Overview of the evaluation and differential diagnosis of glomerular disease

Kidney biopsy specimens should always be analyzed with light microscopy and immunofluorescence. In some cases, electron microscopy is also necessary. Because electron microscopy is not available at some institutions, the biopsy should be analyzed at a different institution (ie, should be sent to a hospital with electron microscopy capabilities) if the clinical scenario, light microscopy, and/or immunofluorescence suggest that the following disorders may be present:

Minimal change disease.
FSGS.
C3 glomerulopathy (C3 glomerulonephritis or dense deposit disease).
Thin basement membrane nephropathy.
Alport syndrome.
Fabry disease.
Fibrillary glomerulonephritis.
Immunotactoid glomerulonephritis.
Monoclonal immunoglobulin deposition disease.
Amyloidosis.

AA amyloidosis: amyloid A amyloidosis; AL amyloidosis: amyloid light-chain amyloidosis; ANA: antinuclear antibody; ANCA: antineutrophil cytoplasmic antibody; anti-dsDNA: anti-double-stranded DNA; anti-PLA2R: anti-phospholipase-A2-receptor; APOL1: apolipoprotein L1; C3: complement component 3; C4: complement component 4; eGFR: estimated glomerular filtration rate; ELISA: enzyme-linked immunoassay; FSGS: focal segmental glomerulosclerosis; GBM: glomerular basement membrane; HbA1c: hemoglobin A1C; HBV: hepatitis B virus; HCV: hepatitis C virus; HIV: human immunodeficiency virus; IgA: immunoglobulin A; immunotactoid GN: immunotactoid glomerulopathy; MPO: myeloperoxidase; NSAIDs: nonsteroidal antiinflammatory drugs; PR3: proteinase 3; RBC: red blood cell.

* Glomerular hematuria and proteinuria are defined as follows:

Glomerular hematuria is established by the presence of urinary RBC casts (of any number) or hematuria in which more than 5% of RBCs are acanthocytes or dysmorphic.
Proteinuria is typically defined as a 24-hour urine protein excretion of ≥150 mg (or a corresponding value using the spot urine protein, spot urine creatinine, and the protein excretion rate equation).
Albuminuria (albumin is a component of urinary protein, is the major component in glomerular disease, and is the protein that is detected by the urine dipstick) is typically defined as a 24-hour urine albumin excretion of ≥30 mg (or a corresponding value using the spot urine albumin, spot urine creatinine, and the albumin excretion rate equation).

¶ A systemic disorder that also involves the kidney should be suspected if there is evidence for inflammation of other organ systems, such as the skin (eg, purpura, rash), joints (eg, arthritis), eye (eg, retinitis, uveitis), nose (eg, epistaxis), mouth (eg, ulcers), lungs (eg, hemoptysis, infiltrates), nervous system (eg, seizures, neuropathy), extremities (eg, digital ischemia or infarction), or abdomen (eg, enteritis, colitis), or if there is an infection (particularly with Staphylococcus, Streptococcus, hepatitis virus, or HIV).

Δ Orthostatic proteinuria is characterized by increased protein excretion while in the upright posture but normal protein excretion when recumbent; it is typically found in adolescents and young adults but not in older adults. The diagnosis is made by establishing that urine protein excretion is normal when the patient is supine, either with an overnight urine collection or a first-morning voided urine specimen.

◊ Some patients with FSGS will have a genetic mutation that results in a defect of podocyte or slit diaphragm function; the most commonly involved genes include nephrin, podocin, alpha-actinin-4, TRPC6, INF2, and MYO1E.

Graphic 113287 Version 5.0

خرید پکیج

Overview of the evaluation and differential diagnosis of glomerular disease