The 31st lecture of Pediatrics

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Hematuria
Today we will talk about 2 subjects which are the core of nephrology, one of them is hematuria, by the end
of the lecture I want you to know how to approach hematuria and to know which is significant hematuria and
which is not ok! We will start talking about hematuria and the next lecture will be about proteinuria.
Hematuria; Red Urine
Hematuria doesnt always mean red urine, on the other hand whenever someone sees red urine it makes him
worry, but should he worry or not?
There are 2 kinds of red urine: heme positive red urine and heme negative red urine
1- Heme positive is the one that when you do a dipstick test you will find it positive with heme because the
dipstick checks for heme and it doesnt check for RBCs, and then the
2- Heme negative which doesnt have heme in it, heme negative urine could be caused by a list of problems;
such as:

dyes,

urates,

certain foods,

and a very important one which is bilirubin.

drugs like Rifampin or Rifampicin,
Sometimes patients with obstructive jaundice come and say we have a red urine but it is not red actually, and
also you have to differentiate between red urine and concentrated urine.
The causes of heme positive [positive dipstick with hemoglobin] are one of 3, either:
1- hemoglobinuria, which is beyond our discussion
2- myoglobinuria which is beyond our discussion or
3- actual RBCs in urine which is called hematuria to be discussed now
Hematuria; Overview
Hematuria means the presence of RBCs in urine and it doesnt mean heme positive only but it means heme
positive + the presence of RBCs in the urine, so when you say that this patient has hematuria then he has to have
RBCs in the urine.
Hematuria could be just a transient sign or phenomenon and have no significant at all, or it could be
something significant as a sign of a serious disease, so it ranges between those 2 limits.
Causes of hematuria could be either:
 Causes that are not related to the urinary tract or the kidneys, or
 Things related only to the urinary tract; lesions along the urinary tract and not related to the glomrulus
itself, so outside the kidneys, [urinary tract not renal tract; you will notice the difference later on] or
 Things inside the kidney either: glomerular or tubular [extra-glomerular], isolated or nephritis.

How to distinguish between those just from a simple test? By 5 aspects:

1- Urine color: hematuria that is related to the kidney itself or what we call glomerular hematuria is
usually not bright in color, here the urine will be dark red or Pepsi-like color or brownish Coca-Cola
color.
2- Blood clots: if we have glomerular hematuria its unlikely to find clots, blood clots are almost absent in
patients urine who has glomerular hematuria, if you see clots usually its something extra-glomerular.
3- RBCs shape: when you look at the RBCs in the glomerular disease they are dysmorphic because they
had passed through small tubules and small capillaries.
4- RBC casts: casts are not usually present in the extra-glomerular disease, they are present in the
glomerular one.
5- Proteins: also proteins are not usually present in the patients urine having extra-glomerular disease, they
are present in the glomerular diseases but sometimes we can find proteinuria in extra-glomerular diseases
such as UTIs.
Cause of hematuria 

Glomerular

Extra-glomerular

Urine color

Dark red, Pepsi-like, brownish coca-cola

Bright red

Blood clots

Unlikely to find

Usually found

RBCs shape

Dysmorphic

Regular, tidy, normal

RBC casts

Usually found

Unlikely to find

Aspect 

Proteins
Usually found
Unlikely to find
We said that clots almost never occur in glomerular diseases, we have something called 3-tubes test in
urology, once the patient voids if the blood is:
 present in the first stream usually its a problem in the urethra,
 if its present in the last stream usually its a problem in the bladder trigone, and
 if its present all through the stream the problem could be anywhere in the bladder or in the ureters
or anywhere.
Again the glomerular hematuria will give us dysmorphic RBCs and the extraglomerular causes will give us
nice well looking RBCs in the urine.
Hematuria; Hematuria Not Related to Kidneys or Urinary Tract
Hematuria that is not due to kidney or urinary tract lesion could be due to:

following regular exercise,

external genitalia or

fever, dehydration,

anything that is not related to the urinary tract or

gastroenteritis,
kidneys themselves
 Hematuria Not Related to Kidneys or Urinary Tract; Exercise Induced Hematuria:
The pathophysiology is actually not known, its said that this happens because of lyses of the RBCs in the
small blood vessels, but I dont think so because if we have such intravascular damage we must have
hemoglobinuria not hematuria, so I dont have a good explanation for it.
By the way you to know the difference between exercise induced hematuria and exercise induced
myoglobinuria which is due destruction of muscle fibers, fortunately both are transient and benign conditions.
 Hematuria Not Related to Kidneys or Urinary Tract; Gastroenteritis Induced Hematuria:
Gastroenteritis by itself; mere gastroenteritis can cause hematuria, away from Shigellosis or HUS Hemolytic
Uremic Syndrome or ATN Acute Tubular Necrosis.
Gastroenteritis-induced hematuria is a transient benign condition, but HUS and ATN are really very
serious frightening conditions.
Hematuria; Hematuria Related to Urinary Tract
Now causes that are related to the urinary tract not to the Kidneys themselves could be:

stones,

obstructions,

infections, tumors,

traumas or


anything affecting the tract outside the kidneys [outside the glomeruli & tubules],

cyclophosphamide can also cause hemorrhagic cystitis,
So the cause could be anything in the bladder or in the urethra
Hematuria; Hematuria Related to Kidneys (Renal Causes)
Renal causes of hematuria are divided into glomerular and extra-glomerular,
 Extra-glomerular are like:

infections [pyelonephritis],

nephrocalcinosis which means calcification around the nephrons,

metabolic diseases like uric acid crystals,

stones,

hypercalciuria,

tumors,

renal tract obstruction[renal tract not urinary tract; inside the kidney but outside the glomrulus ],

cystic kidney or

traumas and many others.
 Glomerular diseases are the important ones to know and differentiate, we mention a way to differentiate
them which is looking at the color of the urine, the shape of the RBCs, the presence of casts, clots and
proteinuriaWe have a long list in this category but the important ones are

:

Post-infectious glomerulonephritis. 

IgA nephropathy. 

Hereditary disorders and the most common one which is Alport Syndrome. 
Primary.

Benign recurrent which is also considered as hereditary. 

Membrano-proliferative. 

Others that are non-primary but associated with other diseases like SLE, Vasculitis
Renal hematuria could be:
 Isolated Hematuria; which is mIcroscopic with no other signs or symptoms, or it could be
 Nephritis; which is an inflammatory process in the glomeruli.
So after all we have this type of hematuria which is related to the kidneys themselves, this renal hematuria has
2 subtypes [or 2 sets of causes]: glomerular and extra-glomerular, and has 2 forms [or 2 clinical pictures]: isolated
hematuria and nephritis.
Hematuria; Hematuria Related to Kidneys (Renal Causes); Isolated Hematuria
 Isolated Hematuria; Overview:
Isolated hematuria is a very common finding, if you take a class of 100 kids at the age of 6 years you will
find that around 5 of them will have mIcroscopic hematuria.
But if you repeat the test after 6 months you will find that the same 100 kids only 0.5-1% of them still have
the mIcroscopic hematuria and the rest are normal.
These patients usually have no renal problems or deficiencies and no abnormal functions and no evidence of
other systemic diseases.
 Isolated Hematuria; Persistent vs. Benign:
MIcroscopic hematuria to call it persistent it should stay or last for more than 1 year and this is when you
must start thinking of something more serious, more serious than isolated hematuria which is a transient benign
condition.
So if you have a patient with this isolated mIcroscopic hematuria you must follow him and check him after 1
year, normally the hematuria will resolve by itself but if its not you must start looking for another serious cause.
Now as we said we have glomerular causes of isolated hematuria and extra- or non-glomerular causes of
isolated hematuria.
 Isolated Hematuria; Non-Glomerular Causes:

Non-glomerular like:

renal tract obstruction[renal tract not urinary tract; inside the kidney but outside the glomrulus ],

tumors,

cystic kidney or

hypercalciuria
These conditions plus the previously mentioned ones [Extra-glomerular are like:]could cause
persistent isolated hematuria.
 Isolated Hematuria; Glomerular Causes:
Or glomerular diseases like:

IgA nephropathy,

Alport disease which is initially presented as mIcroscopic hematuria, to be discussed in a separate block

mis-diagnosed post-strep glomerulonephritis, or

benign persistent hematuria; familial or sporadic. to be discussed in a separate block
These conditions plus the previously mentioned ones [but the important ones are

:]could cause persistent

isolated hematuria.
 Isolated Hematuria; Familial Causes:
We have causes of persistent isolated hematuria that have familial association, they are:

Alport  Glomerular

Benign familial persistent hematuria. 

Hypercalciuria, 

poly-cystic kidney disease,  Non-glomerular

stones; 
 Isolated Hematuria; Hypercalciuria:
Idiopathic hypercalciuria is easy to diagnose, the definite diagnosis is to do a full 24hours-urine collection,
but we have a more simple thing which is to take a spot urine sample and to test for calcium Ca and creatinin
Cr and make a ratio.
If this ratio is more than 0.2 beyond the neonatal period this is enough to diagnose hypercalciuria. In the
neonatal period this ratio is accepted to be up to 1.
The mechanism of hematuria here is said to be that there are small or micro calcium crystals that damage the
tubules while they are passing [tubules so extra-glomerular], this hematuria usually will remain beyond the 1 year.
The treatment of this condition is by giving anti-calciuric therapy which is Hydrochlorothiazide
(HydroDIURIL, Esidrix). The doctor had forgotten the drug, I look for it in Wiki so Im not sure; sorry!
Hematuria; Hematuria Related to Kidneys (Renal Causes); Alport Syndrome
 Alport Syndrome; Overview:
Alport syndrome is well known as an X-linked hereditary disorder, but we have other autosomal recessive
type and another autosomal dominant type, the most common and the most well known one is the X-linked one.
Its well known as a disease which affects males, this x-linked type could also affect the females, but females
will have only mIcroscopic hematuria with nothing else.
While the males will have renal failure and hearing deficits in addition to the hematuria, and thats why xliked Alport syndrome is known as a disease of males.
 Alport Syndrome; Hearing Loss:
The hearing deficit is usually sensori-neural and its bilateral, but never congenital [never congenital means
that they will never have their hearing loss early in their lives as a congenital disease; but they will have later on].
 Alport Syndrome; Clinical Presentation:
Usually it starts with mIcroscopic hematuria, then the patient will have proteinuria, then and at the age of 20
or around that in their 20ths they will develop end-stage renal failure, at the same time as the renal failure
develops they start having their hearing loss, also the hearing loss will not appear at the beginning but it will
happen later on at the age of 20.

We said that Alport syndrome will start usually as mIcroscopic hematuria, and thats why its one of the
diseases that will cause a persistent isolated hematuria [hematuria with no other signs or symptoms for more than 1 year].
And thats why its one of the diseases that you have to think about when you start following and checking
your patient [whether male or female, its not serious in females but you have to know it to give an answer to this hematuria ok!].
By the way you have to check your patients urine protein and test him for the kidney function test in every
couple of months to assure that he is not having X-linked Alport syndrome behind this persistent isolated
hematuria.
 Alport Syndrome; Renal Biopsy:
Why we dont do a renal biopsy from the beginning? Because doing a renal biopsy will not change your
management plan, and also its an invasive thing to do.
You may read in many text books that a persistent hematuria is an indication of doing renal biopsy, but
practically if you will not change your management plan according to the biopsy so why to do such an invasive
test.
 Alport Syndrome; Treatment:
Whatever you give the patient with Alport he will never improve, there is no effective treatment for this
condition, so the treatment will be only supportive therapy.
 Alport Syndrome; Microscopy:
[doctor is talking about a picture] this is the normal basement membrane in the kidney, the glomrulus as
you know is a spherical structure inside which we have small capillaries that will give us the filtration function,
between these capillaries we have what we call a mesangium.
If you take a cross section in the capillary wall you will find this basement membrane, and here in this
basement membrane we have the endothelial cells that have extensions called podocytes.
These podocytes will appear as lines and spaces between the lines or as inter-digitating fingers, now that was
the normal capillary.
In Alport syndrome we have a defect in collagen type 4 [collagen IV], so the basement membrane will be
disrupted, by the way the collagen type IV is affected only in the glomrulus in this Alport syndrome, its normal
elsewhere in the body!!!!!
Hematuria; Hematuria Related to Kidneys (Renal Causes); Familial Benign Hematuria FBH
 Familial Benign Hematuria; Overview:
Familial benign hematuria FBH is another entity, here we do a urine analyses for the whole family to find
that they all have hematuria, and this is how you diagnose it, it could be a type of Alport again but also it could be
this separate disease. Its an autosomal dominant disease so most of the family will have it.
 Familial Benign Hematuria; Microscopic Sign:
Usually these patients will have a very thin basement membrane all over the kidney capillaries, but this sign is
not pathognomonic; so having a thin basement membrane is pathologic but not pathognomonic in familial
benign hematuria, so we may have other diseases that will give us a very thin basement membrane.
We cant diagnose FBH if we dont have a very thin membrane  Pathologic [pathologic: mandatory to exist]
If we see a very thin membrane its not necessary to be FBH  Not Pathognomonic [pathognomonic: present only in it, or 100% diagnostic]

 Familial Benign Hematuria; Thin Basement Membrane TBM:

Thin basement membrane is another disease, they are all [Alport, FBH, TBM] together thought to be part of
one disease called Hereditary nephropathy coming in variant presentations, thin basement membrane patients
will have hematuria and proteinuria, and of course you will find that they have a very thin basement membrane.
Again it could be Alport and its a benign disorder.
 Familial Benign Hematuria; Microscopy:
[doctor is talking about a picture] This is the normal shape of glomeruli, and these are the capillaries that
we have just mentioned, this is the regular basement membrane and this is the thin basement membrane.
Its said that the normal thickness of the basement membrane should be equal to the length of one normal
podocyte, if its less so this is abnormal so this is a finding seen in the above 3 disorders [Alport, FBH, TBM].

 Familial Benign Hematuria; Hereditary Nephropathy:

Hereditary nephropathy could be benign familial hematuria or it could be Alport syndrome or the thin
basement membrane, so all of them are under the umbrella of the same disease as we said.
Again and again hematuria due to renal causes could be:
 Isolated Hematuria; which is mIcroscopic with no other signs or symptoms, or it could be
 Nephritis; which is an inflammatory process in the glomeruli with mAcroscopic hematuria.
By that we have finished the isolated and we will start discussing the Glomerulonephritis [NephrItic
syndrome].
Hematuria; Hematuria Related to Kidneys (Renal Causes); Glomerulonephritis (NephrItic Syndrome)
Its something else and this is the most serious thing in our discussion, when we say nephrItic syndrome this
means that you must have all of these: sorry but it seems that the previous 5 pages were only an introduction!!!
1) Gross mAcroscopic hematuria.
H&A&G&E
3) Edema.
2) Abnormal kidney function.
4) Hypertension.
So these are the meanings of nephrItic syndrome, or these are essential to diagnose a patient with nephritic
syndrome; they are pathologic to nephrItic syndrome.
All the previously discussed diseases could lead to nephritis except the 2 benign ones [FBH, TBM] these they
usually dont lead to nephrItic syndrome.
Hematuria Related to Kidneys (Renal Causes); Glomerulonephritis (NephrItic Syndrome); Post-Infectious
 Pos-Infectious Glomerulonephritis; Overview:
Post-infectious glomerulonephritis was called previously post-strep, but its now called post-infectious
because we have other agents that can give us similar condition such as mycoplasma, staph, influenza and many
others, but the most common one and the most well known one is the post-strep.
Usually it becomes after 10 days of pharyngitis, or 14 days after skin infection.
 Pos-Infectious Glomerulonephritis; Clinical Presentation:
Most of the patients will have mild minor disease, some of them go unnoticed, they will have mild edema,
slight impairment in kidney function, so they go unnoticed having only mIcroscopic hematuria. Others present
with the full-blown picture.
Both of them will have a sort of nephrItic syndrome, both of them will have the 4 signs [H&A&G&E].
 Pos-Infectious Glomerulonephritis; Investigations:
First thing to do is urine analyses, you will find that they will have dysmorphic RBCs and RBC casts, the
RBC casts are tube-like collection of RBCs.
We may find proteinuria but usually its under the nephrOtic range, the presence of nephrOtic range
proteinuria in a nephrItic syndrome patient is alarming, but this is uncommon.
They will have proteinuria because the damaged RBCs in the urine will release their internal proteins but still
this proteinuria is below the nephrOtic range. The nephrOtic range will be discussed in lecture 32
Creatinine is usually elevated as an abnormal kidney function test, C3 will be low, C4 is normal [these are the C3
and the C4 from the complement system proteins family].
If you find any other findings that dont go with this:
 Dysmorphic RBCs.
 Creatinine.
 RBC casts.
  C3.
 Proteinuria below the nephrOtic range.
 Normal C4.
Like for example elevated C3 or normal Creatinine, so this doesnt go with nephritis so it will drive me to
another diagnoses or it will make an indication to do a renal biopsy.
 Pos-Infectious Glomerulonephritis; Microscopy:
In light microscopy the capillaries will be inflamed, this finding is not diagnostic; because this finding can
happen in many other conditions.
Normal mesangium under the light microscope should be 3-5 cells between each 2 capillaries and not more
than that, while here we have many mesangial cells, you can count 15 or 20.

 Pos-Infectious Glomerulonephritis; Immunoflorescence:

If we do Immunoflorescence, we will find C3 deposition with IgG complex and this is the diagnostic for poststrep, this is called hump which is sub-epithelial deposits. They are large and look like the camels hump.
 Pos-Infectious Glomerulonephritis; Treatment:
Is usually supportive, we do correction for the fluids, correction for the potassium K because these patients
are in renal failure, I can give them diuretics and treat the hypertension and thats it.
Some doctors give them penicillin, but penicillin will not treat this disease once it appears, they will eradicate
the cause but they will not treat the disease.
Steroids dont help here, because this is usually a self-limiting disease, except if we have something called
rapidly progressive glomerulonephritis where we have a rapid progression to renal failure, in this case yes we
give them steroids to soften the condition.
So its a self-limiting disease that will resolve by its own, but you have to support them when they are at the
renal failure stage. Some of them may also need dialyses.
Hematuria Related to Kidneys (Renal Causes); Glomerulonephritis (NephrItic Syndrome); IgA
Nephropathy
 IgA Nephropathy; Overview:
IgA nephropathy is the most common primary idiopathic cause of glomerulonephritis, its more common
than the post-strep.
They usually present at first with mild mIcroscopic hematuria and they dont present with nephrItic syndrome
at first [H&A&G&E], they could present with nephritis at the beginning but this is uncommon.
As you can see that nephritis is different from nephrItic syndrome; nephritis is an inflammatory process only,
while nephrItic syndrome is the H&A&G&E, but we can use the 2 terms interchangeably.
 IgA Nephropathy; Presentation:
They have persistent mIcroscopic hematuria, and recurrent gross mAcroscopic hematuria with any infection,
what differentiate this from the post-infectious that the post-infectious needs at least 10 days to give us the
hematuria, while here in the IgA they will have the gross hematuria at the same time of infection, whatever this
infection is.
So in an IgA nephropathy patient, if he gets any infection he will immediately have gross hematuria as a
complication, immediately not after a 10 days duration.
Sometimes they have nephrOtic range proteinuria and sometimes they have rapidly progressive
glomerulonephritis, meaning that they go rapidly into renal failure and sometimes they present with hypertension
only. Usually around 50% of them develop renal failure at the age of adulthood.
 IgA Nephropathy; Microscopy:
In light microscopy usually they dont have a lot of changes, the capillaries are normal, we may see slight
mesangial proliferation but its not that obvious.
And on electron microscopy you will find mesangial deposits of IgA and IgG.
 IgA Nephropathy; Immunoflorescence:
You will find IgA deposits when you do Immunoflorescence.
 IgA Nephropathy; Renal Biopsy:
Usually if they have mIcroscopic hematuria you just keep following them up, if they start having proteinuria
or renal failure or increased blood pressure then you do a biopsy.
The reason behind doing the biopsy is that there is no proven therapy for this disease, they tried many things,
they tried fish oil, tried giving Warfarin, they tried steroids but nothing really helps.
 IgA Nephropathy; Treatment:
But sometimes when they have proteinuria giving them steroids will help them a little bit, but it will only
prolong the duration or it will extend the time for renal failure to happen, it will increase the life expectancy for
the patient but it will not reverse or treat the disease.

Usually around 50% of them develop renal failure at the age of adulthood.
 IgA Nephropathy; Henoch-Schnlein Purpura HSP:
HSP Henoch-Schnlein Purpura nephritis is another variation of IgA nephropathy, so if you do a renal
biopsy for these HSP patients you will find IgA deposits you will find the same findings of the IgA like mesangial
IgA and IgG deposits.
But the distinguished thing in HSP is that it will present with skin rash and arthritis, so its somehow a part
of a syndrome.
HSP is a triad of:
1) Abdominal pain.
2) Arthlargia; arthritis
3) Skin rash.
Its unnecessary for them to be all present at the same time, sometimes the patient will come with abdominal
pain then after 2-3 weeks they will get arthritis with the skin rash, sometimes they only present with skin rash
without the other 2 and so on...
The important thing is that the HSP nephritis doesnt always come with its syndrome [triad], so you have to
follow the patient up to 2 years In order to say that he is not having an associated renal disease.
20-50% of children will have renal involvement at the initial presentation, some of them will have mild
proteinuria and then it will resolve by itself, some of them will have a more sever disease, they also may come
with nephrItic or nephrOtic syndrome.
 Do you remember this? We have a long list in this category but the important ones are

:

Post-infectious glomerulonephritis. 

IgA nephropathy. 

Hereditary disorders and the most common one which is Alport Syndrome. 
Primary.

Benign recurrent which is also considered as hereditary. 

Membrano-proliferative. 

Others that are non-primary but associated with other diseases like SLE, Vasculitis
Now we will talk about the non-primary ones
Hematuria; Hematuria Related to Kidneys (Renal Causes); Glomerular Non-Primary Causes
Other systemic diseases just like

vasculitis,

Wegeners,

polyarteritis nodosa PAN,

anti-GBM; which is the Good-Pasture syndrome where we have antibodies against the GBM
Glomerular Basement Membrane, these patients will present nephritis and respiratory problems,

SLE where we have 11 criteria that must be present in a patient to diagnose him as having SLE, also
in the SLE itself we have stages of nephritis, SLE could come with anything and everything, it could
come with membranous or membrano-proliferative or anything.
 Hematuria Not Related to Kidneys or Urinary Tract; Gastroenteritis Induced Hematuria:
In the hemolytic uremic syndrome HUS we have diarrhea-associated HUS and non-diarrhea associated
HUS.
Diarrhea associated HUS is easy to diagnose where we have diarrhea with E.coli usually with anemia and
thrombocytopenia all that will happen with nephritis.
The non diarrhea associated HUS will have the same symptoms, its hereditary with autosomal recessive
mode of inheritance, they have a defect in the complement inhibitors so they will end up having low complement,
while we have normal complement in the diarrhea associated HUS.
We have to give them frequent plasma those with the non-diarrhea associated HUS, plasma infusion every
month to compensate for the inhibitors that they are deficient with.
 Glomerular Non-Primary Causes; Others & Others:
Shunt nephritis and sub-acute bacterial endocarditis are others
Then we have many other disorders that could have a nephrItic presentation, they are nephrOtic mainly like
focal segmental and membrano-proliferative but they could give us a nephrItic picture but they are primarily
nephrOtic.

Hematuria; Evaluation
 Evaluation of Hematuria; History:
Evaluation of hematuria starts first of all with history where you should take a good detailed history
especially a family history; family history of renal diseases or renal failure, stones, deafness, hematuria.
And we ask about the precipitating factors like diarrhea, gastroenteritis, exercise, urinary tract symptoms,
abdominal pain if you are thinking about HSP or pyelonephritis or stones, you ask also about traumas.
You ask about respiratory problems; difficulty in breathing, cough, skin rash, joint pain and swellings, all
these things may give good hints about many diseases, also you ask about drugs, foods
 Evaluation of Hematuria; Examination:
In examination first of all you have to check the growth factors or parameters and if you find them impaired
this will give you a hint that you are dealing with a chronic disease.
You check for hypertension, if you have hypertension this will give you a hint that this is not a benign
disorder, look for pallor, because it may be a bleeding disorder that is causing the hematuria, you look also for
trauma.
You look for edema if you suspect nephrItic syndrome, you look for rash if you suspect HSP or SLE or
peticheal rash if you suspect bleeding.
You examine the abdomen looking for masses or tenderness, and its important to examine the external
genitalia in anyone who is having hematuria because the lesion could be there.
 Evaluation of Hematuria; Work Up & Investigations:
The work up or the investigations that we have to do, we divide them into 3 phases:
Phase 1: we do them for everyone:
 urine analyses,

 renal ultrasound,

 24 hours urine sample,

 analyses to the other members of the family, 
 urine culture if we suspect UTI,

 in analyses we look at the RBCs and their 
morphology,
Whenever you have a patient with hematuria you have to ask
there or if you didnt you move to phase 2!!!

look for proteins,

then you do a kidney function test,
electrolytes,
C3 and C4,
Calcium Creatinine; Ca: Cr ratio.
Renal X-ray.
about all of those, then if you find something

Phase 2: if we find that the RBCs are normal and regular in their shape, or if we have clots in the urine, no
findings in the X-ray or in the ultra sound, I could do a:
 cystoscopy because the cause could be a tumor.
 I could do a hearing test if he is still 15 or 16 and start having hearing deficits, or if he is having
abnormal kidney function.
Again if I find anything in those, if I find hypertension or abnormal kidney function, or cast or anything I
could do a biopsy which is the phase 3.
Phase 2 is dependent on the results of phase 1, if I find hypercalciuria there is no need to go to phase 2.
Isolated hematuria: I will repeat it again, if you have a patient with isolated hematuria you start to check him
and follow him up every 2-3 months or even 6 months, where you do a urine analyses and a urine culture every
time to look for infections or proteinuria, you check the hypertension, or any changes in the pattern of hematuria,
if it becomes gross or increased or decreased or disappeared, and you do kidney function test.
If I have everything normal and regular then I have to bring him yearly and not to leave him alone.
The outcome of isolated hematuria: it could disappear; resolve by itself, it may persist but without any
problems, and it may become not isolated and present with something else like renal failure or hypertension.
Phase 3: Renal biopsy, we have indications for renal biopsy, I told you that you will find in the text books
that a persistent hematuria for more than 1 year is an indication to do a renal biopsy, but if it wont change
your management then why to do it.

And I believe that you do a biopsy only if you are going to change your management according to it, or if the
parents insist it for example, if there is a strong family history for unknown cause.
Its an advantage to do a biopsy in someone who is strongly suspected to have a renal failure, because you
may detect some important findings of a distinguished disease, but if you wait until the renal failure is there the
biopsy will be not that much useful because the findings will be the same in all renal failure patients whatever the
cause is, the glomeruli will be sclerosed in all the diseases no matter what they were in the beginning ok.
And also we do renal biopsy if we have our patient is getting out his expected range, as a patient who is
having post-strep but the:
 C3 is normal or very severely low, or
 the kidney impairment is severely prolonged, or
 he is getting inside a rapidly progressive renal failure, or
 the hypertension is higher and more prolonged than expected,
So I may change my diagnoses and treatment according to the biopsy.
Just to remind you that hematuria could be just a benign transient phenomenon of no significance, or it could
be a sign of a serious disease.
Hematuria; Summary
 Simple gastroenteritis by itself can cause hematuria.
 Red urine.
 Hematuria doesnt always mean red urine.
 Gastroenteritis induced hematuria is a benign transient condition.
 There are 2 kinds of red urine: heme positive red urine and heme
 Gastroenteritis may give us shigellosis, HUS, ATN.
negative red urine.
 Those 3 complications will give us hematuria but its persistent and
 Dipstick checks for heme and it doesnt check for RBCs.
serious.
 HUS has 2 types, diarrhea induced HUS and non-diarrhea induced
 Heme negative urine could be caused by: dyes, certain foods,
Rifampin, urates, bilirubin.
HUS.
 Heme positive urine could be caused by: myoglobinuria,
 Diarrhea induced HUS will give us: anemia, thrombocytopenia,
hemoglobinuria, hematuria.
nephritis.
 Overview.
 Non-diarrhea induced HUS is an autosomal recessive disease, where
 Hematuria means heme +ve urine plus RBCs in the urine.
we have a deficiency in the complement inhibitors.
 We have to give them frequent plasma those with the non-diarrhea
 Every hematuria is a heme +ve urine but
 Not every heme +ve urine is hematuria, [it could be myo- or hemo-].
associated HUS.
 Hematuria has 3 sets of causes: outside urinary tract or kidneys, in  Hematuria Related to Urinary Tract.
the urinary tract but outside the kidneys, inside the kidneys.
 Urinary tract is the tract outside the kidneys; like pylorus, ureters,
 Those inside the kidneys have 2 sets of causes; glomerular or
bladder, urethra
tubular.
 Renal tract is the tract inside the kidneys but outside the glomeruli;
 Those inside the kidneys have 2 forms; isolated or nephritis.
like tubules, loops of Henley, collecting ducts
 We can distinguish between glomerular and non-glomerular causes
 Those causes could be: stones, infections, tumors, urinary tract
by 5 aspects: urine color, RBCs shape, RBC casts, proteins and
obstructions, traumas.
blood clots.
 Cyclophosphamide could cause hemorrhagic cystitis.
 We have something called 3-tubes test in urology.
 Hematuria Related to Kidneys (Renal Causes).
 If the blood is present in the first stream so the problem is in the
 2 sets of causes; glomerular & extra- or non- glomerular [tubular].
urethra.
 2 forms; isolated hematuria & nephritis.
 If the blood is present in the last stream so the problem is in the
 Extra-glomerular causes like; infections, nephrocalcinosis, uric acid
bladder trigone.
crystals, stones, hypercalciuria, tumors, cystic kidney, traumas,
 If the blood is present all through the stream so the problem could
renal tract obstruction.
be anywhere.
 Glomerular causes are primary and non-primary.
 Hematuria not related to kidneys or urinary tract.
 Primary ones are like; post-infectious, IgA nephropathy, Alport,
 This hematuria could be due to: exercise, fever, dehydration,
benign recurrent hematuria, membrano-proliferative.
gastroenteritis, something in the external genitalia
 Non-primary are associated with other diseases like; vasculitis, SLE,
 The pathophysiology of exercise induced hematuria is not known.
Wegeners, PAN, anti-GBM, shunt nephritis, sub-acute bacterial
 Intravascular damage of RBCs will give us hemoglobinuria not
endocarditis
hematuria.
 Isolated hematuria is mIcroscopic without any other signs or
 Exercise induced myoglobinuria is another disease caused by
symptoms.
destruction of muscle fibers.
 Nephritis is an inflammatory process in the glomeruli.
 NephrItic syndrome is the H&A&G&E. but we can use nephritis
 Both exercise induced hematuria & myoglobinuria are benign
transient conditions.
& nephrItic syndrome interchangeably.

 Usually it becomes after 10 days of pharyngitis, or 14 days after skin

 Isolated Hematuria.
 We have benign and persistent.
infection.
 Persistent is isolated hematuria for more than 1 year.
 Among urine analyses we will find dysmorphic RBCs, RBC casts
 Benign is a transient benign condition that will resolve by itself.
which are tube-like collections of RBCs, proteinuria, high Creatinine,
 Isolated hematuria has glomerular and non-glomerular causes; we
low C3, normal C4.
 This proteinuria is below the nephrOtic range.
have mentioned them.
 Isolated hematuria has familial causes that are; Alport, BFH,
 If we have any deviation from these findings this is an indication for
hypercalciuria, polycystic kidney, stones.
doing renal biopsy.
 Hypercalciuria is an idiopathic disease which is easy to diagnose.
 In light microscopy you will find inflamed capillaries, and
 The definite diagnosis for hypercalciuria is to collect a 24hours
hypertrophied mesangium, both signs are non-diagnostic.
urine sample.
 Normally between each 2 capillaries we have 3-5 mesangial cells.
 Another way is to take a spot urine sample and do Ca:Cr ratio.
 In this disease we have 15-20 mesangial cells between each 2
 In adults if the Ca:Cr ratio is more than 0.2 this is diagnostic for
capillaries.
hypercalciuria.
 In Immunoflorescence we will find C3 IgG complex sub-endothelial
 In neonates the Ca:Cr ratio is accepted up to 1.
deposition looking like a hump, this is the diagnostic sign.
 We have micro calcium crystals that will damage the tubules.
 Treatment is supportive, penicillin is not that much useful, some
 The treatment of this condition is by giving anti-calciuric therapy
patients may need dialyses.
which is Hydrochlorothiazide (HydroDIURIL, Esidrix).
 We dont use steroids unless we have a rapidly progressive renal
 Alport Syndrome.
failure.
 We have X-linked type, autosomal recessive and autosomal dominant
 Its a self-liming disease that will resolve by itself after all.
types.
 IgA Nephropathy.
 The most common one and the most well known one is the X-linked
 Is the most common primary idiopathic cause of glomerulonephritis.
one.
 They usually present at first with mild mIcroscopic hematuria and
 The X-linked type could affect males and females, it will be very mild
they dont present with nephrItic syndrome. H&A&G&E
in females having only mIcroscopic hematuria.
 They have persistent mIcroscopic hematuria, and recurrent gross
 The males will have hematuria, hearing deficits and renal failure.
mAcroscopic hematuria with any infection.
 The hearing loss is sensori-neural, bilateral but not congenital.
 IgA nephropathy patient, if he gets any infection he will immediately
 It will start as mIcroscopic hematuria, proteinuria, then at the 20ths
have gross hematuria as a complication, immediately not after a 10
the end-stage renal failure and the hearing deficit will develop.
days duration.
 There is no effective treatment for it, supportive only.
 In light microscopy usually they dont have a lot of changes, the
 Theoretically we must do a renal biopsy, but practically no we dont.
capillaries are normal, we may see slight mesangial proliferation but
 In Alport syndrome we have a defect in collagen type 4 [collagen IV],
its not that obvious.
so the basement membrane will be disrupted.
 And on electron microscopy you will find mesangial deposits of IgA
 Familial Benign Hematuria FBH.
and IgG.
 We do a renal analyses for the whole family to diagnose it.
 You will find IgA deposits when you do Immunoflorescence.
 Its an autosomal dominant disease.
 If they start having proteinuria or renal failure or increased blood
 You will have a very thin basement membrane which is a pathologic
pressure then you do a biopsy.
but not pathognomonic sign.
 There is no proven therapy for this disease, steroids help a little bit.
 Thin basement membrane TBM is another disease, where we have
 HSP Henoch-Schnlein Purpura nephritis is another variation of IgA
hematuria and proteinuria.
nephropathy.
 Alport + FBH + TBM are thought to be 3 variants of one disease
 The distinguished thing in HSP is that it will present with skin rash
called hereditary nephropathy.
and arthritis.
 The normal thickness of the basement membrane should be equal to  Glomerular Non-Primary Causes.
the length of one normal podocyte, if its less so this is abnormal.
 Focal segmental and membrano-proliferative are nephrOtic
 Glomerulonephritis (NephrItic Syndrome).
diseases but they may give us a nephrItic presentation.
 You must have all of these H&A&G&E to diagnose a patient with
 Non-primary are associated with other diseases like; vasculitis, SLE,
nephrItic syndrome.
Wegeners, PAN, anti-GBM, shunt nephritis, sub-acute bacterial
 All the previously discussed and the following diseases could lead to
endocarditis
nephritis except the 2 benign ones [FBH, TBM] these they usually
 Anti-GBM is the good-pasture syndrome where we have nephritis
dont lead to nephrItic syndrome.
with respiratory problems.
 Evaluation.
 Post-Infectious glomerulonephritis.
 Was called previously post-strep.
 You have to take a good detailed history especially family history.
 Many agents can cause it like; mycoplasma, influenza, staph, but the
 You have to check the growth parameters, external genitalia.
 The investigations are 3 phases; Phase 1 is done for everyone.
commonest and the most well known is strep which is Group A  Phase 2 is cystoscopy and hearing test, Phase 3 is renal biopsy.
hemolytic streptococcus bacteria.