Nephrotic and nephritic syndrome

2. Nephrotic Syndrome
and Nephritic Syndrome
DR. WASIM MD MOHOSIN UL HAQUE

3. Mechanisms of glomerular injury

4. Responses of glomerulus to injury
.
◦ It can leak protein
◦ It can leak blood
◦ It can lose filtration function
◦ It can cause hypertension
Diseases that cause haematuria cause proteinuria if
they leave scarring or progress.

5. Proteinuric diseases
Historically termed ‘nephrosis’
◦ Subtle abnormalities in podocytes
◦ Abnormal glomerular matrix, including the scarring laid down by
inflammatory diseases

6. Diseases that cause proteinuria
Podocyte is central to proteinuria.
◦ Minimal change disease —podocyte dysfunction
◦ Membranous nephropathy—podocyte attack by autoantibodies
◦ Focal segmental glomerulosclerosis —podocyte injury or death
Most of the genetic causes of nephrotic syndrome, almost all involve
podocyte genes
The major metabolic and systemic diseases causing nephrotic syndrome
disturb the function of these highly specialized, highly differentiated cell

7. Haematuric diseases
Breaks in the GBM
◦ Characterized by inflammatory disruption of the glomerular basement
membrane (GBM) (‘nephritis’)
◦ Fragile GBM without inflammation

8. Chapter: Mechanisms of glomerular injuryoverview Author(s): Neil Turner From: Oxford Textbook of Clinical Nephrology

10. Progressive renal disease after glomerular injury
◦ Haemodynamic—increased glomerular perfusion pressure or stretches
Podocyte—podocyte stress and death
◦ Toxicity of proteinuria—proteinuria creates progression by its effects on
the tubulointerstitium
◦ Disordered repair and replacement of cells

11. Nephrotic syndrome
Characterized by
◦ A urine protein excretion of greater than 3500 mg per 24 hours or, iurine
protein-to-creatinine ratio is greater than 3000 mg/g in an adult
◦ Hypoalbuminemia, usually less than 3.5 g/dL
◦ Edema (peripheral or periorbital, occasionally ascites or pleural
effusions)
◦ Hyperlipidemia
◦ Lipiduria

12. Presentation
◦ Edema is the most common presenting feature
◦ Features of complication:
• infections like spontaneous peritonitis in children with ascites
• venous thrombosis or thromboembolism
• manifestations of hyperlipidemia

13. Nephrotic edema
In adults, retention of up to 4 L of salt and water remains undetectable
◦ around the eyes in the morning
◦ around the ankles in the evening
The five characteristics of nephrotic edema
◦ gradually increasing
◦ gravitational
◦ generalized
◦ pitting
◦ softness

14. Example Case

15. Chapter: Nephrotic syndrome Author(s): Premil Rajakrishna, Stewart Cameron, and Neil Turner From: Oxford Textbook of Clinical Nephrology

16. pathophysiology

18. Evaluation of nephrotic syndrome
Kidney biopsy
Kidney biopsy may be deferred in certain patients:
◦ If there is an obvious etiology
◦ If amyloidosis is suspected in a patient with a monoclonal gammopathy
◦ If the patient with nephrotic syndrome has a positive anti-phospholipase A2
receptor (anti-PLA2R) autoantibody
◦ If a biopsy cannot be performed or is refused (later stages of pregnancy )
◦ If ages of 1 and 10 years, with normal renal function, normal complement levels
without hypertension or haematuria
◦ Frail elderly or others with severe comorbid conditions where a pathological
diagnosis is very unlikely to alter best management.

19. Evaluation of nephrotic syndrome
Laboratory tests
◦ Glycated hemoglobin (HbA1C, to diagnose diabetes)
◦ Antinuclear antibody and anti-double stranded DNA (dsDNA) antibody
◦ Anti-PLA2R autoantibody
◦ In patients older than 50 years – serum free light chains and serum protein
immunofixation
◦ Tests for hepatitis B and C viruses and the human immunodeficiency virus
◦ Serum C3 and C4 complement levels
Other serologic, microbiological, and genetic tests are sometimes performed in
patients once a specific histologic diagnosis is established.

20. Causes of nephrotic
Syndrome
In US adult
Primary nephrotic syndrome
◦ FSGS (35%)
◦ Membranous GN(33%)
◦ Minimal change disease (15%)
◦ Membranoproliferative GN (14%).
Secondary nephrotic syndrome
◦ Diabetes
◦ Lupus
◦ Amyloid

21. Management
Conservative
◦ Monitor U&E, BP, fluid balance, weight
◦ Salt and fluid restriction
◦ Avoid high protein diet
Medical
◦ Diuretics
◦ ACE-inhibitors/ARBs
◦ Lipid lowering agents
◦ Corticosteroids/immunosuppression
◦ Dialysis
◦ Anticoagulation
Nephrectomy
o Chemical
o Embolization
o Surgical

22. Management
Salt restriction
oBelow 50-70 mmol/day (about 4 g)
oPatients are advised to avoid salty food, use no added salt
Protein restriction
o0.8 g of protein of high biological value/kg/24 hours, plus 1 g protein per
gram of proteinuria
Diuretics
o 2-3 L of fluid loss per day for short periods
Anticoagulation
o Membranous nephropathy, albumin < 20gm/L

23. Complications
 Increased susceptibility to infection
o Due to reduced serum IgG, reduced complement activity,
reduced T cell function
o Immunization against pneumococci
o Varicella/chicken pox prophylaxis for non immune contact
o Prompt discontinuation of cytotoxic therapy
 Thromboembolism
 Hyperlipidaemia
 AKI

24. Prognosis
Varies
 With treatment, generally good prognosis
o Especially minimal change disease (1% progress to ESRF)

25. Nephritic syndrome
Caused by glomerular inflammation
oOliguria
oHematuria
oHypertension
oVariable degrees of proteinuria
oLeukocyturia
oRenal insufficiency
oInvolvement of other organ
systems
• Pulmonary hemorrhage
• Palpable purpura
• Arthritis

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28. Evaluation
Renal Biopsy
Laboratory tests
◦ Serum C3 and C4 complement levels
◦ Antineutrophil cytoplasmic autoantibodies
◦ Anti-glomerular basement membrane (GBM) autoantibodies
◦ Antinuclear antibodies
◦ Anti-dsDNA antibodies
◦ Serology for hepatitis C virus, hepatitis B virus, and HIV
◦ Serum free light chains and serum immunofixation

29. Evaluation
Other laboratory tests based on clinical context or biopsy findings
A cryocrit
oIf there are features of cryoglobulinemia or a known history of hepatitis C
virus infection.
Blood cultures
oIF persistent fever or other signs of chronic infection

30. Differential diagnosis
Based on serum complement levels
Complement levels are normal
◦ Anti-GBM disease
◦ Pauci-immune glomerulonephritis
Complement levels are typically low
◦ Immune complex-mediated glomerulonephritis (except IgA nephropathy)
◦ PSGN low C3
◦ Dense deposit disease low C3
◦ SLE both C3, C4 low

31. Differential diagnosis
Based on clinical findings
Gross hematuria with upper respiratory infection
oLatent period 7 to 10 days
o Poststreptococcal glomerulonephritis (especially in children)
oConcurrently ("synpharyngitic glomerulonephritis")
o IgA nephropathy.

32. Differential diagnosis
Based on clinical findings
oThe presence of palpable purpura or a petechial rash
oVasculitis
oThe presence of renal failure and pulmonary hemorrhage
oVasculitis
oIn patients with an acute presentation of microangiopathic hemolytic
anemia, thrombocytopenia, and kidney failure
oThrombotic microangiopathy (TMA)

33. Post-streptococcal glomerulonephritis
A complication of Streptococcal infections that is responsible for classic
acute nephritic syndrome, mostly seen in children
oAcute nephritis associated with
oEdema
oHypertension and
oHematuria
oSerum C3 levels are characteristically very low
oRBC cast in urine RME

34. In temperate climates
◦ Pharyngitis and tonsillitis are the usual sites of antecedent infection In the
winter and the spring
In the tropics
◦ Impetigo is more frequent in the summer months
The latent period
◦ Throat infections (about 2weeks)
◦ After pyodermitis (several weeks)

35. Clinical manifestations of
acute PSGN
The clinical features of
PSGN are different in
adults and in children
Male: Female ratio 2:1
Typical age 4–14 years

36. Clinical manifestations of acute PSGN
Typical presentation
◦ Hematuria
◦ Edema
◦ Hypertension
◦ Oliguria
At least two of these manifestations are present in almost all patients
The full clinical picture in about 40% of the patients

37. oImprovement is observed within 2 to 7 days with increasing urine volume
resolution of edema and return of the blood pressure to normal levels
oSerum complement returns to normal usually within 1 month in patients
with uncomplicated PSGN.
oGross hematuria is present in one-third of the patients. Microscopic
hematuria usually persists for many months. Disappears usually within 1
year and always within 4 years in children

38. D/D
◦ Systemic lupus erythematosus
◦ Essential cryoglobulinaemia
◦ Subacute and acute bacterial endocarditis, 'shunt’ nephritis, visceral
abscess
◦ Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis
◦ Anti- glomerular basement membrane (anti-GBM) antibody disease l

39. Evaluation
Lab test
o Urine RME: RBC cast
o High ASO titer in 70% to 80% of throat infection
o High anti-DNAse B titers in about 70% of the cases with pyodermitis
o The streptozyme test, (DNAse B, Streptolysin O, hyaluronidase and
streptokinase) elevated in nearly 80% of the cases
o Serum C3 low, C4 minimally low or normal

40. Evaluation
Lab test
o Serum IgG and IgM are elevated in 80% of the cases
o Serum IgA level is normal
o Cryoglobulins, elevated rheumatoid factor, and anti-C1q antibodies are
present in up to one-third of patients
o Rarely low titters of anti-DNA and ANCA

42. Renal Biopsy
Indication of renal biopsy In children
oNephrotic range proteinuria
oProgressive azotaemia suggesting crescentic GN
oIf serum complement levels not depressed in the acute phase
oIf serum complement levels remain reduced for > 1 month
In adult patients, kidney biopsy is the norm

45. Management
◦ Hospitalization if symptomatic
◦ Salt water restriction
◦ Loop diuretics
◦ Treatment of the infection if still present
◦ Prophylactic antibiotic treatment for household members of index cases
◦ Antihypertensive agents
◦ Management of hyperkalemia
◦ Severe cases may require dialysis
High-dose corticosteroids have often been given in severe crescentic
disease, but there is no evidence that they are effective

46. Prognosis
In children
oRecovery of renal function is often excellent
oThough long-term studies now suggest that it may represent a risk factor
for the development of chronic kidney disease.
In older patients with comorbid conditions and atypical presentations
oResolution may be less complete than in children

47. Prognosis
◦ The early mortality is very low in children but significant in adults
◦ Cardiovascular complications are the main cause of death in acute PSGN
◦ Irreversible renal failure may follow acute GN if widespread extra capillary
(crescentic) proliferation develops
◦ Associations of PSGN with positive ANCA or haemolytic uremic syndrome
carry a worse prognosis
◦ The incidence of abnormal laboratory findings during the follow-up varies
from 3.5% to 60%
◦ Subgroup of adult patients with massive proteinuria as the initial
manifestation had an incidence of chronic renal failure as high as 77%

48. Thank you

50. syndrome in elderly patients.
Chapter: Nephrotic syndrome Author(s): Premil Rajakrishna, Stewart Cameron, and Neil Turner From: Oxford Textbook of Clinical Nephrology

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