Transcript Acute renal failure

Renal Diseases
• Renal failure
1. Acute renal failure: types, signs and
management
2. Chronic renal failure: signs and management
• Specific tubular defects
• Renal stones (urinary calculi)
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Renal disorders:
• Many renal diseases are defined in terms of their clinical presentation and structural
change. Aetiology and pathophysiology of many disorders are not well defined
• Renal failure is the impairment of kidney function:
– In acute renal failure (ARF): the kidneys fail rapidly over a period of hours or
days, producing the syndrome of acute renal failure. This is potentially
reversible and normal renal function can be recovered.
– Chronic renal failure (CRF) develops gradually over months or years and is
irreversible  leading eventually to end-stage renal failure (ESRF)
• Patient with end-stage renal failure require long-term renal replacement treatment
(i.e., dialysis) or a successful renal transplant in order to survive.
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Signs and Symptoms of Renal Failure
• Symptoms of Uraemia (nausea, vomiting, lethargy)
• Disorders of Micturation (frequency, retention, nocturia (is the need to get
up during the night in order to urinate, thus interrupting sleep), dysuria
(difficult or painful discharge of urine))
• Disorders of Urine volume (polyuria: excessive urination, oliguria:
decreased production of urine, anuria: absent urine production)
• Alterations in urine composition (haematuria, proteinuria, bacteriua,
leukocyturia, calculi)
• Pain
• Oedema (hypoalbuminaemia, salt and water retention)
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Acute renal failure
• Acute renal failure is characterized by a rapid loss of renal function, with
retention of urea, creatinine, hydrogen ions and other metabolic products
and usually oliguria (less than 400 ml urine/24hrs).
• The term ‘uraemia’ (meaning ‘urine in blood’) is often used as a synonym for
renal failure (both acute and chronic).
• Azotemia refers to an increase in the blood concentration of nitrogenous
compounds mainly urea.
• ARF could be reversible. But its consequences to homeostatic mechanisms are
so dangerous  associated with high mortality.
• Acute renal failure often develops in patients who are already severely ill.
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• ARF arises from a variety of problems affecting the kidneys and/or
their circulation.
• It usually presents as a sudden deterioration of renal function
indicated by rapidly rising serum urea and creatinine
concentrations. As acute renal failure is common in the severely ill,
sequential monitoring of kidney function is important for early
detection in this group of patients.
• Usually, urine output falls to less than 400 ml/24 hours, and the
patient is said to be oliguric.
• The patient may pass no urine at all, and be anuric.
• Occasionally urine flow remains high when tubular dysfunction
predominates.
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Types of Acute renal failure
• Acute kidney failure or uraemia is conventionally divided into three categories :
• Pre-renal: the kidney fails to receive a proper blood supply (a decrease in renal
blood flow).
• Post-renal: the urinary drainage of the
kidneys is impaired because of an
obstruction (urinary tract obstruction).
• Renal: intrinsic damage to the kidney
tissue. This may be due to a variety of
diseases, or the renal damage may be a
consequence of prolonged pre-renal or
post-renal problems, it is called acute
tubular necrosis.
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Prerenal acute renal failure
• This is caused by circulatory insufficiency and decreased plasma volume, as
sever haemorrhage, burns, fluid loss as in prolonged vomiting, or diarrhoea,
cardiac failure or hypotension  decrease renal perfusion  induces intense
renal vasoconstriction  decrease in GFR but tubular function is normal.
• Prerenal uraemia is a result of normal physiological response to hypovolaemia or
a fall in blood pressure. Stimulation of the renin-angiotensin-aldosterone system
and vassopressin secretion results in production of a small volume of highly
concentrated urine with a low sodium concentration.
• Prerenal uraemia may progress into intrinsic failure (acute tubular necrosis)
 it should be treated before structural damage.
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Biochemical findings in pre-renal uraemia include the following:
 Decreased GFR and normal renal tubular function result in retention of
substances normally excreted by filtration, such as urea and creatinine. Serum urea
and creatinine are increased.
 Urea is increased proportionally more than creatinine because of its reabsorption
by the tubular cells, particularly at low urine flow rates. This leads to a relatively
higher serum urea concentration than creatinine that is not so reabsorbed.
 The decreased delivery of sodium to the distal tubule impairs hydrogen ion and
potassium excretion; acidosis and hyperkalaemia are characteristic features of
acute renal failure.
 Metabolic acidosis: because of the inability of the kidney to excrete hydrogen ions.
 Hyperkalaemia: because of the decreased glomerular filtration rate and acidosis.
 A high urine osmolality.
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Postrenal renal failure
• Obstruction to the flow of urine leads to an increase in hydrostatic pressure 
acts in opposition to glomerular filtration  prolonged obstruction leads to
secondary renal tubular damage.
• Causes of obstruction include renal caliculi (renal stones), prostatic enlargement
and other neoplasms of the urinary tract.
• Complete anuria is strongly indicative of the presence of an obstruction.
• Obstruction may be discontinuous or incomplete and urine production may even be
normal in obstruction with overflow.
• The degree of reversibility of renal damage depends on time of standing
If these pre- or post-renal factors are not corrected, patients will develop intrinsic
renal damage (acute tubular necrosis).
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Intrinsic acute renal failure (Acute tubular necrosis)
• Acute tubular necrosis may develop in the absence of preexisting
pre-renal or post-renal failure. Most causes are due:
 Nephrotoxins, including several drugs such as
aminoglycosides, some cephalosporins, analgesics or herbal
toxins,
 Renal ischaemia: acute blood loss in severe trauma, septic
shock
Specific renal disease, such as glomerulonephritis
• All these causes can lead to renal tubular necrosis.
• The pathogenesis is not completely understood.
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Biochemical changes in plasma in acute renal failure
• Increased: potassium, urea, creatinine, phosphate, magnesium, hydrogen ion, urate
• Decreased: sodium, bicarbonate, calcium
• Hyponatraemia is common; in many patients, water is retained in excess of
sodium. Other factors: increased water formation from oxidative metabolism,
continued intake of water or unwise fluid administration, decreased excretion and,
possibly, loss of intracellular solute.
• Hyperkalaemia occurs as a result of decreased excretion of potassium together with
both a loss of intracellular potassium to ECF (due to tissue breakdown) and
intracellular buffering of retained hydrogen ions.
• Decreased hydrogen ion excretion causes a metabolic acidosis.
Retention of phosphate and leakage of intracellular phosphate into the interstitial
fluid leads to hyperphosphataemia.
• Hypermagnesaemia is also often present as a result of decreased magnesium
excretion.
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• Patients in the early stages of acute tubular necrosis may have only a
moderately increased serum urea and creatinine, then they rise rapidly over a
period of days, in contrast to the slow increase over months and years seen
in chronic renal failure.
• The biochemical features that distinguish pre-renal uraemia from intrinsic
renal damage
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Management of ARF
•
Important issues in the management of the patient with ARF include:
 Correction of pre-renal factors e.g giving fluid in the case of decreased ECF, in
cardiac failure, inotropic agents may be indicated.
 Relieving the obstruction if present.
 Treatment of the underlying disease (e.g. to control infection).
 If oliguria persists and acute tubular necrosis is diagnosed  minimize the sever
adverse consequences of renal failure.
 The general principles of treatment include: strict control of sodium and water
intake, to prevent overload; nutritional support (low protein) minimize nitrogenous
compounds; prevention of metabolic complication, such as hyperkalaemia and
acidosis, and prevention of infection. Avoid the use of potentially nephrotoxic drugs.
 Monitor the patient’s plasma creatinine, sodium, potassium, bicarbonate, calcium
and phosphate concentrations, urinary volume and sodium and potassium excretion.
 Dialysis: in case of rapidly rising serum potassium concentration, severe acidosis,
and fluid overload.
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Chronic renal failure
• Many diseases lead to progressive, irreversible, impairment of
renal function  decrease in the number of functional
nephrons  progression to end-stage renal failure, where
dialysis or transplantation becomes necessary to save the
patient’s life.
• The time between presentation and end-stage renal failure is
very variable; it may be a matter of weeks or as long as several
years.
• The major pathological and clinical features are similar in all
patients with chronic renal failure, whatever the cause.
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The important metabolic features of end-stage renal failure are:
 Impairment of urinary concentration and dilution: the urine
specific gravity tends to be fixed.
 Impairment of electrolyte and hydrogen ion homeostasis
 Retention of waste products of metabolism
 Impaired vitamin D metabolism
 Decreased erythropoietin synthesis
 Disturbances of sodium balance
 Hyperkalaemia is a late feature of chronic renal failure; it may be
precipitated by a sudden deterioration in renal function or by use of
potassium-sparing diuretics.
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• Patients with chronic renal failure tend to be acidotic because of decreased
phosphate excretion, and decreased ammonia synthesis, impaired bicarbonate
reabsorbtion,
• Most patients with chronic renal failure become hypocalcaemic and many develop
renal osteodystrophy (is a bone disease that occurs when kidneys fail to
maintain the proper levels of calcium and phosphorus ).
• Retention of phosphate causes a tendency to hyperphosphataemia
• Decreased testosterone and oestrogen synthesis; abnormalities of thyroid function
tests, and abnormal glucose tolerance with hyperinsulinaemia due to insulin
resistance.
• Anaemia (a normochromic normocytic anaemia) is usual in end-stage renal failure,
due to depression of bone marrow function by retained toxins and a decrease in the
renal production of erythropoietin.
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Management of chronic renal failure
• Identification and subsequent treatment of the cause of chronic renal failure may
prevent, or at least delay, further deterioration, before dialysis or transplantation
becomes necessary,
• Diuretics are often used to promote sodium excretion since adequate dietary salt
restriction may be unacceptable to the patient.
• Bicarbonate can be given orally to control acidosis.
• Hyperkalaemia is usually of less significance in chronic than in acute renal failure,
because it develops more slowly.
• Hyperphosphataemia can be controlled by giving aluminium or magnesium salts
by mouth. These will bind phosphate in the gut and prvent its absorption.
• Some limitation in dietary protein is beneficial to reduce the formation of
nitrogenous waste products,
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Proteinuria and the nephrotic syndrome
•
The glomeruli normally filter 7-10 g of protein / 24
hours, but almost all is reabsorbed by endocytosis and
subsequently catabolized in the proximal tubules.
•
Normal urinary protein excretion is less than about
150 mg/24 h.
•
Approximately half of this is Tamm-Horsfall protein,
a glycoprotein secreted by tubular cells; less than 30
mg is albumin.
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The nephrotic syndrome
•
Nephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to
leak large amounts of protein
•
Glomerulonephritis:is a primary or secondary immune-mediated renal disease characterized by
inflammation of the glomeruli, or small blood vessels in the kidneys. Some types of
glomerulonephritis responds to corticosteroids or immunosuppressive drugs.
•
If large amounts (exceed 5 g/24 h) of protein are excreted in the urine, Hypoproteinaemia with
oedema may develop
•
Much of the filtered protein is catabolized by renal tubular cells and lost from the circulation,
although it is not excreted in the urine.
•
There are two aspects to management: treatment of the underlying disorder, where the disorder
can be identified and treatment is possible, and treatment of the consequences of protein loss.
•
High protein, low salt diet, high protein intake must be introduced with caution when there is parallel
renal failure.
•
Management of edema using diuretics
•
Prevention of infection is vital and antibiotics are often administered prophylactically.
Specific tubular defects
Renal tubular disorders can be congenital or acquired; they can involve single or
multiple aspects of tubular function
Glycosuria
• The presence of glucose in urine may due to:
– Increased blood glucose( hyperglycemia, exceeding the glucose
reabsorption threshold, as in the case of diabetes mellitus)
– Low renal threshold or other tubular disorders
• Glycosuria when blood glucose is normal usually reflects the inability of the
tubules to reabsorb glucose because of a specific tubular lesion.
• This is called renal glycosuria and is a benign condition.
• Glycosuria can also present in association with other disorders of tubular
function
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Renal function and acid-base disorders
• In renal disease, a decreased GFR may result in retention of metabolic acids
with resulting acidosis and accumulation of anions such as phosphates,
sulphates, keto acids, amino acids and so on.
• The decreased filtration of phosphates reduces the ability of the body to
remove H+ by formation of dihydrogen phosphate ion (H2PO4-).
• The decreased ability of ammonia (NH3) formation results in the decreased
formation of ammonium ion (NH4+) and the associated decrease in removal
of H+.
• There may also be an impairment of the Na+-H+ exchange, especially in
renal tubular acidosis (RTA).
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Renal tubular acidosis (RTA):
Impaired of bicarbonate reabsorption and hydrogen ion excretion in the renal tubules
• It could be a component of the Fanconi syndrome or isolated phenomenon.
• RTA is characterized by hyperchloremia, and urinary HCO3- or H+ excretion
inappropriate for the plasma pH.
• Hyperchloremia is caused by enhanced Cl- reabsorption stimulated by contraction of
the extracellular volume and retention of H+.
• RTA is the result of loss of bicarbonate: decreased reabsorption by the
proximal tubules
• The aetiology is not always well established.
• Treatment consists of administering large amounts of bicarbonate
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Renal excretion of amino acids (Aminoaciduria)
•
Amino acids in plasma are filtered by the glomeruli and appear in the glomerular
filtrate in the same proportions as they do in plasma.
•
A great portion of amino acids are reabsorbed by the renal tubular cells (the proximal
tubules) through a process of active transport
•
Thus normal urinary excretion of amino acids is only a small fraction of the filtered
load and is about 50 to 200 mg/day.
•
Amino acids may present in urine in excessive amount because of the plasma
concentration exceeds the renal threshold, or because there is specific failure of
normal tubular reabsorptive mechanisms,
•
Some congenital disorders are characterised by a defect in the reabsorption of amino
acids that results in aminoaciduria.
•
An example of such condition is cystinuria, marked by a failure to reabsorb dibasic
amino acids (cystine, lysine, arginine and ornithine).
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The Fanconi syndrome
• The Fanconi syndrome is a term used to describe the
occurrence of generalized tubular defects such as renal
tubular acidosis, aminoaciduria
and tubular proteinuria.
• It can occur as a result of
heavy metal poisoning, or from
the effects of toxins and
inherited metabolic diseases
such as cystinosis.
Renal stones (Urinary calculi)
•
Renal stones (calculi) are usually composed of products of metabolism present in
normal filtrate at concentrations near their maximum solubility Minor changes in
urinary composition causes precipitation
•
Renal stones produce severe pain and discomfort, and are common causes of
obstruction in the urinary tract
•
Factors predisposing to this are (conditions favouring calculus formation):
1. High urinary concentration of one or more the stone constituents of the glomerular
filtrate, due to:
A. low urinary volume, with normal renal function, because of restricted fluid intake
or excessive fluid loss over a long period of time (dehydration).
B. high rate of excretion of the metabolic product forming the stone, due either to a
high plasma therefore filtrate levels, or to impairment of normal tubular
reabsorption from the filtrate.
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Renal stones (Urinary calculi)
2. Change in pH of the urine, often due to bacterial infection, which
favors precipitation of different salts at different hydrogen ion
concentrations.
3. Urinary stagnation due to obstruction of urinary outflow.
4. Lack of normal inhibitors, such as pyrophosphate, citrate and
glycoproteins, which inhibit the growth of calcium phosphate and
calcium oxalate crystals. The absence of these compounds in the urine
of some patients increases the risk of calcium stones
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Types of stone include:
• Constituents of urinary calculi
1. Calcium-containing salts:
calcium oxalate
calcium phosphate
with or without magnesium ammonium phosphate (‘triple
phosphate’)
2. Uric acid
3. Cystine
4. Xanthine
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Calculi composed of calcium salts
-
Between 70 and 90% of all renal stones contain calcium. Precipitation is favored by hypercalciuria,
and the type of salt depends on urinary pH and on the availability of oxalate.
-
Hypercalcaemia causes hypercalciuria if glomerular function is normal.
-
Hyperoxaluria favors the formation of the very poorly soluble calcium oxalate, even if calcium
excretion is normal.
-
Hyperoxaluria is usually caused by increased intestinal absorption of dietary oxalate or metabolic
disorders,
-
Patients with a variety of GIT disorders as inflammatory bowel diseases and conditions associated with
malabsorption  non-absorbed free fatty acids bind to calcium  this limits the amount of calcium available
to combine with oxalate to form calcium oxalate, an insoluble substance which is normally excreted in the
faeces  an increased amount of oxalate remains in solution and can be absorbed into the bloodstream 
Hyperoxaluria and calcium oxalate stones is formed.
-
Alkaline conditions favoring calcium phosphate precipitation and stone formation are particularly
common in patients with chronic renal infection due to urease-containing (urea-splitting) organisms,
such as Proteus vulgaris. These bacteria convert urea to ammonia and bicarbonate.
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Uric acid stones
•
About 10% of renal caliculi contain uric acid; these are sometimes associated with
hyperuricaemia, with or without clinical gout. Precipitation is favoured in an acid urine.
Cystine and xanthine stones
•
Both are rare and may be a result of rare in born error cystinuria and xanthinuria,
The history and examination may suggest an underlying cause for renal
caliculi
Biochemical investigations that should be performed are:
– Analysis of calculus (if available), the most useful test
– Plasma: calcium, urate and phosphate
– Urine: pH, qualitative test for cystine, 24hr excretion of calcium, oxalate and urate and urinary
acidification test.
– The urine must be examined for evidence of infection in all patients presenting with urinary caliculi.
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Management
• Small calculi are often passed spontaneously.
• Larger calculi may require surgical removal or disintegration by ultrasound.
• Any urinary tract infection should be treated.
• The identification of the cause of urinary calculus formation should make it
possible to design an effective regimen to prevent further stone formation.
• In calcium-containing calculi urinary calcium concentration should be reduced:
– By treating the primary condition, such as urinary infection or
hypercalcaemia.
– If this is not possible, by reducing dietary calcium and oxalate intake.
– By reducing the concentration by maintaining a high fluid intake day and
night, unless there is glomerular failure.
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Management
• Hyperurecaemia should be treated with allopurinol. A low purine diet may
help. If the plasma urate concentration is normal, fluid intake should be kept
high and the urine alkalinised.
• The management of cystinuria: cystine may be kept in solution if the urine is
kept sufficiently dilute and alkaline. If calculi continue to form,
penicillamine may be used; the drug complexes with cysteine (from which
cystine is derived) and reduces the urinary excretion of cystine.
• Alkalinisation of the urine increases the solubility of both cystine and
uric acid but may be difficult to achieve. A high fluid intake is appropriate
in all patients with a tendency to form urinary calculi.
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