Acute Renal Failure. Dr Kawa Ahmad

Transcription

1 62 Acute Renal Failure Dr Kawa Ahmad

2 Acute Renal Failure It is characterised by an abrupt reduction (usually within a 48- h period) in kidney function. This results in an accumulation of nitrogenous waste products and other toxins. Many patients become oliguric (low urine output) with subsequent salt and water retention. The diagnostic criteria for AKI is based on an increase in serum creatinine or the presence of oliguria

3 Classification of acute kidney injury

4 RIFLE criteria for definition and stage of RF

5 The kidneys are pre- disposed to haemodynamic injury owing to hypovolaemia or hypoperfusion. This relates to the high blood flow through the kidneys in normal function; the organs represent 5% of total body weight but receive 25% of blood flow.

6 1. Pre-renal acute kidney injury This is caused by impaired perfusion of the kidneys with blood, and is usually a consequence of decreased intravascular volumes (hypovolaemia) and/or decreased intravascular pressures. Renal perfusion is tightly controlled by RAAS (discussed in lect.1) When the systolic blood pressure (BP) drops below 80mmHg, AKI may develop. Drugs that inhibit the RAAS, such as angiotension converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARBs), or block the production of prostaglandins, such as non- steroidal anti- inflammatory drugs (NSAIDs), can pre- dispose to thedevelopment ofpre- renal AKI.

7 Hypovolaemia This results from any condition that causes intravascular fluid depletion, either directly by haemorrhage or indirectly to compensate for extravascular loss. Examples of this include diarrhoea and vomiting, burns and excessive use of diuretics. Hypotension is a secondary effect of significant hypovolaemia.

8 Hypotension In addition to hypovolaemia, hypotension can result from pump (cardiac) failure, of which there are a number of causes, the most common of which is ischaemic heart disease. Another important cause is septic shock, where there is peripheral vasodilatation and low peripheral resistance which leads to profound hypotension despite a high cardiac output.

9 2. Intra-renal acute kidney injury Most commonly (in >80% of cases) acute tubular necrosis (ATN). ATN occurs usually as a consequence of a combination of factors, including hypotension, often in the setting of sepsis and nephrotoxic agents including drugs or chemical poisons, or endogenous sources such as myoglobin or haemoglobin.

10 Common clinical factors that contribute to ATN

11 Common clinical factors that contribute to ATN

12 Differentiation between pre and intra ARF In intra- renal AKI, the kidneys are generally unable to retain Na+ owing to tubular damage. This can be demonstrated by calculating the fractional excretion of sodium (FENa); in practice this is not often done because it lacks sensitivity and specificity and may be difficult to interpret in the elderly who may have pre- existing concentrating defects. If FENa <1%, this indicates pre- renal AKI with preserved tubular function; if FENa >1% this is indicative of ATN.

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14 3. Post-renal acute kidney injury Post- renal AKI results from obstruction of the urinary tract by a variety of mechanisms; these can be divided into causes within the ureters (e.g. calculi or clots), a problem within the wall of ureter (malignancies, benign strictures) and external compression (e.g. retroperitoneal tumours).

15 Clinical manifestations 1. The patient may exhibit signs and symptoms of volume depletion or overload. 2. The most common sign in AKI is oliguria, where urine production falls to less than 0.5mL/kg/h for several hours. 3. The serum concentration of those substances normally excreted by the kidney will rise and differentially applies to all molecules up to a molecular weight of around 50kDa. This includes serum creatinine, which at a molecular weight of 113Da is normally freely filtered by the kidneys but with loss of kidney function the serum level climbs. 4. Uraemia (Urea) merely describes a surrogate for the overall metabolic disturbances that accompany AKI; these include excess potassium, hydrogen ions (acidosis) and phosphate in blood. 5. Patients may have symptoms that are specifically attributable to AKI; these include nausea, vomiting, diarrhoea, gastro- intestinal haemorrhage, muscle cramps and a declining level of consciousness.

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17 Diagnosis and clinical evaluation In hospitalised patients, AKI is usually diagnosed incidentally by the detection of increasing serum creatinine and/or a reduction in urine output. cause(s) of the condition, such as fluid depletion (hypovolaemia), infection or the use of nephrotoxic drugs, are often apparent on close examination of the clinical history.

18 Monitoring fluid balance in AKI 1. Measurement of BP which needs to be interpreted in respect of the baseline for the affected patient together with the patient's heart rate. 2. A chest X- ray for the presence of pulmonary oedema. 3. The presence of pitting oedema of the legs or sacrum indicates longer term fluid overload 4. Decreased skin turgor is a sign of fluid loss.

19 Monitoring key parameters in acute kidney disease Serum electrolytes including potassium, bicarbonate, calcium, phosphate and acid base balance should be measured on a dailybasis. In patients with severe AKI, acid base balance may need assessing every few hours as this may direct fluid replacement, respiratory support and dialysis treatment.

20 Course and prognosis Pre- renal AKI The majority of cases will recover within days of onset following prompt correction of the underlying causes. The urine output improves and waste products of metabolism are cleared by the kidneys.

21 Course and prognosis Intra- renal AKI ATN may be divided into three phases. 1. The first is the oliguric phase which is usually no longer than 7 14 days but may last for 6 weeks. 2. This is followed by a diuretic phase, which is characterised by a urine output that rises over a few days to several litres per day. This phase lasts for up to 7 days and corresponds to the recommencement of tubular function. The onset of this phase is associated with an improving prognosis unless the patient sustains an intercurrent infection or a vascular event. 3. Finally, the patient enters a recovery phase where tubular cells regenerate slowly over several months, although the glomerular filtration rate often does not return to initial levels. The major causes of death associated with AKI are septicaemia and intercurrent acute vascular events such as myocardial infarction and stroke.

22 Course and prognosis Post- renal acute kidney injury Prompt identification and relief of the obstruction is important. The prognosis is then dependent on the underlying cause of the obstruction of the renal tract and the baseline to which the kidney function returns after the obstruction has been relieved. If the underlying problem is benign then there may be no long- term adverse consequences. However, if the cause of the obstruction is due to an underlying malignancy then long- term survival is dependent on whether this can be cured.

23 ACEi & ARBs in ARF ACE inhibitors and ARBs are not directly nephrotoxic and can be used in most patients with kidney disease. However, profound hypotension (low renal perfusion) can occur if they are initiated in susceptible patients such as those who are receiving high dose diuretics as treatment for fluid overload. This might result in the development of pre- renal AKI. It is, therefore, wise to monitor BP and carefully titrate dosages whilst monitoring renal function in such patients. Nonetheless, it is com- mon to see increases in serum creatinine levels of up to 20% on initiation of an ACE inhibitor or ARB and this is not necessarily a cause for discontinuing therapy with these agents.

24 Management Patients with severe AKI usually require renal replacement therapy with dialysis. Patients with immune- mediated causes of AKI should be treated with appropriate immunosuppressant regimens to treat the underlying cause of the AKI. the drug and treatment regimens should be examined so that potential nephrotoxins are avoided in the future in order to avoid exacerbating the condition. Particular care should be taken with ACE inhibitors, NSAIDs, radiological contrast media, and aminoglycosides. The doses should be adjusted of any drugs that are renally excreted or have active metabolites that are excreted renally.

25 Optimisation of renal perfusion Initial treatment should include rapid correction of fluid and electrolyte balance to maximise renal perfusion. A central line may be considered to facilitate ease of fluid infusion and monitoring of intravascular volumes.. The use of crystalloids in the form of 0.9% sodium chloride is an appropriate choice of intravenous fluid since it replaces both water and sodium ions in a con- centration approximately equal to serum. The effect of fluid replacement on urine flow and intravascular pressures should be carefully monitored. However, fluid loading with 1 1.5L saline at <0.5L/h is unlikely to cause harm in most patients who do not show signs of fluid overload. There is no evidence that colloids such as gelofusin or albumin provide any additional benefit for volume expansion and renal recovery over the use of 0.9% sodium chloride.

26 Establishing adequate diuresis Whilst loop diuretics (most commonly furosemide) may facilitate the management of fluid overload and hyperkalaemia in early or established AKI, there is no evidence that these agents are effective for the prevention of, or early recovery from, AKI. It is reasonable to use these agents whilst the urine output is maintained as this provides space for intravenous drugs and parenteral feeding including oral supplements. In experimental settings, loop diuretics decrease renal tubular cell metabolic demands and increase renal blood flow by stimulating the release of renal prostaglandins, a haemodynamic effect inhibited by NSAIDs. However, there is no demonstrable impact on clinical outcomes. Indeed, diuretic therapy should only be initiated in the context of fluid overload. If not, any diuresis might produce a negative fluid balance and precipitate or exacerbate a pre- renal state.

27 >>>>Establishing adequate diuresis Doses of up to 100 mg/h of furosemide can be given by continuous intravenous infusion. Higher infusion rates may cause transient deafness. The use of continuous infusions of loop diuretics has been shown to produce a more effective diuresis with a lower incidence of side effects than seen with bolus administration. Bolus doses of loop diuretics may induce renal vasoconstriction and be theoretically detrimental to function. The addition of small oral doses of metolazone may also be considered. Metolazone is a weak thiazide diuretic alone but produces a synergistic action with loop diuretics. In this setting, it should be used with great care as it may initiate a profound diuresis and the patient can rapidly develop intra- vascular depletion and worsen renal failure

28 Non-dialysis treatment of established acute kidney injury

29 1. Uraemia and intravascular volume overload In renal failure, the symptoms of uraemia include nausea, vomiting and anorexia, and result principally from accumulation of toxic products of protein metabolism including urea. Unfortunately, since uraemia causes anorexia, nausea and vomiting, many severely ill patients are unable to tolerate any kind of diet. In these patients and those who are catabolic, the use of enteral or parenteral nutrition should be considered at an early stage. Intravascular fluid overload must be managed by restricting NaCl intake to about 1 2g/day if the patient is not hyponatraemic and total fluid intake to less than 1L/day plus the volume of urine and/or loss from dialysis. Care should be taken with the so- called low salt products, as these usually contain KCl, which will exacerbate hyperkalaemia.

30 2. Hyperkalaemia Rapid rises in extracellular potassium are to be expected when there is tissue damage, as in burns, crush injuries and sepsis. Acidosis also aggravates hyperkalaemia by provoking potassium leakage from healthy cells. The condition may be life- threatening causing cardiac arrhythmias and, if untreated,can result in asystolic cardiac arrest. Dietary potassium should be restricted to less than 40 mmol/ day and potassium supplements and potassium- sparing diuretics removed from the treatment schedule. Emergency treatment is necessary if the serum potassium level reaches 7.0mmol/L (normal range mmol/L) or if there are the progressive changes in the electrocardiogram (ECG) associated with hyperkalaemia.

31 Emergency treatment of hyperkalaemia consists of the following: ml ( mmol) of calcium gluconate 10% intravenously over 5 10 min; this improves myocardial stability but has no effect on the serum potassium levels. The protective effect begins in minutes but is short lived (<1 h), although the dose can be repeated ml of 50% glucose together with 8 12 units of soluble insulin over 10 min. Endogenous insulin, stimulated by a glucose load or administered intravenously, stimulates intracellular potassium uptake, thus removing it from the serum. The effect becomes apparent after min, peaks after about 1 h and lasts for 2 3 h and will decrease serum potassium levels by around 1 mmol/l.

32 3. Acidosis The inability of the kidney to excrete hydrogen ions may result in a metabolic acidosis. This may contribute to hyperkalaemia. It may be treated: Orally with sodium bicarbonate 1 6 g/day in divided doses IV: mmol of bicarbonate ions (isotonic sodium bicarbonate 1.4% or 1.26%, mL over min). If calcium gluconate is used to treat hyperkalaemia, care should be taken not to mix it with the sodium bicarbonate (by giving this through the same intravenous access site) as the resulting calcium bicarbonate forms an insoluble precipitate.

33 4. Hyperphosphataemia As phosphate is normally excreted by the kidney,hyperphosphataemia can occur in AKI but rarely requires treatment. Should it become necessary to treat, phosphate- binding agents may be used to retain phosphate ions in the gut. The most commonly used agents are calcium containing such as calcium carbonate or calcium acetate and are given with food.

34 Drug dosage in renal replacement therapy Drug characteristics that favour clearance by the glomerulus are: 1. Low MWt 2. High water solubility 3. Low protein binding 4. Small volume of distribution 5. Low metabolic clearance

35 Factors affecting drug use How the drug to be used is absorbed, distributed, metabolised and excreted, and whether it is intrinsically nephrotoxic are all factors that must be considered. The pharmacokinetic behaviour of many drugs may be altered in renal failure.

36 1. Absorbtion Oral absorption in AKI may be reduced by vomiting or diarrhoea, although this is frequently of limited clinical significance.

37 2. Metabolism The main hepatic pathways of drug metabolism appear unaffected in renal impairment. The kidney is also a site of metabolism in the body. It is clinically important in only two situations: 1. The first involves the conversion of 25- hydroxycholecalciferol to 1,25- dihydroxycholecalciferol (the active form of vitamin D) in the kidney, a process that is impaired in renal failure. Patients in AKI occasionally require vitamin D replacement therapy, and this should be in the form of 1- hydroxycholecalciferol (alfacalcidol) or 1,25- dihydroxycholecalciferol (calcitriol). The latter is the drug of choice in the presence of concomitant hepatic impairment. 2. The second situation involves the metabolism of insulin. The kidney is the major site of insulin metabolism, and the insulin requirements of diabetic patients in AKI are often reduced.

38 3. Distribution Changes in drug distribution may be altered by fluctuations in the degree of hydration or by alterations in tissue or serum protein binding. The presence of oedema or ascites increases the volume of distribution while dehydration reduces it. Serum protein binding may be reduced owing to either protein loss or alteration in binding caused by uraemia. 1. Some drugs that show reduced serum protein binding include diazepam, morphine, phenytoin, levothyroxine, theophylline and warfarin. 2. Tissue binding may also be affected; for example, the displacement of digoxin from skeletal muscle binding sites by metabolic waste products that accumulate in renal failure result in a significant reduction in digoxin's volume of distribution.

39 4. Excretion Alteration in renal clearance of drugs is the most important parameter to consider when considering dosage. The glomerular filtration rate can be used as an estimate of the number of functioning nephrons. Thus, a 50% reduction in the glomerular filtration rate will suggest a 50% decline in renal clearance. Loading doses of renally excreted drugs are often necessary

40 5. Nephrotoxicity Some drugs are directly nephrotoxic, and their effects on the kidney are more predictable. Such drugs include aminoglycosides, amphotericin and ciclosporin. The use of any drug with recognised nephrotoxic potential should be avoided where possible.

41 Adverse effects of drugs on kidney

42 Thank you Kawa A. Obeid PhD Therapeutics