Differential diagnosis and evaluation of glomerular disease
- Lee A Hebert, MD
Lee A Hebert, MD
- Section Editor — Glomerular Diseases
- Professor of Medicine
- Ohio State University
- Wexner College of Medicine and Public Health
- Samir V Parikh, MD
Samir V Parikh, MD
- Assistant Professor of Clinical Medicine
- Division of Nephrology
- The Ohio State University Medical Center
The presence of some form of glomerular disease, as opposed to primary tubulointerstitial or vascular disease, is usually suspected from the history (including a family history of glomerular disease), physical examination (eg, edema), and from one or more of the following urinary findings: hematuria (particularly if the red cells have a dysmorphic appearance), red cell casts, lipiduria (since glomerular permeability must be increased to allow the filtration of large lipoproteins), and proteinuria, which may be in the nephrotic range (greater than 3.5 g/day). (See "Etiology and evaluation of hematuria in adults", section on 'Glomerular versus nonglomerular bleeding' and "Urinalysis in the diagnosis of kidney disease", section on 'The assessment of lipiduria' and "Assessment of urinary protein excretion and evaluation of isolated non-nephrotic proteinuria in adults" and "Evaluation of proteinuria in children".)
Despite these clues, the ability to distinguish glomerular disease from chronic tubulointerstitial disease may be difficult. Although tubulointerstitial disease does not directly increase protein excretion, nephron loss can induce secondary glomerulosclerosis leading to proteinuria that may reach the nephrotic range. Such patients may be erroneously considered to have a primary glomerular disease (see "Epidemiology, classification, and pathogenesis of focal segmental glomerulosclerosis", section on 'Pathogenesis of secondary FSGS'). Severe vascular diseases, such as malignant hypertension or a thrombotic microangiopathy, are other disorders that can be associated with hematuria and proteinuria and thus resemble primary glomerular disease.
Establishing the correct diagnosis usually requires renal biopsy. This topic will review how the clinical features at presentation can allow the clinician to narrow the differential diagnosis prior to biopsy. The mechanisms of glomerular injury are discussed separately. (See "Mechanisms of immune injury of the glomerulus" and "Mechanisms of glomerular crescent formation".)
CLINICAL PATTERNS OF GLOMERULAR DISEASE
Although there are many causes of glomerular disease, most patients present with one of two patterns, nephrotic or nephritic, that are based upon the urine sediment and the degree of proteinuria (table 1).
Nephrotic pattern — The nephrotic pattern is characterized by proteinuria that is usually above 3.5 g/day and lipiduria, but few cells or casts other than fatty casts (picture 1A-B). Patients who also have edema and hyperlipidemia (the full-blown nephrotic syndrome) tend to have a more marked glomerular leak than those with proteinuria alone. Some patients also have microscopic hematuria. Red cell casts are usually not seen and, when present, may result from a concurrent glomerulonephritis as has been described in diabetic nephropathy. (See 'Limitations of this classification' below and "Overview of diabetic nephropathy", section on 'Hematuria'.)
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- CLINICAL PATTERNS OF GLOMERULAR DISEASE
- Nephrotic pattern
- - Acute kidney injury
- Nephritic pattern
- - Pathologic classification
- Limitations of this classification
- Nonspecific nature of the histologic patterns
- Concurrent glomerular disease
- CAUSES OF GLOMERULAR DISEASE ACCORDING TO PRESENTATION
- Nephrotic syndrome without a nephritic sediment
- Mild glomerulonephritis
- Moderate to severe glomerulonephritis
- Effect of race
- Positive family history
- Systemic presentations
- - Acute glomerulonephritis and pulmonary hemorrhage
- - Hematuria following upper respiratory infection
- Clinically evident glomerulonephritis
- - IgA nephropathy versus PSGN
- - C3 glomerulonephritis
- - Hereditary nephritis (Alport syndrome)
- - Thin basement membrane nephropathy
- Microscopic hematuria alone
- LABORATORY TESTING IN PATIENTS WITH SUSPECTED GLOMERULAR DISEASE
- Serologic testing
- - Patients with a nephrotic presentation
- - Patients with a nephritic pattern
- WHEN RENAL BIOPSY MAY NOT BE NECESSARY
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS