Session 9 Flashcards
What is meant by an Acute Kidney Injury?
[*] The kidney receives 25% of the cardiac output. It is one of the two major excretory organs, with the other one being the liver. As such, the kidney is subject to insults from any reduction in perfusion as well as from toxins. Approximately 7% of hospitalised patients will have experienced AKI.
[*] AKI is defined as an abrupt decline in the GFR that occurs during a period of less than 2 weeks. The decline in GFR is currently measured by an increase in serum creatinine although creatinine is not an ideal marker.
- This leads to upset of ECF volume, electrolyte and acid/base homeostasis
- Accumulation of nitrogenous waste products.
[*] AKI is an acute change in renal function in comparison to CKD in which the decline in GFR occurs over months to years.
What are the NICE Guidelines for detecting an AKI?
[*] NICE Guideline for Detecting Acute Kidney Injury (in line with the RIFLE, AKIN or KDIGO definitions by using any of the following criteria)
- A rise in serum creatinine of 26 micromol/L or greater within 48 hours
- A 50% or greater rise in serum creatinine known or presumed to have occurred within the past 7 days.
- A fall in urine output to less than 0.5ml/kg/hour for more than 6 hours in adults and more than 8 hours in children and young people. NB: lots of patients with an AKI do not have any change in urine output so there is ongoing debate about the usefulness of urine output as part of the criteria.
- A 25% or greater fall in eGFR in children and young people within the past 7 days.
Describe the staging of an AKI
[*] Staging of AKI (Serum Cr criteria and Urine Output Criteria)
- Stage 1: Increased SCr of 26micromol or greater/L or increased SCr greater or equal to 150-200% (1.5-2 fold) from baseline; urine output less than 0.5mL/kg/h for >6h
- Stage 2: Increased SCr > 200-300% (>2-3 fold) from baseline; Urine Output Criteria <0.5mL/kg/h for >12hours
- Stage 3: SCr = or greater than 354micromol/L with an acute rise of = or greater than 44 micromol/L in 24 hours or less OR increased SCr >300% (>3 fold) from baseline or initiated on RRT (dialysis) (irrespective of stage at time of initiation; Urine output <0.3 mL/kg/h for 24h or anuria for 12h
[*] Novel markers of AKI that show a change earlier in the course of the illness are currently being investigated and the diagnosis of AKI is likely to be further refined in the future.
Describe the aetiology of AKI
- Incidence difficult to assess – variable criteria
- In UK approximately 200 pmp/year, 50pmp/year need RRT (Some form of dialysis)
- Incidence increases with age
- 5% of hospitalised patients
- 25-30% of patients admitted to intensive care units
- AKI is a medical emergency – delayed treatment leads to irreversible renal failure and increases the risk of the need for dialysis therefore it is of paramount important to diagnose potentially reversible causes quickly and start appropriate treatment promptly (ACT EARLY)
What is meant by Oliguric AKI and Non-Oliguric AKI?
[*] AKI may be oliguric or non-oliguric
- Oliguria (“little urine”) is defined as less than 500ml of urine per day or less than 20ml per hour.
- Anuria (“no urine”) is defined as less than 100ml of urine per day.
- Anuria usually indicates a blockage of urine flow or very severe damage to the kidneys and is a less common form of AKI
[*] Oliguria is diagnosed by examining the obligatory amount of cellular waste products that need to be excreted from an average sized individual. This approximates to 600 mOsmol/day. The maximal concentrating ability of the kidney is 1200mOsmol/L or 0.5 L (500ml)
What is Ureamia?
[*] Uraemia is defined as the clinical signs and symptoms of kidney failure. This results in a lack of secretory as well as excretory function in the kidneys.
Describe the causes of AKI
[*] Classification of AKI: conceptualized into 3 major categories based on whether the insult occurs within the kidney itself or is a consequence of pathology upstream or downstream of the kidneys themselves.
[*] Causes of AKI:
Prerenal azotemia
- Hypovolemia
- Cardiac failure
- Hepatorenal syndrome
Renal Artery
- Renal artery occlusion
- Large- or medium-vessel vasculitis
Small-vessel disease
- Thrombotic microangiopathy
- Renal atheroembolism
- Small-vessel vasculitis
Glomerular disease
- Anti-Glomerular Basement Membrane disease
- Lupus nephritis
- Postinfectious glomerulonephritis
- Infective endocarditis
- Membranoproliferative glomerulonephritis
- Cryoglobulinemia
- IgA nephropathy/Henoch-Scholein purpora
Acute Tubular Necrosis
- Ischaemia
- Nephrotoxins
- Rhabdomyolysis
- Radiocontrast agents
Acute Interstitial nephritis
- Drugs
- Infection
- Systemic disease
Intratubular obstruction
- Cast nephropathy
- Drugs
- Crystalluria
Postrenal obstruction
- Bladder outlet obstruction
- Tumours
- Renal calculi
- Papillary necrosis
- Retroperitoneal fibrosis
Renal vein
- Renal vein thrombosis
Describe pre-renal failure
[*] Pre-renal disease is defined as decreased renal perfusion. This is common and has several causes.
- Causes: either due to a reduced effective ECF volume or due to impaired renal autoregulation.
- Reduced effective ECF volume could be caused by Hypovolaemia (due to blood or fluid loss or fluid moving out of the bloodstream into somewhere else e.g. GI system), Systemic vasodilation (due to sepsis – fluid leaks into interstitial tissues, cirrhosis, anaphylaxis), Cardiac failure (due to LV dysfunction, valve disease or tamponade)
- Impaired renal autoregulation could be due to preglomerular vasoconstriction (sepsis, hypercalcaemia, hepatorenal syndrome, drugs; NSAIDs) or postglomerular vasodilation (due to ACE inhibitors or Angiotensin II antagonists)
Explain about renal autoregulation
- The kidney is an auto-regulated organ that maintains the constancy of blood flow via changes in vasoconstriction and dilation over a wide range of BP. If however, BP falls beneath a threshold level, the kidney is unable to maintain blood flow and the GFR declines.
- Normal renal perfusion leads to normal afferent tone (intrarenal prostacyclin low) and normal efferent tone (circulating vasoconstrictors low) with a GFR normal.
- In pre-renal states, reduced renal perfusion (due to low BP) => high intrarenal prostacyclin (reduced afferent tone) and increased efferent tone (circulating vasoconstrictors high) in order to maintain GFR.
- It is important to note that the kidneys themselves are not yet impaired, they are just unable to maintain the blood flow and hence GFR – tubule function is normal.
- Because kidney injury has not yet occurred, pre-renal failure is reversible if it is recognised quickly enough.
How may intrinsic autoregulatory mechanisms be overriden?
- Extrinsic modulators of renal haemodynamics can override intrinsic autoregulatory mechanisms e.g. NSAIDS inhibit production of prostaglandins thus preventing the afferent arterioles from vaasodilating and ACE-inhibitors/Angiotensin Receptor Blockers inhibit vasoconstriction in the efferent arterioles => body is not able to perform ‘salvage’ mechanisms and not able to maintain GFR.
- Disease of the afferent arteriole (BP, progressive kidney disease, diabetes mellitus) can also lead to too great or too little a response to these stimuli.
- In mild hypoperfusion, autoregulation ensures renal blood is preserved. If compensatory responses are overwhelmed, AKI occurs. Autoregulation causes maximal dilatation of arterioles at mean arterial pressure 80mmHg (higher if hypertensive); below this GFR falls rapidly.
What are the consequences of Pre-Renal AKI?
- Actual GFR reduced due to decreased renal blood flow
- No cell damage so kidneys work hard to restore blood flow
- Avid reabsorption of salt and water (aldosterone and ADH release)
- Responds to fluid resuscitation – reversible
- Unless the cause of poor renal perfusion is recognised and promptly treated, then acute tubular necrosis will develop. Then giving fluids doesn’t necessarily work.
Describe intrinsic kidney disease
[*] Intrinsic Kidney disease: if pre-renal AKI is not identified and treated promptly, kidney cells are eventually starved of oxygen. The cells with highest metabolic requirements and those in the areas that are less well-perfused are particularly the proximal tubules (S3 segment) and the medullary thick ascending limb of the loop of Henle – even under normal conditions they are relatively hypoxic so they get damaged first.
- Therefore if pre-renal AKI is sustained for long enough ‘acute tubular necrosis’ (ATN) ensures. The cells get damaged and stop working but don’t often necrose. This is by far the commonest cause of AKI. 85% of AKI results from pre-renal causes or ATN (it is usually difficult to establish exactly when pre-renal AKI becomes ATN). >90% of “renal” (intrinsic AKI) due to ATN.
- The remainder 15% is approximately 5-10% GN/interstitial nephritis and 5-10% obstruction
- Intrinsic AKI accounts for 30% of all AKIs. It is direct injury to the kidney
What could cause intrinsic kidney disease?
- Causes could be intrarenal vascular, glomerulonephritis, ischaemic ATN (severe acute ischaemia ATN), toxic ATN, interstitial disease, intrarenal obstruction, glomerular and arteriolar disease (immune disease affecting the glomerulus), acute tubule-interstitial nephritis (inflammation of kidney intersticium). These would all affect renal parenchyma.
- Another renal cause could be due to renal vein occlusion or renal artery occlusion
- There are also other types of renal cellular damage that result in AKI and they can be stratified by the compartment in which the injury arises.
Describe Acute Tubular Necrosis in intrinsic AKI
Severe acute ischaemia (depletion of cellular ATP):
- Pre-renal causes
- If the fall in renal perfusion is not treated promptly, tubular necrosis results
Toxic acute tubular necrosis
- Nephrotoxins damage the epithelial cells lining the tubules and cause cell death and shedding into the lumen
- Nephrotoxins can be endogenous or exogenous (drugs)
- ATN is much more likely if there is reduced perfusion and a nephrotoxin
- Muddy Brown casts and a fractional excretion of Na+ of 3% or greater.
Can be caused by ischaemia, nephrotoxins or sepsis – and often a combination of 2 or more
Damaged cells cannot reabsorb salt and water efficiently or expel excess water – the cells have lost the ability to concentrate or dilute urine.
Aggressive fluid resuscitation risks fluid overload.
Give examples of Nephrotoxic drugs
[*] Nephrotoxic Drugs: in patients with AKI, treat every drug that the patient is taking a potential nephrotoxin until proved otherwise. If in doubt, look it up.
- Gentamicin
- ACE inhibitors
- Angiotensin Receptor Blockers
- NSAIDs inhibit prostaglandin production (inhibit COX enzyme). Prostaglandin normally causes vasodilation of afferent arterials in renal autoregulation. Unopposed vasoconstriction of afferent arteriole => reduced glomerular perfusion pressure => AKI
- Gentamicin, ACE inhibitors and Antiotensin Receptor Blockers and NSAIDS are the 3 commonest drugs which promote or aggravate acute renal dysfunction and contribute to AKI.
How do you tell between Pre-Renal and ATN?
- Na+ avidly reabsorbed in pre-renal AKI to restore volume but reduced in renal AKI due to tubular cell damage.
- Most useful measurement is Fe(Na)
Therefore in Pre-renal AKI, urine sodium is low
In ATN, urine sodium is higher
However this not a foolproof method! FE(Na)<1 with renal cause:
- Early AKI due to obstruction
- Acute Glomerulonephritis
- Hepatorenal syndrome
- Early in course of rhabdomyolysis
- Hypercalcaemia
- Vasoactive drugs (vasoconstriction): contrast, cyclosporine, adrenaline/NA
And FE(NA)>1 with AKI
- Impaired concentrating ability (elderly, CKD, diuretics, glucosuria)
Many patients with AKI are given diuretics to try and increase their urine output
What happens in Rhabdomyolysis?
- Due to muscle necrosis – huge release of myoglobin
- A crush injury can lead to an AKI
- Can occur in wars / natural diseases e.g. earthquakes, drug users (unconscious so don’t move), elderly (fall and unable to get up).
- Myoglobin is filtered at glomerulus and toxic to tubule cells. Can also cause obstruction
- Coca-cola coloured, dark urine
Glomerular and Arteriolar Disease => Intrinsic AKI. Describe Acute Glomerulonephritis and other causes of arteriolar/glomerular damage
Acute Glomerulonephritis: immune disease affecting the glomerulus
- Primary: disease only affects the kidneys e.g. IGA nephropathy
- Secondary: kidneys are involved as part of a systemic process. Examples are SLE (lupus), vasculitis,
- Histology: inflammatory crescent – associated with vasculitis
Other causes of arteriolar/glomerular damage
- Haemolytic uraemic syndrome
- Malignant hypertension
- Pre-eclampsia
- Caused by endothelial damage => platelet thrombi => partial obstruction of small arteries => destruction of RBCs
- Microangiopathic haemolytic anaemia
Describe Acute Tubulo-Interstitial Nephritis
Acute Tubulo-Interstitial Nephritis: inflammation of the kidney interstitium
- Infection: acute pyelonephritis (ascending bacterial infection)
- Toxin induced (drugs e.g. NSAIDs, Gentamicin etc) (idiopathic – no dose-reponse)
- Histology: tubules usually spread out – inflammatory infiltrate has destroyed the interstitium
Describe Post-Renal Causes of AKI
[*] Post-Renal Disease indicates an obstruction to urine flow after urine has left the tubules. It accounts for approximately 5-10% of AKI. The obstruction can occur primarily at 3 anatomical sites – ureters (bilateral), bladder, urethra
- E.g. urinary tract obstruction
- More common in elderly
- Pathophysiology: obstruction with continuous urine production causes => rise intraluminal pressure => dilation of renal pelvis (hydronephrosis) => decrease in renal function
- The obstructions can be further classified: Within the lumen (kidney, ureter, bladder), within the wall and pressure from outside
Describe causes of AKI within the lumen
- Calculi (stones) – could be in both renal pelvises/ureters (unless only one functioning kidney), or neck of the bladder or urethra. Stones >10mm will not usually pass, pain and haematuria is common.
- Blood clot
- Papillary necrosis (sloughed papillae – following infection and ischaemia)
- Tumour of renal pelvis, ureter, bladder
Describe causes of AKI within the wall
- Congenital e.g. Pelviureteric neuromuscular dysfunction, megaureter, neurogenic bladder
- Ureteric stricture e.g. develops post TB
- Usually causes Chronic not Acute Kidney Injury
Describe Urine Dipstick Testing
Dipstick testing for:
- Blood
- Protein
- Leucocytes
If lots of blood and/or protein, intrinsic renal disease is like.
Culture urine if dipstick is positive (not necessary if cause is pre-renal)
Microscopy
- Pre-Renal: Hyaline cast – aggregations of protein seen in concentrated urine (normal)
- Acute Tubular Necrosis: muddy brown cast
- Rapidly Progressive Glomerulonephritis: red blood cell cast
Describe urine biochemistry
From history, how would you try to determine the cause of AKI
- Pre-Renal: are the kidneys underperfused? Are nephrotoxins implicated?
- Renal: is ATN established? Is there a parenchymal renal disease other than ATN?
- Post-Renal: is there renal tract obstruction?
Describe Nephritic Syndrome
[*] Nephritic Syndrome: a collection of signs (syndrome) associated with disorders affecting the kidneys (specifically glomerular disorders), characterised by having small pores in the podocytes of the glomerulus large enough to permit proteins and red blood cells.
The classic nephritic syndrome is that which accompanies post-streptococcal glomerulonephritis in children but can be a result of other glomerulonephritidies.
Often self-limiting
Renal biopsy needed for diagnosis
Nephritic Syndrome:
- Rapid onset
- Oliguria
- Hypertension
- Generalised oedema (due to fluid overload)
- Haematuria with smoky brown urine
- Normal serum albumin
- Variable renal impairment
- Urine contains blood protein and red blood cell casts
[*] Some glomeronephritides may cause either nephritic or nephrotic syndrome.
Describe Chronic Renal Failure
[*] Chronic Renal Failure: the natural course of many forms of glomerulonephritis is slowly progressive renal impairment eventually leading to patents presenting with hypertension, dipstick abnormalities and/or uraemic syndrome.
It is often associated with small, smooth, shrunken kidneys
Biopsies are hazardous and unlikely to provide diagnostic material
Symptoms of advanced disease
- Tiredness and lethargy
- Breathlessness
- Nausea and vomiting
- Aches and pains
- Sleep reversal
- Nocturia
- Restless legs
- Itching
- Chest pains
- Seizures and coma
[*] Symptoms of Chronic Kidney Disease
- No symptoms until eGFR
- Even then mild and non-specific
- Most patients start dialysis with eGFR 8-10ml/min
