ChemPath: Assessment of Renal Function 2 Flashcards
Define AKI.
Rapid reduction in kidney function, leading to inability to maintain electrolyte, acid-base and fluid homeostasis.
What are the three stages of AKI?
Stage 1: increase in serum creatinine by 1.5-1.9 times baseline
Stage 2: increase in serum creatinine by 2-2.9 times baseline
Stage 3: increase in serum creatinine by >3 times baseline
What is pre-renal AKI?
AKI caused by reduced renal perfusion
Describe the normal response to reduced circulating volume.
- Activation of central baroreceptors and renin-angiotensin system
- Release of vasopressin
- Activation of sympathetic system
- Results in vasoconstriction, increased cardiac output and renal sodium retention
Name and describe the two mechanisms that maintain renal blood flow despite changes in systemic blood pressure.
- Myogenic stretch - if the afferent arteriole gets stretched due to high pressure, it will constrict to reduce the transmission of that pressure to the glomerulus
- Tubuloglomerular Feedback - high chloride concentration in the early distal tubule (suggestive of high GFR) stimulates constriction of the afferent arteriole which lowers GFR and, hence, chloride concentration
List some causes of pre-renal AKI.
- True volume depletion
- Hypotension
- Oedematous state
- Selective renal ischaemia (e.g. renal artery stenosis)
- Drugs affecting renal blood flow
List some drugs that affect renal blood flow.
- ACE inhibitors - reduce efferent arteriolar constriction
- NSAIDs - decreased afferent arteriolar constriction
- Calcineurin inhibitors - decrease afferent arteriolar constriction
- Diuretics - affect tubular funciton and decrease preload
What is a consequence of prolonged pre-renal insult?
Acute tubular necrosis (ATN)
What might be seen on urine microscopy in a patient with ATN?
Epithelial cell casts
What causes post-renal AKI?
Physical obstruction of urine flow
List some sites of urine obstruction.
- Intra-renal
- Ureteric
- Prostatic/urethral
- Blocked urinary catheter
Outline the pathophysiology of post-renal AKI.
- GFR is dependent on a hydraulic pressure gradient
- Obstruction results in increased tubular pressure
- This results in an immediated decline in GFR
What are some consequences of prolonged renal obstruction?
- Glomerular ischaemia
- Tubular damage
- Long-term interstitial scarring
List the possible sites of disease in intrinsic AKI.
- Vascular (e.g. vasculitis)
- Glomerular (e.g. glomerulonephritis)
- Tubular (e.g. ATN)
- Interstitial (e.g. AIN)
What can cause direct tubular injury?
- Ischaemia (MOST COMMON)
- Endoengous toxins (e.g. myoglobin, immunoglobulin)
- Exogenous toxins (e.g. aminoglycosides, amphotericin, aciclovir)
Which diseases can cause AKI due to infiltration/abnormal protein deposition?
- Amyloidosis (associated with nephrotic syndrome)
- Lymphoma
- Myeloma
List the possible outcomes of AKI.
- Partial recovery of renal function
- Discharged with increased serum creatinine
- Discharged requiring chronic dialysis
- Death
What are the biochemical definitions of AKI?
- Increase in serum creatinine > 26.5µmol/L within 48 hours
- Increase in serum creatinine > 1.5 times baseline within the previous 7 days
- Urine volume < 0.5 ml/kg/hr for 6 hours
What are the four processes of acute wound healing?
- Haemostasis
- Inflammation
- Proliferation
- Remodelling
What are the stages of CKD?
- Stage 1: >90
- Stage 2: 60-89
- Stage 3: 30-59
- Stage 4: 15-29
- Stage 5: <15
List some causes of CKD.
- Diabetes mellitus
- Hypertension
- Chronic glomerulnephritis
- Atherosclerotic renal disease
- Infective or obstructive uropathy
- Polycystic kidney disease
What are the normal roles of the kidney?
- Excretion of water-soluble waste
- Water balance
- Electrolyte balance
- Acid-base homeostasis
- Endocrine (EPO, RAS, vitamin D)
Outline the consequences of CKD.
- Progressive failure of homeostatic function (acidosis, hyperkalaemia)
- Progressive failure of hormonal function (anaemia, renal bone disease)
- Cardiovascular disease (vascular calcifiction, uraemic cardiomyopathy)
- Uraemia and death
What are the consequences of renal acidosis?
- Muscle and protein degradation
- Osteopaenia due to mobilisation of bone calcium
- Cardiac dysfunction
How is renal acidosis treated?
Oral sodium bicarbonate
What are the consequences of hyperkalaemia?
- Cardiac dysfunction (arrhythmia)
- Muscle dysfunction
NOTE: hyperkalaemia causes membrane depolarisation
Which medications can cause hyperkalaemia?
- ACE inhibitors
- Spironolactone
- Potassium-sparing diuretics
What type of anaemia does chronic renal disease cause?
Normochromic, normocytic anaemia
How is anaemia of chronic renal disease treated?
- Erythropoietin alfa (Eprex)
- Erythropoietin beta (NeoRecormon)
- Darbopoietin (Aranesp)
NOTE: if CKD is not responding to erythropoiesis stimulating agents, consider iron deficiency, malignancy, B12 deficiency etc.
List some types of renal bone disease.
- Osteititis fibrosa cystica
- Osteomalacia
- Adynamic bone disease
- Mixed osteodystrophy
Outline the pathophysiology of renal bone disease.
- Damaged kidneys are unable to excrete phosphate and activate vitamin D
- Phosphate retention stimulates the production of FDF23 and Klotho
- This lowers the levels of activated vitamin D
- To try and get rid of the excess phosphate, the body will produce more PTH
- Furthermore, to try and increase levels of vitamin D, the body will produce more PTH (i.e. there are two stimuli for PTH release)
- High levels of PTH will result in the bone becoming resistant to PTH
What is osteitis fibrosa cystica?
Caused by osteoclastic resoprtion of calcified bone and replacement by fibrous tissue (feature of hyperparathyroidism)
What is adynamic bone disease?
Overtreatment leading to excessive suppression of PTH results in low bone turnover and reduced osteoid
Outline the treatment of renal bone disease.
- Phosphate control - dietary, phosphate binders
- Vitamin D activators - 1-alpha calcidol, paricalcitol
- Direct PTH suppression - cinacalcet (works by increasing the sensitivity of the calcium sensing receptor)
What is the most important consequence of CKD?
Cardiovascular disease - this is most likely to kill them
What are the three phases of uraemic cardiomyopathy?
- LV hypertrophy
- LV dilatation
- LV dysfunction
What are the treatment options for patients with CKD?
- Transplantation
- Haemodialysis
- Peritoneal dialysis
