diabetic kidney disease Flashcards
where do the kidneys sit in relation to the peritoneum?
they are retroperitoneal
what are the 3 stages of mammalian kidney development?
pronephros, mesonephros, metanephros
what is the functioning unit of the kidney?
nephron
what happens at the proximal end of the nephron?
filtration
how many nephrons roughly in each kidney? relevance?
about 1 million
having too little is relevant in kidney disease
loose functioning nephrons as we age
what is actually the filtration barrier in the glomerulus?
the wall of the capillaries in the glomerulus
a 70kg adult will filter how many L through the nephrons each day?
180L
what cells line the capillaries of the glomerulus?
endothelial cells
what are podocytes?
- sit on outside of the glomerular capillaries
- specialised epithelial cells
- essential for filtration
what are the 2 main components of matrix?
basement membrane
- glomerular
- tubular
- bowman’s capsule
intestitial matrix (looser)
- mesangium
- tubulointerstitium
what early changes occur due to a variety of diseases to the glomerulus (cellular and matrix defects)?
loss of filtration function
- thickening of basement membrane
- flattening of foot processes of podocytes
reversible however dont present with clinical symptoms!
what can be one of the earliest signs of kidney disease and requires investigation?
persistent leakage of proteins that can be detected in the urine — this is ABNORMAL
what later changes occur due to a variety of diseases to the glomerulus (cellular and matrix defects)?
- podocyte detachment — fall into urine
- accumulation of matrix — thickening of basement membrane
- sclerosis
- infiltration of cells that shouldn’t be there
leads to irreversible loss of function
what is Anti-GBM disease?
get antibodies to the basement membranes in the glomerulus — fairly aggressive disease, not much in the way of proteinuria, but get a rapidly progressive destructive glomerulonephritis
what is IgA nephropathy?
get IgA deposited in the kidneys — assoicated with a range of presentations (range of proteinuria)
what are the 3 characteristic features of nephrotic syndrome?
clinical presentation - not a condition by itself
- massive proteinuria
- low serum albumin (cut off is 25g/L)
- oedema — accumulation of fluid in tissues
what are the different types of proteinuria?
- glomerular = most common (up to 90%)
- tubular
- overflow
- post-exercise
- post-prandial
- infection-associated
what are characteristics of tubular proteinuria?
may be genetic
low molecular weight proteins, such as B2-microglobulin
what is overflow proteinuria?
increased production, that is, light chains in multiple myeloma
characteristics of post-prandial proteinuria
- transient physiological proteinuria
- poss through insulin action in podocytes
what are normal vs nephrotic range values for protein:creatinine ratio (PCR) ?
normal = <20mg/mmol
nephrotic range = 200mg/mmol
what are normal vs nephrotic range values for albumin:creatinine ratio (ACR) ?
microalbuminuria = >3mg/mmol
albuminuria = >30mg/mmol
what % of diabetics develop nephropathy?
40%
what are the stages of injury in diabetic kidney disease?
- hyperfiltration
- microalbuminuria
- macroalbuminuria
- proteinuria
- declining renal function
diabetic mechanism of glomerular hyperfiltration
whole kidney level:
- increase in renal blood flow
- increase in filtration fraction
- vasodilation of afferent arteriole
- proximal tubular sodium reabsorption
- glomerular hypertension
- increase in RAAS
SHE DIDNT GO THROGUH THIS
pathology in the glomerulus
- GMB thickening
- mesangial expansion — proliferate and expansion of matrix
- nodular sclerosis
- advanced sclerosis
how is diabetic nephropathy classified (flow chart)?
treatment goals for DN
- glycaemic control
- BP control
- RAAS blockage ACEi/ARB (RENAAL T2DM Losartan, also in normotensive T1DM, Aliskiren renin inhibitor)
- lipid lowering
- reduce other CV risks
when would diuretics be used?
if there is fluid accumulation or oedema associated with significant proteinuria
what are the 2 main types of diuretics used in clinical practise?
thiazide and loop diuretics
what do diuretics do?
- reduce the ECF volume
- lower BP
- augment effects of RAAS inhibitors
SGLT2 inhibitors can be used for kidney disease and what?
diabetes, heart failure
why are SGLT2 inhibitors not yet approved for T1DM?
there is a risk of ketoacidosis
what is peritoneal dialysis?
- tube is surgically placed into the abdomen = peritoneal dialysis catheter which is connected to a hypotonic fluid bag
- immediate use reduces fluid overload
- no anticoagulation
- cheapest - global application
- continuous
- least likely to cause fluid shifts and hypotension
describe haemodialysis and haemofiltration
- need to access circulation via central venous catheter, surgically if permanent, arteriovenous fistula etc
- specialist nursing care
- tertiary units
- need for good central venous access
- high and efficient solute clearance
- anticoagulation
- intermittent : not tolerated when haemodynamically unstable
- continuous : haemofiltration used in less stable patients eg in ICU, not as aggressive in terms of fluid removal aspect
dialysis - diffusion
filtration - convection
in peritoneal dialysis, where is the hypotonic fluid put in the body?
peritoneal space — pulls out water and waste products from circulation via tissues
what kind of transplants can you get?
- kidney
- combined kidney and pancreas
- islet cell
