Lecture 45b: CKD Pathophysiology Flashcards
what is the clinical relevance of CKD
- CKD is common (10% adults)
- assc. w/ diabetes and hypertension
- assc. w/ premature mortality
what is the most severe form of CKD
end stage renal disease or ESRD
what is CKD
chronic kidney disease
- dec in GFR which occurs over months or years and is usually irreversible
how is renal function measured
- serum creatinine (from U&E)
- GFR from serum creatinine measurement
at what % of kidney function does serum creatinine rise outside of normal range
~ below 50% GFR
what is the normal GFR in adults
~100mL/min
what is eGFR used on
- age
- sex
- ethnicity
- serum creatinine
how is CKD classified
stage 1 = eGFR >90 stage 2 = eGFR 60-89 stage 3 = eGFR 30-59 stage 4 = eGFR 15-29 stage 5 = eGFR <15
what CKD stages typically concern clinical medicine
stage 3-5
how common is CKD
5-6% have stage 1-2
~5% have stage 3-5
list symptoms of CKD
- symptoms often occur very late when kidney function is poor
- fatigue (anaemia 2nd to Epo deficiency)
- SoB (fluid retention +/- acidosis)
- leg oedema (fluid retention)
- nausea, anorexia, weight loss (retained toxins)
- itch (retained toxins)
- bone pain (vit D defect)
why is fatigue a symptom of CKD
in CKD there is reduced Epo production by kidneys which leads to anaemia
give some signs of abnormal kidney function
- pallor (anaemia)
- oedema (salt and fluid retention)
- hypertension ( salt and fluid retention)
- proteinuria +/- haematuria
give some of the causes of CKD
- diabetic kidney disease
- hypertensive and/or atherosclerotic vascular disease of kidneys
- glomerulonephritis
- polycystic kidney disease
- tubulointerstitial disease (chronic pyelonephritis/refluc nephropathy)
what are the risk factors for CKD
- renal disease
- diabetes
- hypertension
- smoking
- dyslipidemia
- age
- male>female
- family history
- cardiac disease
what might be seen histologically in diabetes related CKD
- diabetic glomerulus has expansion of messangial cells and messangial cell matrix
- nodules –> nodular form of glomerular sclerosis
how does diabetes cause kidney disease
- neuropathy in diabetes can cause development of nodules on the glomeruli
- dec number of caps fo blood flow so GFR falls
describe the pathology of diabetic nephropathy
- ^ intraglomerular hypertension
- -> glomerular sclerosis
- hyperglycaemia
- -> messangial expansion
- -> glom BM thickening
how does albumin get into urine in diabetic kidney disease
- BM is thickened but leaky
- ^ pressure in glomerulus
what is the issue with albumin in urine
proteinuria is toxic to tubules
what is the result of progressive diabetic kidney disease
- tubular atrophy
- cellular infiltrate
- interstitial fibrosis
- vasculopathy
what meds are used to treat proteinuria renal disease and why
ACEi and ARBs
- block ang2 formation to allow efferent arteriole to dilate again and reduce glom cap pressure
43 year old woman , type 1 diabetes. BP is 151/93 , urine albumin creatine ratio indicates albuminuria.
Which drug would be used to control her blood pressure to reduce risk of kidney disease
ramipril
- ACEi that dec. BP, intraglomerular cap pressure, dec albuminuria and slow progression of diabetic kidney disease
what are the consequences of reduced GFR
- fluid retention
- -> HF
- -> tissue oedema (pitting oedema)
- reduced metabolite excretion
- -> uraemia
- -> ^ serum creatinine
- -> ^ serum urate ( can cause gout)
what are the 2 key issues w/ drug prescribing in renal disease
- kidney failure (low GFR) prolongs half life of many drugs –> ^ risk of drug toxicity
- some drugs can make kidney failure worse by disturbing renal physiology e.g. NSAIDs
consequences of reduced renal tubular filtration
- reduced fluid reabsorption
- -> polyuria
- -> nocturia
- reduced K+ excretion
- -> hyperkalaemia
- reduced acid secretion and reduced bicarb formation
- -> Metabolic Acidosis
is K+ mor ICF or ECF
ICF
what are the primary issues in renal bone disease
- reduced vit D activation because of kidney damage
- dec Ca absorption from gut
- decreased mineralisation of bone (osteomalacia)
- reduced active vit D and low Ca stimulate release of PTH resulting in bone resorption (hyperparathyroidism)
in normal health what other molecule in the body is calcium normally in balance w/
phosphate
what happens to phosphate levels when calcium levels decrease
phosphate levels ^
how does ^ PTH release (stimulated by low calcium and low active vit D) affect calcium and phosphate levels
- ^ Ca levels
- no change to phosphate levels
- now have high Ca and high phosphate in the body
name an issue that can arise as a result of high calcium and phosphate levels in the body
ectopic calcification of tissues (in Px w/ CKD)
what cells are stimulated by PTH to release calcium
osteoclasts
what cells require active vit D to carry out their function
osteoblasts
explain how renal bone disease can arise as a result of CKD
- CKD = damaged kidney
- reduced vit D activation by kidney
- dec Ca absorption from gut
- dec mineralisation of bone
- -> osteomalacia
- reduced Ca and active vit D stimulate PTH release
- -> hyperparathyroidism
- PTH stimulates osteoclasts to resorb bone to release Ca
- osteoblasts require active vit D to reverse bone resorption; no active vit D so no osteoblast action
83yo man has stage 5 CKD. Clinical blood tests indicate his eGFR is 11mL/min/1.73m2.
Which of the following electrolyte disorders is most likely to be present in this man?
a) hyperkalaemia
b) hypokalaemia
c) hyponatraemia
d) hypernatraemia
e) hypocalcaemia
a) hyperkalaemia
- hyperkalaemia most likely b/c kidney excretion of K is significantly impaired by poor kidney function (very low eGFR)
what is one of the most important signs and most easily modifiable risk factor for CKD
hypertension
outline the management of CKD
- treat hypertension
- slow the progression of proteinuric renal diseases w/ ACEi or ARBs
- reduce assc. CVD risks e.g. statin for hyperlipidaemia
- treat any complications:
- -> anaemia (Epo injections)
- -> renal bone disease (activated vit D)
- -> hyperphosphataemia (phosphate binding drugs)
- -> hyperkalaemia (restrict dietary intake)
outline some renal replacement therapies for ESRD
- haemodialysis
- -> vascular access e.g. arteriovenous fistula or central venous catheter
- peritoneal dialysis
- -> peritoneal dialysis catheter inserted into abdomen w/ incision below umbilicus to insert end exit site on right/left side of lower abdomen
- kidney transplant
- -> placed in left/right iliac fossa (palpable kidney underneath surgical scar)
compare and contrast the two methods of chronic dialysis
haemodialysis
- usually hospital based
- nurse delivered
- 3x per week
- needs access to blood
- very expensive
- restricted to sites w/ dialysis machines
peritoneal dialysis
- home based
- patient performs dialysis
- daily
- uses abdominal cavity
- cheaper
- can be done virtually anywhere in the world
what is the best form of renal replacement therapy for ESRD
kidney transplant
why are kidney transplants preferred in ESRD if Px suitable
- > 95% success rate
- better quality of life for Px
- much better survival for Px
- much cheaper per year than dialysis
what is the downside of having a kidney transplant
- lifelong drug treatment to suppress immune system and prevent rejection of transplant
- so increased risk of infection
