Nephrotic syndrome

Question 1

What is nephrotic syndrome?

Answer 1

Nephrotic syndrome is a collection of symptoms due to kidney damage. This includes protein in the urine, low blood albumin levels, high blood lipids, and significant swelling

Nephrotic syndrome is a type of glomerulopathy

Question 2

What is the pathogenesis of nephrotic syndrome?

Answer 2

Nephrotic syndrome has many causes and may either be the result of a glomerular disease that can be either limited to the kidney, calledprimarynephrotic syndrome (primaryglomerulonephrosis), or a condition that affects the kidney and other parts of the body, calledsecondarynephrotic syndrome.

Question 3

What are the causes of primary glomerulonephrosis?

Answer 3

1. Minimal change disease (most common cause in children for nephrotic syndrome)
2. Focal segmental glomerulosclerosis (most common cause in adults for nephrotic syndrome)
3. Membranous glomerulonephritis (MGN)
4. Membranoproliferative glomerulonephritis (MPGN)
5. Rapidly progressive glomerulonephritis (RPGN)

Question 4

What are the causes of secondary glomerulonephrosis?

Answer 4

1. Diabetic nephropathy
2. Systemic lupus erythematosus
3. Sarcoidosis
4. Syphilis
5. Hepatitis B
6. HIV
7. Cancer

Question 5

What is the pathophysiology of nephrotic syndrome?

Answer 5

In nephrotic syndrome, the glomeruli are affected by an inflammation or a hyalinization (the formation of a homogenous crystalline material within cells) that allows proteins such as albumin, antithrombin or the immunoglobulins to pass through the cell membrane and appear in urine

Question 6

What is the clinical triad of nephrotic syndrome?

Answer 6

1. Proteinuria >3.5 grams per 1.73^2 body surface area
2. Hypoalbuminemia <2.5g/dL
3. Hyperlipidaemia

Also oedema secondary to hypoalbuminemia

Other characteristics are anaemia, dyspnoea, frothy urine

Question 7

How is hypoalbuminaemia caused?

Answer 7

Urinary protein loss of the order 3.5 g daily or more in an adult

Question 8

How is proteinuria in nephrotic syndrome caused?

Answer 8

It occurs partly because structural damage to the glomerular basement membrane leads to an increase in the size and number of pores, allowing passage of more and larger molecules.

Electrical charge is also involved in glomerular permeability. Fixed negatively charged components are present in the glomerular capillary wall, which repel negatively charged protein molecules.

Question 9

How is hyperlipidaemia in nephrotic syndrome caused?

Answer 9

The characteristic disorder is an increase in the low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), and/or intermediate-density lipoprotein (IDL) fractions, but no change or decrease in HDL

Hyperlipidaemia is the consequence of increased synthesis of lipoproteins(such as apolipoprotein B, C-III lipoprotein (a)), as a direct consequence of a low plasma albumin
–> Hypoproteinemia stimulates protein synthesis in the liver, resulting in the overproduction of lipoproteins

Question 10

How is nephrotic syndrome diagnosed?

Answer 10

History, biopsy

1. 24h bedside urinary total protein estimation
2. Comprehensive metabolic panel (CMP) will look for hypoalbuminemia
3. Creatinine clearance test will evaluate kidney function particularly the glomerular filtration capacity

Question 11

How is nephrotic syndrome managed?

Answer 11

1. Dietary sodium restriction + thiazide
2. 80-90 of protein per day
3. Treatment of hypercholesterolaemia starts with an HMG-CoA reductase inhibitor

Question 12

What is the major cause of death in nephrotic patients?

Answer 12

Sepsis