2. Urine dipstick showed 2+ of blood on investigation of a potential female donor who is 31 years old. Urine microscopy confirmed microscopic haematuria (>5 RBCs/HPF), but no casts. No history of DM or hypertension. She has excellent kidney function with no evidence of proteinuria or microalbuminuria.
- How do you proceed?
- What is the significance of haematuria in the absence of proteinuria, microalbuminuria, and casts?
- Would your management differ if there were granular casts in the absence of proteinuria on urine microscopy?
It is necessary to carry out imaging tests of the bladder to rule out malignant disease.
The absence of proteinuria, microalbuminuria, and casts findings suggests that this hematuria is not related to glomerular disease.
Yes. In the presence of cylinders, I would not perform the transplant without a biopsy and histopathological evaluation of this kidney, the result of which may lead to a contraindication for donation.
I should repeat urine exam to confirm hematuria,urine culture ,dysmorphic RBCs ,
US ,some times may be cystoscope
For granular casts I will do the Same work up
BTS recommendations :
Repeat the urine test at least twice to be considered as persistent non-visible hematuria (PNVH)
If PNVH is present, perform urine culture and renal imaging to exclude
common urologic causes including infection, nephrolithiasis and
urothelial carcinoma. (A1)
yes, I will proceed to renal biopsy with cancelling of this donor
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.
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
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 granular casts in the absence of proteinuria on urine microscopy?
The same workup like hematuria
How do you proceed?
The potential donor should have at least two separate urine dipstick urinalyses done to confirm the presence of haematuria while patient doesn’t have fever, menstruation or after exercise.
It is stated that the patient has confirmed to have microscopic haematuria, so she is considered has haematuria
1- Perform urine culture and sensitivity – to rue out any occult infection
2- Renal imaging such as renal ultrasonography and CTU should be done to rule out nephrolithiasis and urothelial carcinoma
3- 24-hour urine stone panel to assess for nephrolithiasis and/or microlithiasis
4- Risk factors for uroepithelial cancer should be assessed including donor age, smoking history, exposure to aniline dye, analgesics or cyclophosphamide, and pelvic irradiation- if there is any risk, cystoscopy will be indicated to rule out uroepithelial carcinoma
5- Renal biopsy is mandate for any haematuria to diagnose glomerulonephritis.
What is the significance of haematuria in the absence of proteinuria, microalbuminuria, and casts?
Haematuria alone and without proteinuria,microalbuminuria, and casts showed that it is not significant changes in glomerulus but they still have risk of proteinuria and worsening kidney function in 11 years as suggested by Dutch study. Studies have shown that presence of haematuria predicts proteinuria in future. If the urological examination is normal, I would proceed to do renal biopsy to exclude IgAN, Alport syndrome and TBMD. Some might argue with the practise but my centre usually will do renal biopsy.
Would your management differ if there were granular casts in the absence of proteinuria on urine microscopy.
Granular casts indicates the glomerulonephritis and kidney biopsy is indicated.
TBMD without hypertension, proteinuria and with normal kidney function should be allowed for donation and prior genetic testing to exclude Alport syndrome is recommended.
References
A thorough medical history is required to rule out:
Following the elimination of sampling error and UTI, a repeat urine examination is performed to confirm the presence of similar findings. If a repeat urine examination reveals the same results, she has persistent asymptomatic non-visible hematuria (PANVH). (1)
Further evaluation includes (1):
If above findings normal, she is deemed fit for donation
Significance of haematuria in the absence of proteinuria, microalbuminuria, and casts:
Hematuria greater than trace on two occasions (dipstick test) requires evaluation in the same way as described above, even in the absence of proteinuria, microalbuminuria, or casts. The presence of proteins and casts (cellular) points more towards glomerular disease.
Significance of granular casts in the absence of proteinuria on urine microscopy:
Granular casts are non-specific and represent degenerated cells; they can appear following strenuous exercise, CKD, or ATN. The workup will be the same even in the presence of granular cast.
Reference:
Question 1
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.
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,Alport syndrome 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.
I will proceed for kidney transplantation, if thin membrane disease, but there is some concern about Thin membrane disease and the donor must be aware of uncertainty over long term safety.
Question 2
Absence of proteinuria and cast raise the suspicion of non glomerular causes.
Question 3
The workup is the same in all cases of haematuria
This 31 years old female donor has microscopic haematuria with no other structural abnormality. This lady needs to be defined as persistent or isolated hematouria. Then the morphology of RBCs need to be defined.if she is a case of persistent dysmorphic hematuria, then she should be excluded due to the significant higher risk of post-donation kidney disease. If she was considered occasional dysmorphic or persistent non-dysmorphic hematuria, then a kidney biopsy need to be done particularly if she has a family history of IgAN or AS. The biopsy is needed to confirm the presence of glomerulo-nephropathy or kidney damage. If she was considered as a case of occasional non-dysmorphic hematuria, kidney biopsy is usually not needed. donor evaluation guidelines, including that of the Amsterdam Forum, have not identified hematuria as a definite or relative contraindication for kidney donation .we need to exclude extraglomerular bleeding through use of computed tomography, sonography and urine cytology. Most of the cases of isolated hematuria in pre- or postdonation donors are of glomerular origin due to thin basement membrane nephropathy (TBMN), IgAN or AS.
In a study 0f 30 potential living related kidney donors who had asymptomatic microscopic hematuria, extensive workup was done that included ENT, laboratory , radiologic assessment and kidney biopsies. There was significant renal causes for their hematouria ( Hereditary nephritis (25/30), isolated C3 deposits disease (3/30), IgA nephropathy (1/30) and IgM nephropathy (1/30). This study confirmed that the relatives with asymptomatic microscopic hematuria have significant kidney pathologies that classify them as high risk of progressive kidney disease . (1)
Potential Donors with asymptomatic idiopathic hematouria had kidney biopsies and those who had a normal kidney biopsy(65%) were accepted for kidney donation.(2)
Nieuwhof followed 49 adults with isolated hematuria for 11 years. 20 of them had normal renal biopsy. The rest had developed complications in form of
· proteinuria in 10/29
· deterioration of kidney function 4/29
· hypertension 14/29.
This proves that the microscopic hematouria is not a benign condition in persons with two kidneys. A cohort studied the donors who had abnormal biopsies. Those with TBMN had less deterioration of renal function but still there are controversial opinion regarding accepting these patients as donors. In one study, a thorough evaluation that included renal biopsies was done before accepting them as donors. The most important issue here is that TBMN is frequently associated with 35–50% subsequent hypertension and 15–21% proteinuria. It was suggested that TBMN can cause secondary FSGS. This was based on the data from Limburg Renal Registry as 50% of patients with a diagnosis of primary FSGS and hematuria had TBMN, and 5% of TBMN patients had nephrotic syndrome. Another study in TBMN patients observed premature glomerular sclerosis on kidney biopsies which was associated with higher prevalence of hypertension. TBMN was noticed to be the carrier state for AR form of Alport’s syndrome. So far, there is no solid evidence that donors with TBMN develop adverse kidney outcomes. keeping in mind that females might have X chromosome inactivation plus the fact that the lower limit of women normal basement membrane width overlaps with the definition of TBMN, persistent microscopic hematuria may be more common in females.moreover, TBMN is difficult to be differentiated from Alport’s carrier state in women. In a small study of 14 of prospective donors with persistent, asymptomatic hematuria,13 were women from which 10 underwent kidney biopsy . 8 women had histologic abnormalities and 7 of which are basement membrane abnormalities. Cystoscopy is usually performed in older population as it rarely detect bladder cancer in young patients below 40 years of age .regarding occult ureteric stones , IVP is recommended despite its sensitivity is less than that of a CT scan.(3)
A study of 242 donors were investigated for the prevalence of persistent hematuria pre- and post-donation. The prevalence pre-donation was 8.3% which was significantly associated with dysmorphic hematuria. The prevalence post-donation was 15.3%. They were followed for 2.3 years after donation and 8.3% developed persistent proteinuria.The incidence was significantly higher in donors with persistent hematuria with dysmorphic red blood cells both before and after donation.
Deterioration of renal function was more in postdonation persistent hematuria with d-RBC. This study did not find a significant association between deterioration of renal function and pre donation hematuria.
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. (i) the possible risk of using potential donors with persistent glomerular hematuria and (ii) the importance of checking the persistence of hematuria and its morphology by multiple urinalyses during not only donor evaluation but also postdonation follow-up.One study observed that IgAN patients with congenitally reduced nephron mass develop more progressive clinical and pathological course than patients with IgAN with intact nephron mass. This study suggested the association of nephron mass and deterioration of kidney function. Donors with latent glomerular IgA deposition comprise 16% (72 of 446) of living kidney donors in one study and these IgA deposition can be an early stage of IgAN . those donors are at risk of persistent hematuria and hence progressive kidney disease. The family history of IgAN or AS was underestimated in this study because the affected donors did not know them. (4)
1-Sobh M, A, Moustafa F, E, El-Din Saleh M, A, Tawfik A, Ghoneim M, A: Study of Asymptomatic Microscopic Hematuria in Potential Living Related Kidney Donors. Nephron 1993;65:190-195. doi: 10.1159/00018747
2-E.A. Hassan, T.Z. Ali, A. Abdulbaki, I.A. Ibrahim, H.M. Almanae, H.A. Aleid,Histopathologic Findings of Potential Kidney Donors With Asymptomatic Microscopic Hematuria: Impact on Donation,Transplantation Proceedings,Volume 49, Issue 8,2017,Pages 1729-1732
3- Koushik, Rahul; Garvey, Catherine; Manivel, J Carlos; Matas, Arthur J.; Kasiske, Bertram, Persistent, Asymptomatic, Microscopic Hematuria in Prospective Kidney Donors,ransplantation: November 27, 2005 – Volume 80 – Issue 10 – p 1425-1429
4-Kido, R., Shibagaki, Y., Iwadoh, K., Nakajima, I., Fuchinoue, S., Fujita, T. and Teraoka, S. (2010), Persistent Glomerular Hematuria in Living Kidney Donors Confers a Risk of Progressive Kidney Disease in Donors After Heminephrectomy. American Journal of Transplantation, 10: 1597-1604.
Non-visible haematuria is routinely detected using semi-quantitative reagent strips. A reagent strip ‘trace positive’ result corresponds to 1-5 red cells/ml.
Ø Firstly, she need to repeat the test as Two or more positive tests, including trace positive, is considered as persistent non-visible haematuria (PNVH). Since she is a female its mandatory to assure she is not menstruating at time of sample collection.
Ø Detailed history, clinical examination and investigation in a form of: urine culture and renal imaging to exclude common urologic causes including infection, nephrolithiasis and urothelial carcinoma.
Ø Contrast phase microscopy: to asses’ glomerular RBCs.
Ø Biopsy if no urological cause and is important as haematuria might be the only sign glomerular disease. all glomerular pathology precludes donation, with the possible exception of thin basement membrane disease.
Isolated haematuria raised the suspicion diseases of non-glomerular origin, and if glomerular the main DD is IgA nephropathy, TBMD, Alport syndrome
No, all workup will be the same
Reference:
BTS/RA Living Donor Kidney Transplantation Guidelines 2018
This potential donor has isolated hematuria. Urine analysis should be repeated after full instructions about how to collect the same, especially it could be just contamination from menstruation.
After confirmation of isolated hematuria (with no proteinuria and eGFR is normal). assessment of the source is needed by examination of the shape of RBCs under microscopy. Normal non-dysmorphic RBCs mean the source is extraglomerular and should be assessed by ultrasound, urine culture and sensitivity, and cystoscopy if needed. Dysmorphic RBCs are from the glomerular origin (now it’s called symptomatic urinary sediment) which need to be assessed by immunological workup and kidney biopsy. The only benign lesion accepted for kidney donation is thin membrane disease although some patients with thin GBM developed ESRD and some transplant centers reject such patients.
Isolated hematuria may be related to glomerular disease or non-glomerular disease but if associated with nephrotic range proteinuria or active urinary sediment that means it’s from a glomerular origin.
Granular casts are not specific to the glomerular disease and should be assessed with non-invasive measures and to be repeated before considering their significant.
References
· Q1: First of all, it must be ensured that she is not menses. Then repeat the test in 2 separate times to make sure it is persistent hematuria and not a transient one. In PNVH, urine culture and imaging modalities are used to exclude UTI, stone or malignancy. The other evaluations include cystoscopy (if above 41 years of age) and kidney biopsy. Glomerular diseases associated with PNVH are: IgA nephropathy, Alport syndrome and TBMD.
· Q2: In the absence of proteinuria, microalbuminuria on cast she should be evaluated for urological or parenchymal diseases and if TBMD is found, proceeding for transplantation with caution and full explanation of possible risks, would be considered.
· Q3: Granular casts are originated from renal tubules and if they contain RBCs may be indicative of glomerular diseases. Therefore, it will be reasonable to perform kidney biopsy.
1) How do you proceed?
The approach to this patient with hematuria should include.
This hematuria should documented at least twice .
History taking :
A) History of smoking .
B) Adequate history of positive family history of hematuria ,deafness, and renal failure which may suggest alports syndrome.
C) History of attacks of gross hematuria during upper respiratory tract infection which may suggest IgA nephropathy.
D) History of any urological disease, stones , and UTI.
Examination :
A) Blood pressure, leg odema .
B) Hearing abnormalities.
C) Palpable kidneys.
D) Bladder distension.
Investigation:
A) GUE , to document hematuria at least twice, for RBC cast , proteinuria, UTI.
B) Phase contrast microscopy for dysmorhpic RBC .
C) Renal function tests.
D) Abdominal ultrasound for stone, mass , cysts.
E) Investigations to exclude bleeding tendency.
F) If dysmorphic RBC renal biopsy may be needed to exclude ( IgA nephropathy, alport s syndrome, thin basement membrane disease).
G) If no dysmorphic RBC then cystoscopy is needed to exclude urological causes.
H) Hearing test for sensory neural deafness.
I) Ophthalmoscopic slit lamp exam. for anterior lenticonus in alports syndrome.
2) What is the significance of haematuria in the absence of proteinuria, microalbuminuria, and casts?
This may suggest bleeding from non- glomerular origin ie urological cause should be excluded. This patient need urology consultation for systoscopy and CT SCAN.
3) Would your management differ if there were granular casts in the absence of proteinuria on urine microscopy?
YES , the finding of granular cast suggest the glomerular origin hematuria especially if there is associated significant proteinuria therefore the renal biopsy will take the prority .
Generally according to BITISH TRANSPLANTA SOCIETY guideline patient with hematuria should be assess as
1. All 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
· infection,
· nephrolithiasis and
· urothelial carcinoma.
4. If no cause is found, cystoscopy is indicated in patients >40 years to exclude bladder pathology.
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, 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.
Refrences :
– KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors.
-BTS/RA Living Donor Kidney Transplantation Guidelines 2018 – 119.
· 31 y old female donor with urine microscopy showing hematuria 2+ and no 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.
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.
No, I will proceed as above
DD commonest glomerular causes 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.
Female donor and has haematuria, first of all, need to confirm the haematuria and 2 separate haematuria is confirmed if there is no menstruation or UTI(by urine culture)
then roll any stone or any structural abnormality.
as this patient is less than 40 no need for a cystoscopy but we proceed with a kidney biopsy if there is any glomerular pathology will preclude kidney donation.
if nonvisible hematuria and family history of alport syndrome and refer to clinical.
The donor is a 32 year female…Urine dipstick showed 2+ blood with urine microscopy confirming microscopic hematuria… There were no casts in the urine routine result.. the donor does not have diabetes or hypertension…The renal functions are normal…There is no associated proteinuria also…
I would first ensure a proper mid stream sample of urine is collected and ensure the urine sample was not given during her monthly menstrual period…
The donor should be evaluated for the presence of dysmorphic RBC on phase contrast microscopy to detect any evidence of glomerulonephritis…The absence of granular cast and microalbuminuria excludes a significant glomerular cause
I will get an USG to rule out structural causes of hematuria namely stones, cancer. I will also get cystoscopy done to rule out bladder pathology…
After ruling out all the above i will get a renal biopsy done before deciding on organ donation..The possibilities are IgA nephropathy, ALports syndrome, Thin Basement Membrane disease….In absence of TBMD all others are contraindicated for organ donation as they progress to CKD..TBMD is benign and will not usually progress to CKD and hence BTS living donor guidelines do recommend organ donation with TBMD…
Granular casts are again non specific to glomerular pathology and can be seen in severe intravascular volume depletion also
This candidate female donor, young aged, presented with hematuria without casts with otherwise free history of DM or HTN, needs step by step approach.
History taking is a must to elaborate whether the test was done on menstruation, history suggestive of stones in the form of colics or dysuria, history of diminution of vision or hearing, history of smoking, family history suggestive of renal impairment or stone formation, history of fever or exercise preceding the test, history of drugs or herbs consumption, NSAIDs abuse. Sexual history is required.
Clinical examination to assess mental, hearing or visual disorders, assisted by audiometry and ophthalmology consultation.
The urine microscopy should be repeated at least on two separate occasions to exclude hematuria.
If hematuria still exists, the next step is to proceed for phase contrast microscopy for dysmorphic RBCs in urine to distinguish between glomerular versus non glomerular hematuria.
If the origin of hematuria was non glomerular, as stones, infection, perform proper urological imaging including cystoscopy and biopsy if needed as suspected malignancy if bladder lesions are suspected.in case of renal stones CTUT may be fully informative .
Glomerular hematuria could be due to IgA nephropathy, hereditary nephritis as Alport syndrome, which can progress further to renal impairment and CKD, while thin membrane disease is known to have benign nature. The fore mentioned causes are contraindications for renal donation with the exception of thin basement membrane disease according to KDIGO guidelines and British Transplantation Society guidelines 2018.
In cases of doubt of glomerular lesions, renal biopsy is a must.
Keeping in mind that this female lady is young to express the burden of renal disease, so thorough investigation and counselling is recommended.
The significance of haematuria in the absence of proteinuria, microalbuminuria, and casts is more probable to be non-glomerular origin, but further investigation by dysmorphic RBCs in urine to exclude isolated hematuria is advised as possible hereditary nephritis or IgA nephropathy may be the hidden cause and it may need even renal biopsy to rule them out.
Granular casts can exist in states of dehydration or fever in the absence of proteinuria on urine microscopy, but as whole granular casts are indicative of subsequent renal pathology which needs further evaluation.
The presence of renal pathology is a clear contraindication for renal donation.
There could be IgAN, TBMD, Alport syndrome, urological cause.
According to scenario there is no such end organ damage.
Need further investigation including imaging, eye examination, and renal biopsy.
if any of them present, there is contraindication to donate except TBMD, there is very mild risk progression to renal disease.
If any cast then should be investigated further for further approval for donation.
There is a need to investigate the cause of microscopic hematuria.
The initial findings suggest that there is no target organ damage, but there is a need to investigate calculi and revisit anamnesis and physical examination, prioritizing recurrent urinary infections, dysuria, and other conditions.
An imaging examination is also necessary.
To proceed with the donation, a kidney biopsy should be considered for investigation. If there are granules, it becomes mandatory due to the risk of associated glomerular disease.
Thin basement membrane nephropathy is a common cause of microscopic hematuria, affecting up to 1% of the population (1). 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 (2). Other glomerular pathologies to consider include Alport syndrome and IgA nephropathy (3). 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
RECOMMMENDATION Potential kidney donors with persistent microscopic hematuria require further evaluation prior to approval for kidney donation. Those with a negative urological workup may need a kidney biopsy to exclude glomerular disease.
References 1. Hass M Thin glomerular basement membrane nephropathy: incidence in 3,471 consecutive renal biopsies examined by electron microscopy. Arch Path Lab Med 130:699-706, 2006. 2. Carasi C, Van’t Hoff WG, Rees L, et al. Childhood thin GBM disease: review of 22 children with family studies and long-term follow-up. Pediatr Nephrol 20:1098- 1105, 2005. 3. Gale DP How benign is hematuria? Using genetics to predict prognosis. Pediatr Nephrol 28:1183-1193, 2013. 4. Vivante A, Afek A, Frenkel-Nir Y, et al. Persistent asymptomatic isolated microscopic hematuria in Israeli adolescents and young adults and risk for endstage renal disease. JAMA 306:729-736, 2011.
How do you proceed?
What is the significance of haematuria in the absence of proteinuria, microalbuminuria, and casts?
The presence of hematuria is not normal and should always be evaluated when found in a donor candidate.
This evaluation can help determine if hematuria is due to
1)correctable cause (eg, urinary tract infection, nephrolithiasis)
2)malignancy
3)glomerular disease : Thin basement membrane disease, IG A nephropathy, Alport.
Appropriate testing may include urinalysis and urine culture to assess for infection, cystoscopy and imaging to screen for urinary tract malignancy, 24-hour urine stone panel, and/or kidney biopsy to assess for glomerular disease.
Would your management differ if there were granular casts in the absence of proteinuria on urine microscopy?
Nope
How do you proceed?
PANVH is 3+ or more RBCs in two separate urine samples
we need to repeat the urine dipstick examination. if >=3 + RBCs
then History looking for menstrual blood, infection, stone, trauma, family history and drugs
then urine microscopy needs to identify the source of RBCs (glomerular or non-glomerular), RBCs cast/ dysmorphic RBCs.
urine culture
image study to the genito-urinary system (U/S) to exclude any stones, cysts, masses
Cystoscopy if > 40 years and no identifiable cause by other investigation
if no cause can proceed to kidney biopsy
What is the significance of haematuria in the absence of proteinuria, microalbuminuria, and casts?
it can be
1- thin basement membrane nephropathy
2- IgA nephropathy
3- Alport syndrome
thin basement membrane nephropathy can donate
Would your management differ if there were granular casts in the absence of proteinuria on urine microscopy?
needs kidney biopsy
*This candidate donor has microscopic hematuria.
*It has to be repeated first , if confirmed microscopic hematuria so, causes of microscopic hematuria should be excluded as; menstruation , infection, nephrolithiasis , glomerular diseases as: ( IgA nephropathy , thin basement membrane disease * although, thin basement membrane disease not considered contra-indication for transplantation* ,Alport syndrome which is considered as a contraindication for kidney donation.
*Investigations should be done to rule out causes of microscopic hematuria: urine culture, pelvi-abdominal us , cystoscopy and even renal biopsy may be needed.
*Isolated hematuria without proteinuria may indicate urological disease rather than glomerular disease.
*Granular casts in the absence of proteinuria on urine microscopy: means glomerular disease which indicate renal biopsy.
References:
BTS guidelines for live kidney donation, 2018.
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.
What is the significance of haematuria in the absence of proteinuria, microalbuminuria, and casts?
Would your management differ if there were granular casts in the absence of proteinuria on urine microscopy?
thanks
A threshold of ≥3 rbc/hpf (red blood cells/high power field) or higher prompts additional testing when evaluating potential living kidney donors.
Microscopichematuria is common finding in donors and must be fully investigated before accepting the donor.
Microscopic hematuria was defined as presence of ≥1 rbc/hpf and persistent by presence on ≥2 separate urinalysis.
Isolated was defined as presence of microscopic hematuria and with preserved GFR, absence of proteinuria, microalbuminuria or hypertension and no identifiable anatomical cause on native kidney imaging.
*Causes of Microscopic hematuria
-menstruation
-infection
-cystitis
-stones and other urological causes
-Family history of hematuria
-glomerular causes( IgA nephropathy,Thin basement membrane disease,Alports disease).
TBMD is not contraindication for donation and
If the biopsy result showed IgA risk of recurrence to be considered and both donor and recipient should be counselled about it
Full investigations including urine culture, ultrasound and CT imaging ,Cystoscopy up to renal biopsy must be done to insure absence of kidney disease.
What is the significance of haematuria in the absence of proteinuria, microalbuminuria, and casts?
Usually inducate a non glomerular cause .
Would your management differ if there were granular casts in the absence of proteinuria on urine microscopy?
-presence of symptomatic hematuria together with granular cast may indicate renal diseases that requires renal biopsy to confirm
· This is non visible hematuria, if it is persistent I should do the following:
1. urine culture and renal imaging to exclude common urologic causes including infection, nephrolithiasis and urothelial carcinoma
2. cystoscopy in patients age >40 years to exclude bladder pathology if no cause was found, but here the patient is younger than 40, so cystoscopy not indicated
3. If no cause is found and the donor still wishes to donate, then a kidney biopsy is recommended as dipstick is +1 or more
4. If Glomerular pathology is found in biopsy, donation should be excluded, with the possible exception of thin basement membrane disease
· If there is family history of hematuria or X-linked Alport syndrome, a renal biopsy and referral to a clinical geneticist are recommended
· If the biopsy result was IgA,the risk of recurrence of IgA nephropathy does not contraindicate donation, but the donor and recipient should be counselled regarding before donation
BTS/RA Living Donor Kidney Transplantation Guidelines 2018
What is the significance of haematuria in the absence of proteinuria, microalbuminuria, and casts?
· This could be due to urological cause, or may indicates a good prognosis of the renal disease
· The presence of proteinuria will preclude donation even in the absence of hematuria
Would your management differ if there were granular casts in the absence of proteinuria on urine microscopy?
Granular casts are nonspecific, indicates the presence of cells that have degenerated. The presence or absence of granular cast was not included in the guidelines and will not alter the flow of investigations
Management
Donor has microscopic hematuria.
`This donor has hematuria above 5 RBCs/HPF. MIcrohematuria is defined as greater than five RBC per high power field. Isolated micro hematuria indicates underlying occult progressive renal disease, and this contradicts this donor from kidney donation unless the cause is determined and proved to be acceptable for donation.
Thus, combination of detailed family history, kidney biopsy or genetic testing can allow a diagnosis to be made and evaluate how to proceed.
Isolated hematuria – no proteinuria, casts, or microalbuminuria
Causes of isolated asymptomatic microscopic hematuria include :
Donor has a higher risk of kidney failure than the general population because of isolated hematuria.
Granular casts in urine – no proteinuria
This is indicative of glomerular disease. The donor needs a kidney biopsy to be done and then evaluated whether to be allowed to donate or not. Some glomerular pathologies such as Alport syndrome are a contraindication to kidney donation and the donor would have to be rejected.
References
How do you proceed?
What is the significance of hematuria in the absence of proteinuria, microalbuminuria, and casts?
This hematuria in absence of proteinuria or casts is suggestive of non-glomerular cause of bleeding. This would include benign causes like fever, exercise or menstruation. The urological causes of bleeding should be ruled out.
Would your management differ if there were granular casts in the absence of proteinuria on urine microscopy?
Granular casts ins absence of proteinuria is suggestive of glomerular disease. I would then prefer kidney biopsy. If it reveals glomerular disease like Alports disease, then with the exception of thin membrane disease, they can’t be accepted as kidney donors.
In the first instance I would repeat a urine dipstick and ensure she does not have a menstrua period. If the urine dipstick confirms hematuria she should be investigated. We need to know if she has family history of hematuria (Thin basal membrane, Alport’s Syndrome, renal stones). We have to ensure she has not had recent strenuous physical activity.. We need to know if she had recent infection such as UTI’s and or sore throat. If she had sore throat we need to know how long after the infection hematuria occurred (for e.g. if she develop hematuria soon after a sore throat this may point out an IgA nephropathy while if she developed hematuria one or two weeks later this may be indicative of post-streptococcal glomerulonephritis). In terms of investigation I would request a urine culture to rule out UTI’s and renal ultrasound or non-contrast CT to exclude kidney stones or anatomical morphological causes of hematuria such as renal cysts or renal masses). If the renal US and or CT KUB are negative I would request a flexible cystoscopy to ensure the hematuria is not from the bladder or ureteric tract, and if the flexible cystoscopy is negative I would proceed with a kidney biopsy.
Isolated haematuria with no casts and no proteinuria may indicate a non-glomerular cause of bleeding. However, some renal disease such as Thin basal membrane and Alport’s syndrome may cause persistent non visible haematuria and this is the reason why we should arrange a kidney biopsy if all other investigations have been negative.
The presence of granular casts is indicative of glomerular pathology. I would, therefore arrange a kidney biopsy. If the kidney biopsy shows IgA nephropathy or Alport’s syndrome I would not proceed with kidney transplantation. Thin basal membrane is not a contraindication for transplantation
References.
Koushik R, Garvey C, Manivel JC, Matas AJ, Kasiske BL. Persistent, asymptomatic, microscopic hematuria in prospective kidney donors. Transplantation. 2005 Nov 27;80(10):1425-9.
BTS/RA Living Donor Kidney Transplantation Guidelines 2018
British guidelines
=================
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)
NB. – Cystoscopy not recommended in age below 40 y especially in females
This hematuria more possible due to urological cause .
No, it will not differ because I need still to exclude urological issues and also need kidney biopsy
The decision of accepting her a a donor depends on the cause of hematuria
1-How do you proceed?
I will evaluate her by
History:
ask about prior kidney stones, and related medical records should be reviewed if available.
Asking about other causes such as:
· Trauma on the urinary tract
· Exercise- induced hematuria
· Sexual activity
· Medications such as aspirin
1-Gynecological history is important in female donors (menstrual cycle).
2-repeat the urine analysis
Two or more positive tests, including trace positive, is considered as persistent non-visible haematuria (PNVH).
3- urine culture and renal imaging to exclude common urologic causes including infection, nephrolithiasis .
3-If no cause is found, then we will perform a kidney biopsy.
4- Donation will be precluded if the result showed a glomerular pathology with exception o thin basement membrane disease .
2-What is the significance of haematuria in the absence of proteinuria, microalbuminuria, and casts?
Absence of cast and microalbumria decrease the threshold for the possibility of glomerular disease. It is usually related to the lower urinary tract pathology .
3-Would your management differ if there were granular casts in the absence of proteinuria on urine microscopy?
Although ,the main causes of granular cast are;exercise or dehydration and acute tubular necrosis,the same approach must be performed before donation .
Reference ;
BTS/RA Living Donor Kidney Transplantation Guidelines 2018,
Cleared
How do you proceed?
*Hematuria is usually caused by a genitourinary disease although systemic diseases can also manifest with blood in the urine. Hematuria is divided into glomerular and non-glomerular hematuria to help in evaluation and management.
*Some common glomerular causes are:
Alport syndrome
Thin basement membrane disease
Post-streptococcal glomerulonephritis
IgA nephropathy
Pauci immune glomerulonephritis
Lupus nephritis
Membranoproliferative glomerulonephritis
Goodpasture syndrome
Nephrotic syndrome
Polycystic kidney disease
*Non-glomerular causes include:
Febrile illness
Exercise
Menstruation
Nephrolithiasis
Cystitis, urethritis, prostatitis
Malignancy: renal cell carcinoma, bladder cancer, prostate cancer
Genitourinary mucosal injury by instrumentation
Trauma
Bleeding tendency: thrombocytopenia, coagulopathy, use of blood thinners, hematological disorders like sickle cell anemia.
*Evaluation of Hematuria
History and physical examinaton
Urinalysis
To establish the diagnosis. Presence of 3 or more RBCs per High Power Field on urine sediments is definedas microscopic hematuria Urine appearance, pH, the presence of proteins WBCs, nitrites, leukocyte esterase, crystals, and casts is helpful.
Urine microscopy
examines urine sediments for RBC morphology, and RBC casts are the single most significant test which can differentiate between glomerular and non-glomerular bleed.
Renal parameters
should be obtained to rule out acute kidney injury.
Imaging: Initial imaging could be in the form of an ultrasound of the kidneys, ureters, and bladder. It can assist in diagnosing anatomical causes of hematuria such as a kidney stone or bladder or renal mass and renal cysts. Abdominopelvic CT scan with or without contrast to detect renal stones and other morphological abnormalities of kidneys. MRI abdomen and pelvis is another useful modality if CT scan is contraindicated or not helpful.
Cystoscopy:
After ruling out urinary tract infection and having negative imaging of kidneys and ureters to detect any abnormality, cystoscopy by a urologist is the next step in the evaluation of hematuria. It can detect urothelial carcinoma, bladder wall inflammation or mucosal thickening. It can also be therapeutic to remove bladder stones.
Urine Cytology
can be performed to detect malignant cells or to detect urothelial carcinoma, but it is not a substitute for a cystoscopy.
Kidney biopsy:
The gold standard to diagnose a glomerular cause of hematuria is a kidney biopsy by a nephrologist or interventional radiologist.The presence of dysmorphic RBCs and RBC casts should be followed by a kidney biopsy. Light microscopy, electron microscopy, and immunofluorescence are performed to look at glomerulus structure to diagnose glomerulonephritis and detect a specific type.
*Management depends on underlying etiology(1,2).
#What is the significance of haematuria in the absence of proteinuria, microalbuminuria, and casts?
*Infection
*Calculi
*Genitourinary cancer
*Prostatitis and prostatic hyperplasia
*Trauma
*Some glomerular diseases
*Vigorous exercise
*Schistosoma haematobium
*Urethral strictures(3).
#Would your management differ if there were granular casts in the absence of proteinuria on urine microscopy?
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.
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.
In fact, hyaline casts are the only casts that should be detected in the urine in absence of kidney, or renal, disease.There is no change in my management and the same evaluation.
#References
1.Froom P, Ribak J, Benbassat J. Significance of microhaematuria in young adults. Br Med J (Clin Res Ed). 1984 Jan 07;288(6410):20-2. [PMC free article] [PubMed]
2.Mariani AJ, Mariani MC, Macchioni C, Stams UK, Hariharan A, Moriera A. The significance of adult hematuria: 1,000 hematuria evaluations including a risk-benefit and cost-effectiveness analysis. J Urol. 1989 Feb;141(2):350-5. [PubMed]
3.Painless Scrotal MassBy Geetha Maddukuri, MD, Saint Louis University
Last full review/revision Jan 2021| Content last modified Sep 2022
references
KDIGO Living Kidney Transplant Donor 2017
How do you proceed:
I will evaluate her by
History:
ask about prior kidney stones, and related medical records should be reviewed if available.
Asking about other causes such as:
· Trauma on the urinary tract
· Exercise- induced hematuria
· Sexual activity
· Medications such as aspirin
Repeat urine microscopy to confirm hematuria not related to the above . if 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)
· Donor candidates with hematuria from a reversible cause that resolves (eg, a treated infection) may be acceptable for donation.
· Donor candidates with IgA nephropathy should not donate.
Isolate hematuria usually signify a urological causes however few glomerular diseases also can be associated with hematuria along with proteinuria such as post infectious GN, IgA nephropathy, in addition to alport syndrome and thin basement membrane disease.
Granular cast will not change my way of evaluating or treating the patients, however it might signify chronicity.
The provided scenario of young female 31 year a potential kidney donor with confirmed non-visible hematuria – defined as 2+ blood on dip stick or more than 3 RBCs on high power field urine microscopy, normal kidney function and absence of proteinuria or albuminuria.
Initially, the presence of persistent non visible hematuria should be confirmed with another test from properly collected urine samples, so that transient causes are excluded. Transient causes include fever, UTI, infection of GI tract, trauma, heavy exercise and menses.
After confirmation of PNVH, and transient causes are excluded by detailed history and physical examination, glomerular and non-glomerular hematuria should be investigated.
Workup should include :
– Urine cultures to rule out(in) infection
– Urine microscopic examination to look for the morphology of RBC, which guide us on the origin of – RBC cells (glomerular vs non-glomerular).
– Kidney imaging – different modality studies can be used to look for nephrolithiasis, cyst, masses, signs of infection or obstruction.
– Cystoscopy- patients with risk factors for urinary tract malignancy, in particular bladder cancers should be evaluated with cystoscopy or urine cytology
– Patients more than 50 years of age, should be screened for prostate cancer, with trans-rectal prostate biopsy if needed.
– Patients with family history of hematuria should be investigated for possible genetic disease- thin basement membrane and Alport’s syndrome.
– Kidney biopsy is the gold standard for screening of glomerular origin of hematuria (LM, EM)
What is the significance of haematuria in the absence of proteinuria, microalbuminuria, and casts?
As explained before, hematuria can be of glomerular or non-glomerular origin. The absence of proteinuria, microalbuminuria or casts is usually reassuring in regards to glomerular disease. However, isolated hematuria can underlay significant glomerular and non-glomerular pathology. Kidney biopsy remains the standard of diagnosis.
Would your management differ if there were granular casts in the absence of proteinuria on urine microscopy?
Presence of granular casts in the urine is usually benign and does not necessitate further investigations, however, in the concomitant presence of PNVH, glomerular pathology should be ruled out.
Hi Dr Habli,
Excellent reply but no references !
How do you proceed?
This potential donor will require more detailed assessment of Hematuria. This will include detailed history and physical examination.
I will arrange Urine culture and urine cytology
Renal imaging like ultrasound or non contrast CT to rule out stones or renal lesions
Cystoscopy to rule out urethral or bladder pathology
If urological workup is negative then I will arrange renal biopsy- To rule out glomerular pathology like Alport Syndrome, IgA nephropathy and Thin Basement membrane disease- TBMD.
What is the significance of haematuria in the absence of proteinuria, microalbuminuria, and casts?
In the absence of proteinuria, microalbuminuria, and casts, the presence of Hematuria is unlikely due to glomerular cause. Isolated Hematuria can be associated with higher risk developing ESRD. In case of negative investigation a long term follow up is required.
Would your management differ if there were granular casts in the absence of proteinuria on urine microscopy?
Presence of granular cast may signify a Glomerular disease. These can be Alport Syndrome, IgA nephropathy and Thin Basement membrane disease- TBMD. In such situation kidney biopsy s indicated.
Transplantation is contraindicated with Alport Syndrome and IgA nephropathy .
With Thin Basement membrane disease transplantation is possible but a good follow up is required .
References.
Koushik R, Garvey C, Manivel JC, Matas AJ, Kasiske BL. Persistent, asymptomatic, microscopic hematuria in prospective kidney donors. Transplantation. 2005 Nov 27;80(10):1425-9.
Choi SR, Sun IO, Hong YA,et al. The role of kidney biopsy to determine donation from prospective kidney donors with asymptomatic urinary abnormalities. Transplant Proc. 2012 Jan;44(1):11-3.
Dear Dr Abdul Rahim Khan,
Your approach is problem-oriented comprehensive, and logical.
Please avoid typing the name of disease or a symptom as a proper noun (Haematuria, Thin Basement and Glomerular, as you typed).
Ajay
How dose we should proceed in such scenario?
she is young female and we need to be sure that this in PNVH AND by doing 2 sample of urine properly collected ,then we need to review her family history if she has nay haemturia run in family to rule out genetic background like aport disease or IgA nephropathy which are contraindication for donation
but if this is thin membrane disease she can donate .
We need also to consider urological problems with calculi or malignancy which is unlikely but still need to be ruled out .
simple urine analysis with looking for RBCS morphology will help ue in knowing is it glomerular or non glomerular origin ,help in 20% of cases ,still urine analysis will help us in diagnosing infections . This prospective donor has no RBCS cast which the most important type of cast to look for.
so in this case if she is still keen to donate we may consider to have kidney biopsy before donation to rule out glomerular cause other wise she may not need for any intervention .
Dear Dr Rihab,
Your approach is problem-oriented. However, your answer is not complete. What will you do if this turns out to be TBMD?
Ajay
Our donor is 31 years of age. In terms of malignancy, the risk is shallow though not zero. Cystoscopy may not be mandatory, but we must evaluate by completing the workup, especially in cases of recurrent nonvisible hematuria. Evaluation should include repetitive urinalysis, urine culture, and radiologic assessment, primarily by urinary system ultrasound and CT when necessary. Family history is very important and may guide us.
A family history of glomerular disease will preclude the donation except for a thin basement membrane. IgA nephropathy or Alport probability is not suitable for donation.
Casts other than RBC casts may be non-significant. Granular casts may be fine or coarse. coarse casts although not always the case, are mostly due to ATN. cellular cats maybe RBC or WBC . RBC casts are significant because the represent glomeurlar pathology.
Granular non-RBC casts without proteinurea are usually due to non glomeeular disease , so after evaluation, followup and treatment we can proceed with donation (e.g WBC casts are due to infection namely piyelonephrits witch is a symptomatic condition). In case of doubt one could perform renal biopsy (in case of RBC probable golmerular pathology).
Dear Dr Islam,
Your approach is problem-oriented. However, your answer is not complete. What will you do if this turns out to be TBMD though you have quote a reference of TBMD?
Ajay
Given data:
31 year lady in the child bearing period who came forward as a potential kidney donor, She has non-visible hematuria(2+ blood on dip stick check confirmed by urine microscopy), normal renal functions with no proteinuria or albuminuria and no BG of hypertension on DM.
· How do you proceed?
1.Confirm the presence of persistent non visible hematuria(PNVH) which is defined as 3 or more RBC/HPF in a urinary sediment from 2 out of 3 properly collected urine samples. This will exclude false causes(eg menses) or transient causes(eg infections, fever, trauma or exercise) of hematuria
2. If confirmed PNVH identify the cause whether glomerular or non-glomerular through
· Proper history: including trauma, drugs, abdominal or loin pain, LUTS, renal calculi, visual or auditory problems, positive family history of hematuria or renal failure and full gynecological history for this young female in the child bearing period.
· Investigations:
-Urine cultures to exclude infection
-Phase contrast microscopy if available will help to identify dysmorphic RBCs(>20%) that points toward glomerular bleeding
-24 hour stone panel to exclude nephrolithiasis
-Renal imaging(US/CT-KUB) to check for stones, features of infection, UT obstruction, renal cysts or suspected malignancies
-Urine cytology and cystoscopy to exclude urolothelial malignancies, no required in this case (Indications are age > 40 years, visible hematuria, smoking history or occupational exposure)
-If all above investigations are negative and the donor is still keen to donate, renal biopsy is done(L/M, IF and E/M) to exclude glomerular pathology that would preclude donation with the exception of thin membrane disease.
· What is the significance of haematuria in the absence of proteinuria, microalbuminuria, and casts?
The absence of albuminuria, proteinuria or casts usually preclude glomerular pathology. However, hematuria can still occur in the absence of proteinuria with glomerular and non-glomerular pathology.
After excluding non-glomerular pathologies, a kidney biopsy is not usually done in the general population(PNVH with no proteinuria and stable renal functions), but in important in the evaluation of kidney donors as only patients with thin membrane disease are allowed to donate , while those with other pathologies like IgA and Alports syndrome are excluded.
· Would your management differ if there were granular casts in the absence of proteinuria on urine microscopy?
Granular casts results from degeneration of the cells in the cellular casts. They may be present with both tubular (ATN) and glomerular pathologies or in a normal urine sample and does not indicate the type of kidney disease and they are non specific.
The management plan will not change as still this potential donor with PNVH + granular casts may have a glomerular pathology even in the absence of proteinuria and still he needs the above mentioned investigations including a kidney biopsy .Glomerular pathologies would preclude him from kidney donation with exception of TMD
References:
========
1) KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors. Transplantation. 2017 Aug;101(8S Suppl 1):S1-S109
2) BTS/RA Living Donor Kidney Transplantation Guidelines 2018.
Dear Omar,
Your approach is comprehensive, logical and problem-oriented.
Ajay
1_ The index case presented with heamturia (presence of RBC in urine), as being female in child bearing period so exclusion of menstrual bleeding or post coital bleeding is essential by history taking ( especially as no protinuria or casts that specify glomerular origin of hematuria).
_ the next step is to do RBCs morphology by phase contrast microscopy to confirm if it is dysmorphic RBC ( so C3, Anti dsDNA will be requested) and renal biopsy can be requested with EM examination for the diagnosis of thon BM disease, alport syndrome and IgA nephropathy
_ all are contraindications for donation except thin GBM disease that can donate with minimal risk of hyperfilteration injury post donation .
_ if RBC are of normal morphology, so urine analysis and culture to exclude UTI , KUB xary and andomainla us to search for stones and further 24 h urinary stone panel to exclude urolithiasis as a cause of recurrent microscopic hematuria as hypercalciuria, hyperuricoduria, etc.
_ if no cause can be detected, cystoscopy is indiacted to search for local lesion or bladder cancer as a cause of bleeding.
2. Presence of hematuria alone ( without protinuria or casts ) raise the possibilty of extra glomerular hematuria either from lower urinary tract or the female genital system
3. Presence of glomerular casts is not specific for glomerular lesions, it acn be degenerated cells , so need for RBC morphology help to narrow the differential diagnosis.
Then evaluation starting with non invasive tests as urine anlaysis and culture till reach cystoscopy or renal biopsy at the end.
Hi Dr Shawky,
Your approach is logical and problem-oriented.
Ajay
● First We should to confirm that haematuria is persistent so repeatiing urinanalysis
● If it is persistent then agood history for familial haematuria and kidney disease to exclude the GBM disease ( alport disease )
And assessment the deafness or eye abnormalities
● Bleeding history and bleeding profile to exclude the haematologic disorders
● Assessment the Menstrual disorders and gynecological problems
● Evaluation other concomitant disorders as proteinuria , hypertention , and decreased GFR . And the origin of RBC , RBC casts
● Renal US to rul out nephrolithiasis or calcinosis and other abnormality
● assessment of Hypercalciuria , hyperuricosuria
● rul out malignancy by cystoscopy
If there isn’t any problem then I will proceed kidney biopsy
# What is the significance of haematuria in the absence of proteinuria, microalbuminuria, and casts?
It Directed to urinary problems not glomerular causes
# Would your management differ if there were granular casts in the absence of proteinuria on urine microscopy?
I will evaluate the glomerular disease as alport disease , TMD , IgAN
and others
Hi Dr HUda,
This time your answer is not complete. What will you do if this turns out to be TBMD?
Ajay
I will accept him
” Many individuals with TBMN but otherwise normal investigations have undoubtedly
donated kidneys, either knowingly (11) or unknowingly”
BTS /RA guidlines 2018
1) How do you proceed?
▪︎In this scenario of a donor who is 31 years old female with 2+ blood in urine dipstick and the urine microscopy confirmed microscopic haematuria with no granular cast,
no proteinuna or micro albuminuria.
▪︎ In such a case we can proceed by requesting another dipstick urine analysis.
▪︎If there is haematuria in 2 urine dipstick; persistent non- visible haematuria (PNVH) should be considered after exclustion of other causes such as fever, exercise or menstruation.
▪︎Isolated hematuria could result from glomerular bleeding or secondary to extraglomerular causes like nephrolithiasis, and urothelial malignancy.
▪︎If there is PNVH we must:
Take a full medical history and family history of Alport syndrome.
▪︎ Urine for culture to rule out infection.
▪︎Urine cytology to see if there is dysmorphic RBCs which goes with glomerular origin pathology.
▪︎ Request 24 hour urine collection for proteins.
▪︎U/S and CT pelvic plus cytology to rule out malignancy.
▪︎ If there is evidence of malignancy we shall consider cystscopy and biopsy
Finally:
If there is a negative urological workup this lady may need a kidney biopsy to exclude glomerular disease [1].
2) What is the significance of haematuria in the absence of proteinuria, microalbuminuria, and casts?
As described above, presence of haematuria in 2 urine dipstick can be considered as PNVH after exclusion of other causes and this may need kidney biopsy.
3) Would your management differ if there were granular casts in the absence of proteinuria on urine microscopy?
▪︎ Granular casts could point to the possibility of glomerular bleeding which in most cases due to one or more of three disorders: thin basement membrane nephropathy (TBMN) [2], IgA nephropathy, and Alport’s syndrome
and it represent degenerate cellular cast or aggregation of protein within cast matrix , this granular last may be in this case we must consider kidney biopsy if there is haematuria more than +1 of blood in dipstick.
____________
References:
[1] C. Hartono, et al. Live Kidney Donors with Microscopic Hematuria
[2]. Hass M Thin glomerular basement membrane nephropathy: incidence in 3,471
consecutive renal biopsies examined by electron microscopy. Arch Path Lab Med
130:699-706, 2006.
Dear Dr Ashmaig,
Your approach is comprehensive, logical and problem-oriented. However, your answer is not complete. What will you do if this turns out to be TBMD though you have quote a reference of TBMD?
Ajay
That potential donor needs to be investigated to rule out significant transmissible disorder and for prognostication of future after donation. Two separate occasions of urine dipstick testing,1-5 rbcs /hpf is considered positive .Reversible causes like infection, exercise, and menstruation to be ruled out .In case of persistent hematuria ,urine cytology and imaging are done to rule out stones and malignancy. In that patient age; less than 40,cystoscopy is indicated if there is risk for malignancy like smoking ,aniline dyes, analgesics or cyclophosphamide .Persistent non visible hematuria mandates renal biopsy especially if the potential recipient has unknown cause of ESRD or the cause is possibly inherited. Biopsy to be done for the kidney selected for donation .Abnormal renal biopsy other than TBMD precludes donation.
_ Hematuria without proteinuria and casts suggests underlying urological non-glomerular cause.
_ Even in the absence of granular casts ,the approach is the same.
Hi Dr Omran,
I like your contribution. May aI push this a bit further: can all patients of TBMD donate kidney?
Ajay
As per BTS guidelines; haematuria has to be confirmed on at least Two or more occasions.. (B1) • If persistent non-visible haematuria (PNVH) is present, then to 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, however, our patient is just 31 years.
• If no cause is found and the donor still wishes to donate, then a kidney biopsy is recommended (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 is recommended. (B2) TBMN is present in 10-50% of patients biopsied for PANVH and although often considered a benign diagnosis may carry some risk of progression.
for individuals with TBMN but otherwise normal investigations, the adverse outcomes have not been reported, however, these donors must be made aware of the uncertainty.
So for this young lady I will perform a kidney biopsy, to exclude GN causes. If TBMN or XLAS alport found, with normal kidney function, no proteinuria and no hearing deficiency, then she can proceed for donation after explaining all risks
Depending on the nature of the cast, for RBC cast definitely not. The presence of red cells and cellular casts could point to the possibility of glomerular bleeding, but for a hyaline cast which is not specific I guess yes she can proceed (no reference I can find for this)
Ref:
1. BTS guidelines
2. Vadivel N, Stankovic A, Rennke HG, Singh AK. Accepting prospective kidney donors with asymptomatic urinary abnormalities: Are we shooting in the dark?. Kidney international. 2007 Jan 2;71(2):173-7.
HI Dr Alalawi,
I like your expression that I am highlighting in bold, “TBMN but otherwise normal investigations, the adverse outcomes have not been reported, however, these prospective donors must be made aware of the uncertainty.”
Moreover, I have added an important adjective here ‘prospective’, since all these individuals that you mention are not donors yet.
1-How do you proceed?
1-Gynecological history is important in female donors (menstrual cycle).
2-repeat the urine analysis
Two or more positive tests, including trace positive, is considered as persistent non-visible haematuria (PNVH).
3- urine culture and renal imaging to exclude common urologic causes including infection, nephrolithiasis .
3-If no cause is found, then we will perform a kidney biopsy.
4- Donation will be precluded if the result showed a glomerular pathology with exception o thin basement membrane disease .
2-What is the significance of haematuria in the absence of proteinuria, microalbuminuria, and casts?
Absence of cast and microalbumria decrease the threshold for the possibility of glomerular disease. It is usually related to the lower urinary tract pathology .
3-Would your management differ if there were granular casts in the absence of proteinuria on urine microscopy?
Although ,the main causes of granular cast are;exercise or dehydration and acute tubular necrosis,the same approach must be performed before donation .
Reference ;
BTS/RA Living Donor Kidney Transplantation Guidelines 2018,
Many thanks Dr Ishag,
Ajay
Thanks professor
>>What is the significance of haematuria in the absence of proteinuria, microalbuminuria, and casts?
>>Would your management differ if there were granular casts in the absence of proteinuria on urine microscopy?
I like reading your reply, dear Dr Mohamed.
1.How do you proceed?
As young female, need to rule out menstruation as a cause of this hematuria.
Repeat test.
Investigate to rule out urinary tract infection, renal stones and malignancy.
Renal biopsy can be considered when there is no abnormality in the above-mentioned urological evaluation. Kidney biopsy should be examined using LM, IF and EM.
Evidence of GN is a contraindication to donation except TBMD.
2.What is the significance of haematuria in the absence of proteinuria, microalbuminuria, and casts?
As young female, may be due to menstruation
Non-glomerular causes will be included in the differential diagnosis as ADPKD, stone, UTI
Glomerular causes include Alport’s syndrome, thin membrane disease and IgA nephropathy
3.Would your management differ if there were granular casts in the absence of proteinuria on urine microscopy?
Granular casts are non-specific.
I like reading your reply, Dr Ansary.
How do you proceed?
· Potential female donor with confirmed microscopic hematuria. No cast. No proteinuria. Normal KFT. No DM nor HTN.
· Being female, I need to rule out menstruation as a cause of this hematuria.
· I need to check the urine for hematuria at least 2 times.
· Urological review and check-up to look after urinary tract infection, renal stones and malignancy;
a) Urine C&S for possible infection.
b) Imaging studies and sonography to rule out stones and masses.
c) Cystoscopy to identify any possible urinary bladder lesions or malignancy.
· Kidney biopsy can be considered when there is no abnormality in the above-mentioned urological evaluation. Kidney biopsy should be examined using LM, IF and EM.
· Evidence of GN (apart from TBMD) is a contraindication to donation1.
What is the significance of haematuria in the absence of proteinuria, microalbuminuria, and casts?
Isolated microscopic hematuria in a female donor may be related to her menses and could be a benign finding, although may be a feature of an underlying urological abnormality(UTI, nephrolithiasis and renal masses). Hematuria may be a sinister of glomerular insult and GN such as TBMD and IgAN. In GN there are commonly cellular casts and proteinuria.
Would your management differ if there were granular casts in the absence of proteinuria on urine microscopy?
No difference, as granular cast may be a feature of strenuous exercise, ATN and CKD. The work-up plan will be almost the same, although the granular cast may strengthen the necessity for kidney biopsy.
Reference
1. BTS/RA Living Donor Kidney Transplantation Guidelines 2018
Many thanks Dr Mahamed
we need to figure out the cause of haematuria by hx , ex and investigations , make sure it is real haematuria ( as shown in dipstick we need to repeated many times to confirm then to check if it is glomerular origin or other ( urological , gyne,surgical or even haematological ) as well as role out infection
after all that if no cause and persistent haematuria may proceed with biopsy
as mentioned above can be non renal cause or can by TBMD ,IgAN ,Alport S
almost same we need to do all the work up to r/o glomerular dis before procced with transplant as granular casts are not specific
Many thanks Dr Farah.