Differentials

Common

Minimal change disease

History

common in children (occasionally found in adults), can be secondary to Hodgkin lymphoma

Exam

typically not hypertensive, otherwise physical exam is nonspecific

1st investigation
  • serial creatinine and estimated GFR:

    typically normal

  • renal biopsy:

    normal by light microscopy, but podocyte effacement on electron microscopy

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Other investigations

    Focal segmental glomerulosclerosis (FSGS)

    History

    asymptomatic, or may have edema and other symptoms of renal dysfunction; HIV, reflux nephropathy, class III obesity (BMI 40 or above), chronic glomerular hyperfiltration from a solitary kidney, or any other cause of extensive nephron loss (e.g., renal obstruction, prior glomerulonephritis), or history of drug use (e.g., pamidronate, heroin)

    Exam

    may be hypertensive, otherwise physical exam is nonspecific

    1st investigation
    • serial creatinine and estimated GFR:

      may be abnormal

    • renal biopsy:

      focal and segmental sclerosis of the glomeruli

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    Other investigations
    • HIV test:

      positive

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    Membranous nephropathy

    History

    may be primary or secondary; secondary disease associated with malignancy, infections (e.g., hepatitis B, hepatitis C, syphilis, malaria, or tuberculosis), autoimmune disease (e.g., lupus membranous nephropathy), or drugs (e.g., gold, penicillamine. and NSAIDs)

    Exam

    physical exam is nonspecific

    1st investigation
    • anti-phospholipase A2-receptor (PLA2R) antibody:

      positive

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    • renal biopsy:

      characteristic thickening of basement membranes seen on biopsy, as well as subepithelial electron-dense deposits

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    Other investigations
    • chest x-ray or chest CT for lung cancer:

      mass (consistent with lung tumor) may be present

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    • occult blood in stool:

      stool may be heme-positive

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    • hepatitis and HIV serologies:

      may be positive

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    • rapid plasma reagin (RPR) syphilis test:

      may be positive

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    • anti-nuclear antibody, anti-double-stranded DNA:

      elevated in systemic lupus erythematosus (SLE)

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    • complement levels (C3 and C4):

      Low in SLE

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    Diabetic nephropathy

    History

    long-standing history of diabetes often in conjunction with symptoms suggestive of diabetic retinopathy (impaired vision) or slowly progressive renal dysfunction (e.g., fatigue, swelling of the extremities)

    Exam

    diabetic retinopathy (microaneurysms, hard and soft exudates, microinfarcts, macular edema, increased tortuosity of veins, and neovascularization) seen on funduscopic exam

    1st investigation
    • HbA1c:

      often elevated

    • renal biopsy:

      diagnostic

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    Other investigations
    • urinalysis:

      may show microscopic hematuria

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    Multiple myeloma-associated AL amyloidosis

    History

    weight loss, symptoms suggestive of anemia (e.g., fatigue, decreased exercise tolerance), bone pain (especially back pain), history suggestive of pathologic fractures (e.g., low-impact fractures)

    Exam

    weight loss, anemia, abnormal bone x-ray (e.g. osteopenia, osteolytic lesions)

    1st investigation
    • CBC:

      normocytic, normochromic anemia

    • serum calcium:

      elevated

    • serum and urine protein electrophoresis with immunofixation:

      presence of monoclonal protein spike

    • serum free light chains:

      positive

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    • renal biopsy:

      diagnostic

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    Other investigations

      IgA nephropathy

      History

      episodes of dark urine that often occur along with pharyngitis; may be a history of liver disease, seronegative arthropathy, celiac disease, Henoch-Schonlein purpura (especially in children), purpuric skin lesions, melena, or bright red blood per rectum

      Exam

      rarely presents with edema, otherwise physical exam is nonspecific

      1st investigation
      • renal biopsy:

        IgA deposits seen on immunofluorescent exam of renal biopsy

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      Other investigations

        Uncommon

        Membranoproliferative (mesangiocapillary) glomerulonephritis

        History

        increased BP, fluid retention, non-visible hematuria, low-grade occasionally heavy proteinuria, variably abnormal kidney function

        Exam

        diagnosis is histological following a renal biopsy

        1st investigation
        • urinalysis:

          hematuria, proteinuria, dysmorphic RBCs, leukocytes, and RBC casts

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        Other investigations
        • renal biopsy:

          histological findings

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        Amyloidosis

        History

        neuropathy (including loss of pain and temperature sensation), easy bruising, positive family history (for familial type)

        Exam

        distal symmetric sensory neuropathy, bruising

        1st investigation
        • renal biopsy:

          diagnostic

          More
        Other investigations

          Lupus nephritis

          History

          rash, photosensitivity, arthralgias, mouth ulcers, fevers

          Exam

          malar rash, petechiae, arthritis

          1st investigation
          • CBC:

            anemia, thrombocytopenia

          • renal biopsy:

            diagnostic

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          • ANA, anti-ds-DNA antibody, C3, C4:

            positive

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          Other investigations

            Fabry disease

            History

            painful neuropathy, rash, exercise intolerance, heat intolerance, nausea, abdominal pain; mostly occurs in males (X-linked disease); positive family history

            Exam

            characteristic skin rash (angiokeratomas), corneal opacities

            1st investigation
            • genetic testing:

              positive for mutation

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            • renal biopsy:

              globotriaosylceramide accumulates in most cell types in the kidney, seen as larger laminated deposits called Zebra bodies or myelin figures on electron microscopy

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            Other investigations

              Alport syndrome

              History

              acquired hearing loss, occurs mostly in males (X-linked disease), positive family history, hearing loss, ocular abnormalities, commonly presents with hematuria, very rarely causes nephrotic syndrome

              Exam

              anterior lenticonus and perimacular flecks on ophthalmic exam

              1st investigation
              • renal biopsy:

                electron microscopy reveals abnormalities of the basement membrane such as thickening and stranding of the lamina densa

              • audiometry:

                possible high-frequency sensorineural hearing loss

              Other investigations
              • molecular genetic testing:

                Identification of pathogenic mutation (COL4A5 or COL4A3/4)

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              Nail-patella syndrome

              History

              positive family history (autosomal dominant)

              Exam

              hypoplastic patella, dystrophic nails

              1st investigation
              • clinical diagnosis:

                diagnosis is clinical

              Other investigations
              • renal biopsy:

                clusters of fibrils of type III collagen seen on electron microscopy

              Malignant hypertension

              History

              prior history of hypertension, blurred vision, dizziness, loss of sensation or movement, chest pain, dyspnea, peripheral edema, decreased urine output

              Exam

              very high blood pressure (often >210/130 mmHg), fundoscopic arteriolar spasm, retinal edema, retinal hemorrhages, retinal exudates, papilledema, or engorged retinal veins, signs of cardiac failure

              1st investigation
              • serum creatinine:

                elevated

              • hemolysis screen:

                increased lactate dehydrogenase (LDH), low serum haptoglobins, increased reticulocyte count, red cell fragmentation (schistocytosis >1%) on blood film

              • urinalysis and microscopy:

                presence of protein

              • echocardiogram:

                signs of cardiac ischemia

              • chest x-ray:

                signs of cardiac failure

              Other investigations

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