Acute Kidney Injury Flashcards
What is acute kidney injury
Acute kidney injury has variably been defined as an abrupt deterioration in parenchymal renal function, which is usually, but not invariably, reversible over a period of days or weeks.
In clinical practice, such deterioration in renal function is sufficiently severe to result in uraemia. Oliguria is usually, but not invariably, a feature. Acute kidney injury may cause sudden, life-threatening biochemical disturbances and is a medical emergency. The distinction between acute and CKD or even acute-on chronic kidney disease, cannot be readily apparent in a patient presenting with uraemia. In view of these difficulties, the Acute Dialysis Quality Initiative group proposed the RIFLE (Risk, Injury, Failure, Loss, End-stage renal disease; Box 12.5) criteria utilizing either increases in serum creatinine or decreases in urine output. It characterizes three levels of renal dysfunction (R, I, F) and two outcome measures (L, E). These criteria indicate an increasing degree of renal damage and have a predictive value for mortality.
The Acute Kidney Injury Network (AKIN) has proposed a modification of the RIFLE criteria. It now includes less severe AKI, a time constraint of 48 hours, and gives a correction for volume status before classification. ‘R’ in RIFLE is stage 1 (a serum creatinine of ≥26.4 umol/L, i.e. a 1.5-fold increase within 48 hours); stage 2 is ‘Y, i.e. a 2-3-fold increase in serum creatinine; and ‘F’ is stage 3, i.e. an increase in serum creatinine of >300% (equal to ≥354 mol/L). Urine output data are the same.
What are the classification of acute kidney injury
Renal failure results in reduced excretion of nitrogenous waste products, of which urea is the most commonly meas-ured. A raised serum urea concentration (uraemia) is classified as:
• pre-renal
• renal or
• post-renal.
More than one category may be present in an individual patient. Other causes of altered serum urea and creatinine concentration
What is pre-renal uremia
In pre-renal uraemia, there is impaired perfusion of the kidneys with blood. This results either from hypovolaemia, hypotension, impaired cardiac pump efficiency or vascular disease limiting renal blood flow, or combinations of these factors. Usually the kidney is able to maintain glomerular filtration close to normal despite wide variations in renal perfusion pressure and volume status - so-called ‘autoregula-tion’. Further depression of renal perfusion leads to a drop in glomerular filtration and development of pre-renal uraemia.
Drugs which impair renal autoregulation, such as ACE inhibitors and NSAIDs, increase the tendency to develop pre-renal uraemia.
All causes of pre-renal uraemia may lead to established parenchymal kidney damage and the development of AKI. By definition, excretory function in pre-renal uraemia improves once normal renal perfusion has been restored. A number of criteria have been proposed to differentiate between pre-renal and intrinsic renal causes of uraemia (Table 12.19).
• Urine specific gravity and urine osmolality are easily obtained measures of concentrating ability but are unreliable in the presence of glycosuria or other osmotically active substances in the urine.
• Urine sodium is low if there is avid tubular reabsorption, but may be increased by diuretics or dopamine.
• Fractional excretion of sodium (FEna) (Table 12.19), the ratio of sodium clearance to creatinine clearance, increases the reliability of this index but may remain low in some ‘intrinsic’ renal diseases, including contrast nephropathy and myoglobinuria.
Laboratory tests, however, are no substitute for clinical assessment. A history of blood or fluid loss, sepsis potentially leading to vasodilatation, or of cardiac disease may be helpful. Hypotension (especially postural), a weak rapid pulse and a low jugular venous pressure will suggest that the uraemia is pre-renal. In doubtful cases, measurement of central venous pressure is often invaluable, particularly with fluid challenge
What is the management for pre-renal uremia
If the pre-renal uraemia is a result of hypovolaemia and hypotension, prompt replacement with appropriate fluid is essential to correct the problem and prevent development of ischaemic renal injury and acute kidney disease (p. 885).
Since pre-renal and renal uraemia may co-exist, and fluid challenge in the latter situation may lead to volume overload with pulmonary edema, careful clinical monitoring is vital.
Blood pressure should be checked regularly and signs of elevated jugular venous pressure and of pulmonary oedema sought frequently. Central venous pressure monitoring is usually advisable (see p. 872). If the problem relates to cardiac pump insufficiency or occlusion of the renal vascu-lature, appropriate measures - albeit often unsuccessful - need to be taken.
What is post-renal uremia
Here, uraemia results from obstruction of the urinary tract at any point from the calyces to the external urethral orifice. The causes and presentation of urinary tract obstruction are dealt with on page 604. Screening for urinary tract obstruction is by renal ultrasonography. Urinary tract obstruction may present in an acute fashion (if obstruction of a single functioning kidney by, e.g. a calculus occurs) but typically is of insidious onset.
What are some causes of acute uremia due to renal parenchymal disease
This is most commonly due to acute renal tubular necrosis (Table 12.20). Other causes include disease affecting the intrarenal arteries and arterioles as well as glomerular capillaries, such as a vasculitis (Chapter 11), accelerated hypertension, cholesterol embolism, haemolytic uraemic syndrome, thrombotic thrombocytopenic purpura (TTP), Preeclampsia and crescentic glomerulonephritis. Acute tubu-lointerstitial nephritis (p. 595) may also cause AKi. This also occurs when renal tubules are acutely obstructed by crystals, for example following sulphonamide therapy in a dehydrated patient (sulphonamide crystalluria) or after rapid lysis of certain malignant tumours following chemotherapy (acute hyperuricaemic nephropathy). Acute bilateral suppurative pyelonephritis or pyelonephritis of a single kidney can cause acute uraemia.
What are the causes of acute tubular necrosis
Acute tubular necrosis (AT) is common, particularly in hospital practice. It results most often from renal ischaemia but can also be caused by direct renal toxins including drugs such as the aminoglycosides, lithium and platinum derivatives (Table 12.20).
Kidneys are particularly vulnerable to ischaemic injury when cholestatic jaundice is present, and more than one ischaemic factor appears to be present in some situations.
For example, disseminated intravascular coagulation complicating Gram-negative septicaemia and complications of pregnancy such as placental rupture, pre-eclampsia and eclampsia may result in occlusion or partial occlusion of intrarenal vessels, exacerbating the ischaemic insult resulting from hypotension associated with the underlying condition.
Myoglobinaemia and haemoglobinaemia consequent upon muscle injury (rhabdomyolysis) complicating trauma, pressure necrosis or heroin use predispose to AT, perhaps in part owing to occlusion of renal tubules by myoglobin and haemoglobin casts. In liver failure, AKI appears to result from rapidly reversible vasomotor abnormalities within the kidney.
A kidney removed from a patient with hepatic cirrhosis and liver failure dying with oliguric renal failure may function normally immediately after transplantation into a normal individual. Efferent glomerular arteriolar dilatation resulting from ACE-inhibitor drug therapy, with consequent lowering of glomerular filtration pressure, may cause acute deterioration in excretory function if renal arterial disease is also present (see Fig. 12.48). The effect is compounded by concomitant use of non-steroidal anti-inflammatory agents which reduce prostaglandin production, opposing this effect.
What is the pathogenesis of acute tubular necrosis
Factors postulated to be involved in the development of AT include:
• Intrarenal microvascular vasoconstriction:
- Vasoconstriction is increased in response to endothelin, adenosine, thromboxane A2, leukotrienes and sympathetic nerve activity. However, endothelin antagonists failed to show any beneficial effect in the clinical setting.
- Vasodilatation is impaired due to reduced sensitivity in response to:
• Nitric oxide, prostaglandins (PGE2), acetylcholine and bradykinin
• Increased endothelial and vascular smooth muscle cell structural damage
- Increased leucocyte-endothelial adhesion, vascular congestion and obstruction, leucocyte activation and inflammation. After success in the prevention of AKI in animal models, anti-ICAM (intercellular adhesion molecule) in the clinical setting failed to live up to its initial promise.
Tubular cell injury. Ischaemic injury results in rapid depletion of intracellular ATP stores resulting in cell death either by necrosis or apoptosis, due to the following:
- Entry of calcium into cells with an increase in cvtosolic cell calcium concentration
- Induction by hypoxia of inducible nitric oxide synthases with increased production of nitric oxide causing cell death
- Increased production of intracellular proteases such as calpain, which cause proteolysis of cytoskeletal proteins and cell wall collapse
- Activation of phospholipase A2 with increased production of free fatty acids, particularly arachidonic acid, due to its action on the lipid layer of cell membranes
- Cell injury resulting from reperfusion with blood after initial ischaemia causing excessive free radical generation
- Tubular obstruction by desquamated viable or necrotic cells and casts
- Loss of cell polarity, i.e. integrins located on the basolateral side of the cell are translocated to the apical surface, which when combined with other desquamated cells forms casts, with tubular obstruction and back leak of tubular fluid.
• Tubular cellular recovery. Tubular cells have the capacity to regenerate rapidly and to reform the disrupted tubular basement membrane, which explains the reversibility of AT. Multiple growth factors, including insulin-like growth factor 1, epidermal growth factor and hepatocyte growth factor, and their receptors are upregulated during the regenerative process after
injury.
In established AT, renal blood flow is much reduced, particularly blood flow to the renal cortex. Ischaemic tubular damage contributes to a reduction in glomerular filtration by a number of interrelated mechanisms:
• Glomerular contraction reducing the surface area available for filtration, due to reflex afferent arteriolar spasm mediated by increased solute delivery to the macula densa. Increased solute delivery is due to impaired sodium absorption in the proximal tubular cells because of loss of cell polarity with mislocalization of the Na/K-ATPase and impaired tight junction integrity, resulting in decreased apical-to-basal transcellular sodium absorption.
• ‘Back leak’ of filtrate in the proximal tubule owing to loss of function of the tubular cells.
• Obstruction of the tubule by debris shed from ischaemic tubular cells; these appear on renal biopsy as flat rather than the normal tall appearance
What are some clinical and biochemical features of acute tubule necrosis
These are the features of the causal condition together with features of rapidly progressive uraemia. The rate at which serum urea and creatinine concentrations increase is dependent upon the rate of tissue breakdown in the individual patient.
This is increased in the presence of trauma, sepsis and following surgery. Hyperkalaemia is common, particularly following trauma to muscle and in haemolytic states. Metabolic acidosis is usual unless hydrogen ion loss by vomiting or aspiration of gastric contents is a feature. Hyponatraemia may be present owing to water overload if patients have continued to drink in the face of oliguria, or if overenthusiastic fluid replacement with 5% glucose has been carried out. Pulmonary oedema owing to salt and water retention is not uncom-mon, particularly after inappropriate attempts to initiate a diuresis by infusion of 0.9% saline without adequate monitoring of the patient’s volume status. Hypocalcaemia due to reduced renal production of 1,25-dihydroxycholecalciferol and hyperphosphataemia due to phosphate retention are common.
Symptoms of uraemia such as anorexia, nausea, vomiting and pruritus develop, followed by intellectual clouding, drow-siness, fits, coma and haemorrhagic episodes. Epistaxes and gastrointestinal hemorrhage are relatively common. Severe infection may have initiated the AKI or have complicated it owing to the impaired immune defences of the uraemic patient or ill-considered management, such as the insertion and retention of an unnecessary bladder catheter with complicating urinary tract infection and bacteraemia.
What are some investigations to make in uremia
Investigations are aimed at defining whether the patient has acute or chronic uraemia, whether uraemia results from pre-renal, renal or post-renal factors, and establishing the cause.
Acute or chronic uraemia?
The distinction between acute and chronic uraemia depends in part on the history, duration of symptoms and previous urinalysis or measurements of renal function.
A rapid rate of change of serum urea and creatinine with time suggests an acute process. A normochromic, normo-cytic anaemia suggests chronic disease, but anaemia may complicate many of the diseases that cause AKI, owing to a combination of haemolysis, hemorrhage and deficient erythropoietin production.
Ultrasound assessment of renal echogenicity and size is helpful. Small kidneys of increased echogenicity are diagnostic of a chronic process, although the reverse is not true; the kidney may remain normal in size in diabetes and amyloido-sis, for instance.
Evidence of renal osteodystrophy (e.g. digital subperio-steal erosions due to hyperparathyroid bone disease) is indicative of CKD.
Pre-renal, renal or post-renal uraemia?
Bladder outflow obstruction is ruled out by insertion of a urethral catheter or flushing of an existing catheter, which should then be removed unless a large volume of urine is obtained. Absence of upper tract dilatation on renal ultrasonography will, with very rare exceptions, rule out urinary tract obstruction.
The distinction between pre-renal and renal uraemia may be difficult (see p. 610). Assessment of the patient’s volume status is essential and central venous pressure measurement is extremely helpful. If volume status is low, appropriate corrective measures are indicated. If no diuresis ensues, AKI is present.
Other investigations
• Urinalysis, urine microscopy, particularly for red cells and red-cell casts (indicative of glomerulonephritis) and urine culture. Urine should be tested for free haemoglobin and myoglobin, where appropriate.
• In AKI it takes 48-72 hours before creatinine rises in the plasma; by that time cell injury is well established and irreversible. Urinary and plasma biomarkers (e.g. kidney injury molecule 1, neutrophil gelatinase associated lipocalin) rise within few hours of AKI and may allow earlier treatment.
• Blood tests include measurement of serum urea, electrolytes, creatinine, calcium, phosphate, albumin, alkaline phosphatase and rate concentrations, as well as full blood count and examination of the peripheral blood film where necessary. Coagulation studies, blood cultures and measurements of nephrotoxic drug blood levels should be carried out.
What is the management for acute tubular necrosis
Management
The aim of management of acute renal tubular necrosis is to keep the patient alive until spontaneous recovery of renal function occurs. Ideally patients should be managed by a nephrologist or intensivist with access to facilities for blood purification and fluid removal (see below). Early specialist referral is advisable. Poor initial management and late referral result in the arrival in the specialist centre of a patient who is severely uraemic, acidotic and hyperkalaemic.
General measures
Good nursing and physiotherapy are vital. Regular oral toilet, chest physiotherapy and consistent documentation of fluid intake and output, and where possible measurement of daily bodyweight to assess fluid balance changes, all have a role.
The patient should be confined to bed only if essential.
Emergency measures
Hyperkalemia
This is a life-threatening complication owing to the risk of cardiac dysrhythmias, particularly ventricular fibrillation.
Treatment is outlined in Emergency Box 13.1.
Correction of acidosis with intravenous sodium bicarbonate will also reduce serum potassium concentration, but administration of sodium is inappropriate if the patient is salt and water overloaded. Rapid correction of acidosis in a hypocalcaemic patient may also trigger tetany, since hydrogen ions displace calcium from albumin-binding sites, thus increasing the physiologically active calcium concentration in blood. Ion exchange resins are used to prevent subsequent hyperkalaemia. In many patients, hyperkalaemia will only be controlled by dialysis or hemofiltration
Pulmonary oedema
Unless a diuresis can be induced with intravenous furosem-ide, dialysis or haemofiltration will be required.
Sepsis
Infections, when detected, should be treated promptly, bearing in mind the need to avoid nephrotoxic drugs and to use drugs with appropriate monitoring and drug levels (e.g. gentamicin, vancomycin). Prophylactic antibiotics or barrier nursing is not recommended in all cases.
Use of drugs
Great care must be exercised in the use of drugs (see p. 607).
Fluid and electrolyte balance
Twice-daily clinical assessment is needed. In general, once the patient is euvolaemic, daily fluid intake should equal urine output plus losses from fistulae and from vomiting, plus an allowance of 500 mL daily for insensible loss. Febrile patients will require an additional allowance. Sodium and potassium intake should be minimized. If abnormal losses of fluid occur, e.g. in diarrhea, additional fluid and electrolytes will be required. The development of signs of salt and water overload (peripheral edema, basal crackles, elevation of jugular venous pressure) or of hypovolaemia should prompt reappraisal of fluid intake. Large changes in daily weight reflecting change in fluid balance status should also prompt a reappraisal of volume stasis.
Diet
With rare exceptions, sodium and potassium restriction are appropriate. The place of dietary protein restriction is con-troversial. If it is hoped to avoid dialysis or haemofiltration, proteinintake is sometimes restricted to approximately 40 g daily. This poses the risk of a negative nitrogen balance despite attempts to reduce endogenous protein catabolism by maintenance of a high energy intake in the form of carbohydrate and fat. Patients treated by blood purification techniques are more appropriately managed by providing 70 g protein daily or more. Hypercatabolic patients will require an even higher nitrogen intake to prevent negative nitrogen balance.
Routes of intake are, in preferred order, enteral by mouth, enteral by nasogastric tube, and parenteral. The last of these is, however, only necessary if vomiting or bowel dysfunction render the enteral route inappropriate.
Vitamin supplements are usually supplied. Vitamin Dana-logue therapy and pharmacological doses of erythropoietin are not employed routinely.
Dialysis and haemofiltration
The main indications for blood purification and/or excess
fluid removal by these techniques are:
• Symptoms of uraemia
• Complications of uraemia, such as pericarditis
• Severe biochemical derangement in the absence of
symptoms (especially if a rising trend is observed in an
oliguric patient and in hypercatabolic patients)
• Hyperkalaemia not controlled by conservative mesures
• Pulmonary oedema
• Severe acidosis
For removal of drugs causing the AKI, e.g. gentamicin,
lithium, severe aspirin overdose.
The main options are intermittent haemodial sis (HD) combined with ultrafiltration if necessary, intermittent haemofiltration, continuous arteriovenous or venovenous haemofiltration,
haemodiafiltration and peritoneal dialysis. For reasons that are incompletely understood, adverse cardiovascular effects are much less during haemofiltration than during haemodialysis. Continuous treatments are superior to intermittent ones in this respect.
Continuous renal replacement
treatments (CRRT)
Blood flow is achieved either by using the patient’s own blood pressure to generate arterial blood flow through a filter or by the use of a blood pump to draw blood from the lumen of a dual-lumen catheter placed in the jugular, subclavian or femoral vein.
Continuous arteriovenous or venovenous haemofiltration (CAVH, CVVH) refers to the continuous removal of ultra-
filtrate from the patient, usually at rates of up to 1000 mL/h, combined with simultaneous infusion of replacement solution. For instance, in a fluid-overloaded patient one might remove filtrate at 1000 mL/h and replace at a rate of 900 mL/h, achieving a net fluid removal of 100 mL/h. Continuous haemodiafiltration (CAVHDF, CVHDF) is a combination of haemofiltration and haemodialysis, involving both the net removal of ultrafiltrate from the blood and its replacement with a replacement solution, together with the countercurrent passage of dialysate (which may be identical to the replacement solution). Both the ultrafiltrate and the spent dialysate appear as ‘waste’.
