On Previous Post we discussed about some Important definitions, Clinical features, Pathophysiology, Types, Causes etc. In this part of lecture we are going to deals with the Necessary Investigations, Indication for renal biopsy in NS, Specific and Supportive treatment, Complications, Causes of susceptibility to infection in MCNS, Some Conditions Associated with Nephrotic Syndrome with their presentation, responsible organisms and treatment. As the treatment is done with Steroid, there are some adverse effects of using Steroid. The possible outcome also vary in some extent depending upon the steroid dependency.
Some problem based questions and Download link is given below. See here the first part of Nephrotic Syndrome lecture.
Investigations for Nephrotic Syndrome:
- 3+ to 4+proteinuria by heat coagulation test or dipstic test.
- 24 hours UTP is the `Gold-standard’ but not essential for young children. Spot urinary Protein : Creatinine >2 is suggestive of nephrotic range of proteinuria.
- Presence of persistent microscopic haematuria suggests the likely hood of significant renal histological lesion.
- Urine culture to exclude UTI.
- Selective P-consisting mainly of albumin.
- Non selective P – containing significant amount of proteins. higher molecular wt. of (Transferrin & IgG)
- U.P transferrin /U.P albumin= < 0.1 highly selective, >0.2 nonselective, moderately selective. 0.1-0.2
- Serum albumin <2.5g/dl.
- STP low with altered A:G ratio.
- Serum cholesterol/Lipid profile TC,LDL,VLDL are increased. HDL normal. ionized Ca is normal.
- Calcium – total Ca is reduced but Blood- cont.
- Blood urea & serum creatinine are usually normal in MCNS.
- Serum electrolyteshyponatraemia. occasional
- Complement: C3,C4 normal
- Serum IgG reduced, IgM raised.
- Hepatitis B serology, AntiHCV,
- CBC, Blood grouping.
- USS KUB
- Renal biopsy. It is not needed usually except in below situation
Indication for renal biopsy in Nephrotic Syndrome:
- Age <1yr or >16 yrs.
- Persistent macro/microscopic haematuria
- Low C3 level
- Sustained HTN
- Impaired RFT, not attributable to iv hypovolumia
- Presence of extrarenal features; arthritis, rash, lymphadenopathy.
After initial therapy
- Steroid resistance initial or late
- Before starting treatment with Cyclosporin A
Management of MCNS
Treatment of initial episode (ISKDC/Modified)-
Oral prednisolone 60mg/m2/day(or 2mg/kg/day) daily in 2-3 divided doses for 6weeks, followed by 40mg/m2/day(or1.5mg/kg/day) as a single morning dose on alternate day for 6 weeks.
Prolong initial treatment results longer remission and fewer relapses.
A meta analysis published by an Australian group- shows that children in their first episode should be treated for at least 6 months.
First 2 month of which are according to the ISKDC regimen.
In month 3-6 – alternate day treatment , the dose being reduced by 25% every 4 weeks.
[Ref. Hodson et al.Arch Dis Child 2000;83:45-51.]
Subsequent courses Relapses are treated with oral prednisolone 60mg/m2/day daily in 2-3 divided doses until the urine become protein free for 3 consecutive days, followed by 40mg/m2/day as a single morning dose on alternate day for 4 weeks.
General care: General care should strictly maintain.
- Diet- a balanced diet consisting of 1.52g/kg/day of proteins & adequate calorie for age is recommended.
- Fat should constitute no more than 30% of total calories.
- Complex carbohydrates are preferred over simple sugars.
- Salt restriction(2mmol/kg/day) with avoidance of salted snacks in edematous HTN pts.
- Drugs: Furosemide with or without Spironolactone may be tried. Oral Penicillin 25-40 Mg/Kg/Day sometimes given.
Complications of Nephrotic Syndrome:
- Infections: Cellulitis, peritonitis, UTI, pneumonia, meningitis, pyogenic infection of bone and joints, T. varicella, measles, fungal infection.
- Acute renal failure
- Hyper lipidemia
Factors predisposing to thrombosis in MCNS
- Increase platelet aggregability
- Increased plasma concentration of clotting factors: factor V,VII,VIII,X, fibrinogen.
- Accelerated thromboplastin generation
- Reduced antithrombin III
- Corticosteroid therapy
Causes of susceptibility to infection in MCNS
- Low plasma IgG
- Low serum factor B
- Impaired opsonization
- Impaired lymphocyte transformation
- Drug induced immunosuppression
Some Conditions Associated with Nephrotic Syndrome:
- Presentation-abdominal pain, diarrhoea, vomiting.
- Organisms-Pneumococci, E. coli, H. influenzae.
- Treatment- iv ceftriaxone/cefotaxime/ampicillin with aminoglycoside for 10-14 days.
- Presentation-Fever, taccypnoea, cough.
- Organisms- Pneumococci, H. influenzae.
- Treatment- oral amoxycillin/Cephalexin/Amoxiclavor Ampicillin with aminoglycoside for 7-10 days in severe infections.
- Presentation-Redness, tenderness or induration.
- Organisms- Beta haemolytic streptococci, Pneumococci, H. influenzae, staphylococci.
- Treatment- I/V cloxacillin with ceftriaxone till resolution of indurations followed by oral cloxacillin and cefixime for 10 days.
- Presentations-usually asymptomatic, non response to steroid, occasional fever, dysuria.
- Organisms: Gram-ve E.coli, pseudomonas, klebsiella.
- Treatment- iv antibiotic(combination) according to culture sensitivity 7-10 days. Withdraw of steroid unless f/up c/s is sterile.
- Presentation- pulmonary infiltrate, persistent fever, unresponsiveness to antibiotics, sputum or urine shows septate hyphae.
- Organisms-Candida, Aspergillus spp.
- Treatment: Skin mucosa-Fluconazole for 10-14 days and Systemic- Amphotericine B for 14-21days.
Adverse effects of steroid
Cushingoid feature, Acne, Hirsutism, HTN, Sub capsular cataract, Osteopenia, Avascular necrosis, Glycosuria, Short stature, Suppressed adrenal activity, Immunocompromised state and prone to infection.
Outcome in Nephrotic Syndrome:
Steroid Sensitive NS:
- The ultimate outcome in MCNS is excellent with most children getting completely cured by the age of 10-15 yrs.
- In a given patient, it is not possible to predict the course or the age at which cure might take place.
- The family should be encouraged to focus on the general well being, growth & development and schooling of the child.
- Unnecessary restriction on diet and activity must not be imposed.
33% —suffers from only one attack. stopping the corticosteroid treatment and a cure takes place usually after 3 or 4 episodes, which responds to standard course of corticosteroid.
10-20% — experience relapse after
40-50% — experience frequent relapse.
Steroid Resistant NS:
- Steroid resistant NS is difficult to treat, the long term prognosis is often poor.
- In children with FSGS, a trial may be given with I.V. Methylprednisolone, and oral cyclophosphsmide. Cyclosporine may also be used.
- ACE Inhibitors and ARB may be used to reduce the intensity of proteinuria.
- Hypertension should be strictly controlled.
Problem Based Questions:
Q1: A 5 year old boy admitted with swelling of whole body and scanty micturation for 15 days. His blood pressure was 90/60 mmHg and bedside urine albumin was 4+. What is your diagnosis and Treatment?
Q2: A 7 years old child presented with scanty micturation, generalised edema with ascities and proteinurea. What is your diagnosis?
Q3: A 5 years old boy child presented with puffy eyelid and face for 3 days, passing less urine for 3 days. Recentlr he had a cold with fever, he has no hematuria and his blodd pressure is normal. What is your diagnosis?
Ans: Diagnosis: NS with Respiratory Tract Infections.
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