08.1 Secondary glomerular disorders

Secondary Glomerular Disorders

• Secondary glomerular disorders are kidney diseases caused by systemic conditions, not intrinsic renal problems.
• Two key examples are multiple myeloma nephropathy and diabetic nephropathy.
• Understanding these disorders is crucial for clinical practice and exams.

Learning Objectives

• Explain how multiple myeloma damages kidneys and why Bence-Jones protein urine assessment is important.
• Understand the natural history, pathophysiology, and clinical progression of diabetic nephropathy.
• Describe the diagnostic process and management strategies for diabetic nephropathy.

Key Concepts

• Primary Glomerular Disorders: Intrinsic kidney diseases, often idiopathic (unknown cause).
• Secondary Glomerular Disorders: Kidney diseases caused by systemic issues like multiple myeloma, diabetes, or lupus.
• Multiple Myeloma: A blood cancer characterized by plasma cells producing harmful light chains (nephrotoxic).
• Diabetic Nephropathy: A specific kidney disorder from diabetes; damaging effects on the kidneys, leading to proteinuria, high blood pressure and gradual kidney failure.

Clinical Applications - Multiple Myeloma

• Case Study: A 70-year-old with back pain, fatigue, anemia, high calcium levels, and Bence-Jones proteins in urine.
• Diagnostic Approach: Serum protein electrophoresis, free light chain assays, and urine Bence-Jones protein tests.
• Treatment Options: Chemotherapy to reduce plasma cells, bisphosphonates for high calcium and rehydration. Dialysis may be necessary for severe kidney problems.

Clinical Applications - Diabetic Nephropathy

• Case Study: A 55-year-old with 15-year history of uncontrolled type 2 diabetes, proteinuria, and reduced kidney function.
• Diagnostic Approach: Monitoring albumin-to-creatinine ratio (ACR) and eGFR, differentiating from other kidney issues.
• Treatment Options: Tight blood sugar control (HbA1c < 53 mmol/mol), RAAS blockers (ACE inhibitors or ARBs), and possibly SGLT2 inhibitors.

Pathophysiology of Multiple Myeloma

• Excess free light chains overwhelm proximal tubules.
• Light chain accumulation causes inflammation and cell death.
• Tubular damage leads to cast formation and interstitial fibrosis.

Pathophysiology of Diabetic Nephropathy

• Persistent high blood sugar causes advanced glycation end-products (AGEs).
• Damage to the glomeruli leads to mesangial expansion, thickening of the basement membrane, and podocyte damage.
• These changes cause hyperfiltration, hypertension, and progressive kidney damage.

Pharmacology

• Multiple Myeloma: Chemotherapy and bisphosphonates are treatments.
• Diabetic Nephropathy: RAAS blockers (ACE inhibitors or ARBs) reduce proteinuria and blood pressure. SGLT2 inhibitors can improve blood sugar control and offer potential benefits to kidneys and heart.

Differential Diagnoses

• Lupus Nephritis: Immune complex-mediated glomerular disease.
• Amyloidosis: Systemic disease with amyloid deposits in kidneys.

Investigations and Diagnostics

• Multiple Myeloma: Serum protein electrophoresis, urine tests for Bence-Jones proteins.
• Diabetic Nephropathy: Albumin-to-creatinine ratio (ACR) and 24-hour creatinine clearance.

Key Diagrams and Visuals (Diagram descriptions)

• Diagrams illustrate the mechanisms of kidney damage in multiple myeloma and diabetic nephropathy, showing the accumulation of proteins (light chains) and the effects of these proteins/processes on kidney tissue structures.