Chapter 17: Glomerular Diseases

Urine Nephrology Now: A Primer for Students in Nephrology

Andrew Bland, MD

Introduction to Glomerular Diseases

Glomerular diseases represent a diverse group of conditions affecting the glomerular filtration barrier. Understanding the clinical presentations and pathophysiology helps distinguish between different types and guides appropriate treatment.

Clinical Syndromes

Nephrotic Syndrome

Characterized by the tetrad of proteinuria (>3.5 g/day), hypoalbuminemia, edema, and hyperlipidemia.

Pathophysiology

Loss of albumin leads to decreased oncotic pressure and fluid retention. Compensatory liver protein synthesis increases cholesterol production.

Common Causes

Primary: Minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy

Secondary: Diabetes, lupus, amyloidosis, medications

Complications

  • Thromboembolism due to hypercoagulable state
  • Infections due to loss of immunoglobulins
  • Protein malnutrition
  • Dyslipidemia and cardiovascular disease

Nephritic Syndrome

Characterized by hematuria, proteinuria (usually <3.5 g/day), hypertension, and reduced GFR.

Pathophysiology

Inflammatory process in glomeruli leads to bleeding and reduced filtration.

Common Causes

  • Post-infectious glomerulonephritis
  • IgA nephropathy
  • Rapidly progressive glomerulonephritis
  • Lupus nephritis

Primary Glomerular Diseases

Minimal Change Disease

Most common cause of nephrotic syndrome in children, but can occur in adults. Normal appearing glomeruli on light microscopy, but electron microscopy shows foot process effacement. Highly responsive to corticosteroid therapy with excellent prognosis.

Focal Segmental Glomerulosclerosis (FSGS)

Most common cause of nephrotic syndrome in adults, particularly African Americans. Sclerosis affects only segments of some glomeruli (focal and segmental). More resistant to treatment than minimal change disease and may require immunosuppressive agents.

Membranous Nephropathy

Common cause of nephrotic syndrome in older adults. Thickening of glomerular basement membrane with subepithelial deposits. Risk stratification determines need for immunosuppressive therapy.

IgA Nephropathy

Most common primary glomerulonephritis worldwide. Often presents with episodic hematuria following upper respiratory infections. IgA deposits in the mesangium. Treatment includes ACE inhibitors or ARBs, with immunosuppression reserved for severe cases.

Secondary Glomerular Diseases

Diabetic Nephropathy

Most common cause of CKD in developed countries. Progresses through stages from hyperfiltration to microalbuminuria, overt proteinuria, and declining GFR. Management includes glycemic control, blood pressure control, ACE inhibitors/ARBs, and SGLT2 inhibitors.

Lupus Nephritis

Kidney involvement occurs in 60% of patients with systemic lupus erythematosus. Classified into six classes based on histological findings, with class IV being most severe. Treatment involves immunosuppressive therapy with careful monitoring for complications.

Rapidly Progressive Glomerulonephritis (RPGN)

RPGN represents a medical emergency requiring urgent evaluation and treatment. Defined as rapid loss of kidney function over days to weeks, often with crescent formation on biopsy.

Types of RPGN

  • Type I: Anti-GBM disease (Goodpasture syndrome)
  • Type II: Immune complex mediated (lupus, post-infectious)
  • Type III: ANCA-associated vasculitis

Treatment

Urgent immunosuppressive therapy, often including plasmapheresis for anti-GBM disease.

Diagnostic Approach

History and Physical Examination

Focus on family history, medications, systemic symptoms, and signs of systemic disease. Look for rashes, joint pain, or other manifestations of autoimmune disease.

Laboratory Tests

Essential studies include comprehensive metabolic panel, complete blood count, complement levels (C3, C4), autoantibodies (ANA, ANCA, anti-GBM), hepatitis and streptococcal serologies, and serum and urine protein electrophoresis.

Kidney Biopsy

Often necessary for definitive diagnosis and treatment planning. Indications include nephrotic syndrome in adults, nephritic syndrome with reduced GFR, AKI of unclear etiology, and CKD with proteinuria and unclear cause.