CONGENITAL KIDNEY DISEASES

Congenital means present at birth, so generally refers to those abnormalities that are

permanent birth defects.   There are many different kinds and categories, and so what
I am going to do here is to give a classification and overview.

 

The categories that I will discuss are:


* Primary defects of the kidney tissue (parenchymal disease)
* Obstruction of the urinary tract  (hydronephrosis with obstruction)
* Hydronephrosis without obstruction, including vesicoureteral reflux
* Cystic diseases
* Metabolic diseases
* Syndromes

 

Primary defects of kidney tissue (parenchymal disease)
In this group of problems of the kidney parenchyma (parenchyma refers to the kidney tissue

in general), the basic structure of the kidney looks normal on ultrasound or on an X-ray
image, but for some reason on a microscopic level something is wrong and the kidneys
don't work right. The most common problem of this class is renal dysplasia, which is a
condition of both kidneys where the tissue is partly normal with some normal filters

(glomeruli) but laced throughout the kidney is fibrosis (like scar tissue), abnormal cell
groups such as little pieces of cartilage, and immature tissue where the kidney just didn't
finish developing.  There are all levels of severity of this defect, so there are babies who have
very poor kidney function at birth and need major support, even sometimes including
dialysis, from that time, and there are other children whose kidneys support them through
much of life but then eventually as the body grows the kidneys just don't have enough
functional tissue to support it.

Occasionally there is a baby with very severe dysplasia and no kidney function at all as a
result.  In this case, no urine is made in utero either.  Since in the last 2/3 of pregnancy the
amniotic fluid comes from fetal urine, and since lung formation is dependent on breathing in
amniotic fluid, the lungs of these babies with very severe dysplasia may be very

underdeveloped, and they may not be able to survive more than a few hours after birth
because of their poor lung function.   This can also be true with severe obstruction
(discussed below) and severely damaged kidneys as a result.

Renal dysplasia is sometimes part of a syndrome, whereby other defects of other organ
systems occur simultaneously with the dysplasia  (see syndromes).

When children are young (the first months and preschool years especially) with renal
dysplasia often the most prominent defect is the inability to concentrate the urine.  Let me
start by explaining some normal kidney function.  The normal kidney has about a million
filters, each of which filters the blood and a filtrate in which the waste products and other

(electrolyte, mineral and chemical) constituents of blood start down the tubule in a
concentration equal to that of blood.  The tubule has multiple segments, each with a specific
job, and as the filtrate travels down the tubule, water and the other constituents are

reabsorbed into blood as needed, so that the final urine is concentrated compared to the
initial filtrate of blood.  The tubule fine tunes how much sodium and potassium and
phosphorus and other substances are kept in the filtrate (urine) as opposed to reabsorbed
back into blood. To give you an idea of the work of the tubule, in an adult 180 liters of the

liquid part of blood is filtered in a day, yet thanks to the tubule, only 1-2 liters comes out as
urine.

When the child has dysplasia, the tubules are affected, and they have a difficult time
reabsorbing all that they should, so the child often has a large volume of urine, and that
volume is fixed, unable to change based on the circumstance.   So, if the child has diarrhea
or poor fluid and food intake or both, the kidney is not able to reabsorb most of the
salt and water filtered and to reduce the amount of urine, as is a normal renal response.

Instead, the child continues to make large volumes of urine and dehydration comes on very
rapidly.  (By the way, to make it a double whammy, the kidney with dysplasia, since it is
abnormal from the beginning, may be adversely affected by dehydration since
dehydration leads to decreased blood flow (carrying oxygen and nutrition) to the kidney, and

sustain further damage, temporarily or permanently.)

Dysplasia may be accompanied by hypoplasia, which means that the kidneys are unusually
small.   Hypoplasia may be isolated or linked to dysplasia

Obstruction of the urinary tract (hydronephrosis with obstruction)
Hydronephrosis means dilatation of the collecting system or the ureter or both and may be

dilatation with or without an obstruction at some point in the system physically to the flow of
urine down and out. Hydronephrosis is often seen on prenatal ultrasounds, but is found at
least 50% of the time to be dilatation without obstruction, which may simply be due to two

facts:  1) that the fetal kidney does not yet concentrate the urine so there is a large flow
volume down the ureter, making it dilated by volume, and 2) the immature ureteral tissues
are stretchy.

When hydronephrosis is associated with obstruction, it may be either unilateral (one kidney)
or bilateral (both).  The most common obstructive lesions are:

* Posterior urethral valves (causes bilateral obstruction and is limited to males)
* Ureteropelvic junction obstruction (present on one or both sides)
* Ureterovesical junction obstruction (present on one of both sides)
* Ureterocele (present on one or both sides)
* Neurogenic bladder-which acts like an obstruction, since the bladder does not empty

If obstruction is unilateral and the contralateral kidney is fine, then there is not a problem
with kidney function.  The reason that one usually wants to try to fix the situation is to
provide the "insurance" of having two functioning kidneys, because one is plenty.  In the
case of a single kidney, that single kidney increases its function in compensation and can
have as much as 90% of the function that two normal kidneys would have.   Usually a single
kidney has 75-80% of the function of two kidneys.  In this circumstance, the child is
absolutely healthy, with normal growth and development.

Posterior urethral valves is a fairly common defect, and it occurs because a fold or two of
extra tissue grow in the urethra and back up urine flow from the bladder and all the way up
the ureters.  This fold is present from early in kidney development, and so it causes the
urine to back up into the kidneys from the time urine is first made, while the kidneys are still
developing.  Renal dysplasia, same as the lesion discussed above that may occur
independently may occur and in fact, usually does occur, as a result.  This means that the
kidneys are inherently defective and so unblocking the urethra may improve kidney function
somewhat, but it doesn't usually cause kidney function to return to normal.   Even if kidney
function comes back to normal or near normal, the problem with the tubules and inability to
concentrate the urine is quite commonly persistent.  As with primary dysplasia, if the
dysplasia is very, very severe and there is little urine production in utero, then lung

maturation may be affected and cause difficulty after birth.

Development of the bladder is also affected by the blockage.   These boys frequently have
defective bladders, which divide into two types:  1) those that are thick walled and have
strong muscle so that they don't hold much and tend to spastically empty frequently, and 2)
those that are large and stretched out and hold a lot.  Boys with the latter type of bladder
have abnormal sensation, too, and often can't tell when the bladder is full.   Their very full
ladders may cause backup of urine with pressure up the ureters to the kidneys.    Boys with
either bladder type may need medication for the bladder; the former may need surgery to
augment the bladder with a piece of intestine sewn into the top to make it larger, after which, since

the intestine doesn't contract, they usually have to catheterize the bladder 5 times a
day to empty it.  Boys with the large bladders without sensation can sometimes make it by
voiding on a time schedule, since they don't get the urge to void; some need intermittent

catheterization, too.    There are some boys whose bladders work fairly well, but I think that
one should always be aware of bladder function in these boys.   The bladder dysfunction
may play a role in making kidney function worse than it would be with good bladder
function, so it needs to be watched indefinitely.  Bladder dysfunction can also damage a

transplanted kidney.

Ureteropelvic junction (UPJ) obstruction is caused by a constriction at the top of the ureter,
where it intersects with the renal pelvis, which is the part of the kidney that collects the urine
before it starts down the ureter.  This can occur because of a constricting band of fibrous
(scar-like) tissue or from a crossing blood vessel.  Though it is generally present at birth,

sometimes it is so mild as to not cause a problem, but the obstruction may worsen with
time later in infancy or in childhood as a result of changing relationships of the structures of
the urinary tract and of surrounding tissues as growth occurs.   A band of tissue or blood
vessel near the ureter may impinge on the ureter with time and growth.    This is usually a
unilateral finding, but it can be bilateral, and it also is associated with problems with the
other kidney.  Multicystic dysplastic kidneys are associated with a UPJ obstruction of the
other kidney.  Twenty percent of babies with a multicystic dysplastic kidney have a UPJ
obstruction of the other kidney.

UPJ obstruction usually must be fixed surgically.  The surgery is safe and successful,
requiring only 2-3 days in the hospital.  Generally if it is discovered in the newborn period
and is unilateral, the surgery is postponed a month or two until the baby is stable and
growing and doing well.

Ureterovesical (UVJ) obstruction is much less frequent than is UPJ obstruction, and like UPJ
obstruction, can be unilateral or bilateral.    It is an abnormality in the insertion of the ureter
into the bladder, blocking the flow of the urine into the bladder, and is fixed by surgically
reinserting the ureter into the bladder, the same as is done for vesicoureteral reflux (see
hydronephrosis without obstruction).

A ureterocele is a cystic dilatation of the ureter as it inserts into the bladder.  The cystic
area "pouches" into the bladder and causes the opening for urine flow from the ureter into
the bladder to be very constricted, resulting in obstruction and hydronephrosis.     It can
often be handled at cystoscopy, with excision of the abnormal tissue with a small knife

passed through the cystoscope.  There can be associated dysplasia on the side of the
ureterocele, but not always.

A neurogenic bladder is usually associated with a problem with the spinal cord, the most
common being a myelomeningocele (often referred to by the lay public as spina bifida).
This is a defect where the vertebrae in the lumbosacral area are not properly fused all the
way around the spinal cord, and so a sac protrudes from the spinal cord with a mass of
nerves all tangled together.   In these nerves are those to the bladder, so that it has no
functional nerve supply.  The bladder then tends to fill and fill and only empty by overflow
when it is quite full.  There is often backpressure to the kidneys.  This can lead to
vesicoureteral reflux (explained later in this treatise) and chronic infection and scarring of the

kidneys, with eventual renal failure.

Hydronephrosis without obstruction, including vesicoureteral reflux

Hydronephrosis without obstruction means dilatation of the ureter and collecting system of
the kidney but not because of backup above an area of narrowing and obstruction, rather
primary dilatation of the collecting system and ureter.  The conditions causing this that I will
discuss are:

* Prune belly syndrome
* Vesicoureteral reflux
* Primary megaureter with or without megacystis

Prune belly syndrome occurs almost exclusively in boys; there is a controversy whether
there is a variant in girls.  It consists of a group of findings including:   decreased or absent
abdominal muscles, cryptorchidism (failure of the testicles to descend into the scrotum;
they remain in the abdomen), and dilatation of the ureters and bladder, often with associated

renal dysplasia.  Frequently the dilated ureters come with vesicoureteral reflux (VUR; see
below).    The boys are sterile and unable to make sperm, even if the testicles are surgically
brought down, but they function normally sexually.  The bladder may be large and floppy and

not contract and empty like it should, or it may be fine.  High-grade reflux is common, but
reimplantation of the ureters surgically into the large, floppy bladder may be difficult.   With
the renal dysplasia, renal failure may be a problem.  The renal dysplasia may be of any
degree of severity.  Some of these boys progress to needing transplantation; others do not.

In boys with prune belly syndrome the abdomen is protuberant because of the decreased or
absent abdominal muscles and the lower part of the rib cage in front may flare out a little,
causing an abnormal profile.  The absence of the muscles of the abdomen causes
surprisingly little functional problem.  Some boys as they get older wear an elastic support
garment around the abdomen to hold it in so that it looks better and clothes fit better.   It also

offers some protection to the abdominal organs.

Vesicoureteral reflux (VUR) involves the two-way flow of the urine up and down the ureters,
and they should be a one-way down system.  The ureter inserts into the bladder down near
its base such that the muscle of the bladder wall does not allow the urine to flow out of the
bladder and back up the ureter towards the kidney.  This insertion can be abnormal and
allow different degrees of back flow, which are graded I to V, depending on severity.  When
grades I to III happen in an infant or young child, the likelihood is that with time and
increasing maturity the problem will resolve itself.  Grade IV reflux occasionally
spontaneously resolves, and grade V reflux virtually never resolves spontaneously.

Grades IV and V usually need surgical correction.

Megaureter and megacystis are two problems that often occur together. Megaureter is the
congenital dilatation of all or a portion of the ureter without obstruction.    Megacystis means
enlargement of the bladder, which may affect function in that the bladder may be slow to
empty, and in some cases this may mean that intermittent catheterization is needed to

empty the bladder.  Both megaureter and megacystis are frequently associated with renal
dysplasia.

Cystic diseases

Most of the cystic diseases occur in both kidneys, but in the great majority of cases a
multicystic dysplastic kidney is confined to one kidney.    In this disorder, the kidney is
worthless and without any functioning filters and the ureter is atretic, meaning that it stops
part way down to the bladder, so is incomplete.    The "kidney", and I put it in parentheses

since it is not really a kidney, as we know it, since something went awry very early in its
development and it became a group of cysts rather than a kidney.  A cyst is a fluid filled
round bag-like structure.    In most cases the other kidney is normal and grows larger than a
normal kidney to make up for the fact that there is only one functioning kidney.     Two
defects do occur in the functioning kidney with enough frequency to be of concern.    The first
is vesicoureteral reflux (discussed previously in this article) so every infant found to have a
multicystic dysplastic kidney should have a VCUG, a voiding cystourethrogram to look for
reflux.  The second is ureteropelvic junction obstruction, also discussed previously, which, if
present, will have been noted on the ultrasound examination that was done to pick up the

multicystic dysplastic kidney.

A multicystic dysplastic kidney is often picked up on prenatal ultrasound, then confirmed on
ultrasound after the baby is born.   Since the bags of cysts can be confused with severe
dilatation of the kidney related to a severe ureteropelvic junction obstruction, the doctor may
want to look at the kidneys with a nuclear renal scan to differentiate between the two.   To

do this scan, the infant is given an IV injection of a radioactive substance that shows blood
flow into the kidney and is filtered by the kidney.   The multicystic dysplastic kidney has no
blood flow and no function, but the kidney with obstruction has blood flowing through it.   The
amount of radioactivity given is no more than one receives getting a standard X-ray.

So the infant felt to have a multicystic dysplastic kidney generally has two tests done, a
VCUG and a nuclear renal scan.   If an associated problem such as reflux or UPJ
obstruction is found, they are treated as noted above, with the need for treatment being
related to the severity of the problem.   The multicystic dysplastic kidney itself is followed
with serial ultrasound examinations at intervals over time.  Most of the time the cysts shrink

progressively and after a few years the end result is a small nubbin of scar tissue which
causes no problem   If the cysts do not shrink, which happens in a few cases, then the
kidney may need to be removed surgically.

Most of the time when cystic kidney disease is mentioned, polycystic kidney disease (PKD)
comes to mind.   There are two types of polycystic kidney disease are:   autosomal
dominant disease (ADPKD), formerly called adult PKD, and autosomal recessive PKD.  
Let me give you a mini-genetics lesson to help explain the two diseases.    Each of us has
a set of genes from each parent, so we have a double of every gene.  In diseases where the

trait is dominant, getting an abnormal gene from either parent gives you the disease.   So in the
typical case of a parent with a dominant disease, the parent got one normal gene from one
parent who was healthy and an abnormal gene from a parent with the disease.      So the child

of that parent has a 50-50 chance of getting the disease, depending on whether he got the
diseased gene or the healthy one.  Having one gene with the disease means you have the
disease.   In the case of parents of a child with a recessive disease, both parents have one normal

and one abnormal gene, and the normal, rather than the abnormal gene, predominates.    A child of
such parents has a one out of two chance of getting the abnormal gene from each parent, or a one
out of four chance of getting an abnormal gene from both parents.  Having both genes of the set
abnormal gives the disease. So parents of the child with ARPKD are healthy and do not know that
they carry the disease until they have a child with the disease.   A parent who has ADPKD knows
that there is a 50-50 chance, one out of two of each child born to that parent having the disease.
There have been three different gene defects found that cause ADPKD.    The gene for ARPKD is
being characterized and is on chromosome 6.

ADPKD is a fairly common cause of kidney failure in adults.    The cysts of the disease may be seen
on a prenatal ultrasound of the developing fetus, but in most cases, the number of cysts in the
kidneys increases slowly and kidney function is normal for most or all of childhood and
into adulthood.   The cysts can start to form in the kidneys in the fetus, or the kidneys may be

normal without cysts until as late as 30 years of age.    At some age cysts start to form and more
and more cysts progressively form in both kidneys.   There is a tendency of the pattern
of development of cysts to be the same in members of a family, but it is a tendency and not a rule.

As more and more cysts form often hypertension becomes a problem, and then after hypertension,
gradual decrease in kidney function.   The age at which kidney failure occurs and dialysis and
transplantation are needed varies from infancy to old age.  A few people die in old age with cysts in
the kidneys but with the kidneys working well enough that they do not need dialysis or
transplantation.   The average age of kidney failure is about 50 years old.

ARPKD is a very uncommon disease.   The baby with ARPKD has many small cysts all throughout
the kidneys right from the time that they form in utero.   The kidneys are larger than normal because
of the cysts, sometimes very large.   In the most severely affected children the kidneys never work
and never make urine.    This leads to a lack of normal lung development, since lung development is
dependent on breathing amniotic fluid, and amniotic fluid comes from baby urine. Without lung
development the baby dies of lack of oxygen soon after birth.   In a few cases, fluid has been
successfully injected into the uterus around the baby every few days for many weeks during
pregnancy, resulting in lung development.    This is tricky and may also result in stimulating labor, so
that the baby is born quite prematurely with poor lung function and dies

Among the infants with the disease who survive, the severity of the kidney disease and the age at
which dialysis and transplantation are needed varies between infancy and adolescence.

Most children with ARPKD also have a condition known as congenital hepatic fibrosis, which means
that there are threads of scar tissue through the liver.  This usually doesn't interfere with liver function
but may obstruct the flow of blood to the liver through the portal vein from the intestines.    This leads

to back up of blood in the spleen and in veins of the esophagus and can cause serious problems, too.
Backup of blood in the spleen means that platelets get trapped in the spleen and so are not in the
general blood circulation.   Platelets are important in the circulation as agents of clotting.   Meanwhile
the blood in the veins of the esophagus is under increased pressure, so that the veins often burst and
bleed.   With low platelets, the esophagus may bleed and bleed if the veins burst.    To prevent this
kind of bleeding, some children with ARPKD need surgery to shunt blood flow away from the
esophagus while those with a more severe form of hepatic fibrosis also need a liver transplant as well

as a kidney transplant.

Another very rare form of bilateral renal cystic disease isglomerulocystic disease, where the cysts
are in the glomeruli, the filters of the kidneys.   This usually leads to kidney failure early in life.

Other diseases which include bilateral (both kidneys) cystic kidney disease in addition to other
health problems include:

* Tuberous sclerosis
*  Von Hippel Lindau syndrome.

Metabolic diseases

Metabolic diseases are those diseases where there is a chemical problem in certain or all cells
of the body.  Most commonly they happen when an enzyme (protein that breaks down a specific
chemical) is missing.  That can result in the accumulation of that substance in cells, causing all
sorts of problems.    In some types of metabolic disease a substance accumulates in cells for

unknown reasons.   In others, an important cellular biochemical process is abnormal.

Cystinosis is a rare disease where cysteine, an amino acid (amino acids are the building blocks of
proteins) accumulates in the cells of the body and causes lots of problems, including kidney failure.
These children clearly are ill as infants, since they grow poorly, are easily and frequently dehydrated,
and develop rickets.   The problem with the kidneys early in life is that they leak multiple substances
(potassium, bicarbonate, sodium, phosphorus, glucose and amino acids) from the blood into the
urine that should stay in the blood.  Some of these substances have to be given back as medication:
potassium, bicarbonate, sodium, and phosphorus.   The kidney also fails to activate vitamin D, so
the active form of vitamin D (calcitriol or dihydrotachysterol) must also be given as a medication.
As time goes on they develop kidney failure, and generally need kidney transplantation sometime
in childhood.

The condition where the kidney tubules leak potassium, glucose (sugar), phosphorus, bicarbonate,
and amino acids into the urine is called Fanconi syndrome.   Fanconi syndrome is seen in children
with cystinosis, Lowe's syndrome, and is rarely seen temporarily after administration of an antibiotic
from the antibiotic grown called aminoglycosides

Oxalosis is another rare disease.   In this disease the liver cells lack an enzyme (an active protein)
that breaks down oxalate, which is a compound made in the natural functioning of the liver cell.
Oxalate then accumulates, spills into blood, links with calcium, and calcium oxalate deposits in
the kidney and then in tissues all over the body. The kidney is first, since the kidney tries to get
rid of the excess calcium oxalate out of the blood by filtering it out, and in the process the kidney
is stopped up with calcium oxalate,    Deposits of crystals are found throughout the kidney and
stones form also.   When there is little or no enzyme in the liver to break down oxalate, the
problems ensue quickly in infancy and complete kidney failure can be seen in the first year of life.
If there is some enzyme, but not enough, then kidney failure can ensue later in childhood.

In the child with oxalosis, putting in a new kidney alone is not the solution, since the new kidney
will be stopped up with calcium oxalate.   A liver transplant must be done to give the child the
enzyme to handle oxalate, and then a kidney transplant can be done.    This is one of the
diseases that will be treated with gene therapy.  If the gene could be placed in the liver to tell
it how to break down oxalate, then there would be no problem, as the liver is otherwise normal.

Other metabolic diseases that may lead to kidney failure include:

Lowe's syndrome, the mitochondrial myopathies, particularly cytochrome C oxidase deficiency,
certain glycogen storage diseases, to name a few. All of these diseases are quite rare.

Syndromes

Prune belly syndrome is one of the commoner syndromes seen as a congenital renal disease.
It is described above.

VATER Syndrome stands for vertebral, anal, tracheal, esophageal, and renal and radial (the
bigger bone of the forearm) abnormalities.   This group of abnormalities tends to occur together.
The kidney abnormalities can include hypoplasia, dysplasia, obstruction.    The child can be born
with one or two kidneys.  Not every child with this syndrome has every part of it.   The child may
also just have one kidney, and it may be normal or abnormal.   There are also related syndrome
like VACTERAL Syndrome.

LOWE'S Syndrome is a syndrome that includes metabolic (cellular biochemical) abnormalities.
The kidneys start out with partial or complete Fanconi syndrome.  In addition the children have
developmental delay and eye problems, usually cataracts that are large and present at birth.

Conclusion

I have tried to give an overview of the diseases of the kidney that occur as birth defects.
Individual cases can vary from the usual case, so remember that when reading about the
individual diseases.   Each child is a little different.   But parents of children with kidney
disease are hungry for knowledge about their children's diseases, and I hope that this can fill that

need to some degree.

Susan B. Conley, M.D.
Chief, Section of Nephrology
St. Christopher's Hospital for Children