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 generalized symptoms of anorexia, nausea, weight loss, malaise; history of fever with post infectious etiology; history of sore throat if poststreptococcal; previous history of HIV, hepatitis B; history of Raynaud phenomenon, sclerodactyly, GERD, digital ulcers, skin thickening, telangiectasias; may have visible hematuria (more commonly nonvisible); may have symptoms of vasculitis in rapidly progressive glomerulonephritis
Exam
edema (if nephrotic syndrome is present), hypertension, uremic signs and symptoms; diffuse hand swelling often worse in the morning (characteristic of scleroderma), can be accompanied by foot swelling
1st investigation
Other investigations
- CBC:
may be normal; microcytic anemia with chronic gastrointestinal bleed; microangiopathic hemolytic anemia with scleroderma renal crisis
- CRP or erythrocyte sedimentation rate:
elevated or normal
More - spot urine ACR:
normal or elevated
More - antistreptolysin O:
poststreptococcal glomerulonephritis: positive
- anti-DNAse:
poststreptococcal glomerulonephritis: positive
- complement titers:
low in postinfectious glomerulonephritis, essential mixed cryoglobulinemia, 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 cryoglobulinemia
- 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 - antiphospholipase A2 receptor antibodies:
may be positive
More - kidney biopsy:
characteristic findings on light, immunofluorescence, and electron microscopy
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Diabetic nephropathy
History
history of diabetes mellitus, often asymptomatic; risk factors include sustained hyperglycemia, hypertension, family history of hypertension or kidney disease, obesity and smoking
Exam
nonspecific findings
1st investigation
- hemoglobin A1c:
elevated
Systemic vasculitis
History
may have history of arthralgias; photosensitive malar (butterfly), generalized, or discoid rash; fatigue, weight loss, purpuric rash
Exam
joint tenderness to palpation, swelling in multiple joints, alopecia, oral ulcers, lymphadenopathy
1st investigation
- urinalysis:
hematuria, 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
- kidney 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, gold sodium thiomalate, nonsteroidal anti-inflammatory drugs, mitomycin C, cyclosporine 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
radiologic 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, prerenal factor that causes decreased kidney perfusion; multiple organ failure; history of acute insult or sepsis; history of chest pain in cardiogenic shock
Exam
low blood pressure, dizziness, tachycardia, edema; cool, clammy or mottled skin; oliguria, mental state changes; progressive organ dysfunction
1st investigation
- urine specific gravity:
elevated (>1.020)
- serum blood chemistries:
elevated creatinine; BUN/serum Cr >20; hyperkalemia in trauma or acute kidney injury
- arterial or venous blood gas:
lactate >18 mg/dL (>2 mmol/L); may show metabolic acidosis (pH <7.35) and low bicarbonate (<134 mg/dL); arterial blood gas may show hypoxemia 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 - CBC:
white blood cell count may be elevated with inflammation or infection; hemoglobin may decrease with acute hemorrhage
- glucose:
may be elevated
- coagulation studies:
may be abnormal in septic shock and trauma
- CRP:
elevated in septic shock
- blood, urine, and sputum cultures:
positive for organism in sepsis
- electrocardiogram:
may show cause of cardiogenic shock or hyperkalemia
Volume depletion
History
decreased fluid intake, vomiting, diarrhea, 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
- BUN to serum Cr:
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 hyperglycemia
- urinalysis:
may show proteinuria
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Chronic heart failure
History
history of chronic heart failure; prerenal factor that causes decreased kidney perfusion; orthopnea and paroxysmal nocturnal dyspnea, nocturia, dyspnea
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
- CXR:
abnormal
More - serum electrolytes:
decreased sodium (usually <135 mg/dL), altered potassium
- serum creatinine or BUN:
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
- CBC:
anemia, high lymphocyte percentage
Preeclampsia
History
rise in serum creatinine in a pregnant woman; reference range for serum creatinine is lower in pregnancy (0.4 to 0.5 mg/dL [36 to 45 micromol/L]), and values above this are a concern for worsening of kidney function, headache, upper abdominal pain, reduced fetal movement, edema
Exam
hypertension, edema
1st investigation
- urinalysis:
proteinuria
More
Other investigations
- placental growth factor:
low
More - CBC:
may reveal low platelet count
- LFTs:
may be elevated
Acute interstitial nephritis
History
patient presents with nonoliguric acute kidney failure with rash, fever, and eosinophilia (the "hypersensitivity triad") triggered by a medication; toxin tubulopathy, hypercalcemia, lithium-induced tubular damage; may be a history of systemic lupus erythematosus, sarcoidosis, or Sjogren syndrome
Exam
pyuria, hematuria, proteinuria, eosinophiluria
1st investigation
- urinalysis:
microhematuria; sterile pyuria; proteinuria; muddy brown granular casts, epithelial casts
More - BUN 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
- CBC with WBC 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
nonspecific findings
1st investigation
- serum creatinine and BUN:
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
- BUN to serum Cr:
10:1 or higher
- random urine electrolytes:
increased excretion of sodium
- fractional excretion of sodium (FENa):
>2%
More - urinary myoglobin:
elevated if acute tubular necrosis is caused by rhabdomyolysis
Cardiac surgery
History
cardiac surgery involving prolonged clamping of main arteries and kidney 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 physiologic state
Exam
normal aside from surgical scars
1st investigation
- serum creatinine:
initial elevation, which resolves following physiologic adaptation
Other investigations
Kidney transplant rejection
History
kidney transplant recipient: serum creatinine elevation is usually the alerting event for the clinician; other reasons for elevated serum creatinine in kidney transplant recipients include surgical and infection complications, immunosuppressive medications, noncompliance 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
- microbiologic testing for infectious causes:
may be positive, cytomegalovirus titer, BK virus titer
More
Biologic serum creatinine variation
History
female sex; older age; variations in creatinine production due to differences in muscle mass; intra- and interpatient variability in the production, tubular secretion, renal and extrarenal excretion, and degradation of creatinine
Exam
nonspecific 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, kidney transplant, systemic lupus erythematosus, or nephrotic syndrome, may be history of hypercoagulable state
Exam
abdominal mass or normal exam hematuria
1st investigation
- duplex ultrasound:
renal vein occlusion
- magnetic resonance venography:
renal vein occlusion
Other investigations
- comprehensive metabolic panel:
abnormal serum creatinine
- urinalysis:
hematuria, proteinuria
Radiation therapy
History
history of radiation therapy
Exam
nonspecific findings
1st investigation
- none:
clinical diagnosis
Other investigations
Endogenous nephrotoxins (myoglobin, uric acid, calciphylaxis)
History
history of rhabdomyolysis, tumor lysis syndrome, calciphylaxis
Exam
nonspecific findings; painful necrotic skin lesions in calciphylaxis
1st investigation
- creatine kinase:
rhabdomyolysis: marked elevation
Other investigations
- urine myoglobin:
rhabdomyolysis: marked elevation
- uric acid:
tumor lysis syndrome: elevated uric acid
- skin biopsy:
calciphylaxis: calcification, fibrointimal 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 ischemic nephropathy
Exam
elevated blood pressure, abdominal bruit
1st investigation
- kidney ultrasound with Doppler:
asymmetric kidney size, decreased renal artery flow
Traumatic kidney infarction
History
nonpenetrating abdominal trauma (traumatic kidney infarct constitutes 1% to 2% of all nonpenetrating 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 catheterization; multiorgan involvement (cutaneous lesions, thrash toes/blue toes, pancreatitis, stroke, ischemic bowel, angina, days or weeks following vascular procedure); gastrointestinal, cardiac, renal, neurologic symptoms
Exam
thrash toes/blue toes, cutaneous lesions; visual field deficits
1st investigation
- serum creatinine:
stepwise rise in serum creatinine
Other investigations
- CBC with differential:
transient peripheral eosinophilia, anemia, 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 - LDH:
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; tumor: weight loss, change in bowel habit
Exam
nonspecific findings; costovertebral tenderness, suprapubic fullness, hematuria, enlarged prostate
1st investigation
Other investigations
- bladder scan:
increased postvoid residual volume
- insertion of Foley catheter:
increased postvoid 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; 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 disease, Alport syndrome, thin basement membrane disease, and nail-patella syndrome)
Exam
nonspecific findings
1st investigation
- serum creatinine:
elevated
- DNA analysis:
mutation in gene of interest
More
Other investigations
- urinalysis:
proteinuria
- spot urine albumin:creatinine ratio (ACR):
ACR of ≥30 mg/g is regarded as clinically important proteinuria in CKD
More
Methodologic 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 <1.13 mg/dL (100 micromol/L)
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; noncreatinine chromogens do not significantly affect urine creatinine levels and have less effect on total reaction in advanced kidney dysfunction than in normal kidney function
Exam
normal
1st investigation
- serum creatinine measured by different method:
normal
More
Other investigations
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