Secondary Glomerular Disorders PDF

Secondary glomerular disorders Lecture Number 8.1 Status Done Type Lecture 8.1 Secondary glomerular disorders Overview Secondary glomerular disorders encompass kidney diseases that are caused by systemic conditions rather than intrinsic renal pathology. This lec...

Secondary glomerular disorders Lecture Number 8.1 Status Done Type Lecture 8.1 Secondary glomerular disorders Overview Secondary glomerular disorders encompass kidney diseases that are caused by systemic conditions rather than intrinsic renal pathology. This lecture focuses on two critical disorders: multiple myeloma nephropathy and diabetic nephropathy. These conditions are explored in terms of their mechanisms of renal injury, clinical manifestations, diagnostic methods, and therapeutic approaches. A clear understanding of these disorders is essential for both clinical practice and examination preparation. Learning Objectives Objective 1: Explain how multiple myeloma causes renal injury and the relevance of Bence-Jones protein urine assessment. Objective 2: Illustrate the natural history, pathophysiology, and clinical progression of diabetic nephropathy. Objective 3: Outline the diagnostic process and multifactorial management strategies for diabetic nephropathy. Key Concepts and Definitions Primary Glomerular Disorders: Intrinsic kidney diseases often of idiopathic origin, not associated with systemic conditions. Secondary Glomerular Disorders: Kidney diseases caused by systemic illnesses such as multiple myeloma, diabetes, or lupus. Multiple Myeloma: A haematological malignancy characterised by a clonal proliferation of plasma cells producing monoclonal immunoglobulins, including nephrotoxic light chains. Diabetic Nephropathy: A specific glomerular disorder caused by the direct effects of diabetes on the kidneys, marked by proteinuria, hypertension, and progressive renal decline. Clinical Applications Multiple Myeloma Case Study: A 70-year-old presents with back pain, fatigue, and weight loss. Laboratory results show anaemia, hypercalcaemia, and a gamma spike on serum electrophoresis. Urinalysis detects Bence-Jones proteins. Diagnostic Approach: Perform serum protein electrophoresis and free light chain assays. Conduct Bence-Jones protein testing on urine samples. Treatment Options: Chemotherapy to reduce plasma cell burden and light chain production. Address hypercalcaemia with bisphosphonates and rehydration. Dialysis may be required for severe renal impairment. Complications/Management: Renal impairment in ~50% of cases. Poor prognosis in those presenting with renal impairment. Diabetic Nephropathy  Case Study: A 55-year-old with a 15-year history of poorly controlled type 2 diabetes exhibits persistent proteinuria and reduced eGFR. Retinopathy is noted on fundoscopy, confirming diabetic nephropathy. Diagnostic Approach: Annual albumin-to-creatinine ratio (ACR) and eGFR measurements. Differentiate from non-diabetic kidney disease by assessing retinopathy and the progression of proteinuria. Treatment Options: Tight glycaemic control (HbA1c < 53 mmol/mol). RAAS blockade (ACE inhibitors or ARBs) to reduce proteinuria and progression. SGLT2 inhibitors for nephroprotection and cardiovascular benefits. Complications/Management: Leads to end-stage renal disease (ESRD) requiring dialysis in advanced stages. Pathophysiology Multiple Myeloma Pathway/Mechanism : 1. Excess free light chains (FLCs) overwhelm proximal tubular reabsorption. 2. FLC accumulation induces pro-inflammatory cytokine release and reactive oxygen species (ROS), causing tubular apoptosis. 3. Distal tubular injury results in cast formation with Tamm-Horsfall protein, leading to obstruction and interstitial fibrosis. Histological Findings: Tubular obstruction by casts. Interstitial fibrosis Diabetic Nephropathy Pathway/Mechanism : 1. Persistent hyperglycaemia produces advanced glycation end-products (AGEs), ROS, and cytokines. 2. Altered haemodynamics lead to glomerular hyperfiltration, hypertension, and renal hypertrophy. 3. Chronic injury results in mesangial expansion, thickened basement membrane, and podocyte effacement. Histological Findings: Diffuse mesangial expansion. Thickened basement membrane. Nodular sclerosis (Kimmelstiel-Wilson lesions). Pharmacology Multiple Myeloma Chemotherapy: Reduces plasma cell proliferation and light chain production. Bisphosphonates: Treat hypercalcaemia and bone disease. Diabetic Nephropathy RAAS Blockade: ACE inhibitors or ARBs reduce proteinuria and glomerular pressure. Target BP: