Nephrotic syndrome

Question 1

Define nephrotic syndrome

Answer 1

Nephrotic syndrome is not a single disease; it is a constellation of several symptoms that can be caused by several renal diseases.

Triad of:

• proteinuria (>3.5 g/24 hours)
• hypoalbuminaemia (<30 g/L)
• peripheral oedema.

Oedema – low albumin means lower serum oncotic pressure so fluid accumulates in interstitial tissue

Hyperlipidaemia and thrombotic disease are also frequently seen.

Question 2

Describe the key differential between nephrotic and nephritic syndrome

Answer 2

Despite heavy proteinuria and lipiduria, the urine contains few cells or casts.

This is in contrast to nephritic syndrome, which is typically defined as the presence of AKI (renal dysfunction), hypertension, and an active urinary sediment (red cells and red cell casts).

Question 3

State some primary causes of nephrotic syndrome

Answer 3

• Minimal change disease accounts for 90% of nephrotic syndrome cases in children <10 years.
• In adults, it may occur:
  
  • idiopathically
  • in relation to NSAIDs
  • due to Hodgkin’s lymphoma.
• ALL forms of glomerulonephritis can cause nephrotic syndrome
  
  • e.g. membranous nephropathy
  • focal segmental glomerulosclerosis

Question 4

State some primary causes of nephrotic syndrome

Answer 4

• Diabetes mellitus – diabetic nephropathy
• Hepatitis B/C
• SLE
• Sickle cell disease
• Amyloidosis
• Malignancies (lung and GI adenocarcinomas) - paraneoplastic
• Drugs (e.g. NSAIDs)
• Alport’s syndrome
• HIV

Question 5

Briefly explain the pathophysiology for each sign of nephrotic syndrome

Answer 5

Injury to podocytes is main cause – this allows the development of high-grade glomerular proteinuria

HYPOALBUMINAEMIA

• Patients become hypoalbuminaemic due to the urinary loss of albumin.

HYPERLIPIDAEMIA

• The liver tries to compensate for this protein loss by increasing the synthesis of albumin
• As well as other molecules including LDL and VLDL and lipoprotein(a)
• → hypercholesterolaemia and hypertriglyceridaemia

HYPERCOAGULABILITY

Hypercoagulability results from:

• the loss of inhibitors of coagulation in the urine
• increased synthesis of procoagulatory factors by the liver

OEDEMA

Oedema is due to a combination of:

• a decrease in oncotic pressure from the hypoalbuminaemia
• primary renal sodium retention in the collecting tubules

Question 6

Recognise the presenting symptoms of nephrotic syndrome

Answer 6

The primary symptoms are:

• Oedema- starts in the legs, may be severe, involving the entire body- face, abdomen, limbs, genitalia (due to hypoalbuminaemia)
• Foamy urine- due to proteinurea

In combination with a history of:

• Atopy (in those with minimal change glomerulonephritis)
• Renal disease
• Underlying cause (e.g. SLE, long-standing diabetes, end-organ damage, multiple myeloma etc)

And symptoms of complications:

• occult malignancy (e.g., cough, weight loss, night sweats, or tarry stools)
• SLE (e.g., rash, photosensitivity, or arthralgias)
• Fabry’s disease (e.g., painful neuropathy).

Question 7

REcognise the presenting signs of nephrotic syndrome

Answer 7

• Ascites: fluid thrill, shifting dullness
• Oedema: periorbital, peripheral, genital
• Leukonychia- white banding of the nails from hypoalbuminaemia
• Xanthelasmata from severe hypercholesterolaemia

Question 8

Identify appropriate investigations for nephrotic syndrome

Answer 8

1. 24-hour urine collection or spot urine protein-to-creatinine ratio (mg/micromol)- assess proteinuria
2. fresh urine sample - for microscopic evaluation
3. Basic blood biochemistries:
   
   • renal function
   • FBC
   • lipid profile (typically total and LDL cholesterol levels are elevated in nephrotic syndrome)
   • serum albumin
   • thyroid hormone testing may be abnormal
4. Tests to differentiate cause:
   
   • imaging for suspected malignancy
   • screening for antibodies: ANA, anti ds-DNA, anti-GBM
   • serology- HIV, infections (haemolytic strep., HBV)
   • complement, cryoglobulins
5. Imaging:
   
   • Renal USS to rule out differentials (e.g. reflux nephropathy) and discover cause
   • Doppler ultrasound, renal angiogram, CT or MRI (if renal vein thrombosis suspected)
6. Renal biopsy:
   
   • In children, almost all cases of nephrotic syndrome are due to minimal change disease- biopsy only if PT is unresponsive to Tx
   • In adults, minimal change disease is relatively uncommon and patients usually require a renal biopsy for definitive diagnosis

Question 9

proteinurea indicates what pathology?

Answer 9

glomerular pathology

USS + biopsy

Question 10

proteinurea management

Answer 10