Proteinuria (7.6)

Question 1

Outline the structure and function of the glomerular filtration barrier

Answer 1

3 layers:

Capillary endothelium: Fenestrated

Glomerular basement membrane: 3 layers (interna, densa and externa).Type IV collagen. Studded with negatively charged glycoproteins which allow for the repulsion of plasma proteins (allowing them to be retained within the blood)

Podocytes: Pedicles with filtration slits seen between. Proteins create filtration diaphragm, e.g. nephrin.

Question 2

Outline the mechanism of proteinuria

Answer 2

Disruption to the glomerular filtration barrier:

• Increased intraglomerular hydraulic pressure → causes larger molecules to the forced through
• Increased pore size
• Loss of negative charges on GBM
• Damage to podocytes → pedicle effacement → causes gaps to form
• Damage to the filtration slit diaphragm of the podocyte (e.g. nephrin)

Question 3

Outline investigations for proteinuria

Answer 3

Urine dipstick: Detects urine ALBUMIN - not all protein.

A measure of concentration, not amount.

SSA (salisyl sulphonic acid) may be added to urine to allow detection of all protein via precipitation.

24 hr urine collection:

• < 150 mg/day of protein is normal
• < 30 mg/day albumin is normal

Urinary albumin or protein:creatinine ratio

Urine protein electrophoresis

Question 4

Outline the adverse effects of proteinuria and nephrotic syndrome

Answer 4

A powerful risk predictor of adverse consequences associated with CKD: Mortality, progression to end-stage, AKI, CV events

• Contributes to progressive kidney damage
• Proteinuria → interstitial fibrosis:

Excessive protein in the PCT causes the reabsorption system to be overloaded. This provokes an inflammatory reaction, with pro-inflammatory and pro-fibrotic factors released onto the basolateral side of the tubule. This leads to interstitial fibrosis as tubular cells take on myofibroblast properties - secreting pro-fibrotic molecules.

Question 5

Outline the basic approach to treating proteinuria

Answer 5

Specific treatment of glomerulopathy: Steroids

Non-specific measures: Lower BP; ACEi, ATII receptor blocker, protein restriction

Question 6

Outline the normal physiology of protein movement within the nephron

Answer 6

Tamm-Horsfall glycoprotein: Uromodulin. Inserted into the apical membrane of tubules. Most abundant protein in urine. Thought to be involved in the protection of the urinary system from infections.

Question 7

Outline the types of proteinura:

Functional

Overproduction/overload

Glomerular

Tubular

Answer 7

Functional: Transient proteinuria in the absence of renal disease e.g. due to acute illness, exercise

Overproduction/overload: Increased plasma concentration of filterable proteins e.g. due to over production of Igs

Glomerular: Disease process causes damage to the glomerular filtration barrier

• Podocyte disorders: Minimal change disease
• Immune complex mediated: Glomerulonephritis → Nephrotic syndrome (also nephritic)
• Secondary glomerulopathies: Diabetes

Tubular: Decreased tubular reabsorption of filtered proteins following damage to the tubules

Question 8

Outline the complications of nephrotic syndrome

Answer 8