07.3 Primary glomerular disorders

Primary Glomerular Disorders

• Primary glomerular disorders affect the glomeruli, the kidney's filtering units
• Classified as proliferative (increased cellularity) or non-proliferative (no significant cellular increase)
• Proliferative disorders often lead to nephritic syndrome (hematuria, hypertension)
• Non-proliferative disorders usually result in nephrotic syndrome (severe proteinuria, hypoalbuminemia, edema)

Learning Objectives

• Identify and describe common primary glomerular disorders (histological and clinical characteristics)
• Distinguish between proliferative and non-proliferative disorders, focusing on pathophysiological mechanisms and clinical presentations
• Recognize diagnostic and therapeutic approaches for nephrotic and nephritic syndromes within the context of primary glomerular disorders

Key Concepts and Definitions

• Proliferative Disorders: Increased glomerular cell growth, often leading to nephritic syndrome
• Non-Proliferative Disorders: No significant cellular increase, usually causing nephrotic syndrome
• Nephrotic Syndrome: Characterized by severe proteinuria (>3.5 g/day), hypoalbuminemia, hyperlipidemia, edema
• Nephritic Syndrome: Often presents with hematuria, mild-to-moderate proteinuria, hypertension, and sometimes oliguria

Clinical Applications

• Case study example: 6-year-old child with facial edema, fatigue, and foamy urine (suggestive of nephrotic syndrome, possibly minimal change disease)
• Diagnostic Approach (Nephrotic Syndrome): Check proteinuria (urinalysis), serum albumin, and lipid panel; empiric steroid therapy often initiated in children
• Diagnostic Approach (Nephritic Syndrome): Order urine microscopy, serum creatinine levels, and consider recent infections (especially post-streptococcal glomerulonephritis)
• Treatment Options (Minimal Change Disease): Steroids are the first-line treatment, often highly effective in children

Pathophysiology

• Non-Proliferative Disorders (e.g., Minimal Change Disease): Loss of podocyte foot process structure (effacement) without other significant histological changes; often steroid-responsive
• Membranous Nephropathy: Immune complex deposit on glomerular basement membrane, resulting in membrane thickening (spike and dome appearance on microscopy)
• Proliferative Disorders (e.g., Post-Streptococcal Glomerulonephritis): Immune complexes deposit in glomeruli, causing inflammation and hypercellularity; often following group A streptococcal infection "humps" on histology
• IgA Nephropathy (Berger's Disease): IgA immune complexes accumulate in the glomerular mesangium often triggered by respiratory or Gl infections; common worldwide

Pharmacology

• Steroids (e.g., Prednisone): primarily used to reduce immune-mediated podocyte damage in minimal change disease; may require prolonged treatment in some cases; ACE inhibitors (e.g., Lisinopril): Reduce proteinuria and protect kidney function

Differential Diagnosis

• Minimal Change Disease vs. Focal Segmental Glomerulosclerosis (FSGS): Both present with nephrotic syndrome; FSGS is less steroid responsive
• IgA Nephropathy vs. Post-Streptococcal Glomerulonephritis: Both are infection-related; IgA Nephropathy typically arises 1-2 days after infection; Post-Streptococcal in 1-3 weeks
• Key Clinical Distinction: IgA nephropathy often presents with elevated serum IgA levels

Investigations

• Renal Biopsy: Essential for diagnosing glomerular disorders that are not responding to empirical treatment. Findings guide further treatment (especially in adults or unusual cases)
• Serum IgA Levels: Used in diagnosing IgA nephropathy (elevated in ~50% of cases)
• Urine Microscopy: Checks for red blood cell casts in the urine to support diagnosis of glomerulonephritis, particularly in post-streptococcal cases

This quiz focuses on primary glomerular disorders, examining their classifications into proliferative and non-proliferative types. You will learn about their clinical characteristics, diagnostic approaches, and the pathophysiological mechanisms underlying nephritic and nephrotic syndromes. Test your knowledge on the common disorders affecting the kidney's glomeruli.