nephrotic and nephritic syndrome

1. Glomerulonephritides
(Nephritic and Nephrotic)
Dr Paul Mashanga
Paediatric Nephrologist

2. Case
 A 9 yr old presents with h/o of seizures for 1 day.
Mom gives a history that the boy was well until 2
days ago when he started c/o a headache,
swelling of feet and eyes, and passing tea
colored urine. No h/o travel but mom says the boy
had sore throat 2 weeks ago

3. Introduction
 Glomerulonephritis, as the term states, is
inflammation of the glomerulus
 Acute Glomerular injury with the following
features:
 Haematuria (Microscopic or Macroscopic)
 Hypertension (due to water and salt retention)
 AKI (Oliguria, Uraemia, elevated creatinine)
 Oedema (Peripheral or Pulmonary)
 The major underlying pathology is inflammation of the
glomerulus
 The primary pathology can be in the kidney, or it can
be a consequence of systemic disorders

4. Etiology Causative agent Examples
Post-Infectious
(Immune complex mediated
following infection)
Bacterial
Post-Streptococcal
(80% of cases)
S. aureus, S. pneumoniae, M,
pneumoiae, E. coli, Sypilis, TB
Viral EBV, CMV, HSV, VZV, Hepatitis
B and C, HIV
Parasites Malaria, Schistosomiasis,
Toxoplamosis, Trypanosomiasis
Fungi Candida, Aspergillus,
Cryptococcus, etc
Autoimmune Immune Complex Mediated
Systemic Lupus Erythematosus
Ig A vasculitis (HSP)
IgA Nephropathy
Anti GBM antibodies Anti GBM
Pauciimmune ANCA Vasculitis GPA, MPA

5. Pathophysiology
 Depends on the underlying cause
 There is a structural disruption of the glomerular basement
membrane
 Glomerular filtration barrier (GFB) is formed by a meshwork
of laminin, proteoglycans, and type IV collagen
 The GFB allows the filtration of water and small and
medium-sized solutes
 The three layers of the glomerular filtration barrier are the
endothelium, glomerular basement membrane (GBM), and
podocytes

6. Pathophysiology

7. Pathophysiology
 The GFB can be damaged by various
mechanisms
 Direct damage to the endothelial cell layer
 Deposition of immune complex in subendothelial,
subepithelial, and mesangial space
 Disruption of glomerular basement membrane by
primary renal or secondary systemic diseases
 Damage to the podocytes' cellular layer

8. Pathophysiology
ofAPSGN
 In children, the most common cause of acute
glomerulonephritis is post-streptococcal glomerulonephritis
 PSGN appears to be caused by glomerular immune complex
disease induced by specific nephritogenic strains of group A
beta-hemolytic streptococcus (GAS)
 The resulting glomerular immune complex disease triggers
complement activation and inflammation
 The latent period between GAS infection and PSGN is
dependent upon the site of infection: between one and three
weeks following GAS pharyngitis and between three and six
weeks following GAS skin infection

9. Clinical Presentation
History and Physical Exam

10. HISTORY
PertinentQuestionstoAsk
 Periorbital puffiness in the early morning
 Edema in legs in the evening
 The change in color, odor, consistency, and output of urine
 Recent upper respiratory tract or skin infection
 Fever, fatigue
 Headache and seizures
 Ulcers and rash on the extremities to rule out vasculitis
 Hemoptysis and dyspnea may be present in
 Goodpasture syndrome (due to cross-reacting antibodies to the alveolar
epithelium)
 GPA or MPA (if lungs are affected)

11. SYMPTOMS
 The classic symptoms of the nephritic syndrome are:
 Periorbital and pedal edema
 Hematuria with red or cola-colored urine
 Proteinuria in non-nephrotic range (i.e., less than 3.5 gm/day)
and may cause foamy urine when protein content is high
 Hypertension or poorly controlled blood pressure (BP) in
patients with previously controlled BP
 Seizures due to Hypertension
 Renal insufficiency characterized by oliguria (reduced urine
output), and azotemia, due to decreased glomerular filtration
rate (GFR)

12. Physical
Examination
 Patient may be Pale
 Elevated blood pressure.
 The signs of fluid overload may be present
 JVP distention
 Pitting edema
 Crackles on chest auscultation (pulmonary edema)
 On cardiovascular examination, a new heart murmur
can be auscultated in patients with infective
endocarditis.
 Palpable purpura and painful and swollen joints are
present in patients with systemic diseases like
vasculitis, Henoch-Schönlein purpura, and SLE.

13. Evaluation
 Urine analysis is the first step in the evaluation of
nephritic syndrome
 Urine can be discoloured by food, medication,
exercise, haemoglobinuria and myoglobinuria
 The upper limit of normal excretion of blood in the
urine is 3 RBCs/HPF
 In nephritic syndrome
 The urine has greater than 5 RBCs/ HPF along with
acanthocytes and dysmorphic RBCs
 RBCs casts and in a few cases WBCs casts
 Glomerular Hematuria is usually marked with
brownish (cola or tea) coloured urine

14. Evaluationof
Heamaturia
a b

15. Investigations
 U&Es, Creatinine
 Full Blood Count, PBS, ESR, C-reactive Protein
 Blood Culture
 ASOT, Anti-DNAse B
 Urine Culture and Microscopy for casts
 UPCR
 Throat Swab
 C3, C4
 ANA, Anti-dsDNA, ANCA, Anti-GBM
 KUB Ultrasound
 Kidney Biopsy (when indicated)
 RF to r/o cryoglobulinemia if suspected
 Hepatitis B Surface Antigen and HCV Antibodies

16. Differential
Diagnosis
 The following renal diseases have a clinical
presentation similar to the nephritic
syndrome:
 Nephrotic syndrome – FSGS, ICGN
 Familial nephritis – Alports, Thin Basement
Membrane Disease
 Idiopathic hematuria
 Anaphylaxis

17. Treatment
 The treatment is mainly supportive and consists of:
 Fluid and Dietary salt restriction
 If fluid overloaded, restrict intake to insensible losses only
 The reduced intake of sodium and potassium helps reduce the
retention of water
 Bed rest
 Antihypertensives
 Some patients may come in Hypertensive emergency and this
should be managed with drugs such as Labetalol, Sodium
Nitroprusside and Hydralazine
 In those who are not in hypertensive crisis, hypertension can be
treated with ACE inhibitors, ARBs, Amlodipine or Nifedipine
 Diuretics: Loop diuretics may be administered to excrete
excess sodium and water retained in the body
 Corticosteroids: Help relieve the inflammation in the kidney
and promote healing. This is indicated in patients with RPGN

18. Treatment
 Immunomodulators: Immunosuppressive drugs reduce and
block the antigenic effects of the inciting agents especially in
RPGN
 Use of corticosteroids and immunomodulators is controversial in
certain causes of the nephritic syndrome, including staphylococcal
endocarditis. It can aggravate the sepsis and result in increased
mortality
 Antibiotics: Post streptococcal GN patients with evidence of
streptococcal infection are administered penicillin. Erythromycin
is preferred for patients allergic to penicillin.
 Dialysis: In some cases, the disease has a fulminating course
leading to severe AKI requiring renal replacement therapy.

19. Complications
 The nephritic syndrome can grossly compromise
renal function and lead to the following
complications.
 Acute Kidney Injury and progression to RPGN
 Uncontrolled hypertension
 Azotemia
 Hyperkalemia
 Hyperphosphatemia
 Hypocalcemia
 Heart failure
 Hypertensive encephalopathy presenting as seizures and
altered consciousness

20. Prognosis
 The prognosis of the nephritic syndrome depends
upon the underlying aetiology, age of the patients
and timely intervention
 APSGN is the commonest in children and has
excellent outcome
 Adults typically have a chronic fulminating course.
 The disease is not resolved in 20 to 74% of the adults
 In these patients, the renal function derangement
persists and will result in Chronic Kidney Disease

21. SUMMARY
 The nephritic syndrome is a common presentation of most proliferative glomerulonephritides (GN) and
is characterised by haematuria, oliguria, hypertension and edema
 The primary pathology can be in the kidney, or it can be a consequence of systemic disorders
 Poststrep GN is the commonest cause of Nephritic Syndrome in children and has a good prognosis
 Nephritic syndrome may have a variable clinical picture depending on the underlying aetiology
 The acanthocytes, dysmorphic red blood cells, and RBC casts are pathognomonic of glomerular
inflammation
 The severity of clinical symptoms at the time of presentation determines the prognosis of the disease
 Patients with severe oliguria, azotemia, raised creatinine level at the time of presentation have a worse
prognosis.
 Supportive treatment should be initiated immediately along with carrying out the evaluation tests for a
specific diagnosis

22. Nephrotic Syndromein Children

23. Outline
1. Introduction
2. Epidemiology
3. Classification
4. Pathogenesis and Pathophysiology
5. Clinical Presentation
6. Complications
7. Investigations
8. Management

24. Scenario
 5 year old presents with generalized body
swelling is referred to the ER.
 His lab tests are as follows:
 Urine 4+ proteinuria; Serum albumin 17mmol/l
Cholesterol 12mmol/l; Creatinine 38umol/l; BP 90/60
 Questions
 Take relevant history
 What is the most likely diagnosis
 What are the possible aetiologies?
 What further investigations would like to do?

25. INTRODUCTION
 Nephrotic Syndrome is the commonest
glomerular disease in children
 It manifests with oedema, hypoalbuminemia,
heavy proteinuria and hyperlipidaemia.

26. Epidemiology
 Incidence 2-7/100000 Children per year - Nandlal
L. et al-2019
 Sex predilection Male:Female 2:1
 Commonly affects Children between 2- 10 years.

27. Definition:NephroticSyndrome
Nephrotic Range Proteinuria
UPCR ≥ 200 mg/mmol (2 mg/mg) in 1st morning void, or 24hr urine
sample ≥ 1000 mg/m2 per day corresponding to 3 + or 4 + by urine
dipstick
Hypoalbuminemia
Serum Alb <30g/L
OR
Edema
When serum albumin is
not available

28. Classification
 Congenital Nephrotic Syndrome
 Manifests in the first 3 months of life
 Infantile N.S
 Manifests after 3 months of life but before 12 months of
life
 Primary/Idiopathic NS
 Most common and cause is unknown
 Secondary NS
 Has an identifiable cause
 Can present at any age

29. 1. Idiopathic 85% of cases
2. Genetics
3. Infections e.g Syphilis, malaria,toxoplasimosis,schistosomiasis
4.Drugs NSAIDS, Lithium, Mercury, Lead.
5. Autoimmune and connective tissue disorders e.g, SLE, Granulomatosus with
Polyangiitis, Microscopic polyangiitis, IgA nephropathy
6. Malignancies; Lymphoma, leukemia
CAUSES OF CHILDHOOD NEPHROTIC SYNDROME

30. IdiopathicNS
 Commonest form of NS
 Affecting from 1.15 to 16.9 per 100,000 children per year
globally
 85–90% are Steroid Sensitive (SSNS)
 70–80% will have at least one relapse during follow-up
 50% of these will experience frequent relapses (FRNS) or
become Steroid dependent (SDNS)
 10–30% continue to have a relapsing course into young
adulthood
 A small percentage will show no response to steroid therapy
of which some will progress to ESKD

31. Pathogenesis
and
Pathophysiology

32.  The podocyte is a polarised epithelial cell with
interdigitating foot processes with a unique cell–cell
junction known as the slit diaphragm
 The podocyte, along with the glomerular basement
membrane and the fenestrated glomerular
endothelium, forms a trilayered structure— the
glomerular filtration barrier
 The podocyte and filtration barrier allow an
ultrafiltrate almost completely devoid of protein to
pass into the Bowman’s space and proceed onto
the proximal tubule
Normal

33.  Podocyte architecture is maintained by an extensive
actin cytoskeleton that enables the glomerular filtration
barrier to withstand the substantial capillary hydrostatic
pressure
 Loss of normal podocyte structure, the foot processes
or the slit diaphragm that spans these interdigitations
can lead to loss of albumin in the ultrafiltrate
 Podocytes are terminally differentiated cells with
minimal regeneration and thus, vulnerable to injury
Abnormal

34. Pathogenesis
and
Pathophysiology

36. Pathophysiology
25-Jul-23
Edema:
 Under fill theory: hypoalbuminemia
 Over fill theory:↑ tubular NaCl reabsorption
secondary to RAAS → intravascular expansion
→ fluid shift following pressure gradient
 Hypercholesterolemia
 hypoproteinemia → hepatic lipoprotein
synthesis
→ ↑serum lipid (cholesterol, lipoprotein) → lipid
metabolism

37. 25-Jul-23
 Sudden onset of dependent pitting oedema
 Periorbital
 scrotal or vulva
 ankle or leg
 Weight gain
 Ascites
 abdominal pain
 Diarrhea (due to intestinal oedema)
 Respiratory distress (due to pulmonary edema/
pleural effusions or massive ascites)
 Decreased urine output
 ±HTN and Hematuria
Clinical
Manifestation

38. 25-Jul-23
Infection
Spontaneous bacterial peritonitis, cellulitis,
bacteriemia (S.pneumoniae, E.coli)
Steroid and immunosuppressant toxicity
Hypovolaemia
abdominal pain and may feel faint, cold
peripheries, poor pulse volume, hypotension, and
haemoconcentration.
A low urinary sodium (<20mmol/L) and a high
packed cell volume
Complications

39.  Thromboembolism
Hypercoagulable state due to decreased
fibrinolytic factors (urinary losses of antithrombin
III, proteins C and S)
Thrombocytosis
exacerbated by steroid therapy
Increased synthesis of clotting factors
Increased blood viscosity from the raised
haematocrit,
This is usually arterial and may affect the brain,
limbs and splanchnic circulation
 Hypercholesteroleamia
 Acute Kidney Injury (rare)
Complications

40. Approachtoa
SwollenChild

41.  First time or relapse???
 History of oedema noted on awakening in the morning or sudden swelling??
Distribution
Colour changes
Initiating factor? (bee sting)
Painful??
 Weight gain (edema)
 Respiratory distress (Breathlessness)
Infection, Pleural Effusion/Pulmonary Edema, Ascites
 Diarrhea
 Urine: frothy
 Past medical and drug history: recent illness, allergies, asthma
 Nutrition history
 Family history
History Taking

42. 25-Jul-23
 Assessment of hydration status identifies fluid imbalances (dehydration,
overhydration)
 Blood pressure: hypertension
 Henoch-Schönlein purpura (purpura)
 Systemic lupus erythematosus (e.g. malar rash)
 Rales heard on lung auscultation suggest extravascular fluid from overload or
hypoalbuminemia
 Palpation and percussion of the abdomen may reveal ascites or masses
 Liver enlargement is present in several multisystem diseases (systemic lupus
erythematosus, infections, polycystic disease) and in glomerulosclerosis
Physical
Examination
Physical Examination

43. Differential
Diagnosis
 Nephrotic syndrome
 Protein losing enteropathy
 Hepatic failure
 Heart failure
 Acute/Chronic Glomerulonephritis
 Protein Energy Malnutrition

44. Lab
Investigations
 Urine Examination
 Full Blood Count & Blood picture
 Urine Analysis for Proteinuria
 Spot Urine Protein : Creatinine ratio
 Urinary protein excretion
 Liver Function Tests
 Renal Function Tests
25-Jul-23

45. Investigations
 Urinalysis
 - 3+ to 4+ proteinuria on dip sticks
 Spot UPC ratio > 2.0mg/mg (>0.2g/mmol)
 UPE > 40 mg/m2/hr
 Serum Creatinine – normal or elevated
 Serum albumin - < 30 g/L
 Serum Cholesterol/ TGA levels – elevated

46. Other
Investigations
Complement levels: decrease
suggest other than MCD
Antistreptolysin O titre and throat
swab
Hepatitis B antigen
Hepatitis C
RPR
Genetics when indicated
Kidney Biopsy when indicated

47. Management

48. InitialEpisode
 High protein diet
 Salt moderation
 Treatment of infections
 If significant edema – diuretics can be used but cautiously
 Mainstay of therapy is Corticosteroid treatment with Prednisolone
 First episode:
Prednisone 2mg/kg(60mg/m2) daily for 6weeks then taper
 Second episode:
Prednisone 2mg/kg(60mg/m2) until protein free for 3 days then taper
 Prevention:
Prednisone 1mg/kg daily x 5 days when URTI/Vaccines
Initial Episode

49. Treatment Related Definitions
• Complete remission
o UPCR (based on first morning void or 24 h urine sample) ≤ 20 mg/mmol (0.2
mg/mg) or < 100 mg/m2 per day, respectively, or negative or trace dipstick on
three or more consecutive days
• Steroid-sensitive nephrotic syndrome (SSNS)
o Complete remission within 4 weeks of PDN at standard dose (60 mg/m2/day or
2 mg/kg/day, maximum 60 mg/day)
• Steroid-resistant nephrotic syndrome (SRNS)
o Lack of complete remission within 4 weeks of treatment with PDN at standard
dose
• SSNS late responder
o A patient achieving complete remission during the confirmation period (i.e.
between 4 and 6 weeks of PDN therapy) for new onset NS

50. Treatment Related Definitions
• Infrequently relapsing Nephrotic Syndrome
o < 2 relapses in the 6 months following remission of the initial episode or <3
relapses in any subsequent 12-month period (modified definition)
• Frequently relapsing Nephrotic Syndrome (FRNS)
o ≥ 2 relapses in the first 6-months following remission of the initial episode or ≥
3 relapses in any 12 months (modified definition)
• Steroid-dependent nephrotic syndrome (SDNS)
o A patient with SSNS who experiences 2 consecutive relapses during
recommended Prednisolone therapy for first presentation or relapse or within
14 days of its discontinuation

51. Definition: Relapse
• Relapse
o Urine dipstick ≥3+ or UPCR ≥ 200 mg/mmol (≥ 2 mg/mg) on a spot urine sample
on 3 consecutive days, with or without reappearance of edema in a child who
had previously achieved complete remission
• Complicated Relapse (New Definition)
o A relapse requiring hospitalization due to one or more of the following: severe
edema, symptomatic hypovolemia or AKI requiring IV albumin infusions,
thrombosis, or severe infections (e.g., sepsis, peritonitis, pneumonia, cellulitis)

52. Treatment-Related Definitions: SSNS
• Steroid toxicity
o New or worsening obesity/overweight
o Sustained hypertension
o Hyperglycemia
o Behavioral/psychiatric disorders, sleep disruption
o Impaired statural growth (height velocity < 25th percentile and/or height
< 3rd percentile) in a child with normal growth before start of steroid
treatment
o Cushingoid features, striae rubrae/distensae,
o Glaucoma, ocular cataract
o Bone pain, avascular necrosis

53.  Mx of oedematous state
 Bed rest to be avoided as there is a tendency of hypercoagulability
 Dietary advice: no added salt, normal protein with adequate calories
 Prophylactic antibiotics: oral penicillin particularly in during relapse with
gross oedema
 Hypovolaemia: infuse salt poor albumin or 5% albumin, plasma protein
derivatives or human plasma.
• Note that the patient should be passing urine as you risk causing pulmonary oedema
• Diuretics: to be given cautiously
MANAGEMENT

54. • Symptomatic therapy:
 diuretic
 blood pressure control : ACEi (captopril, enalapril),
angiotensin II receptor antagonist
 hyperlipidaemia
• Immunosuppressive therapy:
Steroids
Levamisole
Cyclosporin, tacrolimus, mycophenolate mofetil
Cyclophosphamide
Rituximab
Management
ofSteroid
ResistantNS

55. Steroidtoxicity
• Stunting of growth
• Cataracts
• Striae
• Severe cushingoid features
• behavioural changes, a rounded face, central obesity
and the tendency to bruise more easily, hirsutism
• Osteoporosis
• Proximal myopathy
• Recurrent infection due low immunity

56. SteroidToxicity

57. OtherMedication
togivewhen
givingSteroid
Therapy
 Proton pump Inhibitor
 Omeprazole
 Lansoprazole
 Calcium
 Vit D

58. Managementof
Complications
 Infection: parenteral penicillin and a third
generation cephalosporin (in primary
peritonitis)
 If exposed to chickenpox and measles
varicella-zoster immunoglobulin (VZIG) should
be given within 72 hours after exposure to
chickenpox / single dose of intravenous
immunoglobulin
 Thrombosis : Warfarin, low-dose aspirin, and
dipyridamole all have been used to minimize
the risk of clots.
25-Jul-23

59. EDUCATION
 Parents and school teachers should be
provided with information regarding the disease
which includes:
1. Advice and precaution of infection
2. Danger of sudden steroid withdrawal (adrenal
crisis)
3. Immunization:
 While the child is on corticosteroid treatment and
within 6 weeks after its cessation, only killed
vaccines may be safely administered to the child.
 Live vaccines can be administered 6 weeks after
cessation of corticosteroid therapy

60. Vaccines
Haemophilus
Prevenar/Pneumovax given
 Less concern about prophylactic
Penicillin
 Less effective if vaccinate on
Prednisone in terms of building up
immunity

61. PROGNOSIS
Idiopathic NS
Steroid sensitive (90%)
Frequent
relapses/S.dependent (50%)
Infrequent relapses (33%)
No relapses (25%)
Steroid resistant (10%)
ESKD
25-Jul-23

62. How do you
prevent a
Heart Attack?

63. THE END