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: 2017

Common

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
  • serial measurements of serum creatinine:

    rapidly rising

    More
  • urinalysis:

    proteinuria, hematuria (most commonly nonvisible) may show red blood cell casts, epithelial cell casts, waxy casts or granular casts

    More
  • fractional excretion of sodium (FENa):

    <1%

    More
  • random urine sodium (UNa):

    >20 mEq/L

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

    More

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

Other investigations
  • urinalysis:

    proteinuria

    More
  • spot urine ACR:

    ACR of ≥30 mg/g is regarded as clinically important proteinuria in CKD.

    More

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
    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

      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

        More
      Other investigations
      • spot urine albumin:creatinine ratio (ACR):

        ACR of ≥30 mg/g is regarded as clinically important proteinuria in CKD

        More
      • ECG:

        may show evidence of old myocardial infarct or left ventricle hypertrophy

      • lipid panel:

        may show high LDL, low HDL, or high triglycerides

        More

      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

              Other investigations
              • aldosterone-to-renin ratio:

                <20

                More
              • magnetic resonance angiography:

                renal artery stenosis

              • urinalysis:

                normal (in the absence of diabetic nephropathy or hypertensive glomerulosclerosis)

                More

              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
              Other investigations
              • magnetic resonance angiography:

                abnormal

                More
              • CT angiography:

                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
              • genitourinary ultrasound:

                hydronephrosis, hydroureter, distended bladder

              • noncontrast CT scan:

                may show stones in urinary tract

                More
              • urinalysis:

                normal or positive nitrites, leukocyte esterase, and/or blood in presence of infection; microscopic hematuria in renal colic

                More
              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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