Renal replacement therapy (dialysis) is indicated if any of the following cannot be controlled: fluid overload, hyperkalaemia, hypocalcaemia, metabolic acidosis, pericarditis, uremic symptoms, GFR <15ml/min/1.73 m², or poisoning. Different options include haemodialysis, peritoneal dialysis, haemofiltration, and renal transplantation.

Definition

• There is a rise of serum creatinine of >26.5 in <48 hours, OR
• There is a rise in serum creatinine to >1.5x the baseline level which was previously known or assumed 7 days prior to the presentation
• There is a significant reduction in urine output compared to baseline

Epidemiology

• Mortality is about 5-10% in those with isolated AKI which does not normally require admission to ITU.
• In those with other organ failure that then go into AKI, mortality is about 50-70%.
• The presence of sepsis translates into a much worse prognosis.

Diagnosis

1. Is the renal failure acute? Is there is a previous test of renal function that proved normal? It is unlikely that a baseline measure is at hand, but suspect chronic renal failure if:
   1. There is co-existing diabetes.
   2. There is increased blood pressure, and other signs of chronic disease.
   3. Small kidneys are apparent on ultrasound (<9cm), with increased echogenicity.
2. Is there urinary tract obstruction? This is a cause of AKI, and should always be considered because generally treatment is quick and easy and will prevent any permanent renal damage from occurring. Obstruction should be considered in those with a history of renal calculi, a single functioning kidney, or previous surgery in this region. Examine for a palpable bladder, pelvic/abdominal mass, and enlarged prostate.
   1. 25% of cases of severe acute kidney injury are due to obstruction, most commonly caused by prostatic hypertrophy.
   2. The main test for obstruction is USS of the kidneys. The results are highly variable depending on the patient and the operator. Also, renal USS will not detect obstruction, but dilation of the calyces – and in 5% of cases such dilation may not be detected, culminating in a false negative result.
   3. In order to relieve obstruction the following procedures may be carried out:
      1. Catheterization – this is a relatively quick and straightforward technique that carries with it few risks – not withstanding the risk of infection!
      2. Percutaneous nephrostomy
      3. Surgery to allow implant of stents whilst consideration of how to treat the underlying cause is undertaken.
3. Is there something rare that might be causing the acute kidney injury? E.g. glomerulonephritis, vasculitis, or interstitial nephritis. Do a dipstick test on anyone with suspected AKI, and if there are any irregular findings, send off for urgent analysis. Often there will be haematuria and/or proteinuria.

Other investigations

• Dipstick
• Urine microscopy – look particularly for the presence of red cell casts and red cells.
• Blood tests – U+E’s – particularly creatinine and potassium. Also check for free haemoglobin and myoglobin.
• Check if the patient is on any nephrotoxic drugs.

Causes

Prerenal causes

1. Hypovolaemia –  which may be due to reduced blood volume
2. Hypotension
3. Decreased cardiac output
4. Vascular disease – limiting renal blood flow
5. Combinations of any of the above

• Normally the kidney is able to maintain sufficient perfusion despite alterations in these conditions through autoregulation.However, in extreme circumstances, it cannot, thus GFR will fall. This is known as prerenal uraemia.
  • ACE inhibitors and NSAID’s impair autoregulation; for that reason they predispose to prerenal uraemia.
• Excretory function of the kidney improves once normal perfusion has been restored.

• History of blood/fluid loss
• Sepsis – leading to vasodilation)
• Cardiac disease
• Postural hypotension
• Weak, rapid pulse
• Low JVP

Intra-Renal causes

• Vulnerability is also increased when there is more than one factor contributing to the ischaemia. For example, there are many conditions that cause hypotension which directly cause renal artery occlusion, aggravating the damage to a localised area. Such conditions, which perpetuate renal ischemia, include gram-negative septicaemia, pre-eclampsia and other complications of pregnancy

Aetiological factors

• Myoglobinaemia and haemoglobinaemia as a result of muscle injury – this is also often present in trauma.
• Heroin use – this probably contributes, as above, to the formation of myoglobin or haemoglobin casts that occlude the renal artery.
• Liver failure
  • Interestingly, a kidney donated from a patient suffering liver failure with coexisting oliguria will function normally after transplantation into a healthy recipient!
• ACE-inhibitors – this is a complicated situation. ACE-inhibitors can lead to dilation of the efferent arteriole, thus lowering glomerular pressure, resulting in a reduced GFR.  In patients with renal disease, this exacerbates the condition.
• NSAID’s – reduce prostaglandin production. Protaglandins are vasodilators – thus inhibition of their production may lead to vasoconstriction of the afferent arteriole, thereby causing reduced renal and reduced GFR.

Pathology

• Intra-renal vasoconstriction on a microvascular level due to:
  • Decreased vasodilation occuring in the presence of other factors, including endothelial damage, e.g. in trauma or in infection, where leukocyte activation and release of PGE2 (prostaglandin 2), ACh and bradykinin occurs.
  • Increased vasoconstriction
• Tubular cell injury – ischemia initiates rapid utilisation of intracellular ATP stores which, once depleted, will cause the cell to die by necrosis or apoptosis.  Adjacent cells will thereby lose their adherent qualities (perhaps due to lack of polarity, lack of membrane integrity and other effects), and desquamate. As a result, RBCs are able to escape into the tubule, squishing together to form casts. Casts can then block the renal tubule, forming a back-up of tubular fluid.  Consequently, there may also be a leak of tubular fluid into the interstitium, reducing the total filtered volume. The necrosis is worst in the ascending loop of Henle – especially when it lies in a relatively poorly perfused medulla – and the proximal tubule.  This type of cell injury also leads to decreased production of prostaglandins and nitric oxides which are vasodilators, causing vasoconstriction, and reducing perfusion of tubular cells even further!
  • Tubular cell recovery – tubular cells have the ability to regenerate very quickly, and can rapidly repair the damaged basement membrane. This may explain why ATN is reversible. Numerous growth factors are released during cell injury to assist in the regeneration process, such as insulin-like growth factor, epidermal growth factor, and hepatocyte growth factor.

• Glomerular contraction – resulting from increased solute delivery to the macula densa, glomerular contraction reduces the surface area available for filtration. Increased solute delivery is caused by reduced sodium reabsorption due to loss of tight-junction integrity, and reduction in the number and function of Na⁺/K⁺ potassium pumps.
• Back-leak of filtration – due to tubular damage (described above).
• Obstruction of the tubule by debris – such as casts.

Progression of the condition

• There is no evidence to suggest the use of mannitol, furosemide or dopamine is beneficial, however often one of these is given if correction of pre-renal causes produces no benefit.

Chemical and biochemical features

• Hyperkalaemia – this is particularly common, especially following trauma, i.e. muscle related injury.
• Metabolic acidosis – this is usually present.  Some patients may bypass this situation by vomiting, i.e. to reduce H⁺ ion concentration, or aspirating gastric contents.
• Hyponatraemia – many patients will drink significant amounts in the presence of oliguria, leading to ‘dilution’ of body fluids to the extent that hyponatraemia occurs.
• Pulmonary oedema – as a result of salt and water retention.  This is quite common but not always present.  Just as above complication, this condition is often the result of medical intervention – where patients have over-enthusiastically been given fluid infusion, e.g. 0.9% saline in this situation, without adequate monitoring of fluid volume.
• Hypocalcaemia and hyperphosphataemia
• General symptoms of uraemia – these include anorexia, nausea, vomiting, fits, coma and haemorrhagic episodes.

Nephrotoxicity

Aminoglycosides

Contrast nephropathy

Managing Acute Kidney Injury

• JVP – may or may not be invisible
• Low BP
• Low urine output
• Poor tissue turgor
• Fast, weak pulse

In order to avoid fluid overload also look for…

• Raised BP
• Peripheral oedema
• Lung crepitations
• Gallop rhythm heard on heart sounds

• Palpate the bladder –if there is a palpable bladder, then the underlying cause is most likely post-renal!  However, the absence of a palpable bladder does not rule out obstruction as a cause.
• Order an urgent USS – the presence of small kidneys suggests CKD
• Put a catheter in to monitor urine output
• Stop all nephrotoxic drugs – this includes NSAID’s, ACE inhibitors, gentamycin, vanomycin, and if creatinine is >150mmol/L then stop metformin also.
• Take cultures and then use an appropriate antibiotic to treat any sepsis present.
• Nutrition is very important – aim for a normal calorie intake, and if oral feeding is difficult, then consider early naso-gastric feeding.
• Treat hyperkalaemia early and quickly!! –values of above 6mmol/L are particularly dangerous as this may lead to arrhythmias, particularly ventricular fibrilliation, or cardiac arrest.
  • In the setting of VF, the ECG may demonstrate…
    • Tall tented T waves
    • Small or absent P waves
    • Wide QRS complex – normal QRS is 0.12 which can increase 0.24, predisposing to MI.
    • Asystole
    • Sine wave pattern
  • If VF is present, the following is imperative:
    • Calcium gluconate – this is cardio-protective. Give a 10ml dose of 10% solution every 2 mins until the ECG improves.
    • Insulin – this stimulates the uptake of glucose within a cell – and as glucose is taken up it is taken up in co-transport with potassium! Giving insulin will lower serum K+ by 1-2mmol/L over 1 hour. Check glucose level about 30 minutes after initial administration as rendering the patient hypoglycaemic poses great dangers!
    • Consider haemodialysis if the patient is anuric, i.e. producing no urine. This is often the only way the acutely hyperkalaemic patient can be managed. The treatment is often employed for only a few days in the AKI patient whilst they recover.
• Give the following if pulmonary oedemais present:
  • Venodilator,e.g. morphine
  • Oxygen – sit the patient upright
  • Loop diuretic, i.e. furosemide.  Although higher doses may be required,loop diuretics are indicated in this instance as they remain effective in the setting of renal failure despite reduced GFR.
  • If there is no response as a result of the above interventions, then urgent haemodialysis or haemofiltration is needed.
• Give plasma and platelets if bleeding is marked. In most instances where bleeding is apparent only a straightforward blood transfusion is required as blood loss is often detected before the situation becomes life-threatening.
• Consider dialysis if any of the following indications are present:
  • Pulmonary oedema
  • Persistent hyperkalaemia, i.e. K⁺ >7mmol/L
  • Severe metabolic acidosis, i.e. pH <7.2, or base excess <10
  • Uraemic encephalopathy
  • Uraemic pericarditis, aka “uraemic rub”
• Manage any acidosis – Treat this with sodium bicarbonate; this intervention will also help to lower the level of free potassium.
  • BE CAREFUL!  If NaHCO3 is administered too quickly, the patient may become hypocalcaemic, which often causes tetany.

• Treat any sepsis – this needs to be treated quickly, but remember not to use nephrotoxic drugs, e.g. vanomycin, gentamycin.  Prophylactic antibiotics and barrier nursing are not always deemed necessary.

• Assess electrolytes daily.
• Check for signs of fluid overload constantly.
• Monitor weight – rapid fluctuations are indicators of fluid loss or gain.

• Protein intake – some recommendations restrict intake to 40g/day; however, this can lead to excessive metabolism of endogenous protein, thus causing a negative nitrogen balance. To prevent this, a high calorie intake, alongside low protein intake, is recommended.
• Patients treated with haemodialysis require 70g protein daily to prevent negative nitrogen balance.