Differentials
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Chronisch nierlijden (multidisciplinaire aanpak)Published by: WORELLast published: 2017GPC pluridisciplinaire sur la néphropathie chronique (IRC)Published by: Groupe de travail Développement de recommandations de première ligneLast published: 2017Common
Glomerulonephritis
History
often asymptomatic; may cause generalised symptoms of anorexia, nausea, weight loss, malaise; history of fever with post infectious aetiology; history of sore throat if post-streptococcal; previous history of HIV, hepatitis B; history of Raynaud's phenomenon, sclerodactyly, GORD, digital ulcers, skin thickening, telangiectasias; may have visible haematuria (more commonly non-visible); may have symptoms of vasculitis in rapidly progressive glomerulonephritis
Exam
oedema (if nephrotic syndrome is present), hypertension, uraemic signs and symptoms; diffuse hand swelling often worse in the morning (characteristic of scleroderma), can be accompanied by foot swelling
1st investigation
Other investigations
- full blood count:
may be normal; microcytic anaemia with chronic gastrointestinal bleed; microangiopathic haemolytic anaemia with scleroderma renal crisis
- C-reactive protein or erythrocyte sedimentation rate:
elevated or normal
More - spot urine albumin:creatinine ratio (ACR):
normal or elevated
More - antistreptolysin O:
post-streptococcal glomerulonephritis: positive
- anti-DNAse:
post-streptococcal glomerulonephritis: positive
- complement titres:
low in post-infectious glomerulonephritis, essential mixed cryoglobulinaemia, systemic lupus erythematosus, subacute bacterial endocarditis and membranoproliferative glomerulonephritis
- hepatitis B virus and hepatitis C virus serology:
may be positive
- HIV serology:
may be positive
- cryoglobulins:
positive in cryoglobulinaemia
- rheumatoid factor:
may be positive
More - anti-neutrophil cytoplasmic antibody:
may be positive
More - anti-glomerular basement membrane antibody:
may be positive
More - anti-double-stranded DNA:
may be positive
- antinuclear antibody:
may be positive
- serum and urine electrophoresis:
monoclonal or polyclonal gammopathy or normal
More - anti-phospholipase A2 receptor antibodies:
may be positive
More - renal biopsy:
characteristic findings on light, immunofluorescence, and electron microscopy
More
Diabetic nephropathy
History
history of diabetes mellitus, often asymptomatic; risk factors include sustained hyperglycaemia, hypertension, family history of hypertension or kidney disease, obesity and smoking
Exam
non-specific findings
1st investigation
- haemoglobin A1c:
elevated
Systemic vasculitis
History
may have history of arthralgias; photosensitive malar (butterfly), generalised, or discoid rash; fatigue, weight loss, purpuric rash
Exam
joint tenderness to palpation, swelling in multiple joints, alopecia, oral ulcers, lymphadenopathy
1st investigation
- urinalysis:
haematuria, proteinuria, red blood cell casts
More - antinuclear antibodies:
positive in systemic lupus erythematosus (SLE)
- antiglomerular basement membrane antibodies:
positive in Goodpasture syndrome
- antineutrophil cytoplasmic antibodies:
positive in granulomatosis with polyangiitis, polyarteritis nodosa
Other investigations
- anti-double-stranded DNA:
positive in SLE
- renal biopsy:
vasculitis; pattern of blood vessels affected depends on underlying cause
Drug-related creatinine increase
History
use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers; history of use of chemotherapy agents (e.g. cisplatin), penicillamine, sodium aurothiomalate, non-steroidal anti-inflammatory drugs, mitomycin C, ciclosporin or aminoglycosides, and also heroin; history of use of cimetidine, gentamicin, fibric acid derivatives (other than gemfibrozil), or trimethoprim; serum creatinine may increase within a few months after starting fenofibrate
Exam
normal
1st investigation
- trial of discontinuation of causative medication:
creatinine returns to baseline
Other investigations
Contrast-induced acute kidney injury
History
radiological imaging with contrast agent in 48 hours preceding rise in serum creatinine
Exam
no specific findings; may have features of underlying disease
1st investigation
- urinalysis:
high urine specific gravity, trace proteinuria
- fractional excretion of sodium (FENa):
<1%
More
Other investigations
Shock
History
history of hypotension, pre-renal factor that causes decreased renal perfusion; multiple organ failure; history of acute insult or sepsis; history of chest pain in cardiogenic shock
Exam
low blood pressure, dizziness, tachycardia, oedema; cool, clammy or mottled skin; oliguria, mental state changes; progressive organ dysfunction
1st investigation
- urine specific gravity:
elevated (>1.020)
- serum urea and electrolytes:
elevated creatinine; blood urea nitrogen/serum creatinine ratio >20; hyperkalaemia in trauma or acute kidney injury
- arterial or venous blood gas:
lactate >2 mmol/L (>18 mg/dL); may show metabolic acidosis (pH <7.35) and low bicarbonate (<22 mmol/L); arterial blood gas may show hypoxaemia or hypercapnia
Other investigations
- urine osmolality:
elevated (>500 mOsm/kg H₂O)
- random urine sodium (UNa):
>20 mEq/L
More - fractional excretion of sodium (FENa):
>1%
More - full blood count:
white blood cell count may be elevated with inflammation or infection; haemoglobin may decrease with acute haemorrhage
- glucose:
may be elevated
- coagulation studies:
may be abnormal in septic shock and trauma
- C-reactive protein:
elevated in septic shock
- blood, urine, and sputum cultures:
positive for organism in sepsis
- electrocardiogram:
may show cause of cardiogenic shock or hyperkalaemia
Volume depletion
History
decreased fluid intake, vomiting, diarrhoea, burn injury; symptoms of volume depletion: thirst, postural dizziness, fatigue, confusion, muscle cramps
Exam
orthostatic hypotension, tachycardia, decreased skin turgor, dry mucous membranes
1st investigation
- orthostatic blood pressure:
abnormal
- urea to serum creatinine ratio:
15-20:1
- urine specific gravity:
elevated (>1.020)
Other investigations
- urine osmolality:
elevated
- random urine sodium (UNa):
<20mEq/L
- fractional excretion of sodium (FENa):
<1%
More
Hypertension
History
history of hypertension
Exam
elevated blood pressure if not well controlled
1st investigation
- fasting metabolic panel:
elevated serum creatinine; may show hyperglycaemia
- urinalysis:
may show proteinuria
More
Congestive heart failure
History
history of congestive heart failure; pre-renal factor that causes decreased renal perfusion; orthopnea and paroxysmal nocturnal dyspnoea, nocturia, dyspnoea
Exam
signs of right or left heart failure, presence of elevated jugular venous pressure and a third heart sound, rales
1st investigation
- ECG:
evidence of underlying coronary artery disease, left ventricular hypertrophy, or atrial enlargement; may be conduction abnormalities and abnormal QRS duration
- chest x-ray:
abnormal
More - serum electrolytes:
decreased sodium (usually <135 mg/dL), altered potassium
- serum creatinine or urea:
elevated
Other investigations
- transthoracic echocardiogram:
systolic heart failure: depressed and dilated left and/or right ventricle with low ejection fraction; diastolic heart failure: left ventricular ejection fraction normal, but left ventricular hypertrophy and abnormal diastolic filling patterns
- full blood count:
anaemia, high lymphocyte percentage
Pre-eclampsia
History
rise in serum creatinine in a pregnant woman; reference range for serum creatinine is lower in pregnancy (36 to 45 micromol/L [0.4 to 0.5 mg/dL]), and values above this are a concern for worsening of renal function, headache, upper abdominal pain, reduced fetal movement, oedema
Exam
hypertension, oedema
1st investigation
- urinalysis:
proteinuria
More
Other investigations
- placental growth factor:
low
More - FBC:
may reveal low platelet count
- liver function tests:
may be elevated
Acute interstitial nephritis
History
patient presents with non-oliguric acute renal failure with rash, fever, and eosinophilia (the 'hypersensitivity triad') triggered by a medication; toxin tubulopathy, hypercalcaemia, lithium-induced tubular damage; may be a history of systemic lupus erythematosus, sarcoidosis, or Sjogren syndrome
Exam
pyuria, haematuria, proteinuria, eosinophiluria
1st investigation
- urinalysis:
microhaematuria; sterile pyuria; proteinuria; muddy brown granular casts, epithelial casts
More - urea and serum creatinine:
elevated
- fractional excretion of sodium (FENa):
>1%
More - random urinary sodium (UNa):
>20 mEq/L
- trial of discontinuation of causative medication:
creatinine returns to baseline
More
Other investigations
- urine specific gravity:
1.012-1.015
- urine osmolality:
<350 mOsm/kg H₂O
- full blood count with white blood cell differential:
eosinophilia
- anti-neutrophil cytoplasmic antibody:
may be positive
More - anti-double-stranded DNA:
positive in systemic lupus erythematosus
- antinuclear antibody:
positive in systemic lupus erythematosus
- complement studies:
low C3/C4 levels in systemic lupus erythematosus
Acute tubular necrosis
History
hypotension insult; prolonged drop in blood pressure
Exam
non-specific findings
1st investigation
- serum urea and creatinine:
elevated serum creatinine, elevated urea
- urinalysis:
coarse granular casts; muddy brown granular casts; epithelial cell casts
- urine osmolality:
<450 mOsmol/kg supports acute tubular necrosis
Other investigations
- blood urea nitrogen to serum creatinine ratio:
10:1 or higher
- random urine electrolytes:
increased excretion of sodium
- fractional excretion of sodium (FENa):
>1%
More - urinary myoglobin:
elevated if acute tubular necrosis is caused by rhabdomyolysis
Cardiac surgery
History
cardiac surgery involving prolonged clamping of main arteries and renal hypoperfusion, extensive blood loss
Exam
fluid overload, decreased urine output
1st investigation
- none:
clinical diagnosis
Other investigations
Nephrectomy
History
kidney donor or after unilateral or partial nephrectomy; altered physiological state
Exam
normal aside from surgical scars
1st investigation
- serum creatinine:
initial elevation, which resolves following physiological adaptation
Other investigations
Renal transplant rejection
History
renal transplant recipient: serum creatinine elevation is usually the alerting event for the clinician; other reasons for elevated serum creatinine in renal transplant recipients include surgical and infection complications, immunosuppressive medications, non-compliance with medications
Exam
fever, oliguria, graft site tenderness, or asymptomatic
1st investigation
- basic metabolic panel:
rise in serum creatinine
Other investigations
- immunosuppressive medication blood levels:
may be elevated
- microbiological testing for infectious causes:
may be positive, cytomegalovirus titre, BK virus titre
More
Biological serum creatinine variation
History
female sex; older; variations in creatinine production due to differences in muscle mass; intra- and inter-patient variability in the production, tubular secretion, renal and extrarenal excretion, and degradation of creatinine
Exam
non-specific findings
1st investigation
- none:
clinical factor to consider in the absence of other cause of elevated creatinine
Other investigations
Uncommon
Renal vein thrombosis
History
loin, testicular, or flank pain in patient with solitary kidney, renal transplant, systemic lupus erythematosus, or nephrotic syndrome, may be history of hypercoagulable state
Exam
abdominal mass or normal examination haematuria
1st investigation
- duplex ultrasound:
renal vein occlusion
- magnetic resonance venogram:
renal vein occlusion
Other investigations
- comprehensive metabolic panel:
abnormal serum creatinine
- urinalysis:
haematuria, proteinuria
Radiotherapy
History
history of radiotherapy
Exam
non-specific findings
1st investigation
- none:
clinical diagnosis
Other investigations
Endogenous nephrotoxins (myoglobin, uric acid, calciphylaxis)
History
history of rhabdomyolysis, tumour lysis syndrome, calciphylaxis
Exam
non-specific findings; painful necrotic skin lesions in calciphylaxis
1st investigation
- creatine kinase:
rhabdomyolysis: marked elevation
Other investigations
- urine myoglobin:
rhabdomyolysis: marked elevation
- uric acid:
tumour lysis syndrome: elevated uric acid
- skin biopsy:
calciphylaxis: calcification, fibro-intimal hyperplasia, and thrombosis in microvessels in the subcutaneous adipose tissue and dermis
More
Renal artery stenosis
History
history of hypertension, kidney dysfunction, or acute kidney injury, leading to ischaemic nephropathy
Exam
elevated blood pressure, abdominal bruit
1st investigation
- renal ultrasound with Doppler:
asymmetrical kidney size, decreased renal artery flow
Traumatic renal infarction
History
non-penetrating abdominal trauma (traumatic renal infarct constitutes 1% to 2% of all non-penetrating abdominal trauma); evidence of lumbar vertebral injury
Exam
trauma to lumbar vertebral region
1st investigation
- basic metabolic panel:
elevated serum creatinine
- CT abdomen and pelvis with contrast:
abnormal
More
Multiple cholesterol emboli syndrome
History
acute or subacute rise in serum creatinine following arterial manipulation, such as surgery, stent placement, or cardiac catheterisation; multi-organ involvement (cutaneous lesions, thrash toes/blue toes, pancreatitis, stroke, ischaemic bowel, angina, days or weeks following vascular procedure); gastrointestinal, cardiac, renal, neurological symptoms
Exam
thrash toes/blue toes, cutaneous lesions; visual field deficits
1st investigation
- serum creatinine:
step-wise rise in serum creatinine
Other investigations
- full blood count with differential:
transient peripheral eosinophilia, anaemia, leukocytosis
- urinalysis:
may show eosinophiluria
- random urine electrolytes:
fractional excretion of sodium
- erythrocyte sedimentation rate:
elevated
- complement studies (C3, C4):
low
- amylase:
may be elevated
More - lipase:
may be elevated
More - lactate dehydrogenase:
may be elevated
- creatine kinase:
may be elevated
More
Obstructive uropathy
History
obstructive (voiding) and irritative (storage) symptoms, dysuria, flank pain, increased urinary urgency or frequency, feeling of bladder fullness, urinary retention, renal colic, overflow incontinence, history of kidney stones; tumour: weight loss, change in bowel habit
Exam
non-specific findings; costovertebral tenderness, suprapubic fullness, haematuria, enlarged prostate
1st investigation
Other investigations
- bladder scan:
increased post-void residual volume
- insertion of Foley catheter:
increased post-void residual volume
Creatine supplementation
History
creatine taken as a supplement to boost muscle mass and to increase athletic performance
Exam
normal
1st investigation
- serum creatinine:
may be elevated if prolonged intake of >10 g/day supplemental creatine; a return to baseline levels within 3 to 4 weeks of discontinuing creatine supplement
Other investigations
- urinary creatinine:
elevated
- creatine kinase:
mild elevation
Inherited kidney disease
History
family history of inherited kidney diseases (e.g., Fabry's disease, Alport's syndrome, thin basement membrane disease, and nail-patella syndrome)
Exam
non-specific findings
1st investigation
- serum creatinine:
abnormal
Other investigations
- urinalysis:
proteinuria
- spot urine albumin:creatinine ratio (ACR):
ACR of ≥3 mg/mmol is regarded as clinically important proteinuria in CKD
More
Methodological variations of measurement of creatinine
History
differences between the alkaline picrate (Jaffe) method and enzymatic serum creatinine results can exceed the recommended 5% target, especially at concentrations <100 micromol/L (1.13 mg/dL)
Exam
normal
1st investigation
- none:
clinical factor to consider in the absence of other cause of elevated creatinine
Other investigations
Assay-interfering substances
History
measurement assays are subject to various interfering substances (glucose, fructose, pyruvate, acetoacetate, uric acid, ascorbic acid, cephalosporins, bilirubin, exogenous and endogenous substances, and proteins); interfering chromogens can falsely increase serum creatinine values by 20% or even higher with the Jaffe method in conditions such as diabetic ketoacidosis; non-creatinine chromogens do not significantly affect urine creatinine levels and have less effect on total reaction in advanced renal dysfunction than in normal renal function
Exam
normal
1st investigation
- serum creatinine measured by different method:
elevated
More
Other investigations
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