medicine

1. APPROACH TO NEPHROTIC
SYNDROME IN ADULTS

2. NEPHROTIC SYNDROME
•Heavy proteinuria (often greater than 3.5g/day)
•Hypoalbuminemia (less than 3g/dL)
•Peripheral edema
•Hyperlipidemia and lipiduria

3. Massive proteinuria:
•qualitative proteinuria: 3+ or 4+
•quantitative proteinuria : more than 40 mg/m2/hr in
children (selective).

4. Causes of Nephrotic syndrome
Primary causes
1.Membranous glomerulopathy (30% in adults)
2.Focal segmental glomerulosclerosis (15% in adult)
3.Minimal change disease (10-15% in adults and 70-90% in
children)

5. Secondary causes:
1.Diabetes mellitus
2.Lupus erythematosus
3.Amyloidosis and paraproteinemias
4.Viral infections (Hep B, Hep C, HIV)
5.Preeclampsia
6.Drugs and toxins – mercury, snake venom, NSAIDs

6. NEPHROTIC SYNDROME
1. MINIMAL CHANGE DISEASE
•nil lesion
•70-90% of nephrotic syndrome in childhood
•10-15% of nephrotic syndrome in adults
•On renal biopsy- No obvious glomerular lesion by light
microscopy
•Immunofluorescence - no evidence of immune complex
deposition
•diffuse effacement of epithelial cell foot processes on

7. •Selective proteinuria: principally contains albumin with
minimal amounts of higher-molecular-weight proteins
•30% children have spontaneous remission
•All children treated with steroids
•Non-responders are biopsied

8. 2. FOCAL SEGMENTAL GLOMERULOSCLEROSIS:
▶Most common cause of idiopathic nephrotic syndrome in adults
▶35% of all cases in United States and over 50% of cases among blacks
▶On light microscopy, presence of segmental glomerular scars that involve
some but not all glomeruli
▶C/F: hematuria, hypertension and decreased renal function are more
common, any level of proteinuria

9. 3. MEMBRANOUS NEPHROPATHY:
▶Most common cause of primary nephrotic syndrome in adults
▶Most often secondary disorder in children
▶Uniform thickening of basement membrane along the peripheral capillary
loops in light microscopy
▶Diffuse granular deposits of IgG and C3
▶Electron dense sub-epithelial deposits
▶Autoantibodies against Phopholipase A2 Receptors (PLA2R) may be present
in most adults in idiopathic nephropathies

10. Work-up
•CBC
•Serum albumin
•Renal function test
•Urinalysis and urine sediment examination
•Urine protein measurement (24-hr)

11. Work-up
•Lipid profile
•Serologic studies for infection and immune abnormalities
•Renal ultrasonography
•Renal biopsy

12. Indications of renal biopsy in
nephrotic syndrome
•Features s/o diagnosis other than MCD
•NS presenting in 1st
year of life
•NS presenting after 6 years
•Failure to respond to adequate dose of steroid therapy in 28 days
•Relapsing Nephrotic Syndrome
•Development of steroid resistance
•Change in clinical course
•Patient with renal insufficiency and nephrotic syndrome
•Before starting immunosuppressive therapy

13. COMPLICATIONS OF
NEPHROTIC SYNDROME

14. COMPLICATIONS IN NEPHROTIC
SYNDROME
•Thromboembolism
•Acute Renal Failure
•Hypovolemic crisis
•Infections
•Cardiovascular complication
•Anemia

15. THROMBOEMBOLISM
•Nephrotic syndrome is associated with increased risk of
thromboembolic complications
•Incidence of arterial and venous thrombosis(10-40%)
•Risk is particularly increased with lower serum albumin levels
Ref: Barbano B, Gigante A, Amoroso A, Cianci R. Thrombosis in nephrotic syndrome. Semin Thromb Hemost.
2013;39(5):469–76.

16. Why patients are at increased risk?
•Loss of antithrombotic factors in the urine
•Increase in plasma procoagulant cofactors, as factor V,
factor VIII, and fibrinogen
•Lack of balance between procoagulant/anticoagulant
factors
•Abnormalities in platelet activation that promote in situ
thrombosis

17. •Fibrinogen, factor V, and factor VIII synthesis are increased out of
proportion to urinary losses
•Increased von Willebrand factor levels are associated with increased
platelet adhesion

21. Clinical Predictors of Thrombotic Risk
1. Histologic diagnosis of NS is of paramount importance in
assessing the risk of thrombosis- Prevelance high in Membranous
Nephropathy (10-40%)
2. Low albumin level
•<2.8g/L in MN
•<2g/L in other nephrotic syndrome
3. Age- Adults have 7 to 8 fold increased risk of thombotic events

22. Renal vein thrombosis
RVT has been reported in approximately 25 to 30% of
nephrotic patients
↖membranous glomerulonephritis (37%),
↖membranoproliferative glomerulonephritis (26%),
↖minimal-change disease (24%)

23. DVT in Nephrotic Syndrome
•Most common thrombotic complication
•Risk stratification to be done by Wells score
• Wells score ≥1, Doppler ultrasound of lower extremities must be
performed to exclude DVT
•Confirmed DVT, anticoagulation therapy is warranted
•IVC filters in contraindicated patients

24. Pulmonary Thromboembolism
•DVT is major risk factor for PTE
•The origin of pulmonary embolus from renal vein has also
been reported
•Management of PTE depends on cardiovascular instability
and presence of right ventricular disfunction

25. Prophylaxis against Increased Thrombotic
Risk in Patients with NS
•Because of lack of randomised clinical trials optimal
approach to prophylactic anticoagulation is not well
defined
•Decision is based on serum albumin level and bleeding
risk with anticoagulation

26. Prophylactic anticoagulation
1.Incidence of thrombotic events
2.Bleeding risk
Choice of anticoagulants:
▶Aspirin
▶Heparin
▶Warfarin
▶Not recommended in asymptomatic RVT

27. Prophylaxis is given in membranous nephropathy –
▶Low bleeding risk and albumin <3
▶Intermediate bleeding risk and Sr.albumin <2g/dl
•Regardless of the cause of nephrotic syndrome if patient
has potential indications for anticoagulation and low
bleeding risk prophylaxis is given
•Ref: Primary Nephrotic Syndrome in Adults as risk factor for pulmonary embolism (Aibek Et al)

28. Treatment of hypercoagulability in
NS
•Anticoagulation to prevent thromboembolic events
•Anticoagulation for dissolution or removal of thrombus

29. Symptomatic RVT, DVT and PTE
↖Treatment consists of anticoagulation, initially with
heparin and then with warfarin
Nephrotic patients resistant to heparin
↖Direct thrombin inhibitors
↖Ref: Glassock RJ, Prophylactic anticoagulation in nephrotic syndromes: a clinical corrundrum (2007)

30. Platelet abnormalities in nephrotic
syndrome
•Increased platelet counts and platelet hyperactivity have been observed in
nephrotic patients
•Walter et al reported for the first time a statistically significant increase in
mean platelet count in adult patients with nephrotic syndrome
•There is controversy concerning the need of prophylactic treatment in the
prevention of thromboembolic events in Nephrotic syndrome
•REF: Benedicte et al .Platelet abnormalities in Nephrotic Syndrome

31. Pathogenesis of quantitative platelet
changes in NS
•Hypoalbuminemia is suggested to play a role in increased
platelet counts
•Hypercholesterolemia
•Urinary loss of PACAP (Pituitary Adenylate Cyclase
Activating Polypeptide), inhibitor of megakaryopoiesis

32. Infection
•Children are mainly susceptible to infection
•Infections in patients with NS have been described as a
hallmark of idiopathic nephrotic syndrome
•Most common infections – URTI, Peritonitis, UTI
•Increased risk of developing serious bacterial infections
especially with encapsulated bacteria

33. Factors contributing for infections
•Reduced serum concentrations of immunoglobulin G
•Decreased levels of the alternative complement pathway
factors B and D
•Impaired ability to make specific antibodies
REF: Emilia et al, Influence of Nephrotic state on the infectious profile in childhood idiopathic nephrotic
syndrome (2004)

34. Acute kidney injury
•Acute onset nephrotic syndrome does not typically present
with AKI
•In Minimal Change Disease and FSGS, AKI may be
present at the time of presentation
•In 25-30% of adults with MCD, AKI had been reported

35. •AKI in adults with MCD
▶Acute tubular necrosis
▶Use of NSAIDs
▶Excessive diuresis
▶Contrast induced nephropathy
▶Severe renal interstitial edema
▶Increased urinary viscosity

36. •AKI in other forms of Nephrotic Syndrome
▶Due to glomerular and concurrent tubular injury
▶RVT
▶Drugs
Ref: Waldman et al, Adult – minimal change disease (2007)

37. Anemia in nephrotic syndrome
•Increased urinary losses of iron and transferrin
•Urinary losses of erythropoietin
•Losses of transcobalamin and vitamin B12 in the urine
•The role of metals and drugs -Urinary losses of
ceruloplasmin, can lead to copper deficiency and consequent
anemia in patients with nephrotic syndrome.
Ref: Franca Iorember, Diego Aviles, Anemia in Nephrotic Syndrome: approach to evaluation and treatment

38. Protein malnutrition
•Marked proteinuria
•Loss in lean body mass with negative nitrogen balance
•Anorexia and vomiting secondary to edema of the GI tract

39. Cardiovascular complications
•As a result of dyslipidemia, cardiovascular complications may occur

40. Hypovolemia
•Symptomatic hypovolemia may occur
•As a result of over diuresis in those with serum albumin
level of less than 1.5g/dl
•Volume depletion due to severe hypoalbuminemia causing
fluid movement into interstitium