Kidney Lecture 2 Non-immune Glomerular Disease, Systemic Diseases, Infections, Vascular Diseases

Learning Objectives Describe the clinical and pathologic features of: –Minimal Change Nephropathy –Focal Segmental Glomerulosclerosis –Chronic Glomerulonephritis –Lupus Erythematosis –Diabetes Mellitus –Amyloidosis –Pyelonephritis –Drug-Induced Acute Interstitial Nephritis –Hypertensive Nephropathy –Thrombotic Microangiopathy

Non-Immune Glomerulopathies Minimal Change Nephropathy Focal Segmental Glomerular Sclerosis Focal Segmental Glomerular Sclerosis –Idiopathic –HIV Nephropathy Hereditary Nephritis –Alport –Thin Basement Membrane Chronic Glomerulonephritis

Minimal Change Nephropathy AKA Nil Disease, Lipoid Nephrosis No abnormalities by light, IF Fusion of foot processes by EM –AKA foot process effacement Usually children 2 – 6 Nephrotic syndrome Responds to steroids

Minimal Change Disease – Epithelial Cell Foot Process Effacement

FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS) Clinical - proteinuria, often nephrotic syndrome Primary: Idiopathic FSGS - pathogeneis unknown possibly apolipoprotein L1 (ApoL1) mutation - related to trypanosome resistance Primary: Heredetary FSGS - rare - pathogeneis due to nephrin, podocin,  -actinin 4 mutation Secondary – most common: - HIV - Heroin nephropathy - Adaptive response to lack of renal tissue (Compensatory) - Obesity related glomerulopathy Variable steroid response, tends to progress to renal failure

Focal Segmental Glomerulosclerosis

HIV Nephropathy

Chronic Glomerulonephritis Common cause of chronic renal failure May follow any other glomerulonephritis but frequently insidious without prior history Small granular kidneys Widespread glomerular scarring +/– clues

Chronic Glomerulonephritis

Systemic Disease Lupus Erythematosis Diabetes Mellitus Amyloidosis

Lupus Nephritis – WHO Classification Class I – Minimal or no alteration Class II – Mesangial Proliferation –Mildly increased mesangium, mesangial deposits by IF, EM Class III – Focal Proliferative GN –Segmental proliferation, fibrinoid, in < 50% of glomeruli –Hematuria, proteinuria, subendothelial deposits, capillary and mesangial deposits of many types of Ig, complement Class IV – Diffuse Proliferative GN –More severe clinically than Class III, including nephrotic syndrome and renal insufficiency –>50% glomerular involvement, “wire loops”, morphologic, IF and EM changes more pronounced Class V – Membranous Glomerulonephritis –Morphologically identical to idiopathic membranous

Lupus Nephritis WHO Class IV

Lupus – Subendothelial Deposits

Lupus- Endothelial Tubuloreticular Bodies

Activity Index Indication of level of inflammation –Cresents –Glomerular inflammation –Necrosis and karyorrhexis –Interstitial inflammation –Wire loops –Endocapillary proliferation Worse prognosis for higher score

Chronicity Index Indication of irreversible damage –Interstitial fibrosis –Glomerular sclerosis –Fibrous Crescents –Tubular atrophy Worse prognosis for higher score

Question 1 A patient with lupus erythematosis has basement membrane spikes on histology and subepithelial deposits by electron microscopy, the WHO classification is which of the following: – –Class I – –Class II – –Class III – –Class IV – –Class V

Question 1 A patient with lupus erythematosis has basement membrane spikes on histology and subepithelial deposits by electron microscopy, the WHO classification is which of the following: – –Class I – –Class II – –Class III – –Class IV – –Class V

Kidney Lesions in Diabetes End stage renal disease in up to 40% Glomerular lesions –Diffuse mesangial sclerosis –Nodular (Kimmelstiel-Wilson) glomerulosclerosis –Capillary basement membrane thickening –Exudative lesions Hyalinizing arteriolosclerosis Papillary necrosis Mechanisms –Metabolic defect –Non-enzymatic protein glycosylation –Hemodynamic effects

Kimmelsteil-Wilson Nodule

Question 2 The abnormality commonly seen in diabetic nephropathy by light microscopy is referred to as – –Crescent – –Spikes – –Kimmelsteil-Wilson nodules – –Fenestrated endothelium

Question 2 The abnormality commonly seen in diabetic nephropathy by light microscopy is referred to as – –Crescent – –Spikes – –Kimmelsteil-Wilson nodules – –Fenestrated endothelium

Papillary Necrosis

Other Systemic Diseases Affecting Glomeruli Amyloidosis –Inflammatory – Amyloid AA –Plasma Cell Dyscrasias – Amyloid AL –Heredetary Bacterial Endocarditis Essential Mixed Cryoglobulinemia

Amyloidosis

Congo Red

IgG Immunofluorescence

Infectious and Inflammatory Tubulointerstitial Diseases Pyelonephritis –Acute –Chronic –Reflux Nephropathy Viral Infection Acute Interstitial Nephritis

Pyelonephritis Pathogenesis –Gram neg– E. coli, Proteus, Klebsiella, etc –Hematogenous infection –sepsis, obstruction –Ascending infection - AcuteChronic –Reflux Nephropathy –Chronic Obstructive Pyelonephritis

Figure Schematic representation of pathways of renal infection. Hematogenous infection results from bacteremic spread. More common is ascending infection, which results from a combination of urinary bladder infection, vesicoureteral reflux, and intrarenal reflux. Downloaded from: Robbins & Cotran Pathologic Basis of Disease © 2005 Elsevier

Acute Pyelonephritis- Ascending

Acute Pyelonephritis - Hematogenous

Acute Pyelonephritis

Bacteria in Tubules H and E Gram

Urine

Polyoma Virus

Polyoma Virus Immunoperoxidase

Chronic Pyelonephritis

Chronic Pyelonephritis Predisposing factors Progression of acute pyelonephritis Chronic obstruction Reflux nephropathy

Reflux Nephropathy

Drug-Induced Nephritis Tubulointerstitial Nephritis –Sulfonamides, synthetic penicillins and other antibiotics –Diuretics, NSAIDS, Misc Drugs (Allupurinol, Cymetidine) Fever, eosinophilia, rash, renal abnormalities –Rising creatinine, hematuria, leukocyturia Analgesic Nephropathy –Papillary Necrosis

Drug-Induced Acute Interstitial Nephritis

Vascular Diseases Hypertensive Nephropathy –Essential –Malignant –Renal Artery Stenosis Thrombotic Microangiopathy Arteriosclerosis Renal Infarct Scleroderma renal crisis Preeclampsia

Hypertensive Nephropathy Benign Nephrosclerosis Malignant Hypertension –Hyperplastic arteriolitis –Fibrinoid necrosis of afferent arteriole Renal Artery Stenosis –Increased renin secretion, conversion of angiotensinogen

Benign Nephrosclerosis

Arteriolar Hyalinization

Hyperplastic Arteriolitis

Malignant Hypertension

Fibrinoid Necrosis of Afferent Arteriole

Thrombotic Microangiopathy Hemolytic Uremic Syndrome (HUS) –Childhood – verocytoxin – uncooked meat –GI bleeding, oliguria, hematuria, hemolytic anemia –Adult –infection, SLE, pregnancy, immunosuppression –Familial Thrombotic Thrombocytopenic Purpura (TTP) –Usually adult –CNS changes, hemolytic anemia, thrombocytopenia Pathogenesis –Endothelial injury –Platelet aggregation –Vascular obstruction and vasoconstriction –Distal ischemia

Hemolytic Uremic Syndrome

Atherosclerotic Ischemic Renal Disease

Renal Infarct