1. A 2-year-old male toddler weighing 15 kg presented with a history of fever
which is high grade continuous type associated with chills and rigors. The
patient had cough (wet cough more in amount) whitish colour sputum not foul
smelling. Swelling over face was present which initially started around peri-
orbital (which is more during morning) and gradually progressed to face which
decreases by evening. The toddler had decreased urine output (oligouria).
The baby was delivered by C-section and weighed 2.75 kg after birth. On
examination pitting type of oedema was present over lower limbs and swelling
over face was present.
1. What is your most likely diagnosis?
- Nephritic on nephrotic syndrome
o Edema- suggestive of renal cause start at periorbital@morning
and generalised through face and relive by evening
o Oliguria- feature of nephritic
o Precipitated by infectious cause (probably lung infection-
pneumonia) as child have fever, chill, rigor, wet cough with
whitish non purulent sputum
2. Based on these clinical presentations, nephrotic syndrome was suspected and
specific laboratory testing was performed to establish diagnosis.
2. List Five (5) important investigations to establish diagnosis.
The urine dipstick indicated for proteinuria, no signs of haematuria.
Blood testing showed a significantly depressed C3level of 0.638 g/L (reference
interval 0.9- 1.8 g/L) and hypoalbuminaemia of 2.0 g/dL (reference interval 3.5-
5.5 g/dL) indicating nephrotic syndrome (NS).
The urine creatinine level was – 620 mg/L (reference interval 400-3000mg/L)
and APTT was prolonged- 47.7 Sec (reference interval 24-30 Sec).
Serologic testing for active infections: anti-streptolysin-O titer was positive. The
lipid levels were markedly increased as outlined .
The urine protein/creatinine ratio was found to be high (7.3). Mantoux test was
done before administration of steroids which was negative.
DISCUSSION
The hallmark of INS is massive proteinuria, leading to decreased circulating
albumin levels. The initiating event that produces proteinuria remains unknown.
However, strong evidence suggests that INS, at least in part, has an immune
pathogenesis.
The classical explanation for oedema formation is a decrease in plasma oncotic
pressure, as a consequenceof low serum albumin levels, causing an
extravasation of plasma water into the interstitial space. The resulting
contraction in plasma volume (PV) leads to stimulation of the renin angiotensin-
3. aldosterone axis and anti-diuretic hormone secretion. The resultant retention of
sodium and water by the renal tubules contributes to the extension and
maintenance of oedema.
A more recent theory of oedema formation posits that massive proteinuria leads
to tubule-interstitial inflammation, release of local vasoconstrictors and
inhibition of vasodilation. This leads to reduction in glomerular filtration rate
and sodium and water retention4.
INS is accompanied by disordered lipid metabolism. Apolipoprotein (apo)-B–
containing lipoproteins are elevated, including very-low-density lipoprotein
(VLDL), intermediate-density lipoprotein (IDL), low-density lipoproteins
(LDL), with resultant increases in total cholesterol and LDL-cholesterol.
Elevations in triglyceride levels occurwith severe hypoalbuminemia. Also
contributing to the dyslipidemia of INS are abnormalities in regulatory
enzymes, such as lecithin-cholesterol acyltransferase, lipoprotein lipase, and
cholesterol ester transfer protein (4,5).
Nephrotic syndrome is a hypercoagulable state; the increased risk of thrombosis
can be attributed to two basic mechanisms:
1. urine losses of antithrombotic proteins and
2. increased synthesis of prothrombotic factors.
Abnormalities described in INS include decreased antithrombotic factors and
increased synthesis of pro-thrombotic factors (6).
Risk of infection may be increased in INS because of low immunoglobulin IgG
levels, which do not appear to be the result of urinary losses. Instead, low IgG
levels seem to be the result of impaired synthesis, again pointing to a primary
disorder in lymphocyte regulation in INS. The medications used to treat INS,
such as corticosteroids and alkylating agents, further suppress the immune
system and increase the risk of infection (7). The ASO test done in this patient
had a positive result.
TAKE HOME MESSAGES/LEARNING POINTS
In order to establish the presence of nephrotic syndrome, laboratory tests should
confirm nephrotic-range proteinuria, hypoalbuminemia, and hyperlipidemia.
A 3+ proteinuria on dipstick is highly suggestive of nephrotic syndrome to be
confirmed by appropriate laboratory work-up.
4. Serologic testing for active infections should be done as the patients with NS
are more prone to it.
Mantoux test [purified protein derivative (PPD)] should be performed prior to
steroid treatment to rule out TB infection.
Ahmed is a 8 year old male who is referred by his primary care physician with
the chief complaint of dark "cola colored" urine, facial puffiness and abdominal
pain for the past 2 days. He has no previous history of significant illnesses. He
was in a state of good health until 2 weeks ago when he had a sore throat and
fever. His sore throat and fever resolved. Over the past 2 days facial puffiness
has been noted, but no swelling on his hands or feet. He has had some
nonspecific abdominal pain that comes and goes which does not seem to be
related to eating or bowel movements.
There is no nausea or vomiting. No colicky abdominal pain. His urine is dark
brown and he has not been voiding as much as usual, only 2 times in the past 24
hrs. There is no urinary frequency, urgency, dysuria or foul smell to the urine.
His appetite has been pooralthough he is still drinking fluids well. He is also
complaining of some back pain in the flank area that he describes as a dull pain
that comes and goes and does not seem to be related to activity. His energy level
is down and he has not felt up to going to schoolfor the past 2 days.
He is also complaining of a dull generalized headache that has not been relieved
with acetaminophen. No history of trauma, medication use, bleeding from any
other site. No history of any rash, photosensitivity, joint pain, fever, weight loss
or seizuresThere is no previous history of hematuria. No history of passage of
stones through the urethra. Review of systems is unremarkable.No family
history of renal failure, hearing loss or renal transplant. He is immunised up to
date. Social history is unremarkable.
Exam: T 37, P 100, RR 20, BP 120/75, oxygen saturation 100% in RA. Height
and weight at 50th %tile. He is tired appearing but in no acute distress. Pupils
are equal and reactive. Optic disc margins are sharp. Sclera are white and
conjunctiva are clear. Mild periorbital is edema noted. TMs are normal. Throat,
oral mucosaand nose are normal.
His neck is supple without lymphadenopathy. Heart is regular without murmurs
No gallop rhthm. Lungs are clear, no basal crepitations. Abdomen is diffusely
tender (mild), without guarding or rebound. Bowel sounds are normal. No
organomegaly is noted.
His extremities are warm, with strong pulses. Capillary refill is less than 2
seconds. No edema is noted in his legs, feet or hands. No skin rashes or
5. impetigo scars are noted. His genitalia are normal. No scrotal edema is present.
Neurologic exam is normal.
1. State the most likely diagnosis.
2. What Investigations will you consider?
3. What is the significance of finding red cell casts in the urine?
4. What is the significance of finding white cell casts in the urine?
Summary
• On the basis of strong research evidence, the prevalence of poststreptococcal
glomerulonephritis (PSGN) is decreasing worldwide, although it still remains
the leading cause of glomerulonephritis in children. The overall decrease in
prevalence of PSGNhas been mainly driven by a significant decrease in
pyoderma seen in the last half-century, such that postpharyngitic PSGNis most
commonly seen in developed nations.
• On the basis of primarily consensus becauseof a lack of relevant clinical
studies, the latency period between streptococcalinfection and the development
of nephritis is a hallmark of PSGN, with this period lasting 1 to 2 weeks with
pharyngeal infections or 2 to 6 weeks with skin infections. Concurrent
infectious and nephritis symptoms should elicit further suspicion of other causes
of glomerulonephritis.
• On the basis of expert opinion, PSGN is one of a handful of nephritic disorders
with hypocomplementemia (low C3 level). The decrease in C3 is found in more
than 90% of PSGNcases and is typically seen earlier than an increase in
6. antistreptolysin O titers. Measuring C3 and C4 may also be helpful in the
evaluation of other causes of acute nephritis.