Primary Glomerular Disorders PDF

Primary glomerular disorders Lecture Number 7.3 Status Done Type Lecture 7.3 Primary glomerular disorders Overview Primary glomerular disorders are kidney diseases where the pathology is intrinsic to the glomeruli, the functional filtering units of the kidney...

Primary glomerular disorders Lecture Number 7.3 Status Done Type Lecture 7.3 Primary glomerular disorders Overview Primary glomerular disorders are kidney diseases where the pathology is intrinsic to the glomeruli, the functional filtering units of the kidneys. They are classified based on whether the disorder leads to an increase in cellularity (proliferative) or structural damage without increased cellularity (non-proliferative). Proliferative disorders often manifest as nephritic syndrome, which includes haematuria and hypertension, while non-proliferative disorders usually present as nephrotic syndrome, marked by severe proteinuria and hypoalbuminemia. These disorders differ from secondary glomerular diseases, which are associated with systemic diseases affecting multiple organs. Understanding the classification, pathogenesis, and clinical presentation of each type is critical for diagnosis and management. Learning Objectives Objective 1: Identify and describe the main features of common primary glomerular disorders, including their histological and clinical characteristics. Objective 2: Distinguish between proliferative and non-proliferative glomerular disorders, with a focus on their pathophysiological mechanisms and clinical manifestations. Objective 3: Recognize the diagnostic and therapeutic approaches for nephrotic and nephritic syndromes within the context of primary glomerular disorders. Key Concepts and Definitions Glomerular Disorders Classification : Primary glomerular disorders are divided into: Proliferative: Increased cellularity in glomeruli, often leading to nephritic syndrome. Non-Proliferative: No significant cellular increase; primary damage to glomerular basement membrane and podocytes, leading to nephrotic syndrome. Nephrotic Syndrome: Characterized by severe proteinuria (>3.5 g/day), hypoalbuminemia, hyperlipidemia, and edema. Mnemonic: "HELP" - Hyperlipidemia, Edema, Loss of albumin, Proteinuria. Nephritic Syndrome: Often presents with hematuria, mild-to-moderate proteinuria, hypertension, and sometimes oliguria. Mnemonic: "HEMAT" - Hematuria, Elevated blood pressure, Mild proteinuria, Azotemia, Tubular damage. Clinical Applications Case Study: A 6-year-old child presents with facial edema, fatigue, and foamy urine, all indicative of nephrotic syndrome. Based on age and presentation, minimal change disease is highly suspected. Initial management with steroids is recommended, with monitoring for response. If proteinuria resolves, a diagnosis of minimal change disease can be confirmed without a kidney biopsy. Diagnostic Approach: Nephrotic Syndrome: Check for proteinuria (urinalysis), serum albumin, and lipid panel. In children, empiric steroid therapy is often started without a biopsy for presumed minimal change disease. Nephritic Syndrome: Order urine microscopy to check for red blood cell casts, serum creatinine, and other signs of kidney damage. History of recent infections is also relevant in post-streptococcal glomerulonephritis. Treatment Options: Minimal Change Disease: Steroids are first-line, with a high response rate in children.  Membranous Nephropathy: May require immunosuppressants (e.g., corticosteroids, cyclophosphamide) if progressive or unresponsive to supportive therapy. Post-Streptococcal Glomerulonephritis: Supportive care with antihypertensives, diuretics; usually self-limiting. Complications/Management: Nephrotic syndrome complications include infections (loss of immunoglobulins), thromboembolism (due to hypercoagulability), and potential kidney failure if untreated. Monitoring for signs of infection and clotting is crucial. Pathophysiology Non-Proliferative Disorders: Minimal Change Disease: Loss of podocyte foot process structure (effacement) without major histological changes. It primarily affects children and leads to reversible nephrotic syndrome. Key Point: Minimal change disease is steroid-responsive, which helps avoid biopsy in many cases. Membranous Nephropathy: Immune complex deposition on the outer side of the glomerular basement membrane (GBM), resulting in membrane thickening. Characteristic "spike and dome" appearance on microscopy is due to the GBM thickening around the immune deposits. Mnemonic: "MEMory spikes" - Membranous nephropathy and spike-like projections on histology. Proliferative Disorders: Post-Streptococcal Glomerulonephritis: Following group A streptococcal pharyngitis, immune complexes deposit in glomeruli, causing inflammation and hypercellularity. Subepithelial immune deposits (humps) lead to nephritic syndrome. Mnemonic: "Post-Strep Pops" - Post-streptococcal glomerulonephritis with humps (immune deposits) like "pops" on histology. IgA Nephropathy (Berger’s Disease): IgA immune complexes accumulate in the glomerular mesangium, often triggered by respiratory or GI infections. The disease is chronic with variable progression and is the most common glomerulonephritis worldwide. Clinical Connection: More frequent in Asian and Indigenous populations; monitor for chronic kidney disease progression. Pharmacology Steroids (e.g., Prednisone): Used primarily in minimal change disease to reduce immune-mediated podocyte damage. High success rate in children, but some adults may require prolonged treatment or additional immunosuppressants. Cross-reference: Immunosuppressive agents like cyclophosphamide may be necessary in steroid-resistant cases. ACE Inhibitors (e.g., Lisinopril): Reduces proteinuria and protects kidney function in chronic glomerular disease by lowering intraglomerular pressure. Commonly used in membranous nephropathy and other proteinuric conditions. Memory Aid: "ACE = Alleviates Cardiac and End-renal stress." Differential Diagnosis Minimal Change Disease vs. Focal Segmental Glomerulosclerosis (FSGS): Both present with nephrotic syndrome but differ histologically. FSGS shows segmental glomerular sclerosis on biopsy and is less steroid-responsive. Diagnostic Tip: FSGS often progresses to chronic kidney disease, unlike minimal change disease. IgA Nephropathy vs. Post-Streptococcal Glomerulonephritis: Both are triggered by infections, but IgA nephropathy occurs 1–2 days post-infection, whereas post-streptococcal glomerulonephritis appears after 1–3 weeks. Key Clinical Distinction : IgA nephropathy typically has elevated serum IgA levels in about 50% of cases. Investigations Renal Biopsy: Essential for diagnosing glomerular disorders not responding to empirical therapy. Biopsy findings guide specific disease management, especially in adults or atypical cases. Serum IgA Levels: Elevated in about 50% of IgA nephropathy cases, aiding in diagnosis when clinical presentation aligns. Urine Microscopy: Detects red blood cell casts in nephritic syndrome, supporting the diagnosis of glomerulonephritis, particularly in post-streptococcal cases. Key Diagrams and Visuals Summary and Key Takeaways Takeaway 1: Primary glomerular disorders are classified by the type of cellular or structural changes (proliferative vs. non- proliferative) and are distinguished by nephritic vs. nephrotic syndromes. Takeaway 2: Minimal change disease and membranous nephropathy primarily present with nephrotic syndrome, while post-streptococcal glomerulonephritis and IgA nephropathy present with nephritic syndrome. Takeaway 3: Treatment varies by disorder; minimal change disease typically responds to steroids, while membranous nephropathy may require additional immunosuppressants for progressive cases. Further Reading/References Resource 1: "Clinical Nephrology and Glomerular Disorders," edited by M. Kazmierczak, offers in-depth explanations of glomerular disease pathophysiology. Resource 2: "Nephrotic and Nephritic Syndromes: Diagnosis and Treatment," Journal of Renal Medicine, 2022, provides an overview of diagnostic features and therapy. Questions/Clarifications Question 1: What are alternative immunosuppressive options for patients with membranous nephropathy who are unresponsive to steroids? Question 2: Are there genetic markers or specific immunological profiles that increase the risk for progression to end- stage renal disease in IgA nephropathy?