Acute Kidney Injury

Question 1

Functions of the kidneys

Answer 1

remove waste products from the body
remove drugs from the body
balance the body’s fluids
release hormones that regulate blood pressure
produce an active form of vitamin D that promotes strong, healthy bones
control the production of red blood cells

Question 2

What is AKI?

Answer 2

Acute kidney injury is an abrupt deterioration in parenchymal renal function, which is usually but not invariably, reversible over a period of days or weeks.
 It is a rapid reduction in kidney function over hours to days, as measured by serum urea and creatinine and leading to failure to maintain fluid, electrolyte and acid-base homeostasis.

AKI can also be defined as any 1 of the following:
- Urine output <0.5 ml/kg/hr for 6 hours or 8 hours consecutive in kids
- Creatinine x 1.5 from baseline in 1 week
- Creatinine increase greater than 26 mol/L in 48 hours
- Decrease in GFR 25% in children over 7 days

Question 3

AKI is characterized by…

Answer 3

Acute renal failure is a syndrome characterized by:
- Rapid decline in glomerular filtration rate (hours to days)
- Retention of nitrogenous wastes due to failure of excretion
- Disturbance in extracellular fluid volume and
- Disturbance in electrolyte and acid base homeostasis.

Question 4

Explain the hallmarks of AKI

Answer 4

The hallmark of acute renal failure is azotemia, often with oliguria
 Azotemia: increase in nitrogenous waste products in the blood (Blood urea nitrogen and creatinine) without symptoms (GFR is about 20-35% of normal).
 Uremia implies a deterioration of renal function associated with symptoms (GFR <20% of normal)
 Oliguria is a condition in which a person does not produce enough urine. Oliguria is usually but not invariably, a feature.

Question 5

Classify acute renal failure based on urine output

Answer 5

Based on the amount of urine output acute renal failure may be classified as:
- Anuric: if urine volume is less than 100ml/day
- Oliguric- if urine volume is less than 400ml/day
- Non-oliguric- if urine volume is greater than or equal to 400ml/day

Question 6

What is the RIFLE criteria?

Answer 6

 It characterizes 3 levels of renal dysfunction (R, I, F) and 2 outcome measures (L, E). These criteria indicate an increasing degree of renal damage and have a predictive value for mortality.

GFR CRITERIA and URINE OUTPUT
Risk (KDIGO Stage 1): Serum creatinine x 1.5 baseline or increase >26 MICRO mol/L in 48 hours
Urine output <0.5ml/kg/h for 6 hours
Injury (KDIGO Stage 2): Serum creatinine x 2-2.9 baseline
Urine output <0.5 ml/kg/h for 12 hours
Failure (KDIGO Stage 3): Serum creatinine x 3 or Serum creatinine >350 micro m with an acute rise >40 micromol/L or dialyzed
Urine output <0.3 ml/kg/h for 24 hours or anuria for 12 hours

LOSS: Persistent AKI >4 weeks (1 month)
ESKD (end stage Kidney disease): Persistent renal failure >3 months

Question 7

RF for developing AKI

Answer 7

Risk factors for developing AKI
 Age>75
 Chronic kidney disease
 Cardiac failure
 Peripheral vascular disease
 Chronic liver disease
 Diabetes
 Drugs (especially newly started)
 Sepsis
 Poor fluid intake/increased losses
 History of urinary symptoms

Question 8

Signs and symptoms of uremia

Answer 8

 Signs and symptoms of uremia include:
 General: Nausea and vomiting, fatigue, weight loss, anorexia (loss of appetite), fetor uremicus (urine like odor of the breath), metallic taste, hiccups, pruritus, uremic frost, muscle cramps, metabolic flap/asterexis
 Neurologic: encephalopathy (change in mental status, Intellectual clouding, confusion, drowsiness, fits, coma, decreased memory and attention), seizures, neuropathy.
 Cardiovascular: Pericarditis, hypertension, volume overload, CHF, cardiomyopathy, hyperlipidemia, accelerated atherosclerosis
 Hematologic: Anemia, and bleeding (due to platelet dysfunction)
 Metabolic: hyperkalemia, hyperphosphatemia, acidosis, hypocalcemia, secondary hyperparathyroidism, osteodystrophy

Question 9

How is uremia classified? AKI

Answer 9

 Renal failure results in reduced excretion of nitrogenous waste products, of which urea is the most commonly measured. A raised serum urea concentration (Uremia) is classified as:
- Pre-renal (40-70%)
 - Renal/Intrinsic/Intrarenal (10-50%)
 - Post-renal (10-25%)
 More than one category may be present in an individual patient.

Prerenal AKI:
Reduced blood flow to the kidneys due to conditions like volume depletion (dehydration), heart failure, or obstruction of blood vessels. –> Decreased glomerular filtration rate (GFR), leading to a build-up of waste products in the blood.
Intrarenal AKI:
Direct damage to the kidney tissue, including the tubules (responsible for filtering waste), glomeruli (responsible for filtration), and blood vessels. –> Impaired filtration and absorption, leading to a build-up of waste products and fluid retention.
Postrenal AKI:
Obstruction of urine flow within the urinary tract, including the ureters, bladder, or urethra. –> Backup of urine into the kidneys, causing pressure and damage to the kidney tissue

Question 10

What are the mon renal causes of altered serum urea and creatinine?

Answer 10

DECREASED
UREA:  Low protein intake
 Liver failure
 Sodium valproate treatment
CREATININE: low muscle mass

INCREASED
UREA :  Corticosteroid treatment
 Tetracycline treatment
 Gastrointestinal bleeding
CREATININE :  High muscle mass
 Red meat ingestion
 Muscle damage (rhabdomyolysis)
 Decreased tubular secretion e.g. Cimetidine, trimethoprim therapy

Question 11

Pre renal uremia

Answer 11

This accounts for nearly 55% of all cases of acute renal kidney. It is also known as pre-renal azotemia. There is impaired perfusion of the kidneys with blood.
 Usually the kidney is able to maintain glomerular filtration close to normal despite wide variations in renal perfusion pressure and volume status- so called ‘autoregulation’. Further depression of renal perfusion leads to a drop in the glomerular filtration and development of pre-renal uremia.
 Renal hypoperfusion leads to a decrease in GFR as an appropriate response to retain Na+/H2O. There is no renal cell injury and restoration of perfusion restores function.
 Prolonged hypoperfusion can lead to acute tubular necrosis, thus ischemic AKI is a spectrum from pre-renal to intrinsic AKI, differentiated by presence of renal cell injury.

Question 12

Causes of prerenal uremia

Answer 12

This results either from :
1. Hypovolemia: hemorrhage, severe diarrhea, severe vomiting, burns dehydration, renal fluid loss (diuretics, osmotic diuresis e.g. diabetes mellitus), hypoadrenalism, third spacing (pancreatitis, peritonitis, trauma, burns, severe hypoalbuminemia).
2. Low cardiac output and hypotension: diseases of myocardium (dilated cardiomyopathy), valves, and pericardium, arrhythmias, tamponade, congestive heart failure, others (pulmonary hypertension, massive pulmonary embolism)
3. Altered renal systemic vascular resistance ratio: systemic vasodilatation (sepsis, anaphylaxis, renal hypoperfusion with impairment of renal autoregulatory response e.g. with NSAIDs, ACE inhibitors. NSAIDs constrict the afferent arterioles while ACEi and ARBs dilate efferent arterioles than afferent arterioles)
4. Vascular disease limiting renal blood flow

Question 13

C/F of pre renal failure/uremia

Answer 13

 Pre-renal failure is suggested by clinical signs of:
- Intravascular volume depletion (e.g. orthostatic hypotension, rapid pulse and poor skin turgor).
- Congestive heart failure e.g. raised JVP, S3, dependent edema and pulmonary rales.

Question 14

history taking of pre-renal uremia

Answer 14

Careful history is essential:
 Exposure to nephrotoxins and drugs
 Anuria may indicate post-renal causes
 Skin rashes may indicate allergic nephritis
 Evidence of volume depletion: diarrhea, bleeding
 Pelvic and per-rectal examination: look for evidence of abortion
 Ischemia or trauma to the legs or arms may indicate rhabdomyolysis
 Recent surgical or radiologic procedures
 Past and present use of medications
 Family history of renal disease

Question 15

diagnosis of pre renal uremia

Answer 15

DIAGNOSIS
 Physical examination should be focused to rule out possible differential diagnosis.
 In pre-renal uremia:
 There is decrease in GFR (due to decreased blood flow), azotemia and oliguria.
 Urine sodium (<20mmol/L) is low if there is avid (eager) tubular reabsorption, but may be increased by diuretics or dopamine.
 The urine osmolarity is also >500mOsm/kg also indicating there is no damage to the tubules yet.
 The urine specific gravity is >1.020
 The serum BUN: Cr increases (20mg/dl) and is more than 15mg/dl (normal)
o Recall BUN and Creatinine are both filtered by the glomerulus but only BUN is reabsorbed and creatinine is not.
o In pre-renal uremia because of decreased renal perfusion the renin angiotensin system is activated resulting in release of aldosterone from the adrenal glands causing resorption of sodium and water. Resorption of water will also result in resorption of some filtered BUN, this increased the BUN: Cr ratio.
 The fractional excretion sodium (FENa) i.e. a ratio of sodium clearance to creatinine clearance, is less than 1% indicating there is no damage to the tubules yet. It may remain low in some ‘intrinsic’ renal disease, 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 uremia is pre-renal
 In doubtful cases, measurement of central venous pressure is often invaluable, particularly with fluid challenge.

Question 15

Tx of pre renal uremia

Answer 15

MANAGEMENT
 Treat the underlying cause. There is no specific treatment indicated for AKI, it is just supportive.
 If the pre-renal uremia is a result of hypovolemia and hypotension, prompt replacement with appropriate fluid is essential to correct the problem and prevent development of ischemic renal injury and acute kidney disease.
 Severe hypovolemia due to hemorrhage should be corrected with packed red blood cells, whereas normal saline is usually appropriate replacement for mild to moderate hemorrhage or plasma loss (e.g. burns, pancreatitis).
 Urinary and gastrointestinal fluids can vary greatly in composition but are usually hypotonic. Hypotonic solution (e.g. 0.45% saline) are usually recommended as initial replacement in patient with Pre-renal failure due to increased urinary or GI fluid losses, although normal saline may be more appropriate in severe cases.
 If difficult balance with risk of fluid overload, consider titrating input hourly by matching previous hours output + 25ml/h for insensible losses. If Euvolemic review balance daily over 24 hour period aim to match input to loss + 500ml for insensible loss.
 Consider fluid boluses if you think the patient is dehydrated and has pre-renal AKI.
o Fluid challenge if patient dehydrated: give 250-500ml of saline over 30 minutes. Repeat challenge if still dehydrated (give fluids until JVP and systolic BP >100mmHg) caution in patients with cardiac dysfunction
o Once fluid replete continue fluids at 20ml + Previous hour’s urine output per hour
 For bleeding is still in shock despite 2L crystalloid then cross-match blood and transfuse FFP alongside packed red cells (1:1 ratio) and aim for platelets >100 and fibrinogen >1.
 Listen to lungs to assess for fluid overload. Signs of fluid overload: increased BP, increased JVP, lung crepitations, peripheral edema, gallop rhythm on cardiac auscultation.
 Since pre-renal and renal uremia 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 edema sought frequently.
 Central venous pressure monitoring is usually advisable. If the problem relates to cardiac pump insufficiency or occlusion of the renal vasculature, appropriate measures- albeit often unsuccessful need to be taken.
 Serum potassium and acid-base status should be monitored carefully.
 Antibiotics should also be given to treat any infection (Sepsis).
 Give Antiemetics for patients vomiting
 Stop NSAIDs, ACE inhibitors, angiotensin receptor antagonists and Diuretics.
 The role of Furosemide is uncertain. Some advocate it for fluid overload but NICE doesn’t and there is no good trial evidence.
 Dialysis can be done in refractory cases.

Question 16

causes of intrarenal uremia

Answer 16

Causes include:
1. Acute tubular interstitial necrosis (most common cause): can either be ischemic (common) or nephrotoxic
o Ischemic: prolonged pre-renal
 Hemorrhage. PPH, abruptio placenta
 Burns
 Diarrhea and vomiting, fluid loss from fistulae
 Pancreatitis, Diuretics
 Myocardial infarction, Congestive cardiac failure, Endotoxic shock, Snake bite
 Hepatorenal syndrome
 Pre-eclampsia and eclampsia
o Nephrotoxic:
 Myoglobinemia
 Hemoglobinemia (due to hemolysis e.g. in Falciparum malaria, ‘blackwater fever’)
 Radiological contrast
 Drugs e.g. aminoglycosides, platinum derivatives, heavy metals, Lithium
myoglobiuria (e.g. from crush injury to muscle, rhabdomyolysis, electric burns), ethylene glycol (associated with oxalate crystals in urine), and urate (e.g. tumor lysis syndrome)
2. Acute Interstitial nephritis (AIN): glomerulonephritis, including rapidly progressive glomerulonephritis (RPGN)
o Allergic: sulfa, beta lactams, NSAIDs, traditional meds
o Infection: pyelonephritis
o Infiltrative: sarcoid, lymphoma, leukemia
penicilins
diuretics
 3. Disease of glomeruli or renal microvasculature (renovascular):
o Renal artery stenosis,
o Vasculitis, accelerated/malignant hypertension,
o Cholesterol embolism,
o Microangiopathy: hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, pre-eclampsia and DIC
o Crescentic glomerulonephritis

Question 17

outline

Answer 17

ACUTE TUBUOINTERSTITIAL NECROSIS
 This is injury and necrosis of tubular epithelial cells.
 Etiology may be ischemic or nephrotoxic:
1. Ischemic- decreased blood supply results in necrosis of tubules.
o Often preceded by pre-renal azotemia (Hypovolemia, low cardiac output, renal vasoconstriction, systemic vasodilatation).
o Proximal tubule and medullary segment of the thick ascending limb are particularly susceptible to ischemic damage.
 2. Nephrotoxic- toxic agents result in necrosis of tubules.
o Proximal tubule is particularly susceptible.
o Hydration and allopurinol are used prior to initiation of chemotherapy to decrease risk of urate-induced acute tubular necrosis.

Necrotic cells plug tubules, obstruction decreases GFR. Brown, granular casts are seen in the urine in 75% of cases.
Dysfunctional tubular epithelium results in decreased reabsorption of BUN (serum BUN:Cr <15mg/dl), decreased reabsorption of sodium (FENa> 2%) and inability to concentrate urine (urine osm< 350mOsm/kg).

Question 18

what is the pathogenesis of acute tubulointestitial necrosis?

Answer 18

Factors implicated in the development of Acute tubulointestitial necrosis include:
1. Intrarenal microvascular vasoconstriction:
o Vasoconstriction is increased in response to endothelin, adenosine, thromboxane A2, leukotrienes and sympathetic nerve activity.
o Vasodilation is impaired due to reduced sensitivity in response to nitric oxide, prostaglandins (PGE2), acetylcholine and bradykinin. There is also increased endothelial and vascular smooth muscle cell structural damage
o Increased leucocyte-endothalial adhesion, vascular congestion and obstruction, leucocyte activation and inflammation.
 2. Tubular cell injury: ischemic injury results in rapid depletion of intracellular ATP stores resulting in cell death by necrosis or apoptosis due to:
o Entry of calcium into the cells
o Induction by hypoxia of inducible nitric oxide synthase with increased production of nitric oxide causing cell death
o Increased production of intracellular proteases such as calpain which causes proteolysis of cytoskeleton protein and cell wall collapse
o 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.
o Cell injury resulting from reperfusion with blood after initial ischemia causing excessive free radical generation.
o Tubular obstruction by desquamated viable or necrotic cells and casts
o Loss of cell polarity i.e. integrins located on the basolateral side of the cell are translocated to the apical surface when combined with other desquamated cells forms casts, with tubular obstruction and back leak of tubular fluid
 3. Tubular cellular recovery: tubular cells have the capacity to regenerate rapidly and to reform the disrupted tubular basement membrane, which explains the reversibility of ATN.

Question 19

explain the mechanism by which acute tubular intestitial necrosis causes a reduction in GFR

Answer 19

In established ATN, renal blood flow is much reduced, particularly blood flow to the renal cortex. Ischemic tubular damage contributes to a reduction in glomerular filtration by the following mechanisms:
 1. 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.
2. ‘Back leak’ of filtrate: in the proximal tubule owing to loss of function of the tubular cells
 3. Obstruction of the tubules: by debris shed from ischemic tubular cells, these appear on renal biopsy as flat rather than the normal tall appearance.

Question 20

how does oliguria in acute tubular interstitial necrosis affect mortality and morbidity?

Answer 20

Morbidity and mortality are affected by the presence of oliguria: GI bleeding, septicemia, metabolic acidosis and neurologic abnormalities are common in oliguric patients than non-oliguric patients. The mortality rate for oliguric patients is 50% where as that of non-oliguric patients is only 26%.

Question 21

outline the course of acute kidney injury due to acute tubular interstitial necrosis

Answer 21

Stages: acute kidney injury due to ATN typically occurs in 3 stages: Azotemic, Diuretic and recovery phases. The initial azotemic stage can either be oliguric or non-oliguric type.
 Oliguria is common in the early stages. Non-oliguric AKI is usually a result of less severe renal insult.
 Note: in the polyuric (aka diuretic) phase of kidney injury as the kidney heals from AKI, tubules regenerate but water concentration is last function to return. There may also be increased osmotic load from renal toxin accumulation and this leads to massive polyuria. Treatment is with IV fluids to replace the loss.
 Recovery of renal function typically occurs after 7-21 days, although recovery is delayed by continuing sepsis.
 In the recovery phase GFR may remain low while urine output increases sometimes to many liters a day owing to defective tubular reabsorption of filtrates.
 Clinical course is variable and ATN may last for up to 6 weeks even after a relatively short lived initial insult.
 Eventually renal function usually returns to almost normal or normal (except in renal cortical necrosis).
 No treatment is currently available to reduce the duration of ATN once it has occurred.

Question 22

C/F of acute tubular interstitial necrosis

Answer 22

CLINICAL FEATURES
 Clinical features:
 Oliguria with brown, granular casts.
 Elevated BUN and creatinine.
 Hyperkalemia (Due to decreased renal excretion, particularly following trauma to muscle and in hemolytic states) with metabolic acidosis (decreased excretion of organic acids).
 Hyponatremia (due to water overload if patients have continued to drink in the face of oliguria or overenthusiastic fluid replacement with 5% glucose has been carried out)
 Fluid overload:
o Pulmonary edema (due to salt and water retention, particularly after inappropriate attempts to initiate diuresis by infusion of normal saline without adequate monitoring of patient’s volume status)
o Orthopnea, Paroxysmal nocturnal dyspnea, peripheral edema
 Hypocalcemia (due to reduce renal production of 1,25-dihydroxycholecalciferol)
 Hyperphosphatemia (due to phosphate retention)
 Signs: Symptoms of uremia
 Severe infection may have initiated the AKI or have complicated it owing to the impaired immune defenses of the uremic patient or ill-considered management such as the insertion and retention of an unnecessary bladder catheter with complicating UTI and bacteremia.

Question 22

what is ACUTE INTERSTITIAL NEPHRITIS? also state its presentation and Tx

Answer 22

Drug-induced hypersensitivity involving the interstitium and tubules results in acute renal failure (intrarenal azotemia).
 Presents as oliguria, fever and rash days to weeks after starting a drug, eosinophils may be seen in urine.
 Resolves with cessation of drug.
 May progress to renal papillary necrosis.

Question 23

briefly describe renal papillary necrosis

Answer 23

RENAL PAPILLARY NECROSIS  Necrosis of renal papillae.  Presents with gross hematuria and flank pain.  Causes include:  Chronic analgesic abuse (e.g. long term phenacetin or aspirin use)  Diabetes mellitus  Sickle cell trait or disease  Severe acute pyelonephritis

Question 24

what is POST-RENAL UREMIA?

Answer 24

 Uremia results from obstruction of the urinary tract at any point from the calyces to the external urethral orifice (meatus). This results in dilation of the tract above the obstruction. Dilation of the renal pelvis is known as hydronephrosis.

Question 24

pathophysiology of post renal uremia

Answer 24

PATHOPHYSIOLOGY  Obstruction which may be intra renal i.e. tubules including collecting ducts or extra-renal i.e. renal calyces to uretheral meatus causes a back flow of filtrate and resultant pressure on the glomerulus thus reducing the GFR.  Lower urinary tract obstruction may be suggested by suprapubic or flank mass or symptoms of bladder dysfunction (e.g. hesitancy, urgency)  Decreased outflow results in decreased GFR, azotemia and oliguria.  During early stage of obstruction, increased tubular pressure “forces” BUN into the blood (Serum BUN:Cr ratio >15), tubular function remains intact (FENa <1% and urine osm> 500mOsm/kg)  With longstanding obstruction, tubular damage ensues, resulting in decreased reabsorption of BUN (serum BUN:Cr ratio <15), decreased reabsorption of sodium (FENa>2%) and inability to concentrate urine (Urine osm <350 mOsm/Kg)

Question 25

causes of post renal uremia

Answer 25

 Causes can be  1. Within the lumen: calculus, blood clot, sloughed papilla (diabetes, analgesia abuse, sickle cell disease or trait), schistosomiasis, tumor of renal pelvis or ureter bladder tumor  2. Within the wall: pelviuretetic neuromuscular dysfunction (congenital, 10% bilateral), ureteric stricture (TB, especially after treatment, calculus, after surgery), ureterovesical stricture (congenital, ureterocele, calculus, schistosomiasis), congenital megaureter, congenital bladder neck obstruction, neuropathic bladder, urethral stricture (calculus, gonococcal, after instrumentation), congenital urethral valve, pin-hole meatus.  3. Pressure from outside: pelviureteric compression (bands, aberrant vessels), tumors, diverticulitis, aortic aneurysm, retroperitoneal fibrosis, accidental ligation of ureter, retrocaval ureter (right sided obstruction), prostatic obstruction (CA prostate, BPH), phimosis.  Screening for urinary obstruction may present in an acute fashion (if obstruction of a single functioning kidney e.g. a calculus) but typically is of insidious onset.

Question 26

management of post renal uremia

Answer 26

MANAGEMENT  Obstruction of urethra or bladder neck is usually managed initially by transurethral or suprapubic placement of a bladder catheter which provides temporary relief while the obstructing lesion is identified and treated definitively.  Similarly, ureteric obstruction may be treated initially by percutaneous catheterization of the dilated renal pelvis or ureter.

Question 27

what are the investigation aims of AKI

Answer 27

Investigations are aimed at:  Determining whether the patient has acute or chronic uremia  Determining the cause of uremia i.e. pre-renal, renal or post-renal  Determining the underlying cause

Question 28

outline the history taking that determines whether its acute or chronic uremia

Answer 28

History:  Consider these things for all patients. Remember, Kidney injury in the hospital is often tied into another problem (infection, heart failure, medications).  Decreased or no urine output, flank pain, edema, hypertension or discolored urine? Hesitancy, Frequency?  Weakness and easy fatigability (from anemia), anorexia, vomiting, diarrhea, mental status changes or seizures and edema?  Fever, cough, dysuria? Bleeding (i.e. melena, blood per rectum)? New/changed doses in medications?  Does the patient have medical problems that pre-dispose to CKD (i.e. HIV, diabetes, HTN)

Question 28

outline the exam and investigations to differentiate between AKI or CKD

Answer 28

Examination: vital signs (including orthostatics), Tenderness, Prostate exam A rapid rate of change of serum urea and creatinine with time suggests an acute process.  A normochromic normocytic anemia suggests chronic disease but anemia may complicate many diseases that cause AKI owing to a combination of hemolysis, 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 amyloidosis for instance.  Evidence of renal osteodystrophy (e.g. digital subperiosteal erosions due to hyperparathyroid bone disease) is indicative of CKD

Question 29

HOW TO DIFFERENTIATE BTWN PRE-RENAL, RENAL OR POST RENAL UREMIA

Answer 29

 Bladder outflow obstruction is ruled out by insertion of a urethral catheter or flushing of an existing catheter which should be removed unless a large volume of urine is obtained.  Absence of upper tract dilation on renal ultrasound will with very rare exceptions rule out urinary tract obstruction.  The distinction between pre-renal and renal uremia may be difficult.

Question 29

WHAT ARE THE INDICATIONS FOR A RENAL BIOPSY?

Answer 29

 Indications o Any suspicion of rapid progressive glomerulonephritis o Prolonged ATN (not recovered <3 weeks) o No cause found for AKI.

Question 29

OUTLINE THE INVESTIGATIONS DIAGNOSTIC OF RENAL FAILURE

Answer 29

INVESTIGATIONS  Urinalysis o Trace or no proteinuria with pre-renal and post-renal acute failure o Mild to moderate proteinuria with acute tubulointerstitial necrosis. o Moderate to severe proteinuria with glomerular diseases. o WBCs (pyuria): UTI, Acute interstitial nephritis o Blood (hematuria) and protein (albuminuria): Glomerulonephritis, stones, UTI, tumor, trauma. Blood is microscopic in Acute interstitial nephritis.  Microscopy o RBCs and RBC casts in glomerular disease (glomerulonephritis, Rapid progressive glomerulonephritis) o Presence of a few formed elements or hyaline casts is suggestive of prerenal or postrenal failure. o Crystal RBCs and WBCs in post-renal failure. o Many RBCs may suggest calculi, trauma, infection or tumor o Eosinophilia (with Eosinophil casts): occurs in 95% of patients with acute allergic nephritis. Neutrophils may also be seen. o Brownish pigmented granular or tubular epithelial cellular casts and many renal epithelia cells are seen in patients with acute tubular necrosis.  Urine culture if there are signs of infection.  Urine chemistry: Urine Sodium: <1% in prerenal, as the kidneys retain their function. >2% in renal causes  Bloods:  Full blood count: decreased Hemoglobin (CKD), increased WBC (infection, eosinophilia in AIN), decreased platelets (hemolytic uremic syndrome, Thrombotic thrombocytopenic purpura)  Serum urea, creatinine and electrolytes (Sodium, potassium, chloride, phosphate, calcium, bicarbonate)  Liver function test and Liver enzymes: hepatorenal syndrome o Serum albumin o PT, PTT, INR: DIC in sepsis, altered clotting in CKD. Serum Creatinine Kinase: rhabdomyolysis  C reactive protein: infection  Arterial blood gasses: metabolic acidosis  Blood culture in sepsis  Radiography/imaging  Ultrasound of kidneys: kidney size & shape, and for detecting hydronephrosis (dilated calyces) or hydroureter. It also helps to seen renal calculi and renal vein thrombosis  Retrograde pyelography: done when obstructive uropathy is suspected.  Abdominal X-ray  ECG: increased potassium  Chest X-ray: pulmonary edema, systemic disease  Abdominal CT  Renal biopsy

Question 30

OUTLINE THE MANAGEMENT OF AKI

Answer 30

MANAGEMENT  General measures:  Exclude reversible causes: obstruction should be relieved; infection should be treated.  Good nursing and physiotherapy  Regular oral toilet and chest physiotherapy  Fluid input and output chart  Monitoring and maintenance urine output: although the prognostic importance of oliguria is debated, management of non-oliguric patients is easier. Loop diuretics may be useful to convert the oliguric form of ATN to the non-oliguric form. High doses of loop diuretics such as Furosemide (up to 200 to 400mg IV) may promote diuresis in patients who fail to respond to conventional doses.  Daily weighing  The patient should be confined to bed only if essential  Avoid drugs which may cause damage to the kidneys e.g. loop diuretics, beta blockers, ACE inhibitors, ARBs, aminoglycosides (gentamicin, streptomycin), amphotericin B, Penicillins, Sulphonamides, NSAIDs, corticosteroids, and penicillamine  Avoid intravenous cannulae, bladder catheters and other invasive devices to avoid infection.  Diet: o Adequate calorie intake is essential in patients with AKI. o Diet should be reduced in protein but contain carbohydrates o Routes of administration, in preferred order are enteral by mouth, enteral by NG tube and parenteral. The last of these is however only necessary if vomiting or bowel dysfunction render the enteral route inappropriate. o Vitamin supplementation.  Fluid and electrolyte balance (potassium, phosphate, calcium)  Management of complications:  Dialysis: dialysis replaces renal function until regeneration and repair takes place to restore renal function. Hemodialysis and peritoneal dialysis appears equally effective for management of AKI.

Question 30

WHAT ARE THE ABSOLUTE INDICATIONS FOR DIALYSIS IN AKI?

Answer 30

Absolute indications o Symptoms or signs of uremic syndrome o Refractory hypervolemia o Severe hyperkalemia o Metabolic acidosis INDICATIONS OF DIALYSIS A- acid-base imbalance (Acidosis) E-electrolyte imbalance (Hyperkalemia) I- intoxication (methanol, ethylene glycol, lithium, salicylates) O-overload of volume (pulmonary edema) U-uremia (pericarditis, encephalopathy, severe bleeding)

Question 31

MANAGEMENT OF FLUID AND ELECTROLYTE BALANCE DUE TO AKI

Answer 31

 Twice daily clinical assessment is needed. In general, once the patient is euvolemic.  Daily fluid intake should equal urine output plus losses from fistulae and from vomiting, plus an allowance of 500ml daily for insensible loss. Febrile patients will require an additional allowance.  Sodium and potassium intake should be minimized.  If abnormal loss of fluid occurs 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 hypovolemia should prompt reappraisal of fluid intake.  Large changes in daily weight reflecting change in fluid balance status should also prompt a reappraisal of volume status.  Hypervolemia can usually be managed by restriction of salt and water intake and diuretics.

Question 31

MANAGEMENT OF HYPERKALEMIA DUE TO AKI

Answer 31

HYPERKALEMIA  Cardiac (cardiac dysrhythmias i.e. ventricular fibrillation) and neurologic complications may occur if serum potassium level is >6.5mEq/L  Management:  Restrict dietary potassium intake  Give calcium gluconate 10ml of 10% solution over 5 minutes  Glucose solution 50ml of 50% glucose plus insulin 10 units IV  Give potassium binding ion exchange resin (Kayexalate)  Dialysis: if medical therapy fails or the patient is very toxic

Question 32

ECG findings in hyperkalemia

Answer 32

 Peaked T-waves best seen in precordial leads,  Shortened QT interval  sometimes ST segment depression  Widened QRS complex

Question 33

MANAGEMENT OF SEPSIS DUE TO AKI

Answer 33

 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.

Question 33

MANAGEMENT OF PULMONARY EDEMA DUE TO AKI

Answer 33

 Salt and water restriction  Diuretics (IV furosemide)  Dialysis or hemofiltration

Question 34

MANAGEMENT OF METABOLIC ACIDOSIS DUE TO AKI

Question 34

MANAGEMENT OF HYPERPHOSPHATEMIA DUE TO AKI

Answer 34

 Is usually controlled by restriction of dietary phosphate and by oral aluminium hydroxide or calcium carbonate which reduce gastrointestinal absorption of phosphate.

Question 35

MANAGEMENT OF ANEMIA DUE TO AKI

Answer 35

 Blood transfusion if severe or if recovery is delayed

Question 36

MANAGEMENT OF GI BLEEDING DUE TO AKI

Answer 36

 Regular doses of antacids appear to reduce the incidence of GIT hemorrhage significantly and may be more effective in this regard than H2 antagonists or proton pump inhibitors.

Question 37

COMPLICATIONS OF ACUTE RENAL FAILURE

Answer 37

 Intravascular overload: may be recognized by weight gain, hypertension, elevated central venous pressure (raise JVP), pulmonary edema.  Electrolyte disturbances:  Hyperkalaemia (serum potassium> 5.5mEq/L): develops as a result of decreased renal excretion combined with tissue necrosis or hemolysis.  Hyponatremia (serum sodium <135mEq/L): results from excessive water intake in the face of excretory failure (dilution)  Hyperphosphotemia (serum phosphate >5.5mg/dl): results from failure of excretion or tissue necrosis  Hypocalcemia (Serum calcium <8.5 mg/dl) results from decreased active Vit-D, hyperphosphatemia or hypoalbuminemia (as necrosis is taking place remember calcium is needed and is used up)  Hypercalcemia (Serum calcium> 10.5mg/dl) may occur during the recovery phase following rhabdomyolysis induced acute renal failure.  Metabolic acidosis (arterial blood pH< 7.35) is associated with sepsis or severe heart failure  Hyperuricemia: due to decreased uric acid excretion  Bleeding tendency: may be due to platelet dysfunction and coagulopathy associated with sepsis.  Seizure: may occur related to uremia  Chronic renal failure

Question 38

PROGNOSIS OF AKI

Answer 38

PROGNOSIS  Mortality rate among patients with AKI approximates 50. It should be stressed however, that patients usually die from sequelae of the primary illness that induced AKI and not from AKI itself.  Mortality is affected by severity of the underlying disease and the clinical setting in which acute renal failure occurs. E.g. the mortality of ATN is 60% when it results from surgery or trauma, 30% when it occurs as a complication of medical illnesses, and 10-15% when pregnancy is involved.  Mortality rates are higher in older debilitated patients and in those with multiple organ failure.  Patients with no complicating factors who survive an episode of acute renal failure have 90% chance of complete recovery of kidney function.