History
Focus the history on the causes of diffuse proliferative glomerulonephritis (DPGN) and the associated clinical manifestations. While a minority (< 15%) of patients may be asymptomatic and are diagnosed on the basis of routine laboratory test findings, most patients manifest signs and symptoms of the primary disease as well as those relating to renal injury. Nonspecific manifestations (eg, nausea, vomiting, fatigue, weight loss) may indicate uremia or the primary disease process.
Suspect DPGN in patients with systemic lupus erythematosus (SLE), infectious disease processes, a recent streptococcal throat infection, or in patients with sinopulmonary disease who have recent onset of the following:
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Hypertension
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Microscopic or gross hematuria
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Non-nephrotic or nephrotic-range proteinuria or an increase in proteinuria from baseline
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Serum creatinine of more than 0.4 mg/dL above the reference range or the patient's baseline
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Oliguria or anuria and symptoms of uremia in severe cases of rapidly progressive glomerulonephritis (RPGN) with crescent formation
Also suspect DPGN in a patient with other systemic diseases who has recent onset of the same findings listed above.
Features in the history may provide clues to an undiagnosed primary disease process. The following suggest SLE as the primary disease:
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Rash
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Photosensitivity
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Oral ulcers
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Arthralgias, arthritis
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Serositis
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A renal, neurologic, hematologic, or immunologic disorder
A history of cough, dyspnea, hemoptysis, and kidney disease suggests Goodpasture syndrome, but other pulmonary-renal syndromes must be ruled out, including the following:
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SLE pneumonitis
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Granulomatosis with polyangiitis (GPA; formerly Wegener granulomatosis)
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Cryoglobulinemia
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Renal vein thrombosis with pulmonary embolism
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Legionella infection
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Congestive heart failure
GPA presents as follows:
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Sinopulmonary disease (ie, paranasal sinus pain and drainage with purulent or bloody nasal discharge and occasional nasal mucosal ulceration/perforation, leading to saddle nose deformity)
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Serous otitis media (ie, blockage of the eustachian tube)
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Cough, dyspnea, and hemoptysis
Patients with IgA nephropathy (ie, Berger disease) may present with the classic findings of flank pain and gross hematuria following upper respiratory infections. Others may simply have indolent microhematuria found incidentally. Much less commonly, patients present with acute glomerulonephritis, kidney failure, and nephrotic syndrome.
Physical Examination
If azotemia is present, exclude prerenal and postrenal causes. Hypertension and fever (present in infectious and noninfectious glomerulonephritis) are nonspecific findings that suggest DPGN.
Findings pertaining to SLE include the often acute onset of conjunctivitis, episcleritis, photosensitivity, oral ulcers, malar rash (eg, erythema of the nose and malar eminences in a butterfly distribution), discoid lupus, pleural or pericardial friction rub, psychosis, seizures, nonerosive arthritis, or arthralgia
Findings relating to pauci-immune disease (eg, anti–glomerular basement membrane (GBM) disease, GPA) and Goodpasture syndrome include the following:
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Sinusitis, otitis, saddle nose deformity, hemoptysis
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Lung consolidation, which suggests pulmonary hemorrhage
Findings relating to IgA nephropathy (usually postinfectious) and other infectious glomerulonephritides include the following:
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Pharyngitis
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Gastroenteritis
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Impetigo, which is the most common cause of poststreptococcal glomerulonephritis worldwide
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Light microscopy (trichrome stain) shows globally increased cellularity, numerous polymorphonuclear cells, cellular crescent (at left of photomicrograph) and fibrinoid necrosis (brick red staining at right of photomicrograph). These findings are characteristic of diffuse proliferative glomerulonephritis.
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Diffuse proliferative glomerulonephritis (DPGN). Immunofluorescent microscopy shows (except for anti–glomerular basement membrane [GBM] disease) a granular deposition of immunoglobulins, complement, and fibrin along the GBM, tubular basement membranes, and peritubular capillaries (image 2a). Linear deposition occurs in the GBM in anti-GBM disease (image 2b).
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Diffuse proliferative glomerulonephritis (DPGN). Using electron microscopy, electron-dense deposits are visible in the mesangial, subendothelial, intramembranous, and subepithelial locations.
