Approach to Nephrotic Syndrome

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Important Definitions for Nephrotic Syndrome

Nephrotic Syndrome: It is characterized by nephrotic range proteinuria (>40mg/m2/hr), hypoalbuminemia (serum albumin <2.5gm/dl), hyperlipidemia (serum cholesterol >200mg/dl) and edema.

Remission: Proteinuria <4mg/m2/hr OR urine albumin nil/trace for 3 consecutive early morning specimens.

Relapse: Proteinuria >40mg/m2/hr OR urine albumin >3+ for 3 consecutive early morning specimens.

Frequent Relapses: >2 relapses in initial 6 months, OR >4 relapses in any 12 months.

Steroid dependence: 2 consecutive relapses while on alternate day steroids OR within 14 days of its discontinuation.

Steroid resistance: Failure to achieve remission with 2mg/kg/day of prednisolone for 6 weeks.

Investigations :

24 hour urinary protein estimation

R/E urine, C/S urine

CBC with PBS

S. Total protein and albumin

S. Cholesterol

S. Urea and creatinine

Mantoux test

HIV, HBsAg, Anti-HCV

Chest X-Ray (PA)

USG, KUB,  Renal Artery Doppler

MANAGEMENT

Steroid Sensitive Nephrotic Syndrome (SSNS)

Treatment of 1st episode

Oral prednisolone 2mg/kg/day (max 60mg) OD morning for 6 weeks        Document remission          Oral prednisolone 1.5mg/kg (max 40mg) EOD for 6 weeks                                  Document persistent remission      Taper steroid over next 3 months          Document persistent remission

Treatment of infrequent relapse

Oral prednisolone 2mg/kg/day OD morning for 2 weeks Document remission     Oral prednisolone 1.5mg/kg EOD for 4 weeks          Document persistent remission STOP steroid without tapering

Treatment of frequent relapse & dependence 

Long term, alternate day prednisolone

Daily prednisolone @ 2mg/kg/day until remission          

Alternate day prednisolone @ 1.5mg/kg EOD for atleast 3 months          Document persistent remission

               Small dose of prednisolone (0.5-0.75mg/kg) EOD for 9-12 months or longer, provided no side effects occurs.

Levamisole

    2-2.5 mg/kg on alternate days for 1-2 years + oral         prednisolone 0.75 to 1.0 mg/kg  EOD         dose of prednisolone is decreased every 2-4 weeks to 0.25-0.5mg/kg EOD         prednisolone stopped, if possible

Cyclophosphamide 

2.0-2.5 mg/kg/day for 8-12 weeks + prednisolone  @1-1.5 mg/kg EOD         prednisolone is tapered and discontinued over next 2-3 months

Chlorambucil 

In view of its toxicity, the use of chlorambucil, unless under close supervision, is not recommended

Mycophenolate Mofetil

600-1000 mg/m2/day in 2 divided doses for 1-2 years + tapering dose prednisolone for 6-12 months

Cyclosporine A 

4-5 mg/kg/day (100-150 mg/m2/day) in 2 divided doses for 1-2 year + EOD steroid for 12-24 weeks which is then gradually tapered off.

Tacrolimus

0.1-0.2 mg/kg/day in 2 divided doses for 1-2 years +EOD steroid for 12-24 weeks which is then gradually tapered off

Rituximab

375mg/m2 Intravenously weekly for 2-4 doses

Treatment of steroid resistant nephrotic syndrome

High dose corticosteroid with Cyclophosphamide

Methylprednisolone 20-30mg/kg IV per dose 

                                 OR

 Dexamethasone 4-5mg/kg IV per dose

Administer pulses on alternate days×6   once       weekly ×8      fortnightly× 4      monthly ×8       bimonthly×2

                                      +

Prednisolone  1.5mg/kg  EOD  for  4 weeks         1.25mg/kg  EOD for 4 weeks           1mg/kg EOD for 4 months        0.5-0.75mg/kg EOD for 12-18 months

                                      +

Cyclophosphamide 2-2.5mg/kg/day during weeks 3-15

Cyclosporine A

4-5mg/kg/day in 2 divided doses for 12-36 months + tapering dose of EOD prednisolone

Tacrolimus

0.1-0.2mg/kg/day in 2 divided doses for 12-26 months + tapering dose of EOD prednisolone

IV Cyclophosphamide

1st dose of 500-750mg/m2 (max. 1000mg) ,next dose may be increased by 125mg/m2 upto maximum of 750-1000mg/m2, given monthly for 6 doses + tapering dose of EOD prednisolone 

Oral Cyclophosphamide

Complications of Nephrotic Syndrome

Disease-associated:

  • Infections: peritonitis, sepsis, pneumonia
  • Thrombotic tendency: Venous thrombosis, pulmonary embolism
  • Anemia
  • Hypovolemic crisis: tachycardia, hypotension, abdominal pain
  • Acute renal failure

Drug-related :

  • Corticosteroids: Cushing syndrome (obesity, hypertension, cataract and glaucoma)
  • Cyclosporin: Nephrotoxicity, hirsutism
  • MMF: Nausea, vomiting, bone marrow suppression
  • Hormonal and mineral alterations: hypothyroidism, bone disease, hypocalcaemia

Causes of Nephrotic Syndrome

  • Diabetic kidney disease. Diabetes can lead to kidney damage (diabetic nephropathy) that affects the glomeruli.
  • Minimal change disease. This is the most common cause of nephrotic syndrome in children. Minimal change disease results in abnormal kidney function, but when the kidney tissue is examined under a microscope, it appears normal or nearly normal. The cause of the abnormal function typically can’t be determined.
  • Focal segmental glomerulosclerosis. Characterized by scarring of some of the glomeruli, this condition can result from another disease, a genetic defect or certain medications or occur for no known reason.
  • Membranous nephropathy. This kidney disorder is the result of thickening membranes within the glomeruli. The thickening is due to deposits made by the immune system. It can be associated with other medical conditions, such as lupus, hepatitis B, malaria and cancer, or it can occur for no known reason.
  • Systemic lupus erythematosus. This chronic inflammatory disease can lead to serious kidney damage.
  • Amyloidosis. This disorder occurs when amyloid proteins accumulate in your organs. Amyloid buildup often damages the kidneys’ filtering system.

Differential Diagnosis of Acute Kidney Injury in Nephrotic Syndrome

  1. Acute allergic interstitial nephritis secondary to use of various drugs, including diuretics
  2. Acute tubular necrosis caused by volume depletion or sepsis
    Adverse effects of drug therapy
  3. Hemodynamic response to nonsteroidal anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers
  4. Intrarenal edema
  5. Prerenal failure caused by volume depletion
  6. Renal venous thrombosis
  7. Transformation of underlying glomerular disease (e.g., crescentic nephritis superimposed on membranous nephropathy)

Advice On Discharge :

  1. TAB PREDNISOLONE 40mg PO OD with milk in the morning after food for 6 weeks at 2 mg/kg/day and then plan for Alternate day dosing at 1.5mg/kg/day ( Dose Started on 15/11/22 till 27/12/22 )
  2. Tab AMLODIPINE 2.5mg PO BD to continue for 7 days at 0.3mg/kg/day, plan to taper on followup
  3. TAB PANTOP 20mg PO OD 30 minutes before breakfast to continue for 2 weeks at 1mg/kg/day.
  4. TAB Lasilactone (20/50) 1 tab PO BD to continue for 7 days.
  5. Syrup Calcimax P 5ml PO OD to continue.
  6. Salt restricted and protein rich diet.
  7. Continue home monitoring of urine albumin using dipstick and maintain hygiene and charting on Notebook
  8. BP Monitoring regularly
  9. Review after 1 weeks in Nephrology clinic on Tuesday in Paediatric medicine OPD between 9AM-5PM / PAED MED ER SOS.

Last updated on November 19th, 2022.

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