12.1 Diabetic Kidney Disease Flashcards
Describe the pathophysiology of diabetic nephropathy
- Diabetes can cause hyperglycaemia, hyperinsulinaemia, and insulin resistance
- Hyperglycaemia, hyperinsulinaemia and insulin resistance results in production of advanced glycation endproducts (AGEs) and ROS
- These activate intracellular signalling pathways relating to fibrosis, inflammation, leading to cell injury (glomerulosclerosis)
What is renal hyperfiltration? How does it damage the kidneys
- Hyperfiltration is supraphysiologic GFR level
- Increases shear/tensile stress on glomerular capillaries, which may initiate and cause the progression of cell damage
How can diabetes cause glomerular hyperfiltration, and how does this contribute to diabetic nephropathy?
- Increased RAAS activation due to diabetic milieu (more efferent constriction due to angiotensin 2’s action)
- Other mediators (such as prostaglandins) increase other aspects of renal flow
- Tensile capillary stress from hyperfiltration leads to damage
What happens to GFR during the course of diabetic kidney disease? What about urinary albumin?
- We see initial hyperfiltration due to various factors in “diabetic milieu”
- Eventually, GFR declines, at which point we pick it up
- For earlier detection, we can use albumin excretion, which increases at faster and faster rates as the disease progresses
What pathological changes occur in the glomerulus as dfiabetic kidney disaease progresses?
- Thickening of GBM (?glycation)
- Mesangial expansion
- Kimmelstiel-Wilson nodules deposited in mesangium (made of hyualine, found in capillary loops)
- Arteriolar widening (?stiffening of GBM from glycation)
Using a mnemonic, list causes of high anion gap metabolic acidosis (HAGMA)
MUDPILESS
M: Methanol
U: Uraemia
D: DKA (or any other ketoacidosis)
P: Paracetamol
I: Iron (excess)
L: Lactic acidosis
E: Ethanol
S: Sepsis, Salicylates
How can DKA cause AKI? By explaining the mech, work out what kind of AKI it is
- DKA occurs in the setting of hperglycaemia
- This hyperglycaemia causes osmotic polyuria, leading to volume depletion
- Hypovolaemia -> prerenal kidney failure
List the three most common known causes of treated kidney failure
- Diabetic nephropathy (44% of new cases)
- Glomerulonephritis
- Hypertension
Risk factors for diabetic nephropathy
- Old age (vascular compliance)
- Male sex (more diabetes; more visceral fat deposition)
- Low socioeconomic status
Clinical features of diabetic nephropathy
- Most don’t occur until late stage
- When they do, we see oedema, proteinuria, decreased GFR
We screen for chronic kidney disease with a “kidney health check”. What are the components of this?
- Blood test (eGFR from creatinine)
- Urine test (ACR for kidney function)
- Blood pressure (checks for symptoms/risk)
The most common cause of kidney replacement in Australia is…
Diabetic kidney disease
Why is diabetic kidney disease incidence increasing, despite improvements in therapies?
Because the prevalence of diabetes is increasing.
Why does DKA widen the anion gap?
- Ketones are unmeasured anions; widen gap
- Hypovolemia -> hypoxia -> lactate anions, widens gap
How are SGLT2 inhibitors renoprotectice
- Inhibit sodium/glucose resorption
- More sodium in urine
- Macula densa detects more sodium; less Renin, less prostaglandin
- Afferent arteriole constriction; lower net filtration pressure, less shear stress on glomerular capillaries, preserved kidney function
