Renals 101121 Flashcards
normal glomerular filtration rate
120ml/hr
How is AKI classified
Pre-renal, intrinsic renal, post-renal
Causes of pre-renal AKI
o True volume depletion (e.g. haemorrhage) Hypotension
o Oedematous state Selective renal ischaemia (e.g. renal artery stenosis)
o Drugs affecting renal blood flow
ACE inhibitors or ARBs – reduce efferent constriction
• ACEi are very contraindicated in RAS
NSAIDs or Calcineurin inhibitors – decrease afferent dilatation
Diuretics – affect tubular function, decrease preload
AKI vs tubular necrosis
o Pre-Renal AKI is NOT associated with structural renal damage
Responds immediately to restoration of circulating volume
However, a prolonged AKI insult ischaemic injury (ATN)
o ATN does NOT respond to restoration of circulating volume
o Epithelial cell casts would be seen in the urine on microscopy
causes of postrenal AKI
• Hallmark is physical obstruction (at any level) to urine outflow
o (Intra-renal obstruction) Ureteric obstruction (bilateral)
o Prostatic / urethral obstruction Blocked urinary catheter
o Retroperitoneal fibrosis / Ormond’s disease
Pathophysiology of post renal AKI
o GFR is dependent on the hydraulic pressure gradient
o Obstruction results in increased tubular pressure
o This results in an immediate decline in GFR
causes of renal aki
• Pathophysiology is more diverse (abnormality could be anywhere in the nephron):
o Vascular disease (e.g. vasculitis)
o Glomerular disease (e.g. glomerulonephritis)
o Tubular disease (e.g. ATN) = MOST COMMON
o Interstitial disease (e.g. analgesic nephropathy – long-term excessive use of analgesics)
causes of direct tubular injury
Most commonly ischaemic
Endogenous toxins myoglobin (i.e. rhabdomyolysis from muscle injury), immunoglobulins
Exogenous toxins contrast medium > aminoglycosides, amphotericin, aciclovir
infiltrative causes of renal AKI
Amyloidosis (causes nephrotic syndrome)
Lymphoma
Multiple Myeloma
Define severity of AKI
o Serum creatinine
o Urine output
How is AKI staged
stage 1 (1.5-1.9x baseline serum creatinine , <0.5ml/kg/h 6-12 hours urine output) stage 2 (2-2.9 x creatine, <0.5ml/kg/h for 12 hours) stage 3 (3x creatinine, anuria for 12 hours)
Consequences of CKD
o (1) Progressive failure of homeostatic function
(1a) Acidosis
(1b) Hyperkalaemia
o (2) Progressive failure of hormonal function
(2a) Anaemia
(2b) Renal bone disease
o (3) Cardiovascular disease
Vascular calcification (renal osteodystrophy)
Uraemic cardiomyopathy
o (4) Uraemia and death
Anaemia of CKD
o Progressive decline in EPO-producing cells
o Usually occurs when GFR <30 ml/min
o Causes normochromic, normocytic anaemia
This helps distinguish it from other causes of anaemia (e.g. iron deficiency, B12 deficiency)
o TREATMENT: use artificial erythropoiesis-stimulating agents (ESAs)
Erythropoietin alfa (Eprex)
Erythropoietin beta (NeoRecormon)
Darbopoietin (Aranesp)
o NOTE: reasons for CKD not responding to an erythropoiesis-stimulating agent:
Iron deficiency, TB, malignancy, B12 and folate deficiency, hyper-parathyroidism
Hyperkalaemia of CKD
o Hyperkalaemia causes membrane depolarisation
o This impacts on:
Cardiac function
Muscle function
o Medications that cause hyperkalaemia:
ACE inhibitor
Spironolactone (potassium-sparing diuretics)
Reasons for CKD not responding to EPO
Iron deficiency, TB, malignancy, B12 and folate deficiency, hyper-parathyroidism
Renal bone disease types
o Complex entity resulting in reduced bone density, bone pain and fractures: Osteitis fibrosa cystica Osteomalacia Adynamic bone disease Renal osteodystrophy
Cardiovascular disease in CKD
Cardiovascular disease (vascular calcification, uraemic cardiomyopathy):
o This is the MOST IMPORTANT consequence of CKD (it is most likely thing to kill them)
o The risk of a cardiac event seems to be directly related to GFR
o Atherosclerosis:
Traditional risk factors such as cholesterol and hypertension contribute towards the risk
Renal vascular lesions are characterised by heavily calcified plaques (rather than lipid-rich atheromas)
o Uraemic Cardiomyopathy (THREE phases):
LV hypertrophy LV dilatation LV dysfunction
Indications for dialysis
o Refractory hyperkalaemia o Refractory fluid overload o Metabolic acidosis o Uraemic symptoms (encephalopathy, nausea, pruritis, malaise, pericarditis) o CKD stage 5 (GFR <15mL/min)
What is the best measure of kidney function
GFR (normally = 120mL/minute; 7.2L/hour)
o There is an age-related decline of around 1 mL/min per year
Clearance
o Clearance can be used to calculate GFR
o There are THREE criteria* that need to be fulfilled for a marker to be used to measure GFR:
Marker is NOT bound to serum proteins
Freely filtered by the glomerulus
NOT secreted or reabsorbed by tubular cells
o If these conditions are fulfilled, then clearance = GFR; at any one point:
C = (U x V)/P
perfect GFR marker in research
insulin
CKD-EPI
CKD-Epidemiology Collaboration (CKD-EPI)
• The equation is based on the same four variables as MDRD but models the relationship between GFR and serum creatinine, age, sex and race differently
• It is an improvement on MDRD, but it is still imprecise at higher GFRs
o Reduces bias at GFRs >60mL/min (but imprecise at higher GFRs)
o I.E. Accurate at LOW GFRs and less accurate at HIGH GFRs
cYSTATIN c
This is an alternative endogenous marker
This is constitutively produced by all nucleated cells at a constant rate and is freely filtered
Almost completely reabsorbed and catabolised by tubular cells
NOTE: CKD NICE guidelines have included cystatin C, however, it is not used that frequently
Urine protein: creatinine ratio
o This is a quantitative assessment of the amount of proteinuria
o Measurement of creatinine corrects for urinary concentration
o Two methods to do PCR:
24hr urine collection (cumbersome and messy; highly inaccurate without patient education)
Spot urine measurement
Renal imaging
o 1st line: CT KUB
o 2nd line: Ultrasound KUB
This can differentiate AKI and hydronephrosis
o Plain KUB films (can show ‘staghorn calculi’)
o IV urogram (done more in paediatrics to look for anatomical defects)
o MRI KUB
o Functional imaging (static and dynamic renograms)
IV radiolabelled nuclei are injected, and kidney uptake is measured
Any kidney not showing up on scans signifies a non-functional kidney
o Renal biopsy is often necessary for various diagnoses (ultrasound or CT guided)
