ChemPath: Assessment of Renal Function 2

AKI • Abrupt decline in GFR • Potentially reversible • Treatment to precise diagnosis and reversal of disease CKD • Longstanding decline of GFR • Irreversible • Treatment targeted to prevention of complications and limiting progression

Rapid reduction in kidney function, leading to inability to maintain electrolyte, acid-base and fluid homeostasis. It is a medical emergency necessitating referral to a nephrologist for diagnosis and treatment

• Stage 1: increase in serum creatinine by 1.5-1.9x baseline (or by >26.5 µmol/L) • Stage 2: increase in serum creatinine by 2-2.9x baseline • Stage 3: increase in serum creatinine by ≥3x baseline

AKI caused by reduced renal perfusion No structural abnormality

• 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

• 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

• True volume depletion (dehydration) • Hypotension (e.g. septic shock) • Cardiac failure • Selective renal ischaemia (e.g. BILATERAL renal artery stenosis) • Drugs affecting renal blood flow

• NSAIDs - decreased afferent arteriolar dilatation • Calcineurin inhibitors - decrease afferent arteriolar dilatation • ACE inhibitors - reduce efferent arteriolar constriction • Diuretics - affect tubular function and decrease preload

Acute tubular necrosis (ATN)

Epithelial cell casts

• Vascular (e.g. vasculitis) • Glomerular (e.g. glomerulonephritis) • Tubular (e.g. ATN) • Interstitial (e.g. AIN)

Ischaemia (MOST COMMON) Toxins • Endoengous: myoglobin, immunoglobulin • Exogenous toxins: aminoglycosides, amphotericin, aciclovir Ischaemia = pre-renal progressing to ATN

• Glomerulonephritis e.g. lupus, Goodpasture’s • Vasculitis e.g. GPA

• Amyloidosis (associated with nephrotic syndrome) • Lymphoma • Myeloma

Physical obstruction of urine flow

• Intra-renal • Ureteric • Prostatic/urethral • Blocked urinary catheter

• GFR is dependent on a hydrostatic pressure gradient • Obstruction results in increased tubular pressure • This results in an immediated decline in GFR

• Glomerular ischaemia • Tubular damage • Long-term interstitial scarring Immediate relief of short-term obstruction restores GFR fully, with no structural damage

Decreased renal perfusion is the most common cause of AKI Iatrogenic causes: - Medications - Radiographic contrast

• Complete recovery of renal function • Partial recovery of renal function • Discharged with increased serum creatinine • Discharged requiring chronic dialysis • Death

• Increase in serum creatinine >26.5µmol/L within 48 hours • Increase in serum creatinine >1.5x baseline within the previous 7 days • Urine volume < 0.5 ml/kg/hr for 6 hours

• Haemostasis • Inflammation • Proliferation • Remodelling

Determines scarring i.e. whether a patient will recover kindey function or have chronically impaired kidney function

eGFR - mL/min • Stage 1: >90 • Stage 2: 60-89 • Stage 3: 30-59 • Stage 4: 15-29 • Stage 5: <15 or dialysis (end-stage renal failure)