Clinical picture, whereby kidneys leak protein, leading to hypoalbuminaemia. This results in oedema, particularly noticeable around the eyes, but also peripherally and as ascites. Mechanism is thought to be loss of negative charge on basement membrane. Usually idiopathic, mostly Minimal change glomerulonephritis. Otherwise can be focal segmental gomerulosclerosis (10-20%), secondary (eg HSP, SLE).

Mostly boys, 2 to 1 ratio. 5% go on to Chronic Renal Failure. Hypertension unusual so consider non minimal change glomerulonephritis if hypertensive at presentation. Classic features are:

• Urinary protein:creatinine (PCR) more than 200mg/mmol (0.2g/mmol), and usually more than 500 (early morning sample is more reliable)
• Strict definition is protein loss more than 1g/m2/d but noone collects 24hr urines anymore!
• Low albumin (<25g/l)
• Oedema
• High Hb
• Low Calcium

Check FBC, U&Es, creat, albumin, LFTs, varicella IgG (to check status before starting steroids), cholesterol, HBV/HCV, C3/4. Urinalysis, urine culture, protein:creatinine ratio. Urine sodium <10mmol/l indicates hypovolaemia.

Complications

• Oedema – if symptomatic, give albumin (see below).
• Intravascular depletion (despite massive oedema) – BP not useful as paradoxical hypertension may be seen; instead, judge by heart rate, perfusion, urinary sodium (<10 = hypovolaemia).
• Infection – at risk due to loss of complement and immunoglobulins, esp cellulitis, primary pneumococcal peritonitis. Consider antibiotic prophylaxis with penicillin V if severe proteinuria.
• Risk of thrombosis – loss of anti-thrombin III and other anti-coagulants, +/- hypovolaemia.  Esp renal vein thrombosis (pain, haematuria, worse renal function, palpable kidney. Do USS)
• Hypocalcaemia – adjusted or ionised value.
• Hyperlipidaemia  – characteristic, so part of diagnosis!  Only seen during flare, so only needs treated if other risk factors or frequent relapses.

Those with minimal change tend to be responsive to steroids and do not need a biopsy. But if atypical or unresponsive (allow 4 weeks) then biopsy indicated; or if:

• Age under 1 yr, over 10yrs
• Hypertensive
• Elevated creatinine
• Macroscopic haematuria (microscopic sometimes seen with minimal change)

Treatment

• Steroids – Cochrane suggests at least 3 months.  PREDNOS trial did not find benefit from 16 weeks cf 8 (median time to relapse 139 vs 87 days. RHC protocol is:
  • 60mg/m2 for 4 weeks (max 80mg)
  • 40mg/m2 alt days for 4 weeks (max 60mg)
  • Wean by 5-10mg/m2 weekly for a total of 12 weeks treatment
• Low salt diet, fluid restriction eg 50-70%.  Beware thirst driving consumption of wet foods to cheat restriction! Or drinking with tooth brushing, showering.
• Albumin: not for low albumin itself, but for hypovolaemia or severe, symptomatic oedema (esp scrotal, where skin starts to break down). If shock, give 4.5% albumin as resuscitation fluid (without diuretic!). Otherwise, 1g/kg 20% albumin (=5ml/kg) over 4-6 hours, with IV frusemide (2mg/kg) mid-infusion.
• Diuretics – not usually regular.  Some need, metazolone and spironolactone are synergistic with frusemide.
• Varicella protection – check serology at diagnosis.  Vaccinate when on low dose; consider vaccinating close contacts.  May need post exposure prophylaxis if susceptible.

Remission defined as 3 consecutive days neg or trace protein. Most remit within 1 month, refer if no response by then – allow 8/52 before labelling steroid resistant .

Prognosis

1/3 no relapse, 1/3 infrequent, 1/3 frequent. Nephrotic relapse defined as 3+ protein for 3 days, but also refer if 2+ for 7 days. Treat relapse with prednisolone 2mg/kg until proteinuria suppressed for 3 days, then taper over 4-8 weeks.  In frequent relapsers (ie 2+ within first 6 months, or 4+ within any 12 month period), may become steroid dependent (ie relapses during weaning) so consider Levamisole (2.5mg/kg alternate days, SE reversible neutropenia), cyclophosphamide, ciclosporin etc.

As with any condition requiring high dose steroids, remember vaccinations, varicella, bones.

Children with steroid-resistant nephrotic syndrome who are homozygous or compound heterozygous for NPHS2 (podocin) mutations do not respond to standard steroid treatment and have a reduced risk for recurrence of nephrotic syndrome (with focal segmental glomerulosclerosis) after renal transplantation. Available through UK Genetic Testing Network for children with nephrotic syndrome that is resistant to treatment with steroids, presents in the first 3 months of life or has a histological picture of focal segmental glomerulosclerosis on renal biopsy.