Acute and chronic renal failure. Etiology,
pathogenesis. Diagnostics. Clinical picture.
Complications. Principles of treatment. The
role of a doctor-dentist in early
diagnostics and prophylaxis.
Epidemiology
Recent studies have found an
overall incidence of acute
kidney injury (AKI) of almost
500 per million per year and
the incidence of AKI needing
dialysis being more than 200
per million per year.
Prerenal AKI and ischaemic
acute tubular necrosis (ATN)
together account for 75% of
the cases of AKI.
Causes of acute kidney injury
Prerenal:
 Volume depletion (eg haemorrhage, severe vomiting or
diarrhoea, burns, inappropriate diuresis)
 Oedematous states: cardiac failure, cirrhosis, nephrotic
syndrome
 Hypotension (eg cardiogenic shock, sepsis,
anaphylaxis)
 Cardiovascular (eg severe cardiac failure, arrhythmias)
 Renal hypoperfusion: non-steroidal anti-inflammatory
drugs (NSAIDs) or selective cyclooxygenase-2 (COX-2)
inhibitors, angiotensin-converting enzyme (ACE)
inhibitors or angiotensin-II receptor antagonists,
abdominal aortic aneurysm, renal artery stenosis or
occlusion, hepatorenal syndrome
Intrinsic acute kidney injury (AKI):
 Glomerular disease: glomerulonephritis, thrombosis,
haemolytic uraemic syndrome
 Tubular injury: acute tubular necrosis (ATN) following
prolonged ischaemia; nephrotoxins (eg aminoglycosides,
radiocontrast media, myoglobin, cisplatin, heavy metals, light
chains in myeloma kidney)
 Acute interstitial nephritis due to drugs (eg NSAIDs),
infection or autoimmune diseases
 Vascular disease: vasculitis (usually associated with
antineutrophil cytoplasmic antibody), cryoglobulinaemia,
polyarteritis nodosa, thrombotic microangiopathy,
cholesterol emboli, renal artery stenosis, renal vein
thrombosis, malignant hypertension
 Eclampsia
Postrenal:
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Calculus
Blood clot
Papillary necrosis
Urethral stricture
Prostatic hypertrophy or malignancy
Bladder tumour
Radiation fibrosis
Pelvic malignancy
Retroperitoneal fibrosis
Risk factors
 People with the following comorbid
conditions are at a higher risk for
developing AKI:[2]
 Elderly
 Hypertension
 Vascular disease
 Pre-existing renal impairment
 Congestive cardiac failure
 Diabetes
 Myeloma
 Chronic infection
 Myeloproliferative disorder
The presentation will
depend on the underlying
cause and severity of AKI.
There may be no
symptoms or signs, but
oliguria (urine volume less
than 400 mL/24 hours) is
common. There is an
accumulation of fluid and
nitrogenous waste
products demonstrated
by a rise in blood urea and
creatinine.
Symptoms
 Urine output: AKI is usually
accompanied by oliguria or
anuria, but polyuria may occur.
 Abrupt anuria suggests an acute
obstruction, acute and severe
glomerulonephritis, or acute
renal artery occlusion.
 Gradual diminution of urine
output may indicate a urethral
stricture or bladder outlet
obstruction, eg benign prostatic
hyperplasia.
 Nausea, vomiting
 Dehydration
 Confusion
Signs
 Hypertension
 Abdomen: may reveal a large,
painless bladder typical of
chronic urinary retention
 Dehydration with postural
hypotension and no oedema
 Fluid overload with raised JVP,
pulmonary oedema and
peripheral oedema
 Pallor, rash, bruising: petechiae,
purpura, and nosebleeds may
suggest inflammatory or
vascular disease, emboli or
disseminated intravascular
coagulation
 Pericardial rub
Distinguish acute and chronic kidney disease
 Factors that suggest CKD
include long duration of
symptoms, nocturia,
absence of acute illness,
anaemia,
hyperphosphataemia,
hypocalcaemia.
 Previous creatinine
measurements if available
are very useful.
 Reduced renal size and
cortical thickness on
ultrasound is characteristic
of CKD (renal size is typically
Exclude urinary tract obstruction:
 History of previous stones or symptoms of bladder outflow
obstruction
 Palpable bladder
 Complete anuria suggests renal tract obstruction
 Renal ultrasound is the best method to detect dilatation of the
renal pelvis and calyces (obstruction may be present without
dilatation, especially in patients with malignancy)
Evidence of renal
parenchymal disease:
 Features of underlying
systemic disease, eg rashes,
arthralgia, myalgia
 Use of antibiotics and
NSAIDs
 Urine dipstick and
microscopy: dipstick blood
or protein, or dysmorphic
red cells, red cell casts
(suggestive of
glomerulonephritis), or
eosinophils (suggestive of
acute interstitial nephritis)
on microscopy
Differential diagnosis
 Chronic kidney disease: factors
that suggest CKD include:
 Long duration of symptoms
 Nocturia
 Absence of acute illness
 Anaemia
 Hyperphosphataemia,
hypocalcaemia (but similar
laboratory findings may
complicate acute kidney injury
(AKI))
 Reduced renal size and cortical
thickness on renal ultrasound (but
renal size is typically preserved in
patients with diabetes
Investigations
 Urinalysis:
 Urinalysis: blood and/or protein suggests a renal inflammatory
process; microscopy for cells, casts, crystals; red cell casts diagnostic
in glomerulonephritis; tubular cells or casts suggest acute tubular
necrosis (ATN)
 Urine osmolality: osmolality of urine is over 500 mmol/kg if the cause
is pre-renal and 300 mmol/kg or less if it is renal; patients with ATN
lose the ability to concentrate and dilute the urine and will pass a
constant volume with inappropriate osmolality
 Biochemistry: Traditional blood (creatinine, blood urea nitrogen) and
urine markers of kidney injury (epithelial cells, tubular casts,
fractional excretion of Na+, urinary concentrating ability, etc.) are
insensitive and nonspecific for the diagnosis of acute kidney injury
(AKI). Work continues to find an appropriate biomarker, eg cystatin C
(Cys-C).
Investigations
 Serial urea, creatinine, electrolytes: important metabolic consequences of
AKI include hyperkalaemia, metabolic acidosis, hypocalcaemia,
hyperphosphataemia (serum urea is a poor marker of renal function
because it varies significantly with hydration diet, it is not produced
constantly and it is reabsorbed by the kidney).
 Serum creatinine has significant limitations. The level can remain within the
normal range despite the loss of over 50% of renal function.
 Creatine kinase, myoglobinuria: markedly elevated creatine kinase and
myoglobinuria suggest rhabdomyolysis.
 Haematology:
 Full blood count, blood film: eosinophilia may be present in acute
interstitial nephritis, cholesterol embolisation, or vasculitis;
thrombocytopenia and red cell fragments suggest thrombotic
microangiopathy.
 Coagulation studies: disseminated intravascular coagulation associated
with sepsis.
Immunology:
Cys-C: over the past decade serum Cys-C has been extensively studied and found to be a
sensitive serum marker of GFR and a stronger predictor than serum creatinine of risk of death
and cardiovascular events in older patients.
C reactive protein: nonspecific marker of infection or inflammation.
Serum immunoglobulins, serum protein electrophoresis, Bence Jones' proteinuria: immune
paresis, monoclonal band on serum protein electrophoresis, and Bence Jones' proteinuria
suggest myeloma.
Antinuclear antibody (ANA): ANA positive in systemic lupus
erythematosus (SLE) and other autoimmune disorders; anti-double
stranded (anti-dsDNA) antibodies more specific for SLE; anti-dsDNA
antibodies; antineutrophil cytoplasmic antibody (ANCA) (associated
with systemic vasculitis; classical antineutrophil cytoplasmic
antibodies (c-ANCA) and antiproteinase 3 (anti-PR3) antibodies
associated with Wegener's granulomatosis; protoplasmic-staining
antineutrophil cytoplasmic antibodies (p-ANCA) and
antimyeloperoxidase (anti-MPO) antibodies present in microscopic
polyangiitis), anti-PR3 antibodies, anti-MPO antibodies.
Complement concentrations: low in
SLE, acute postinfectious
glomerulonephritis, cryoglobulinaemia.
Antiglomerular basement membrane
(anti-GBM) antibodies: present in
Goodpasture's disease.
Antistreptolysin O and anti-DNAse B
titres: high after streptococcal infection.
Virology:
Hepatitis B and C; HIV: important
implications for infection control within
dialysis area
Radiology:
Renal ultrasonography: renal size, symmetry, evidence of obstruction
Chest X-ray (pulmonary oedema); abdominal X-ray if renal calculi are
suspected
Contrast studies such as intravenous urogram (IVU) and renal angiography
should be avoided because of the risk of contrast nephropathy
Doppler ultrasound of the renal artery and veins: assessment of possible
occlusion of the renal artery and veins
Magnetic resonance angiography: for more accurate assessment of renal
vascular occlusion
ECG: recent myocardial infarction, tented T waves in hyperkalaemia
Renal biopsy
Principles of management of acute kidney injury
 No drug treatment has been shown to limit the progression of, or
speed up recovery from, AKI.
 Identify and correct prerenal and postrenal factors.
 Optimise cardiac output and renal blood flow.
 Review drugs: stop nephrotoxic agents; adjust doses and monitor
concentrations where appropriate.
 Accurately monitor fluid balance and daily body weight.
 Identify and treat acute complications (hyperkalaemia, acidosis,
pulmonary oedema).
 Optimise nutritional support: adequate calories, minimal
nitrogenous waste production, potassium restriction.
 Identify and aggressively treat infection; minimise indwelling lines;
remove bladder catheter if anuric.
 Identify and treat bleeding tendency: prophylaxis with proton pump
inhibitor (PPI) or h2-receptor antagonist (H2RA), transfuse if
required, avoid aspirin.
Principles of management of acute kidney injury
 Accurate control of fluid balance (avoid volume overload
or depletion)
 Daily measurement of serum electrolytes, potassium and
sodium restriction, nutritional support
 Prevention of gastrointestinal haemorrhage
 Careful drug dosing and avoidance of nephrotoxic drugs
 Specific treatment of underlying intrinsic renal disease
where appropriate
 Dialysis or haemofiltration
Complications Life-threatening complications include:
 Volume overload (severe pulmonary oedema)
 Hyperkalaemia
 Metabolic acidosis
 Spontaneous haemorrhage, eg gastrointestinal
The definition of chronic kidney disease (CKD) is based on
the presence of kidney damage (ie albuminuria) or
decreased kidney function (ie glomerular filtration rate
(GFR) <60 ml/minute per 1·73 m²) for three months or
more, irrespective of clinical diagnosis.
A large primary care study (practice population 162,113) suggests an age
standardised prevalence of stage 3-5 chronic kidney disease (CKD) of 8.5%
(10.6% in females and 5.8% in males).
Chronic renal failure (CRF) is
characterized by progressive
destruction of renal mass with
irreversible sclerosis and loss of
nephrons over a period of at
least months to many years,
depending on the underlying
etiology. Glomerular filtration
rate (GFR) progressively
decreases with nephron loss,
and the term CRF should be
reserved more specifically for
patients whose GFR is less than
30 cc/min.
Aetiology
In developed countries, CKD
is often associated with old
age, diabetes, hypertension,
obesity and cardiovascular
disease (CVD).
Arteriopathic renal disease.
Hypertension.
Glomerulonephritis.
Diabetes.
Infective, obstructive and reflux nephropathies.
Family history of stage 5 CKD or hereditary kidney disease
Hypercalcaemia.
Multisystem diseases with potential kidney involvement.
Neoplasms.
Myeloma.
Risk factors
 Factors other than the underlying
disease process that may cause
progressive renal injury include the
following:
 Acute insults from nephrotoxins or
decreased perfusion.
 Proteinuria.
 Increased renal ammonia formation
with interstitial injury.
 Hyperlipidaemia.
 Hyperphosphataemia with calcium
phosphate deposition.
Factors other than the underlying disease process and
glomerular hypertension that may cause progressive
renal injury include the following:
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Systemic hypertension
Acute insults from nephrotoxins or decreased perfusion
Proteinuria
Increased renal ammoniagenesis with interstitial injury
Hyperlipidemia
Hyperphosphatemia with calcium phosphate deposition
Decreased levels of nitrous oxide
Classification of chronic kidney disease
 Kidney function should be assessed by eGFR and CKD is
classified on this basis:[2]
 Stage 1: normal; eGFR >90 ml/minute/1.73 m2 with other
evidence of chronic kidney damage (see below).
 Stage 2: mild impairment; eGFR 60-89 ml/minute/1.73 m2 with
other evidence of chronic kidney damage.
 Stage 3a: moderate impairment; eGFR 45-59 ml/minute/1.73
m2.
 Stage 3b: moderate impairment; eGFR 30-44 ml/minute/1.73
m2.
 Stage 4: severe impairment; eGFR 15-29 ml/minute/1.73 m2.
 Stage 5: established renal failure (ERF); eGFR less than 15
ml/minute/1.73 m2 or on dialysis.
Use the suffix (p) to denote
the presence of proteinuria
when staging CKD.
NB: patients with a GFR of
>60 ml/minute/1.73 m2
without evidence of chronic
kidney damage should NOT
be considered to have CKD
and do not necessarily need
further investigation.
The other evidence of chronic
kidney damage may be one of
the following:
 Persistent microalbuminuria.
 Persistent proteinuria.
 Persistent haematuria (after
exclusion of other causes - eg,
urological disease).
 Structural abnormalities of the kidneys, demonstrated
on ultrasound scanning or other radiological tests - eg,
polycystic kidney disease, reflux nephropathy.
 Biopsy-proven chronic glomerulonephritis.
Symptoms
 it usually presents with nonspecific
symptoms caused by renal failure,
complications - eg, anaemia in chronic renal
failure (CRF), and the underlying disease.
 It may be discovered by chance following a
routine blood or urine test.
 Specific symptoms usually develop only in severe renal failure, and
include anorexia, nausea, vomiting, fatigue, weakness, pruritus,
lethargy, peripheral oedema, dyspnoea, insomnia, muscle cramps,
pulmonary oedema, nocturia, polyuria and headache.
 Sexual dysfunction is common.
 Hiccups, pericarditis, coma and seizures are only seen in very
severe renal failure.
Signs
The physical examination is often not
very helpful but may reveal findings
characteristic of the underlying cause
(eg SLE, severe arteriosclerosis,
hypertension) or complications of CRF
(eg, anaemia, bleeding diathesis,
pericarditis).
Signs of CKD include increased skin pigmentation or
excoriation, pallor, hypertension, postural hypotension,
peripheral oedema, left ventricular hypertrophy,
peripheral vascular disease, pleural effusions, peripheral
neuropathy and restless legs syndrome.
Differential diagnosis
Acute kidney injury (acute renal failure):
 Making the distinction between AKI and CRF can be very difficult. A history of chronic
symptoms of fatigue, weight loss, anorexia, nicturia, and pruritus all suggest CKD.
 The history and examination will provide clues, but renal ultrasound will provide the most
important information. Renal abnormalities on ultrasound, such as small kidneys in chronic
glomerulonephritis or large cystic kidneys in adult polycystic kidney disease, will almost
always be present in patients with CKD.
 Acute on chronic renal failure: may have features indicating CKD but also features
suggesting a cause of an acute deterioration of renal function - eg, infection.
Investigations
Investigations are focused on assessment of
renal function and therefore stage of CKD,
identification of the underlying cause and
assessment of complications of CKD.[1]
Assessment of renal function:
Serum urea is a poor marker of renal function,
because it varies significantly with hydration
and diet, is not produced constantly and is
reabsorbed by the kidney.
Serum creatinine also has significant limitations. The level can remain within the normal
range despite the loss of over 50% of renal function.
A gold-standard measurement is an isotopic GFR, but this is expensive and not widely
available.
For most purposes in primary care, the best assessment or screening tool is the eGFR.[5] see separate article Assessing Renal Function and the Estimated Glomerular Filtration
Rate Calculator. Most laboratories now provide an eGFR when requesting serum
creatinine, which should be used in preference to calculator above.
Biochemistry:
Plasma glucose: to detect undiagnosed diabetes or assess control of
diabetes.
Serum sodium: usually normal, but may be low.
Serum potassium: raised.
Serum bicarbonate: low.
Serum albumin: hypoalbuminaemia in patients who are nephrotic
and/or malnourished (low levels at the start of dialysis are associated
with a poor prognosis).
Serum calcium: may be normal, low or high.
Serum phosphate: usually high.
Serum alkaline phosphatase: raised when bone disease develops.
Serum parathyroid hormone: rises progressively with declining renal
function.
Serum cholesterol and triglycerides: dyslipidaemia is common.
Haematology:
Normochromic normocytic anaemia; haemoglobin falls with
progressive renal failure.
White cells and platelets are usually normal.
Serology:
Autoantibodies, particularly antinuclear antibodies, classical
antineutrophil cytoplasmic antibodies (c-ANCA), protoplasmicstaining antineutrophil cytoplasmic antibodies (p-ANCA),
antiglomerular basement membrane (anti-GBM) antibodies (very
suggestive of underlying Goodpasture's syndrome) and serum
complement.
Hepatitis serology: ensure not infected
and vaccinate against hepatitis B.
HIV serology: performed before dialysis
or transplantation.
Urine:
Urinalysis: dipstick proteinuria may suggest glomerular
or tubulointerstitial disease. Urine sediment with red
blood cells and red blood cell casts suggests proliferative
glomerulonephritis.
Pyuria and/or white cell casts suggest interstitial
nephritis (especially if eosinophils are present in the
urine) or urinary tract infection (UTI).
Spot urine collection for total protein:creatinine ratio
allows reliable estimation of total 24-hour urinary protein
excretion. The degree of proteinuria correlates with the
rate of progression of the underlying kidney disease and
is the most reliable prognostic factor in CKD.
24-hour urine collection for total protein and creatinine clearance. To detect and
identify proteinuria, use urine albumin:creatinine ratio (ACR) in preference, as it has
greater sensitivity than protein:creatinine ratio (PCR) for low levels of proteinuria. For
quantification and monitoring of proteinuria, PCR can be used as an alternative. ACR
is the recommended method for people with diabetes.
Patients in whom initial urinalysis reveals microscopic haematuria should have a
urine culture performed to exclude a UTI. If a UTI is excluded, two further tests
should be performed to confirm the presence of persistent microscopic
haematuria.[6]
Patients over 40 years of age with persistent non-visible/microscopic haematuria in
the absence of significant proteinuria or a reduced GFR should be referred to a
urology department for further investigation.[6]
Serum and urine protein electrophoresis: to screen for a monoclonal protein
possibly representing multiple myeloma.
ECG and echocardiography: to detect left ventricular hypertrophy
and ischaemia, and to assess cardiac function.
Imaging of the renal tract:
Plain abdominal X-ray: may show radio-opaque stones or
nephrocalcinosis.
Intravenous (IV) pyelogram: not often used because of potential for
contrast nephropathy.
In newly diagnosed with eGFR less than
60 ml/minute/1.73 m2
Review all previous measurements of
serum creatinine to estimate GFR and
assess the rate of deterioration.
Review all medication including over-thecounter drugs; particularly consider
recent additions (eg, diuretics, NSAIDs, or
any drug capable of causing interstitial
nephritis, such as penicillins,
cephalosporins, mesalazine).
Urinalysis: haematuria and proteinuria suggest glomerulonephritis, which may
progress rapidly.
Clinical assessment: eg, look for sepsis, heart failure, hypovolaemia, palpable bladder.
Repeat serum creatinine measurement within five days to exclude rapid progression.
Check criteria for referral (above). If referral is not indicated, ensure entry into a
chronic disease management register and programme.
Renal ultrasound:
 Small echogenic kidneys are seen in advanced renal failure.
 Kidneys are usually initially large and then become normal in size in advanced
diabetic nephropathy.
 Structural abnormalities may be seen - eg, polycystic kidneys.
 It is also used to screen for hydronephrosis caused by urinary tract obstruction, or
involvement of the retroperitoneum with fibrosis, tumour or diffuse adenopathy.
 Retrograde pyelogram: may be indicated if there is clinical suspicion of obstruction
despite a negative ultrasound study finding.
 Renal radionuclide scan:
 Useful to screen for renal artery stenosis when performed with captopril
administration but is unreliable for GFR of less than 30 ml/minute.
 Also quantifies differential renal contribution to total GFR.
 CT scan: to define renal masses and
cysts, seen on ultrasound, better; this is
the most sensitive test for identifying
renal stones.
 MRI:
 For patients who require a CT scan but
who cannot receive IV contrast.
 Like CT scan and renal venography, it is
reliable in the diagnosis of renal vein
thrombosis.
 Magnetic resonance angiography is also
useful for diagnosis of renal artery
stenosis, although renal arteriography
remains the investigation of choice.
 Micturating cystourethrogram: for
diagnosis of vesicoureteric reflux.
 Renal biopsy.
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Complications
Anaemia: left ventricular hypertrophy, fatigue, impaired cognitive
functioning.
Coagulopathy.
Hypertension: left ventricular hypertrophy, heart failure, stroke, CVD.
Calcium phosphate loading: cardiovascular and cerebrovascular
disease, arthropathy, soft tissue calcification.
Renal osteodystrophy: disorders of calcium, phosphorus and bone,
most commonly osteitis fibrosa cystica.
Bone changes of secondary hyperparathyroidism: bone pain and
fractures.
Neurological: uraemic encephalopathy, neuropathy including
peripheral neuropathy.
Dialysis amyloid: bone pain, arthropathy, carpal tunnel syndrome.
Fluid overload: pulmonary oedema, hypertension
Malnutrition: increased morbidity and mortality, infections, poor
wound healing.
Glucose intolerance due to peripheral insulin resistance.
When symptoms are severe they can be treated only by
dialysis and transplantation (end-stage renal disease).
Kidney failure is defined as a GFR of less than 15
ml/minute per 1·73 m², or the need for treatment with
dialysis or transplantation
Prognosis
Early diagnosis, regular monitoring and early treatment can prevent development and slow
disease progression, reduce complications and the risk of cardiovascular disease, and improve
survival and quality of life.[1]
Much of the damage caused by CKD occurs early, when interventions may be much more
effective.
Rapidly progressive diseases can lead to kidney failure within months. However, most diseases
evolve over decades and some patients do not progress during many years of follow-up.[1]
Patients on chronic dialysis have a high incidence of morbidity and mortality. Patients with
end-stage renal disease (ESRD) who undergo renal transplantation survive longer than those
on chronic dialysis.
CVD is the most common cause of death in patients with CKD. Cardiovascular mortality is
doubled in patients with a GFR below 70 ml/minute.
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