CKD 1

Question 1

Major Causes of CKD

Answer 1

● Diabetes Mellitus (#1)
● Hypertension (#2)
Diabetes or Hypertension account for ~55-70%
of cases of CKD
● Glomerulonephritis
● Chronic interstitial nephritis
● Polycystic kidney disease
● Vasculitis
● Neoplasms
● Other

Question 2

explain how diabetes can lead to glomerulosclerosis

Answer 2

Excess glucose, glycation, Hyaline arteriosclerosis ofefferent arteriole –> glomerular mesangial expansion –> glomerulosclerosis (loss of nephron mass, glom hypertension, proteinuria)

- Diabetic nephropathy hyperfiltration and hyperperfusion leading to albuminuria, increased afferent arterial dilation to to dysfxn in vasoconstrictive response
- Increased intraglomerular pressure
- Greater mesangial cell matrix pdtn
- Decreased FGR and surface area for filtraiton
- Glom   basmement membrane thickens leading to glom sclerosis

Question 3

explain how hypertension can lead to glomerulosclerosis

Answer 3

thickening of arteries supplying blood to kidneys –> decreased oxygen, ischemic injury –> glomerulosclerosis (loss of nephron mass, glom hypertension, proteinuria)

Question 4

angiotensin pathway

Answer 4

angiotensinogen –> ang I by renin –> ang II by ACE –> bind to angiotensin receptor

compensate by the regulation of angiotensin II
- Ang II restricts effefernt arteriole to try to maintain or increase hydrostatic pressure/blood flow through glomerulus
(when kidneys are stressed)

Question 5

Role of Angiotensin II

Answer 5

● Enhances vascular tone (vasoconstricts) of both the afferent and efferent arterioles
● Increases hydrostatic pressure
● Increases glomerular permeability
● Increased filtration of plasma proteins (albuminuria)
● Excessive tubular reabsorption
● Renal scarring

Meant for short term sltn
Compensation mech lasts for a long time elads to high hydro pressure

Inflamm and scarring and further loss of nephrons

Question 6

Hemodynamic effect of ang II

direct effects on glomerular membrane?

Answer 6

○ Initially compensatory response to a loss in nephrons
○ Becomes maladaptive due to prolonged increase in hydrostatic pressure
● Direct effect on the glomerular membrane
○ Modulates renal cell growth
○ Leads to tubulo-interstitial injury
○ Structural damage, inflammation and fibrosis

Question 7

Progression Factors

Answer 7

● Hyperglycemia
● Hypertension
● Smoking
● Obesity
● Proteinuria

If initial insults to kidnes are nto managed properly, they can lead to progession of CKD

Question 8

Role of Proteinuria

Answer 8

● Consequence of glomerular hyperfiltration
● Contributes to progressive nephron damage
○ Filtered proteins are reabsorbed by proximal tubular cells
○ Ultrafiltered proteins activate inflammatory and fibrogenic pathways leading to further damage
of the interstitium and progressive loss of nephrons (See role of angiotensin II)

Proteins that should not be filtered through glomerulus, some of them get reabsorbed by proximal tubular cells and then ultrafilter proteins activate inflamm and fibergenic pathways

Question 9

Proteinuria

Answer 9

● Marker of kidney damage
● Strong risk factor for cardiovascular mortality and morbidity
● Higher proteinuria = higher risk of end stage renal disease (ESRD)

ESRD = on dialysis or need transplant

Question 10

ALBUMINURIA
(DIABETIC NEPHROPATHY)

what does ACR say?

Answer 10

ACR =
[albumin (mg/L)]
[creatinine (mmol/L)

the higher it gets, the worse it is
- overt nephropathy = macroalbuminuria
Progress from normal to overt nephrophathy - leading to ESRD