Kidney Lecture 2Kidney Lecture 2

Non-immune Glomerular Non-immune Glomerular Disease, Systemic Diseases, Disease, Systemic Diseases, Infections, Vascular DiseasesInfections, Vascular Diseases

Learning ObjectivesLearning Objectives

Describe the clinical and pathologic features of:Describe the clinical and pathologic features of:– Minimal Change NephropathyMinimal Change Nephropathy– Focal Segmental GlomerulosclerosisFocal Segmental Glomerulosclerosis– Chronic GlomerulonephritisChronic Glomerulonephritis– Lupus ErythematosisLupus Erythematosis– Diabetes MellitusDiabetes Mellitus– AmyloidosisAmyloidosis– PyelonephritisPyelonephritis– Drug-Induced Acute Interstitial NephritisDrug-Induced Acute Interstitial Nephritis– Hypertensive NephropathyHypertensive Nephropathy– Thrombotic MicroangiopathyThrombotic Microangiopathy

Non-Immune GlomerulopathiesNon-Immune Glomerulopathies

Minimal Change NephropathyMinimal Change Nephropathy

Focal Segmental Glomerular SclerosisFocal Segmental Glomerular Sclerosis– IdiopathicIdiopathic– HIV NephropathyHIV Nephropathy

Hereditary NephritisHereditary Nephritis– AlportAlport– Thin Basement MembraneThin Basement Membrane

Chronic GlomerulonephritisChronic Glomerulonephritis

Minimal Change NephropathyMinimal Change Nephropathy

AKA Nil Disease, Lipoid NephrosisAKA Nil Disease, Lipoid Nephrosis

No abnormalities by light, IFNo abnormalities by light, IF

Fusion of foot processes by EMFusion of foot processes by EM– AKA foot process effacementAKA foot process effacement

Usually children 2 – 6Usually children 2 – 6

Nephrotic syndromeNephrotic syndrome

Responds to steroidsResponds to steroids

Minimal Change Disease – Epithelial Minimal Change Disease – Epithelial Cell Foot Process EffacementCell Foot Process Effacement

FOCAL SEGMENTAL FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS)GLOMERULOSCLEROSIS (FSGS)

Clinical - proteinuria, often nephrotic syndromeClinical - proteinuria, often nephrotic syndrome

Primary: Idiopathic FSGS Primary: Idiopathic FSGS

- pathogeneis unknown possibly apolipoprotein L1 (ApoL1) - pathogeneis unknown possibly apolipoprotein L1 (ApoL1) mutation - related to trypanosome resistancemutation - related to trypanosome resistance

Primary: Heredetary FSGS - rarePrimary: Heredetary FSGS - rare

- pathogeneis due to nephrin, podocin, - pathogeneis due to nephrin, podocin, -actinin 4 mutation -actinin 4 mutation

Secondary – most common: Secondary – most common: - HIV- HIV

- Heroin nephropathy- Heroin nephropathy

- Adaptive response to lack of renal tissue (Compensatory)- Adaptive response to lack of renal tissue (Compensatory)

- Obesity related glomerulopathy- Obesity related glomerulopathy

Variable steroid response, tends to progress to renal failure Variable steroid response, tends to progress to renal failure

Focal Segmental Focal Segmental GlomerulosclerosisGlomerulosclerosis

HIV NephropathyHIV Nephropathy

Chronic GlomerulonephritisChronic Glomerulonephritis

Common cause of chronic renal failureCommon cause of chronic renal failureMay follow any other glomerulonephritis but May follow any other glomerulonephritis but frequently insidious without prior historyfrequently insidious without prior historySmall granular kidneysSmall granular kidneysWidespread glomerular scarring +/– cluesWidespread glomerular scarring +/– clues

Chronic GlomerulonephritisChronic Glomerulonephritis

Chronic GlomerulonephritisChronic Glomerulonephritis

Systemic DiseaseSystemic Disease

Lupus ErythematosisLupus Erythematosis

Diabetes MellitusDiabetes Mellitus

AmyloidosisAmyloidosis

Lupus Nephritis – WHO ClassificationLupus Nephritis – WHO Classification

Class I – Minimal or no alterationClass I – Minimal or no alterationClass II – Mesangial ProliferationClass II – Mesangial Proliferation– Mildly increased mesangium, mesangial deposits by IF, EMMildly increased mesangium, mesangial deposits by IF, EM

Class III – Focal Proliferative GNClass III – Focal Proliferative GN– Segmental proliferation, fibrinoid, in < 50% of glomeruliSegmental proliferation, fibrinoid, in < 50% of glomeruli– Hematuria, proteinuria, subendothelial deposits, capillary Hematuria, proteinuria, subendothelial deposits, capillary

and mesangial deposits of many types of Ig, complementand mesangial deposits of many types of Ig, complement

Class IV – Diffuse Proliferative GNClass IV – Diffuse Proliferative GN– More severe clinically than Class III, including nephrotic More severe clinically than Class III, including nephrotic

syndrome and renal insufficiencysyndrome and renal insufficiency– >50% glomerular involvement, “wire loops”, morphologic, IF >50% glomerular involvement, “wire loops”, morphologic, IF

and EM changes more pronouncedand EM changes more pronounced

Class V – Membranous GlomerulonephritisClass V – Membranous Glomerulonephritis– Morphologically identical to idiopathic membranousMorphologically identical to idiopathic membranous

Lupus Nephritis WHO Class IVLupus Nephritis WHO Class IV

Lupus – Subendothelial DepositsLupus – Subendothelial Deposits

Lupus- Endothelial Tubuloreticular BodiesLupus- Endothelial Tubuloreticular Bodies

Activity IndexActivity Index

Indication of level of inflammationIndication of level of inflammation– CresentsCresents– Glomerular inflammationGlomerular inflammation– Necrosis and karyorrhexisNecrosis and karyorrhexis– Interstitial inflammationInterstitial inflammation– Wire loopsWire loops– Endocapillary proliferationEndocapillary proliferation

Worse prognosis for higher scoreWorse prognosis for higher score

Chronicity IndexChronicity Index

Indication of irreversible damageIndication of irreversible damage– Interstitial fibrosisInterstitial fibrosis– Glomerular sclerosisGlomerular sclerosis– Fibrous CrescentsFibrous Crescents– Tubular atrophyTubular atrophy

Worse prognosis for higher scoreWorse prognosis for higher score

Question 1Question 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 1Question 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 DiabetesKidney Lesions in DiabetesEnd stage renal disease in up to 40%End stage renal disease in up to 40%Glomerular lesionsGlomerular lesions– Diffuse mesangial sclerosisDiffuse mesangial sclerosis– Nodular (Kimmelstiel-Wilson) glomerulosclerosisNodular (Kimmelstiel-Wilson) glomerulosclerosis– Capillary basement membrane thickeningCapillary basement membrane thickening– Exudative lesionsExudative lesions

Hyalinizing arteriolosclerosisHyalinizing arteriolosclerosisPapillary necrosisPapillary necrosisMechanismsMechanisms– Metabolic defectMetabolic defect– Non-enzymatic protein glycosylationNon-enzymatic protein glycosylation– Hemodynamic effectsHemodynamic effects

Kimmelsteil-Wilson NoduleKimmelsteil-Wilson Nodule

Question 2Question 2

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

Question 2Question 2

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

Papillary NecrosisPapillary Necrosis

Other Systemic Diseases Other Systemic Diseases Affecting GlomeruliAffecting Glomeruli

AmyloidosisAmyloidosis– Inflammatory – Amyloid AAInflammatory – Amyloid AA– Plasma Cell Dyscrasias – Amyloid ALPlasma Cell Dyscrasias – Amyloid AL– HeredetaryHeredetary

Bacterial EndocarditisBacterial Endocarditis

Essential Mixed CryoglobulinemiaEssential Mixed Cryoglobulinemia

AmyloidosisAmyloidosis

Congo RedCongo Red

IgG ImmunofluorescenceIgG Immunofluorescence

Infectious and Inflammatory Infectious and Inflammatory Tubulointerstitial DiseasesTubulointerstitial Diseases

PyelonephritisPyelonephritis– AcuteAcute– ChronicChronic– Reflux NephropathyReflux Nephropathy

Viral InfectionViral Infection

Acute Interstitial NephritisAcute Interstitial Nephritis

PyelonephritisPyelonephritis

PathogenesisPathogenesis– Gram neg– E. coli, Proteus, Klebsiella, etcGram neg– E. coli, Proteus, Klebsiella, etc– Hematogenous infection –sepsis, obstructionHematogenous infection –sepsis, obstruction– Ascending infection -Ascending infection -

AcuteAcute

ChronicChronic– Reflux NephropathyReflux Nephropathy– Chronic Obstructive PyelonephritisChronic Obstructive Pyelonephritis

Figure 20-35 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- Acute Pyelonephritis- AscendingAscending

Acute Pyelonephritis -Acute Pyelonephritis -HematogenousHematogenous

Acute PyelonephritisAcute Pyelonephritis

Bacteria in TubulesBacteria in TubulesH and E GramH and E Gram

UrineUrine

Polyoma VirusPolyoma Virus

Polyoma Virus ImmunoperoxidasePolyoma Virus Immunoperoxidase

Chronic PyelonephritisChronic Pyelonephritis

Chronic PyelonephritisChronic Pyelonephritis

Chronic PyelonephritisChronic Pyelonephritis

Chronic PyelonephritisChronic PyelonephritisPredisposing factorsPredisposing factors

Progression of acute pyelonephritisProgression of acute pyelonephritis

Chronic obstructionChronic obstruction

Reflux nephropathyReflux nephropathy

Reflux NephropathyReflux Nephropathy

Drug-Induced NephritisDrug-Induced Nephritis

Tubulointerstitial NephritisTubulointerstitial Nephritis– Sulfonamides, synthetic penicillins and other Sulfonamides, synthetic penicillins and other

antibioticsantibiotics– Diuretics, NSAIDS, Misc Drugs (Allupurinol, Diuretics, NSAIDS, Misc Drugs (Allupurinol,

Cymetidine)Cymetidine)

Fever, eosinophilia, rash, renal Fever, eosinophilia, rash, renal abnormalitiesabnormalities– Rising creatinine, hematuria, leukocyturiaRising creatinine, hematuria, leukocyturia

Analgesic NephropathyAnalgesic Nephropathy– Papillary NecrosisPapillary Necrosis

Drug-Induced Drug-Induced Acute Interstitial NephritisAcute Interstitial Nephritis

Vascular DiseasesVascular Diseases

Hypertensive NephropathyHypertensive Nephropathy– EssentialEssential– MalignantMalignant– Renal Artery StenosisRenal Artery Stenosis

Thrombotic MicroangiopathyThrombotic Microangiopathy

ArteriosclerosisArteriosclerosis

Renal InfarctRenal Infarct

Scleroderma renal crisisScleroderma renal crisis

PreeclampsiaPreeclampsia

Hypertensive NephropathyHypertensive Nephropathy

Benign NephrosclerosisBenign Nephrosclerosis

Malignant HypertensionMalignant Hypertension– Hyperplastic arteriolitisHyperplastic arteriolitis– Fibrinoid necrosis of afferent arterioleFibrinoid necrosis of afferent arteriole

Renal Artery StenosisRenal Artery Stenosis– Increased renin secretion, conversion of Increased renin secretion, conversion of

angiotensinogenangiotensinogen

Benign NephrosclerosisBenign Nephrosclerosis

Arteriolar HyalinizationArteriolar Hyalinization

Hyperplastic ArteriolitisHyperplastic Arteriolitis

Malignant HypertensionMalignant Hypertension

Fibrinoid Necrosis of Afferent ArterioleFibrinoid Necrosis of Afferent Arteriole

Thrombotic MicroangiopathyThrombotic Microangiopathy

Hemolytic Uremic Syndrome (HUS)Hemolytic Uremic Syndrome (HUS)– Childhood – verocytoxin – uncooked meatChildhood – verocytoxin – uncooked meat– GI bleeding, oliguria, hematuria, hemolytic anemiaGI bleeding, oliguria, hematuria, hemolytic anemia– Adult –infection, SLE, pregnancy, immunosuppressionAdult –infection, SLE, pregnancy, immunosuppression– Familial Familial

Thrombotic Thrombocytopenic Purpura (TTP)Thrombotic Thrombocytopenic Purpura (TTP)– Usually adult Usually adult – CNS changes, hemolytic anemia, thrombocytopeniaCNS changes, hemolytic anemia, thrombocytopenia

PathogenesisPathogenesis– Endothelial injuryEndothelial injury– Platelet aggregationPlatelet aggregation– Vascular obstruction and vasoconstrictionVascular obstruction and vasoconstriction– Distal ischemiaDistal ischemia

Hemolytic Uremic SyndromeHemolytic Uremic Syndrome

Atherosclerotic Ischemic Renal DiseaseAtherosclerotic Ischemic Renal Disease

Renal InfarctRenal Infarct