CLINICAL PHARMACY
NEPHROTIC SYNDROME
A. Definition
Nephrotic syndrome is the combination of
nephrotic-range proteinuria with a low
serum albumin level and edema.
Nephrotic-range proteinuria is the loss of 3
grams or more per day of protein into the
urine or, on a single spot urine collection,
the presence of 2 g of protein per gram of
urine creatinine.
B. Epidemiology
It primarily affects adults with an adult to
child ratio or 26:1. The condition is more
common in women than in men with a ratio
of 2:1. Higher rates of nephrotic syndrome
have been reported in children of Arabian
and Asian racial origins, in contrast to
Caucasian children.
C. Etiology
Common primary causes of nephrotic
syndrome include kidney diseases such as
minimal-change nephropathy,
membranous nephropathy, and focal
glomerulosclerosis. Secondary causes
include systemic diseases such as diabetes
mellitus, lupus erythematosus, and
amyloidosis. Congenital and hereditary
focal glomerulosclerosis may result from
mutations of genes that code for podocyte
proteins, including nephrin, podocin, or the
cation channel 6 protein. Nephrotic
syndrome can result from drugs of abuse,
such as heroin.
D. Pathophysiology
In a healthy individual, less than 0.1% of
plasma albumin may traverse the
glomerular filtration barrier. Controversy
exists regarding the sieving of albumin
across the glomerular permeability barrier.
On the basis of studies in experimental
animals, it has been proposed that ongoing
albumin passage into the urine occurs in
many grams per day, with equivalent
substantial tubular uptake of albumin, the
result being that the urine contains 80 mg
or less of albumin per day. However, studies
of humans with tubular transport defects
suggest that the glomerular urinary space
albumin concentration is 3.5 mg/L. [4] At this
concentration, and a normal daily
glomerular filtration rate (GFR) of 150 liters,
one would expect at most 525 mg per day
of albumin in the final urine. In health, urine
albumin is less than 50 mg/day, because
most of the filtered albumin is re-absorbed
by the tubules. Amounts above 500
mg/day point to glomerular disease.
The glomerular capillaries are lined by a
fenestrated endothelium that sits on the
glomerular basement membrane, which in
turn is covered by glomerular epithelium, or
podocytes, which envelops the capillaries
with cellular extensions called foot
processes. In between the foot processes
are the filtration slits. These three
structures—the fenestrated endothelium,
glomerular basement membrane, and
glomerular epithelium—are the glomerular
filtration barrier.
E. Risk Factors
1. Diabetes
2. High blood pressure (hypertension)
3. Being overweight
4. Age over 65
5. Family history of kidney disease
6. Preeclampsia (high blood pressure
and proteinuria during pregnancy)
7. Race and ethnicity: African-
Americans, Native Americans,
Hispanics and Pacific Islanders are
more likely to develop proteinuria
than those of European ancestry.
Abraham, Kristine D.
F. Detection
1. A urine test can check for the amount
of protein, blood and other things to
indicate kidney damage.
2. A blood test can indicate how well
your kidneys are working.
3. The doctor will also check for other
diseases that may be causing the
nephrotic syndrome.
4. Diagnosis may also require a kidney
biopsy.
G. Management
MEDICATION
Children
 Prednisone: For minimal-change
nephropathy
 Rituximab: an antibody against
B-cells, has proved an effective
steroid-sparing agent in children
with steroid-dependent
idiopathic nephrotic syndrome.
However, children dependent
on both steroids and calcineurin
inhibitors are less likely to
achieve drug-free remission with
rituximab. Rituximab may also
be used in children with steroid-
resistant disease.
Adults
 Prednisone: For minimal change
nephropathy.
 Prednisone with
cyclophosphamide or
mycophenolate mofetil: Should
induce remission in lupus
nephritis.
 Anti-inflammatory treatment: For
secondary amyloidosis with
nephrotic syndrome
 In membranous nephropathy,
management with angiotensin
blockade but without
immunosuppression can be
used for the first 6 months in
patients at low risk for
progression (ie, those with serum
creatinine level <1.5 mg/dL and
less than 4 g of proteinuria per
day). Patients with renal
insufficiency (serum creatinine
level >1.5 mg/dL) or those with
higher amounts of urine protein
are at risk for loss of kidney
function and should receive
immunosuppressive therapy. This
includes regimens that combine
prednisone with
cyclophosphamide or
chlorambucil. *Mycophenolate
mofetil is not helpful in
membranous nephropathy.
 Rituximab: effective in
membranous nephropathy in
adults, but controlled trials are
lacking.
DIET AND ACTIVITY
 The diet in patients with
nephrotic syndrome should
provide adequate caloric
intake and adequate protein (1
g/kg/d). Supplemental dietary
protein is of no proven value. A
diet with no added salt will help
to limit fluid overload. Fluid
restriction per se is not needed.
 There are no activity restrictions
for patients with nephrotic
syndrome. Ongoing activity,
rather than bedrest, will reduce
the risk of blood clots.
H. Reference
Nephrotic Syndrome. (2017, November
03). Retrieved May 1, 2018, from
4B-Pharmacy
2 CLINICAL PHARMACY LECTRURE

https://www.kidney.org/atoz/content/neph
rotic
Smith, Y. (2016, November 15). Nephrotic
Syndrome Epidemiology. Retrieved May 01,
2018, from https://www.news-
medical.net/health/Nephrotic-Syndrome-
Epidemiology.aspx
Nephrotic Syndrome. (2018, January 02).
Retrieved May 01, 2018, from
https://emedicine.medscape.com/article/
244631-overview#a2
Living with Kidney Disease. (n.d.).
Retrieved May 01, 2018, from
https://nephcure.org/livingwithkidneydiseas
e/proteinuria-resource-center/what-are-
the-risk-factors/

Abraham, Kristine D. 4B-Pharmacy