CVD in Renal Dysfunction and Diabetes Flashcards
What is Glomerulo-atherosclerosis?
This is characterised by low glomerular density and severe glomerulomegaly, and is a result of obesity – especially DM-related obesity.
What does gomerulo-athersclerosis cause?
This reduces renal function significantly and results in dysfunction largely because the podocytes that form part of the filtration layer are unable to proliferate to match the glomerular growth, allowing proteins to enter the loop of Henle and hence be excreted.
What occurs to lipids in healthy nephrons?
Lipids pass through the healthy glomerulus and are taken up by the tubular cells in the loop as a source of energy.
What effect can chronic dyslipidaemia have on the nephrons?
Chronic dyslipidaemia as well as oxHDL and oxLDL are associated with FSGS, focal segmental glomerulosclerosis.
Immunostaining of diabetic/obese FSGS patients has identified high levels of ApoB deposition (B) and foam cell formation (C) have been identifies within the scarred glomeruli and within the tubular cells.
Lipid accumulation similar to as occurs within the vasculature implies a similar mechanism and cause, and can cause chronic kidney disease (CKD) thus linking the two disorders.
What kind of dyslipidaemia is caused by DM?
DM does not lead to a change in cholesterol or even blood LDL levels, but diabetic men and women had about twice the prevalence of low HDL and high TG in their plasma.
Low levels of HDL have a significantly greater association with CHD than high LDL levels anyway.
Why does DM lead to reduced HDL?
This occurs because insulin resistance leads to continuous secretion of FFAs by adipose cells, leading to increased FFA uptake by the liver and thus increased VLDL production.
The increased VLDL levels lead to more CETP activity, allowing more of the many more numerous HDLs to be swollen with TGs; a state in which they are more quickly degraded by hepatic lipase.
What effect does DM have on LDLs?
The increased CETP activity in diabetes also increases the TG:CE ratio in LDLs, increasing their propensity to form small, dense, atherogenic LDLs (also due to the action of HL).
These are more dangerous due to reduced clearance, greater infiltration into the intima, greater retention within it and faster oxidation.
How does chronic kidney disease cause dyslipidaemia?
Kidney disease leads to proteinuria (the loss of protein in urine). This causes the loss of many lipoproteins and those involved in lipostasis, including ApoA1 and ApoCII.
This ultimately leads to this less favourable lipoprotein profile, increasing risk of CVD.
What is the effect of the loss of ApoA1 due to CKD?
ApoAI loss prevents HDL formation and thus reduces cholesterol efflux and contributes to cellular rediistribution of cholesterol and thus sclerosis.
What is the effect of the loss of ApoCII due to CKD?
The loss of ApoCII (and relative increase in ApoCIII) and albumin prevents LPL activity, leading to a failure to lipolyse VLDLs and CMs, further contributing to dyslipidaemia.
This leads to a compensatory increase in ApoB100, further increasing VLDL and LDL plasma concentration, as well as increasing delivery of loosely bound FFA to the liver increasing VLDL synthesis
To what extent is CKD a risk factor for CVD?
Patients on haemodialysis and peritoneal dialysis have a 32 and 33 (resp.) fold increase in CVD mortality over the general population, with those who undergo kidney transplants have on a 2x greater incidence.
This means that a 25 y.o. patient with CKD is similar to that of an 80 y.o. patient without it. CVD is hence a large killer of those with CKD.
How does CKD correllate with CVD risk factors?
Association of CKD with inflammatory biomarker CRP is even higher than that of CVD. However, as noted, cholesterol does not correlate with CRP.
These explain one another, as CKD leads to chronic inflammation and hence cellular redistribution of cholesterol, decreasing the plasma cholesterol levels.
