ACUTE KIDNEY INJURY

DR MOSES KAZEVU

MK’S MEDICAL REVIEW SERIES INTERNAL MEDICINE

 INTERNAL MEDICINE

WARM UP: SINGLE BEST ANSWER

• Renal biopsy is contraindicated in:
A. Solitary kidney
B. Thrombocytopenia
C. Uncontrolled hypertension
D. CKD
E. All the above

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

ACUTE KIDNEY INJURY

• 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.
• Acute kidney injury (AKI) used to be referred to as acute renal failure
however AKI is a broader term that also includes subtle decreases in
kidney function.
• In clinical practice such deterioration in renal function is sufficiently severe
to results in uremia.
MK’S MEDICAL REVIEW SERIES
 INTERNAL MEDICINE

NORMAL VALUES
• Normal urine output= 0.5-1 ml/kg/hr
• Normal Creatinine
• Male= 53-106 mmol/L (0.6-1.2mg/dl
• Female= 44-97 mmol/L (0.5-11mg/dl)
• Normal Urea 2.5 to 7.2 mmol/L (7 to 20mg/dl)
• Normal BUN 3.6 to 7.1 mmol/L (10 to 20mg/dl)

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

ACUTE KIDNEY INJURY

• 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.
• 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 (<400ml/day).
• Oliguria is usually but not invariably, a feature.

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

ACUTE KIDNEY INJURY

• Based on the amount of urine output acute kidney injury 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
• AKI may cause sudden life-threatening biochemical disturbances and is a
medical emergency.

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

ACUTE KIDNEY INJURY

• 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 mmol/L in 48 hours
➢ Decrease in GFR 25% in children over 7 days
• The distinction between acute and CKD or even acute-on chronic kidney disease cannot be readily
apparent in a patient presenting with uremia.
• In view of these difficulties, the Acute Dialysis Quality initiative group proposed the RIFLE (Risk,
Injury, Failure, Loss, End-stage renal disease) criteria utilizing either increases in serum creatinine
or decreases in urine output.
• 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.
(See the table below for RIFLE classification for acute kidney injury)

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

NOTE: KDIGO (KIDNEY DISEASE IMPROVING

GLOBAL OUTCOME)
Grade GFR criteria Urine output
Risk (KDIGO Stage 1) Serum creatinine x 1.5 baseline or Urine output <0.5ml/kg/h for 6
increase >26mmol/L in 48 hours 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 Urine output <0.3 ml/kg/h for
creatinine >350 mm with an acute 24 hours or anuria for 12 hours
rise >40 mmol/L or dialyzed
Loss Persistent AKI >4 weeks (1 month)
ESKD (end stage Kidney Persistent renal failure >3 months
disease)

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

RISK FACTORS FOR AKI

• Age>75
• Cardiac failure
• Peripheral vascular disease
• Chronic liver disease
• Diabetes
• Drugs (especially newly started)
• Sepsis
• Poor fluid intake/increased losses
• History of urinary symptoms

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

SIGNS AND SYMPTOMS OF UREMIA

• 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, metabolic acidosis, hypocalcemia,
secondary hyperparathyroidism, osteodystrophy

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

RECALL: EXCRETION OF
CREATININE AND UREA
• Blood reaches the kidney through the renal artery and filtered out in the glomeruli; the
filtrate moves into the renal tubule. Sometimes fluid/electrolytes can be reabsorbed into
the blood stream (tubular reabsorption) and sometimes more fluid/electrolyte can be
secreted into the renal tubule (tubular secretion)
• Waste such as urea and creatinine are also filtered in the kidney. Some urea is
reabsorbed and very little to none creatinine is reabsorbed back into the blood. The ratio
of Blood urea nitrogen to Creatinine (BUN: Cr) is thus between [5-20]:1 meaning the
blood carries about 5 to 20 molecules of BUN for every 1 molecule of creatinine- this is a
good diagnostic for looking at kidney function.
• Ultimately the filtrate is turned into urine and is excreted from the kidneys through the
ureter into the bladder and micturated out of the body as the filtered blood drains into the
renal vein.

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

Decreased concentration Increased concentration

Urea • Low protein intake • Corticosteroid treatment
• Liver failure • Tetracycline treatment
• Sodium valproate • Gastrointestinal bleeding
treatment
Creatinine • Low muscle mass • High muscle mass
• Red meat ingestion
• Muscle damage
(rhabdomyolysis)
• Decreased tubular secretion
e.g. Cimetidine, trimethoprim
therapy

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

CLASSIFICATON OF AKI
• Acute kidney injury 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 (10-50%)
➢ Post-renal (10-25%)
• More than one category may be present in an individual patient.

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

PRE-RENAL AKI
• 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.

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

ETIOLOGY
➢ 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).
➢ Low cardiac output and hypotension: diseases of myocardium (dilated cardiomyopathy), valves, and
pericardium, arrhythmias, tamponade, congestive heart failure, others (pulmonary hypertension, massive
pulmonary embolism)
➢ Altered renal systemic vascular resistance ratio: systemic vasodilatation and distributive shock (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)
➢ Vascular disease limiting renal blood flow:
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
MK’S MEDICAL REVIEW SERIES
 INTERNAL MEDICINE

CLINICAL FEATURES
• 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.

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

DIAGNOSIS
• Careful history is essential:
➢ Evidence of volume depletion: vomiting, diarrhea, bleeding
➢ Ischemia or trauma to the legs or arms may indicate rhabdomyolysis
➢ Skin rashes may indicate allergic nephritis
➢ Exposure to nephrotoxins and drugs
➢ Anuria may indicate post-renal causes
➢ Recent surgical or radiologic procedures
➢ Past and present use of medications
➢ Family history of renal disease

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

DIAGNOSIS
• Physical examination should be focused to rule out possible differential diagnosis.
➢ Pelvic and per-rectal examination: look for evidence of abortion
➢ Hypotension (especially postural), a weak rapid pulse and a low jugular venous pressure will suggest that the uremia is
pre-renaL
➢ There is decrease in GFR (due to decreased blood flow), If less blood is being filtered then less urea and creatinine are
filtered out and more stay in the blood (azotemia), this also results in oliguria (urine output <400ml/day).
➢ With less blood being filtered the renin-angiotensin-aldosterone system is activated producing more aldosterone that
causes sodium and water reabsorption. Water and sodium reabsorption also correlates to urea reabsorption therefore
more urea is present in the blood causing the BUN:Cr ratio to rise >20:1.
➢ With more sodium and water retained there is less sodium excreted in urine so the Urine sodium (<20mmol/L) is low
especially if there is avid (eager) tubular reabsorption, but may be increased by diuretics or dopamine.
➢ The fractional excretion sodium (FENa) i.e. a ratio of sodium clearance (fraction of sodium excreted/ fraction of sodium
filtered) to creatinine clearance (fraction of creatinine excreted/fraction of creatinine filtered), 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
➢ The urine is more concentrated as less water is excreted therefore the urine osmolarity is also >500mOsm/kg (mostly of
urea) also indicating there is no damage to the tubules yet.
➢ The urine specific gravity is >1.020
• 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.
• In doubtful cases, measurement of central venous pressure is often invaluable, particularly with fluid challenge.
MK’S MEDICAL REVIEW SERIES
 INTERNAL MEDICINE

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

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.

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

MANAGEMENT
• 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.

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

INTRARENAL AKI
• This accounts for nearly 40% of all Acute kidney injury cases.
• Intrarenal/intrinsic is due to damage to either:
➢ Tubules: Acute tubular necrosis
➢ Glomerulus: Glomerulonephritis
➢ Interstitium: Acute interstitial nephritis

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

ACUTE TUBULAR NECROSIS

• This is the most common cause of intrarenal AKI
• This is characterized by necrosis of the epithelial cells which line the
tubules.
• Causes:
➢ Ischemic (common)
➢ Nephrotoxic

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

ISCHEMIC ACUTE TUBULAR

NECROSIS
• Due decreased blood supply results in necrosis of tubules.
• It is Often preceded by pre-renal azotemia
• Causes include: (Hypovolemia, low cardiac output, renal vasoconstriction, systemic vasodilatation)
➢ Hemorrhage
➢ 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
➢ Other causes include obstetric complications (abruptio placentae, postpartum hemorrhage).
• Proximal tubule and medullary segment of the thick ascending limb are particularly susceptible to
ischemic damage.

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

NEPHROTOXIC ATN
• Toxic agents result in necrosis of tubules.
• Proximal tubule is particularly susceptible.
• Causes include
➢ Drugs: aminoglycosides (most common),
➢ Heavy metals (e.g. lead and platinum derivative), lithium,
➢ Myoglobinuria (e.g. from crush injury to muscle, rhabdomyolysis, electric burns),
➢ Hemoglobinemia (due to hemolysis e.g. in Falciparum malaria, ‘blackwater fever’)
➢ Ethylene glycol (associated with oxalate crystals in urine)- it is antifreeze, blue, sweet tasting
and a risk for poisoning in children,
➢ Radiocontrast dye and
➢ Urate (e.g. tumor lysis syndrome with cancer treatment)
o Hydration and allopurinol + urate oxidase are used prior to initiation of chemotherapy to
decrease risk of urate-induced acute tubular necrosis.

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

• When the cells die, the necrotic cells plug tubules and this generates high pressures in the tubules
and ultimately causes pressure on the glomerulus and the glomerular filtration rate is lowered.
With less blood being filtered less urine is produced (oliguria) and less urea and creatinine are
filtred so more remains in the blood (Azotemia). Along with these the dead cells of the tubules are
not good at reabsorbed and secreting molecules into the tubule so there is a build up of potassium
(hyperkalemia) and acids (metabolic acidosis) in the blood.
• Dysfunctional tubular epithelium results in decreased reabsorption of BUN (serum BUN:Cr 15:1),
decreased reabsorption of sodium (FENa> 2%) and inability to concentrate urine (urine osm<
350mOsm/kg).
• The necrotic cells in the tubule also form a brown granular cast. Brown, granular casts are seen in
the urine in 75% of cases.
• If the underlying cause of ATN is addressed recovery can happen because epithelial cells of the
tubule can regenerate over the course of a few weeks.

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

STAGES OF ATN
• 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.
o Oliguria is common in the early stages.
o Non-oliguric AKI is usually a result of less severe renal insult.
➢ Recovery of renal function typically occurs after 7-21 days, although recovery is delayed by continuing sepsis.
o 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.
o Clinical course is variable and ATN may last for up to 6 weeks even after a relatively short lived initial insult.
o Eventually renal function usually returns to almost normal or normal (except in renal cortical necrosis).
o No treatment is currently available to reduce the duration of ATN once it has occurred.
o The used of IV mannitol, furosemide or ‘renal-dose’ dopamine (1-5mcg/kg/min) is not supported by controlled trial
evidence and none of these treatments is without risk.
➢ 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.

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

GLOMERULONEPHRITIS
• This is inflammation of the glomerulus.
• It is often due to antigen-antibody complexes depositing in the glomerular tissue activating the
complement system that recruits other immune cells like macrophages and neutrophils to the site which
then release lysosomal enzymes causing inflammation and damaging the podocytes (The cells that line
the glomerulus).
• Recall that the filtration membrane is a barrier to both size and charge (it is negatively charged)
therefore this prevents large molecules from filtering through.
• When damaged, membrane permeability increases and large molecules can be filtered into the urine
resulting in
➢ Proteinuria
➢ Hematuria
• The fluid leakage also reduces the pressure differences that drive filtration of small molecules and
electrolytes like sodium so the GFR is actually reduced because of this leakage. Lower GFR means less
blood gets filtered and so less urine is produced (oliguria) and more fluid is circulating in the blood
(edema) and hypertension from excess fluid volume.
• If the nitrogen containing compounds are not being filtered out, more stays in the blood (azotemia).

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

ACUTE INTERSTITIAL NEPHRITIS

• This is inflammation of the interstitium over the course of days to weeks.
• This inflammation is caused by infiltration by immune cells like neutrophils and esoinophils which then
cause inflammation.
• This is thought to be a type I or IV hypersensitivity reaction and a typically caused by:
➢ Drugs: sulfa, beta lactams/penicillins, NSAIDs, traditional meds, diuretics
➢ Infection: pyelonephritis
➢ Infiltrative conditions: sarcoid, lymphoma, leukemia
• Early symptoms include oliguria and eosinophiluria but also general symptoms like fever and a rash.
• The symptoms abate once inciting agent is removed, if it persists the immune cells continues to damage
the cells in the interstitium and the kidney cells may begin to die off (Renal Papillary necrosis- Necrosis
of renal papillae) resulting in hematuria and flank pain.
➢ Other causes of renal papillary necrosis: Chronic use of analgesics e.g. aspirin, Diabetes mellitus,
sickle cells disease and pylenephritis
• If less urea is absorbed, less urea stays in the blood relative to creatinine so the BUN:Cr ratio is <15:1
and also the cells cannot reabsorb sodium so the urine sodium is >40mmol/L and FeNa>2%. Since water
is not reabsorbed as well urine osmolality <350 mOsm/kg

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

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:
• 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)
• Orthopnea, Paroxysmal nocturnal dyspnea, peripheral edema
• Hypocalcemia (due to reduce renal production of 1,25-dihydroxycholecalciferol)
• Hyperphosphatemia (due to phosphate retention)

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

CLINICAL FEATURES
➢ Signs: Symptoms of uremia
o Intellectual clouding, confusion, drowsiness, fits, coma,
o Uremic frost, hiccups, metallic taste
o Hemorrhagic episodes (Epistaxis and GIT bleeding)
o Metabolic flap/Asterixis
o Anorexia, Nausea and vomiting
o Fatigue
o Pruritus
➢ 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.
• Reversible but often requires supportive dialysis since electrolyte imbalances can be fatal.
➢ Oliguria can persist for 2-3 weeks before recovery, tubular cells (stable cells) take time to
reenter the cell cycle and regenerate.
.
MK’S MEDICAL REVIEW SERIES
 INTERNAL MEDICINE

POST-RENAL AKI
• Accounts for 5% of all acute renal failure cases.
• 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.

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

ETIOLOGY
➢ 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
➢ 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.
➢ 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.

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

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 >15:1), 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 <15:1), decreased reabsorption of sodium
(FENa>2%) and inability to concentrate urine (Urine osmolality <350 mOsm/Kg)

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

MANAGEMENT
• Management of post-renal AKI requires close collaboration between nephrologist,
urologist and radiologist.
• 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.

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

DIAGNOSTIC APPROACH
• 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

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

ACUTE ON CHRONIC UREMIA

• This depends on:
➢ History and Duration of symptoms
➢ Examination
➢ Previous urinalysis or measurements of renal function
• 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)
• 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

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

PRE-, INTRA-, AND –POST RENAL AKI

• 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.
PARAMETER PRE-RENAL RENAL POST RENAL
BUN:Cr >20:1 <15:1 Early stage >15:1
Late stage <15:1
Urine sodium (mmol/L) <20 >40 Early stage <20 Note: Fe= Fraction of excreted
Late >40 sodium, U=Urine, P=Plasma,
Urine specific gravity >1.020 <1.010 Early >1.020
Late <1.010 BUN=Blood urea nitrogen,
Urine osmolality >500 <350 Early >500 Cr=creatinine, Na= sodium
(mOsm/kg) Late <350
𝑼 𝑼
Fe = 𝑵𝒂 + 𝑪𝒓 × 𝟏𝟎𝟎 <1%
Na 𝑷
>2% Early <1%
𝑷𝑪𝒓
𝑵𝒂 Late >2%

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

INVESTIGATIONS
➢ Urinalysis
o Trace or no proteinuria (pre-renal and post-renal acute failure)
o Mild to moderate proteinuria (acute tubular necrosis)
o Moderate to severe proteinuria (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.

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

INVESTIGATIONS
• Urine chemistry: Urine Sodium: <1% in prerenal, as the kidneys retain their function. >2% in renal
causes and late stage of postrenal failure
• 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
MK’S MEDICAL REVIEW SERIES
 INTERNAL MEDICINE

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

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

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.

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

MANAGEMENT
• Fluid and electrolyte balance (potassium, phosphate, calcium)
• Management of complications: Pulmonary edema, anemia, sepsis, metabolic acidosis, electrolyte imbalances and GIT bleeding
• 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.
➢ Absolute indications
o Symptoms or signs of uremic syndrome
o Refractory hypervolemia
o Severe hyperkalemia
o Metabolic acidosis

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

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)

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

EMERGENCY MEASURES
FLUID AND ELECTROLYTE BALANCE
• 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.

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

EMERGENCY MEASURES
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
➢ Protect the heart: Give calcium gluconate 10ml of 10% solution over 5 minutes
➢ Push potassium into cells: Glucose solution 50ml of 50% glucose plus insulin 10 units IV
➢ Excrete excess potassium: Give potassium binding ion exchange resin (Kayexalate)
➢ Dialysis: if medical therapy fails or the patient is very toxic
• ECG findings in hyperkalemia
• Peaked T-waves best seen in precordial leads,
• Shortened QT interval
• sometimes ST segment depression
• Widened QRS complex

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

EMERGENCY MEASURES
PULMONARY EDEMA
• Salt and water restriction
• Diuretics (IV furosemide)
• Dialysis or hemofiltration
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, penicillin, sulfonamides).
• Prophylactic antibiotics or barrier nursing is not recommended in all cases.
HYPERPHOSPHATEMIA
• Is usually controlled by restriction of dietary phosphate and by oral aluminium hydroxide or
calcium carbonate which reduce gastrointestinal absorption of phosphate.
HYPOCALCEMIA
• Does not usually require treatment.

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

EMERGENCY MEASURES
METABOLIC ACIDOSIS
• Is not treated unless serum bicarbonate concentration fall below 15mmol/L or arterial pH falls below
7.2.
• More severe acidosis is corrected by oral or intravenous sodium bicarbonate. Initial rates of
replacement are guided by estimates of bicarbonate deficit and adjusted thereafter according to
serum levels.
• Patients are monitored for complications of bicarbonate administration e.g. hypervolemia, metabolic
alkalosis, hypocalcemia and hypokalemia.
• From a practical point of view most patients requiring sodium bicarbonate need emergency dialysis
within days.
• ANEMIA
• Blood transfusion if severe or if recovery is delayed
• GI BLEEDING
• 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.

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

COMPLICATIONS
• Intravascular overload: may be recognized by weight gain, hypertension, elevated central venous
pressure (raised 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) as well as tubular damage reducing sodium reabsorption.
➢ 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

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

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.

MK’S MEDICAL REVIEW SERIES

 INTERNAL MEDICINE

WARM UP: SINGLE BEST ANSWER

• Renal biopsy is contraindicated in:
A. Solitary kidney
B. Thrombocytopenia
C. Uncontrolled hypertension
D. CKD
E. All the above

MK’S MEDICAL REVIEW SERIES

THANK YOU
“Better late than never”