What Are Common Causes of Glomerular Disease in Adults?

Electron microscopy shows effacement of podocytes. Complement levels are normal. Treatment of primary idiopathic FSGS includes use of renin-angiotensin inhibitors and steroids.⁴ Immunosuppressives are reserved for relapses. Treatment of secondary FSGS involves identifying the underlying cause.

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Table 1. Differences between Nephrotic and Nephritic Syndromes

Membranous nephropathy. MN is twice as common in males as in females and is the most common cause of adult-onset idiopathic nephrotic syndrome, with the average presentation in the fifth or sixth decade of life.^7,8 Aside from its idiopathic form, up to 25% of MN cases have an underlying disease process, such as solid organ tumors or hepatitis B.^7,9 While nephrotic syndrome overall can increase the risk of thromboembolic complications, MN is the most common nephrotic disorder predisposing the development of renal vein thrombosis.⁷ Diffuse capillary wall thickening is seen on light microscopy, and electron microscopy shows sub-epithelial immune deposits. Complement levels are normal. Steroids and immunosuppressive agents are used for treatment.¹⁰

Membranoproliferative glomerulonephritis. MPGN is a nephrotic syndrome that is more common in children and young adults and can present with features of nephritic syndrome.^1,11 It is associated with hepatitis C, SLE, and cryoglobulinemia.¹¹ Light microscopy shows mesangial and endocapillary proliferation, as well as glomerular basement membrane thickening and splitting (“tram track” appearance). Electron microscopy shows subendothelial and dense deposits. It presents with reduced complement levels (C3 and C4).¹¹ Treatment depends on the associated disease.

Nephritic Syndromes

Post-streptococcal glomerulonephritis. PSGN is seen in children and young adults and is associated with skin (impetigo) and throat infections (pharyngitis).¹² Hematuria usually presents two to three weeks after a streptococcal infection. The urine is classically dark and smoky-colored. Levels of C3 and CH50 are low, but C4 levels are normal.1 In addition, there are positive antibody titers for ASO and anti-DNase. Light microscopy shows hypercellularity of glomeruli. Electron microscopy shows dome-shaped sub-endothelial deposits. Treatment is usually supportive.

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Table 2. Summary of Findings of Major Glomerulonephritides

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Table 3. Complement Levels In Major Glomerulonephritides

IgA nephropathy. IgA nephropathy is the most common form of glomerular disease worldwide and the most common form of glomerular-related microscopic hematuria in all age groups.^2,13 It occurs in all ages but more frequently in males.¹⁴ It occurs during or immediately after an upper respiratory infection. Light microscopy shows mesangial cell proliferation and crescentic GN. Electron microscopy shows immune deposits in the mesangium. Complement levels are normal. There has been no proven therapy, but ACE inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), fish oil, steroids, and tonsillectomy have been used with some success.¹⁴ The clinical course of IgA nephropathy can be highly variable, with the potential for a benign course to rapidly progressive renal failure, with 15% to 40% of patients developing end-stage renal disease.¹⁴

Henoch-Schonlein purpura. HSP affects children more than adults and is the systemic form of IgA nephropathy.14 Most cases are idiopathic. Clinical

manifestations include: HTN; purpuric palpable rash on buttocks, ankles, and legs; bloody diarrhea with abdominal cramps; and pain in wrist, ankle, and knee joints.¹⁵ Light microscopy shows mesangial cell proliferation. Immune deposits in the mesangium are seen on electron microscopy. Complement levels are normal. Treatment is supportive.

Rapidly progressive glomerulonephritis types I, II, and III. RPGN represents a wide variety of disease states in which rapid progression to renal failure is seen within days to weeks.¹⁶ They are categorized into three sub-categories: I, II, and III.

Type I is an anti-GBM disease, an example being Goodpasture’s syndrome. This condition presents with hemoptysis, pulmonary infiltrates, and hematuria with RBC casts. Anti-GBM antibodies are classically found.¹ Complement levels are normal and a linear immunofluorescence pattern is seen. Treatment is steroids, immunosuppressive agents, and plasmapheresis.¹⁷