The clinic door opens, letting your next patient in.
You are pleasantly surprised to see Gabriela, a normally bubbly seven-year-old who goes to school with your daughter. She is accompanied by her mother, Mrs. Morales.
"Hi, doctor! My legs are real thick. I don't like them, they're not pretty anymore", says the little girl sulkily.
Her mother explains - "Her legs began to swell around a week ago. It was barely noticeable at first and I didn't think much of it, but it seems to have gotten much worse now."
Gabriela is 123 cm tall (82nd centile) and weighs 26 kg (77th centile).
There was no history of fever or joint pain. Her medical history is unremarkable, save for "colds once or twice a year", and she is currently not on any medications.
On examination, her blood pressure is 110/70 mmHg, while her heart rate is 78 bpm. You find no rashes on her face or elsewhere, and the abdominal exam is unremarkable.
Her lower limbs demonstrate a symmetrical, pitting edema.
You request several investigations, of which the results are as follows:
Hb: 12.6 g/dL (11.5-15.5)
Hct: 38% (35-45)
WBC: 10,900 /mm3 (5,000-14,500)
Neutrophils: 66% Lymphocytes: 31%
Plt: 200,000/mm3 (150,000 - 450,000)
Serum Creatinine: 0.65 mg/dL (0.0-0.7 mg/dL)
Serum Albumin: 18 g/L (35-55)
Urinalysis: 3+ proteinuria; no hematuria or cell casts.
It is now clear that Gabriela has nephrotic syndrome. You admit her to your ward for treatment and monitoring.
Following admission, you order a morning urine sample for proteins and creatinine (which is 2.5 mg/mg) and a 24-hour urine protein (later found to be 6.2g), which confirm your diagnosis.
You also start investigating Gabriela for secondary causes of nephrotic syndrome, and recommend a low-sodium diet, and water restriction.
At this point, you are interrupted by a very anxious Mrs. Morales.
"¡Dios Mío, doctor! My friend Miriam's brother had this too, and they had to take out part of his kidney for a test. Will you do the same to Gabriela?"
"Calm down, Mrs. Morales. Are you talking about a renal biopsy?", you ask.
"Yes, yes! That's the one", she replies.
Mrs. Morales calms down when you explain that a biopsy is not indicated right now.
Subsequently, you start Gabriela on 50 mg/d oral prednisone.
You also inform her mother of the importance of immunization, and ensure that Gabriela has been adequately vaccinated.
Once the edema subsides and her condition stabilizes, you discharge the little girl, letting her mother know that she must be followed up regularly.
A week later, Gabriela shows up for her appointment. "Doctor, I feel so much better now!", she says.
You notice that she remains free of edema.
Gabriela's labs reveal a serum albumin of 22 g/L and a 24h-proteinuria of 3.8 g/L.
Her renal functions remain stable as well, with a serum creatinine of 0.66 mg/dL.
Some time later, Gabriela returns for her third follow-up. However, she is not her usual cheery self.
You learn that the swelling returned yesterday but is different from the last time.
"Doctor, my left leg is much fatter than my right leg!", she says morosely.
You examine her to find that the entire left leg shows significant swelling, with no obvious flushing or tenderness, while her right leg is normal. The girth of the left calf is 3.5 cm more than that of the right calf.
Although the dorsal arterial pulse is palpable bilaterally, it is weaker on the left.
The rest of the examination is unremarkable, while her complete blood count shows no abnormalities, and C-reactive protein levels are normal.
Serum albumin levels remain stable at 23 g/L.
You decide to readmit Gabriela.
Having confirmed your clinical diagnosis, you now need to figure out the best course of treatment.
You initiate treatment with subcutaneous low-molecular-weight heparin, while simultaneously monitoring anti-factor-Xa activity, as a measure of efficacy.
You also start Warfarin, in anticipation of converting her to parenteral anticoagulation in several days.
Five days pass, and the leg swelling has diminished significantly. You request a follow-up doppler, which confirms that the thrombus has resolved.
Subsequently, you stop Heparin, and discharge the little girl on Warfarin therapy.
It has now been 8 weeks since the initiation of corticosteroid treatment, and Gabriela has yet to achieve even partial remission.
"Mrs. Morales, it appears that your daughter has a steroid-resistant variety of nephrotic syndrome. I'm afraid we can't avoid a renal biopsy any longer."
"I understand, doctor. I'll talk to Gabriela", she sighs.
You go on to explain that Gabriela needs to be on "blood thinners" for another 4 weeks, following which you can tail them off, and perform the biopsy safely.
True to her word, one month later, Mrs. Morales brings Gabriela back to your hospital, and a renal biopsy is performed.
The specimen contains 20 glomeruli, eight of which show segmental obliteration of the capillary loops with an accumulation of extracellular matrix, hyaline cells in the sclerotic regions, and adhesions to the Bowman's capsule. The interstitium and arterioles are unremarkable.
There is no staining upon immunofluorescence studies.
You are now quite certain that Gabriela has focal segmental glomerulosclerosis (FSGS).
As you know the underlying renal pathology now, you re-evaluate her treatment, supplementing the ongoing prednisone with oral cyclosporine and enalapril.
At the 4-week follow-up, Gabriela is in partial remission for the first time; her serum albumin has risen to 32 g/L and urine proteins are now 1.5 g/L.
However, Mrs. Morales is still unsettled.
"Doctor, my daughter's serum triglycerides are 4.5 mmol/L. Isn't that quite high? Do we need to do something about this?"
You explain that dyslipidemia is quite common in children with nephrotic syndrome.
Unless the hypertriglyceridemia is very severe (> 11.3 mmol/L), there is no need for intervention other than lifestyle changes such as dietary modification, weight reduction, and increased physical activity.
Mrs. Morales admits that Gabriela is very fond of fries and soda. "I'll watch what she eats and make sure she plays outdoors every day", she says, sounding relieved.
Some time later, Gabriela achieves complete remission. You gradually taper the prednisone and cyclosporine doses.
Six months later, she is maintained on just 10 mg of enalapril daily.
A few more weeks pass, and you see Gabriela at your daughter's parent-teacher meet, contentedly painting a picture.
Your heart fills with joy when you see that it shows her all grown up, wearing a doctor's white coat.
You are about to tell Mrs. Morales, that yes, you plan to perform a biopsy on little Gabriela.
Before you open your mouth, however, you realize that a renal biopsy would be premature at this stage, especially for a child of Gabriela's age.
"Let's start with some corticosteroid tablets first", you say to the very happy little girl.
You suspect that Gabriela is suffering from an infection, and prepare to start her on intravenous cefuroxime.
The nurse, however, seems hesitant.
"Doctor, she doesn't have a fever. Are you sure it's an infection? A child who was here last week had a venous thrombosis and presented quite similarly."
You realize that she is right and thank her. A thrombotic complication is far more likely, and should definitely be excluded first.
Gabriela takes your advice, and stays in bed continuously.
Later that afternoon, you receive a call from the head of the department.
"Gabriela is severely dyspneic. We suspect a pulmonary embolism. Was it you who ordered strict bed-rest? Wasn't she administered anticoagulants at all?"
"I think it would be best if you don't manage this case anymore!", he continues, before cutting the line off ....
You contact the surgical team and inform them of your plans. However, they seem rather unenthusiastic about a thrombectomy.
"We don't see a need for surgical intervention right now. Why don't you try managing her medically?"
You realize this makes good sense - a medical intervention is far more appropriate.
You're about to suggest a change in medication, but realize that a renal biopsy is the best way forward, given that you're dealing with steroid-resistant nephrotic syndrome.
You explain the situation to the mother and daughter.
You begin to suggest the addition of lipid-lowering drugs to her regimen, when it dawns upon you that this is, in fact, unnecessary.
Lipid abnormalities in nephrotic syndrome are amenable to diet and lifestyle modifications ...
The phone rings - it's the radiologist, sounding concerned.
"Why expose this child to radiation, when a doppler would be quite sufficient?", he asks.
Realising that he is correct, you quickly arrange for a doppler scan.
The doppler scan reveals a left femoral vein thrombosis, confirming your suspicions.