Acute Kidney Injury Flashcards
Physiological Function of Kidney
- Filtration, reabsorption and secretion
- Regulation of volume and composition of body fluids e.g. ADH, RAAS
- Endocrine functions – renin/ PGs/ bradykinin for haemodynamics; erythropoietin for RBC production; vitamin D in Ca and PO4 metabolism
Normal Na, K handling, urine concentration
Sodium
- fractional excretion <0.5% i.e. 99.5% of filtered Na is reabsorbed (at PCT and TAL)
Water concentration
- maximum urine conc is 1200 mmol/L and 1200 mmol obligatory excretion of solutes
- -> minimum 1 L output per day
- concentration gradient at loop, ADH action at collecting duct
Potassium
- majority reabsorbed in PCT
- control by secretion in DCT and MCT
- tight control to meet requirement e.g. renin and aldosterone
Measurement of Renal function
Glomerular filtration: GFR (normal 120 ml/min), Creatinine Clearance
** Calculation of Creatinine Clearance (ml/min) Urine volume (ml) x [Cr]Ur in mg/dL // [Cr]p in mg/dL x collection time (min; 24hr or 1440 min)
Clcr = 1/[Cr]p (assuming daily production and excretion of Cr are constant)
GFR = Clcr
- -> decrease GFR = increase [Cr]p
- -> BUT [Cr]p NOT SENSITIVE TO PICK UP EARLY DROP IN GFR (only becomes abnormal when GFR = 60ml/min)
Uses of Creatinine
Calculation of creatinine clearance
Monitoring rate of progression of CRF
Detection of acute deterioration of RF (acute on chronic)
Planning future therapy (time of ESRD require dialysis around [Cr]p 800-1000 mcmol/L)
Limitations of Creatinine
Interfering chromogens
Proximal tubular secretion (assume no PCT handling when calculate)
Drug interference e.g. cotrimoxazole
Tubular creatinine secretion increases in severe CRF when GFR <20 (hence Clcr > GFR)
Muscle mass falls in advanced CRF (less creatinine production; not constant as assumed)
Measurement of creatinine clearance
24 hr urine collection
- issue of compliance
- more reliable due to variation in plasma creatinine during the day
To avoid 24 hr urine collection –> eGFR
- MDRD study or CKD-EPI study
- based on 1/[Cr]p
- have limitations and restrictions
Factors affecting urea
Increased
- production: protein diet, catabolic state, GI bleeding
- decreased excretion: low GFR (both Ur and Cr increase) or dehydration (Ur increase more than Cr to establish gradient)
Decreased
- production: fasting, low protein intake, liver disease
- increased excretion: high GFR
Useful as:
- index of acute on chronic failure (plasma Ur:Cr >80)
- indicator of retention of toxic metabolites
Limitations
- varying levels of reabsorption and secretion
- small amount excreted by sweat and faeces
Urea:Creatinine Ratio
Increase:
- pre-renal AKI: increased urea reabsorption for osmotic gradient but Cr not reabsorbed
- UGIB: high protein meal
- catabolic state e.g. trauma, severe infection, starvation
- decreased muscle mass
Acute Kidney Injury
Oliguria
= urine output <0.5 ml/kg/hr or <400 ml/day
Auria
= <50 ml/day
Definition of AKI
- increase in [Cr]p by >26.5 mcmol/L within 48 hrs (abrupt)
- increase in [Cr]p to >1.5 x baseline within 7 days (sustained)
- oliguria for 6 hrs
Acute deterioration of renal function that is potentially (but not always) reversible
- oliguria and auria are symptoms of AKI but not all AKI are oliguric
Pre-renal AKI (40-70%) causes
Caused by decrease in blood flow due to DECREASE IN ECV
Causes
1. renal hypoperfusion
- dehydration, increased GI loss, bleeding, increased renal loss e.g. diuretics/diuresis, salt-wasting nephropathies, increased skin and respiratory loss e.g. sweating, burns, sequestration into third space
- drugs: NSAIDs, ACEi/ARB – precipitate AKI in renal artery stenosis or chronically low ECV e.g. CHF, nephrotic syndrome or elderly
(NSAID inhibits PGs which dilates afferent arterioles; ACEi/ARB inhibits RAAS which constricts efferent arterioles)
- acute cardiac failure/ cardiogenic shock
- acute systemic vasodilation e.g. septic shock –> hypotension
Pre-renal AKI adaptation and progression
REVERSIBLE
Adaptation:
- constriction of efferent arteriole to increase filtration fraction in order to maintain GFR
- increased proximal tubule reabsorption
- decrease in urine volume and urine Na excretion due to ADH and Aldosterone (further Na reabsorption)
- increased passive reabsorption of urea
==> BOTH Ur and Cr RISES
Progression:
- deterioration (further drop in GFR) if not promptly treated
- -> remains immediately and fully reversible if blood flow sufficient to maintain integrity of kidney cells
==> if not treated, auto regulation fails and progress to irreversible ATN
Intrinsic AKI Causes
IRREVERSIBLE acute tubular necrosis due to renal ischaemia or toxins
Causes
- Progression from pre-renal injury
- efferent arteriolar constriction from auto regulation leads to reduced blood flow to tubules –> ischaemia
- increased risk in elderly, HT, DM, pre-existing renal disease - Specific renal diseases
- GN, interstitial nephritis (allergic reaction to various drugs) - Nephrotoxins
- exogenous: aminoglycosides (MC), amphotericin, tetracyclines; XR contrast media; cisplatin, heavy metal e.g. mercury
- endogenous: free Hb, myoglobin, light chains, uric acid crystals
Natural History of ATN
3 phases
- oliguric – urine <400ml/day (filtration resumes once fluids given)
- diuretic – urine >400ml/day (poor tubular fx)
- recovery – return of GFR to 70-80% normal
Each phase around 1 week, recovery phase can take up to a year
Not every phase present
Post-renal AKI (azotaemia) causes
OBSTRUCTIVE nephropathy
- luminal: stones, clots, sloughed papillae
- mural: malignancy, BPH, strictures
- extrinsic compression: malignancy, retroperitoneal fibrosis
Investigations of AKI
Hx and PE
- Hx of kidney disease, DM, drugs, poor fluid intake etc.
Ix
Urine
- urine dipstick –> infection (leukocytes and nitrites), glomerular disease (haematuria, proteinuria)
- microscopy –> red cell casts, crystals, cells
- urine culture for infection
- urine electrolytes (and plasma electrolytes)
Blood
- CBC, LRFT, Clotting, CK, ESR, CRP, ABG
- culture if suspect infection
- serum Ab/ ANCAs/ complements if suspect systemic causes
Imaging
- renal USG: distinguish obstruction vs hydronephrosis, also abnormalities e.g. cysts, small kidneys, masses
- CT without contrast: if inconclusive renal USG
- CXR: if signs of fluid overload
