Steroid Resistant Nephrotic syndrome in Children

Definition

ISPN has defined steroid resistance as lack of response to 4 weeks of 2mg/kg/day of steroid treatment.

Initial Steroid resistance.

Late steroid resistance Response to immunisuppressive drugs Genetic mutations not found

Frustrating for parents

Will the remission occur?

When will it occur?

Financial burden

Leave from the work

Doctor shopping

Burn out

Frustrating for the treating physician

Sleepless nights- recurrent admissions

Grey Hair- Multiple OPD consultations

Competition

Fame & Blame- depend on response

Frustrating problem for the child

Edema

Infections

Recurrent Admissions

Multiple blood tests

Malnutrition

Side effects of drugs

Risk of renal failure

Initial SRNS

Genetic mutations

Primary NS

MCNS

FSGS

Mesangio PGN

Ig A, membranous, MPGN

SRNS

Kidney Biopsy must

C3, ANA, Ds DNA, ANCA, Hbs Ag, HIV leukemia, lymphoma, drugs, etc to be ruled out

Rule out infection

Genetic cause

Specific treatment for SRNS

CSA /Tacrolimus

Pulse steroids

Cyclophosphamide IV / Oral

Rituximab Choice of the initial therapy depends on physician’s preference & cost of therapy

What to choose

CSA suspension available

No hospitalization required for therapy

Trough level monitoring available

Short term side effects are temporary

Remission rate is high

Pulse steroids or pulse Cyclophosphamide needs admission.

Risk of infections very high

In edematous child giving fluids is difficult.

Long term irreversible complications like growth failure, cataracts, gonadal toxicity etc

Remission rate variable

Monitoring

Urine Protein / Creat spot ratio very useful to define complete, partial or no response

CBC

S.Albumin

S.Creatinine

S.Electrolytes

S.Cholesterol

Other blood tests as indicated

 

Symptomatic treatment

Mainstay of treatment

Treatment of edema

Salt restriction

Diuretics

IV Albumin- Resistant edema, Severe cellulitis, Hypotension / shock, Watery non infected diarrhea

Use of ACEI/ RB

Reno protection

Antiproteinuric

For control of Hypertension

Monitor S.Potasium, S.Creatinine & Hemoglobin

To stop it if child develops LM, vomiting, fever or refusal to feed

No soups, juices & coconut water

Recurrent infections

Monitor Ig G if low may need IV Ig G

Pneumococcal vaccine must be given

Treat Edema if present

Questionable role of prophylactic penicillins

Other measures

Non selective proteinuria Monitor S.Iron, S.Calcium, Ig G, TSH May need iron & Calcium supplements

Statins Better effect of CSA, Reno protection

Require 2gm/kg of proteins: No extra proteins

Prognosis of SRNS

Depends on remission

Children with complete remission have much better outcome

Persistent proteinuria, edema, malnutrition, infections, dyslipidemia, renal failure

Risk of recurrence after kidney transplant

Cyclosporine

Depends on remission

Dose 3-6mg/kg/day

Oral suspension available

Side effects: cosmetic, drug interaction, Nephrotoxicity, Hypomagnesemia, HT

Need of kidney biopsy on prolonged use

Tacrolimus

Remission rate 50-80%

Dose 0.1-0.2mg/kg/day

Drug level monitoring required

Available in capsule form

Side effects: Blood sugar, Neuron & Nephrotoxicity

Pulse Steroids

Remission rate 40-70%

Dose- 10-30mg/kg Ad, Weekly, fortnightly, monthly, bimonthly

Steroid toxicity: Growth, cataracts, ulcers, cataracts, osteoporosis, cushingoid facies,

Risk of infections: Very high Multiple hospitalizations

Cyclophosphamide

Remission rate Oral - 25-30% or IV- 40-65%

Better response in patients with partial remission

Side effects: Alopecia,hemorrhagic cystitis, leucopenia, vomiting, infections

Cyclosporine

Depends on remission