Nephrotic
Syndrome
INTRODUCTION
Wee
Seng is a 19-year-old Chinese young man with a past history of nephrotic
syndrome now presenting with progressive bilateral lower limb edema of one-week
duration.
HISTORY
Presenting complaint
Wee
Seng first noticed bilateral swelling of his lower limbs a week ago which
gradually progresses till the mid-shin level. He was well previously with no
fever, cough, headache, gastrointestinal upset or other illnesses. (exclude
intercurrent illnesses and signs of hypovolaemia) He has no dypsnoea or
decreased effort tolerance. (exclude congestive heart problems) The edema is
localized to the lower limbs only and is not present elsewhere in the body. He
complains of oliguria and passing of frothy urine without haematuria or dysuria.
He did not complain of any lethargy, anorexia, abdominal pain or headache.
Past medical history
Wee
Seng was first diagnosed with nephrotic syndrome at 5 years of age after an
episode of fever and generalized swelling of the entire body. He was commenced
on prednisolone 40mg per day but suffer a relapse within 2 months of initial
response (frequent relapser). A year later, he was commenced on cyclosporin A
and mycophenolate. The prednisolone was increased to 60 mg per day when he was
8. Steroid treatment was stopped between October 1999 and July 2001 during a
period of 1 year 10 months as he was responding well to the other two drugs. He
had 5 episodes of hospitalizations between now and when he was first diagnosed
for a relapse manifesting as generalized edema, abdominal pain and oliguria. He
stayed in the hospital for no more than a week during each admission, was given
IV albumin and discharged later without any complications or sequelae. He is
currently on follow-up with Prof Yap once a month during which his blood will be
drawn to check the serum creatinine level.
He
has 3 renal biopsies done in 1989, 1996 and 2002. The biopsy done in 1996 showed
he had minimal change nephrotic syndrome while the latest biopsy showed focal
sclerosis possibly due to cyclosporin A toxicity.
Complications
of steroid treatment are bilateral cataracts diagnosed in 1990 which were
removed in 1992; short stature and delayed puberty. He does not have frequent
respiratory or skin infections.
Birth
and developmental history are unremarkable.
Present treatment
He
is currently on frusemide (40 mg), spironolactone (25 mg), cyclosporin A (110
mg), prednisolone (60 mg) and mycophenolate (1000 / 750 mg). He is compliant
with taking his medications. He does daily home urine testing with a urine
dipstick for presence of albumin whose result he will record in a logbook. Prof
Yap has informed him she will be adding a new drug to his present regimen soon
but he was not able to recall the name of the drug. He is negative for hepatitis
B and C. He is advised to be on salt and fluid restriction, but there is no
special diet prescribed for him.
Social
Wee
Seng is now studying Logistics at Ngee Ann Polytechnic. He missed school once a
while in a few months due to his medical appointments and sometimes for a few
days at a go due to hospital admissions, but other than these occasional
episodes, he did not miss school much and was generally able to keep up with his
school work. He has no restriction in lifestyle and is able to engage in sports
and strenuous activities as his peers. He does not smoke or drink alcohol.
Finance
Both
his parents work as factory workers. He has an older sister at 23 years of age
who is now working in the air force. His mother is currently paying for his
medical bills which amounts to 400 dollars monthly after subsidies from MSW. He
feels that the amount is too much and he hopes to start working soon to earn
money to pay for his own medical expenses.
Family
There
is no family history of chronic renal failure, hypertension or other renal
disease.
PHYSICAL EXAMINATION
Signs to look out for in this patient
Wee
Seng has a history of nephrotic syndrome and is currently on steroid and
cyclosporin treatment. From the history itself, it appears that Wee Seng is now
suffering from a relapse of the nephrotic syndrome. This may be due to
under-treatment or unresponsiveness to treatment. Though rare, a small
percentage of patients with nephrotic syndrome do develop end-stage renal
failure. They are also susceptible to infection with encapsulated bacteria (e.g.
Pneumococcus, Haemophilus, E.coli), including cellulitis, peritonitis and
urinary tract infection.
During
the physical examination, I will look out specifically for signs of:
1)
Renal failure and its complications.
2)
Signs of infections. e.g. fever.
3)
Complications of steroid and cyclosporin A therapy, e.g. hypertension.
General Inspection
Wee
Seng is alert, comfortable at rest and able to respond to speech in full
sentences. He has no dysmorphic features. His height is 160cm which is below the
3rd percentile of his age group while his weight is 50kg at the 10th percentile.
He is not pale or jaundiced and his complexion is not sallow. He is well
hydrated and nourished. There were no signs of easy bruising such as ecchymoses.
Vital signs
His
vital signs are stable:
Pulse
rate: 80 / min.
Respiratory
rate: 14 / min
Temperature:
36.7C
Blood
pressure: 120 / 70 mmHg
CVS and Respiratory review
The
JVP is not raised. The apex beat is not displaced and no pathologic heart sounds
or murmurs were heard. The lung fields are clear.
GI review
The
abdomen is symmetrical, moves with respiration and is not distended. There are
no surgical scars, superficial veins, striae or other forms of interventions.
There is no organomegaly, ascites, sacral or genitalia edema. Renal punch is
negative.
Steroid toxicity
Besides
his short stature and bilateral cataracts which were removed in 1992, there are
no other signs of steroid toxicity such as Cushingoid facies, truncal obesity,
striae, easy bruising or proximal muscle wasting.
Lower limb
There
is a pitting bilateral lower limb edema till the mid-shin level. No edema is
detected elsewhere in the body.
SUMMARY
Wee
Seng is a 19-year-old Chinese young man with a past history of nephrotic
syndrome and complications of steroid treatment now presenting with a gradual
onset of bilateral lower limb edema of one-week duration associated with
oliguria and proteinuria. He is currently on frusemide, spironolactone,
prednisolone, cyclosporin A and mycophenolate.
Differential diagnoses
1)
Relapse of nephrotic syndrome
2)
Early onset of renal impairment.
INVESTIGATIONS
I
would conduct to the following investigations to confirm my diagnosis and to
exclude other causes:
1)
Urinalysis: proteinuria, haematuria.
2)
FBC: anaemia, raised WBC indicating possible underlying infection.
3)
U&E: albumin level (degree of hypoalbuminaemia), urea and creatinine
level (renal function).
I
would like to follow-up with a renal ultrasound to assess the renal status of
the patient.
Laboratory results obtained on 20 July 2002
WBC:
8.64 (4.00 � 11.00 x 109/L)
HB:
13.4 (10.5 � 13.5 g/dL)
Platelets:
446 (130 � 400 x 109/L)
Urea:
14.0 (2.5 � 7.5 mmol/L)
Sodium:
137 (135 � 150 mmol/L)
Potassium:
4.1 (3.5 � 5.0 mmol/L)
Chloride:
105 (98 � 107 mmol/L)
Carbon
dioxide: 30 (22 � 31 mmol/L)
Creatinine:
99 (65 � 125 mmol/L)
Glucose:
5.1 (4.0 � 7.8 mmol/L)
Anion
gap: 16 (10 � 18 mmol / L)
Albumin:
15 (38 � 48 g/L)
ALP:
137 (40 � 130U/L)
Calcium:
1.91 (1.13 � 1.32 mmol/L)
Phosphate:
1.54 (0.85 � 1.4 mmol/L)
Analysis
Wee
Seng�s serum albumin level is low at 15 g/L. His creatinine level is within
the normal range though his urea level is slightly raised. His serum calcium and
phosphate levels are raised too. He is not anaemic and his WBC levels are not
raised. His sodium and potassium levels are within normal range.
QUESTIONS
As a HO, what will be your immediate management of the patient?
�
Give IV albumin and frusemide.
�
Resume on steroid therapy.
What is the definition of nephrotic syndrome?
�
Proteinuria: above 40 mg/m2/hr; or urinary protein (mg/dL) /
creatinine (mg/dL) ratio of 2.0 or more.
�
Hypoalbuminaemia: serum albumin less than 25 g/L.
�
Hypercholesterolaemia.
�
Edema.
What are the definitions of specific subgroups on steroid therapy?
�
Frequent subgroups: children with two or more relapses within first 6
months of initial response, or more than four relapses in 12 months.
�
Steroid-dependent: relapse while on prednisolone or within 2 weeks of
ceasing prednisolone.
�
Steroid-resistant: failed response after 4 � 8 weeks of 2 mg/kg/day
prednisolone.
What are the complications of nephrotic syndrome?
�
Infection: children with NS have increased susceptibility to infection
with encapsulated bacteria including cellulitis, peritonitis and urinary tract
infections. This is due to multiple factors, including urinary loss of
immunoglobulin, loss of factor B of alternate complement activation path, loss
of transferrin plus the burden of steroid therapy.
�
Treatment: steroids often cause Cushingoid effects, but poor growth is
the most common complication. Cyclophosphamide causes bone marrow suppression,
increased risk of viral infections, gonadal toxicity and secondary tumors.
Cyclosporin A can cause nephrotoxicity, hypertension, gingival hyperplasia and
hirsutism.
�
Thrombosis and embolism: NS can be associated with hypercoagulability,
due to increase in plasma fibrinogen and clotting factors V and VIII and
decrease in plasma antithrombin III. This leads to increased risk of major
vessel thrombosis.