CKD and Cardiovascular Risk Flashcards
What is chronic kidney disease characterised by?
- GFR of less than 60 mL/min/1.73 m2
- Albuminuria of at least 30 mg per gram per 24 hours
- Or markers of kidney damage (e.g., haematuria or structural abnormalities such as polycystic kidneys)
- Persisting for more than 3 months
Kidney disease is a very economically burdening disease on the NHS. What factor mainly drives this?
Dialysis costs and expenses
What are two major factors involved in the rise of CKD prevalence?
- Increased ageing population
- Prevalence of T2DM and cardiovascular disease contributing to CKD
To make a diagnosis of chronic kidney disease based on risk, what two factors are needed?
- eGFR and UACR
Describe nephron development.
- Nephrons are generated in weeks 12–36 of gestation in humans, with a mean of 950,000 nephrons per kidney (with a range of∼200,000 to >2.5 million)
- No new nephrons can be generated after this period.
- During growth, the available nephrons increase in size to accommodate increased renal demands.
Give examples of times when GFR can decrease.
- Ageing
- Hypertension
- Constriction of afferent arterioles/dilation of efferent arterioles
- BUN
- Diabetes
- Obesity
Give examples of causes of CKD within each age group.
- In utero - genetic defects and maternal malnutrition
- Infancy - environmental toxin exposure and nephrotoxic drugs
- Adolescence - T1DM, autoimmune glomerulonephritis
- Early adulthood - obesity and T2DM
- Middle age - Atherosclerosis and age-related nephron loss
Describe a mechanism by which pre-CKD can advance to advanced stage CKD.
- Proteinuria and misdirected filtration
- Tubular cell stress and activation - cytokine secretion promote interstitial inflammation
- Tubular cell loss and tubule obstriuction cause atrophy
- Scar formation due to fibrosis and ischaemia
- Tubular hypertrophy
Give some outcomes of CKD that can lead to cardiovascular disease.
- Anaemia
- Sodium and volume overload
- Inflammation and increased oxidative stress
- Haemostatic abnormalities
What cardiovascular outcomes can occur as a result of CKD?
- Heart failure
- Stroke
- Coronary artery disease
- AAA
- VTE
- Atrial fibrillation
RECAP: What is the mechanism of action of SGLT2 inhibitors?
- Reversible competitive inhibition of SGLT2 channels in the PCT of the kidney.
- SGLT2 is responsible for 90% of glucose reabsorption from the nephron, therefore inhibition leads to increased secretion of glucose in the urine
- Decreased blood glucose levels.
What are the current guidelines regarding CKD in patients with type 2 diabetes?
- CKD screening
- Blood pressure control using RAAS inhibition
- SGLT2 inhibition - studies proving that in patients with kidney disease or T2DM, it reduces risk of renal failure and cardiovascular events
Despite its positive effects in normal circumstances, aldosterone can exacerbate CKD. Suggest how.
- Overactivation of the mineralocorticoid receptor
- Increases sodium retention and hypertension and provokes inflammation and fibrosis in the kidneys, blood vessels, and the heart
- Progression of cardiorenal disease.
Describe how mineralcorticoid receptor antagonists can be used in cases of mineralcorticord overactivation.
EXAMPLE: Finerenone
- Inhibits the effects of mineralocorticoids like aldosterone and cortisol when the MR is overactivated
- Reduces inflammation and fibrosis in the heart and kidney
RECAP: Describe how antihypertensive drugs are chosen for patients with hypertension.
https://d1z8zkw1yi6kd7.cloudfront.net/uploads/ckeditor/pictures/data/000/001/601//content/management_of_htn.jpg
Where A is ACE inhibitor/ARB , C is CCB and D is thiazaide like diuretic
