1. Nephrosis and Nephritis
Dr M White, Paediatric SpR
TCD Lecture
Mon 11th May 2009

2. 1) Nephrotic Syndrome
2) Glomerulonephritis

3. Nephrotic Syndrome

4. Nephrotic Syndrome
Characterised by proteinuria (3.5g per 24 hours), hypoalbuminemia (serum <30g/dL), oedema, hypercholesterolemia
Almost always idiopathic in childhood

5. Classification
Primary vs Secondary
Histology
Therapeutic

6. Primary Nephrotic Syndrome
Post-infectious aetiologies
Congenital Nephrotic Syndrome
Collagen vascular disorders (SLE/RA/PAN)
Henoch-Schonlein Purpura
Hereditary Nephritis
Sickle cell disease
Diabetes Mellitus
Amyloidosis
Malignancy

7. Secondary Nephrotic Syndrome
Group A beta-haemolytic strep
Syphilis
Malaria TB
Viral infections (varicella, HBV, HIV-1, infectious mononucleosis)

8. Histological Classification
Minimal-change nephrotic syndrome (MCNS) = 84.5%
Focal Segmental glomerulosclerosis (FSGS) = 9.5%
Mesangial proliferation = 2.5%
Membranous nephropathy & others = 3.5%

9. Therapeutic Classification
Steroid sensitive (85-90%)
Steroid resistant (10-15%)
Steroid dependent
Frequently relapsing

10. Pathophysiology
Two important issues; 1)mechanism of glomerular injury 2)proteinuria
Circulating non-immune factors in MCD and FSGS
Circulating immune factors in disorders membranoproliferative GN, poststreptococcal GN and SLE nephritis
Mutations in podocyte or slit diaphragm in inherited form of congenital, infantile or glucocorticoid resistant nephrotic syndrome

11. Incidence = 2-7 cases per 100,00 per year
15 times more common in children than adults
Age of onset varies with type of disease
Mortality rate related to primary disease process

12. Definitions
Remission – negative urinalysis on 1st morning urine for 3 consecutive mornings
Relapse – 3+ proteinuria on 3 or more consecutive 1st morning urines
Frequently relapsing – 2 or more relapses within 6 months of diagnosis; or 4 or more relapses per year
Steroid resistant – no remission after 4 weeks of prednisolone 60mg/m2/day

13. Presentation First sign usually facial swelling – periorbital oedema
Increasing oedema over days to weeks
Lethargy, poor appetite, weakness, abdominal pain
May follow an apparent viral URTI
Haematuria/hypertension unusual

14. Differential Diagnoses
Congestive heart failure
Cirrhosis
Protein losing states

15. Physical Examination Overall inspection Vital signs
Periorbital oedema
Pitting oedema of legs
Scrotal oedema
Sacral oedema
Ascites
Loss of skin creases

16. Laboratory studies Diagnosis based on history and clinical findings
Urine dipstick
24 hour urine collection
U&E
FBC
+/- Hepatitis serology, HIV, serum complement, varicella serology
Renal US
Others – Antistreptolysin O titres, serum protein electrophoresis, antinuclear antibodies

17. Renal biopsy Rarely performed in Paediatric cases Consider if;
Congenital Nephrotic Syndrome
> 8 years at onset
Steroid resistance
Frequent relapses
Significant nephritic manifestations

18. Treatment
Prednisolone 60mg/m2/day x 4 weeks, 40mg/m2 alternate days for 4 weeks then STOP
For relapse – prednisolone 60mg/m2/day until remission, then 40mg/m2 alt doses for 3 doses, and reduce alt day dose by 10mg/m2 every 3 days until 10mg/m2 alt days – then 5mg/m2 alt days for three doses then STOP
Consider antithrombotic agents, oral penicillin
VZIG for varicella contacts, aciclovir for varicella infection

19. Frequently Relapsing or Steroid dependent NS
Cyclosporin A
Tacrolimus
Cyclophosphamide
Mycophenolate mofetil

20. SRNS Should be referred to specialist unit Full remission not achieved
Aim to reduce proteinuria so not in nephrotic range
Significant chance of hypertension and progression to renal failure
If histology shows FSGS – 20-40% chance of recurrence post transplant

21. Clinical Features SSNS Toddler, pre-school No HTN
Mild, intermittent haematuria
Normal renal function
Excellent prognosis, even if frequently relapsing
Usually not biopsied
SRNS
<1 year, > 8 years
HTN common
Persistent haematuria
Renal function often abnormal
Risk of long term HTN and renal failure
Usual histology FSGS

22. Complications
Infection – typically with Strep pneumoniae (pneumonia or peritonitis) (oedema &peritoneal fluid, loss of immunoglobulins, immunosupression)
Thrombosis – loss of antithrombin III and proteins S&C in urine, increased procoagulant factors by liver, increased haematocrit, relative immobility, steroid therapy
Hypovolemia – shift of fluid from intravascular space, symptoms – oliguria, abd pain, anorexia, postural hypotension
Drug toxicity – side effects of steroid treatment, nephrotoxcity from cyclosporin A or tacrolimus

23. Congenital Nephrotic Syndrome
Onset in first 3 months of life
Large placenta – usually 40% of birth weight
Almost always resistant to drug treatment
High morbidity from protein malnutrition & sepsis
Finnish type- most severe, AR
Diffuse mesangial sclerosis – less severe, AR
Denys-Drash syndrome – includes pseudohermaphroditism and Wilms tumour
FSGS
Secondary congenital nephrotic syndrome – congenital syphilis
Intensive supportive care – 20% albumin, nutritional support, early unilateral nephrectomy
Dialysis and transplantation

24. Glomerulonephritis

25. Glomerulonephritis
Refers to a specific set of renal diseases in which an immunologic mechanism triggers inflammation and proliferation of glomerular tissue that result in damage to the basement membrane, mesangium or capillary endothelium

26. Glomerulonephritis
Sudden onset of haematuria, proteinuria and red blood cell casts
Often accompanied by hypertension, oedema and impaired renal function
Represents 10-15% of glomerular disease
Chronic GN may lead to scarring of the tubulo-interstitial areas of the kidney, with progressive renal impairment

27. Pathophysiology
Lesions are the result of glomerular deposition or immune complex formation
Kidneys may be enlarged up to 50%
Histological appearance – swelling of glomerular tufts, infiltration with polymorpholeucocytes
Immunoflouresence reveals deposition of immunoglobulins and complement

28. Causes Post infectious – most common, Strep, viral/fungal/parasitic
Systemic causes – vasculitis, collagen vascular disease, hypersensitivity, HSP, Goodpasture, drugs (gold penicillamine)
Renal disease – membranoproliferative GN, Berger disease, Idiopathic rapidly progressive glomerulonephritis

29. Morbidity/Mortality
Up to 100% of post-streptococcal GN recover completely
Sporadic cases progress to chronic form in 10% of children
GN most common cause of chronic renal failure (25%)
Mortality 0-7%
Male : Female 2:1
Most cases aged 5-15 years
Can occur at any age

30. Clinical
Most common year old boy, presenting with peri-orbital pufffiness after a strep infection
Urine is dark (‘Coca-Cola’ urine) and output is reduced
BP may be elevated
Abrupt onset of symptoms
Weakness, fever, abd pain, malaise

32. Clinical
Most common year old boy, presenting with periorbital pufffiness after a strep infection
Urine is dark (‘Coca-Cola’ urine) and output is reduced
BP may be elevated
Abrupt onset of symptoms
Weakness, fever, abd pain, malaise

33. Clinical course
Latent period of up to 3 weeks after infection(1-2 weeks postpharyngitis, 2-4 weeks postdermal inf)
Haematuria universal
Oliguria
Oedema
Headache (sec to hypertension)
SOB or dyspnoea on exertion
Possible flank pain (stretching of renal capsule)
Latent period of up to 3 weeks after infection(1-2 weeks postpharyngitis, 2-4 weeks postdermal inf)

34. Laboratory studies FBC – dilutional anaemia, increased WCC
U&E – ?Elevated urea ± creatinine
Urinalysis – haematuria, Red cell casts present, 24 hour collection helpful
ASOT (increased in 60-80%), anti-DNAse b
ESR ?CRP
Cultures (throat, blood, urine)
Complement (Decreased C3, normal C4)

35. Other tests Radiography – CXR if cough +/- haemoptysis
Echo if new murmur/repeated + blood culture
ANA
Targeted tests

36. Renal Biopsy Acute GN self limited, good prognosis
Significant Renal Impairment, atypical presentation, family history, massive proteinuria, nephrotic syndrome

37. Management Treatment mainly supportive
Correct electrolyte abnormalities if present
Post Streptococcal – penicillin therapy
Admission if oliguria and renal failure
Fluid restriction with significant oedema

38. Complications Rare in post-strep GN
Microhaematuria may persist for years
Marked decline in GFR is rare
Chronic renal failure
Nephrotic Syndrome

39. Acute Post-streptococcal GN
Onset of reddish-brown (‘Coca-Cola’) urine days after strep throat or skin infection
Deposition of immune complexes in glomeruli
Treatment mainly supportive
Excellent recovery
Check C3/C4 after recovery – should normalise

40. Henoch-Schonlein purpura
70% will have some degree of renal involvement
Usually microscopic haematuria +/- proteinuria
May have relapsing course
Refer if nephritic/nephrotic/sustained hypertension
Severe cases – steroids, azathioprine
Histologically identical to IgA nephropathy
Follow until urinalysis normal
Accounts for 5-20% of children in ESRF

42. Summary Nephrotic Syndrome
Minimal Change Disease most common, majority steroid sensitive, peri-orbital oedema most common presenting feature
Glomerulonephritis
Presents with haematuria, usually post infectious in children, mainly self limiting, supportive treatment