Renal biopsy can show IgA nephropathy, Alport’s syndrome or thin basement nephropathy….If there is IgA or Alports syndrome renal donation is rules out….Thin basement nephropathy can be considered for renal donation according to BTS as the rate of progression to CKD is very less…But the donor is young, I would counsel the family about the diagnosis and speak about a very small risk of progression to Alport’s syndrome….If there are alternative donors or counselling about cadaver transplant would be ideal….
The BTS guidelines recommend urine dipstick examination atleast 2 times of 2 different time frames to identify hematuria or proteinuria… So we need to repeat the urine examination….
Granular casts are present in chronic glomerulonephritis, CKD, severe dehydration, fever and after exercise….If there are granular casts in associated with microscopic hematuria it needs evaluation…If there were no granular casts in the urine I will repeat the urine routine and look for the presence of hematuria both by dipstick and microscopy ….If there is persistent dipstick positive I would do a cystoscopy to rule out bladder pathology…
*What is the significance of this urine picture (hematuria and casts)?
-Since; asymptomatic microscopic hematuria in a healthy potential donors is considered a common finding but, persistent hematuria which is > three or more RBCs/ HPF on urinary sediment from 2 of three collected urine samples.
This hematuria in 2 urine dipstick is considered Persistent Non-visible hematuria after exclusion of : fever, exercise or menstruation. ( could be urinary tract infection or glomerulo-nephritis or even malignancy although ; is rare below age of 40 years, but reach up to 10% above age of 60 years.
-Granular Casts ( coarse or fine) could be mostly of glomerular origin as; TBMN ,Thin basement membrane nephropathy; also called ;( benign familial hematuria), IgAN , and Alport’s syndrome. which needs renal biopsy and examination with electron microscopy.
*I will proceed with no problem if donor diagnosed to be TBMN because ; good long term outcome of the potential donors with TBM and safety of kidney donation from TBM donor.
*How do you proceed?
· If PNVH is present,
1.Full history including good family history and if present for possible genetic study.
2. urine culture and renal ultra-sound should be done.
3.Hypercalciuria and hyperuricosuria are shown to be important causes of isolated hematuria. so,24hours urinary ca, urica should be done.
4. Cystoscopy is done in patients age >40 years to exclude bladder pathology.
5. kidney biopsy is recommended if hematuria is more than +1 on dipstick testing.
6. Serology tests : ( C3 , C4 , ANA ,P -ANCA , C-ANCA )
– Glomerular pathology precludes donation, except for TBMN which is a benign condition.
*Would your management differ if there were no granular casts on urine microscopy?
No, will not differ , As recommendation for PANVH not include granular cast.
1.BTS/RA Living Donor Kidney Transplantation Guidelines 2018
2.Uptodate
3.Seung-Kee Min , Jongwon Ha , etal.,: Midterm Outcome of Kidney Transplantation From Donors With Thin Basement Membrane Nephropathy. Transplantation. 2018 ;102(4):e180-e184.
1) It may indicate underlying glomerular disease
2) I will delay transplant to give way for further investigation of hematuria . eg renal biopsy.
3)No.
Indications for kidney biopsy
kidney biopsy generally be limited to patients with suspected TBMN who also have proteinuria. However, kidney biopsy might be considered in patients with hematuria alone:
1) kidney donor.
2) when conception with another individual with isolated hematuria being planned.
reference
PNVH diagnosed when 2 of 3 of consecutive strip urinalysis test is positive. It present in 1-21% of general population & in 2.7% of live potential donors in US & in 8.3% of Japan live potential donors.
Presence of hematuria & cast mean presence of glomerular lesion.
Workup :
References:
Ans; 1.
Hematuria is a sign/ symptom of upper renal (GN, ATN, AIN, Nephrolithiasis, calcinosis, cyst rupture etc ) while lower renal tract from ureter to urethra.
More then 3 cells per HPF is significant.
The granular casts could be from ATN, NS.
Ans,2;
As discussed above will R/O first GN(Nephrotic/nephritic).
ultrasound KUB, urine for dysmorphic, peripheral smear for schistocytes, ANA profile, autoimmune profile. If all become negative will consider further lower tract evaluation, but casts will not be present.
Ans; 3.
Again need to r/o other lower tract causes like cystitis, UTI, ureteric stone etc.
Ans;4.
Lecture,
KDIGO guidelines 2017,
BTS guidelines 2018.
If diagnosed case of(biopsy proven/ genetic) TBM, its not contraindication for donation, but, if there is mild risk of progression, should see for other options too.
What is the significance of this urine picture (hematuria and casts)?
The hematuria in this case along with casts is suggestive of nephrological cause of hematuria
How do you proceed?
This patient needs to undergo urine culture to rule out urinary infection
this donor also merits kidney biopsy to rule out glomerular disease
Any glomerular pathology precludes kidney donation for the fear of ESRD progression
Thin basement membrane disease donors should also be warned about lack of long-term follow-up studies about safety of kidney donation.
Would your management differ if there were no granular casts on urine microscopy?
If there would not have been casts in the urine, then there is urological cause of hematuria.
in the case the investigations would
CT urography
urine cytology
and cystoscopy to rule out causes of hematuria before clearance for donor
BTS/RA Living Donor Kidney Transplantation Guidelines 2018
All potential living donors must have reagent strip (dipstick) urinalysis performed on at least two separate occasions. (B1)
Two or more positive tests, including trace positive, is considered as persistent non-visible haematuria (PNVH). (B1)
If PNVH is present, perform urine culture and renal imaging to exclude common urologic causes including infection, nephrolithiasis and urothelial carcinoma. (A1)
If no cause is found, perform cystoscopy in patients age >40 years to exclude bladder pathology. (B1)
If no cause is found and the donor still wishes to donate, then a kidney biopsy is recommended if haematuria is 1+ or greater on dipstick testing. (B1)
Glomerular pathology precludes donation, with the possible exception of thin basement membrane disease. (B1)
For donors with persistent asymptomatic non-visible haematuria (PANVH) and a family history of haematuria or X-linked Alport syndrome, a renal biopsy (B1) and referral to a clinical geneticist are recommended. (B2)
*Urinary casts are tiny tube-shaped particles that can be found when urine is examined under the microscope during a test called urinalysis.
Urinary casts may be made up of white blood cells, red blood cells, kidney cells, or substances such as protein or fat. The content of a cast can help tell your health care provider whether your kidney is healthy or abnormal
*Other names:
Hyaline casts; Granular casts; Renal tubular epithelial casts; Waxy casts; Casts in the urine; Fatty casts; Red blood cell casts; White blood cell casts
*This test to see if kidneys are working properly. It may also be ordered to check for certain conditions, such as:
Glomerular disease
Interstitial kidney disease
Kidney infections
*Abnormal results may include:
Fatty casts are seen in people who have lipids in urine. This is most often a complication of nephrotic syndrome.
Granular casts are a sign of many types of kidney diseases.
Red blood cell casts mean there is a microscopic amount of bleeding from the kidney. They are seen in many kidney diseases.
Renal tubular epithelial cell casts reflect damage to tubule cells in the kidney. These casts are seen in conditions such as renal tubular necrosis, viral disease (such as CMV nephritis), and kidney transplant rejection.
Waxy casts can be found in people with advanced kidney disease and long-term (chronic) kidney failure.
White blood cell (WBC) casts are common with acute kidney infections and interstitial nephritis.
*References:
BTS /RA Living Donor KidneyTransplantaton Guidelines 2018
Judd E, Sanders PW, Agarwal A. Diagnosis and clinical evaluation of acute kidney injury. In: Feehally J, Floege J, Tonelli M, Johnson RJ, eds. Comprehensive Clinical Nephrology. 6th ed. Philadelphia, PA: Elsevier; 2019:chap 68.
Riley RS, McPherson RA. Basic examination of the urine. In: McPherson RA, Pincus MR, eds. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 23rd ed. St Louis, MO: Elsevier; 2017:chap 28.
Review Date: 07/04/2019
It is a patient that can fit into different clinical contexts, mainly Alport syndrome, Berger’s disease and TBMD.
With this evolution suggesting benign findings (without diabetes mellitus and without proteinuria), the transplant could theoretically be carried out after proper guidance on the risks involved.
Regardless, a closer post-transplant evolution and for a longer period is suggested. Genetic variables and the inability to make an adequate differential diagnosis can have consequences for the post-nephrectomy donor.
I will procceed with donation.
♧What is the significance of this urine picture (haematuria and casts)?
▪︎This haematuria in 2 urine dipstick can be considered as PNVH after exclusion of other causes such as fever, exercise or menstruation.
▪︎Casts could point to the possibility of glomerular bleeding.
(Glomerular bleeding, in most cases, is due to one or more of three disorders: thin basement membrane nephropathy (TBMN, also called benign familial hematuria), IgAN, and Alport’s syndrome (AS, also known as hereditary nephritis) or a carrier state.
So, this granular cast means glomerular injury and need kidney biopsy.
♧How do you proceed?
▪︎ In this case scenario of a 31yrs prospective donor to with 2+ of blood with granular cast we can proceed by taking a careful history plus renal function assessment, as well as repeated urinalysis of all family members. This can suggest the type of inheritance and the most likely genetic basis of the disease.
▪︎The clinical evaluation should include any previous history of kidney stones, symptoms of pain, dysuria.
▪︎Afamily history of hematuria, hypercalciuria and hyperuricosuria are shown to be important causes of isolated hematuria. Both disorders are often associated with a positive family history and could be screened by analysis of a 24-h urine collection sample.
▪︎After exclusion of all causes of haematuria and If PNVH is present, urine culture and renal imaging should be done, to exclude common urologic causes including infection, nephrolithiasis and urothelial carcinoma. cystoscopy to exclude bladder pathology.
▪︎If no cause is found and the donor still wishes to donate, then a kidney biopsy is recommended if haematuria is 1+ or greater on dipstick testing.
♧Would your management differ if there were no granular casts on urine microscopy?
No, I will follow the same plan of management to exclue all causes of haematuria.
________________
Ref
N. Vandiver. etal. Accepting prospective kidney donors with asymptomatic urinary abnormalities: Are we shooting in the dark?
What is the significance of this urine picture (haematuria and casts)?
· Potential living donors must have reagent strip urinalysis performed on at least two occasions not related to fever, menstruation or exercise.
· Non-visible haematuria can be transient or persistent
· If two out of three consecutive tests are positive then the donor is considered to have persistent non-visible haematuria
· Malignant disease of the urinary tract, present in 3- 5% of patients overall, is rare under the age of 40 but diagnosed in up to 10% of those aged >60.
· In patients with normal urological investigations, kidney biopsy is frequently abnormal.
· In a UK-based study 46% were found to have glomerular pathology, most commonly IgA nephropathy, mesangial proliferative glomerulonephritis without IgA deposition, or thin basement membrane nephropathy
Granular cast significance:
· Granular casts may be coarse or fine in nature, Coarse, deeply pigmented granular casts (“muddy brown”) are considered characteristic of ATN, the leading cause of AKI in hospitalized patients.
· In patients with ischemic or toxic injury to the tubular epithelial cells, cell sloughing into the tubular lumen, may lead to the formation of granular and/or epithelial cell casts.
How do you proceed?
· If PNVH is present, urine culture and renal imaging should be done, to exclude common urologic causes including infection, nephrolithiasis and urothelial carcinoma.
· cystoscopy is done in patients age >40 years to exclude bladder pathology.
· If no cause is found and the donor still wishes to donate, then a kidney biopsy is recommended if haematuria is 1+ or greater on dipstick testing.
· Glomerular pathology precludes donation, with the possible exception of thin basement membrane disease.
· If the donor has a family history of haematuria or X-linked Alport syndrome, a renal biopsy and referral to a clinical geneticist are recommended.
Would your management differ if there were no granular casts on urine microscopy?
No. As recommendation for PANVH dose not include or exclude the presence of granular cast
1)BTS/RA Living Donor Kidney Transplantation Guidelines 2018
2)https://www.uptodate.com/contents/urinalysis-in-the-diagnosis-of-kidney-disease/abstract/
the presenace of hematuria have a wide range of differnial starting from simple UTI , GN Malignancy … etc
Granular casts are casts that contain either proteins, tubular cells or leukocytes that have broken down. The presence of granular casts in the urine does not indicate the type of kidney disease present could be ATN or nephrotic syndrome . so hematuria with cast needs more attention .
we needs to repeat the urine analysis , IF still positive for blood its now termed PNVH and because we have also Cast this patient needs kidney biopsy to R/O GN + serology work up ( C3 , C4 , ANA , ENA screen , C+P ANCA .. etc ) .
according to the lecture .
thanks
-Microscopic hematuria in asymptomatic, healthy potential kidney donors is an increasingly common finding .
-Persistent hematuria is defined as three or more red blood cells per high-power field on microscopic evaluation of urinary sediment from two of three properly collected urinalysis specimens.
-minimum of two urine dipstick tests should be performed on separate occasions during the course of the donor assessment to exclude the possibility of intermittent microscopic hematuria.
-The dipstick is the most reliable and sensitive test (can detect even 1–2 red blood cells per high-power field).
▪︎persistent hematuric staterequires full investigation
1.careful history and renal functional assessment of the prospective donor
2. repeated urinalysis on all family members can suggest the type of inheritance and the most likely genetic basis of the disease.
3.The clinical evaluation should include any previous history of kidney stones, symptoms of pain, dysuria or prostatism, and a family history of hematuria. Hypercalciuria and hyperuricosuria are shown to be important causes of isolated hematuria both in children and adults.
4. rule out urothelial malignancy by performing urine cytology.
5. cystourethroscopy, and renal imaging in those with persistent microscopic hematuria.
6.obvious factors such as menstruation or infection
7.extraglomerular causes like nephrolithiasis, urothelial malignancy, and( prostatic disease in male donors).
8.Glomerular bleeding, in most cases, is due to one or more of three disorders: thin basement membrane nephropathy (TBMN, also called benign familial hematuria), IgAN, and Alport’s syndrome (AS, also known as hereditary nephritis) or a carrier state.
•How do you proceed?
kidney donors should be informed that the presence of persistent, isolated, asymptomatic microscopic hematuria generally precludes the continued possibility of donation.
If the potential donor candidate remains determined to proceed with a workup then a biopsy is essentially the next step in the workup. As mentioned earlier, kidney biopsy, in most cases, is likely to reveal IgAN, TBMN, or AS.
In individuals with TBMN and normal investigations who have donated kidneys, adverse out comes wasn’t reported but follow-up period wasn’t long enogh to ensure
long-term safe.
N.vadivem .Accepting prospective kidney donors with asymptomatic urinary abnormalities: Are we shooting in the dark?.THE RENAL CONSULT| VOLUME 71, ISSUE 2, P173-177, 2007.
BTS/RA Living Donor Kidney Transplantation Guidelines 2018 119
This patient has granular casts and they often indicate a renal disease. However granular casts can be seen after strenuous physical activity. Therefore I would repeat a urine microscopy and if this confirm the presence of granular casts it is very likely that this patient has a renal disease.
We need to know if the patient has had any recent infection (for e,g Sore throat) and how soon after the infection the patient has developed haematuria (if patient develop haematuria soon after an infection this would be more in keeping with an IgA Nephropathy; on the other hand if the patient develops haematuria one or two weeks after an infection than a post streptococcal glomerulonephritis is more likely).
We need to know if there is any family history of renal disease. We need to know if the patient is on any medications as some of them are associated with haematuria (e.g. penicillin) and if the patient had any recent strenous physical activity.
In terms of investigations I would request a vasculitic screen (Immunology test). In terms of radiological investigations I would arrange a renal US or CT to exclude infection, renal stones nephrolitiasis or cancer as possible cause of haematuria. If the above tests are negative a flexible cystoscopy should be arranged to exclude bladder disease.
However, in this particular case I would arrange a kidney biopsy if repeated urine microscopy confirms the presence of granular casts. If the donor renal biopsy shows IgA nephropathy, Alport’s syndrome I would consider the patient not suitable for donation. Patient with TBMD may donate, however TBMD is seen in heterozygous carriers of COL4A3, COL4A4 mutations and this should be considered before considering the donor suitable for donation
In case of haematuria with no granular casts, I would repeat the urine dipstick to confirm the presence of haematuria. If haematuria is confirmed, I would arrange a urine culture to rule out urinary infection, US renal or CT to exclude renal stones (nephrolitiasis) or carcinoma. If all this test are negative I would request a flexible cystoscopy to exclude bladder disease as a cause of bleeding and if this is negative I would arrange a kidney biopsy.
Midterm Outcome of Kidney Transplantation From Donors With Thin Basement Membrane NephropathyChanjoong Choi 1 , Sanghyun Ahn 1 , Seung-Kee Min 1 , Jongwon Ha 1 , Curie Ahn 2 , Yonsu Kim 2 , Hajeong Lee 2 , Sang-Il Min 1
BTS/RA Living Donor Kidney Transplantation Guidelines 2018.
Danovitch G.M .Handbook of kidney transplantation. sixth edition. Wolters Kluwer .Press:2017
It points more toward non glomerular or isolated hematuria. We will concentrate on this differential, unlikely to be GN.
Substantiate your answer:
KDIGO guidelines:
Donor candidates should be assessed for microscopic hematuria.
7.2: Donor candidates with persistent microscopic hematuria should undergo testing to identify possible causes, which may include:
• Urinalysis and urine culture to assess for infection
• Cystoscopy and imaging to assess for urinary tract malignancy
• 24-hour urine stone panel to assess for nephrolithiasis and/or microlithiasis
• Kidney biopsy to assess for glomerular disease (eg, thin basement membrane nephropathy, IgA nephropathy, Alport syndrome)
Selection
7.3: Donor candidates with hematuria from a reversible cause
that resolves (eg, a treated infection) may be acceptable
for donation.
7.4: Donor candidates with IgA nephropathy should not donate
References:
BTS guidelines 2018
KDIGO kidney donor guidelines 2017
First to confirm presence of persistent isolated microscopic hematuria as RBCS more than 2-5 cells/hpf repeatedly over one month. That hematuria may be due to infection ,stones, malignancy urologic causes or of glomerular origin. Needed investigations include urine c/s, cystoscopy, urine stone panel, and even renal biopsy to rule out glomerular origin. Those of more than 35 years old get more benefit from cystoscopy than younger ones .If both cystoscopy and biopsy revealed no abnormality, donation could be done after patient discussion
Kidney donation with TBMD is controversial as still there is risk for slow progression to ESRD despite the benign nature of the disease. Potential donors with age more than 40 years in absence of proteinuria and hypertension could be considered for donation.
A 31-year-old female potential donor with a urine dipstick of 2+, granular cast and no proteinuria. The first thing that need to be done is to take a proper history of the donor to see if she had her monthly cycle. After which a differential diagnosis of the causes of haematuria must be made and investigated. Pathology that can give false haematuria can me haemolysis, drug use, myoglobinuria and possible rhabdomyolysis. This is why the history taking is important. Also one must think about urinary infections, trauma to abdomen, and heavy or strenuous exercises and possible kidney stones and possible GN. Once the proper history has been taken the next step is investigations,
How you we proceed with the investigations:
1) Abdominal ultrasound
2) Cystoscopy
3) Urine test to look for Hb dysmorphic or phase contrast microscopy
4) CT urogram
5) Investigation for a possible GN
6) And possible kidney biopsy
Granular cast give information that there is some kidney disease but doesn’t indicate the type of kidney disease. So it is not specific and will not differ management or investigation to find the cause.
Two or more positive tests, including trace positive, should be considered as persistent non-visible haematuria (PNVH).
If PNVH is present, perform urine culture and renal imaging and genetic study and kidney biopsy might be also considered .
detailed history including family history
Glomerular pathology precludes donation, with the possible exception of thin basement membrane disease.
The data support the safety of kidney donation by patients with PANVH, although long term follow up of larger patient groups is required
REFERENCES
1. Reese PP, Bloom RD, Feldman HI, et al. Mortality and cardiovascular disease among older live kidney donors. Am J Transplant 2014;14:1853-61.
2. Massie AB, Wang MC, et al. Risk of end-stage renal disease following live kidney donation. JAMA 2014;311:579-86.
3. UK guidelines for living donor kidney transplantation 3rd edition 2011. http://www.bts.org.uk.
What is the significance of this urine picture (Hematuria and casts)?
This 31 year old potential donor has non visible Hematuria -Blood ++ ,
There are medical co morbidities like hypertension and diabetes.
Renal functions are normal without any proteinuria but there granular cast on urine microscopy.
There can concern about glomerular diseases like Alport syndrome, TBMD and IgA Nephropathy. Kidney biopsy and screen for dysmorphic RBC and Acanthocytes will help.
How do you proceed?
The next step will depend on biopsy results. In case of IgA nephropathy and Alport syndrome we cannot proceed. With TBMD the usual course is benign and one can proceed with donation.
With TBMD there still some risk of ESRD, so it will be good idea to explore other options like other donors in family or cadaveric donors. Donor with TBMD can be kept in reserve.
If there is no glomerular disease and Hematuria investigations like imaging and urine cytology and cystoscopy are negative then we can proceed.
Would your management differ if there were no granular casts on urine microscopy?
It will sensible to investigate further like urine culture, urine cytology, renal imaging and cystoscopy. If there is no urological cause then we proceed with donation.
Substantiate your answer
Oxford Handbook of Nephrology and Hypertension 3rd Edition
BTS Living Donor Kidney Transplantation guidelines 2018
Haematuria and granular casts raises the possibility of renal disease or ATN, but further assessment is needed
Key Points of Importance in the Medical +/- Family History of a Potential Kidney Donor
Haematuria/proteinuria/urinary tract infection Difficulty in passing urine, including urgency, frequency, dysuria History of peripheral oedema Nephrolithiasis
Start by repeating the urine test. *Dipstick for protein, blood and glucose (at least twice)
Two or more positive tests, including trace positive, is considered as persistent non-visible haematuria (PNVH).
perform urine culture and renal imaging to exclude common urologic causes including infection, nephrolithiasis and urothelial carcinoma.
If no cause is found cystoscopy is not indicated in this patient as her age is < 40 * she is 31.
Her Urine dipstick showed 2+ of blood so she can go for kidney biopsy to exclude any glomerular disease.
Glomerular pathology precludes donation, with the possible exception
of thin basement membrane disease.
Reference:
British Transplantation Society Living Donor Kidney Transplantation Guidelines 2018
Non-visible haematuria is the preferred term (replacing microscopic haematuria) for blood identified in a urine sample either by microscopy or by reagent strip analysis.
Non-visible haematuria is a common finding in the general population, may indicate either urological or renal parenchymal disease, and must be carefully evaluated in prospective living kidney donors.
High degrees of non-visible haematuria (1+ or greater) mandate biopsy before donation with histological evaluation include immunofluorescence or immunohistochemistry, and electron microscopy.
Non-visible haematuria is routinely detected using semi-quantitative reagent strips. A reagent strip ‘trace positive’ result corresponds to 1-5 red cells/ml, while >10 red cells/ml are conventionally considered to be significant in urological practice
Potential living donors must have reagent strip urinalysis performed on at least two occasions not related to fever, menstruation or exercise. If two out of three consecutive tests are positive then the donor is considered to have persistent non-visible haematuria.
According to the guidelines for living donor with hematuria we should do the following:-
1-All potential living donors must have reagent strip (dipstick) urinalysis performed on at least two separate occasions.
2-Two or more positive tests, including trace positive, is considered as persistent non-visible haematuria (PNVH).
3-If PNVH is present :-
-perform urine culture
-renal imaging to exclude common urologic causes including infection, nephrolithiasis and urothelial carcinoma.
4- If no cause is found
-perform cystoscopy in patients age >40 years to exclude bladder pathology.
5- If no cause is found and the donor still wishes to donate
– a kidney biopsy is recommended if haematuria is 1+ or greater on dipstick testing.
6-Glomerular pathology precludes donation, with the possible exception of thin basement membrane disease.
7-For donors with persistent asymptomatic non-visible haematuria (PANVH) and a family history of haematuria or X-linked Alport syndrome, a renal biopsy and referral to a clinical geneticist are recommended.
High degrees of non-visible haematuria (1+ or greater) mandate biopsy before donation will histological evaluation must include immunofluorescence or immunohistochemistry, and electron microscopy.
Reference
Guidelines for Living Donor Kidney Transplantation Fourth Edition March 2018
BTS/RA Living Donor Kidney Transplantation Guidelines 2018 United Kingdom Guidelines
What is the significance of this urine picture (haematuria and casts)?
First it must be confirmed in 2 urine dipstick then considered PNVH
Presence of cast indicating glomerular disease with dysmorphic RBCs
But we need to exclude other causes as fever , exercise , menstruation
Also ask about family history , sign and symptoms of any autoimmune disease
.How do you proceed?
If confirmed hematuria with dysmorphic RBCs, indicating kidney biopsy and full immunological profile.
It may be Alpert syndrome ,IgA nephropathy , TBMD
Pt has IgA nephropathy is not accepted while TBMD can be safely donate but also still some risk
If no cast :
Proper history taking to exclude exercise cause , menstruation , pain in urolithiasis , dysuria in uti
Wt loss in malignancy
KUB CT and Ultrasound are needed
Urine CS
Cystoscope to rule out Urinary bladder malignancy
What is the significance of this urine picture (haematuria and casts)?
Hematuria is defined as the detection of >5 RBCs per high power field.
Detection of casts or dysmorphic RBCs in the urine sediment (with or without proteinuria) could indicate underlying intrinsic renal disease.
Casts must be properly identified so that meaningful diagnoses can be made:
– RBC casts are glomerular disease
– WBC casts indicate tubular disease (infection & acute pyelonephritis).
– Granular casts result from degeneration of cells in cellular casts; their significance lies with the cast from which they were formed.
Granular casts may also result from direct aggregation of serum proteins & other substances into a matrix of Tamm-Horsfall mucoprotein. Generally, the presence of granular casts suggests stasis in the nephron. The casts are associated with tubule-interstitial disease.
========================
How do you proceed?
Careful evaluation is needed as workup may reveal occult renal disease that may contraindicate kidney donation.
Stones & tumors should be excluded.
Cystoscopy may be indicated to exclude any bladder pathology.
Urinary tract infection, uncontrolled HTN & latent DM must be excluded.
Ig A glomerulonephritis: 10% of first-degree relatives of patients with IgA GN suffer from microhematuria &/or proteinuria that may require consideration of renal biopsy.
Other known hereditary renal diseases that may be associated with microhematuria:
C3 deposits disease, IgM nephropathy, ADPKD, Alport’s syndrome or TBM disease.
========================
Would your management differ if there were no granular casts on urine microscopy?
Substantiate your answer
In the absence of casts, the sole presence of non-visible hematuria will warrant further workup to exclude intrinsic renal disease.
Isolated microhematuria indicates that there are no other associated clinical or laboratory manifestations of kidney disease; so, it is necessary to thoroughly evaluate (full history, clinical examination & detailed laboratory & imaging studies) this donor before a decision of kidney donation can be made.
Reference
1.Ayman Karkar. The Renal Allograft Donor with Isolated Microhematuria. Saudi J Kidney Dis Transplant 2006;17(3):316-319 © 2006 Saudi Center for Organ Transplantation
2. Karen M. Ringsrud. Interpretation [cytology] Casts in the Urine Sediment. laboratorymedicine> april 2001> number 4> volume 32
potential kidney donor with persistent microscopic haematuria and Granular casts
Casts are clusters of urinary sediment elements (red blood cells, white blood cells, fat bodies, etc.) wrapped in a protein matrix. Cast formation necessarily occurs in the kidney tubules, and the contents of the casts indicate the nature of normal or abnormal occurrences found in the kidney itself.
So in this donor Glomerular diseases should also be considered in with microscopic hematuria when obvious anatomic or infectious etiologies are not present.
Thin basement membrane nephropathy is a common cause of microscopic hematuria, affecting up to 1% of the population .Thin basement membrane nephropathy, while generally benign, is associated with an increased risk for CKD when there is proteinuria or a family history of CKD .Other glomerular pathologies to consider include Alport syndrome and IgA nephropathy .An important consideration when evaluating a potential donor is that in contrast to the favorable short-term prognosis of isolated microscopic hematuria, the lifetime risk of ESRD is increased.
—————————————————————————-
potential kidney donor with persistent microscopic hematuria, variably defined as > 3 or > 5 RBCs per high power field, requires further evaluation prior to kidney donation, including urine cytology, renal/bladder imaging and cystoscopy, to rule out urological malignancy, infections (including tuberculosis) and stone disease.
Those with a negative urological workup may need a kidney biopsy to exclude glomerular disease which mentioned above .
If, after counselling, the prospective donor with non-visible haematuria remains committed to donation and a kidney biopsy is performed, histological evaluation must include immunofluorescence or immunohistochemistry, and electron microscopy.
Postdonation persistent hematuria with d-RBC was also associated with a progressive decline in renal function. These results indicate that persistent glomerular hematuria is strongly associated with a higher incidence of postdonation progressive kidney disease. Potential donors with persistent glomerular hematuria should be excluded, while those with isolated hematuria need to be evaluated with heightened caution.
—————————————————————————————————-
The causes will be different and the management also beside there is treatable causes before donation in general the most common causes include:
all needs to be evaluated by nephrologist and urologist
——————————————
pin genaral and according to BTS/RA Living Donor Kidney Transplantation Guidelines 2018
NON-VISIBLE HAEMATURIA
Recommendations
All potential living donors must have reagent strip (dipstick) urinalysis performed on at least two separate occasions. (B1)
Two or more positive tests, including trace positive, is considered as persistent non-visible haematuria (PNVH). (B1)
If PNVH is present, perform urine culture and renal imaging to exclude common urologic causes including infection, nephrolithiasis and urothelial carcinoma. (A1)
If no cause is found, perform cystoscopy in patients age >40 years to exclude bladder pathology. (B1)
If no cause is found and the donor still wishes to donate, then a kidney biopsy is recommended if haematuria is 1+ or greater on dipstick testing. (B1)
Glomerular pathology precludes donation, with the possible exception of thin basement membrane disease. (B1)
For donors with persistent asymptomatic non-visible haematuria (PANVH) and a family history of haematuria or X-linked Alport syndrome, a renal biopsy (B1) and referral to a clinical geneticist are recommended. (B2)
References
Live Kidney Donors with Microscopic Hematuria
Author: C. Hartono, MD
Editor: D. Lapointe Rudow, DNP
Persistent glomerular hematuria in living kidney donors confers a risk of progressive kidney disease in donors after heminephrectomy
R Kido 1 , Y Shibagaki, K Iwadoh, I Nakajima, S Fuchinoue, T Fujita, S Teraoka
Affiliations expand
BTS/RA Living Donor Kidney Transplantation Guidelines 2018
What is the significance of this urine picture (haematuria and casts)?
The positive dipstick reaction with an absence of RBCs in the urine may indicate false positive associated conditions like hemoglobinuria following intravascular hemolysis , myoglubinuria after rhabdomyolysis or the presence of oxidizing agents in urine.
Microscopic hematuria may occur incidentally during illness or after exertion . Further evaluation is required only if there’s persistent microscopic hematuria on at least two of three consecutive samples.
The presence of cast may be occur as incidental finding after exertion or CKD , or it may be originated from glomeruli and must be taken seriously especially with the presence of hematuria .
How do you proceed?
A careful history and physical examination followed by urinalysis is crucial.
History include:
Duration and timing of hematuria
Recent respiratory or skin infection
Recent trauma, exercise, passage of stones
Intake of medications or herbal compounds
Fever, dysuria urinary frequency and urgency, back pain skin rashes , joint pain and face and leg swelling
Any family history of hematuria, hypertension,renal stones, renal failure, deafness and coagulopathy.
Physical examination for the presence of HT , edema, skin rash , any abdominal masses.
Investigation:
The first step is to confirm the presence of hematuria by urine microscopy. Then determine if the hematuria is of glomerular or non-glomerular in Origen by doing urine routine phase contrast microscopy for RBCs morphology
If dysmorphic RBCs more than 20% with presence of cast this mean glomerular in origin and include:
PIGN
IgAN
HSP
MPGN
TBMD
LN
MN
Alport syndrome
If all work up was normal , the DDx mostly persistent asymptotic hematuria TBMD , IgAN , alport syndrome
So for This potential donor young female with dipstick showed 2+ blood and granular casts on microscopy. No hypertension, normal kidney function, no proteinuria willing to donate we must make sure from the diagnosis by renal biopsy and genetic study as the benign course of TBMD may by early progressive renal disease or spectrum of Alport syndrome
If the patient has negative family history of renal failure and positive family history of hematuria clinically it suggest TBMN. TBMN must be distinguished from the carrier state of X-linked Alport syndrome , which is associated with a 5-20% risk of progressive renal impairment. genetic study must be done to exclude Alport syndrome prior to transplant.
Non -glomerular causes of hematuria include :
Hypercalciuria
Renal calculi
UTI
Hemorrhagic cystitis
Trauma
Exercise
Cystic renal disease
Vascular malformation
Coagulation disorder
Thrombocytopenia
Nutcracker syndrome
Malignancy renal or bladder
The work-up include:
Urinalysis and urine C/S
Phase contrast
24hr urine for protein , Ca,creatinine,urate
C3 , C4, ANA , antidsDNA
ASOT
Albumine
Cholesterol
CBC PT PTT
Renal Doppler
CT abdomin
According to BTS :
Would your management differ if there were no granular casts on urine microscopy?
The same work up although concentrated more on the non -glomerular causes since the presence of cast may be incidental
Thank You.
What is the significance of this urine picture (haematuria and casts)?
The concurrent presence of urinary casts or dysmorphic red blood cells with or without proteinuria is indicative of underlying intrinsic renal disease.
How do you proceed?
I would like to repeat reagent strip (dipstick) urinalysis at least two separate occasions. Two or more positive tests, including trace positive, is considered as persistent non-visible haematuria (PNVH). If the patient had only one reading, then another two sample will be confirmatory of PVNH. The test should be done without UTI, exercise induced haematuria, fever, menstruation and etc
If two or more positive tests of haematuria with cast, the patient requires further evaluation such as detailed family history to rule out ADPKD, Thin membrane disease, Alport syndrome, IgA Nephropathy and rarely Fabry’s Disease. Ultrasonography of kidneys indicated to rule out ADPKD. Kidney biopsy indicated to rule out glomerular pathology such as Alport syndrome, thin basement membrane disease, and IgA Nephropathy.
If the patient has positive family history of haematuria and negative family history of renal failure, clinically it suggest TBMN. TBMN must be distinguished from the carrier state of X-linked Alport syndrome (XLAS – caused by mutations in the COL4A5 gene encoding the α5 chain of type 4 collagen), which is associated with a 5-20% risk of progressive renal impairment. Ideally, referral to a geneticist and genetic testing to exclude Alport should be done prior to transplant.
Would your management differ if there were no granular casts on urine microscopy?
Donor candidates with persistent isolated microscopic hematuria still require a complete urologic evaluation. A cystoscopy to exclude bladder pathology may be necessary especially those who more than 35 years old.
In the absence of any specific abnormalities, a kidney biopsy still indicated to rule out glomerular pathology such as Alport syndrome, thin basement membrane disease, and immunoglobulin A (IgA) nephropathy.
What will you do if the investigations of PNVH came back negative including cystoscopy, imaging and kidney biopsy?
She will be accepted for donor nephrectomy
The guidelines suggested that potential donors with TBM can proceed to donation. What is the long-term outcome of these donors as far the renal function is considered?
Study by Choi, Chanjoong MD showed all the donors maintained their renal function upon clinical for 41.0 ± 39.1 months and additionally contacted via telephone survey (in total, 56.8 ± 32.0 months) without significant complications and denied any discomfort at the time of the telephone interview.
Kidney transplant donors with TBMN and their recipients maintained their renal function through midterm follow-up without significant complications. Therefore, kidney transplantation from donors with TBMN could be a safe option.
Thank You.
-This female patient has urinary hematuria and granular casts Concerning hematuria in this case it showed +2 blood by urine dipstick so it need to be repeated if positive it will be considered persistent non visible hematuria indicating the need for further investigations as urine culture ,and renal imaging to exclude UTI , nephrolithiasis and carcinoma.
In this case the presence of granular cast indicates the possibility of renal pathology which preclude donation except thin basement membrane disease
-If there were no granular cats and only hematuria is +2 then renal biopsy will be needed if the donor wants to donate , the only acceptable pathology is thin basement membrane disease.
– Kidney donors with TBMN and their recipients sustained their renal function through midterm follow-up without significant complications. So kidney transplantation from donors with TBMN could be a safe choice.
Meanwhile Alport syndrome carriers can be considered as potential donors with thin basement membrane nephropathy and normal COL IV immunostaining, therefore genetic testing is needed and those found to have COL IV alpha chain mutations should not donate.
Reference
– Prof Roberto Cacciola lecture
– Concepcion B . Communities Weekly Rewind: Thin Basement Membrane Nephropathy and Kidney Donation. KidneyNews Online 2018.
– Choi C, Ahn S, Min SK, Ha J, Ahn C, Kim Y, Lee H, Min SI. Midterm Outcome of Kidney Transplantation From Donors With Thin Basement Membrane Nephropathy. Transplantation. 2018 Apr;102(4):e180-e184.
Well done.
This potential donor is young female with dipstick showed 2+ blood and granular casts on microscopy. No hypertension, normal kidney function, no proteinuria.
First we need to confirm with history that, she was menstruating at that time of urine test or not; then think about the etiology of false positive dipstick test, haemoglobinuria, myoglobinuria in case of intra vascular hemolysis and rhabdomyolysis. Granular cast can occur with ATN from whatever cause.
Confirmed hematuria, without proteinuria, RBCs casts, not associated with menstruation, urinary tract infection, LUTS, stone or trauma), we will need CT KUB or US KUB to assess kidneys, ureters and bladder then cystoscopy if local bladder cause is suspected and there is risk factor. Urine routine with phase contrast microscopy can lead the path as well.
If no cause identified and the hematuria persists and she is still willing to donate, she should be offered kidney biopsy to find out the cause. The differential includes thin membrane disease, Ig A nephropathy and Alport’s syndrome. With thin membrane disease she can go for donation, but not the other two causes
If no cast, then it could be non glomerular or isolated hematuria. We will concentrate on this differential, unlikely to be GN.
According to BTS :
Thank You, Eusha for this excellent answer. I like your last paragraph. See the question I posted above and give me your thoughts
Granuar cast with hematuria have no significance. It will be significant if it is associated with proteinuria and RBC cast.
First I will take history- Is she on menstruation?
Does she has any features of UTI?
Any trauma?
Past history of hematuria?
Drug history
Any connective tissue disease
I will do the test twice. I positive, then I will do urine culture, exclude structural renal disease by USG of KUB, CT KUB.
If all found normal, I will proceed for renal biopsy.
If normal or thin GBM disease found, she can donate if she wish knowing some risk.
No, management will not differ
Thank You, Tufayel, you made it look easy, well done.
· How do you proceed?
Our potential donor is female at her 31st year of age with dipstick showed 2+ blood and granular casts on microscopy. No hypertension, normal kidney function, no proteinuria.
First we need to confirm this positive dipstick by microscopy, since false positive dipstick can happen with haemoglobinuria, myoglobinuria in case of intra vascular hemolysis and rhabdomyolysis respectively. Granular cast can occur with ATN from whatever cause, also CKD and exercise can cause it.
If confirmed hematuria, no proteinuria, no RBCs casts then after good history ( no recent period, urinary tract infection, LUTS, stone or trauma), we will need CT KUB or US KUB to assess kidneys, ureters and bladder then cystoscopy if local bladder cause is suspected and there is risk factor.
If no cause identified and the hematuria persists and she is still willing to donate, she should be offered kidney biopsy to find out the cause. The differential includes thin membrane disease, Ig A nephropathy and Alport’s syndrome. With thin membrane disease she can go for donation, but not the other two causes.
It points more toward non glomerular or isolated hematuria. We will concentrate on this differential, unlikely to be GN.
Substantiate your answer:
KDIGO guidelines:
Donor candidates should be assessed for microscopic hematuria.
7.2: Donor candidates with persistent microscopic hematuria should undergo testing to identify possible causes, which may include:
• Urinalysis and urine culture to assess for infection
• Cystoscopy and imaging to assess for urinary tract malignancy
• 24-hour urine stone panel to assess for nephrolithiasis and/or microlithiasis
• Kidney biopsy to assess for glomerular disease (eg, thin basement membrane nephropathy, IgA nephropathy, Alport syndrome)
Selection
7.3: Donor candidates with hematuria from a reversible cause
that resolves (eg, a treated infection) may be acceptable
for donation.
7.4: Donor candidates with IgA nephropathy should not donate
References:
BTS guidelines 2018
KDIGO kidney donor guidelines 2017
Thank You.
What is the significance of this urine picture (haematuria and casts)?
– presence of haematuria in 2 urine dipstick include trace positive considered PNVH
.after exclude other causes as fever, exercise or menstruation.
– dysmorphic red blood cells or granular cast means glomerular injury and need kidney biopsy.
– granular cast represent degenerate cellular cast or aggregation of protein within cast matrix , this granular last may be fine or coarse in nature , coarse deeply pigmented granular cast ( muddy brown heme granular cast) characterised of ischemia or toxic injury of tubular epithelial call , so we must consider kidney biopsy for diagnosis.
–
– all potential kidney donor must undergrow dipstick urine analysis at least 2 separate occasion.
– two or more positive test including trace positive consider persistant non visible haematuria in absence of other factors as fevers exercise or menstration.
– if PNVH is present must undergrow:
* family history for TBMD ‘ ALPORT syndrome.
* cytology of urine RBCs , if dystrophic means glomerular origin.
* urine culture to rule out of infection.
* 24h whine collection for proteins calcium and urate .
* cytology for malignancy.
– if no cause and age more than 40y , cystscopy is considered to exclude bladder
-CT angiogram or IV pyelography for Nephrolithesis, urolethial cancer or any abnormalities in anatomy of renal vasculture.
– if no cause and donor wishes to donate she must consider kidney biopsy and it is recommended if whine dipstick > +1.
– if there were any glomerular pathology, donor must be excluded with the exception of TBMD.
–Would your management differ if there were no granular casts on urine microscopy?
Even in absence of granular cast, we must consider kidney biopsy if haematuria more than +1 in dipstick.
References:
BTS guidelines.
Very good.
According to KDIGO guidelines;2017, Donor candidates with persistent microscopic hematuria should undergo testing to identify possible causes, which may include:
• Urinalysis and urine culture to assess for infection
• Cystoscopy and imaging to assess for urinary tract malignancy
• 24-hour urine stone panel to assess for nephrolithiasis and/or microlithiasis
• Kidney biopsy to assess for glomerular disease (eg, thin basement membrane nephropathy, IgA nephropathy, Alport syndrome).
If Donor candidates with hematuria from a reversible cause that resolves (eg, a treated infection) may be acceptable for donation. However, if a biopsy of a Donor candidate showed IgA nephropathy, then he should not donate
The management plan will be the same since Granular casts represent degenerated cellular casts or the aggregation of proteins within a cast matrix and the clinical significance of this distinction is unclear.
1. 2017-KDIGO-LD-GL.pdf, accessed on 21/9/22
2. Ron Wald, Urinalysis in the diagnosis of kidney disease. UpToDate.
Thank You.
+2 hematuria+ granular casts in a young 31 year old female potential donor, no HTN or DM.
What is the significance of this urine picture (haematuria and casts)?
Hematuria with granular cast indicates a glomerular disease,first will repeat urinalysis,[2] and the patient should be evaluated carefully, first by history if he ever noticed a red color urine or cola colored urine, if it is related to any infections or few weeks after any feverish event.
Family history of hematuria or ESRD, and if any of them had hematuria and what is the course.
Physical exam – blood pressure measurement , if there HTN widens the differential diagnosis( ie MPGN , ANCA vasculitis, IgA nephropathy…. etc).
Isolated heamaturia with granular cast and normal blood pressure in young patient,the following are DDx (IgA nephropathy, thin membrane disease and Alport syndrome) hens hearing loss history, and careful eye exam is a must r/o anterior lenticonus.
Should do urine culture and if there is pyuria, should be treated.
If there is history of renal stones[1].
Kidney biopsy if all investigations were normal, it may help to identify etiology and predict
How do you proceed?
First will do CBC, PT,PTT, INR,KFT, urinalysis and culture, 24 hours urine for stone panel, renal imaging (KUB, Ultrasound abdomen and pelvis.when all are clear i will proceed with her as a donor.
Would your management differ if there were no granular casts on urine microscopy?
Sure, if no granular casts i’ll do ultrasound when normal would review , kub , renal CT may be needed, and urinalysis and culture, in some cases cystoscopy would be done ruling out structural diseases or stones requiring urological intervention.
Substantiate your answer
According to BTS :
[1] Vedula R, Iyengar AA. Approach to Diagnosis and Management of Hematuria. Indian J Pediatr. 2020 Aug;87(8):618-624. doi: 10.1007/s12098-020-03184-4. Epub 2020 Feb 6. PMID: 32026313.
[2] Andrews PA, Burnapp L. British Transplantation Society / Renal Association UK Guidelines for Living Donor Kidney Transplantation 2018: Summary of Updated Guidance. Transplantation. 2018 Jul;102(7):e307. doi: 10.1097/TP.0000000000002253. PMID: 29688993; PMCID: PMC7228639.
Thankyou well done
Let us arrive at a consensus.
Dr Ben, Dr Abdulrahman, and Dr Riham Marzouk suggest going ahead with donor operation, while Dr Nandita Sugumar implies waiting for 5 year to watch natural history.
What is the best approach?
Firstly, let us have some historical perspectives.
Haematuria
‘March Haematuria’, haematuria after exertion, was mentioned in 1881. Red urine, or red cells, or even sometimes red cell casts and fragmented red cells suggestive of glomerular bleeding, have been repeatedly described after sustained running or marching. The exertion causing it is associated with repeated impacts that might conceivably fragment red cells. A series from Uruguay (Tobal 2008) describes epidemic rusty urine after prolonged hand drumming at carnival, with rare cases of dialysis-requiring acute kidney injury. Marathons and other long-distance running are the most common cause of this in the present day. Some runners see red or rusty urine, while dipsticks may be abnormal in 25%. Reports of this phenomenon are mixed with occasional patients with rhabdomyolysis, and probably some with underlying renal disease, but in most the haematuria resolves within 2-3 days – so more slowly than post-exertional proteinuria.
The alarming combination of red cell casts and proteinuria after severe exertion has given rise to the names such as Athletic Pseudo-nephritis (Gardner 1956).
Donor evaluation:
Isolated haematuria could result from glomerular bleeding or secondary to extraglomerular causes like nephrolithiasis, urothelial malignancy, and prostatic disease. Glomerular bleeding (characterised by dysmorphic RBCs) in most cases, is due to one or more of three disorders: thin basement membrane nephropathy (TBMN, also called benign familial haematuria), IgA nephropathy, and Alport syndrome (hereditary nephritis) or carrier state. A careful history and renal functional assessment of the prospective donor, as well as repeated urinalysis on all family members, can suggest the type of inheritance and the most likely genetic basis of the disease.
The presence of persistent, isolated, asymptomatic haematuria generally precludes the possibility of donation. Usually, a biopsy is not necessary at this point as the presumptive glomerular diagnosis is usually quite clear and benign, with no consequences for the potential donor. Only if the candidate donor is determined to proceed with the workup, then a biopsy is essentially the next step in the workup. Patients with Alport’s and IgA nephropathy are not candidates for donation. Similarly, patients with TBMS and family history of progressive renal disease, or any risk factors for progressive disease (hypertension, proteinuria or overt renal function impairment), any evidence of extra-renal manifestation, or in the presence of GBM lamellation on biopsy are excluded from donation. However, there still remains some controversy regarding whether patients with TBMN and isolated haematuria should be accepted as donors. However, there still remains some controversy regarding whether patients with TBMN with isolated haematuria should be accepted as donors. However, it seems reasonable in this case as well to defer from donation those candidate donors with evidence of extra-renal manifestations, hypertension, or proteinuria.
BTS guidelines on Non-Visible Haematuria
• All potential living donors should have reagent strip (dipstick) urinalysis performed on at least 2 separate occasions. Two or more positive tests, including trace positive, should be considered as persistent nonvisible haematuria (PNVH).
• If PNVH is present, perform urine culture and renal imaging to exclude common urologic causes including infection, nephrolithiasis and urothelial carcinoma.
• If no cause is found, perform cystoscopy in patients age >40 years to exclude bladder pathology
• If no cause is found and the donor still wishes to donate, then a kidney biopsy should be considered, and is recommended if haematuria is >1+ on dipstick testing.
• Glomerular pathology precludes donation, with the possible exception of thin basement membrane disease. The patient should then be assessed by a nephrologist, independent of the transplanting team, whose role includes donor advocacy, risk assessment, and exclusion of those with significant chronic kidney disease. Renal biopsy is an invasive, expensive but potentially useful diagnostic test to clarify these dilemmas. if an individual with hematuria remains committed to donation (as many are at these later stages of evaluation), then histology with immunofluorescence for IgA (who are excluded from donation) and electron microscopy for thin membrane disease (allowed in the absence of other renal risk factors, sensorineural deafness or negative family history for renal failure) or hereditary nephritis (excluded), is used to stratify risk.