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Overview of Glomerular Disorders

By Navin Jaipaul, MD, MHS

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The hallmark of glomerular disorders is proteinuria, which is often in the nephrotic range (≥ 3 g/day).

Glomerular disorders are classified based on urine changes as those that manifest predominantly with

  • Nephrotic range proteinuria, and nephrotic urine sediment (fatty casts, oval fat bodies, but few cells or cellular casts)

  • Hematuria, usually in combination with proteinuria (which may be nephrotic range); the RBCs are usually dysmorphic and often there are RBC or mixed cellular casts (nephritic urine sediment)

Nephrotic syndrome is nephrotic urine sediment plus edema and hypoalbuminemia (typically with hypercholesterolemia and hypertriglyceridemia).

Nephritic syndrome is nephritic urine sediment with or without hypertension, elevated serum creatinine, and oliguria.

Several glomerular disorders typically manifest with features of both nephritic and nephrotic syndromes. These disorders include, but are not limited to, fibrillary and immunotactoid glomerulopathies, membranoproliferative glomerulonephritis (GN), and lupus nephritis.

The pathophysiology of nephritic and nephrotic disorders differs substantially, but their clinical overlap is considerable—eg, several disorders may manifest with the same clinical picture—and the presence of hematuria or proteinuria does not itself predict response to treatment or prognosis.

Disorders tend to manifest at different ages (see Table: Glomerular Disorders by Age and Manifestations) although there is much overlap. The disorders may be

Glomerular Disorders by Age and Manifestations

Age (yr)

Nephritic Syndrome

Nephrotic Syndrome

Mixed Nephritic and Nephrotic Syndrome

< 15

Mild PIGN

IgA nephropathy

Thin basement membrane disease

Hereditary nephritis

IgA–associated vasculitis

Lupus nephritis

Congenital nephrotic syndromes

Minimal change disease

Focal segmental glomerulosclerosis

Lupus nephritis (membranous subtype)

Lupus nephritis

Membranoproliferative GN

15–40

IgA nephropathy

Thin basement membrane disease

Lupus nephritis

Hereditary nephritis

RPGN

PIGN

Focal segmental glomerulosclerosis

Lupus nephritis (membranous subtype)

Minimal change disease

Membranous nephropathy

Diabetic nephropathy

Preeclampsia

Late PIGN

IgA nephropathy

Membranoproliferative GN

Fibrillary and immunotactoid GN*

IgA nephropathy

Lupus nephritis

RPGN

> 40

IgA nephropathy

RPGN

Vasculitides

PIGN

Focal segmental glomerulosclerosis

Membranous nephropathy

Diabetic nephropathy

Minimal change disease

IgA nephropathy

Amyloidosis (primary)

Light chain deposition disease

Benign hypertensive arteriolar nephrosclerosis (protein excretion is usually < 1 g/day)

Late PIGN

IgA nephropathy

Fibrillary and immunotactoid GN*

RPGN

*More commonly manifests as nephrotic syndrome.

GN = glomerulonephritis; PIGN = postinfectious glomerulonephritis; RPGN = rapidly progressive glomerulonephritis.

Adapted from Rose BD: Pathophysiology of Renal Disease, ed. 2. New York, McGraw-Hill, 1987, p. 167.

Diagnosis

  • Serum creatinine level and urinalysis

A glomerular disorder is usually suspected when screening or diagnostic testing reveals an elevated serum creatinine level and abnormal urinalysis (hematuria with or without casts, proteinuria, or both). Approach to the patient involves distinguishing predominant-nephritic from predominant-nephrotic features and identifying likely causes by patient age, accompanying illness (see Table: Glomerular Disorders by Age and Manifestations and see Table: Causes of Nephrotic Syndrome), and other elements of the history (eg, time course, systemic manifestations, family history).

Renal biopsy is indicated when diagnosis is unclear from history or when histology influences choice of treatment and outcomes (eg, lupus nephritis).

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